Nucleophiles carbon,

An aromatic carbon atom of an electron rich benzene derivative can also trap seleniranium intermediates. Deziel has reported recently, that the reaction of 

230 by methanol or by the aromatic carbon atom, respectively. The addition product 231 can be transformed into the cyclization product 232, via the seleniranium intermediate 230, by treatment with trifluoromethanesulfonic acid. The tetrahydronaphthalene derivative 232 was obtained with 70% yield in 98% dia-stereomeric excess. 

The most investigated ctirbon nucleophiles are p-dicarbonyl or related enolates, generally cyclic in structure and fully substituted (i. e., tertiary) at the nucleophilic carbon. The products of reaction of these enolates with alkynyliodonium salts are p-dicarbonyl compounds, and their formation is mostly dependent upon the migratory aptitude of the substituent on the ethynyliodonium salt. 

A similar interaction of (2-oxoazetidinyl)malonates 51 with sila-ethynyliodonium triflate (52) in THF at — 78°C affords the corresponding ethynylmalonates, 53, in 92% yield [50] [Eq. (20)1. 

Analogously, malonate 54 gave exclusively alkynylation products 55 in 33-95% yields with a variety of alkynyliodonium triflates [Eq. (21)] [20 a]. 

Furans 61 are obtained if activated carbonyl compounds with acidic methylene protons 60 are employed as nucleophiles [51). In these cases, insertion of the carbene into the enolic 0-H bond occurs [Eq. (23)]. 

Reaction of vinylcopper reagents, 62, with alkynyliodonium tosylates results in conjugated enyne 63, [53] [Eq. (24)]. The reaction is stereospecific with retention of olefin geometry. By appropriate order of addition, either of the two possible isomeric trisubstituted olefin isomers, 63, can be obtained in good isolated yields and excellent ( 99%) stereoselectivity. Likewise, conjugated diynes, 65, are obtained [54] in the reaction of dialkynylcuprates, 64, with alkynyliodonium tosylates [Eq. (25)]. This method may be used for the preparation of unsym-metrical diynes. The mechanism of these coupling reactions is not understood at present. 

The reaction of allyl acetates, halides and sulfides derived from the MBH adducts with carbon nucleophiles has been well investigated. In fact, Drewes and co-workers first reported the utilization of the nucelophilic addition of a MBH adduct in the stereoselective synthesis of (2 )-integerrinecic acid, a natural product with a trisubstituted olefinic moiety. Subsequently, Drewes et a/ 34,40d,ii9 carried out stereo- and regioselective addition of carbon nucleophiles derived from ethyl acetoacetate, malonate and phenylacetylide derivatives to various MBH halides and MBH acetates. 

Rezgui and El Gaied have reported an interesting synthesis of bicyclic dienones 190 in sequential and also in a one-pot process via the reaction of 

Amri and co-workers have prepared 2-methylenealkanoate 202 via the treatment of ethyl 2-acetoxymethylprop-2-enoate with Grignard reagents in the 

The addition of several trialkyl or triarylindium reagents to the acetates of MBH adducts proceeds readily under the catalysis of copper and palladium derivatives. The reactions of trialkylindiums are catalyzed efficiently by Cul whereas additions of triarylindiums produce better results with Pd(PPh3)4. The reactions with 3-acetoxy-2-methylenealkanoates provide ( )-alkenes 213, 

An efficient procedure for propenylation of MBH acetates in the presence of allyl bromide, zinc, copper iodide and silica gel has been reported by Srihari, leading to substituted 1, 5-dienes 215, in good yields, that may find further use in synthetic chemistry. Recently, it was found acetates of MBH adducts 

The carbocation that is formed upon protonation of a carbonyl compound can lose H+ from the a-carbon to give an enol. Enols are good nucleophiles. Thus, under acidic conditions, carbonyl compounds are electrophilic at the carbonyl C 

Enols are particularly reactive toward carbonyl compounds and toward electrophilic alkenes such as a, 8-unsaturated carbonyl compounds. For example, the Robinson annulation proceeds under acidic conditions as well as under basic conditions, as shown in the next example. Under acidic conditions, the electrophilic carbonyl compound is protonated to make a carbocation before it is attacked by the enol. 

