Multigram Synthesis of 2-Azabicyclo[2.1.1]hexane-1-Carboxylates (2,4-Methanoprolines) – Promising Bicyclic Proline Analogs

Abstract

An optimized approach towards 4-substituted 2,4-methanoproline derivatives is reported. Careful selection of the starting materials and optimized isolation procedure provided easy access to a key bicyclic building block in a preparative yield of 32% over five laboratory steps of up to 0.7 kg. Further modifications allowed us to obtain a number of useful derivatives, including those containing NH2, COOH, CH2NH2, and CH2F fragments with orthogonally protected functionalities.

Keywords

• bicyclic compounds
• building blocks
• proline analog
• bridged pyrrolidine
• amino acid