Photosensitized Dioxygen Enables Intermolecular Cyclopropanation of Alkenes Directly with Active Methylene Compounds DOI Creative Commons
Dhruba P. Poudel, Amrit Pokhrel, Raj Kumar Tak

et al.

Published: March 20, 2023

Cyclopropane, a versatile synthetic intermediate, is forged as key structural feature in many preclinical, clinical and commercial drugs, occur skeletal motif numerous natural products. The most prolific technique for its synthesis the metal-catalyzed reaction of an alkene with diazoalkane, highly energetic, reactive explosive reagent requiring stringent safety precautions. expedient construction cyclopropyl ring on alkenes convenient innocuous reagents under nonhazardous conditions remains ongoing challenge. Herein, we report simple photoredox-catalyzed intermolecular cyclopropanation unactivated diverse set active methylene compounds that demonstrates striking conceptual practical advances over known methods. proceeds photoredox catalyst (PC*) excited blue LED light air/O2 neutral presence catalytic amounts iodine, either form added molecular I2 or generated situ from alkyl iodides. . remarkably broad scope applicability 19 different 5 clusters standpoint tolerability, tolerates wide range functional groups. Moreover, also amenable complex architectures, pharmaceuticals Mechanistic investigation through isolation series intermediate products, probes, control experiments, UV-Vis fluorescence studies indicate photosensitized dioxygen plays vital role generation carbon-centered radicals both addition to closure, catalytically iodine recycles PC.

Language: Английский

Practical and General Alcohol Deoxygenation Protocol DOI Creative Commons
Oliver P. Williams, Alyah F. Chmiel, Myriam Mikhael

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(18)

Published: Feb. 25, 2023

Herein, we describe a practical protocol for the removal of alcohol functional groups through reductive cleavage their benzoate ester analogs. This transformation requires strong single electron transfer (SET) reductant and means to accelerate slow fragmentation following substrate reduction. To accomplish this, developed photocatalytic system that generates potent from formate salts alongside Brønsted or Lewis acids promote reduced intermediate. deoxygenation procedure is effective across structurally electronically diverse alcohols enables variety difficult net transformations. no precautions exclude air moisture remains efficient on multigram scale. Finally, can be adapted one-pot benzoylation-deoxygenation sequence enable direct deletion. Mechanistic studies validate role acidic additives key C(sp

Language: Английский

Citations

42
Photocatalyzed Borylcyclopropanation of Alkenes with a (Diborylmethyl)iodide Reagent DOI Creative Commons
Jiefeng Hu, Man Tang, Jing Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(38)

Published: Aug. 2, 2023

Cyclopropane skeletons play a prominent role in the development of organic synthesis and pharmaceutical chemistry. Herein, we report design stable, multifunctional (diborylmethyl)iodide reagent (CHI(Bpin)2 ) for photoinduced cyclopropanation alkenes, providing an array 1,2-substituted cyclopropylboronates good yields. This α-haloboronic ester can be readily synthesized on multigram scale from commercially available starting materials. Furthermore, protocol displays high chemo- diastereoselectivity, excellent functional-group tolerance, allows late-stage borylcyclopropanation complex molecules. Mechanistic studies reveal that proceeds through radical addition/polar cyclization pathway mediated by photocatalyst fac-Ir(ppy)3 visible light.

Language: Английский

Citations

34
Photosensitized O 2 enables intermolecular alkene cyclopropanation by active methylene compounds DOI
Dhruba P. Poudel, Amrit Pokhrel, Raj Kumar Tak

et al.

Science, Journal Year: 2023, Volume and Issue: 381(6657), P. 545 - 553

Published: Aug. 3, 2023

Cyclopropanes are key features in many preclinical, clinical, and commercial drugs, as well natural products. The most prolific technique for their synthesis is the metal-catalyzed reaction of an alkene with a diazoalkane, highly energetic reagent requiring stringent safety precautions. Discovery alternative innocuous reagents remains ongoing challenge. Herein, we report simple photoredox-catalyzed intermolecular cyclopropanation unactivated alkenes active methylene compounds. proceeds neutral solvent under air or dioxygen (O 2 ) photoredox catalyst excited by blue light-emitting diode light iodine co-catalyst that either added molecular generated situ from alkyl iodides. Mechanistic investigations indicate photosensitized O plays vital role generation carbon-centered radicals both addition compounds to ring closure.

