Prochiral cyclic

Scheme 6.77 Product range of the 12-catalyzed enantio- and diastereoselective Mannich addition of prochiral cyclic 1,3-dicarbonyl compounds to N-Boc-protected benzaldimine.

The push toward enaotiomerically-pure carbocyclic intermediates has led to the development of new methods for the enantiodifferentiation of inexpensive prochiral cyclic starting materials. For instance, Robert H. Morris of the University of Toronto recently reported (Organic Lett. 2005, 7, 1757) that a family of enantiomerically-pure Ru complexes originally developed for asymmetric transfer hydrogenation also mediate the enantioselective addition of malonatc to cyclohexenone. 

Enantioselective reduction of the prochiral cyclic acylsilane 42 with growing cells of the yeast Kloeckera corticis (ATCC 20109) yielded the optically active reduction product (R)-43 (Scheme 8)53. On a preparative scale, the l-silacyclohexan-2-ol (R)-43 was isolated in 60% yield with an enantiomeric purity of 92% ee. Repeated recrystallization of the biotransformation product from n-hexane raised the enantiomeric purity to 99% ee. 

A hydrolase-type reaction is otherwise rare in homogeneous catalysis, but the opening of prochiral cyclic anhydrides mediated by cinchona alkaloid in the presence of methanol leads to optically active hemiesters (Bolm, 2000). Very structurally di-... 

Most work on this subject is based on the use of alcohols as reagents in the presence of enantiomerically pure nucleophilic catalysts [1, 2]. This section is subdivided into four parts on the basis of classes of anhydride substrate and types of reaction performed (Scheme 13.1) - desymmetrization of prochiral cyclic anhydrides (Section 13.1.1) kinetic resolution of chiral, racemic anhydrides (Section 13.1.2) parallel kinetic resolution of chiral, racemic anhydrides (Section 13.1.3) and dynamic kinetic resolution of racemic anhydrides (Section 13.1.4). 

Desymmetrization of prochiral cyclic anhydrides In the presence of the chiral nucleophilic catalyst (e.g. A, Scheme 13.1, top) one of the enantiotopic carbonyl groups of the prochiral (usually meso) cyclic anhydride substrate is selectively converted into an ester. Application of catalyst B (usually the enantiomer or a pseudoenantiomer of A) results in generation of the enantiomeric product ester. Ideally, 100% of one enantiomerically pure product can be generated from the starting anhydride. No reports of desymmetrizing alcoholyses of acyclic meso anhydrides appear to exist in the literature. 

Asymmetric reduction of oi, -enones. Prochiral cyclic and acyclic a,p-enones are reduced by lithium aluminum hydride complexed with 1 to (S)-allylic alcohols in optical yields of 30-100% (equation 1). 

Asymmetric reduction of cyclic ketones. Prochiral cyclic ketones arc reduced to (R)-alcohols in 75-96% ee by a chiral hydride obtained by refluxing a mixture of lithium aluminum hydride, (— )-N-methylephedrine (I equiv.), and 2-ethylaminopyridine (2 cquiv.) in ether for 3 hours. Reduction of prochiral acychc ketones with this hydride also results in (R)-alcohols, but only in moderate yield. 

Chiral Reagent The diamino phenyl borane (6) derived from (15,25)-l,2-diaminocyclohexane has been used as a chiral proton source for the enantioselective protonation of prochiral cyclic lithium enolates, with ee s up to 93% (eq 9). (15,25)-1,2-Dia-minocyclohexane proved to be highly superior to 1,2-diphenyl ethylenediamine or bis-naphthylamine. 

Table 18 Enantioselective hydroxylation of prochiral cyclic ketone enolates. ... 

Table 11.7-1. Pig liver esterase-catalyzed enantiotopos-differentiating hydrolysis of prochiral cyclic dicarboxylic acid diesters in aqueous solution.

Table 11.1-11. Lipase-catalyzed enantiotopos-differentiating hydrolysis of prochiral cyclic diol dialkanoates in aqueous solution (CCL Candida cylindracea lipase, PFL Pseudomonas jiuorescens lipase, MML Mucor miehei lipase, CVL Chromobacterium viscosum lipase, PPL pig pancreas lipase, MJL Mucor javanicus lipase, RSL Rhizopus sp. lipase, PCL Pseudomonas cepacia lipase, CCL, Ceotricum candidum lipase, ANL Aspergillus niger lipase, FSPC Fusarium solani pisi cutinase, CRL Candida rugosa lipase, CAL-B Candida antarctica B lipase, LIP Pseudomonas sp. lipase-Toyobo, RDL Rhizopus delemar lipase, MSL Mucor sp. lipase, CAL Candida antarctica lipase, not specified).

Ma, L. and WiUiard, P.G. (2006) Synthesis of polymer-supported chiral lithium amide bases and application in asymmetric deprotonation of prochiral cyclic ketones. Tetrahedron Asymmetry, 17, 3021-3029. 

Hydroamination of prochiral cyclic dienes such as 1,3-cycloheptadiene (19) with aniline gave rise to 3-(A/ -phenylamino)cycloheptene (20) smoothly using Pd-PPh3. This reaction suggests the possibility of asymmetric amination. Actually Hartwig carried out successful asymmetric hydroamination of 1,3-cyclohexadiene with 4-aminobenzoate using (R, 7 )-(XIII-l) as a chiral ligand and obtained N-(3-cyclohexenyl)-4-aminobenzoate (21) in 83 % yield with 95 % ee [7],... 

The desymmetrization of prochiral cyclic anhydrides promoted by cinchona alkaloid derivatives is archetypal of this reaction class. First investigated by the groups of Oda and Aitken using cinchonine and quinine respectively, Bolm subsequently showed that cinchona alkaloids could desymmetrize prochiral anhydrides with exquisite enantioselectivities, with the pseudoenantiomeric... 

Fig. 13 Enantioselective hydrogenation of prochiral cyclic imides via desynunetiization...

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