Cα-Quaternary proline derivatives have been of great interest due to the wide range of applicability in chemistry and biology. Thus, a number of strategies has been developed involving ‘self-reproduction of chirality’ and ‘C→N→C chirality transfer’. Although the latter has great potential, it has not received much attention because of the low level of C→N chirality transfer. To overcome this limitation, we investigated a proper <i>N</i>-substituent of proline and achieved high diastereoselectivity in the allylic amination of proline ester (C→N chirality transfer, up to 50:1 dr). The diastereopurity of quaternary ammonium salt was completely transmitted to the α-carbon chirality via stereoselective [2,3]-Stevens rearrangement (N→C chirality transfer) to provide β-substituted α-quaternary proline esters with great enantiocontrol. The scope was explored with various allylic electrophiles. This protocol was applied to total synthesis, and the results will be also presented.

Synthesis of enantioenriched α-quaternary prolines using a C→N→C chirality transfer

253rd National Meeting (2017)

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