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

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 to the synthesis of a key precursor of antagonists of the neurokinin-1 receptor. In 2 addition, the mechanism of the reaction was inferred from several observations. Thus, the oxidative addition complex [(XPhos)PhPdBr] and its dimer were observed by 31 P{ 1 H} NMR and these complexes were shown to be catalytically and kinetically competent. Moreover, a complex resulting from the transmetallation 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 transmetallation of and the subsequent deprotonation are rate-determining in the catalytic cycle.

Cooperative copper-squaramide catalysis for the enantioselective N–H insertion reaction with sulfoxonium ylides

“…Our attempts, as well as of other groups, to prepare them have failed so far. 30,43 We also evaluated the scalability of the reaction. Insertion product 10 was synthesized on a 1 mmol scale, as depicted in Scheme 4.…”

Enantioselective S−H Insertion Reactions of α‐Carbonyl Sulfoxonium Ylides

“…Industrial applications are of particular relevance as Mangion and co‐workers from Merck noted that sulfoxonium ylides may be more suitable for large scale work as they do not lead to the production of gas or rapid exotherms . Further adding to their allure, recent methodologies developed separately in the Burtoloso and Aissa laboratories enable direct access to more decorated sulfoxonium ylides from safe commercially available starting materials in a single step …”

“…[5] Further adding to their allure, recent methodologies developed separately in the Burtoloso and Aissa laboratories enable direct access to more decorated sulfoxonium ylides from safe commercially available starting materials in a single step. [6][7][8] Due to their promising synthetic profile, the application of sulfoxonium ylides in insertion chemistry has been gaining traction in the past decade. To date, efforts have typically focused on transition metal catalyzed insertion chemistry of sulfoxonium ylides (Scheme 1 A).…”

Asymmetric transformations from sulfoxonium ylides

“…Aerwards, Aïssa and co-workers overcame some of these limitations by developing versatile palladium-catalyzed cross coupling reactions of aryl bromides or triates with acarbonyl sulfoxonium ylides, providing a-(hetero)aryl functionalized products (83, Scheme 12B). 127,128 This reaction works with a broad range of structurally diverse aryl and heteroaryl substrates, which are applied in the synthesis and post functionalization of drug candidates and natural compound analogues. Palladium cross coupling reactions are also efficient for the production of dicarbonyl sulfoxonium ylides (84) by carbonylation of aryl halides or azides with sulfoxonium ylides, conducted under CO (g) .…”