Development of an Aryl Amination Catalyst with Broad Scope Guided by Consideration of Catalyst Stability
Name
nihms-1679399.pdf
Description
Accepted version
Size
2.48 MB
Format
Unknown
Checksum (MD5)
81d40096737817f36a61d0a87ef8f44a
Author(s)
McCann, Scott D.
Reichert, Elaine C.
Arrechea, Pedro Luis
Buchwald, Stephen L.
Date Issued
August 2020
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
McCann, Scott D, Reichert, Elaine C, Arrechea, Pedro Luis and Buchwald, Stephen L. 2020. "Development of an Aryl Amination Catalyst with Broad Scope Guided by Consideration of Catalyst Stability." Journal of the American Chemical Society, 142 (35).
Version
Author's final manuscript
Abstract
Copyright © 2020 American Chemical Society. We have developed a new dialkylbiaryl monophosphine ligand, GPhos, that supports a palladium catalyst capable of promoting carbon-nitrogen cross-coupling reactions between a variety of primary amines and aryl halides; in many cases, these reactions can be carried out at room temperature. The reaction development was guided by the idea that the productivity of catalysts employing BrettPhos-like ligands is limited by their lack of stability at room temperature. Specifically, it was hypothesized that primary amine and N-heteroaromatic substrates can displace the phosphine ligand, leading to the formation of catalytically dormant palladium complexes that reactivate only upon heating. This notion was supported by the synthesis and kinetic study of a putative off-cycle Pd complex. Consideration of this off-cycle species, together with the identification of substrate classes that are not effectively coupled at room temperature using previous catalysts, led to the design of a new dialkylbiaryl monophosphine ligand. An Ot-Bu substituent was added ortho to the dialkylphosphino group of the ligand framework to improve the stability of the most active catalyst conformer. To offset the increased size of this substituent, we also removed the para i-Pr group of the non-phosphorus-containing ring, which allowed the catalyst to accommodate binding of even very large α-tertiary primary amine nucleophiles. In comparison to previous catalysts, the GPhos-supported catalyst exhibits better reactivity both under ambient conditions and at elevated temperatures. Its use allows for the coupling of a range of amine nucleophiles, including (1) unhindered, (2) five-membered-ring N-heterocycle-containing, and (3) α-tertiary primary amines, each of which previously required a different catalyst to achieve optimal results.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/jacs.0c06139