The Robinson annulation consists of a Michael addition, an aldol reaction, and a dehydration. In the Michael addition the nucleophilic ketone is converted into an enol by protonation and deprotonation. The enol then adds to the protonated Michael acceptor. Deprotonation of the positively charged O, protonation of C of the enol, and deprotonation of O then give the overall Michael addition product. 

In the dehydration the ketone is first converted into an enol by protonation and deprotonation. Protonation of the alcohol O is then followed by an El elimination reaction (loss of H2O and then loss of H+) to give the product. It s not absolutely necessary to convert the ketone into an enol before executing El elimination, but the intermediate carbocation is much lower in energy when the ketone is in the enol form. 

The carbocation that is formed upon protonation of a carbonyl compound can lose H+ from the a-carbon to give an enol. Enols are good nucleophiles. Thus, under acidic conditions, carbonyl compounds are electrophilic at the carbonyl C and nucleophilic at the a-carbon and on oxygen, just like they are under basic conditions. Resonance-stabilized carbonyl compounds such as amides and esters are much less prone to enolize under acidic conditions than less stable carbonyl compounds such as ketones, aldehydes, and acyl chlorides in fact, esters and amides rarely undergo reactions at the a-carbon under acidic conditions. 

Problem 3.18. Draw a mechanism for the following Hell-Vollhard-Zelinsky reaction. 

The combination of silyl enol ethers and fluoride ion provides more reactive anions to give alkylated nitro compounds in good yields after oxidation with DDQ, as shown in Eq. 9.22.36 This process provides a new method for synthesis of indoles and oxyindoles (see Chapter 10, Synthesis of Heterocyclic Compounds). 

Alkyl lithium and alkyl Grignard reagents react with aromatic nitro compounds in a similar way to give alkylated products (Eq. 9.23).37 

Typical base/solvent system used for the reaction KOH, NaOH, f-BuOK/DMF, THF, NH3 (/). 

Carbanions of a-chloroalkyl phenyl sulfones react with nitrobenzenes to effect direct nucleophilic replacement of hydrogens located ortho and para to the nitro group (Eq. 9.24).38 A very important feature is that VNS of hydrogen usually proceeds faster than conventional SNAr of halogen located in equally activated positions (Eq. 9.25).38 The rule that VNS of 

Alkyl 2-chloropropionates react with nitroaromatic compounds on treatment with base to give alkyl 2-(4-nitroaryl)propionates in good yield (Eq. 9.26).40 

Alkyl Lithium and alkyl Gngnard reagents react with way to give alkylated products fEq 9 23  

The VNS reacdon of 3-nitrothiophene occurs only at the C-2 posidon for example, VNS vdth chloromethylphenylsulfone gives 2-phenylsulfonylinethyl-3-nitrothiophenein 93% yield fEq. 9.271.  

This section has been the subject of many papers and it is covered very well by CHEC(1984) 1984CHEC(2)1 and CHEC-IK1996) 1996CHEC-II(6)1 . 

10mol% chiral pyrrolidine catalyst, NEts, CH2CI2, -40 °C, overnight 

With triphosgene also 2-trichloromethoxycarbonyl derivatives were formed. More examples on nucleophilic substitution of hydrogen by cyano in pyridazin-3(2//)-ones have also appeared. Substrates 70 and 71 were used in 

Pyridine reacts with lithium alkyls and aryls under rather vigorous conditions (e.g. xylene at 100°C) to afford 2-alkyl- and 2-aryl-pyridines. The reaction proceeds by way of the corresponding dihydropyridines (e.g. 275 or a tautomer), and these may be isolated at lower temperatures. The less reactive Grignard reagents give poorer yields of the same products. 

Benzopyridines are attacked by organometallic compounds at a position a to the nitrogen unless both a-positions are blocked. The dihydro derivatives of quinoline and isoquinoline are more stable and less easily aromatized than those from pyridine, and are hence more frequently isolated. 

