Applications of the Reaction

Clearly, for symmetry reasons, the reverse process should also be considered. In fact, early versions of our reaction prediction and synthesis design system EROS [21] contained the reaction schemes of Figures 3-13, 3-15, and 3-16 and the reverse of the scheme shown in Figure 3-16. These four reaction schemes and their combined application include the majority of reactions observed in organic chemistry. Figure 3-17 shows a consecutive application of the reaction schemes of Figures 3-16 and 3-13 to model the oxidation of thioethers to sulfoxides. 

A simple application of the reaction may bo mentioned. Refluxing of (I) with 48 per cent, hydrobromic aeid and glacial acetic acid leads to hydrolysis and decarboxylation and the production of a mixture of the yl tctone yr-di-phonylbutyrolaotone (II) and the isomeric unsaturated acid yY-dlphenyl-vinylacotic acid (III) reduction by the Clemmonsen method or catalytically... 

As a further application of the reaction, the conversion of an endocyclic double bond to an c.xo-methylene is possible[382]. The epoxidation of an cWo-alkene followed by diethylaluminum amide-mediated isomerization affords the allylic alcohol 583 with an exo double bond[383]. The hydroxy group is eliminated selectively by Pd-catalyzed hydrogenolysis after converting it into allylic formate, yielding the c.ro-methylene compound 584. The conversion of carvone (585) into l,3-disiloxy-4-methylenecyclohexane (586) is an example[382]. 

Unstrained difluorotetramethyldisilane (84) gives the 1 1 adduct 85 as the main product and the 1 2 adduct 86 as a minor product[78,79]. On the other hand, the dimerization and double silylation of conjugated dienes with (Me3Si)2 catalyzed by PdCl2(PhCN)2 take place at 90" C[80]. Pd(dba)2 without phosphine is an active catalyst for the reaction, which proceeds in DMF to give 87 at room temperature[81], A five-membered ring is formed by the application of the reaction to the di-(2,4-pentadienyl)malonate (69)[82]. 

A two-step synthesis of indoles from o-nitrobenzaldehydes proceeds by condensation with nitromcthanc followed by reductive cyclization. Like the Leim-gruber Batcho method, the principal application of the reaction is to indoles with only carbocyclic substituents. The forniation of the o,p-dinitrostyrenes is usually done under classical Henry condensation conditions but KF/18-crown-6 in propanol was found to be an advantageous reaction medium for acetoxy-substituted compounds[1]. The o,p-dinitrostyrenes can also be obtained by nitration of p-nitrostyrenes[2]. 

The wide range of applicability of the reaction can be seen from Table I. Formaldehyde, aliphatic aldehydes, and aromatic and hetero-... 

A practical process had earlier been developed for the transformation of chlortetracycline (2) into tetracycline (1) by catalytic hydrogenolysis of the aromatic chloro group. Application of the reaction under suitable conditions to demethylchlortetra-... 

In addition to simple halides, the method was used to prepare chol-esteryl iodide (30%) and cyclohexyl iodide (34%) from the corresponding alcohols, thus demonstrating the applicability of the reaction to cyclic secondary alcohols. An early adaptation to carbohydrates was reported by Lee and El Sawi (75). They claimed that treatment of l,2 5,6-di-0-isopropylidene-D-glucofuranose (49) with triphenylphosphite methiodide... 

Application of the reaction to the 2-azidobenzoyl derivative of diethylene glycol monomethyl ether 92, in a mixture of tetrahydrofuran and diethylene glycol monomethyl ether as the nucleophile, affords 2-(2-methoxyethoxy)ethyl 2-[2-(2-methoxyethoxy)ethoxy]-37/-azepine-3-carbo-xylate (93), which displays metal cation complexing properties towards lithium, potassium, and. to a lesser extent, barium and calcium cations.198... 

In the synthesis of the taxol skeleton, two successive applications of the reaction on a masked equivalent for 2,3-bis(bromomethyl)-l,3-butadiene are the key steps59. 

An application of the reaction is the synthesis of ( )-norpseudoephedrine hydrochloride (4). Enantiomerically pure alcohol 3 is diastereoselectively converted into 4 without significant racemization [80% yield d.r. (1 R,2R)[(iR,2S) 96 4]2 ... 

As an application of the reaction, the synthesis of enantiomerically pure (-)-A-acetylam-phetamine (3) is described4. 

On the basis of the mechanistic pattern for oxymercuration-demercuration, predict the structure and stereochemistry of the alcohol(s) to be expected by application of the reaction to each of the following substituted cyclohexenes. 

Scheme 5.15 shows some examples of the Shapiro reaction. Entry 1 is an example of the standard procedure, as documented in Organic Syntheses. Entry 2 illustrates the preference for the formation of the less-substituted double bond. Entries 3, 4, and 5 involve tosylhydrazone of a, (3-unsaturated ketones. The reactions proceed by a -deprotonation. Entry 6 illustrates the applicability of the reaction to a highly strained system. 

