Catalytic Asymmetric Deoxygenative Cyclopropanation Reactions by a Chiral Salen-Mo Catalyst

Abstract

The catalytic asymmetric cyclopropanation reaction of alkenes with diazo compounds is a direct and powerful method to construct chiral cyclopropanes that are essential to drug discovery. However, diazo compounds are potentially explosive and often require hazardous reagents for their preparation. Here, we report on the use of 1,2-dicarbonyl compounds as safe and readily available surrogates for diazo compounds in the direct catalytic asymmetric deoxygenative cyclopropanation reaction. Enabled by a class of simple and readily accessible chiral salen-Mo catalysts, the reaction proceeded with generally good enantioselectivities and yields toward a wide range of substrates (80 examples). Preliminary mechanistic studies suggested that the proposed μ-oxo bridged dinuclear Mo(III)-species was the catalytically active species. This strategy not only provides a promising route for the synthesis of chiral cyclopropanes but also opens a new window for the potential applications of chiral salen-Mo complexes in asymmetric catalysis.

Modular Access tometa-Substituted Benzenes via Mo-Catalyzed Intermolecular Deoxygenative Benzene Formation

“…A central research program of our laboratory has been the development of novel Mo-catalyzed deoxygenative functionalization reactions of carbonyl compounds, thus circumventing the use of hazardous diazo compounds. , A major challenge of this goal is to both cleave the strong CO double bonds ,, and control the selectivities including regio-, chemo-, and stereoselectivities. Enabled by the (chiral) low-valent molybdenum catalysts, an intramolecular deoxygenative C–H bond functionalization, an intramolecular (asymmetric) deoxygenative cyclopropanation, , an intramolecular deoxygenative C–N bond formation, an intermolecular deoxygenative formal N–H insertion/carbonyl–carbonyl olefination cascade process, and homodimerization of aldehydes as well as intramolecular deoxygenative olefination of dicarbonyl compounds have been respectively developed by Asako, Takai, Ilies et al, and our laboratory.…”

“…Despite these elegant advances, the Mo-catalyzed direct intermolecular deoxygenative coupling of carbonyl compounds with suitable coupling partners has been scarcely investigated, likely due to the reactivity and selectivity issues . Inspired by the powerful low-valent molybdenum catalysts that possess unique Lewis acidity, oxophilicity, and reducing ability, ,,− we envisioned that the Mo-catalyzed direct intermolecular deoxygenative coupling of readily available ynones with allylic amines might provide a general approach to the 1,3-di- and 1,3,5-trisubstituted benzene derivatives (Scheme C). In this design, the Mo-catalyst should not only play multiple vital roles in promoting the aza-Michael addition/[1,5]-hydride shift/cyclization/aromatization cascade processes but also control the regio- and chemoselectivities.…”

“…The feasibility of Mo-catalyzed intermolecular deoxygenative benzene-forming reaction was initially investigated using ynone 1a and allylic amine 2a as the model substrates (Table ). In the presence of 10 mol % of Mo­(CO) 6 , 10 mol % of 3,5-di- tert -butyl- o -benzoquinone ( o -quinone), ,− and 2 equiv of PPh 3 , the meta -substituted benzene product 3a was obtained in 51% yield (entry 1). Next, reductants such as phosphine, bisphosphine, silane, and B 2 pin 2 were investigated (entries 2–9).…”

“…Based on the experimental observations and the literature precedent, ,− a plausible reaction pathway was proposed (Scheme ). At first, the intermolecular 1,4-addition of allylic amine 2a to ynone 1a promoted by the Mo­(II)-catalyst M-1 , which formed through oxidation of Mo­(CO) 6 by o -quinone, generated intermediate Int-2 .…”

“…Then, the Mo-catalyzed [1,5]-hydride shift of intermediate Int-2 occurred to produce intermediate M-2 , which subsequently underwent the intramolecular nucleophilic addition to afford the bis-vinyl-substituted aziridine Int-3 and oxo-Mo - species M-3 . The regeneration of Mo-catalyst M-1 was achieved through reduction of oxo-Mo-complex M-3 by phosphine. ,, Meanwhile, the regioselective ring opening of the aziridine ring promoted by the Lewis acidic Mo-catalyst, followed by a cyclization reaction, provided intermediate Int-4 . Finally, a reaction sequence of deprotonation, protodemetalation, and retro -hydroamination occurred to afford meta -substituted benzene product 3a and methanamine, which might be captured by the excess amount of ynone substrate 1a .…”