Catalytic Asymmetric Access to α,β Unsaturated δ-Lactones through a Vinylogous Aldol Reaction:  Application to the Total Synthesis of the Prelog-Djerassi Lactone

Abstract

[reaction--see text] A one-step catalytic asymmetric access to alpha,beta unsaturated delta-lactones is described, using a vinylogous Mukaiyama-aldol reaction between a gamma-substituted dienolate and various aldehydes in the presence of Carreira catalyst CuF.(S)-tolBinap. This methodology has been further applied to a straightforward access to the Prelog-Djerassi lactone.

Catalytic, Enantioselective, Vinylogous Aldol Reactions

“…[33] Campagne and co-workers also studied the effect of g substitution on the dienolate in the addition to aldehydes in the presence of the (S)-Tol-binap·CuF 2 catalyst (Scheme 26). [43] The addition of the methyl pentenoate derived silyl dienol ether 74 to various aldehydes yielded mixtures of lactones 75 and vinylogous aldol products 76. Whereas lactones 75 were formed with excellent anti selectivity (> 98:2) along with high enantioselectivity in all cases, the linear products 76 were isolated as a 1:1 mixture of racemic syn and anti diastereomers.…”

“…[43] Felkin-Heathcock analysis of the S-configScheme 22. The Ti(OiPr) 4 /(R)-binol-catalyzed vinylogous aldol reaction of the ester-derived dienolate 62 (absolute configurations were not established by the authors).…”

1.04 Regio-, Diastereo-, and Enantioselective Addition of Organocopper Reagents onto CO and CN Bonds

“…These reactions might thus proceed through a reversible non selective α-aldolization followed by an irreversible γ-aldolization. 69 This methodology has been applied to the syntheses of the Prelog-Djerassi lactone, 68 disorazole, 70 the three main fragments of discodermolide, 71 and C1-C12 fragment 72 of iriometeolide. …”

The Vinylogous Mukaiyama Aldol Reaction in Natural Product Synthesis

“…The synthetic potential of such an example has been excellently illustrated in the quick access that it provides to the Prelog-Djerassi lactone (121) [57] and the three main fragments of (+)-discodermolide (122) [58] starting from α,β-unsaturated lactone (120) (Scheme 2.29). This lactone was obtained as a single diastereoisomer in 60%, or 68% isolated yield depending on the ester used to form the ketene acetal.…”