Inner- and Outer-Sphere Cross-Coupling of High Fsp3 Fragments DOI

Simona Kotesova,

Ryan A. Shenvi

Accounts of Chemical Research, Год журнала: 2023, Номер 56(21), С. 3089 - 3098

Опубликована: Окт. 27, 2023

ConspectusNatural product research originates from a desire to explore, understand, and perturb biological function with atomic precision. To reach these goals at all, let alone efficiently, requires thoughtful creative problem solving. Often this means bold disconnections that would simplify access complex structures, if only the methods existed bridge theoretical gaps. Whereas interrogations provide long-term intellectual value impetus, come as attractive fringe benefits of natural synthesis. This Account describes strategic, methodological solutions syntheses products [(−)-eugenial C, Galbulimima alkaloids GB18, GB22, GB13, himgaline] featuring new, convergent important problem-solving steps, which themselves were inspired by recent arose our group. Each target required invention first-row transition metal-catalyzed cross-coupling procedures satisfy project. In cases, synthetic strategy identified gap (the absence stereo- chemoselective couplings appropriate fragments), but tactical advantage conferred metals met challenge. These competent handle dense, sterically encumbered motifs common due to, in many elementary steps did not require bond formation between hindered substrate metal center. Instead, lenient reactions appeared involve metal–ligand–substrate (i.e., outer-sphere steps), contrast metal–substrate, coordinative precious inner-sphere steps). Key observations previous studies, combined seminal publications other laboratories (Mattay, Weix, MacMillan), led optimization ligand-controlled, stereoselective introduction complementary catalytic cycles revealed new modes reactivity generated novel structural motifs. Optimized bioactive space accelerated timeline characterization, fulfilling premise research. The integration methodology, synthesis, diversification, bioassay into single Ph.D. dissertation have been unmanageable prior era. unique ability effect Csp3–Csp3 high chemo- stereoselectivity has significantly lowered barrier avowed goal synthesis reduced burden (real or perceived) integrating functional campaigns.

Язык: Английский

Rapid and Modular Access to Quaternary Carbons from Tertiary Alcohols via Bimolecular Homolytic Substitution DOI
Colin A. Gould, Andria L. Pace, David W. C. MacMillan

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(30), С. 16330 - 16336

Опубликована: Июль 20, 2023

Quaternary carbons are ubiquitous in bioactive molecules; however, synthetic methods for the construction of this motif remain underdeveloped. Here, we report synthesis quaternary from tertiary alcohols, a class structurally diverse, bench-stable feedstocks, via merger photoredox catalysis and iron-mediated SH2 bond formation. This alcohol-bromide cross-coupling is enabled by novel halogen-atom transfer (XAT) reagent, which first reductively activated XAT reagent to be reported. A wide variety sterically congested products can accessed through mild practical protocol including derived both alkylation benzylation fragments. We further demonstrate utility method expedited liver receptor agonist two-step conversion ketones esters products, enables modular control up three four substituents on center.

Язык: Английский

Процитировано

49
Alcohol-alcohol cross-coupling enabled by S H 2 radical sorting DOI
Ruizhe Chen, Nicholas E. Intermaggio, Jiaxin Xie

и другие.

Science, Год журнала: 2024, Номер 383(6689), С. 1350 - 1357

Опубликована: Март 21, 2024

Alcohols represent a functional group class with unparalleled abundance and structural diversity. In an era of chemical synthesis that prioritizes reducing time to target maximizing exploration space, harnessing these building blocks for carbon-carbon bond-forming reactions is key goal in organic chemistry. particular, leveraging single activation mode form new C(sp

Язык: Английский

Процитировано

49
Alkene dialkylation by triple radical sorting DOI
Johnny Wang, William L. Lyon, David W. C. MacMillan

и другие.

Nature, Год журнала: 2024, Номер 628(8006), С. 104 - 109

Опубликована: Фев. 13, 2024

Язык: Английский

Процитировано

40
Carbon quaternization of redox active esters and olefins by decarboxylative coupling DOI
Xu-cheng Gan,

Benxiang Zhang,

Nathan Dao

и другие.

Science, Год журнала: 2024, Номер 384(6691), С. 113 - 118

Опубликована: Апрель 4, 2024

The synthesis of quaternary carbons often requires numerous steps and complex conditions or harsh reagents that act on heavily engineered substrates. This is largely a consequence conventional polar-bond retrosynthetic disconnections in turn require multiple functional group interconversions, redox manipulations, protecting chemistry. Here, we report simple catalyst reductant combination converts two types feedstock chemicals, carboxylic acids olefins, into tetrasubstituted through quaternization radical intermediates. An iron porphyrin activates each substrate by electron transfer hydrogen atom transfer, then combines the fragments using bimolecular homolytic substitution (S

Язык: Английский

Процитировано

32
A Bimolecular Homolytic Substitution-Enabled Platform for Multicomponent Cross-Coupling of Unactivated Alkenes DOI
Fei Cong,

Guo‐Quan Sun,

Si‐Han Ye

и другие.

