Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 20, 2016
Previous Article Next Article

Optimization and multigram scalability of a catalytic enantioselective borylative migration for the synthesis of functionalized chiral piperidines

Author affiliations

Abstract

The development of new, efficient and economical methods for the preparation of functionalized, optically enriched piperidines is important in the field of drug discovery where this class of heterocycles is often deemed a privileged structure. We have optimized a Pd-catalyzed enantioselective borylative migration of an alkenyl nonaflate derivative of the simple precursor, N-Boc-4-piperidone. This anomalous borylation reaction lends access to a chiral optically enriched piperidinyl allylic boronate that can be employed in carbonyl allylboration and stereoselective cross-coupling to produce substituted dehydropiperidines related to numerous pharmaceutical agents. A systematic fine-tuning of reaction conditions revealed that diethyl ether and the green solvent cyclopentyl methyl ether are suitable reaction solvents providing the highest enantioselectivity (up to 92% ee) under a low catalyst loading of 3 mol%. Optimization of the aldehyde allylboration step led to higher yields with further solvent economy. The multigram-scalability of the entire process was demonstrated under the reaction conditions that provide optimal atom-economy and efficiency.

Graphical abstract: Optimization and multigram scalability of a catalytic enantioselective borylative migration for the synthesis of functionalized chiral piperidines

Back to tab navigation

Supplementary files

Article information


Submitted
31 Mar 2016
Accepted
27 Apr 2016
First published
27 Apr 2016

Org. Biomol. Chem., 2016,14, 4739-4748
Article type
Paper
Author version available

Optimization and multigram scalability of a catalytic enantioselective borylative migration for the synthesis of functionalized chiral piperidines

Y. Kim and D. G. Hall, Org. Biomol. Chem., 2016, 14, 4739
DOI: 10.1039/C6OB00685J

Social activity

Search articles by author

Spotlight

Advertisements