Diazines also react more readily than pyridine. Thus, pyrimidine and phenylmagnesium bromide give adduct (276), which can be oxidized to 4-phenylpyrimidine. Aryl- and heteroaryl-lithium reagents at low temperature (79AG1, 80RTC234) add across the 3,4-double bond of pyrimidines to give dihydropyrimidines. 2,5-Dimethylpyrazine and lithium aryls afford the 3-aryl derivatives. 

Grignard reagents add to 1,2,4-triazines. Initial attack at the 5-position is favored (277 — 278 — 279) if this position is substituted the nucleophile adds to the 6-position, and finally to the 3-position. Starting from the parent 1,2,4-triazine, 3,5,6-triaryl-l,2,4-triazines (280) have been prepared by successive addition of Grignard reagents to the ring and oxidation of the dihydro-1,2,4-triazine so formed. 

The regioselectivity of Grignard addition to /V-acylpyridinium salts can often be controlled by changing the conditions. Thus, e.g., the regioselectivity towards C-4 addition products can be enhanced by the presence of catalytic amounts of copper salts. Direct reaction of salt (281, R = OMe) with lithium dialkyl cuprate gives also almost exclusively the 1,4-dihydro product (283, R = OMe, R1 = Me). 

The reactions of Grignard and organolithium reagents, especially with pyridazine derivatives, was discussed in CHEC-I 84CHEC-i(3B)i . Pyridazine derivatives tend to undergo addition to C- 

4(5) to give dihydro products while some lithium reagents may add to C-3 (this may depend on the solvent). Some of these reactions are complicated by the hydrolytic and/or oxidative stability of the initial adducts. With 3(2//)-pyridazinones, addition of PhLi or PhMgBr appears to occur at the 6-, 

and 5-positions to give di- or tetrahydro adducts, while 1 (2//)-phthalazinones give addition at the 

Among examples of reactions of (benzo)pyridazines with activated CH reagents reviewed in CHEC-I 84CHEC-l(3B)i are the methylation and ethylation of 3(27/)-pyridazinones, substituted with, for example, 4-carboxy, by the corresponding nitroalkanes in DMSO, and the application of the Reissert reaction to phthalazines. More recent examples, including those utilising an acylated intermediate similar to the Reissert reaction, are discussed in Section 6.01.5.4.5.iii. 

6-Dichloropyridazine reacts with the potassium enolate of diisopropyl ketone by nucleophilic 

Active methylene groups undergo Mitsunobu reactions with alcohols. Thus, when ethyl cyanoacetate is reacted with ethyl L-lactate, diethyl 2-cyano-3-methylsuccinate (113) is formed in 61% yield [42]. Acidic hydrolysis furnishes (5)-( — )-methylsuccinic acid (114) in 29% yield with an optical purity of 99% [43]. 

A close analog, 115, is critical in establishing the stereochemistry of the tetramic acid subunit (119) of streptolydigin [44]. Amination of 115 followed by nitrile hydration of 116 

This reaction has been screened with a tremendous quantity of chiral catalysts and indeed is routinely used to test the performance of new ligands in spite of its limited synthetic usefulness and that good or bad results with this system do not necessarily translate to other substrates.  

An early report of Bosnich and co-workers describes that DiPAMP yields a racemic alkylated product but since then many mono- and bidentate P-ste-reogenic ligands have been used in the benchmark reaction for allylic substitution with very good results in some cases. Table 8.3 lists some the systems giving rise to good conversions and enantioselectivities. 

The diminished enantioselectivity of this substrate is due to the much smaller steric hindrance of methyl groups to compared to phenyl groups and to the absence of 7i-stacking interactions of 14 with the chiral ligands. Ferrocenyl ligands 16 and biarylic 17 have been used, leading to good yields but low stereoselectivities. 

With these substrates, achiral 1-24 is strongly favoured with Pd catalysts (for other metals, the situation is different) except in special cases. Diazaphos-pholidine-oxazoline 20 shows moderate performance in the alkylation of butenyl acetate compared to the exceptionally good results with SiocPhox phosphonamidate ligands for alkyl- and aryl-substituted substrates. The same type of ligands have also been applied to the alkylation of other challenging substrates such as polyenyl esters and acyclic ketone enolates.  

