Catalytic Enantioselective Primary C–H Borylation for Acyclic All-Carbon Quaternary Stereocenters

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(2), P. 1635 - 1643

Published: Jan. 5, 2024

Creating a perfect catalyst to operate enzyme-like chiral recognition has been long-sought aim. A challenging example in this context is constructing acyclic all-carbon quaternary stereogenic centers by transition metal-catalyzed enantioselective C–H activation. We now report highly iridium-catalyzed primary borylation of α-all-carbon substituted 2,2-dimethyl amides enabled tailor-made bidentate boryl ligand (CBL). The success the current transformation attributed CBL/iridium catalyst, which confined pocket. This protocol provides diverse array stereocenters with excellent enantiocontrol and distinct structural features. Computational study reveals that steric hindrance CBL could regulate type dominant orbital interaction between substrate, crucial conferring high induction.

Language: Английский

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2-Aminophenanthroline Ligands Enable Mild, Undirected, Iridium-Catalyzed Borylation of Alkyl C–H Bonds

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(11), P. 7124 - 7129

Published: March 8, 2024

The catalytic, undirected borylation of alkyl C–H bonds typically occurs at high reaction temperatures or with excess substrate, both, because the low reactivity bonds. Here we report a new iridium system comprising 2-anilino-1,10-phenanthroline as ligand that catalyzes little to no induction period and rates. This superior activation profile 2-aminophenanthroline-ligated catalysts leads broader scope, including reactions sensitive substrates, such epoxides glycosidic acetals, enhanced diastereoselectivity, higher yields borylated products. These also enable alkanes, amines, ethers room temperature for first time. Mechanistic studies imply facile N-borylation under conditions complexes containing N-boryl aminophenanthrolines are competent precatalysts reaction.

Language: Английский

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Direct C–H Hydroxylation of N-Heteroarenes and Benzenes via Base-Catalyzed Halogen Transfer

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(14), P. 9755 - 9767

Published: March 26, 2024

Hydroxylated (hetero)arenes are valued in many industries as both key constituents of end products and diversifiable synthetic building blocks. Accordingly, the development reactions that complement address limitations existing methods for introduction aromatic hydroxyl groups is an important goal. To this end, we apply base-catalyzed halogen transfer (X-transfer) to enable direct C–H hydroxylation mildly acidic N-heteroarenes benzenes. This protocol employs alkoxide base catalyze X-transfer from sacrificial 2-halothiophene oxidants aryl substrates, forming SNAr-active intermediates undergo nucleophilic hydroxylation. Key process use 2-phenylethanol inexpensive hydroxide surrogate that, after substitution rapid elimination, provides hydroxylated arene styrene byproduct. Use simple 2-halothiophenes allows 6-membered 1,3-azole derivatives, while a rationally designed 2-halobenzothiophene oxidant extends scope electron-deficient benzene substrates. Mechanistic studies indicate reversible, suggesting deprotonation, halogenation, steps operate synergy, manifesting unique selectivity trends not necessarily dependent on most position. The utility method further demonstrated through streamlined target molecule syntheses, examples regioselectivity contrast alternative methods, scalable recycling thiophene oxidants.

Language: Английский

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Electrochemical generation of aryl radicals from organoboron reagents enabled by pulsed electrosynthesis

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(31)

Published: May 16, 2024

Aryl radicals play a pivotal role as reactive intermediates in chemical synthesis, commonly arising from aryl halides and diazo compounds. Expanding the repertoire of sources for radical generation to include abundant stable organoboron reagents would significantly advance chemistry broaden their reactivity profile. While traditional approaches utilize stoichiometric oxidants or photocatalysis generate these reagents, electrochemical conditions have been largely underexplored. Through rigorous mechanistic investigations, we identified fundamental challenges hindering generation. In addition high oxidation potentials aromatic compounds, electrode passivation through grafting, homocoupling radicals, decomposition issues were identified. We demonstrate that pulsed electrosynthesis enables selective efficient by mitigating challenges. Our discoveries facilitated development first conversion potassium trifluoroborate salts into C-P bonds. This sustainable straightforward oxidative approach exhibited broad substrate scope, accommodating various heterocycles chlorides, typical substrates transition-metal catalyzed cross-coupling reactions. Furthermore, extended this methodology form C-Se, C-Te, C-S bonds, showcasing its versatility potential bond formation processes.

Language: Английский

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The role of silicon in drug discovery: a review

RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 15(10), P. 3286 - 3344

Published: Jan. 1, 2024

This review aims to highlight the role of silicon in drug discovery.

