Development of New Methods for Acyclic Stereocontrol and Their Application

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(1) The Lewis acid mediated conjugate addition of organocopper reagents to the trans-gamma-alkoxy- alpha, beta-unsaturated ester produces the anti-isomer, while addition to the cis-derivatives gave the syn-isomer. This change in diastereoselectivity indicates the importance of the double bond geometry in controlling the 1,2-asymmetric induction of gamma-alkoxy-alpha, beta-unsaturated carbonyl compounds. The conjugate addition of RCu (organocopper) and R_2CuLi (organocuprate) to the trans-gamma-alkyl-alpha, beta-unsaturated esters produced the anti-isomer, while addition of cuprates to the cis esters gave the syn-isomers. This change indicates the importance of reagent type in controlling 1,2-asymmetric induction during conjugate addition. Taken together, the new models for the transition state geometry have been proposed in the conjugate addition. (2) Quite similarly, the 1,2-asymmetric induction in conjugate reduction has been investigated. Here again, the reagent types play an import … More ant role in controlling the induction. Remarkable stereochemical difference is observed between one- and two-electron events. (3) Lithium N-benzyltrimethylsilylamide (LSA) adds to crotonates selectively in a 1,4-manner, though the reaction of ordinary lithium amides with alpha, beta-unsaturated esters is accompanied with a 1,2-addition and hydrogen abstraction at the gamma-position. The conjugate addition via LSA followed by enolate trapping with electrophiles produces the corresponding alpha-substituted beta-amino esters, which are in turn converted into beta-lactam and alpha-substituted alpha, beta-unsaturated esters. Methods for highly stereoselective generation of both Z- and E-enolates of a beta-amino ester are developed on the basis of a conjugate addition of LSA to methyy crotonate. (4) The reaction of gamma-mesiloxy-alpha, beta-unsaturated esters with organocyanocopper-BF_3 reagents produces alpha-alkyl-beta, gamma-unsaturated esters in very high yields. The substitution proceeds in an anti-S_N2' manner, and this 1,3-chiral transfer always takes place with nearly 100 % ee or de. (5) The reaction of organometallic-Lewis acid complexes (R_4Pb-TiCl_4, R_2Zn-BF_3...) with acyliminium ions proceeds with very high diastereofacial and diastereo-selective manner. The reaction is applied for the synthesis of statine. Less