Strategic Synthesis of γ-Nitroketones between Nitroalkanes and Cyclopropanols: Harnessing Free-Radical Nucleophilic Substitution for Chemical Innovation DOI

Yi-Wei Xu,

Zhongyu Zhang,

Cong Wei

et al.

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

Published: March 25, 2025

The alkylation of nitro compounds is an efficient technique to augment molecular complexity, as exemplified by the Henry reaction and Michael addition involving sp2-hybridized carbon. However, a challenge arises in with sp3-hybridized carbon due competing nonproductive O-alkylation. In this study, we have developed manganese-promoted oxidative nitroalkanes using cyclopropyl alcohols via solvent-caged free-radical nucleophilic substitution pathway. This process yields variety γ-nitroketones, including sterically hindered tertiary nitroalkanes, thereby introducing novel approach for C-alkylation nitroalkanes. Subsequent reduction facilitates synthesis pyrroline pyrrolidine derivatives.

Language: Английский

Single Electron Transfer-Induced Redox Processes Involving N-(Acyloxy)phthalimides DOI

Sushanta Kumar Parida,

Tanumoy Mandal,

Sanju Das

et al.

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(3), P. 1640 - 1683

Published: Jan. 20, 2021

The past decade has witnessed the emergence of N-(acyloxy)phthalimides (NHPI esters) and its derivatives at forefront synthetic methods facilitating construction diverse molecular frameworks from readily available carboxylic acid feedstock. NHPI esters are predisposed to undergo reductive fragmentation via a single electron transfer (SET) process under thermal, photochemical, or electrochemical conditions generate corresponding carbon- nitrogen-centered radicals that participate in multitude transformations forge carbon–carbon carbon–heteroatom bonds. chemistry involving received broad applicability not only well-designed cascade annulations but also medicinal natural product synthesis. This comprehensive Review, broadly categorized according nature bond formation, details progress made this field since initial discovery by providing representative examples with mechanistic details, an emphasis on challenges future directions.

Language: Английский

Citations

274
Selective Carbon–Carbon Bond Cleavage of Cyclopropanols DOI
Tyler McDonald, L. Reginald Mills,

Michael S. West

et al.

Chemical Reviews, Journal Year: 2020, Volume and Issue: 121(1), P. 3 - 79

Published: Oct. 21, 2020

The carbon–carbon (C–C) bond cleavage of cyclopropanols is a wide area research with much current activity. This review highlights new developments in this over the past two decades. A summary made three main reactivity modes, namely, homoenolate chemistry, β-keto radical and acid-catalyzed ring-opening, as well all other methods for C–C functionalization cyclopropanols, including base-mediated metal-catalyzed insertions eliminations, oxidative fragmentation using hypervalent iodine reagents, reactions donor–acceptor pericylic reactions. Emphasis placed on synthetic utility related derivatives, which have emerged unique three-carbon synthons.

Language: Английский

Citations

235
On the Origin of Rh-Catalyzed Selective Ring-Opening Amidation of Substituted Cyclopropanols to Access β2-Amino Ketones DOI
Minhan Lee, Joon Heo, Dongwook Kim

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(8), P. 3667 - 3675

Published: Feb. 15, 2022

β2-Amino carbonyls, an α-substituted β-amino scaffold, hold a prominent place in the development of new pharmaceuticals and peptidomimetics. Herein, we report highly efficient Rh-catalyzed ring-opening amidation substituted cyclopropanols, which turned out to serve as linchpin for selective synthesis β2-amino ketones outcompete formation β3-isomers. Instead generally accepted rationale consider steric factors β2-selectivity, orbital interaction was elucidated play more critical role amidative cyclopropanols generate key Rh–C intermediate. Subsequent inner-sphere acylnitrene transfer achieved excellent efficiency (TON > 5000) by using readily accessible dioxazolones amino source afford with broad applicability.

Language: Английский

Citations

43
Effect of 6,6′-Substituents on Bipyridine-Ligated Ni Catalysts for Cross-Electrophile Coupling DOI

Haotian Huang,

Jose L. Alvarez-Hernandez, Nilay Hazari

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(9), P. 6897 - 6914

Published: April 19, 2024

A family of 4,4′-tBu2-2,2′-bipyridine (tBubpy) ligands with substituents in either the 6-position, 4,4′-tBu2-6-Me-bpy (tBubpyMe), or 6 and 6′-positions, 4,4′-tBu2-6,6′-R2-bpy (tBubpyR2; R = Me, iPr, sBu, Ph, Mes), was synthesized. These were used to prepare Ni complexes 0, I, II oxidation states. We observed that 6′-positions tBubpy ligand impact properties complexes. For example, bulkier 6,6′-positions better stabilized (tBubpyR2)NiICl species resulted a cleaner reduction from (tBubpyR2)NiIICl2. However, hindered prevented coordination tBubpyR2 Ni0(cod)2. In addition, by using type (tBubpyMe)NiCl2 (tBubpyR2)NiCl2 as precatalysts for different XEC reactions, we demonstrated 6,6′-substituents lead major differences catalytic performance. Specifically, while (tBubpyMe)NiIICl2 is one most active catalysts reported date can facilitate reactions at room temperature, lower turnover frequencies containing ligands. detailed study on intermediates (tBubpy)Ni(Ar)I (tBubpyMe2)Ni(Ar)I revealed several factors likely contributed activity. whereas are low spin relatively stable, high-spin less stable. Furthermore, captures primary benzylic alkyl radicals more slowly than (tBubpy)Ni(Ar)I, consistent activity former catalysis. Our findings will assist design tailor-made Ni-catalyzed transformations.

