Miscellaneous Reaction

Some reactions of propargylic compounds which do not belong to the above-mentioned types are known. These reactions are surveyed in this section, although their mechanisms are not always clear. 

A Pd-catalysed variant of the Nazarov cyclization of 1 -ethynyl-2-propenyl acetate derivatives to form cyclopentenone dierivatives involving 1,2-acetoxy migration is 

Mandai, M. Ogawa, H. Yamaoki, T. Nakata, H. Murayama, M. Kawada and J. Tsuji, Tetrahedron Lett., 33, 3397 (1991). 

Konishi, T. Okano, S. Kometani and A. Iwasa, Chem. Lett., 313 (1987). 

Other reactions that have been tried in solution-phase combinatorial chemistry comprise  

Ring system Starting material(s) Presence of other Reference 

P-lactams P-amino acids, aliphatic and ester, aminocarbonyl, [58] 

P-keto-carboxylic acid benzyl esters, (Bu-cyano-acetate, sulfur 

Several minor reactions of alkylpyrazines are illustrated in the following examples  

6-Dimethylpyrazine gave 2-methyl-6-trimethylsilylmethylpyrazine (335) [PryMLi (made in situ), THF, -78°C then Me3SlCl, -78°C, 3 h 70%] somewhat similarly, 2-[(but-3-ynyl)oxymethyl]pyrazine (336, R = H) gave 2-[(4-trimethylsilylbut-3-ynyl)oxymethyl]pyrazine (336, R = SiMe3) (lithia-tion with Phi i etc. 74%).366 

4-DimethyIpiperazine (337) gave piperazine dihydrochloride (339) [CIC-(=O)()( II( IMe, CICH2CH2CI, reflux, 1 h residue from evaporation, MeOH, 50°C, 30 min 96% proceeds via the diquatemary intermediate (338) by loss of 2 MeCl, 2 CO2, and 2 MeCH(OMe)2]. In a somewhat similar way, l-benzyl-2,4-dimethylpiperazine (340) gave ethyl 2,4-dimethyl-l-piper-azinecarboxylate (341) (ClCO2Et, PhH, reflux, 48 h 25% via a monoquaternary intermediate), and thence 1,3-dimethylpiperazine (342) (6 M HCl, 48 h 67% by hydrolysis and decarboxylation) also other related examples.  

4 Miscellaneous Reactions of Phosphines.- The role of chiral phosphines as ligands in the catalysis of reactions leading to the formation of chiral products has been reviewed.1111 A procedure for the determination of the enantiomeric excess in chiral phosphines has been developed, based on 13C n.m.r. studies of the diastereoisomeric complexes formed by phosphines with the chiral pinenyl nickel bromide complex. 111 Studies of the sulphonation of triphenylphosphine and of chiral arylphosphines have been reported in attempts to prepare water soluble ligands which aid 

Phenyl-phosphorus cleavage has also been observed in a 

Constant current electrolysis of triphenylphosphine in dichloromethane in the presence of amides and N,N -disubstituted 

Valence isomerism of the 7,8-bis(phosphino)cycloocta-l,3,5-trienes (73) has been studied in a range of compounds, and the 

Me3P(F)CF = CFCF3 Me2PCF=CFCF3 Me2P AsMe2 

4 Miscellaneous Reactions of Phosphines.- Full details have 

In connection with the formation of modern electronic materials such as gallium phosphide, there have been a number of fundamental studies of the course of pyrolysis of t-butyl-phosphine.. in a related area, adducts of diphenyl-phosphine with trialkylgallium acceptors have been described.  

The bis(dimethylamino)methyl group of the phosphine (79) is easily cleaved from phosphorus on treatment with electrophilic reagents.Examples of phosphorus-carbon cleavage in phosphines coordinated to transition metals continue to appear. Yet another route for the deactivation of 

4 Miscellaneous Reactions. Wittig technology has been used to prepare ylide-, phosphate-, phosphite- and phosphinate-terminated dendrimers, and calixarenes bearing pyridyl podands on their upper rim 7° 

The incompletely condensed silsesquioxane [(c-C6Hn)7Si709(0H)3] has been shown to react rapidly with methylenetriphenylphosphorane to afford the salt [Ph3PCH3][(c-QHn)7Si70,o(OH)3] 7  

Reaction of ketenylidene- or thioketenylidenetriphenylphosphoranes with a,P-unsaturated carbonyls, e.g. 2-benzylidene-l,3-indandione yields pyranones and thioxopyranones IQP Treatment of the same phosphoranes with o-chloroanil (tetrachloro-l,2-benzoquinone) yields 71Ketenylidenetriphenylphosphorane 

The reaction of 2-amino-1,4-quinones and Ph3P=CHC02R (R = Me, Et) proceeds via 1,2- and 1,4-addition reactions to yield the pyrroline-ylide phos-phorane 11  

Acyclic phosphoranes bearing a fluoroalkyl side chain (75), undergo intramolecular Wittig reactions when heated, producing cyclic benzoates. Shen and Gao have reported a stereoselective synthesis of trifluoromethylated a-chloro-a,P-unsaturated esters and nitriles by employing trifluoromethylated phosphoranes (scheme 13). 

8 Miscellaneous reactions. Formation of ArF has been achieved from aryl- 

PhjSi] to give BuTH2CHYHgCi, and with Ar2C=CH2 and (ii) reactions of PhC=CY (Y=PhS02, I, PhS, BUjSn, PhC=CHg) with RHgX, which yields PhC=CR. 

Fehr and J. Galindo, Helv. Chlm. Acta, 1986, 69. 228 C.G. Screttas and H. Hlcha-Screttas, J. Organomet. Chem.. 1986, 316, 1. 

Volden, and I. Weldleln, Acta Chem. Scand., Part A. 1986, 113. 

FUrstner and H. Ueidmann, J. Chem. Soc.. Chem. Commun., 

Several additional reactions have been used to prepare condensation polymers, although relatively little is known about their kinetics. Some are indicated here, to illustrate more fully the scope of poly condensations. 

Friedel—Crafts reactions have been used to prepare low- 

Free radicals may also be intermediates in poly condensation reactions, in special cases, such as 

A variety of unusual polymerizations falling into this class has been reviewed by Sokolov [5]. 

Transition-metal-catalyzed reactions between and alkynes are also useful for the 

Many other important organic reactions, such as the Mannich S eAi and Wittig reactions are accelerated by high pressure. 

For example, pressure has an effect on Friedel-Crafts benzoylation. 

The high-pressure technique is also very useful when organometalloid reagents are used for difficult organic synthesis. 

When pressure (1.5 GPa) is applied at room temperature on the reaction of [Pt2(p-S)2(dppp)] (189) with an excess of a-a -dichloro-o-xylene (190) a product mixture is obtained from which 3,8-dibenzo-l,6-dithiacyclodecane 192 (35%) has been isolated. Apart from its pharmacological value, it could be used in molecular sensors and conductive polymers. The one-pot formation of 192 at 

Another application of high pressure in combinatorial chemistry has been reported by Matsumoto and Jenner. For the first time, uncatalysed, high-pressure (0.6 GPa) three-component Strecker synthesis of a-amino nitriles 202 was carried out in high yields by reacting aniline (200) with various ketones 201 

Tautomeric quinoxalines undergo a variety of other reactions that have not been used to a great extent in recent years. They are illustrated by the classified examples that follow. 

2(l//)-Quinoxalinone (76) gave 2-trifluoromethanesulfonyloxyquinoxaline (77, R = CFa)[substrate, EtaN, CH2CI2, 0°C then (F3CS02)20i slowly, 0°C, 2 h 78%] or 2-tosyloxyquinoxaline (77, R = CgH4Me-p) (substrate, 4-dimethyl- 

4//)-Quinoxalinedione (79) and trimethylenephosphorochloridate (80) gave crude 2,3-bis(trimethylenedioxyphosphmooxy)quinoxalLne (81), which 

3-Diphenyl-5(l//)-quinoxahnone (83) gave 5-(dunethoxyphosphinyloxy)-2,3-diphenylquinoxaline (85) via intermediate (84) (neat POCI3, reflux, 18 h then cooled mixture into excess MeOH, 0°C 60%).  

Note Such deoxygenation is usually accompanied by partial nuclear reduction. 3-phenyl-2(177)-quinoxalinone (90) gave 2-phenyl-3,4-dihydroquinoxaline (91) (LiAlH4, THF, N2, 0°C reflux, 24 h 65%).  

