Advances in the Synthesis of Cyclopropylamines

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Март 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.

Язык: Английский

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Modern Cyclopropanation via Non‐Traditional Building Blocks

ChemCatChem, Год журнала: 2024, Номер 16(14)

Опубликована: Март 13, 2024

Abstract Small, strained carbocyclic systems have fascinated organic chemists from both a theoretical and synthetic standpoint. These often challenge conventional wisdom when it comes to molecular structure tactics for chemical construction. The cyclopropyl motif is one such ring system that remains at the forefront of method development in modern era. With advent an array non‐traditional building blocks, range new cyclopropanation processes using one‐ two‐electron strategies been developed not only overcome shortcomings classical approaches but also provide entry into wide classes cyclopropanes. This review discusses recent advances this area with emphasis on their mechanistic underpinnings potential applications. Additionally, concise overview properties traditional cyclopropanes provided.

Язык: Английский

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Redox Approaches to Carbene Generation in Catalytic Cyclopropanation Reactions

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(29)

Опубликована: Май 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.

Язык: Английский

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Reductive Cyclopropanation through Bismuth Photocatalysis

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(32), С. 22140 - 22144

Опубликована: Авг. 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.

Язык: Английский

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Flow Electroreductive Nickel‐Catalyzed Cyclopropanation of Alkenes Using gem‐Dichloroalkanes

Angewandte Chemie International Edition, Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

Abstract Cyclopropanes are valuable motifs in organic synthesis, widely featured pharmaceuticals and functional materials. Herein, we report an efficient electrochemical methodology for the cyclopropanation of alkenes, leveraging a nickel‐catalyzed process continuous‐flow. The developed protocol demonstrates broad substrate scope, accommodating both electron‐rich electron‐poor alkenes with high group tolerance. Beyond dichloromethane as feedstock methylene source, enables synthesis methylated, deuterated, chloro‐substituted cyclopropanes. Mechanistic investigations suggest electro‐generation nickel carbene key intermediate. Notably, reaction operates under ambient conditions, tolerates air moisture, achieves scalability through continuous‐flow technology, offering straightforward route to multi‐gram quantities enhanced throughput.

Язык: Английский

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Nitrocyclopropanes as Valuable Building Blocks in Organic Synthesis and Biology: Exploring the Origin of the Nitro Group

Chemistry - A European Journal, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Cyclopropane derivatives serve as important building blocks in organic synthesis, due to their three-membered stretched ring. Nitro-substituted cyclopropanes (NCPs) represent a special class of donor-acceptor (DACs) that contain strong electron-withdrawing nitro group substituent on the cyclopropyl moiety. Due versatile nature group, which can be converted into other functional azo groups or heterocyclic scaffolds, NCPs are considered design complex compounds. Herein, present review is organized two main sections focused synthesis and application NCPs. The part containing synthetic methodologies has been further divided distinct based mainly starting materials, such as: a) from nitroalkenes, b) nitro-bearing diazo compounds, c) nitroalkanes combination with alkenes, d) aminocyclopropanes under oxidative conditions, e) various through miscellaneous processes. In concerning applications use NCPs, categorization includes three subcategories, reduction 1-aminocyclopropane-1-carboxylic acids (ACC), ring opening leading valuable open-chain heterocycles, expansion larger cyclic

Язык: Английский

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Building Efficient Diastereo- and Enantioselective Synthetic Routes to trans-Cyclopropyl Esters for Rapid Lead Scale-Up

Organic Process Research & Development, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Язык: Английский

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

European Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 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.

Язык: Английский

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Stereoselective Cyclopropanation of Multisubstituted Enesulfinamides: Asymmetric Construction of α-Tertiary Cyclopropylamine Derivatives Containing β-Quaternary Stereocenters

Organic Letters, Год журнала: 2024, Номер 26(13), С. 2606 - 2611

Опубликована: Март 21, 2024

Enesulfinamides with α,β,β-trisubstitution undergo a Simmons–Smith reaction to yield multisubstituted cyclopropylamine derivatives high stereocontrol. The resulting α-tertiary derivatives, which feature β-quaternary stereocenters bearing two electronically and sterically similar substituents (e.g., methyl ethyl), are seldom achieved by using conventional methods. By adjusting the stereochemistry of carbon–carbon double bond and/or sulfinyl group within enesulfinamides, it is feasible selectively produce four stereoisomers cyclopropylamines, each different absolute configurations at α- β-carbons.

Язык: Английский

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Dichloromethane as C1 Synthon for the Photoredox Catalytic Cyclopropanation of Aromatic Olefins

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Июнь 11, 2024

Dichloromethane, as a readily available and inexpensive C

Язык: Английский

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