Language: Английский

Citations

9
Ni-Catalyzed Denitrogenative Cross-Coupling of Benzotriazinones and Cyclopropanols: An Easy Access to Functionalized β-Aryl Ketones DOI
Jincan Li, Yan Zheng, Mingxian Huang

et al.

Organic Letters, Journal Year: 2020, Volume and Issue: 22(13), P. 5020 - 5024

Published: June 11, 2020

A novel Ni-catalyzed denitrogenative cross-coupling between benzotriazinones and cyclopropanols is reported herein. This neoteric reactivity allows for the convenient synthesis of β-(o-amido)aryl ketones from readily available starting materials with good yields (up to 93%) general substrate scope.

Language: Английский

Citations

56
Metal-Catalyzed Transformations of Cyclopropanols via Homoenolates DOI Open Access
Yoshiya Sekiguchi, Naohiko Yoshikai

Bulletin of the Chemical Society of Japan, Journal Year: 2020, Volume and Issue: 94(1), P. 265 - 280

Published: Sept. 28, 2020

Abstract Metal homoenolates represent uniquely useful organometallic intermediates in synthetic chemistry, allowing umpolung synthesis of β-functionalized carbonyl compounds. While siloxycyclopropanes had been established as reliable precursors to homoenolates, often stoichiometric, for diverse carbon–carbon bond forming reactions, unprotected cyclopropanols have emerged alternative and attractive catalytically generated, carbon–heteroatom bond-forming reactions. This review article provides an overview the development such homoenolate transformations, classified with respect metals involved cyclopropane ring opening.

Language: Английский

Citations

56
Nickel-Catalyzed Carbonylation of Cyclopropanol with Benzyl Bromide for Multisubstituted Cyclopentenone Synthesis DOI

Liting Hou,

Wenyi Huang,

Xianqing Wu

et al.

Organic Letters, Journal Year: 2022, Volume and Issue: 24(14), P. 2699 - 2704

Published: April 7, 2022

Herein, we reported a Ni-catalyzed carbonylation of cyclopropanol with benzyl bromide to afford multisubstituted cyclopentenone under 1 atm CO. The reaction proceeds through cascade bromides, followed by generation nickel homoenolate from cyclopropanols via β-C elimination 1,4-diketones, which undergoes intramolecular Aldol condensation furnish highly substituted derivatives in moderate good yields. exhibits high functional group tolerance broad substrate scope.

Language: Английский

Citations

30
Enantioselective Copper‐Catalyzed Radical Ring‐Opening Cyanation of Cyclopropanols and Cyclopropanone Acetals DOI
Lianqian Wu, Lei Wang, Pinghong Chen

et al.

Advanced Synthesis & Catalysis, Journal Year: 2020, Volume and Issue: 362(11), P. 2189 - 2194

Published: March 17, 2020

Abstract A novel approach for enantioselective cyanation of cyclopropanols and their derivatives through copper‐catalyzed radical relay processes has been developed. Various cyclopropanone acetals are compatible to the catalytic conditions, providing β‐carbonyl nitriles with excellent enantioselectivity. These products can be readily converted chiral γ‐amino acids drugs such as (R)‐baclofen. Preliminary mechanistic studies have supported a ring‐opening process cyclopropanoxy radicals followed by benzylic form C−CN bonds in an manner. magnified image

Language: Английский

Citations

48
The Cyclopropane Ring as a Reporter of Radical Leaving-Group Reactivity for Ni-Catalyzed C(sp3)–O Arylation DOI
L. Reginald Mills,

John J. Monteith,

Gabriel dos Passos Gomes

et al.

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(30), P. 13246 - 13254

Published: July 1, 2020

The ability to understand and predict reactivity is essential for the development of new reactions. In context Ni-catalyzed C(sp3)–O functionalization, we have developed a unique strategy employing activated cyclopropanols aid design optimization redox-active leaving group arylation. this chemistry, cyclopropane ring acts as reporter leaving-group reactivity, since ring-opened product obtained under polar (2e) conditions, ring-closed radical (1e) conditions. Mechanistic studies demonstrate that optimal are consistent with Ni(I)/Ni(III) catalytic cycle. optimized reaction conditions also used synthesize number arylcyclopropanes, which valuable pharmaceutical motifs.

Language: Английский

Citations

46
Rhodium-Catalyzed Room Temperature C–C Activation of Cyclopropanol for One-Step Access to Diverse 1,6-Diketones DOI
Bedadyuti Vedvyas Pati, Asit Ghosh, Ponneri C. Ravikumar

et al.

Organic Letters, Journal Year: 2020, Volume and Issue: 22(7), P. 2854 - 2860

Published: March 25, 2020

A rhodium-catalyzed room temperature C-C activation of cyclopropanol has been demonstrated for the single-step synthesis a range electronically and sterically distinct 1,6-diketones. This reaction proceeds efficiently in shorter time following highly atom-economical pathway. To illustrate synthetic potential 1,6-diketones, aldol macrocyclization reactions have successfully demonstrated. Preliminary mechanistic studies revealed involvement nonradical pathways.

Language: Английский

Citations

43