5-Hydroxy-6,7-dimethoxy-2,3(1/7,4/7)-quinoxalinedione (78, R = H) gave 6,7-dimethoxy-5-phenylacetoxy-2,3(1/7,4/7)-quinoxalinedione [78, R = C( 0)-CH2Ph] (PhCH2COCl, Et3N, CH2C12, 20°C, h 77% note regioselectiv-ity)681 

A number of papers have been concerned with substitution reactions of Vitamin B12 model compounds. Kinetics of the substitution of the alkylaquo-l,3-bis(acetyl monoximeimino)propanato-cobalt ions (MH2O) by L are consistent with formation of an intermediate MH20,L only when L contains an aromatic group. Sjxl substitution reactions of the axial aquo-ligand in methyl aquo-cobaloxime by thiols, primary amines, and 4-substituted pyridines have been described. 

Prompted by earlier results which indicated that the rate law for substitution of Cl in square-planar rran -[Pt(PEt3)2(R)Cl] (R = phenyl, jp-tolyl, or mesityl) complexes included an associative as well as the normal dissociative path only in the case of substitution by strong biphilic ligands (e.g. CN, SeCN ), Ricevuto et al. have re-examined the reaction with weakly nucleophilic pyridine in methanol  

The reaction is anomalous (i) in obeying the rate law koMs = ki + k py and (ii) in having kx different from the constant value found in the reaction with other nucleophiles. Careful analysis shows that Atods is determined by competition for the intermediate tranj-[Pt(PEt3)2(R)(MeOH)]+ by Cl and py  

Condorelli, L. Giallongo, A. Giufifrida, and G. Romeo, Inorg. Chim. Acta, 1973,7, 7. G. Tauzher, R. Dreos, G. Costa, and M. Green, J.C.S. Chem. Comm., 1973, 413. 

Wan and his co-workers have reported the photohydration and photosolvolysis of the alkenes (45). The reactions involve the intermediacy of quinone-methide type intermediates. Flash photolysis of coniferyl alcohol (46) and isoeugenol (47) in acetonitrile has supplied evidence for the formation of the corresponding radical cations. These transient species react readily with water and other hydroxylic solvents to afford 4-vinylphenoxyl radicals.  

The influence of substitution on the alkenes (49) has been assessed. The study has shown that styrenes with 6 -methyl and oc-methyl groups adopt orthogonal geometry. This results in a blue shift in the tttt transition.The ocimene derivative (50) is formed on irradiation of the pinene derivative (51). There is no evidence for [2 + 2]-cycloaddition, and the rearrangement occurs on irradiation in benzene or methanol. Excitation results in triplet energy transfer from the benzene moiety to the pinene. The ring opening affords the cis isomer (50), but continued irradiation affords a ratio, trans xis, of 52  

1 Addition Reactions. A patent has described a method for the formation of perfluoroalkyl iodides. This consists of irradiating (254 nm) a mixture of perfluoroethyl iodide with tetrafluoroethene at elevated temperatures and 

Methanol addition results on irradiation of 2,3-dimethylbut-2-ene in a mixture of 1,4-dicyanobenzene and phenanthrene in the presence of acrylonitrile or methyl acrylate. Inoue and co-workers have studied the enantio-differentiating addition of alcohols to the 1,1-diphenylethene derivatives (52). The reactions are sensitized by the naphthalenecarboxylates (53) and (54), where the R groups are saccharide moieties. The ee of the products (55) is influenced by steric, electronic and solvent effects. Efficient addition of water to 3-hydroxystilbene can be brought about on irradiation in acetonitrile-water mixtures.Pincock has highlighted the importance of the discovery in 1973 of the formation of the radical cation of 1,1-diphenylethene. Grainger and Patel have described a new photochemical approach to cuparene (56). The reaction involves the electron-transfer induced cyclization of the styrene 

A silacyclopropene intermediate is involved in the photochemical cyclization of l-(3-hydroxy-2-pyridyl)-2-(pentamethyldisilanyl)ethyne.  

7 Other catalytic C-C bond formations 6.7.1 Miscellaneous reactions 

A review of the use of cyclic peroxides in organic synthesis including photochemical decomposition has been published.17 Photochemical reactions of carbohydrate molecules have been the subject of another review.177 

Chapman et /.178 have re-examined the photoreactions of the benzene oxide-benzoxepin rearrangement and at 235.7 nm obtained evidence that the deuterio-isomer (258a) isomerizes into (258b) by an oxygen-walk reaction. At low temperature (77 K) a keten [(259), xw 2112 cm-1] is obtained which is converted 

Kloster-Jensen and J. Wirz, Helv. Chim. Acta, 1975, 58, 167. 

Kaupp180e has rationalized the orientational selectivity observed in the ringopening of phenylcyclobutanes in terms of relief of steric strain present in the molecules as a result of phenyl-phenyl crowding. In accord with this, in a study of stilbene dimers it was shown that the cis-anti-cis-dimer (262) decomposed 

180 (o) G. Kaupp, Angew. Chem. Internal. Edit., 1974, 13, 817 (b) G. Kaupp, Houben-Weyl , Thieme, Stuttgart, Vol. IV/5. 

Kobayashi earlier demonstrated the first use of enamides and enecarbamates as nucleophiles in several enantioselective copper-catlayzed reactions [30]. Inspired by this precedent, Terada reported that 0.1mol% of Im effectively 

Given the rich chemical diversity accessible from aminohydrazones. Rueping investigated the imino-azaenamine reaction of N-Boc protected imines and 

There are a host of chemical reactions of coal that are dispersed throughout the scientific and engineering literature but are too voluminous to report here. Many of these reactions are miscellaneous in nature and do not appear to have a bearing on chemistry and coal utilization. However, there are 

Other reactions of coal that do have importance in terms of coal utilization insofar as they provide valuable information about the behavior of coal under various conditions and are reported here. 

To summarize, applications of NHC-cobalt complexes in homogeneous catalysis only emerged a few years ago, with emphasis on the comparison between NHC and phosphine ligands in known cobalt catalysis such as the Pauson-Khand or hydroformylation reactions. However, it appears that the introduction of NHCs in cobalt catalysts may lead to interesting and previously unknown patterns of reactivity. For this reason and in view of the accelerating research activity since 2007/2008, a growing interest in NHC-cobalt catalysis is expected. 

The nickel compounds NiRa(bipy) react with a variety of alkenes, including ethylene, norbomadiene, maleic anhydride, and tetracyanoethylene, to produce Ni(bipy)(alkene) or Ni(bipy)(alkene)2. A kinetic study, supported by characterization of intermediates from the reactions with aorolein and with acrylonitrile, indicates that the reaction mechanism involves the intermediacy of transient complexes NiR2(bipyXalkene), containing the alkene TT-bonded to the nickel as in the products. There is a correlation between the rates of these reactions and the stabilities of the respective complexes Ni(bipy)(alkene). The unstable species CoH(LL)2, where LL = bipy or phen, undergo substitution reactions with, for example, carbon monoxide, in which one LL ligand is replaced. One LL can also be replaced by alkyl halides here the reaction is oxidative elimination rather than simple substitution.  

P(OEt)2Ph, and X = Cl or Br, by the action of phosphorus ligands. The reactions are first-order, and have positive activation entropies, between + 9 and + 17 caldeg mol. These observations imply a dissociative mechanism. Activation enthalpies are between 27 and 34 kcalmol such high values may be compared with, for instance, the activation enthalpy of 28 kcal mol for displacement of dinitrogen from the [Ru(NH3)5(Na)]2+ cation.  

Metal-Alkyl, -Aryl, and -Allyl Bond Formation and Cleavage 

Vanadium.—Vanadium oxochloride, VOCI3, reacts with diphenylmercury to form PhVOCl2 and some biphenyl. There is evidence, from deuterium labelling experiments, that the biphenyl is formed via an intermediate which contains two phenyl groups a-bonded to the vanadium.  

LUMO mixing. The photochemical C-Br fission in the bromo-alkenes (217) continues to be of synthetic value. Thus Irradiation of (217) in a nixed solvent, water / methylene dichloride, with a phase transfer agent and potassium isoeyanata affords the isoquinollnones (218). The reactions are quite 

The benzyl ethers (223) photochemically cleave to form alcohols ROH (R = alkyl, cycloalkyl, or 2-pyrrolidinoethyl) in acetonitrile/water. The reaction involves sinsls electron 

D-galactose (233) yielding the lyxopyranose (234). The arabinopyranose (232) has now been used as a starting material in the 

Karatsu, H. Misawa, Y. Kuriyama, H. Okamoto, T. Hiresaki, H. Furuuchi, H. Zeng, H. Sakuragi, and K. i tjV. nimaru, Pure Appl. Cham., 1989, 60, 989. 

Kumagai, T. Segawa, T. Miyashi, and T. Mukai, Cham. Lett., 1989, 475. 