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(15), С. 10274 - 10280

Опубликована: Апрель 3, 2024

The construction of C(sp3)–C(sp3) bonds remains one the most difficult challenges in cross-coupling chemistry. Here, we report a photoredox/nickel dual catalytic approach that enables simultaneous formation two linkages via trimolecular alkenes with alkyl halides and hypervalent iodine-based reagents. reaction harnesses bimolecular homolytic substitution (SH2) mechanism chemoselective halogen-atom transfer (XAT) to orchestrate regioselective addition electrophilic nucleophilic radicals across unactivated without need for directing auxiliary. Utility is highlighted through late-stage (fluoro)alkylation (trideutero)methylation C═C bearing different patterns, offering straightforward access drug-like molecules comprising sp3-hybridized carbon scaffolds.

Язык: Английский

Процитировано

26
Engaging Alkenes in Metallaphotoredox: A Triple Catalytic, Radical Sorting Approach to Olefin-Alcohol Cross-Coupling DOI
Qinyan Cai, Iona M. McWhinnie, Nathan W. Dow

и другие.

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(18), С. 12300 - 12309

Опубликована: Апрель 24, 2024

Metallaphotoredox cross-coupling is a well-established strategy for generating clinically privileged aliphatic scaffolds via single-electron reactivity. Correspondingly, expanding metallaphotoredox to encompass new C(

Язык: Английский

Процитировано

21
Alkene Hydrobenzylation by a Single Catalyst That Mediates Iterative Outer-Sphere Steps DOI

Lingran Kong,

Xu-cheng Gan, Vincent A. van der Puyl

и другие.

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(4), С. 2351 - 2357

Опубликована: Янв. 17, 2024

Cross-coupling catalysts typically react and unite functionally distinct partners via sequential inner-sphere elementary steps: coordination, migratory insertion, reductive elimination, etc. Here, we report a single catalyst that cross-couples styrenes benzyl bromides iterative outer-sphere metal–ligand-carbon interactions. Each partner forms stabilized radical intermediate, yet heterocoupled products predominate. The system is redox-neutral and, thus, avoids exogenous oxidants, resulting in simple scalable conditions. Numerous variations of alkene hydrobenzylation are made possible, including access to the privileged heterodibenzyl (1,2-diarylethane) motif challenging quaternary carbon variants.

Язык: Английский

Процитировано

19
Aminoalkylation of Alkenes Enabled by Triple Radical Sorting DOI
William L. Lyon, Johnny Wang, Jesús Alcázar

и другие.

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

The direct synthesis of C(sp3)-rich architectures is a driving force for innovation in synthetic organic chemistry. Such scaffolds impart beneficial properties onto drug molecules that correlate with greater clinical success. Consequently, there strong impetus to develop new methods by which access sp3-rich from commercial feedstocks, such as alkenes. Herein, we report three-component aminoalkylation reaction utilizes the principles triple radical sorting regioselectively add N-centered and C-centered radicals across This process relies upon photoredox catalysis transform alkyl bromides reductively activated precursors into high-energy species redox-neutral fashion. A broad scope coupling partners demonstrated, multiple applications, including facile syntheses pharmacophoric substituted N-heterocycles.

Язык: Английский

Процитировано

5
Iron-Catalyzed Aerobic Carbonylation of Methane via Ligand-to-Metal Charge Transfer Excitation DOI Creative Commons
Hui Pan, Qing An, Binh Khanh

и другие.

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

The integration of ligand-to-metal charge transfer (LMCT) catalytic paradigms with radical intermediates has transformed the selective functionalization inert C-H bonds, facilitating use nonprecious metal catalysts in demanding transformations. Notably, aerobic carbonylation methane to acetic acid remains formidable due rapid oxidation methyl radicals, producing undesired C1 oxygenates. We present an iron terpyridine catalyst utilizing LMCT achieve exceptional C2/C1 selectivity through synergistic photoexcitation, generation, and carbonylation. Mechanistic studies highlight critical roles Fe(II) Fe-carbonyl complexes bypassing via a rebound-like pathway, unlocking unprecedented efficiency

Язык: Английский

Процитировано

3
Iron-Catalyzed Hydrobenzylation: Stereoselective Synthesis of (−)-Eugenial C DOI
Xu-cheng Gan,

Simona Kotesova,

Alberto Castanedo

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(29), С. 15714 - 15720

Опубликована: Июль 12, 2023

Metal-hydride hydrogen atom transfer (MHAT) has emerged as a useful tool to form quaternary carbons from alkenes via hydrofunctionalization. Methods date that cross-couple with sp3 partners rely on heterobimetallic catalysis merge the two cycles. Here, we report an iron-only cross-coupling putative MHAT/SH2 steps solves key stereochemical problem in synthesis of meroterpenoid eugenial C and obviates need for nickel. The concise benefits conformationally locked o,o′-disubstituted benzyl bromide locally sourced chiral pool terpene coupling partner.

Язык: Английский

Процитировано

41