Enantioselective, Palladium-Catalyzed 伪-Arylation of N-Boc Pyrrolidine: In Situ React IR Spectroscopic Monitoring, Scope, and Synthetic Applications

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• 作者：Graeme Barker ; Julia L. McGrath ; Artis Klapars ; Darren Stead ; George Zhou ; Kevin R. Campos ; Peter O鈥橞rien
• 刊名：Journal of Organic Chemistry
• 出版年：2011
• 出版时间：August 5, 2011
• 年：2011
• 卷：76
• 期：15
• 页码：5936-5953
• 全文大小：1468K
• 年卷期：v.76,no.15(August 5, 2011)
• ISSN：1520-6904

文摘

A comprehensive study of the enantioselective Pd-catalyzed 伪-arylation of N-Boc pyrrolidine has been carried out. The protocol involves deprotonation of N-Boc pyrrolidine using s-BuLi/(鈭?-sparteine in TBME or Et₂O at 鈭?8 掳C, transmetalation with ZnCl₂ and Negishi coupling using Pd(OAc)₂, t-Bu₃P-HBF₄ and the aryl bromide. This paper reports several new features including in situ React IR spectroscopic monitoring of the process; use of (鈭?-sparteine and the (+)-sparteine surrogate to access products with opposite configuration; development of a catalytic asymmetric lithiation鈥揘egishi coupling reaction; extension to a wide range of heteroaromatic bromides; total synthesis of (R)-crispine A, (S)-nicotine and (S)-SIB-1508Y via short synthetic routes; and examples of 伪-vinylation of N-Boc pyrrolidine using vinyl bromides exemplified by the total synthesis of naturally occurring (+)-maackiamine (thus establishing its configuration as (R)). In this way, the full scope and limitations of the methodology are delineated.