Pfizer synthesis pregabalin

A similar problem was noted by researchers from Pfizer and Dowpharma in their synthesis of (S)-3-aminomethyl-5-methylhexanoic acid (Pregabalin, 5) via the enantioselective hydrogenation of an acrylonitrile-type substrate 3 (Scheme 44.6) [41]. 

The first enantioselective synthesis of pregabalin (2) was developed by Yuen and co-workers at Pfizer using Evans chiral oxazolidinone chemistry (Yuen et al., 1994). 

Kissel, Ramsden, and other researchers at Pfizer and Chirotech jointly published a novel chiral synthesis of pregabalin (2) in 2003 based on asymmetric hydrogenation (Burk et al., 2001, 2003). Their synthesis started with the condensation of isobutyralde-hyde with acrylonitrile under Baylis-Hillman conditions to give allylic alcohol 65. This alcohol was activated as the carbonate 66 and subjected to palladium-catalyzed car-bonylation conditions to give cyanoester 67. The ester 67 was hydrolyzed and converted to... 

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