Alcohol Benzylic, enantioselective allylation

The scope of the Pd(II)-catalyzed enantioselective oxidation system has been the most extensively explored. The conditions are able to selectively oxidize a wide variety of benzylic alcohols with high selectivity (Table 1, entries 1-3,7) [4, 6-8]. Electron-withdrawing groups on the aromatic ring lead to lower oxidation rates and selectivity. Other types of aromatics can also be resolved successfully (entry 9), although N-containing heterocycles have little reactivity. Allylic and cyclopropyl alcohols are also well tolerated in the resolution (entries 5, 6), occasionally with extraordinary levels of selectivity (entry 4) [19]. As already mentioned, Sigman has shown that use of t-BuOH as solvent can also lead to useful enantioselective oxidation for some saturated alkyl alcohols (entries 10-12). 

A simple, divergent, asymmetric synthesis of the four stereomers of the 3-amino-2,3,6-trideoxy-L-hexose family has been proposed by Dai and co-workers [523] which is based on the Katsuki-Sharpless asymmetric epoxidation of allylic alcohols ( )-408. iV-Trifluoroacetyl-L-daunosamine, A-trifluoro acetyl-L-acosamine, A-benzoyl-D-acosamine, and A-benzoyl-D-nitrosamine have been derived from methyl sorbate via the methyl 4,5-epoxy-( )-hex-2-enoates obtained via a chemoenzymatic method [524]. Application of the Katsuki-Sharpless enantioselective epoxidation to racemic mono-O-benzylated divinylglycol has allowed us to prepare enantiomerically pure L-lyxo and D-/yro-pentoses and analogs [525,526,527, 528],... 

This promising result have led Vedejs and Daugulis to design and synthesize efficient catalysts lb-c [16] belonging to the P-aryl-phospha-bicyclo [3.3.0] octane (PBO) family for the enantioselective catalyzed acylation of benzylic alcohols 2b-d or unconstrained allylic alcohols 2e-l. 

The effect of solvent was also studied and complexing solvents such as THF or Et20 inhibited the cyclopropanation reaction. Furthermore, the presence of an unprotected allylic alcohol was found to be essential, since the methyl or benzyl ether derived from cinnamyl alcohol afforded almost racemic cyclopropanes. This method has also been extended to the enantioselective cyclopropanation of vinylsilanes and -stannanes (Scheme 4) [13]. The corresponding optically active silyl- and stannyl-substituted cyclopropyhnethanols were obtained in the presence of the chiral N,iV-bis(p-nitrobenzenesulfonyl)-l,2-cyclohexane-diamine 9. 

Resolution by transesterification. Using vinylic acetates to esterify allyl alcohols, propargyl alcohols, 2-phenylthiocycloalkanols, a-hydroxy esters," methyl 5-hydroxy-2-hexenoates, and 2-substituted 1,3-propanediols, the enantioselective esterification provides a means of separation of optical isomers. Vinyl carbonates are also resolved by lipase-mediated enantioselective conversion to benzyl carbonates. Other esters that have also been used in the kinetic resolution include 2,2,2-tri-fluoroethyl propionate. There is a report on a double enantioselective transesterification" of racemic trifluoroethyl esters and cyclic meso-diols by lipase catalysis. 

Asymmetric allylation of aldehydes with allyhc agents catalyzed by Lewis acid is a practical method for synthesizing optically active hranoallylic alcohols [10]. The chloro complex 1 serves as an efficient catalyst for asymmetric allylation of aldehydes with allylstannane [8, 9, 11]. In the presence of 5 mol% of the benzyl-phebox-Rh complex 1-Bn, the coupling reaction of benzaldehyde with allyltributyl-stannane in CH2CI2 at room temperature proceeded smoothly to provide the corresponding homo-aUyl alcohol 7a in 88% yield with 61% ee (Scheme 2). When methaUylstannane was subjected to the reactiOTi, enantioselectivity of the allylated product 8 significantly increased to be over 90% ee. 

Several other stabilized carbocations were utilized for asymmetric organocata-lyzed transformations. A comparable and similar benzylic situation is given by the utilization ofallylic alcohols (Scheme 4.16). These substrates are completely unre-active under organocatalyzed reactions conditions. But, by a combination of metaland organocatalysis, the same authors were able to realize an enantioselective a-alkylation of enolizable aldehydes with allylic alcohols [47]. The corresponding allylic cations were formed by the use of catalytic amounts of indium salts. Thus, various several different aromatic allylic alcohols were converted into the corresponding aldehydes 52a-c with high enantioselectivity. 

Higher Alkyl Cyanoformates. A range of other alkyl cyanoformates has been successfully utilized for the acylation of enolate anions, including ethyl, allyl, benzyl, and p-methoxybenzyl, but not r-butyl cyanoformate, which appears to be insufficiently reactive. Enantiomerically enriched cyanoformates derived from (+)-menthol, (-)-bomeol, and the Oppolzer alcohol were reported to furnish good chemical yields, but the level of enantioselectivity was disappointingly low (eq 18). ... 

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