Irradiation of a mixture of ortho or para-nitrochlorobenzene and ethanol in the presence of sodium hydroxide and a phase-transfer agent yields the corresponding ethoxy aromatic compounds within a few minutes (Eq. 66) [92]. The same procedure was subsequently applied to 2-chlorophenol [93]. In both reactions, PEG 400 was shown to be the most efEcient catalyst (Table 6.25). 

Solvent-free SNAr reactions under solid-liquid PTC conditions were realized by use of methoxide or phenoxide as nucleophiles. The main results and comparison with those from classical heating are indicated in Table 6.26 for activated (e.g. 4-nitrohalobenzenes) or nonactivated (e.g. j8-naphthyl halides) substrates [94]. 

Diaryl ethers were easily obtained from reactions of phenols with nitroarylfluor-ides under solvent-free + MW conditions by use of a KF/alumina + Aliquat system (Eq. 67) [95]. 

Etherifications of heterocyclic compounds have been performed with good efficiency by solid-liquid PTC coupled with MW irradiation (Eq. (68), Table 6.27) [96]. Yields and conditions involved here are a noticeable improvement over classical methods from the standpoint of green chemistry. 

Selective and efficient ffuorinations of chlorodiazines were obtained under solvent-free MW-assisted PTC conditions (Eq. 69) [97]. 

A kinetic study has been made of the oxidation of ascorbic acid (H A) by neptunium(vi). The rate law is of the form — d[NpVi]/dr=A 2[H2A] [Np i] with no evidence for a hydrogen-ion dependence over the range 0.05 [H+] l.OOM. In aqueous media Np i exists as the [O—Np—0] + ion with between four and six equatorial water molecules. A comparison with the reactions with aquo-ions, e.g. or where inner-sphere reactivity is established and with [Fe(phen)3] + indicates that the preferred pathway is outer sphere. The exchange rate for [(5-nitrophen)gFe] +/ + and the redox potential are both greater than for the Np VNp couple and these features are considered- the reason for the rate of the present reaction being 40 times slower than that of the iron system. 

Radiochromatographic techniques have been used to determine the rates of oxidation of cysteine by pertechnate ion, Tc04. The technetium(vu) is reduced by the thiol (and cysteine ethyl ester) to form a Tc complex which involves both S- and 7V-co-ordination of the amino-acid. The rate law is first order with respect to both [Tc ] and [RSH]. A hydrogen-ion dependence observed is attributed to the formation of pertechnic acid, the rate-determining step being the nucleophilic attack by the thiol at the metal centre of HTCO4. The oxidation of RSH (R=Et, Pr, or Bu) has been studied over the range 20—40 °C in aqueous alkaline solutions in the presence of metal phthalo-cyanines. The reaction is zero order with respect to [thiol], first order in phthalocyanin and decreases in the order M = Co Mn V Feii. No effects are observed from the nature of the alkali cation. 

Thallium(iii) acetate has been used as the reactant in the oxidative hydrolysis of aldoximes RCH=NOH (R=Me, Et, Pr, or Ph) to the corresponding ketones. The reactions were studied in 50% aqueous acetic acid with a rate law Rate = A 2[TPi ] [oxime], A rate-limiting decomposition of an outer-sphere complex to yield an iminoxyl radical is considered to take place prior to further hydrolysis. 

Mixed complex formation has been postulated in the oxidation of sulphite catalysed by transition-metal ions. Several reactions are observed in the presence of copper(ii). The auto-oxidation rate is catalysed with formation of the species [00(803)202] as intermediate. In the presence of propan-2-ol (ROH), however, an inhibition reaction, dependent on [SOs ] and [ROH], is observed. Induced oxidation of the inhibitor by copper(n) is also a factor, the rate being a function of [Cu ]. In the latter system the complex [Cu(SO )-(R0H)02] is considered as the reactive species, 

In a similar manner, three-component coupling of allyl chlorides or acetates with 1-alkynes and alkynyltins in the presence of a nickel catalyst prepared in situ from Ni(acac)2 and DIBALH provides a convenient regio- and stereoselective synthesis of 3,6-dien-l-ynes [231,232], It is interesting to note that no phosphine ligands are required in these reactions. A Jt-allylnickel intermediate is proposed. 

In the presence of a phosphine ligand, coupling of alkynyltin with allyl chloride is obtained [233]. 

The tandem reaction of allyl electrophiles with alkynes and MejAl or Mc2Zn occurs in the presence of Ni(acac)2 to give a regioisomeric mixture of the three-component coupling products [234]. The reaction can also proceed intramolecu-larly to give cyclic nonconjugated dienes. 

Inteamolecular three omponent assembly of allenes, aryl iodides and alkenyl-zirconium reagents provided the synthesis of 1,4-dienes [235]. Both vinyl and aryl iodides are active participants for generating highly regio- and stereoselective assembUes. 

In a similar manner, acylstannanes also undergo acylstannylation of alkynes under similar conditions. In addition, carbostannylation can also be achieved with alkynylstannnes regioselectively. 

The photochemical reversion of the cage compound (274) into the diene (275) has been studied by Mukai and his co-workers.The process can be brought about by various catalysts such as ZnO or CdS. These experiments are related to the utilization of strained cage compounds as a means of energy storing. Mukai et have further reported on their detailed study of the cycloreversion reactions of cage compounds (276) involving electron-transfer processes. Another report has described work with cationic sensitizers (277). °  

The cycloreversion of the cyclobutane (278) to the olefin occurs from the singlet state on irradiation at 265 nm. Triplet-state reactivity is reported for cycloreversion using A = 347 nm. The isomerization of 1,2-diphenylcyclobutanes has been used as a means of establishing the efficiency of electron-transfer processes in the phenanthrene-dicyanobenzene system. 

The regio- and stereo-selective ring opening of the oxaziridines (288) on photolysis to yield the lactams (289) has been reported. The stereo-electronic 

Irradiation of the chromene (290) in benzene afforded the styrene (291) and the ketene (292) which was detected by low-temperature i.r. The presence of a ketene intermediate was confirmed chemically by irradiation of the chromene 

The acetophenone-initiated reactions of tetrahydropyrans (299) have been described. 

4- arylidenepyrazol-3-ones 728a-j with equimolar amounts of 1,2-phenylenediamine 

With this method a fluorine atom can be attached to an activated aromatic ring, effectively by displacement of the pyrazol-3-one moiety M750. This method is suitable for incorporation of the important 18F isotope into biologically interesting compounds, for position emitting tomography (PET) studies. 

Wiley and P. Wiley, Pyrazolones, Pyrazolidones and Derivatives (A. Weissberger ed.), The Chemistry of Heterocyclic Compounds, Vol. 20, Interscience Publishers, New York, (1964), pp. 142, 143, 266. 

Ciernik and A. Mistr, Collect. Czech. Chem. Commun., 31, 4669 (1966). 

Yoshikawa, S.-I. Kitahura, and N.-E. Aoki, Chem. Pharm. Bull., 17, 1467. 

1-Phenyl-1,4-hcxadicnc (122) is obtained as a major product by the codimerization of butadiene and styrene in the presence of a Lewis acid[110]. Pd(0)-catalyzed addition reaction of butadiene and aiiene (1 2) proceeds at 120 C to give a 3 1 mixture of trans- and c -2-methyl-3-methylene-l,5.7-octatriene (123)[lll]. 

Opening of a cyclobutane ring fused to a quinolizine system under reductive conditions has been described. Thus, the previously mentioned compound 128 was obtained by treatment of 132 with samarium diiodide (Equation 8) 

Whereas enyne 429 is formed in excellent yield from allenyl sulfone 428 as a stable product of 1,4-elimination of water [118], short-lived butatrienones 431 can only be characterized by argon matrix infrared spectroscopy after 1,2-elimination of HX from precursors 430 by flash vacuum pyrolysis [373, 374]. 

Allenic esters can be generated by palladium-catalyzed carbonylation of propargyl compounds (see Section 7.2.6). Under the reaction conditions applied, however, succeeding reactions occur directly in many cases, for instance by introduction of a second ester function. Many examples of such carbonylation reactions of allenic esters were summarized in a review by Tsuji and Mandai [136], 

Although this review is by no means comprehensive, it should give an impression of the great number of feasible syntheses of acceptor-substituted allenes and their possibilities of reactions. The unique combination of the C=C=C unit and the acceptor group often allows not only the common reactions of these parts but also specific transformations into a variety of very different products. Much attention was paid to the results of the last 20 years, but we have tried to mention all important facts about the chemistry of the title compounds. At the latest during the last two decades, it turned out that acceptor-substituted allenes are not only compounds for experts in organic chemistry but also very useful and general tools in synthetic chemistry. 