They are also useful in the kinetic resolution of 2,3-dihydro-4-quinolones by enantioselective allylic allylation.  

Hydride cannot function as a ieaving group because it is too strongiy basic. 

12-crown-4 is added to the reaction mixture, the lithium ions are solvated (as described in Section 14.4), and reduction does not occur. Clearly, the hthium cation plays a pivotal role in the mechanism. However, a full treatment of the mechanism of hydride reducing agents is beyond the scope of this text, and the simplified version above will suflSce. 

The reduction of a carbonyl group with LAH or NaBH4 is not a reversible process, because hydride does not function as a leaving group. Notice that the mechanism above employs oneway arrows (rather than equilibrium arrows) to signify that the reverse process is insignificant. 

31 Predict the major product for each of the following reactions  

32 When 2 moles of benzaldehyde are treated with sodium hydroxide, a reaction occurs in which 1 mole of benzaldehyde is oxidized (giving benzoic acid) while the other mole of benzaldehyde is reduced (giving benzyl alcohol)  

Although there are a number of interesting organic nitriles, the main value of this process lies in the other functionalities into which we can convert the CN group. Reduction with lithium 

Grignard reagents, organomagnesium halides, are prepared by the reaction of metallic magnesium with a wide range of organic halides (reaction 9.3). Dry ether type solvents are essential. 

However, Grignard reagents do react well with epoxides, opening them at the less hindered site, in an 8 2 process with clean inversion of configuration. This reaction can be used for 

FIGURE 9.63 Synthesis of hydrocarbons by coupling of Grignard reagents with very reactive alkyl 

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Alkenes in (alkene)dicarbonyl(T -cyclopentadienyl)iron(l+) cations react with carbon nucleophiles to form new C —C bonds (M. Rosenblum, 1974 A.J. Pearson, 1987). Tricarbon-yi(ri -cycIohexadienyI)iron(l-h) cations, prepared from the T] -l,3-cyclohexadiene complexes by hydride abstraction with tritylium cations, react similarly to give 5-substituted 1,3-cyclo-hexadienes, and neutral tricarbonyl(n -l,3-cyciohexadiene)iron complexes can be coupled with olefins by hydrogen transfer at > 140°C. These reactions proceed regio- and stereospecifically in the successive cyanide addition and spirocyclization at an optically pure N-allyl-N-phenyl-1,3-cyclohexadiene-l-carboxamide iron complex (A.J. Pearson, 1989). 

Formation of a Tr-allylpalladium complex 29 takes place by the oxidative addition of allylic compounds, typically allylic esters, to Pd(0). The rr-allylpal-ladium complex is a resonance form of ir-allylpalladium and a coordinated tt-bond. TT-Allylpalladium complex formation involves inversion of stereochemistry, and the attack of the soft carbon nucleophile on the 7r-allylpalladium complex is also inversion, resulting in overall retention of the stereochemistry. On the other hand, the attack of hard carbon nucleophiles is retention, and hence Overall inversion takes place by the reaction of the hard carbon nucleophiles. 

Alkenes coordinated by Pd(II) are attacked by carbon nucleophiles, and carbon-carbon bond formation takes place. The reaction of alkenes with carbon nucleophiles via 7r-allylpalladium complexes is treated in Section 3.1. 

Facile reaction of a carbon nucleophile with an olefinic bond of COD is the first example of carbon-carbon bond formation by means of Pd. COD forms a stable complex with PdCl2. When this complex 192 is treated with malonate or acetoacetate in ether under heterogeneous conditions at room temperature in the presence of Na2C03, a facile carbopalladation takes place to give the new complex 193, formed by the introduction of malonate to COD. The complex has TT-olefin and cr-Pd bonds. By the treatment of the new complex 193 with a base, the malonate carbanion attacks the cr-Pd—C bond, affording the bicy-clo[6.1,0]-nonane 194. The complex also reacts with another molecule of malonate which attacks the rr-olefin bond to give the bicyclo[3.3.0]octane 195 by a transannulation reaction[l2.191]. The formation of 194 involves the novel cyclopropanation reaction of alkenes by nucleophilic attack of two carbanions. 

