Rights statement: 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
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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Palladium-Catalyzed Synthesis of α-Carbonyl-α′-(hetero)aryl Sulfoxonium Ylides
T2 - Scope and Insight into the Mechanism
AU - Janot, C.
AU - Chagnoleau, J.-B.
AU - Halcovitch, N.R.
AU - Muir, J.
AU - Aïssa, C.
N1 - 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
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
U2 - 10.1021/acs.joc.9b03032
DO - 10.1021/acs.joc.9b03032
M3 - Journal article
VL - 85
SP - 1126
EP - 1137
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
SN - 0022-3263
IS - 2
ER -