Engineered enzymes for the synthesis of pharmaceuticals and other high-value products

Nature Synthesis, Journal Year: 2024, Volume and Issue: 3(1), P. 19 - 32

Published: Jan. 4, 2024

Language: Английский

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Stereodivergent 1,3-difunctionalization of alkenes by charge relocation

Nature, Journal Year: 2024, Volume and Issue: 626(7997), P. 92 - 97

Published: Jan. 31, 2024

Abstract Alkenes are indispensable feedstocks in chemistry. Functionalization at both carbons of the alkene—1,2-difunctionalization—is part chemistry curricula worldwide 1 . Although difunctionalization distal positions has been reported 2–4 , it typically relies on designer substrates featuring directing groups and/or stabilizing features, all which determine ultimate site bond formation 5–7 Here we introduce a method for direct 1,3-difunctionalization alkenes, based concept termed ‘charge relocation’, enables stereodivergent access to 1,3-difunctionalized products either syn - or anti -configuration from unactivated without need features. The usefulness approach is demonstrated synthesis pulmonary toxin 4-ipomeanol and its derivatives.

Language: Английский

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Copper-Catalyzed Asymmetric Yne-Allylic Substitution Using Electron-Rich Arenes

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(4), P. 2746 - 2757

Published: Feb. 7, 2024

Remote stereocontrol in transition-metal catalysis is a challenging but interesting research topic. In this work, we achieved copper-catalyzed asymmetric yne-allylic substitution using electron-rich arenes and acyclic carbonates through remote enantioselectivity control. The reaction delivers variety of enantioenriched products that contain diverse set valuable moieties, such as conjugated enynes, indoles, indolizines, allenes, dihydrofurans, which are widely used organic synthesis act key units bioactive molecules natural products. synthetic value protocol has been demonstrated series further transformations, mechanistic studies have conducted to gain more insight into the reaction.

Language: Английский

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Nickel‐Catalyzed Switchable Site‐Selective Alkene Hydroalkylation by Temperature Regulation**

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(31)

Published: May 25, 2022

Regiodivergent alkene functionalization that produces either regioisomer starting from the same raw materials is desirable. Herein, we report a nickel-catalyzed switchable site-selective hydroalkylation. The selection of reaction temperatures leads to protocols provide regiodivergent hydroalkylated products single substrate. This protocol allows convenient synthesis α- and β-branched protected amines, both which are important fields pharmaceutical chemistry biochemistry. In addition, enantioenriched alkylamines can be accessed in catalytic asymmetric variant. Preliminary mechanistic studies indicate formation more stable nickelacycle provides driving force migration. thermodynamic kinetic properties different reduction elimination intermediates responsible for site-selectivity.

Language: Английский

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Remote Enantioselective [4 + 1] Annulation with Copper-Vinylvinylidene Intermediates

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(46), P. 21347 - 21355

Published: Nov. 11, 2022

The first copper-catalyzed enantioselective [4 + 1] annulation of yne-allylic esters with 1,3-dicarbonyl compounds was realized through an elegant remote stereocontrol strategy. very ε regioselective nucleophilic substitution developed by employing a novel chiral copper-vinylvinylidene species from the new C4 synthon esters. Thus, greatly diverse spirocycles were obtained ample scope and excellent levels chemo-, regio-, enantioselectivities. Moreover, detailed mechanistic studies suggest Conia-ene cascade pathway on stereochemical induction progress.

Language: Английский

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Multi-site programmable functionalization of alkenes via controllable alkene isomerization

Nature Chemistry, Journal Year: 2023, Volume and Issue: 15(7), P. 988 - 997

Published: May 18, 2023

Language: Английский

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Chain Walking as a Strategy for Iridium-Catalyzed Migratory Amidation of Alkenyl Alcohols to Access α-Amino Ketones

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(9), P. 4277 - 4285

Published: Feb. 24, 2022

Catalytic carbon–nitrogen bond formation in hydrocarbons is an appealing synthetic tool to access valuable nitrogen-containing compounds. Although a number of approaches have been developed construct bifunctional α-amino carbonyl scaffold this realm, installation amino functionality at the remote and unfunctionalized aliphatic sites remains underdeveloped. Here we present tandem iridium catalysis that enables redox-relay amidation alkenyl alcohols via chain walking metal-nitrenoid transfer, which eventually offers new route various ketones with excellent regioselectivity. The virtue transformation unrefined isomeric mixture can be utilized as readily available starting materials lead regioconvergent amidation. Mechanistic investigations revealed reaction proceeds process involving two key components intermolecular nitrenoid transfer assistance hydrogen bonding, thus representing competence Ir for olefin migratory C–N coupling high efficiency exquisite selectivity.

Language: Английский

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Ligand‐Dictated Regiodivergent Allylic Functionalizations via Palladium‐Catalyzed Remote Substitution

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(28)

Published: March 15, 2023

Different from classical allylic substitutions that require a vicinal leaving group, an olefin bearing remote group is scarcely viewed as potential allylation substrate. Herein, we describe feasible protocols to achieve regiodivergent C-H functionalizations via palladium-catalyzed substitution, which provides novel strategy for the seldomly studied migratory Tsuji-Trost reaction. Dictated by suitable ligand, process involved 4,3-hydrofunctionalization of generated conjugated diene intermediate metal walking observed in generally >20 : 1 regioselectivity. Unexpectedly, related 1,4-hydrofunctionalization pathway found be major route with newly synthesized electron-rich bisphosphine challenges conventional viewpoint on regioselectivity hydrofunctionalizations linear internal dienes η3 -substitution. A series deuterium experiments and kinetic studies provide preliminary insight into catalytic cycle.

Language: Английский

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Enantioselective Palladium‐Catalyzed Directed Migratory Allylation of Remote Dienes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(34)

Published: June 30, 2023

Chain walking has been an efficient route to realize the functionalization of inert C(sp3 )-H bonds, but this strategy is limited mono-olefin migration and functionalization. Herein, we demonstrate feasibility tandem directed simultaneous migrations remote olefins stereoselective allylation for first time. The adoption palladium hydride catalysis secondary amine morpholine as solvent critical achieving high substrate compatibility stereochemical control with method. protocol also applicable three vicinal bonds thus construct continuous stereocenters along a propylidene moiety via short synthetic process. Preliminary mechanistic experiments corroborated design dienes.

Language: Английский

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Iridium‐Catalyzed Remote Site‐Switchable Hydroarylation of Alkenes Controlled by Ligands

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(41)

Published: Aug. 23, 2023

An iridium-catalyzed remote site-switchable hydroarylation of alkenes was reported, delivering the products functionalized at subterminal methylene and terminal methyl positions on an alkyl chain controlled by two different ligands, respectively, in good yields with to excellent site-selectivities. The catalytic system showed functional group tolerance a broad substrate scope, including unactivated activated alkenes. More importantly, regioconvergent transformations mixtures isomeric were also successfully realized. results mechanistic studies demonstrate that reaction undergoes chain-walking process give [Ar-Ir-H] complex alkene. subsequent processes proceed through modified Chalk-Harrod-type mechanism via migratory insertion alkene into Ir-C bond followed C-H reductive elimination afford hydrofunctionalization site-selectively.

Language: Английский

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