The phenylation of styrene with phenyl Grignard reagents as a hard carbon nucleophile proceeds in 75% yield in the presence of PdCl2, LiCl, and K2CO3 at room temperature to give stilbene (207). Selection of the solvent is crucial and the best results are obtained in MeCN. The reaction can be made catalytic by the use of CuCl2[197]. Methyllithium reacts with styrene in the presence of Pd(acac)2 or Pd(OAc)2 to give /3-methylstyrene (208) in 90% yield[198]. 

TT-Aliylpalladium chloride reacts with a soft carbon nucleophile such as mal-onate and acetoacetate in DMSO as a coordinating solvent, and facile carbon-carbon bond formation takes place[l2,265], This reaction constitutes the basis of both stoichiometric and catalytic 7r-allylpalladium chemistry. Depending on the way in which 7r-allylpalladium complexes are prepared, the reaction becomes stoichiometric or catalytic. Preparation of the 7r-allylpalladium complexes 298 by the oxidative addition of Pd(0) to various allylic compounds (esters, carbonates etc.), and their reactions with nucleophiles, are catalytic, because Pd(0) is regenerated after the reaction with the nucleophile, and reacts again with allylic compounds. These catalytic reactions are treated in Chapter 4, Section 2. On the other hand, the preparation of the 7r-allyl complexes 299 from alkenes requires Pd(II) salts. The subsequent reaction with the nucleophile forms Pd(0). The whole process consumes Pd(ll), and ends as a stoichiometric process, because the in situ reoxidation of Pd(0) is hardly attainable. These stoichiometric reactions are treated in this section. 

The enamine 315 as a carbon nucleophile reacts with 7r-allylpalladium complexes to give allyl ketones after hydrolysis[265],... 

Hard carbon nucleophiles of organometallic compounds react with 7r-allyl-palladium complexes. A steroidal side-chain is introduced regio- and stereo-selectively by the reaction of the steroidal 7T-allylpalladium complex 319 with the alkenylzirconium compound 320[283]. 

The TT-allylpalladiLim complexes formed as intermediates in the reaction of 1,3-dienes are trapped by soft carbon nucleophiles such as malonate, cyanoacctate, and malononitrile[ 177-179). The reaction of (o-iodophenyl-methyl) malonate (261) with 1,4-cyclohexadiene is terminated by the capture of malonate via Pd migration to form 262. The intramolecular reaction of 263 generates Tr-allylpalladium, which is trapped by malononitrile to give 264. o-[odophenylmalonate (265) adds to 1,4-cyciohexadiene to form a Tr-allylpalladium intermediate via elimination of H—Pd—X and its readdition, which is trapped intramolecularly with malonate to form 266)176]. 

Allenes also react with aryl and alkenyl halides, or triflates, and the 7r-allyl-palladium intermediates are trapped with carbon nucleophiles. The formation of 283 with malonate is an example[186]. The steroid skeleton 287 has been constructed by two-step reactions of allene with the enol trillate 284, followed by trapping with 2-methyl-l,3-cyclopentanedione (285) to give 286[187]. The inter- and intramolecular reactions of dimethyl 2,3-butenylmalonate (288) with iodobenzene afford the 3-cyclopentenedicarboxylate 289 as a main product) 188]. 

Formation of ketones. Ketones can be prepared by the carbonylation of halides and pseudo-halides in the presence of various organometallic compounds of Zn, B, Al, Sn, Si, and Hg, and other carbon nucleophiles, which attack acylpalladium intermediates (transmetallation and reductive elimination). 

Arylation or alkenylation of soft carbon nucleophiles such as malonate is carried out by using a copper catalyst, but it is not a smooth reaction. The reaction of malononitrile, cyanoacetate, and phenylsulfonylacetonitrile with aryl iodide is possible by using a Pd catalyst to give the coupling products. 

