Palladium-Catalyzed Synthesis of α-Carbonyl-α′-(hetero)aryl Sulfoxonium Ylides:Scope and Insight into the Mechanism

Janot, C. and Chagnoleau, J.-B. and Halcovitch, N.R. and Muir, J. and Aïssa, C. (2020) Palladium-Catalyzed Synthesis of α-Carbonyl-α′-(hetero)aryl Sulfoxonium Ylides:Scope and Insight into the Mechanism. Journal of Organic Chemistry, 85 (2). pp. 1126-1137. ISSN 0022-3263

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Abstract

Despite recent advances, a general method for the synthesis of α-carbonyl-α′-(hetero)aryl sulfoxonium ylides is needed to benefit more greatly from the potential safety advantages offered by these compounds over the parent diazo compounds. Herein, we report the palladium-catalyzed cross-coupling of aryl bromides and triflates with α-carbonyl sulfoxonium ylides. We also report the use of this method for the modification of an active pharmaceutical ingredient and for the synthesis of a key precursor of antagonists of the neurokinin-1 receptor. In addition, the mechanism of the reaction was inferred from several observations. Thus, the oxidative addition complex [(XPhos)PhPdBr] and its dimer were observed by 31P{1H} NMR, and these complexes were shown to be catalytically and kinetically competent. Moreover, a complex resulting from the transmetalation of [(XPhos)ArPdBr] (Ar = p-CF3–C6H4) with a model sulfoxonium ylide was observed by mass spectrometry. Finally, the partial rate law suggests that the transmetalation and the subsequent deprotonation are rate-determining in the catalytic cycle.

Item Type:
Journal Article
Journal or Publication Title:
Journal of Organic Chemistry
Additional Information:
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Organic Chemistry, copyright ©2019 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/abs/10.1021/acs.joc.9b03032
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1600/1605
Subjects:
ID Code:
140061
Deposited By:
Deposited On:
17 Jan 2020 12:05
Refereed?:
Yes
Published?:
Published
Last Modified:
23 Sep 2020 05:54