Diastereoselectivity of conjugate addition to γ-alkoxy-α,β-unsaturated esters via organocopper–Lewis acids and related reagents. Importance of the double bond geometry in controlling the selectivity

Abstract

The Lewis acid mediated addition of organocopper reagents to the trans-ester (7a) produced the anti-isomer (8a) predominantly, while addition to the cis-derivative (7b) gave the syn-isomer (9a) preferentially, and addition of organometallic compounds to the diester (7c) also afforded the syn-isomer (9b) predominantly; this change in diastereoselectivity indicates the importance of the double bond geometry in controlling the 1,2-asymrnetric induction of y-alkoxy-a$-unsaturated carbonyl compounds. ~ ~~~The diastereoselectivity of nucleophilic addition to y-alkoxya,P-unsaturated carbonyl derivatives (1) is puzzling. Some additions have been interpreted in terms of a modified Felkin-Anh model (2), which produces the anti-isomer (3) (Scheme 1).1 1H N.m.r. analyses2 and calculations3 suggest that conformer (4), which would also give (3) as the major product, would be preferred in the ground state. It has not so far been possible to determine whether (2) or (4) is the more reactive conformer. Further, in some cases the opposite diastereoselectivity is observed; the syn-isomer (6) is pro-

Design of Pseudodiproline Dimers as Mimetics of Pro-Pro Units: Stereocontrolled Synthesis, Configurational Relevance, and Structural Properties

“…In 1987, Yamamoto first reported a study in which the geometry of the unsaturated ester determined the stereochemical outcome. 62 Soon after, a report by Dorigo and Morokuma rationalized the stereoselectivity based on steric and electronic effects which were substantiated by ab initio molecular orbital studies. 63 Their results were in close agreement with the experimental data of Yamamoto favoring the formation of antiproducts from trans-esters and syn-products from cis-esters as major isomers.…”

“…The origins of the observed diastereoselectivity in cuprate conjugate addition reactions of enoate esters remain somewhat enigmatic. In 1987, Yamamoto first reported a study in which the geometry of the unsaturated ester determined the stereochemical outcome . Soon after, a report by Dorigo and Morokuma rationalized the stereoselectivity based on steric and electronic effects which were substantiated by ab initio molecular orbital studies .…”

“…In previous studies, cuprate additions to unsaturated esters bearing a γ-ether − or acetal , led to anti -products. However, the presence of a γ- N -Boc group substituent or N -Boc/ O -acetal groups afforded syn -products.…”

“…Although the formation of major products in both series can be rationalized on the basis of the Felkin–Ahn transition-state models, ,, another study carried out with computational methods to better understand the role of the δ- N -Boc pyrrolidinyl unit in combination with the OBOM and ester groups leading to the formation of syn - or anti -products may be of interest. In their seminal studies, Yamamoto and Morokuma did not address the influence of the configuration of the carbon carrying the γ-alkoxy group on the stereoselectivity of conjugate additions to enoate esters.…”

Stereoselectivity

“…This is determined by the relative magnitude of the repulsion between the inside substituent and the enal fragment on the one hand, and the repulsion between the outside substituent and the incoming nucleophile on the other: 114 reactions. This is determined by the relative magnitude of the repulsion between the inside substituent and the enal fragment on the one hand, and the repulsion between the outside substituent and the incoming nucleophile on the other: 114 reactions.…”