106] F. Kato, M. Tokairin, K. Hiroi, Annu. Rep. Tohoku Coll. Pharm. 1995, 42, 123-129. 

136] J. Tsuji, T. Mandai, Angew. Chem. 1995, 307, 2830-2854 Angew. Chem., Int. Ed. Engl. 

Hydroboration of alkenes in non-ethereal solvent has been reported using diborane generated in situ from a quaternary ammonium borohydride and bromoethane (see Section 11.5). Almost quantitative yields of the alcohols are reported [e.g. 1 ]. As an alternative to the haloalkane, trimethylsilyl chloride has also been used in conjunction with the ammonium borohydride [2]. Reduction of the alkene to the alkane also occurs as a side reaction ( 20%) and diphenylethyne is converted into 1,2-diphenylethanol (70%), via the intermediate /ra 5-stilbene. 

The analogous hydroxylation of alkynes to produce ketones is enhanced by the co-catalytic effect of Aliquat and platinum(IV) chloride-carbon monoxide [3] it is assumed that HPtCI(CO) is the active hydration species. C-S and C-Br bonds are cleaved under the reaction conditions. 

Me SiCl (0.43 g, 4 mmol) in CH2Cl2 (2 ml) is added with stirring to the alkene (4 mmol) and TEBA-BH4 (0.83 g, 4 mmol) in CH2Cl2 (6 ml) at 0°C and the mixture is stirred for 0.5-7 h. Aqueous K,CO, (10%, 3 ml) is added and the mixture is stirred for a further 10 min and then extracted with CH2C12 (2x10 ml). The dried (MgS04) extracts are evaporated to yield the alcohol. 

Thiocarbonyl compounds are converted into the corresponding carbonyl derivatives in good yield (70-99%) by their reaction with concentrated aqueous sodium hydroxide and dichloromethane in the presence of tetra-n-butyiammonium hydrogen sulphate [4], The reaction is general for thioeslers, thioamides, thioureas and thiones (Table 3.28), and no reaction occurs in the absence of the phase-transfer catalysts. The reaction is also aided by the initial 5-methylation of the thiocarbonyl group [5]. 

Conversion of thiocarbonyl compounds into carbonyl derivatives 

Some unusual transformations will follow. The term unusual refers to unexpectedly smooth processes of H atom replacements obtained with (TMS)3SiH under radical conditions. Reaction (4.42) reports the replacement of a pyridinium moiety by hydrogen, with (TMS)3SiH under standard experimental conditions using t-BuOH as the solvent. In fact the two substrates (R = Me, Et) afforded 3-fluoro-2-aminopyridine derivatives in good yields [78], leaving the fluorine substituent untouched. 

Tris(trimethylsilyl)silane reacts with phosphine sulfides and phosphine selen-ides under free radical conditions to give the corresponding phosphines or, after treatment with BH3-THF, the corresponding phosphine-borane complex in good to excellent yields (Reaction 4.45) [82]. Stereochemical studies on P-chiral phosphine sulphides showed that these reductions proceed with retention of configuration. An example is given in Reaction (4.46). 

The photochemical reduction of 1-methylquinolinium ions by (TMS)3SiH proceeds regioselectively to afford the corresponding 1,4-dihydroquinones in a water-acetonitrile solvent system (Reaction 4.47) [83]. Mechanistic studies demonstrated that the reactions are initiated by photoinduced electron transfer from the silane to the singlet excited states of 1-methylquinolinium ions to give the silane radical cation-quinolinyl radical pairs, followed by hydrogen transfer in the cage to yield 1,4-dihydroquinones and silicenium ion. Silyl cations are quenched by water. 

Dextrose is widely used as an isotonic media in parenteral formulations. Sterilisation using autoclaving has been reported to induce the formation of fructose via an isomerisation reaction, with the resultant formation of 5-hydroxymethyl-furfural [90]. 

Aspartame is relatively unstable in solution, undergoing cyclisation by intramolecular self-aminolysis at pH values in excess of 2.0 [91]. This follows nucleophilic attack of the free base N-terminal amino group on the phenylalanine carboxyl group resulting in the formation of 3-methylenecarboxyl-6-benzyl-2, 5-diketopiperazine (DKP). The DKP further hydrolyses to L-aspartyl-L-phenyl-alanine and to L-phenylalanine-L-aspartate [92]. Grant and co-workers [93] have extensively investigated the solid-state stability of aspartame. At elevated temperatures, dehydration followed by loss of methanol and the resultant cyclisation to DKP were observed. The solid-state reaction mechanism was described as Prout-Tompkins kinetics (via nucleation control mechanism). 

The Maillard condensation is one of the most extensively studied reactions within the field of degradation chemistry, particularly in the area of food and nutritional science. Louis Mallard reported in 1912 that some amines react with reducing carbohydrates to produce brown pigments. The condensation typically yields a simple glycosylamine, which then readily undergoes the Amadori rearrangement to produce 1 -amino-1 -deoxy-2-ketoses [95]. Reducing carbohydrates 

BMS-204352, a novel substituted 3-fluorooxindole, is a potassium channel opener being developed for the treatment of stroke. Nassar et al. [96] reported on the development of a non-aqueous parenteral formulation of BMS-204352. This formulation was composed of a mixture of PEG 300, polysorbate 80, ethanol and water. The authors reported on the formation of 1-hydroxymethyl adduct of BMS-204352 (formaldehyde adduct), which was linked with residual levels of formaldehyde in the polymeric excipients. 

Duloxetine hydrochloride, a novel anti-depressive, is known to be acid labile and, consequently, it has been formulated as an enteric-coated tablet. Interestingly, Jansen et al. [97] subsequently found that the drug was destabilised by degradation products within these enteric polymers. The authors found that succinyl and phthalyl residues from the hydroxypropyl methylcellulose acetate succinate (HPMCAS) and hydroxypropyl methylcellulose phthalate (HPMCP) formed 

Ketones or aldehydes can be reacted to form /3-hydroxy esters. 

The structure in the box comes from the carbonyl compound (acceptor) the structure in the oval comes from the o-bromoester (carbanion source). 

The chemistry of the aldehydic H, except for oxidation to OH, is meager. The C—H bond can be homolytically cleaved by participation of a free radical. 

Problem 15.44 Propanal reacts with 1-butene in the presence of uv or free-radical initiators (peroxides, sources of RO ) to give CHjCHjCOCHjCH CHjCH,. Give steps for a likely mechanism.  

Step 1 is the initiation step. Steps 2 and 3 propagate the chain. 

Other examples of the application of organometallic catalysis in water are Oligomerization of ethylene using Ni/tppms523 and Ni/20 (Table 2 n=0, R=Me, 

Na-salt n=0, R=H, Li-salt) catalysts524 (the latter was used in polar solvents such as ethanol and sulfolane) or of terminal alkynes catalysed by Rh/tppms and Rh/42 (Table 3 n=2) systems.525 

Ruthenium-catalysed Ring-Opening Metathesis Polymerization (ROMP) 29 526 529 (Equation 10) and Pd(tppms)3-catalysed synthesis of water soluble poly-(p-phenylene) derivatives (Equation ll).530 The latter is a special example of a Suzuki coupling (see earlier). 

Alternating Copolymerization of Olefins with CO catalysed by palladium complexes generated from the sulfonated ligands 29 (Table 2 x=3 m=0,l n=0) and 108 (Table 6) in aqueous media263 or from 20 (Table 2 n=0 R=H acid-form) and 21 (Table 2 R=Ph n=2,3 acid-form) in methanol.335 

A Hylic Substitutions with a variety of nucleophiles catalysed by Pd/ tppts147 510,531 533 or Pd/29 (Table 2 x=2,4 m=0 n=0)531 532 in aqueous-organic media (Equation 12). 

Cyclic nitrones 695 react with di-t-butylcarbodiimide in the presence of a catalytic amount of tetrafluoroboric acid by dehyration to give the heterocycle 696.  

Unsaturated aminoacid esters 698 are obtained in the reaction of carbobenzoxy protected Q -hydroxyamino acid esters 697 with diisopropylcarbodiimide in the presence of CuClJ  

The reaction of carbodiimides with hydrogen chloride affords chloroformamidine hydrochlorides 699.  

Suitably substituted carboxyhc acids 700 can be dehydrated with DCC to give the heterocycle 701. 1  

Carboxylic acid chlorides react with carbodiimides to give N-acychloroformamidines 702. Further reaction of the N-acylchloroformamidines with tfaiosemicarbazide affords 

The transformation of aziridines that do not involve ring opening are rare due to the reactivity of the aziridine ring. Considering the somewhat more difficult synthesis of aziridines (relative to epoxides), the ability to convert one aziridine into another represents a significant expansion of the scope of any aziridine synthesis. 

