Combining Matteson Homologations and Claisen Rearrangements – An Efficient Protocol for Amino Acid Synthesis

Abstract

The Matteson homologation with vinyl nucleophiles was found to be an efficient and versatile protocol for the synthesis of substituted chiral allyl alcohols in a highly stereoselective fashion. These alcohols can be coupled with N‐protected glycine and subsequently subjected to zinc‐chelated ester‐enolate Claisen rearrangements to yield highly substituted unsaturated amino acids. By varying the nucleophiles used in the Matteson homologations, the method allows control over not only the stereogenic centers but also the side‐chain substitution pattern in the newly formed γ,δ‐unsaturated amino acids.

A Straightforward Synthesis of Emericellamide A Using Matteson’s Homologation Approach

“…[𝛼] 𝐷 20 = -18.6 (c = 1.0, CHCl3). 1 H-NMR (400 MHz, CDCl3): δ = 0.85-0.94 (m, 12 H), 0.95-0.97 (m, 6 H), 1.13 (d,J = 7.0 Hz,3 H),10 H),1.38 (d,J = 7.3 Hz,3 H),1.42 (d,J = 7.2 Hz,3 H),1.46 (s,9 H),1 H),3 H),1 H),2.75 (quint,J = 7.3 Hz, 1 H), 3.79 (t, J = 5.0 Hz, 1 H), 4.02 (dd, J = 18.0, 4.9 Hz, 1 H), 4.20 (dd,J = 17.6,5.9 Hz,1 H),1 H),4.49 (quint,J = 7.5 Hz,1 H),4.60 (quint,J = 7.6 Hz,1 H),4.96 (d,J = 4.9 Hz, 1 H), 5.08 (dd, J = 8.8, 3.1 Hz, 1 H), 5.11-5.18 (m, 2 H), 6.43 (d, J = 6.4 Hz, 1 H), 6.86 (bs, 1 H), 7.02 (d,J = 8.0 Hz,1 H),7.11 (d,J = 7.2 Hz,1 H),5 H) ppm. 13 C-NMR (100 MHz, CDCl3): δ = 13.0, 14.…”