Modular Cyclopentenone Synthesis through the Catalytic Molecular Shuffling of Unsaturated Acid Chlorides and Alkynes

Abstract

We describe a general strategy for the intermolecular synthesis of polysubstituted cyclopentenones using palladium catalysis. Overall, this reaction is achieved via a molecular shuffling process involving an alkyne, an α,β-unsaturated acid chloride, which serves as both the alkene and carbon monoxide source, and a hydrosilane to create three new C–C bonds. This new carbon monoxide-free pathway delivers the products with excellent yields. Furthermore, the regioselectivity is complementary to conventional methods for cyclopentenone synthesis. In addition, a set of regio- and chemodivergent reactions are presented to emphasize the synthetic potential of this novel strategy.

Catalytic Carbochlorocarbonylation of Unsaturated Hydrocarbons via C−COCl Bond Cleavage**

“…Other very electron poor acid chlorides such as 4‐nitrobenzoyl chloride and pentafluorobenzoyl chloride did not afford the desired product. Excitingly, we could show that benzoic acids could be used directly with Ghosez's reagent [13b] to generate the acid chloride in situ, as demonstrated by the reaction of 4‐(trimethylsilyl ethynyl) benzoic acid which provided the product 17 in a very good yield of 82 %. An acid chloride containing a boronic ester gave the product 18 in 54 % yield, highlighting the tolerance of an orthogonal functional handle to the acid chloride.…”

Recent Advances in the Functionalization of Terminal and Internal Alkynes

“…In 2020, Morandi et al elegantly developed palladiumcatalyzed synthesis of polysubstituted cyclopentenones via a molecular shuffling process from alkyne, α,β-unsaturated acid chloride and hydrosilane (Scheme 11). [17] In this protocol, α,βunsaturated acid acts as both the alkene and carbon monoxide source. The highlights of this protocol include broad substituent group tolerance, carbon monoxide free conditions and the formation of quaternary carbon centre at the 5-position in carbocycles.…”

Katalytische Carbochlorocarbonylierung von ungesättigten Kohlenwasserstoffen durch C‐COCl‐Bindungsspaltung**

“…Andere, sehr elektronenarme Säurechloride konnten nicht zum gewünschten Reaktionsprodukt umgesetzt werden. Benzoesäuren konnten mittels Ghosez′ Reagenz [13b] in situ in die entsprechenden Säurechloride umgewandelt werden. Exemplarisch ergibt die Reaktion von 4‐[(Trimethylsilyl)ethinyl)]benzoesäure Produkt 17 mit einer sehr guten Ausbeute von 82 %.…”

“…Die Reaktion zwischen NBD (2)u nd Benzoylchlorid wurde als Modellsystem festgelegt (Abbildung 1), um verschiedene denkbare Reaktionspfade zu beurteilen. In Anbetracht bisheriger Resultate unserer Arbeitsgruppe [13,16] [40][41][42] Die 21)l ediglich 10.7 kcal mol À1 beträgt. [43] Die Rekoordination der zweiten Phosphineinheit des Xantphos-Liganden vom Komplex Die beobachtete temperaturabhängige Stereodivergenz ist mçglicherweise durch eine b-Hydrideliminierung zu erklären, die ausgehend vom Acylkomplex I-NBE über den Übergangszustand ÜZ7 (Abbildung 2) abläuft.…”