Heteroatom-stabilized Allylic Anions

Abstract

Heteroatom-stabilized allylic anions (1 and 2; X = Y = heteroatom) can be used as homoenolate anion synthons (3) and (4) or reversed polarity equivalents (5) and (6), as shown in Scheme 1. Homoenolates are important synthetic species since they are capable of converting aldehydes or ketones into γ-lactols or γ-lactones (Volume 2, Chapter 1.14). Acyl anion equivalents are also very important in organic synthesis.1d Electrophiles may react at either of the termini of allylic anions. A great deal of effort has been exerted to control the regioselectivity (α:γ ratio); regioselective attack at the γ-position of (1) leads to homoenolate anion equivalents, whereas the attack at the α-position leads to reversed polarity euivalents. The α/γ-selectivity is dictated by a number of factors, such as the nature of the heteroatom, the substituents attached to the heteroatom, the countercation, the type of electrophile, additives and solvent, reaction temperature, and reaction time.1 The following rule of thumb is useful for predicting the regioselectivity of an allylic anion like (1; R = H, M = Li; Scheme 1),2 in which lithium and the allylic anion are associated, thus free anions or anions bearing strong electron-withdrawing groups are excluded. When X is an anion-destabilizing substituent, higher electron density would be expected at the -γ-position and (1a) would be preferred over (1b). Accordingly, alkyl halides and protons would react at the γ-position (the site of higher electron density), while carbonyl compounds would react at the α-position via a rearrangement process involving lithium. When X is an anion-stabilizing substituent, (1b) or (1c) would be preferred over (1a) and thus complementary regioselectivity would be observed. In fact, allylic anions substituted by anion-destabilizing groups (X = OR, NR2, alkyl) undergo alkylation and protonation preferentially at the γ-position and react with carbonyl compounds predominantly at the α-position. Anions bearing anion-stabilizing groups (X = SR, BR2) react with carbonyl compounds at the γ-position and with alkyl halides and protons at the α-position. However, these tendencies may be modified by a number of factors mentioned above.