An Experimental and Computational Investigation of the Enantioselective Deprotonation of Boc-piperidine

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• 作者：William F. Bailey ; Peter Beak ; Shawn T. Kerrick ; Sunghoon Ma ; and Kenneth B. Wiberg
• 刊名：Journal of the American Chemical Society
• 出版年：2002
• 出版时间：March 6, 2002
• 年：2002
• 卷：124
• 期：9
• 页码：1889 - 1896
• 全文大小：189K
• 年卷期：v.124,no.9(March 6, 2002)
• ISSN：1520-5126

文摘

The asymmetric deprotonation of N-Boc-piperidine (3) by the 1:1 complex of a sec-alkyllithiumand (-)-sparteine has been investigated both experimentally and computationally. The lithiation of 3 withsec-BuLi-(-)-sparteine at -78 mages/entities/deg.gif">C, which is a much slower process than is the analogous deprotonationof N-Boc-pyrrolidine (1) and a minor reaction relative to the competing addition of sec-BuLi to the carbamate,proceeds with a moderate degree of selectivity (er = 87:13) for removal of the pro-S hydrogen of 3. Therelated deprotonation of N-Boc-4-tosyloxypiperidine (6) with two molar equiv of sec-BuLi-(-)-sparteinealso involves preferential transfer of the pro-S hydrogen. The computational study of the deprotonation of(3) by i-PrLi-(-)-sparteine found that the proton that is preferentially transferred within three-componentintermediate complex is the thermodynamically least acidic mages/gifchars/alpha.gif" BORDER=0>-hydrogen of 3. The asymmetric deprotonationof 3 is calculated to proceed with poor enantioselectivity and to have an activation energy considerablyhigher than that calculated for deprotonation of N-Boc-pyrrolidine (1). The experimental and computationalresults are in good agreement.