Phenol may be methylated with methyl sulfate in cool alkaline medium to give anisole  

Arylatlon. The introduction of arylamino groups is often needed in the synthesis of intermediates and dyes. An important intermediate, 3-ethoxy-4-methyldiphenylamine is prepared from resorcinol and p-methylaniline as follows  

Condensation and addition. In both condensation and addition reactions, two or more molecules combine by the elimination of a simple molecule (condensation), or the reaction is stopped after the molecules are joined (addition). There are only a few intermediates manufactured in any considerable quantity by these reactions. An example of a condensation reaction is the formation of the diphenylamine derivative, commonly called nitro delta acid [5]. 

The formation of cyanuric acid from cyanogen chloride is a good example of an addition reaction. 

The reduction of alcohols with a trialkylsilane in the presence of a protic acid can be complicated by skeletal rearrangement and alkene formation as a result of carbonium ion formation. This problem is significantly reduced when using BF3 as the acid (Eq. 85) [140]. Peptide isosteres (Eq. 86) can be prepared by the alkylative ehmina-tion of y-oxygenated-a,y3-unsaturated carboxylates by use of BF3 complexes of alkyl-copper reagents [141]. 

BF3 Et20 is effective in the direct amidation of carboxylic acids to form carboxamides (Eq. 88) [144]. The reaction is accelerated by bases and by the azeotropic removal of water. 

BF3 Et20 catalyzes the decomposition of /3,y-unsaturated diazomethyl ketones to cyclopentenone derivatives (Eq. 89) [145,146]. 

A new method, employing 0-(2-aminobenzoyl)hydroxylamine and BF3 Et20, has been discovered for the synthesis of nitriles from aldehydes yields are 78-94 % (Eq. 90) [147]. 

5-corane (84) is obtained in SOX yield on photo-decarbonylation of the pentacyclic ketone (85). Photochemical decomposition of the carbonate (86), by the loss of carbon dioxide, affords a mixture of products containing oxirane. styrene oxide, bibenzyl and phenylacetaldehyde. Triplet sensitized irradiation yields products solely from benzyl radicals. - An earlier study of the irradiation (at 254 nm) of the carbonate (87) reported that benzaldehyde, phenyl carbene, and carbon dioxide were produced. A reinvestigation of the irradiation of this compound (at 254 nm in acetonitrile) has provided evidence that the cis- and trans-stilbene oxides (88) and (89) are formed as well as deoxybenzoin and smaller amounts of diphenylacetaldehyde and bibenzyl. When methanol is used as the solvent the same products are produced accompanied by benzylmethyl ether, 1,2-diphenylethanol, and 2,2-diphenylethanol. These authors suggest that the oxiranes (88) and (89) are formed by way of 

Irradiation of the iodoketones (99) has shown that the products obtained are formed by competing radical and cationic processes. A previous account of the photochemical solvolysis of the chloroketone (100) reported the formation of two photoproducts (101) and the solvolysis product (102). A reinvestigation of this reaction has shown that the only photoproduct from the reaction is the alcohol (101). The second product (102) is formed by an acid catalysed thermal process.  

A study of the photoreduction of the oxoamides (103) in acetonitrile/triethylamine has shown that the oxoamides (103 a,b) afford the alcohols (104) in high yield. However, the amides (103 c,d) and (105) are also reactive and afford the cyclized compounds (106 - 108) respectively. The failure of the oxoamides (103 a,b) to undergo cyclization is presumed to be due to intramolecular hydrogen bonding. The ease with which this reductive cyclization occurs with amides or unsaturated ketones has been exploited in a new synthesis of hirsutene (109). Thus irradiation (254 nm) of the ketone (110) in acetonitrile/triethylamine affords the alcohol (111, 20X) and the desired cyclic compound (112, S8X). This latter material is readily converted to hirsutene. The ketone 

Wavelength dependence of the photolytic behaviour of the bicyclobutane (116) has been studied in inert solvents. At 254 nm and 300 nm the irradiation affords the three products (117), (118), and (119) but the ratio of products is different at the different wavelengths. The authors believe that the reactions arise from the ic-ic state. Irradiation at 300 nm in diisopropyl ether or in toluene yields only the methylene cyclobutane (117). 

Takuwa and his coworkers have demonstrated that the irradiation of the aromatic carbonyl compounds (120) in the presence of the stannanes (121) affords the unsaturated alcohols (122) as the principal products. An electron transfer mechanism is proposed. Electron transfer is also involved in the reaction of amines with alkenes such as the phenylethylenes (123). The electron transfer in this instance affords an alkenyl radical anion the presence of which has been demonstrated by a variety of techniques. A further reaction has been uncovered in the photoreaction of, for example, the alkene (123a) with iV, AT-diethylani lino in the presence of carbon dioxide. This treatment affords the three carboxylated derivatives (124), (125), and (126) by trapping of the radical anion by carbon dioxide. Similar carboxylation was demonstrated for (123b) and biphenyleno. The influence of the amine on the yield of product was studied.  

Addition of alcohol to an internal alkyne can occur in the presence of a diiridium-palladium or -platinum sulfido cluster and gives rise to the corresponding acetal [53]. 

The dithiolate complex [l,5-bis(mercaptoethyl)-l,5-diazacyclooctane]Ni or -Pd reacts with SO2 to produce sulfur-site SO2 adducts and then with O2 to form sulfato complexes. Exogenous thiolates used as an electron source allow SO2 oxygenation to 864 ions [56]. The complex cw-[Pt(SH)2(PPh3)2] catalyzes 

Dithioacetals react with [Cp3Ti P(OEt)3 2] to produce [Cp2Ti(SR)2] and an alkylidene species [Cp2Ti=C(R )(R )] which is an excellent entry to the Wittig-type reactions from carbonyl, alkene, and alkyne substrates [59]. 

D2/H exchange between D2 and ethanol can be catalyzed by [RhH(CO)( S4 )] or the PCys analogue, being the 1,2-bis(2-mercapto- 

5-di-terr-butylphenylthio)ethane ligand, and should model the reaction at the metal-sulfur sites of hydrogenases [60]. Allylamines can be efficiently depro-tected by 2-mercaptobenzoic acid in the presence of catalytic amounts of a Pd° complex [61]. 

Lewis acid activates the nitrile function in the intermediate (97), which yields the product upon hydrolysis.Treatment of 3-(aryliminomethyl)-chromones (98) with ylides results in the formation of phosphorane-adducts (99).  

The need for new classes of strong non-ionic, non-nucleophilic bases has led Palacios and co-workers to investigate ylide (101) and its polymer-supported analogue (102) in this capacity. It was found that ylides (101) and (102) acted as versatile bases for selective A -alkylation reactions of P-amino phosphine 

Pentacoordinate 1,2-thiaphosphetenes (103) are obtained when ylide (104), which contains a Martin ligand, is treated with aryl isothiocyanates. A series of stabilised ylides (105) has been studied as thermally latent catalysts for 

A = thiophene-2,5-diyl R = Ph, 2-thienyl, C02Et A = biphenyl-4,4 -diyl R = Ph, C02Et A = 1,3-CeH4- R = C02Et 

The interaction of triphenylmethylenephosphoranes (108) with tertiary butyl lithium has been studied by proton and lithium-7 NMR. It was found that treatment of simple ylides such as (108 a) and (108b) with one equivalent of the butyl lithium resulted in ortho-metallation of one of the phenyl rings 

The trapping of a cation by a nucleophile. An, can be considered the electrophilic addition of a cation to a lone pair. 

The electrophilic addition of a Lewis acid to a lone pair to form a Lewis salt is an isoelectronic reaction. An example is the first step of borate ester hydrolysis  

Since the product of the carbocation addition to an alkene via path Ag is also a carbocation that can rearrange and/or attack another alkene molecule (polymerization), unwanted product mixtures can result. 

Borane, 2BH3 B2H6, isoelectronic with carbocations, adds exclusively syn to multiple bonds. Initially a pi-complex is believed to form, followed by rapid hydride donation to the largest d atom (4e path. Fig. 7.12). The reaction repeats to produce dialkyl and occasionally trialkyIboranes, R3B. 

One equivalent of R2AIH at low temperature will add once to nitriles or many carboxylic acid derivatives to give aldehydes after an acidic aqueous workup (see Section 9.2.2). 

