Chiral a,P-unsaturated acetals

The reaction of chiral acetals with organoaluminum reagents has been thoroughly investigated [72,73]. Noteworthy is the unprecedented regio- and stereochemical control observed in the addition of trialkylaluminums to chiral cx,P-unsaturated acetals derived from optically pure tartaric acid diamide [74-76]. The course of the reaction appeared to be strongly influenced by the nature of substrates, solvents, and temperature. These findings provide easy access to optically active a-substituted aldehydes. (3-substituted aldehydes, a-substituted carboxylic acids, or allylic alcohols. Since both (R,R)- and (5, S )-tartaric acid diamide are readily obtainable in optically pure form, this method allows the synthesis of both enantiomers of substituted aldehydes, carboxylic acids, and allylic alcohols from a,p-unsaturated aldehydes in a predictable manner. 

Cyclopropanes are efficiently obtained from alkenes by Simmons-Smith reaction applying CH2l2/Zn-Cu couple or CH2l2/Et2Zn as reagents. A variety of compounds bearing a chiral moiety have been studied, as for example a,P-unsaturated acetals and oxazolidines, enolethers, allylic alcohols, alkenylboronic esters as well as a,p-unsaturated carbonyl compounds. 

Highly diastereoselective acetate aldol additions using chlorotitanium enolates of mesityl-substituted JV-acetylthiazolidinethione 136 has been documented <07OL149>. These aldol reactions proceed in high yields and diastereoselectivities (94/6 to 98/2) for aliphatic, aromatic, and a,P-unsaturated aldehydes. Compound 136 also undergoes double diastereoselective aldol additions with chiral aldehyde 139 to give adduct 140 in high yields. 

Protected a,3-dihydroxy aldehydes have been prepared by oxidation of acetals of a,B-unsaturated aldehydes with osmium tetroxide in the presence of (23), and a remarkable level of enantioselection ee 2 90%) thereby achieved. Oxidation of chiral acetals of a,p-unsaturated aldehydes in which chirality resides in the noncarbonyl moiety with osmium tetroxide-t ydroquinine acetate (or dihydroquitudine acetate) may be regard as a process in which double stereoselection is at work and a high dia-stereoisomeric ratio of products may be obtained. 

Zhu and Panek s total synthesis [148] is described in Scheme 89. After conversion of aldehyde 609 to di-benzyl acetal, treatment with chiral crotylsilane 610 afforded l,2-5y -611 with high stereo- and enantioselectivity. The oxidative cleavage of the double bond and subsequent aldol reaction with silyl ketene acetal 612 provided 613, which was converted into a,P-unsaturated ester 614 via Wittig olelination. The C8 methyl group was stereoselectively introduced by treatment with dimethylcuprate in the presence of TMSCl. DIB AH treatment differentially reduced the C3 and CIO esters to alcohol and aldehyde, respectively. Protection of the alcohol as silyl ether followed by the Wittig reaction afforded 615. In a manner similar to Danishefsky s synthesis [142d], an inteimolecular Suzuki... 

Easily accessible acetals and ketals of a,p-unsaturated aldehydes and ketones derived fi-om C2-symmetric chiral 1,2-diols have been successfully used with Simmons-Smith reagents furnishing cyclopropane aldehydes with high selectivity and recovery of the auxiliary. Thus, dialkyl tartrates proved to be superior compared to 1,2-diphenyl-ethanediols as chiral auxiliaries in reactions of a,p-unsaturated aldehydes. 

By treatment of acetals, obtained from chiral 1,3-diols and cyclic a,p-unsaturated ketones with /BU3AI, enolethers are obtained bearing an alcohol functionality, which proved to be necessary to obtain high diastereoselectivity. ... 

The synthesis of nonracemic a,P-unsaturated sulfoxides bearing an electron-withdrawing group at the a-position has received attention [28-30] because these types of substrates have proved useful as chiral dienophiles (see Section 5.5) [28,29]. These methods suffered from the disadvantage that several steps were involved. Maignan and coworkers [31] have recently described a one-pot synthesis of nonracemic a-acyl- and a-hydroxyalkyl-a,P-unsaturated sulfoxides from 2-ethoxyethyl p-tolyl sulfoxide (16), readily prepared from (/ )-p-tolyl vinyl sulfoxide by addition of sodium ethoxide in ethanol. Thus, treatment of (16) with LDA in THF, followed by the addition of ethyl acetate, gave enantiomerically pure a-acyl-a,P-unsaturated sulfoxide (18) in 69% yield via the intermediate (17) (Scheme 5.6). 

In addition to the preceding methods that involve catalyzed additions to a,p-unsaturated carbonyls, enantioselective additions to unsaturated acetals have also been developed as a synthetic equivalent to traditional conjugate addition processes. By using chiral bis-phosphine ligands, asymmetic additions of Grignard reagents to unsaturated acetals were realized. ... 

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