Application of 7r-allylpalladium chemistry to organic synthesis has made remarkable progress[l]. As deseribed in Chapter 3, Seetion 3, Tt-allylpalladium complexes react with soft carbon nucleophiles such as maionates, /3-keto esters, and enamines in DMSO to form earbon-carbon bonds[2, 3], The characteristie feature of this reaction is that whereas organometallic reagents are eonsidered to be nucleophilic and react with electrophiles, typieally earbonyl eompounds, Tt-allylpalladium complexes are electrophilie and reaet with nucleophiles such as active methylene compounds, and Pd(0) is formed after the reaction. 

In addition, a catalytic version of Tt-allylpalladium chemistry has been devel-oped[6,7]. Formation of the Tr-allylpalladium complexes by the oxidative addition of various allylic compounds to Pd(0) and subsequent reaction of the complex with soft carbon nucleophiles are the basis of catalytic allylation. After the reaction, Pd(0) is reformed, and undergoes oxidative addition to the allylic compounds again, making the reaction catalytic.-In addition to the soft carbon nucleophiles, hard carbon nucleophiles of organometallic compounds of main group metals are allylated with 7r-allylpalladium complexes. The reaction proceeds via transmetallation. These catalytic reactions are treated in this chapter. 

In addition to the catalytic allylation of carbon nucleophiles, several other catalytic transformations of allylic compounds are known as illustrated. Sometimes these reactions are competitive with each other, and the chemo-selectivity depends on reactants and reaction conditions. 

The stereochemistry of the Pd-catalyzed allylation of nucleophiles has been studied extensively[5,l8-20]. In the first step, 7r-allylpalladium complex formation by the attack of Pd(0) on an allylic part proceeds by inversion (anti attack). Then subsequent reaction of soft carbon nucleophiles, N- and 0-nucleophiles proceeds by inversion to give 1. Thus overall retention is observed. On the other hand, the reaction of hard carbon nucleophiles of organometallic compounds proceeds via transmetallation, which affords 2 by retention, and reductive elimination affords the final product 3. Thus the overall inversion is observed in this case[21,22]. 

Interestingly, the allylation of a stabilized carbon nucleophile has been found to be reversible. Complete isomerization of dimethyl methylmalonate, involving bis-allylic C—C bond cleavage, from a secondary carbon 38 to a primary carbon 39 was observed by treatment with a Pd catalyst for 24 h. The C—C bond cleavage of a monoaliylic system proceeds slowly[40]. 

The intramolecular allylation of soft carbon nucleophiles with allylic acetates as a good cyclization method has been extensively applied to syntheses of various three, four, five and six-membered rings, and medium and macrocyclic compounds[44]. Only a few typical examples of the cyclizations are treated among numerous applications. 

The allyl-substituted cyclopentadiene 122 was prepared by the reaction of cyclopentadiene anion with allylic acetates[83], Allyl chloride reacts with carbon nucleophiles without Pd catalyst, but sometimes Pd catalyst accelerates the reaction of allylic chlorides and gives higher selectivity. As an example, allylation of the anion of 6,6-dimethylfulvene 123 with allyl chloride proceeded regioselectively at the methyl group, yielding 124[84]. The uncatalyzed reaction was not selective. 

The allylic esters 189 and 191 conjugated with cyclopropane undergo regio-selective reactions without opening the cyclopropane ring. The soft carbon nucleophiles are introduced at the terminal carbon to give 190, and phenylation with phenylzinc chloride takes place on the cyclopropane ring to form 192[120]. 

Asymmetric allylation of carbon nucleophiles has been carried out extensively using Pd catalysts coordinated by various chiral phosphine ligands and even with nitrogen ligands, and ee > 90% has been achieved in several cases. However, in most cases, a high ee has been achieved only with the l,3-diaryl-substitiitcd allylic compounds 217, and the synthetic usefulness of the reaction is limited. Therefore, only references are cited[24,133]. 