The reaction in Entry 5 is a case in which the thermal conditions were preferable to the basic conditions because of the base sensitivity of the product. Entries 6 to 10 show anionic oxy-Cope reactions. Entries 6 and 7 are early examples of the application of the reaction in synthesis. Entries 8 and 9 involve rearrangements of bicyclo[2.2.1]hept-2-en-2-ol derivatives to give cw-fused bicyclo[4.3.0]non-7-en-3-ones. 

A number of these alkylation reactions are illustrated in Scheme 9.2. Entries 1 and 2 are typical examples of a-halo ester reactions. Entry 3 is a modification in which the highly hindered base potassium 2,6-di-f-butylphenoxide is used. Similar reaction conditions can be used with a-halo ketones (Entries 4 and 5) and nitriles (Entry 6). Entries 7 to 9 illustrate the use of diazo esters and diazo ketones. Entry 10 shows an application of the reaction to the synthesis of an amide. 

Abstract Recent advances in synthetic aspects of the rhodium-catalyzed hydroformylation of alkenes are reviewed. Emphasis is given to practical improvements, efficient new catalysts for regioselective and enantioselective hydroformylation, and to applications of the reaction in organic synthesis. Furthermore, new developments in directed hydroformylation are covered as well as new approaches toward efficient hydroformylation catalysts employing the concept of self-assembly. 

Representative of recent applications of the reaction to the synthesis of heterocycles are the photodehydrochlorination of chlorobenzo[b]thiophen (347) to give the fused pyrimidone 348,287 the photoelimination of HI from iodobenzene derivatives 349 to give the benzazepines 350,288 and the synthesis of the medium ring aza-heterocycle 351 by irradiation of the chloro precursor 352.289 Included among the many other examples of... 

Palladium-catalyzed allylic substitution reactions are popular in the chemical community and the number of applications of the reaction, perhaps in particular for asymmetric procedures, continues to grow [53]. The efficiency of asymmetric chemistry is best described in terms of the enantiomeric excess (ee) of the reaction, and it... 

These studies have allowed the spectroscopic identification of a number of electronically excited states of the metal oxides, but there appear to have been no analytical applications of the reactions to date. The emitting states, as summarized by Toby [14], are CaO(A n), SrO(ATl), PbO(a32+, b32+), ScO(C2II), YO(C2n), FcO(C ), A10(A2ni B2X+), and BaO(A i)1, D 2+). Nickel carbonyl reacts with ozone to produce chemiluminescence from an excited electronic state of NiO, which is probably produced in the Ni + 03 reaction [42, 43],... 

Diels, O. Alder, K. Justus Liebigs Arm. Chem. 1928, 460, 98. Otto Diels (Germany, 1876-1954) and his stndent, Kurt Alder (Germany, 1902—1958), shared the Nobel Prize in Chemistry in 1950 for development of the diene synthesis. In this article they claimed their territory in applying the Diels-Alder reaction in total synthesis We explicitly reserve for ourselves the application of the reaction developed by us to the solution of such problems. ... 

Complex bioactive compounds made following the application of the reaction... 

Significant synthetic application of the reaction products of the acridizinium ion with alkenes has been made by Fields et Although... 

Application of the reaction sequence periodate oxidation - cyclization with nitromethane hydrogenation to rt6o-nucleosides provides a general synthetic entry to 3-aminohexosyl p5nimidines i7-20) and purines 21-as) which otherwise are not readily accessible. That this sequence can be extended to nitroethane to give 3 -C-methyl branched aminosugar nucleosides, has been demonstrated, starting from uridine 4.10,26)... 

The Favorskii reaction has been used to effect ring contraction in the synthesis of strained ring compounds. Entry 4 in Scheme 10.3 illustrates this application of the reaction. With 7,7 -dihalo ketones, the rearrangement is accompanied by dehydrohalo-genation to yield an a,/ -unsaturated ester, as illustrated by entry 3 in Scheme 10.3. 

An interesting application of the reaction with sulfuryl chloride consisted in the synthesis of a fully chlorinated hexoside.27 Treatment of methyl 2-chloro-2-deoxy-/3-D-galactopyranoside with sulfuryl chloride and pyridine in chloroform, followed by heating of the product with an excess of pyridinium chloride, afforded a tetrachloride, presumably methyl 2,3,4,6-tetrachloro-2,3,4,6-tetradeoxy-/3-D-allopy-ranoside. 

The first application of the reaction in the carbohydrate field was to the chlorination of l,2 3,4-di-0-isopropylidene-a-D-galactopyran-ose65(b) treatment of this compound with triphenylphosphine in carbon tetrachloride for 3 hours at reflux temperature gave the corresponding 6-chloro-6-deoxy derivative66 in good yield, and a small proportion of 6-deoxy-l,2 3,4-di-0-isopropylidene-/3-L-arafcino-hex-... 

---