Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 5936-5953 |
| Journal | Journal of Organic Chemistry |
| Volume | 76 |
| Issue number | 15 |
| Early online date | 29 Jun 2011 |
| DOIs | |
| Publication status | Published - 5 Aug 2011 |
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Enantioselective, Palladium-Catalyzed α-Arylation of N-Boc Pyrrolidine: In Situ React IR Spectroscopic Monitoring, Scope, and Synthetic Applications. / Barker, Graeme; McGrath, Julia L.; Klapars, Artis; Stead, Darren; Zhou, George; Campos, Kevin R.; O'Brien, Peter.
In: Journal of Organic Chemistry, Vol. 76, No. 15, 05.08.2011, p. 5936-5953.Research output: Contribution to journal › Article
TY - JOUR
T1 - Enantioselective, Palladium-Catalyzed α-Arylation of N-Boc Pyrrolidine: 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 Et2O at −78 °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 (−)-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 Et2O at −78 °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 (−)-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.
U2 - 10.1021/jo2011347
DO - 10.1021/jo2011347
M3 - Article
VL - 76
SP - 5936
EP - 5953
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
SN - 0022-3263
IS - 15
ER -