Catalytic asymmetric synthesis of silicon-stereogenic organosilanes

Chem, Journal Year: 2023, Volume and Issue: 9(12), P. 3461 - 3514

Published: Oct. 19, 2023

Language: Английский

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Catalytic Kinetic Resolution of Monohydrosilanes via Rhodium‐Catalyzed Enantioselective Intramolecular Hydrosilylation

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(25)

Published: April 12, 2024

The catalytic access of silicon-stereogenic organosilanes remains a big challenge, and largely depends on the desymmetrization symmetric precursors with two identical substitutes attached to silicon atom. Here we report construction via kinetic resolution racemic monohydrosilanes good excellent selectivity factors. Both Si-stereogenic dihydrobenzosiloles could be efficiently accessed in one single operation Rh-catalyzed enantioselective intramolecular hydrosilylation, employing (R,R)-Et-DuPhos as optimal ligand. This protocol features mild conditions, low catalyst loading (0.1 mol % [Rh(cod)Cl]

Language: Английский

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Organocatalytic enantioselective construction of Si-stereocenters: recent advances and perspectives

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(17), P. 8546 - 8562

Published: Jan. 1, 2024

Silicon-stereogenic chiral organosilanes have found increasing applications in synthetic chemistry, medicinal and materials science. In this context, various asymmetric catalytic methods been established for the diverse synthesis of silicon-stereogenic silanes. particular, organocatalysis is emerging as an important complementary tool enantioselective construction silicon-stereocenters, along with rapid development chiral-metal catalyzed protocols. Its advent provides a powerful platform to achieve functionalized structural diversity, should lead great organosilicon chemistry. Tutorial Review, we highlight these latest achievements from two aspects: desymmetrizations prochiral tetraorganosilanes dynamic kinetic transformations racemic by employing five organocatalytic activation modes. The advantages, limitations value each protocol, well opportunities still open further exploration, are also discussed.

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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Lewis Base-Catalyzed Dynamic Kinetic Asymmetric Transformation of Racemic Chlorosilanes en Route to Si-Stereogenic Silylethers

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(33), P. 23092 - 23102

Published: Aug. 7, 2024

Enantiopure Si-stereogenic organosilanes are highly valued in the fields of organic synthesis, development advanced materials, and drug discovery. However, they not naturally occurring, their synthesis has been largely confined to resolution racemic silanes or desymmetrization symmetric silanes. In contrast, dynamic kinetic asymmetric transformation (DYKAT) offers a mechanistically distinct approach would broaden accessibility an enantioconvergent manner. this study, we report Lewis base-catalyzed DYKAT chlorosilanes. The chiral isothiourea catalyst, (S)-benzotetramisole, facilitates silyletherification with phenols, yielding (R)-silylethers good yields high enantioselectivity (27 examples, up 86% yield, 98:2 er). Kinetic analysis, control experiments, DFT calculations suggest that two-catalyst-bound pentacoordinate silicate is responsible for Si-configurational epimerization ion-paired tetracoordinated silicon intermediates.

Language: Английский

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Copper-catalyzed intermolecular Regio- and Enantioselective Hydrosilylation of Alkenes with Prochiral Silanes

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 3, 2025

This study presents a copper-catalyzed, substrate-controlled regio- and enantioselective intermolecular hydrosilylation method capable of accommodating broad scope alkenes prochiral silanes. The approach offers an efficient versatile pathway to generate enantioenriched linear branched alkyl-substituted Si-stereogenic Key features this reaction include mild conditions, simple catalytic systems, compatibility with diverse substrates, high yields enantioselectivities. While methods create chiral carbon centers stereochemically defined silicon have been developed, the ability both simultaneously would be value. Here authors present substratecontrolled

Language: Английский

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Peroxycarbenium-Mediated Asymmetric Synthesis of 1,2-Dioxanes and 1,2-Dioxolanes

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(4), P. 3353 - 3359

Published: Jan. 17, 2025

The endoperoxide scaffold is found in numerous natural products and synthetic substances of pharmaceutical interest. main challenge to their access remains the preparation chiral compounds due weakness peroxide bond, which limits scope available or applicable methods. Here, we demonstrate how peroxycarbenium species can be trapped by silylated nucleophiles with high enantioselectivities diastereoselectivities when applicable, using a imidophosphorimidate (IDPi) as catalyst. methodology broad, encompassing large variety enoxysilanes yielding 1,2-dioxanes 1,2-dioxolanes. Peroxides converted into alcohols trans-epoxides, was applied key step total synthesis ethyl plakortide Z, enhancing selectivity compared conventional Lewis acid-catalyzed transformation. Kinetic studies have shown that reaction necessitates an induction period, indicating formation silylium behaves true

