Intramolecularly competitive Ireland-Claisen rearrangements: Scope and potential applications to natural product synthesis

by Hong, Sang-Phyo; Lindsay, Harriet A.; Yaramasu, Tripura; Zhang, Xiaowei; McIntosh, Matthias C.

A variety of bis-allylic esters were prepared by vinylmetal addition to cycloalkenones followed by esterification either in situ or in a separate operation. For chiral cyclohexenones, the vinyl additions generally occurred with > 10:1 diastereoselectivity. Although in some cases the bis-allylic esters proved to be sensitive to silica gel or other adsorbents, all of the esters examined could be isolated in acceptable purity. The Ireland-Claisen rearrangement of the bis-allylic esters occurred with complete regioselectivity via the exocyclic alkene. The alkene stereochemistry and the stereochemistry at C-2 and C-3 of the pentenoic acid products were consistent with a chairlike transition state in the rearrangement. Substituents at the carbons adjacent to the allylic carbinol carbon (i.e., C-2 or C-6 in cyclohexenone-derived substrates) directed the stereochemical course of the rearrangement. The rearrangements generally proceeded so as to place the larger of the C-2 or C-6 substituents in the pseudoequatorial position with respect to the chairlike transition state. For a bis-allylic ester bearing both a C-2-CH3 and a C-6-OMEM substituent, the rearrangement product resulted from the nominally smaller OMEM substituent occupying a pseudoequatorial position with respect to the chairlike transition state.

Journal
Journal of Organic Chemistry
Volume
67
Issue
7
Year
2002
Start Page
2042-2055
URL
https://dx.doi.org/10.1021/jo010752r
ISBN/ISSN
1520-6904; 0022-3263
DOI
10.1021/jo010752r