title: Asymmetric Synthesis of N-Boc-(R)-Silaproline via Rh-Catalyzed Intramolecular Hydrosilylation of Dehydroalanine and Continuous Flow N-Alkylation.
abstract: 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.
authors.affiliation: Department of Process Chemistry, Merck Research Laboratories , P.O. Box 2000, Rahway, New Jersey 07065, United States.
authors.forename: John Y L
authors.initials: JY
authors.lastname: Chung
authors.affiliation: Department of Process Chemistry, Merck Research Laboratories , P.O. Box 2000, Rahway, New Jersey 07065, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Shevlin
authors.affiliation: Department of Process Chemistry, Merck Research Laboratories , P.O. Box 2000, Rahway, New Jersey 07065, United States.
authors.forename: Artis
authors.initials: A
authors.lastname: Klapars
authors.affiliation: Department of Process Chemistry, Merck Research Laboratories , P.O. Box 2000, Rahway, New Jersey 07065, United States.
authors.forename: Michel
authors.initials: M
authors.lastname: Journet
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D000478:Alkylation; D002384:Catalysis; D003500:Cyclization; D017646:Organosilicon Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: C000611010:N-Boc-(R)-silaproline; D017646:Organosilicon Compounds; C455420:silaproline; C015102:dehydroalanine; D011392:Proline; D000409:Alanine