Asymmetric Tandem Conjugate Addition-Allylation of Chiral (p-Tolylsulfinyl)pyrrolyl Cinnamoyl Amide

Abstract

The alkylation by allyl halides of the intermediate enolate, prepared in situ by conjugate addition of di-p-tolylcuprate to chiral (p-tolylsulfinyl)pyrrolyl cinnamoyl amide, gave the (2R,3R)-adducts as the major products with 81% to 94% de’s. Methanolysis of the products afforded the corresponding methyl esters, together with efficient recovery of the chiral sulfinyl auxiliary without loss of optical purity.

Key words

tandem reactions - conjugate addition reactions - chiral sulfoxide - cuprate - diastereoselectivity

References

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17

Alcoholysis of other tandem products produced the esters 12a-15a (84% yield), 12b-15b (79% yield) and 12c-15c (79% yield) with efficient recovery of 6 (>99% ee, in high yields). Although the stereochemistry of 12a-15a was not determined, determination of the product ratios of 12b-14b and 12c-14c was essentially deduced in a similar manner, but slightly complicated. Unfortunately, because two esters 12 and 13, derived from the original mixture of 8-11, were not well enough separated from each other on chiral HPLC, the ratio of 12 and 13 was calculated on the basis of the ratio of a pair of MeO signals by ¹H NMR analysis (see text).
Analytical samples of 12b-15b and 12c-15c for HPLC were also prepared from optically active 4 or racemic 4 and 5 (1:1) by allylation and methallylation in 57% and 61% yields, respectively. The poor selectivities (syn/anti, ca.1:0.9) observed are comparable to that observed for prenylation of the ester enolate.