Asymmetric Radical Cyclopropanation of α,β-Unsaturated Amides with α-Boryl and α-Silyl Dibromomethanes via Cr(II)-Based Metalloradical Catalysis

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(9), P. 7282 - 7292

Published: Feb. 20, 2025

Transition-metal-catalyzed asymmetric carbene-transfer reactions represent a powerful strategy for synthesizing chiral cyclopropanes. However, current methods predominantly rely on stabilized carbene-bearing α-π-conjugated groups, restricting access to less carbenes, such as α-silyl and α-boryl carbenes. Herein, we present an unprecedented Cr(II)-based metalloradical system the cyclopropanation of α,β-unsaturated amides with dibromomethanes in presence Mn reducing agent. Employing chromium complex, reaction proceeds under mild conditions, yielding cyclopropanes three contiguous stereocenters high diastereo- enantioselectivities. This method features Cr-catalyzed radical-based stepwise mechanism. The broad substrate scope, encompassing various amides, demonstrates protocol's versatility robustness. Mechanistic insights, supported by experimental computational studies, suggest formation α-Cr(III)-alkyl radical intermediates, delineating pathway distinct from that classical concerted cyclopropanations. approach provides tool highly functionalized cyclopropanes, offering potential applications drug discovery development.

Language: Английский

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Advances in the Synthesis of Cyclopropylamines

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Cyclopropylamines are an important subclass of substituted cyclopropanes that combine the unique electronic and steric properties with presence a donor nitrogen atom. In addition to their in diverse array biologically active compounds, cyclopropylamines utilized as synthetic intermediates, particularly ring-opening or cycloaddition reactions. Consequently, synthesis these compounds has constituted significant research topic, evidenced by abundant published methods. widely used Curtius rearrangement, classical cyclopropanation methods have been adapted integrate function (Simmons-Smith reaction, metal-catalyzed reaction diazo on olefins, Michael-initiated ring-closure reactions) advances enantioselective synthesis. More recently, specific developed for preparation aminocyclopropane moiety (Kulinkovich reactions applied amides nitriles, cyclopropenes, involving C-H functionalization, ...). The topic this review is present different cyclopropylamine derivatives, aim covering methodological best possible, highlighting scope, stereochemical aspects future trends.

Language: Английский

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Chromium‐Catalyzed Reductive Cross‐Coupling to Construct C−SS Bonds from Unactivated Alkyl Electrophiles

ChemCatChem, Journal Year: 2024, Volume and Issue: 16(15)

Published: March 15, 2024

Abstract Low‐valent chromium catalysts are cheap and less toxic compared to other transition metal catalysts. Here in, we reported a ligand‐free chromium(III)‐catalyzed manganese reductive cross‐coupling of unactivated alkyl electrophiles, such as sulfonates chlorides, with trisulfide dioxides thiolation agents form carbon−sulfur bonds. The powerful method featured ample substrate scope wide functional group tolerance, constructing large number unsymmetrical disulfides under simple conditions.

Language: Английский

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Redox Approaches to Carbene Generation in Catalytic Cyclopropanation Reactions

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(29)

Published: May 16, 2024

Abstract Transition metal‐catalyzed carbene transfer reactions have a century‐old history in organic chemistry and are primary method for the synthesis of cyclopropanes. Much work this field has focused on use diazo compounds related precursors, which can fragment to catalyst with concomitant loss stable byproduct. Despite utility approach, there persistent limitations scope viable carbenes, most notably those lacking stabilizing substituents. By coupling two‐electron redox cycles, it is possible expand available starting materials that be used as precursors. In Minireview, we discuss emerging catalytic reductive cyclopropanation using either gem ‐dihaloalkanes or carbonyl compounds. This strategy inspired by classic stoichiometric transformations, such Simmons–Smith Clemmensen reduction, but instead entails formation catalytically generated transition metal carbenoid. We also present recent efforts generate carbenes directly from methylene (CR 2 H ) groups via formal 1,1‐dehydrogenation. These currently restricted substrates containing electron‐withdrawing substituents, serve facilitate deprotonation subsequent oxidation anion.

Language: Английский

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Reductive Cyclopropanation through Bismuth Photocatalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(32), P. 22140 - 22144

Published: Aug. 5, 2024

We present here a catalytic method based on low-valent Bi complex capable of cyclopropanation double bonds under blue LED irradiation. The catalysis features various unusual Bi-based organometallic steps, namely, (1) two-electron inner sphere oxidative addition Bi(I) to CH2I2, (2) light-induced homolysis the Bi(III)–CH2I bond, (3) subsequent iodine abstraction-ring-closing, and (4) reduction Bi(III) with an external reducing agent close cycle. Stoichiometric experiments support proposed mechanism. This protocol represents unique example reductive photocatalytic process bismuth radical catalysis.

Language: Английский

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Cyano migration-mediated radical-polar crossover cyclopropanation

Science China Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 3, 2024

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Photocatalyzed Deuterodichloromethylation of Olefins Using Silacarboxylic Acids as Halogen‐Atom Transfer Reagents

European Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Abstract A visible‐light‐induced deuterodichloromethylation of alkenes was developed with readily available and inexpensive deuterochloroform as the reagent. Silacarboxylic acids, which could generate silyl radicals through efficient decarboxylation, were applied halogen atom transfer agents. series deuterium‐containing gem ‐dichloroalkanes prepared in good yields.

Language: Английский

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A Modular and Scalable Route to Protected Cyclopropane Amino Acid Building Blocks

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

An improved method for the synthesis of noncanonical cyclopropane amino acids from common laboratory reagents is described, avoiding use neurotoxic oxidants or precious metal catalysts. Intramolecular isocyanate trapping via a Hofmann rearrangement permits bicyclic carbamates in an enantioenriched and diastereopure manner. Subsequent ring-opening these species allows access to which can be further functionalized oxidation SN2 pathways incorporated into peptides solid-phase peptide synthesis.

Language: Английский

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Rapid and Practical Synthesis of gem‐Dibromoalkanes from Aldehydes by Tribromide Reagent

Chemistry - An Asian Journal, Journal Year: 2024, Volume and Issue: 19(5)

Published: Jan. 6, 2024

Abstract gem ‐Dibromoalkanes are important synthetic building block in organic chemistry, but their preparation is still troublesome. Herein, we have developed a simple and practical protocol for the synthesis of ‐dibromoalkanes from aldehydes using tetrabutylammonium tribromide triphenyl phosphite. A variety alkyl aromatic can be transformed into corresponding products within 10 minutes. This also applicable to alcohols, configuration chiral alcohol inverted during process with excellent enantiopurity.

Language: Английский

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Organoelectrocatalytic cyclopropanation of alkenyl trifluoroborates with methylene compounds

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 7, 2024

Cyclopropanes are not only privileged motifs in many natural products, agrochemicals, and pharmaceuticals, but also highly versatile intermediates synthetic chemistry. As such, great effort has been devoted to the cyclopropane construction. However, novel catalytic methods for cyclopropanation with two abundant substrates, mild conditions, high functional group tolerance, broad scope still desirable. Herein, we report an intermolecular electrocatalytic of alkenyl trifluoroborates methylene compounds. The reaction uses simple diphenyl sulfide as electrocatalyst under base-free conditions. And thus, a various compounds well vinyltrifluoroborates is demonstrated, including styrenyl, 1,3-dienyl, fluorosulfonyl, base-sensitive substrates. Preliminary mechanistic studies presented, revealing critical role boryl substituent facilitate desired pathway water hydrogen atom source.

Language: Английский

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