Asymmetric hydrogenations for the synthesis of Boc-protected 4-alkylprolinols and prolines |
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Authors: | Del Valle Juan R Goodman Murray |
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Institution: | Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla 92093-0343, USA. |
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Abstract: | The utility of 4-substituted prolinols and their corresponding prolines in peptides, peptidomimetics, and natural products has motivated researchers to find new and efficient routes for their preparation. Herein, we report a general approach to the synthesis of Boc-protected 4-alkylprolinols and prolines via a divergent asymmetric hydrogenation strategy. Intermediate exocyclic olefins were prepared by Wittig-type reactions with ketone 6 and subjected to hydroxyl and sterically directed reductions. The Crabtree catalyst (IrCOD]PyPCy(3)PF(6)) proved to be highly effective in diastereoselective hydrogenations to give trans-substituted pyrrolidines (9). Good facial selectivities were also observed in heterogeneous hydrogenations with Raney-nickel to obtain cis-substituted pyrrolidines (11). Employing this strategy, we describe the synthesis of novel prolinol and proline-based building blocks for incorporation into biologically relevant peptidomimetics. |
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