Language: Английский

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Electrochemical meta-C–H sulfonylation of pyridines with nucleophilic sulfinates

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

Published: Aug. 28, 2024

Considering the indispensable significance and utilities of meta-substituted pyridines in medicinal, chemical as well materials science, a direct meta-selective C-H functionalization is paramount importance, but such reactions remain limited highly challenging. In general, established methods for meta rely on utilization tailored electrophilic reagents to realize intrinsic polarity match. Herein, we report complementary electrochemical methodology; diverse nucleophilic sulfinates allow meta-sulfonylation through redox-neutral dearomatization-rearomatization strategy by tandem dearomative cycloaddition/hydrogen-evolution electrooxidative sulfonation resulting oxazino-pyridines/acid-promoted rearomatization sequence. Besides, several salient features, including exclusive regiocontrol, remarkable substrate/functional group compatibility, scale-up potential, facile late-stage modification, have been demonstrated, which further contributes practicality adaptability this approach.

Language: Английский

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Enantioselective Total Syntheses of Vallesamidine and Schizozygane Alkaloids

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

A general streamlined strategy for the enantioselective total syntheses of schizozygane family natural products and related alkaloid vallesamidine is described. Specifically, a catalytic enantioconvergent cross-coupling sets quaternary stereogenic center in pluripotent intermediate adorned with an olefin three orthogonal carboxylate groups, upon which modularity synthesis relies. late-stage oxidative lactamization alkyne instrumental first-generation alkaloids. In second-generation approach, novel application van Leusen reaction generation lactams pivotal to accessing alkaloids from common intermediate. The strategies outlined here are expected enable detailed biological investigations as well facilitate access provide solutions modification bioactive

Language: Английский

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C–H borylation: a tool for molecular diversification

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 11(3), P. 929 - 953

Published: Dec. 19, 2023

Iridium-catalyzed C–H activation and borylation has become as a powerful synthetic tool in the past few decades because of widespread applicability versatility organoboron compounds.

Language: Английский

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Stereospecific Enzymatic Conversion of Boronic Acids to Amines

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(28), P. 19160 - 19167

Published: July 3, 2024

Boronic acids and esters are highly regarded for their safety, unique reactivity, versatility in synthesizing a wide range of small molecules, bioconjugates, materials. They not exploited biocatalytic synthesis, however, because enzymes that can make, break, or modify carbon–boron bonds rare. We wish to combine the advantages boronic molecular assembly with biocatalysis, which offers potential unsurpassed selectivity efficiency. Here, we introduce an engineered protoglobin nitrene transferase catalyzes new-to-nature amination using hydroxylamine. Initially targeting aryl acids, show enzyme produce array anilines high yields total turnover numbers (up 99% yield >4000 TTN), water boric acid as only byproducts. also demonstrate is effective bench-stable esters, hydrolyze situ corresponding acids. Exploring enzyme's capacity enantioselective catalysis, found racemic alkyl ester affords enantioenriched amine, transformation achieved chemocatalysts. The formation exclusively unrearranged product during radical clock reaction's stereospecificity support two-electron process akin 1,2-metallate shift mechanism. developed enables new routes chiral amines.

Language: Английский

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Mercury‐Group 13 Metal Covalent Bonds: A Systematic Comparison of Aluminyl, Gallyl and Indyl Metallo‐ligands

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(23)

Published: March 28, 2024

Abstract Bimetallic compounds containing direct metal‐group 13 element bonds have been shown to display unprecedented patterns of cooperative reactivity towards small molecules, which can be influenced by the identity group element. In this context, we present here a systematic appraisal metallo‐ligands type [(NON)E] − (NON=4,5‐bis(2,6‐di iso propylanilido)‐2,7‐di‐tert‐butyl‐9,9‐dimethylxanthene) for E=Al, Ga and In, through comparison structural spectroscopic parameters associated with trans L or X ligands in linear d 10 complexes types LM{E(NON)} XM′{E(NON)}. These studies are facilitated convenient syntheses (from In(I) precursor, InCp) potassium indyl species [{K(NON)In}⋅KCp] n ( 1 ) [(18‐crown‐6) 2 K Cp] [(NON)In] 1′ ), lead first characterisation Ag−In Hg−E (E=Al, In) covalent bonds. The resulting structural, quantum chemical probes Ag/Hg consistent markedly stronger σ‐donor capabilities aluminyl ligand, [(NON)Al] , over its gallium indium counterparts.

Language: Английский

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