Enantioconvergent Cross-Couplings of Racemic Alkylmetal Reagents with Unactivated Secondary Alkyl Electrophiles: Catalytic Asymmetric Negishi α-Alkylations of N-Boc-pyrrolidine
Abstract
Although enantioconvergent alkyl–alkyl couplings of racemic electrophiles have been developed, there have been no reports of the corresponding reactions of racemic nucleophiles. Herein we describe Negishi cross-couplings of racemic α-zincated N-Boc-pyrrolidine with unactivated secondary halides, thus providing a one-pot, catalytic asymmetric method for the synthesis of a range of 2-alkylpyrrolidines (an important family of target molecules) from N-Boc-pyrrolidine, a commercially available precursor. Preliminary mechanistic studies indicated that two of the most straightforward mechanisms for enantioconvergence (dynamic kinetic resolution of the organometallic coupling partner and a simple β-hydride elimination/β-migratory insertion pathway) are unlikely to be operative.
Additional Information
© 2013 American Chemical Society. Received: May 30, 2013; Published: July 19, 2013. We thank the NIH NIGMS (R01-GM62871) for support and Dr. Scott C. Virgil (Caltech Center for Catalysis and Chemical Synthesis) and Dr. David G. VanderVelde (Caltech NMR facility) for assistance.Attached Files
Accepted Version - nihms508343.pdf
Supplemental Material - ja4054114_si_001.pdf
Files
Name | Size | Download all |
---|---|---|
md5:4f636bdc3391ab88bd11d886608a840e
|
969.4 kB | Preview Download |
md5:1c57488a274039a5d2d855cedc87adb1
|
3.0 MB | Preview Download |
Additional details
- PMCID
- PMC3803154
- Eprint ID
- 42041
- Resolver ID
- CaltechAUTHORS:20131024-101621144
- NIH
- R01-GM62871
- Created
-
2013-10-24Created from EPrint's datestamp field
- Updated
-
2021-11-10Created from EPrint's last_modified field