Language: Английский

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Catalytic Asymmetric Dehydrogenative Si–H/X–H Coupling toward Si-Stereogenic Silanes

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

ConspectusChiral organosilicon compounds bearing a Si-stereogenic center have attracted increasing attention in various scientific communities and appear to be topic of high current relevance modern organic chemistry, given their versatile utility as chiral building blocks, reagents, auxiliaries, catalysts. Historically, access these non-natural silanes mainly relies on resolution, whereas asymmetric synthetic methods dramatically lagged compared carbon counterparts. Over the past two decades, transition-metal-catalyzed desymmetrization prochiral organosilanes has emerged an effective tool for synthesis enantioenriched silanes. Despite progress, catalytic reactions usually suffer from limited substrate scope, poor functional-group tolerance, low enantioselectivity. The growing demand with structural diversity continued drive development new practical assembly molecules.Five years ago, our research group embarked project aimed at developing general approach that can unlock functionalized efficiency. This Account describes laboratory's endeavor exploration dehydrogenative Si–H/X–H coupling toward features (1) readily accessible dihydrosilane starting materials; (2) diverse X–H (X═C, N, O, etc.) partners; (3) platform transformable monohydrosilane products; (4) efficiency atomic economy.At initial stage research, biaryl was selected model conduct enantioselective intramolecular C–H/Si–H reaction. Rh/Josiphos system found early this process, while final enantiocontrol elusive. Mechanistic studies indicated rhodium silyl dihydride complex is resting state cycle, which may undergo racemization center. Enlightened by mechanistic investigations, strategies, tandem alkene hydrosilylation strategy bulky alkene-assisted strategy, were adopted avoid racemization, delivering corresponding 9-silafluorenes excellent yields enantioselectivities. Further C(sp2)–H or C(sp3)–H silylation gave series five-, six- seven-membered heterocycles Next, we extended reaction intermolecular version, realizing Si–H/C–H, Si–H/O–H, Si–H/N–H variety acyclic monohydrosilanes, ethers, siloxanes, silanols, silazanes. We also presented endeavors apply resulting compounds, including further derivatization, polymerization, chiroptical property successfully introduced Si-stereocenters into bioactive molecules, polymers, materials. Lastly, based understanding metal species, developed type ligand applied enable atroposelective anticipate methodology, insights, studies, will not only inspire chemistry but contribute creation novel molecules medicinal materials science.

Language: Английский

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Atroposelective Silylation of 1,1′‐Biaryl‐2,6‐diols by a Chiral Counteranion Directed Desymmetrization Enhanced by a Subsequent Kinetic Resolution

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(27)

Published: May 2, 2023

A desymmetrizing silylation of aromatic diols is reported. The previously unknown asymmetric silyl ether formation phenol derivatives achieved by applying List's counteranion directed technique. silylium-ion-like silicon electrophile generated from an allylic silane paired with imidodiphosphorimidate (IDPi) enables enantioselective discrimination achiral 1,1'-biaryl-2,6-diols. enantioselectivity that desymmetrization further improved a downstream kinetic resolution, converting the monosilylated minor enantiomer into corresponding, again bissilylated diol.

Language: Английский

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Organocatalytic Activation of Donor–Acceptor Cyclopropanes: A Tandem (3 + 3)-Cycloaddition/Aryl Migration toward the Synthesis of Enantioenriched Tetrahydropyridazines

Organic Letters, Journal Year: 2023, Volume and Issue: 25(29), P. 5470 - 5475

Published: July 17, 2023

An organocatalytic enantioselective (3 + 3)-cycloaddition reaction of racemic cyclopropane carbaldehydes and aryl hydrazones has been demonstrated for the first time. A wide range enantioenriched tetrahydropyridazines with an exocyclic double bond were obtained moderate to good yields excellent enantiomeric excesses. Mechanistic investigations hinted toward a matched/mismatched kinetic resolution, control experiments DFT calculations unveiled that 1,3-aryl migration was concerted intramolecular proceeds via four-membered transition state.

Language: Английский

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