Enantioselective Pd-Catalyzed α-Arylation of N-Boc-Pyrrolidine: The Key to an Efficient and Practical Synthesis of a Glucokinase Activator
The Journal of Organic Chemistry2008Vol. 73(13), pp. 4986–4993
Citations Over TimeTop 12% of 2008 papers
Abstract
A short and practical synthesis of glucokinase activator 1 was achieved utilizing a convergent strategy involving S(N)Ar coupling of activated aryl fluoride 11 with hydroxypyridine 9. The key to the success of the synthesis was the development of a novel method for enantioselective formation of alpha-arylpyrrolidines during the course of the project. In this method, (-)-sparteine-mediated enantioselective lithiation of N-Boc-pyrrolidine was followed by in situ transmetalation to zinc and Pd-catalyzed coupling with aryl bromide 3, proceeding in 92% ee. This transformation allowed the preparation of compound 1 in a 31% overall yield over six steps.
Related Papers
- → Efficient Pd‐Catalyzed Direct Coupling of Aryl Chlorides with Alkyllithium Reagents(2020)22 cited
- → Recent Trends in Enantioselective Diorganozinc-Additions to Aldehydes(2006)25 cited
- → ChemInform Abstract: Coupling of Aldehydes, Amines, and Trimethyl Phosphite Promoted by Amberlyst‐15: Highly Efficient Synthesis of α‐Aminophosphonates.(2008)
- → ChemInform Abstract: A Convenient Route to Pyrrolidine‐2‐phosphonic Acid Dipeptides.(1989)
- → ChemInform Abstract: Chemistry of Aryl‐Lead(IV) Tricarboxylates. Reaction with Vinylogous β‐Keto Esters.(1988)