COCIF is reported not to attack aluminium, brass or stainless steel. It is only slightly 

On prolonged contact with SO 3 at -35 C, COCIF appears to react according to the stoichelometry [ICIl 14 ]  

COCIF is said to react with phosphorus(V) halides upon heating in an autoclave, according to [903]  

These reactions are very unlikely to yield clean products, however. 

The interaction between COCIF and SbF has been investigated in SOjClF by sp n.m.r. spectroscopy [99]. In dilute solution, the sp n.m.r. spectroscopic data were interpreted in terms of the formation of SbFj.COClF at -95 C at higher temperatures, or in more concentrated solutions, halide exchange occurs, and COFj and SbF. COFj were detected [99]. The same adduct is also formed, as a by-product, in the reaction between phosgene and SbFj in SOjClF (see Section 9.1.4.4) [1653c] the COCIF ligand is O-bonded. 

Salt effects ( addition of lithium tetrafluoroborate and magnesium perchlorate) have been evaluated in the photochemical electron transfer reaction between 

10-dicyanoanthracene and 1,2-bis -(4-methoxyphenyl) cyclopropanes. Direct irradiation of the cyclopropanes (183) results in fission into alkene and dimethylcarbene as the minor reaction path. The major process encountered is ring opening to afford a butene derivative. 

Adam eind his coworkers have carried out a detailed study of the irradiation of 

The behaviour of the cation radicals derived from bicyclobutane systems has been under intensive study by Gassman and his coworkers. Currently they have observed that the substituted derivative (185) photorearranges in good yield, using 1-cyanonaphthalene as the electron acceptor, to the isomer (186). Although this product can be synthesized independently by the photocyclization of the diene (187) the authors argue that this route is not in operation. The formation of the product (186) follows the one electron transfer path with subsequent rearrangement within the radical cation (188).  

The photochemical reactivity of the epoxides (189) and (190) and (191) have been studied. A detailed examination of the photo-ring opening of the epoxides (192) to yield carbonyl ylid has been reported by George ei Laser flash photolysis of 

As mentioned in Section VI, acid treatment of the p-quinol acetates of 

5-tetrahydroisoquinolinol gave a C-O coupling dimer (493) in addition to a C-C coupling dimer (494). On the other hand, bistetrahydroisoquinolyl ethers 496-499, which were formed by intermolecular C-O coupling, were obtained by treatment of 8,8a-epoxy p-quinol 495 with tetrahydro- 

Reagents a. PbfOAcJ j, AcOH b. tetrahydroisoquinolinols, CF COOH, CH2CI2 c. AC2O, pyridine 

Reagents o. PbtOAc), AcOH b. R OH, BF3.Et2O c. NaBH/j, MeOH  

The authors are grateful to Drs. H. Mishima and H. Hara for valuable suggestions with respect to the manuscript. 

SET processes can be used to effect ring opening within strained 

A review of the photochemical reactions of 2 3H) and 2(5tf)-furanones has been published. The former group of compounds undergoes decarbonylation from the singlet state. The latter group undergo a variety of reactions such as dimerization, 

Decarbonylation also arises during the gas-phase irradiation of 

Aryl acetic acid derivatives are notable for their failure to 

Norrish type I cleavage of the lactone C-0 bond followed by the 

Rigby synthesized a [5.3.1] oxa-bridged nucleus in the context of a perhydro-azulene synthesis [89]. Upon treatment of 81 with BF3 etherate, a hetero-Diels-Alder reaction between the aldehyde and the diene occurred to give 82 in good yield, Eq. 62. 

Gebel and Margaretha have reported a photochemical intramolecular [22] reaction between an olefin and a furanone which resulted in the construction of a [2.2.1] oxabicydic nucleus as well as a cyclobutane in 83, Eq. 63 [90]. 

Vogel has applied the Tiffeneau-Demjanov ring-expansion reaction to convert oxabicyclo[2.2.1] substrates into oxabicyclo[3.2.1] compounds [91]. The reduction of nitrile 4 a generates 84 which, under deamination conditions, yielded 85, Eq. 64. Because 4a can be obtained in enantiomerically pure form, this constitutes a enantioselective synthesis for oxabicyclo[3.2.1] substrate 85. 

The elimination of hydrogen from 1,1-difluoroethene occurs by a three-centre mechanism, a postulate that has been supported by calculations. The photodissociation of 2-chloro-l,l-difluoroethene shows the fast elimination of chlorine atoms. Photodissociation of 2-chloro-l,l-difluoroethene at 193 nm proceeds by elimination of HCl via a three or a four-centre pathway. Both CCl and CC double bond fission processes contribute to the decomposition of 1,1- and 

2-dichloro-difluoroethene on irradiation at 195 nm. Morton et alF have described the photodissociation of cis-1-bromopropene by irradiation at 193 nm. This treatment results in the formation of the 1-propenyl radical by CBr bond fission. The decomposition pathways for this species were observed. In a later publication the authors have revised the earlier work. Apparently the incorrect assignment had been made regarding the nature of the bromine atom part of the fission process.  

Gilbert and co-workers have described the dehydrogenation of a-terpinene to p-cymene by reaction of benzophenone in the presence of cupric ions under 40 suns concentrated sunlight. The cyanovinyl radical can be obtained by irradiation of acrylonitrile. A review article has discussed the methods for formation and the behaviour of allyl radicals. The principal product from such a species is allene. However, 1,2- and 1,3-hydrogen migrations are also observed, with the formation of 1- and 2-propenyl radicals. The photochemical reactivity of 

2-substituted allyl chloride with t-BuHgCl in various solvents has been studied.  

1 Addition Reactions. The irradiation of gaseous mixtures of tetra-fluoroethene and CF3I results in the formation of linear perfluoroalkanes. A variety of aromatic sensitizers such as (31) have been used to bring about the 

Full details of Michael-type nucleophilic additions to coordinated 

Except with sterically crowded reagents,nucleophilic ring-opening of coordinated phosphiranes (88) involves initial attack at 

The new phosphines (90) have been used as ligands in a homogeneous 139 

2-bis(diphenylphosphino)ethane enable the separation of gallium and indium by reversible adduct formation. Trimethylaluminium forms a very strong complex with diphos which only dissociates on distillation. 

Whereas both tri(t-butyl)phosphine and secondary phosphines react with perfluoropropene to give the perfluorovinylphosphines (91), the corresponding reactions of triethylphosphine (and methylaryl- 

The use of chiral sulfoxides to transfer the chirality from sulfur to the a carbon has been investigated, and the high asymmetric induction observed in chiral acyclic sulfoxides using a silicon-induced Pummercr-typc reaction is noteworthy [249]. 

An interesting oxidative decarboxylation which bears some analogy to the Pummerer reaction has been reported [250]. 

A plethora of other functional modifications are more or less directly associated with sulfur compounds. A few examples are discussed below. 

An efficient synthesis of ethers involves hydrozirconation of thioketones with hydrochlorobis(cyclopentadienyl)zirconium [251]. 

Appropriate cleavages of the zirconium sulfide (1) has led to sulfonyl halides, thioesters, and other derivatives. 

in The chemistry of organophosphorus compounds , ed. F. R. Hartley, John Wiley Sons, Chichester 1996, vol. 4, p. 1-45. 

Comprehensive Heterocyclic Chemistry II , ed.-in-chief A. R. Katritzky, C. W. Rees, and E. F. V. Scriven, Elsevier Science, Oxford 1996. 

Bandini, G. Martelli, G. Spunta, and M. Panunzio, Tetrahedron-Asymmetry, 

Frenzel, M. Gluth, R. Herbstirmer, and U. Klingebiel, J. Organometal. Chem., 

Sekine, H. Tsuruoka, S. limura, H. Kusuoku, T. Wada, and K. Furusawa, 

It has been reported that a chiral ferrocenylphosphine-gold(I) complex catalyses the asymmetric aldol reaction of an isocyanoacetate 

Radical cyclizations in the presence of cobalt(I) species lead to alkylcobalt(III) complexes which undergo 1,2-elimination of H-Co 

The ferrocenylmethyl group has been used to mask peptide bonds 91 

1 A Yamamoto, 1Organotransition Metal Chemistry Fundamental Concepts and Applications, Wiley - Interscience, Chichester, 1986. 

2 AW Parkins and R C Poller, An Introduction to Organometa11ic Chemistry, Macmillan, Basingstoke, 1986. 

The tervalent tautomer (162) of dimethyl phosphonate (163) has an enthalpy 6.5 kcal mol higher than (163), as estimated from gas-phase studies of deprotonation, relative to dedeuteriation, of (164). The value, although lower than previous estimates, is high enough to explain why tautomers like (162) have not been observed. They exist, however, as ligands, e.g., in (165) and (166).  

