Decarboxylative Grob-Type Fragmentations in the Synthesis of Trisubstituted Z Olefins: Application to Peloruside A, Discodermolide, and EpothiloneD

摘要

The stereocontrolled synthesis of methyl branched trisubstituted Z olefins has been pursued intensively during the past few years, as this structural motif is found in numerous polyketides with promising anticancer activity, such as epothilone D (1), discodermolide (2), and peloruside A (3).As a result of these extensive efforts, a variety of approaches have emerged based on carbonyl olefination, olefin metathesis, alkyne functionalization, allylic rearrangements, and cross-coupling reactions.111 As most of these protocols make use of expensive and/or toxic reagents, we wondered why E2 elimination reactions, and in particular Grob fragmentations with their simple operability and virtually "green" conditions, have been neglected in the construction of acyclic olefins. After all, Grob fragmentations have been rediscovered for the generation of cycloolefins.