High yielding allylation of a chiral secondary alcohol containing base sensitive functional groups

Abstract

Inhibitors of neuronal nitric oxide synthase, based on a chiral pyrrolidine scaffold, show promise for the treatment of certain neurodegenerative diseases. We recently reported the synthesis of a series of selective inhibitors, but the method was limited at a key step of formingan allyl ether intermediate. Yields for this step were very inconsistent, and the presence of base sensitive functional groups limited the range of available methods for forming this ether bond. This work describes a novel application of palladium catalyzed decarboxylativeallylation, consistently resulting in 90% isolated yields, which is crucial for the synthesis of the critical allyl ether late stage intermediate. We also report a new quantitative yielding and straightforward synthesis of the allyl-t-butylcarbonate precursor.

Trienamine catalyzed asymmetric synthesis and biological investigation of a cytochalasin B-inspired compound collection

“…Finally metathesis of 13d–e successfully afforded the macrocyclic compounds 14a–b 21 with the same ring-size as CB. Several of the synthesized compounds were also prepared asymmetrically using trienamine catalysis, followed by reduction with sodium borohydride, and then either methylation with TMS-diazomethane, or allylation with tert -butyl-allyl carbonate 22 ( Scheme 3 ).…”

Synthesis of Amide Enol Carbamates and Carbonates through Cu(OTf)2-Catalyzed Reactions of Ynamides with t-Butyl Carbamates/Carbonates

“…General Procedure for Synthesis of O-Boc Esters 6. 28 To a solution of DMAP (0.25 mmol) and alcohol (10 mmol) in DCM (10 mL) was slowly added Boc 2 O (5 mmol) at rt. After stirring for 1 h, the mixture was concentrated in vacuo, and the residue was purified by flash chromatography to give pure O-Boc esters.…”