Concise Formation of 4-Benzyl Piperidines and Related Derivatives Using a Suzuki Protocol
Susan Vice*, Tom Bara, Annette Bauer, C. Anderson Evans, Jennifer Fort, Hubert Josien, Stuart McCombie, Michael Miller, Dennis Nazareno, Anandan Palani and Jay Tagat
*Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth,
New Jersey, 07033-0593, Email: sfvice
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S. Vice, T. Bara, A. Bauer, C. A. Evans, J. Fort, H. Josien, S. McCombie, M. Miller, D. Nazzareno, A. Palani, J. Tagat, J. Org. Chem, 2001, 66, 2487-2492.
DOI: 10.1021/jo0007682
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Abstract
An efficient method of constructing 4-benzyl piperidines and related substances is described. This protocol tolerates a wide variation in both reaction partners and allows the concise formation of a variety of building blocks.
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Details
The document describes a method for synthesizing 4-benzyl piperidines and related derivatives using a Suzuki coupling protocol. The authors, from Schering-Plough Research Institute, aimed to develop a versatile method that could accommodate various substituents on the aryl and piperidine portions of the molecule. Traditional methods for synthesizing these compounds often involve harsh conditions and are limited in scope. The Suzuki reaction, known for its success in C-C bond formation, was employed to achieve the desired synthesis. The process involves hydroboration of N-Boc 4-methylene piperidine followed by reaction with PdCl2dppf and 2,5-dibromopyridine, yielding the target compound in high efficiency. The method tolerates a wide range of bromide, iodide, and triflate substrates, and functional groups that can be further modified. Variations in the piperidine nitrogen group were also explored, leading to the synthesis of amine, sulfonamide, and amide derivatives. The protocol's adaptability to different reaction partners and its potential for solid-phase applications make it valuable for drug discovery programs. The document includes detailed experimental procedures and characterization data for the synthesized compounds.
Key Words
Hydroboration, Suzuki Coupling, Arenes
ID: J42-Y2001-540
