Qiu Liqin, Prashad Mahavir, Hu Bin, Prasad Kapa, Repic Oljan, Blacklock Thomas J, Kwong Fuk Yee, Kok Stanton H L, Lee Hang Wai, Chan Albert S C
Process Research and Development, Chemical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA.
Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16787-92. doi: 10.1073/pnas.0704461104. Epub 2007 Oct 17.
We describe highly enantioselective synthesis of beta-amino acid derivatives (1a-c) using asymmetric hydrogenation of alpha-aminomethylacrylates (2a-c), which contain a free basic N H group, as the key step. The alpha-aminomethylacrylates (2a-c) were prepared using the Baylis-Hillman reaction of an appropriate aldehyde with methyl acrylate followed by acetylation of the resulting allylic alcohols (4a-b) and S(N)2'-type amination of the allylic acetates (3a-b).
我们描述了以含有游离碱性NH基团的α-氨基甲基丙烯酸酯(2a - c)的不对称氢化反应为关键步骤,高度对映选择性地合成β-氨基酸衍生物(1a - c)。α-氨基甲基丙烯酸酯(2a - c)是通过合适的醛与丙烯酸甲酯的Baylis - Hillman反应制备的,随后将所得的烯丙醇(4a - b)进行乙酰化,并对烯丙基乙酸酯(3a - b)进行S(N)2'-型胺化反应。