Acyclic Diastereoselection in Conjugate Additions

Diastereoselective conjugate radical additions to control stereochemistry at the P center has been approached in a number of ways. Chiral auxiliaries have been exploited on the radical trap as well as the radical itself, producing products with high diastereoselectivities in both cases. 1,2-Selectivity has been induced by the 

Entry R Lewi.s acid (eq) Solvent Yield (%) Ratio ) 

After the evaluation of several Lewis acids some highlights emerged. Lanthanide Lewis acids provided the highest levels of selectivity (entries 4 and 8) as did appropriate selection of the R group (compare entries 4 and 8). The use of sub-stoichiometric Lewis acids had negligible effects on stereoselectivity or reaction efficiency (entry 5), and limited amounts of water did not hinder either the progress or the selectivity in this reaction (entry 6). It must also be noted that the lev- 

In a similar manner, conjugate radical additions to differentially protected fuma-rates allowed access to functionalized succinates [55]. Regioselectivity in these radical additions is provided by preferential Lewis acid activation of the p carbon by coordination of the imide carbonyl. The general scheme is illustrated in Eq. (13.42) (Table 13-8). 

This conjugate addition proceeds in excellent yields. High regio- and diastereo-selectivity is observed with lanthanide and other Lewis acids (entries 3, 4 and 6), but little selectivity is seen in the absence of a chelating Lewis acid (entries I and 2) and with substoichiometric amounts of Lewis acid (entry 5). It had previously been established that radical addition to crotonates and cinnamates could be accomplished with catalytic amounts of Lewis acid. However, the fumarate substrate is orders of magnitude more reactive, and hence radical addition to the uncom-plexed substrate presumably competes, leading to lower observed selectivity. 

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