Oximes react with tervalent chlorophosphorus compounds to give rearranged products (167), and the intermediates (168) have now been detected by n.m.r. and some have been isolated evidence is presented that the rearrangement (168) (167) proceeds via horaolytic O-N bond cleavage.  

Yoshifuji, K. Shibayama, N. Inamoto, and T. Watanabe, Chem. Lett., 1983, 58S. 

Dialkyl phosphoriodites add to acetylenic ethers to give vinylphosphonites (169). Ethyl diphenylthiophosphinite (170) and hydrogen iodide do not give the expected Arbuzov product (171) but instead give (172) and (173) the result was explained by protonation on sulphur instead of on phosphorus.  

The synthesis, structure, and reactivity of phospha(m)adamantanes and tricyclic analogues have been reviewed. The basicity of the amino groups in some aminophosphines have been estimated by i.r. measurements. An Arbuzov reaction between trimethyl phosphite and an iodo-cobalt complex has been studied by H and P n.m.r.  

A mechanistically interesting method for the formation of diazomethane was found by Staudinger and Kupfer (1912). They obtained diazomethane from hydrazine and chloroform in 25% yield. In spite of the ready availability of the reagents, the method is not attractive for the synthesis of diazomethane, even after Sepp et al. (1974) were able to increase the yield to 48% by adding small amounts of 18-crown-6. The mechanism (2-44), which was tentatively proposed by Hegarty (1978, p. 579), is, however, interesting because of the hydrazonyl chloride 2.97 formed primarily elimination of HCl gives the zwitterionic nitrile imine 2.98, which is an isomer of diazomethane (for a discussion of diazomethane isomers, see Sect. 5.4). 

2 Methods for the Preparation of Alkane, Athene, and Alkyne Diazo Compounds 

A new method for the synthesis of 1,1-dialkyldiazomethanes (2.101) has been developed by Warkentin s group (Majchrzak et al., 1989). A-Acylhydrazones of ketones (2.99) are oxidized with lead tetraacetate to 2,5-dihydro-l,3,4-oxadiazoles (2.100). This intermediate undergoes a photolytic cleavage if irradiated with UV light (300 nm) at room temperature in benzene (2-45). 

Several other syntheses of diazomethane have been reported, but they are rarely used (see Regitz and Maas, 1986, and in Klamann and Hagemann s volume of Houben-Weyl, 1990). 

In diazo transfer reactions both N-atoms, i. e., the entire diazo group, are introduced into a suitable substrate from a diazo donor (2-46). In most cases this transfer reagent is a sulfonyl azide (Y=N2 = Ar-S02N=N2 or R-S02-N=N2), from which the N(yff)- and N(y)-atoms will form the diazo group in the product. There are, however, also cases in which the diazo group of an aromatic diazonium ion or of a diazoalkene is transferred. Such examples are of minor importance. 

A paper on new approaches to the generation of arylphosphinidenes has been published. The stable bis-azide precursor (133) upon photolysis, or vapour phase thermolysis, gave (134), obviously via the phosphinidene (135) the same product was obtained by photolysis of the phosphaketene (136). The reduction of aryldiazonium salts to arenes with triethyl phosphite or triphenylphosphine is shown to proceed by a radical-chain mechanism. The previously described photo-Arbuzov rearrangement of benzyl phosphites has been used to prepare several acyclic phosphonate nucleotide analogues, e.g. (137).  

A series of dialkylsilylene diphosphites (138) has been prepared for use as chelating ligands.Chlorophosphines react sluggishly with trialkyl phosphites, but the reaction has now been shown to be catalysed by Lewis acids and then to give high yields of diphosphine oxides, e.g. 

Agback, L. H. Koole, A. Sandstrbm, and J. Chattopadhyaya, Tetrahedron, 

Nozaki, K. Mashima, and H. Takaya, Tetrahedron-Asymmetry, 1992,3, 683. 

Results presented during the year appear to indicate a further shift in interest away from fundamental phosphate ester chemistry towards that of phosphonic and phosphinic acids and. in all areas, towards compounds of potential pharmacological interest. 

Solvent-free Preparation of Ionic Liquids Using Microwaves 

The surge of interest in this area continues, including the use of ultrasonic irradiation to prepare these solvents [142] and their use as catalysts for alkylation of isobutane with 2-butene [145] or for ruthenium-catalyzed tandem migration [146a] or silver-catalyzed coupling reactions [146b]. 

Some halides of sp carbons can be carbonylated. Carbonylation of a-halo ketones and esters is a known reaction [68,69]. jS-Keto esters are prepared by the carbonylation of halomethyl ketones [70,71]. Methyl benzoylacetate (160) was obtained in 86 % yield by the carbonylation of 2-chloroacetophenone (159) in MeOH using PdCl2(PPh3)2 as a catalyst at 110°C and 10 atm in the presence of n-BusN [71]. 

Cyclization and dicarbonylation of 4-pentenyl iodide afforded the keto ester 161 in 82 % yield in benzene in the presence of Pd(PPh3)4, Et3N, and DMAP at 100 °C and 40 atm under irradiation with a xenon lamp [72]. 

Couve-Bonnarie, J. F. Carpentier, Y. Castanet, and A. Mortreux, Tetrahedron Lett, 

Szarka, R. Skoda-Foldes, A. Kuik, Z. Berente, and L. Kollar, Synthesis, 545 (2003). S. Cacchi, G. Fabrizi, and F. Marinelli, Synlett, 997 (1996). 

Garrido, S. Raeppel, A. Mann, and M. Lautens, Tetrahedron Lett, 42, 265 (2001). 

Shi et al7 reported a highly enantioselective allylic substitution of Morita-Baylis-Hillman (MBH) acetate with TMSOF that could be achieved by chiral prolinamide phosphane organocatalysts 43 in good yield and high ee. 

In spite of the plethora of prolinamide-derived catalysts developed until now, some problems, such as the high catalyst loading or long reaction times, remain unresolved. The search for catalysts that improve the reactivity of both the donor or acceptor will continue to be an area of development in the future. 

Aratake, T. Itoh, T. Okano, N. Nagae, T. Sumiya, M. Shoji and 

Pedrosa, J. M. Andres, A. Gamarra, R. Manzano and C. Perez-Lopez, Tetrahedron, 2013, 69, 10811. 

For some recent reviews see (a) A. Zamboulis, N. Moitra, J. J. E. Moreau, 

Ethylene glycol derived acetals are hydrolysed under mild con- 

Owing to its ready removal under mild conditions by brief treatment 

Pearson, Metallo-organio Chemistry, J. Wiley, New York, 1985- 

Lukehart, Fundamental Transition Metal Organometallic Chemistry,  

Atwood, Inorganic and Organometallic Reaction Mechanisms, Brooks/Cole, Monterey, 1985. 

Unelius, J. Kozak, and T. Norin, Acta Chim. Scand., 1992,46,686. 

Bianchini, A. Meli, M. Peruzzini, F. Vizza, and F. Zanobini, Coord, Chem. Rev., 1992,120,193. 

Raoult, R. Choukroun, M. Basso-Bert, and D. Gervais, J. MoL Catal., 1992,72,47. 

Inagaki, S. Nishimuia, and K. Wada, Chem. Lett., 1992,1983. 

Isotani, and J. Kiji, Tetrahedron Lett., 1992, 33,5547. 

In order to prepare the ( + )-Rove beetle pheromone. Node and colleagues reported a novel tandem Michael/Meerwein-Ponndorf-Werley reduction 

In 2002, Viani s group reported the synthesis of both enantiomers of tri-fluoro-y-valerolactone and pentafluoro-y-caprolactone, which involved chiral y-fluoroalkyl-jS-sulfinylcarboxylic acids as intermediates. These latter were 

In 2000, Roland and Mangeney developed a diastereoselective synthesis of tert-butyl-1,2-diamines from the addition of tert-butylmagnesium chloride to 

2- bis-imines derived from glyoxal and chiral amines. Evidence of a DKR during the bis-addition process of the organometallic reagent, leading to the 

A DKR of a 5-hydroxytricyclodecadienone using (S)-prolinol or its methyl ether as the chiral mediator led to the corresponding enaminones. This approach, which constituted an asymmetric desymmetrisation of a Diels Alder 

It is appropriate to mention here that [60] fiillerene reacted with ethyl bromoacetate in presence of Zn dust (the reaction was carried out by vigorously agitating the mixture for 20 min at room temperature) and the adduct (A) was 

Chlorocarbonyl addition followed by carbon dioxide and hydrogen chloride eliminations is also a typical reaction sequence in the case of carbonyl substrates, e.g., aldehydes, amides, ureas or oxygenated sulfur or phosphorus compounds. 

