Enantioselective, palladium-catalyzed α-arylation of N-Boc pyrrolidine: in situ react IR spectroscopic monitoring, scope, and synthetic applications.
Graeme Barker, Julia L McGrath, Artis Klapars, Darren Stead, George Zhou, Kevin R Campos, Peter O'Brien
Index: J. Org. Chem. 76(15) , 5936-53, (2011)
Full Text: HTML
Abstract
A comprehensive study of the enantioselective Pd-catalyzed α-arylation of N-Boc pyrrolidine has been carried out. The protocol involves deprotonation of N-Boc pyrrolidine using s-BuLi/(-)-sparteine in TBME or Et(2)O at -78 °C, transmetalation with ZnCl(2) and Negishi coupling using Pd(OAc)(2), t-Bu(3)P-HBF(4) and the aryl bromide. This paper reports several new features including in situ React IR spectroscopic monitoring of the process; use of (-)-sparteine and the (+)-sparteine surrogate to access products with opposite configuration; development of a catalytic asymmetric lithiation-Negishi 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 α-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.
Related Compounds
Related Articles:
Asymmetric synthesis of enantioenriched (+)-elaeokanine A.
2006-07-21
[J. Org. Chem. 71(15) , 5674-8, (2006)]
Enantioselective, palladium-catalyzed α-arylation of N-boc-pyrrolidine. Campos KR, et al.
[J. Am. Chem. Soc. 128(11) , 3538-3539, (2006)]
Copper mediated scalemic organolithium reagents in alkaloid syntheses. 3Dieter RK, et al.
[Tetrahedron 61(13) , 3221-3230, (2005)]
Stereoselective synthesis of hydroxyindolizidines via sparteine-assisted deprotonation of N-Boc-pyrrolidine. Majewski M, et al.
[Tetrahedron Lett. 39(38) , 6787-6790, (1998)]
Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites. Davies HML, et al.
[Bioorg. Med. Chem. Lett. 14(7) , 1799-1802, (2004)]