Since allylation with allylic carbonates proceeds under mild neutral conditions, neutral allylation has a wide application to alkylation of labile compounds which are sensitive to acids or bases. As a typical example, successful C-allylation of the rather sensitive molecule of ascorbic acid (225) to give 226 is possible only with allyl carbonate[l 37]. Similarly, Meldrum s acid is allylated smoothly[138]. Pd-catalyzed reaction of carbon nucleophiles with isopropyl 2-methylene-3,5-dioxahexylcarbomite (227)[I39] followed by hydrolysis is a good method for acetonylation of carbon nucleophiles. 

Some nucleophiles other than carbon nucleophiles are allylated. Amines are good nucleophiles. Diethylamine is allylated with allyl alcohol[7]. Allylammes are formed by the reaction of allyl alcohol with ammonia by using dppb as a ligand. Di- and triallylamines are produced commercially from allyl alcohol and ammonia[l74]. 

Cross-Couplinf of Allylic Groups with Hard Carbon Nucleophiles... 

Dienes and allylarcncs can be prepared by the Pd-catalyzcd coupling of allylic compounds with hard carbon nucleophiles derived from alkenyl and aryl compounds of main group metals. Allylic compounds with various leaving groups can be used. Some of them are unreactive with soft nucleophiles, but... 

The reaction of 2,3-butadienyl acetate (843) with soft carbon nucleophiles such as dimethyl malonate gives dimethyl 2,3-butadienylmalonate (844)[520]. On the other hand, the reaction of the 2,3-butadienyl phosphate 845 with hard carbon nucleophiles such as Mg and Zn reagents affords the 2-allcyl-1,3-butadiene 846[520,521]. The 3-methoxy-1,3-butadiene 848 is obtained by the reaction of the 2-methoxy-2,3-butadienyl carbonate 847 with organozinc reagent. 

When a bidentate phosphine is used as a ligand for the reaction of J-keto esters or /i-diketones, no dimerization takes place. Only a 2-butenyl group is introduced to give 68[49,62], Substituted dienes such as isoprene, 1,3-cyclohexa-diene, and ocimene react with carbon nucleophiles to give a mixture of possible regio- and stereoisomers of 1 1 adducts when dppp is used as a ligand[63,64]. 

Among several propargylic derivatives, the propargylic carbonates 3 were found to be the most reactive and they have been used most extensively because of their high reactivity[2,2a]. The allenylpalladium methoxide 4, formed as an intermediate in catalytic reactions of the methyl propargylic carbonate 3, undergoes two types of transformations. One is substitution of cr-bonded Pd. which proceeds by either insertion or transmetallation. The insertion of an alkene, for example, into the Pd—C cr-bond and elimination of/i-hydrogen affords the allenyl compound 5 (1.2,4-triene). Alkene and CO insertions are typical. The substitution of Pd methoxide with hard carbon nucleophiles or terminal alkynes in the presence of Cul takes place via transmetallation to yield the allenyl compound 6. By these reactions, various allenyl derivatives can be prepared. 

In addition to alcohols, some other nucleophiles such as amines and carbon nucleophiles can be used to trap the acylpalladium intermediates. The o-viny-lidene-/j-lactam 30 is prepared by the carbonylation of the 4-benzylamino-2-alkynyl methyl carbonate derivative 29[16]. The reaction proceeds using TMPP, a cyclic phosphite, as a ligand. When the amino group is protected as the p-toluenesulfonamide, the reaction proceeds in the presence of potassium carbonate, and the f>-alkynyl-/J-lactam 31 is obtained by the isomerization of the allenyl (vinylidene) group to the less strained alkyne. 

No reaction of soft carbon nucleophiles takes place with propargylic acet-ates[37], but soft carbon nucleophiles, such as / -keto esters and malonates, react with propargylic carbonates under neutral conditions using dppe as a ligand. The carbon nucleophile attacks the central carbon of the cr-allenylpal-ladium complex 81 to form the rr-allylpalladium complex 82, which reacts further with the carbon nucleophile to give the alkene 83. Thus two molecules of the a-monosubstituted /3-keto ester 84, which has one active proton, are... 

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