Direct transformation of N-benzyl-protected tertiary amines 1759 into carbamoyl chlorides 170, which are versatile intermediates for the direct preparation of amides, ureas, carbamates, and heterocycUc derivatives, is an attractive alternative to save deprotection and activation steps involving the free amine as an intermediate [135, 735]. 

Simandi (Ed.), Dioxygen Mdvation and Homogeneous Catdt Oxidatkm in Surface Science and Catedysiy Volume 66, Elsevier, Amstodam, 1991. 

Takaya and R. Noyori in Comprehensive Organic Synthesis, Eds. B. M. lYost and 1. Fleming, Pergamon Press, Oxford, 1991, Volume 8, Chapter 3.2, pp 443 to 469. 

Takahashi, N, Suzuki, M. Kageyama, Y. Nitto, M. Sabuii, and E.-I. Negishi, Chem. Lett., 1991,1579. 

Bouachir, B. Chaudret, F. Dahan, F. Agbossou, and I. Tkalchenko, Organometallics, 1991,10,455. 

An optically pure y-silyloxyvinylboronate rearranged in the presence of thionyl chloride to afford the a-chloro-( )-crotylboronate with a high level of chirality transfer [122]. Important apphcations of this rearrangement are in the synthesis of polyke-tide natural products and a-aminoboronates [123,124). A few examples of transition metal catalyzed isomerizations of alkenylboronates have been reported, providing al-lylboronates in good yields [125,126). 

Mikhailov, P. M. Aronovich, Ivtz. Akad. Nauk SSSR, Ser. Khim. 1961, 927-929. 

Ochiai, M. Toyonari, T. Nagaoka, D. W. Chen, M. Kida, Tetrahedron Lett. 1997, 38, 6709-6712. 

LeGoaster, A. Jegou, B. Carboni, Synth. Commun. 1999, 29, 1183-1194. 

19 (a) F. Possdme, PhD Thesis, University of Rennes 1, 2001. (b) M. Deligny, PhD Thesis, University of Rennes 1, 2003. 

In addition to the elassie aldol reaction, several modified versions have been reported. These methods are based on the use of nueleophiles related to the standard ketones. In partieular, nitromethane is an interesting carbon nucleophile in aldol reaetions and the use of this type of substrate has been 

In addition, an unprecedented organocatalysed nitroaldol condensation of fluoromethyl ketones in the presence of cinchona alkaloids was reported by Umani-Ronchi et al. The aldol products derived from both tri- and difluoro-methyl ketones were obtained with high levels of stereoinduction (76-99% ee) under mild conditions and a low loading of catalyst (1-5 mol %). As shown in 

An indirect aldol condensation between trichlorosilyloxicyclohexene and benzaldehyde was reported by Juaristi et al. in the presence of novel chiral thioureas, incorporating chiral moieties derived from (i )- or (iS)-a-phenyl-ethylamine, (i )-phenylglycine or (l/ ,25)-ephedrine. However, the enantios-electivities of the formed aldol products remained low ( 10% ee). 

In the same context, other novel chiral bipyridine A,A -dioxides derived from terpenes were employed by Maikov et al. to catalyse similar reactions. A 

A series of other nucleophiles have been condensed onto C=0 double bonds in the presence of chiral organocatalysts. As an example, Rueping et al. described the use of chiral silylated A-triflylphosphoramides derived from 

Very effective catalysts for the hydrosilylation of alkynes were developed by Lee and coworkers. They prepared a series of rhodium(I) and rhodium (III) complexes containing their PCP pincer 10 (e.g., ter-[(10)Rh(CO)Cl], jer-[(10)RhCl3]), all of which showed high activities in the hydrosilylation of phenylacetylene with HSiMe2Ph, yielding the ( )-p-silylalkenyl products in 80% selectivity at 0.1-0.001 mol% catalyst loadings [21]. 

Recent Advances in Asymmetric Catalysis with Chiral NHCP Ligands 

103 Recent Advances in Asymmetric Catalysis with Chiral NHCP Ligands 217 H2, cat. 

MAA Methyl W-acetamido acrylate MAC Methyl W-acetamido oinnamate DMI Dimethyl itaconate (R, R = C02Me R2 = Me) 

Substrate ( )-1,3-diphenylptop-3-en-1yl acetate, Nucleophile DMM = dimethyl malonate Ph 

The conjugate addition of trialkylstannyl copper reagents to a,/3-acetylenic esters or /3-substituted acrylates, leads to the stereoselective preparation of potentially useful stannyl acrylates. The stereochemical course of the conjugate addition to a,/3-acetylenic esters was shown to be dependent on the constitution of the reagent and upon the structure of the substrate.  

Tricarbonyl(Ti -l-methylindole)chromium(0) can be lithiated by butyl-lithium at C-2, whereas the 2-trimethylsilyl analogues was lithiated predominantly at C-7. This selective C-7 lithiation permits substitution at this position in the indole nucleus by a range of functionalized electrophiles.  

Angular triquinanes can be synthesized starting from the readily available (5)-campholenaldehyde. The diazoketone formed from the y, 6-unsaturated acid 

Vicinal nitro-nitrates, readily available by reaction of olefins with nitrogen oxides and oxygen, are cleanly converted into terminal nitroalkanes by reduction with sodium borohydride in non-acidic conditions the intermediate nitro-olefin is reduced very rapidly, precluding dimerization.  

Oximes are reduced in benzene solution to hydroxylamines by sodium borohydride adsorbed on silica gel. In turn, silver carbonate on Celite cleanly oxidizes hydroxylamines to C-nitroso-compounds, isolate as nitroso-dimers no oximes are formed. Such dimers can be thermally dissociated to the more reactive monomers, whichare tautomerized to oximes on thermal or red-light treatment.  

A convenient synthesis of the spin-trap reagent, t-butyl nitroxide, has been reported a cautionary note on the use of such traps has been sounded, nitroxyl radicals being produced by reaction of the reagents with anions. 

A new reactive leaving group, 2,2,2-trifluoroethanesulphonate (tresylate) has been described solvolysis rates for a range of substrates are intermediate between those of the corresponding toluene-/-sulphonate and tri-fluoromethanesulphonate esters. 

This system, but with Mg in place of Al, was used in their earlier work on pinacol coupling [284]. 

In(III) salts were also featured prominently in many rearrangement reactions. The Lewis acidity of InCl3 was exploited by Ranu et al. to weaken C-O bonds 

Baker s yeast-mediated decarboxylation of substituted cinnamic acids. 

Baker s yeast seems to be compatible with several metal-containing or organometal-lic species, as shown for the reduction of ferrocenyl derivatives [459], arylketone-Cr(CO)3 complexes [460], indanone-Cr(CO)3 complexes [460], and a planar chiral metallocene aldehyde [461]. This approach allowed the synthesis of all four enantio-pure stereoisomers of l-ferrocenyl-l,3-butanediol [462] and of 1,1-disubstituted ferrocenyl amino alcohols [463]. The reduction of porphyrins and hemoglobins by baker s yeast is long known there are only a few reports for the reduction of inorganic materials [17]. 

There are only a few examples for the transformations of phosphorus-containing compounds witii baker s yeast [475, 476]. Thus baker s yeast has been used for the synthesis of a-aminophosphonates in a one-pot reaction from aldehyde, diethyl phosphite, and an amine [477]. The reduction of (3-chloro-2-oxo-propyl)-phosphonic acid diethyl ester by baker s yeast gave (2R)-3-chloro-2-hydrox5qjropyl-phosphoric acid diethyl ester, which could be used for the synthesis of (R)-camitine [478-480]. The 

Bialecka-Florjanczyk, A. U. Kapturowska, Genetically modified baker s yeast Saccharomyces cerevisiae in chemical S5mthesis and biotransformations, in D. Ekinci (Ed.) Chemical Biology, InTech, Rijeka, Groatia, 2012, pp. 211-234. 

Groger, W. Hummel, R. Metzner, Reduction asymmetric biocatalytic reduction of ketones, in E. M. Carreira, H. Yamamoto (Eds.) Synthetic Methods/Comprehensive Chirality, Elsevier B.V., Amsterdam, 2012, pp. 181-215. 

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Chapters V-X deal respectively with Heterocyclic and Alicyclic Compounds Miscellaneous Reactions Organic Reagents in Inorganic and Organic Chemistry Dyestuffs, Indicators and Related Compounds Some Physiologically-Active Compounds and Synthetic Polymers. Many of these preparations are of course intended for advanced students, but a mere perusal of the experimental details of selected preparations by those whose time for experimental work is limited may assist to impress them on the memory. Attention is particularly directed to the chapter... 

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