Chung JY1, Shevlin M1, Klapars A1, Journet M1.
Org Lett. 2016 Apr 15;18(8):1812-5. doi: 10.1021/acs.orglett.6b00548. Epub 2016 Mar 25.An asymmetric synthesis of a silicon-containing proline surrogate, N-Boc-(R)-silaproline (1), is described. Starting from N-Boc-dehydroalanine ester, deprotonation, followed by N-alkylation with chloromethyldimethylsilane under flow conditions, afforded the N-alkylated product 8 in 91% yield. An unprecedented enantioselective (NBD)2RhBF4/Josiphos 404-1 catalyzed 5-endo-trig hydrosilylation afforded the silaproline ester in 85-90% yield and >95% ee. Subsequent saponification and salt formation upgraded 1 to >99% ee.