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

TY - JOUR

T1 - Enantioselective, Palladium-Catalyzed α-Arylation of N-Boc Pyrrolidine

T2 - In Situ React IR Spectroscopic Monitoring, Scope, and Synthetic Applications

AU - Barker, Graeme

AU - McGrath, Julia L.

AU - Klapars, Artis

AU - Stead, Darren

AU - Zhou, George

AU - Campos, Kevin R.

AU - O'Brien, Peter

PY - 2011/8/5

Y1 - 2011/8/5

N2 - 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 2O at -78 °C, transmetalation with ZnCl 2 and Negishi coupling using Pd(OAc) 2, t-Bu 3P-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.

AB - 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 2O at -78 °C, transmetalation with ZnCl 2 and Negishi coupling using Pd(OAc) 2, t-Bu 3P-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.

UR - http://www.scopus.com/inward/record.url?scp=79961091837&partnerID=8YFLogxK

U2 - 10.1021/jo2011347

DO - 10.1021/jo2011347

M3 - Article

C2 - 21714542

AN - SCOPUS:79961091837

SN - 0022-3263

VL - 76

SP - 5936

EP - 5953

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 15

ER -