Building constrained peptidomimetics: A convenient approach to 3-phenyl-5-vinyl substituted proline derivatives

An approach to the synthesis of 3-phenyl-5-vinyl substituted prolines starting from readily available 2,3-disubstituted pentenoic acid derivatives is reported. The route converts the pentenoic acid derived starting materials into cyclic N-acyliminium ion precursors with the use of a hydroboration-Swern oxidation sequence. This overall transformation worked best when the initial alkylborane product was treated sequentially with excess MCPBA and then acetone prior to the Swern oxidation. In this way, a 70% yield of the desired N-acyliminium ion precursor could be obtained. Once in hand, the cyclic N-acyliminium ion precursor was used to make the desired 3-phenyl-5-vinyl substituted prolines.