Proline 3  , a key precursor in one of our medicinal chemistry programs, needed to be prepared on scale. Since the chemical literature indicated that Simmons-Smith cyclopropanation of 1  , containing either an ester or an amide functionality at C-2, results in a cis-stereoselectivity, the feasibility of cyclopropanating (R)-ester 1  followed by C-2 epimerization was investigated. Aspects of this epimerization study and details of an alternate scalable route to proline 3  that was eventually devised via the intermediacy of (S)-silyl ether 2  , highlighting how the stereo-preference of the cylopropanation step could be controlled by C-2 functionality choice, will be discussed.

Scalable synthesis of (1R,3S,5R)-2-(<i>tert</i>-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid

244th National Meeting (2012)

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Scalable synthesis of (1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid