Palladium-Catalyzed Enantioselective β-C(sp³)–H Activation Reactions of Aliphatic Acids: A Retrosynthetic Surrogate for Enolate Alkylation and Conjugate Addition

Accounts of Chemical Research, Год журнала: 2022, Номер 55(4), С. 537 - 550

Опубликована: Янв. 25, 2022

Enolate alkylation and conjugate addition into an α,β-unsaturated system have served as long-standing strategic disconnections for the installation of α- or β-substituents on carbonyl-containing compounds. At onset our efforts to develop C-H activation reactions organic synthesis, we set eye toward developing asymmetric β-C-H aliphatic acids with perspective that this bond-forming event could serve a more flexible retrosynthetic surrogate both canonical carbonyl-related transformations.In Account, describe early using strongly coordinating chiral oxazolines probe reaction mechanism stereochemical nature cleavage transition state. The characterization key reactive intermediates through X-ray crystallography computational studies suggested state Pd-OAc bonds being approximately coplanar optimum interaction. We then moved forward practical, weakly monodentate amide directing groups, necessary advance achieving native carboxylic acids. Throughout journey, gradual deconvolution between substrate's effect its intimate interplay ligand properties has culminated in design new classes ultimately allowed competency activation. These established importance acceleration Pd-catalyzed activation, where weak coordination is responsible positioning catalyst cleavage, while direct participation from bifunctional enthalpically stabilizing state.Building upon these principles, developed five ligands (MPAA, MPAQ, MPAO, MPAThio, MPAAM) enable enantioselective reactions, including carbon-carbon carbon-heteroatom bond formation. accumulated data indicate possessing point chirality are most effective imparting stereoinduction step, application which enabled desymmetrization subsequent functionalization enantiotopic carbon protons across range arylamides and, recently, free Progress design, conjunction enabling alkali metal countercations, led realization suite β-methyl now methylene C(sp

Язык: Английский

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Catalyst-controlled site-selective methylene C–H lactonization of dicarboxylic acids

Science, Год журнала: 2022, Номер 376(6600), С. 1481 - 1487

Опубликована: Май 26, 2022

Catalyst-controlled site-selective activation of β- and γ-methylene carbon-hydrogen (C-H) bonds free carboxylic acids is a long-standing challenge. Here we show that, with pair palladium catalysts assembled quinoline-pyridone ligands different chelate ring sizes, it possible to perform highly monolactonization reactions wide range dicarboxylic acids, generating structurally diverse synthetically useful γ- δ-lactones via or C-H activation. The remaining carboxyl group serves as versatile linchpin for further synthetic applications, demonstrated by the total synthesis two natural products, myrotheciumone A pedicellosine, from abundant acids.

Язык: Английский

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Palladium (II)‐Catalyzed C−H Activation with Bifunctional Ligands: From Curiosity to Industrialization

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(19)

Опубликована: Фев. 29, 2024

Abstract In 2001, our curiosity to understand the stereochemistry of C−H metalation with Pd prompted first studies in Pd(II)‐catalyzed asymmetric activation (RSC Research appointment: 020 7451 2545, Grant: RG 36873, Dec. 2002). We identified four central challenges: 1. poor reactivity simple salts native substrates; 2. few strategies control site selectivity for remote bonds; 3. lack chiral catalysts achieve enantioselectivity via metalation, and 4. low practicality due limited coupling partner scope use specialized oxidants. These challenges necessitated new catalyst reaction development. For , we developed approaches enhance substrate–catalyst affinity together novel bifunctional ligands which participate accelerate cleavage step. site‐selectivity introduced concept systematically modulating distance geometry between a directing template, catalyst, substrate selectively access bonds. devised predictable stereomodels catalyst‐controlled enantioselective based on participation ligands. Finally, have varied catalytic manifolds Pd(II) accommodate diverse partners while employing practical oxidants such as peroxides. advances culminated numerous reactions, setting stage broad industrial applications.

Язык: Английский

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Sustainable Aerobic Allylic C–H Bond Oxidation with Heterogeneous Iron Catalyst

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(4), С. 2769 - 2778

Опубликована: Янв. 19, 2024

Emerging techniques are revolutionizing the realm of chemical synthesis by introducing new avenues for C–H bond functionalization, which have been exploited pharmaceuticals, natural compounds, and functional materials. Allylic oxidation alkenes serves as possibly most employed functionalization reaction. However, sustainable selective approaches remain scarce, majority existing conditions still hinge on hazardous oxidants or costly metal catalysts. In this context, we introduce a heterogeneous iron catalyst that addresses above-mentioned concerns showcasing aerobic steroids, terpenes, simple olefins to corresponding enone products. This novel method provides powerful tool arsenal allylic while minimizing environmental concerns.

Язык: Английский

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Ligand-Enabled C–H Hydroxylation with Aqueous H₂O₂at Room Temperature

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(39), С. 18109 - 18116

Опубликована: Сен. 22, 2022

With the large number of Pd(II)-catalyzed C–H activation reactions native substrates developed in past decade, development catalysts to enable use green oxidants under safe and practical conditions has become an increasingly important challenge. Notably, compatibility Pd(II) with sustainable aqueous H2O2 been a long-standing challenge catalysis including Wacker-type oxidations. We report herein bifunctional bidentate carboxyl-pyridone (CarboxPyridone) ligand that enables room-temperature Pd-catalyzed hydroxylation broad range benzoic phenylacetic acids industry-compatible oxidant, hydrogen peroxide (35% H2O2). The scalability this methodology is demonstrated by 1000 mmol scale reaction ibuprofen (206 g) using only 1 mol % Pd catalyst loading. utility protocol further illustrated through derivatization products synthesis polyfluorinated natural product coumestan pterocarpene from phenol intermediates prepared methodology.

Язык: Английский

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One-Step Synthesis of β-Alkylidene-γ-lactones via Ligand-Enabled β,γ-Dehydrogenation of Aliphatic Acids

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(28), С. 12924 - 12933

Опубликована: Июль 8, 2022

Ligand-enabled Pd-catalyzed regioselective α,β-dehydrogenation of carbonyl compounds via β-methylene C–H activation has recently emerged as a promising transformation. Herein, we report the realization β,γ-dehydrogenation and subsequent vinyl olefination reactions free carboxylic acids, thus providing unique method for structural diversification aliphatic acids containing α-quaternary centers through sequential functionalizations two β-C–H bonds one γ-C–H bond. This tandem dehydrogenation–olefination–lactonization reaction offers one-step preparation β-alkylidene-γ-lactones, which are often difficult to prepare conventional methods, from inexpensive abundant acids. A variety such isosteviol grandiflorolic acid natural products, olefins compatible with reported protocol. The newly designed bidentate oxime ether-pyridone morpholine-pyridone ligands crucial this proceed. Notably, these also enable preferential methylene over previously reported, competing process methyl bond olefination.

Язык: Английский

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Cobalt-catalyzed chemoselective dehydrogenation through radical translocation under visible light

Chemical Science, Год журнала: 2022, Номер 13(26), С. 7947 - 7954

Опубликована: Янв. 1, 2022

The transformations that allow the direct removal of hydrogen from their corresponding saturated counterparts by dehydrogenative strategy are a dream reaction has remained largely underexplored. In this report, straightforward and robust cobaloxime-catalyzed photochemical dehydrogenation

Язык: Английский

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Transannular C–H functionalization of cycloalkane carboxylic acids

Nature, Год журнала: 2023, Номер 618(7965), С. 519 - 525

Опубликована: Май 31, 2023

Язык: Английский

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Dual-Ligand Catalyst for the Nondirected C–H Olefination of Heteroarenes

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(14), С. 8198 - 8208

Опубликована: Март 28, 2023

Pd(II)-catalyzed nondirected C-H functionalization of heteroarenes is a significant challenge for the following reasons: poor reactivity electron-deficient heterocycles and unproductive coordination Lewis basic nitrogen atoms. Existing methodologies using palladium catalysis often employ large excess heterocycle substrates to overcome these hurdles. Despite recent advances in arenes that allow them be used as limiting reagents, reaction conditions are incompatible with heteroarenes. Herein we report dual-ligand catalyst enables olefination without substrate. In general, use 1-2 equiv was sufficient obtain synthetically useful yields. The rationalized by synergy between two types ligands: bidentate pyridine-pyridone ligand promotes cleavage; monodentate substrate acts second form cationic Pd(II) complex has high affinity arenes. proposed cooperation supported combination X-ray, kinetics, control experiments.

Язык: Английский

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Regio-controllable [2+2] benzannulation with two adjacent C(sp ³ )–H bonds

Science, Год журнала: 2023, Номер 380(6645), С. 639 - 644

Опубликована: Май 11, 2023

Regiocontrol in traditional cycloaddition reactions between unsaturated carbon compounds is often challenging. The increasing focus modern medicinal chemistry on benzocyclobutene (BCB) scaffolds indicates the need for alternative, more selective routes to diverse rigid carbocycles rich C(sp

Язык: Английский

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