Amino-zinc-ene-enolate cyclization: a short access to cis-3-substituted prolino-homotryptophane derivatives.

Proline chimeras are useful tools for medicinal chemistry and/or biological applications. The asymmetric synthesis of cis-3-substituted prolines can be easily achieved via amino-zinc-ene-enolate cyclization followed by transmetalation of the cyclic zinc intermediate for further functionalization. Syntheses of prolino-homotryptophane derivatives were achieved through Negishi cross-coupling of the zinc intermediate with indole rings. The use of Pd catalyst derived from Fu's [(t-Bu3)PH]-BF4 was required to avoid the undesired beta-hydride elimination. Optically pure and orthogonally protected compounds were obtained readily usable for peptide synthesis.