Language: Английский

Citations

34
Generating Fischer-Type Rh-Carbenes with Rh-Carbynoids DOI Creative Commons

Eric Palomo,

Akhilesh K. Sharma, Zhaofeng Wang

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(9), P. 4975 - 4981

Published: Feb. 22, 2023

We describe the first catalytic generation of Fischer-type acyloxy Rh(II)-carbenes from carboxylic acids and Rh(II)-carbynoids. This novel class transient donor/acceptor evolved through a cyclopropanation process providing access to densely functionalized cyclopropyl-fused lactones with excellent diastereoselectivity. DFT calculations allowed analysis properties Rh(II)-carbynoids as well characterization mechanism.

Language: Английский

Citations

30
Silver(I)-Catalyzed Stereochemical Isomerization of Cyclopropanols DOI Creative Commons

Rajat Shankhdhar,

Sylwia Górczyńska, Kacper Błaziak

et al.

Organometallics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Isomerization of cyclopropane-containing molecules offers a direct pathway to access all their diastereoisomers. Current catalytic methods, however, are largely confined isomerization carbonyl- and vinyl-substituted cyclopropanes. We report cyclopropanols, which converts readily accessible cis-1,2-disubstituted cyclopropanols into more stable, yet often less accessible, trans-isomers. This enables straightforward both diastereoisomers these small-ring molecules. Mechanistic studies indicate the reactivity silver homoenolates.

Language: Английский

Citations

1
Advances in the Synthesis of Cyclopropylamines DOI
Philippe Bertus,

Julien Caillé

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

Citations

1
Site‐ and Stereoselective C(sp3)−H Borylation of Strained (Hetero)Cycloalkanols Enabled by Iridium Catalysis DOI
Qian Gao, Senmiao Xu

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(8)

Published: Dec. 30, 2022

Transition metal-catalyzed site- and stereoselective C-H activation of strained (hetero)cycloalkanes remains a formidable challenge. We herein report carbamate-directed iridium-catalyzed asymmetric β-C(sp3 )-H borylation cyclopropanol derivatives. A variety densely functionalized cyclopropanols were obtained in good enantioselectivities via desymmetrization kinetic resolution. In addition, site-selective C(sp3 methine groups furnished α-borylated (hetero)cycloalkanols moderate to yields. The synthetic utility the method was further shown gram-scale synthesis diverse downstream transformations borylated products.

Language: Английский

Citations

30
Redox Approaches to Carbene Generation in Catalytic Cyclopropanation Reactions DOI Creative Commons
Mingxin Liu, Christopher Uyeda

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

Citations

7
Ti-Catalyzed Modular Ketone Synthesis from Carboxylic Derivatives and gem-Dihaloalkanes DOI

Jiabin Ni,

Xiaowen Xia,

Danyu Gu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(27), P. 14884 - 14893

Published: June 26, 2023

Ketones are ubiquitous in organic synthesis. However, the general method to convert widely available carboxylic acids, unactivated esters, and amides into ketones remains elusive. Herein, we describe Ti-catalyzed modular ketone synthesis from derivatives easily accessed gem-dihaloalkanes. Notably, this protocol could achieve direct catalytic olefination of acids. This features a sequence electrophilic transformation good functional group compatibility allows rapid access various functionalized ketones. Preliminary mechanistic studies provide insights reaction pathway support intermediacy plausible alkylidene titanocene gem-bimetallic complexes.

Language: Английский

Citations

13
Manganese-catalyzed cyclopropanation of allylic alcohols with sulfones DOI Creative Commons

Ke Yu,

Qin Nie,

Qianjin Chen

et al.

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

Published: Aug. 9, 2024

Cyclopropanes are among the most important structural units in natural products, pharmaceuticals, and agrochemicals. Herein, we report a manganese-catalyzed cyclopropanation of allylic alcohols with sulfones as carbene alternative precursors via borrowing hydrogen strategy under mild conditions. Various arylmethyl trifluoromethyl work efficiently this transformation thereby deliver corresponding cyclopropylmethanol products 58% to 99% yields. Importantly, major benefit is that versatile free alcohol moiety retained resultant which can undergo wide range downstream transformations provide access series functional molecules. Mechanistic studies support sequential reaction mechanism involves catalytic dehydrogenation, Michael addition, cyclization, hydrogenation.

Language: Английский

Citations

4