General Cyclopropane Assembly via Enantioselective Redox-Active Carbene Transfer to Aliphatic Olefins

Montesinos‐Magraner, Marc; Costantini, Matteo; Ramírez-Contreras, Rodrigo; Muratore, Michael E.; Johansson, Magnus J.; Mendoza, Abraham

doi:10.26434/chemrxiv.7436795

Cited by 4 publications

(13 citation statements)

References 25 publications

(42 reference statements)

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“…2i , 2k , 2n , 2p , 2q Recently, Mendoza and co-workers disclosed the use of a new N -hydroxyphthalimide diazoacetate (NHPI-DA, 1a ) reagent, which displayed unique reactivity in combination with Iwasa’s ruthenium-phenyloxazoline catalyst (Ru-Pheox, 2 ). 4 , 5 This system enabled the synthesis of highly enantioenriched cyclopropanes 3 from olefin starting materials 4 , including challenging aliphatic alkenes ( Scheme 1 A). 5 The performance in the cyclopropanation reaction bestowed by the redox-active ester group in NHPI-DA ( 1a ) surpassed that of any comparable diazo compound reagent in terms of olefin scope and enantioselectivity.…”

Section: Introductionmentioning

confidence: 99%

Combined Experimental and Computational Study of Ruthenium N-Hydroxyphthalimidoyl Carbenes in Alkene Cyclopropanation Reactions

et al. 2021

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A combined experimental–computational approach has been used to study the cyclopropanation reaction of N -hydroxyphthalimide diazoacetate (NHPI-DA) with various olefins, catalyzed by a ruthenium-phenyloxazoline (Ru-Pheox) complex. Kinetic studies show that the better selectivity of the employed redox-active NHPI diazoacetate is a result of a much slower dimerization reaction compared to aliphatic diazoacetates. Density functional theory calculations reveal that several reactions can take place with similar energy barriers, namely, dimerization of the NHPI diazoacetate, cyclopropanation (inner-sphere and outer-sphere), and a previously unrecognized migratory insertion of the carbene into the phenyloxazoline ligand. The calculations show that the migratory insertion reaction yields an unconsidered ruthenium complex that is catalytically competent for both the dimerization and cyclopropanation, and its relevance is assessed experimentally. The stereoselectivity of the reaction is argued to stem from an intricate balance between the various mechanistic scenarios.

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Section: Introductionmentioning

confidence: 99%

Combined Experimental and Computational Study of Ruthenium N-Hydroxyphthalimidoyl Carbenes in Alkene Cyclopropanation Reactions

et al. 2021

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“…Gold(I) catalysts are one type of several metal complexes that are able to promote this transformation. 246 Some of the most often used metals in this type of cyclopropanation of alkenes are rhodium, 247 , 248 ruthenium, 249 − 252 copper, 253 , 254 cobalt, 255 − 257 and palladium. 258 − 260 Over the past 15 years, several gold(I) complexes have been employed to promote carbene transfer reactions to different nucleophiles.…”

Section: Construction Of 3-membered Rings Catalyzed By Goldmentioning

confidence: 99%

Gold-Catalyzed Synthesis of Small Rings

et al. 2020

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Three- and four-membered rings, widespread motifs in nature and medicinal chemistry, have fascinated chemists ever since their discovery. However, due to energetic considerations, small rings are often difficult to assemble. In this regard, homogeneous gold catalysis has emerged as a powerful tool to construct these highly strained carbocycles. This review aims to provide a comprehensive summary of all the major advances and discoveries made in the gold-catalyzed synthesis of cyclopropanes, cyclopropenes, cyclobutanes, cyclobutenes, and their corresponding heterocyclic or heterosubstituted analogs.

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“…8c − 8e In contrast, the N -hydroxyphthalimide (NHPI) esters ( 2 ) can be orthogonally activated in the presence of other carboxylates via single-electron reduction. 8a , 8b , 8f − 8l Recent methods based on desymmetrization 8n and late-stage carbene transfer 12 illustrate the potential of redox-active esters to be introduced through strategies unavailable to the parent carboxylic acids.…”

Section: Introductionmentioning

confidence: 99%

“…During our synthetic studies with redox-active carbenes, 12 we recognized that the coupling of redox-active esters and Michael acceptors 8a , 8b , 8f − 8l could significantly expand its capabilities with a suitable biocompatible reductant ( Scheme 1 B). The reduced nicotinamide adenine dinucleotide (NADH) would be ideal because it is a native component of biological systems.…”

Section: Introductionmentioning

confidence: 99%

Decarboxylative Alkyl Coupling Promoted by NADH and Blue Light

Chowdhury

Tong

et al. 2020

J. Am. Chem. Soc.

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Photoexcited dihydronicotinamides like NADH and analogues have been found to generate alkyl radicals upon reductive decarboxylation of redox-active esters without auxiliary photocatalysts. This principle allowed aliphatic photocoupling between redox-active carboxylate derivatives and electron-poor olefins, displaying surprising water and air-tolerance and unusually high coupling rates in dilute conditions. The orthogonality of the reaction in the presence of other carboxylic acids and its utility in the functionalization of DNA is presented, notably using visible light in combination with NADH, the ubiquitous reductant of life.

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General Cyclopropane Assembly via Enantioselective Redox-Active Carbene Transfer to Aliphatic Olefins

Abstract: Ap riority patent application has been filed (1850940-6), where A.M.,M .M-M.,M .C.a nd E.M.-C.a re listed as inventors.

Cited by 4 publications

References 25 publications

Combined Experimental and Computational Study of Ruthenium N-Hydroxyphthalimidoyl Carbenes in Alkene Cyclopropanation Reactions

Combined Experimental and Computational Study of Ruthenium N-Hydroxyphthalimidoyl Carbenes in Alkene Cyclopropanation Reactions

Gold-Catalyzed Synthesis of Small Rings

Decarboxylative Alkyl Coupling Promoted by NADH and Blue Light

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