ConspectusChiral organosilicon compounds bearing a Si-stereogenic center have attracted increasing attention in various scientific communities and appear to be a topic of high current relevance in modern organic chemistry, given their versatile utility as chiral building blocks, chiral reagents, chiral auxiliaries, and chiral catalysts. Historically, access to these non-natural Si-stereogenic silanes mainly relies on resolution, whereas their asymmetric synthetic methods dramatically lagged compared to their carbon counterparts. Over the past two decades, transition-metal-catalyzed desymmetrization of prochiral organosilanes has emerged as an effective tool for the synthesis of enantioenriched Si-stereogenic silanes. Despite the progress, these catalytic reactions usually suffer from limited substrate scope, poor functional-group tolerance, and low enantioselectivity. The growing demand for Si-stereogenic silanes with structural diversity has continued to drive the development of new practical methods for the assembly of these chiral molecules.Five years ago, our research group embarked on a project aimed at developing a general catalytic approach that can unlock access to various functionalized Si-stereogenic organosilanes with high efficiency. This Account describes our laboratory's endeavor in the exploration and development of catalytic asymmetric dehydrogenative Si-H/X-H coupling toward Si-stereogenic silanes. This approach features (1) readily accessible dihydrosilane starting materials; (2) diverse X-H (X═C, N, O, etc.) coupling partners; (3) platform transformable Si-stereogenic monohydrosilane products; and (4) high efficiency and atomic economy.At the initial stage of the research, a biaryl dihydrosilane was selected as the model substrate to conduct an enantioselective intramolecular C-H/Si-H dehydrogenative coupling reaction. Rh/Josiphos catalytic system was found to be effective at the early stage of this process, while the final enantiocontrol was elusive. Mechanistic studies indicated that a rhodium silyl dihydride complex is the resting state in the catalytic cycle, which may undergo racemization of the Si-stereogenic center. Enlightened by the mechanistic investigations, two strategies, the tandem alkene hydrosilylation strategy and bulky alkene-assisted dehydrogenative strategy, were adopted to avoid racemization, delivering the corresponding Si-stereogenic 9-silafluorenes with excellent yields and enantioselectivities. Further enantioselective intramolecular C(sp)-H or C(sp)-H silylation gave access to a series of five-, six- and seven-membered Si-stereogenic heterocycles with high efficiency. Next, we extended the reaction to an intermolecular version, realizing asymmetric Si-H/C-H, Si-H/O-H, and Si-H/N-H dehydrogenative coupling reactions toward a variety of acyclic Si-stereogenic monohydrosilanes, silyl ethers, siloxanes, silanols, and silazanes. We also presented our endeavors to apply the resulting Si-stereogenic compounds, including further derivatization, polymerization, and chiroptical property investigations, which successfully introduced Si-stereocenters into bioactive molecules, polymers, and chiroptical materials. Lastly, based on the understanding of silyl metal species, we developed a new type of chiral silyl ligand that can be applied to enable an atroposelective intermolecular C-H/Si-H dehydrogenative coupling reaction. We anticipate that our research, including synthetic methodology, mechanistic insights, and property studies, will not only inspire the further development of chiral organosilicon chemistry but also contribute to the creation of novel chiral molecules to be applied in synthetic chemistry, medicinal chemistry, and materials science.
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http://dx.doi.org/10.1021/acs.accounts.4c00667 | DOI Listing |
Acc Chem Res
January 2025
Shenzhen Grubbs Institute and Department of Chemistry, Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
ConspectusChiral organosilicon compounds bearing a Si-stereogenic center have attracted increasing attention in various scientific communities and appear to be a topic of high current relevance in modern organic chemistry, given their versatile utility as chiral building blocks, chiral reagents, chiral auxiliaries, and chiral catalysts. Historically, access to these non-natural Si-stereogenic silanes mainly relies on resolution, whereas their asymmetric synthetic methods dramatically lagged compared to their carbon counterparts. Over the past two decades, transition-metal-catalyzed desymmetrization of prochiral organosilanes has emerged as an effective tool for the synthesis of enantioenriched Si-stereogenic silanes.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Chemistry, University of Science and Technology of China, Hefei, PR China.
This study presents a copper-catalyzed, substrate-controlled regio- and enantioselective intermolecular hydrosilylation method capable of accommodating a broad scope of alkenes and prochiral silanes. The approach offers an efficient and versatile pathway to generate enantioenriched linear and branched alkyl-substituted Si-stereogenic silanes. Key features of this reaction include mild reaction conditions, simple catalytic systems, compatibility with diverse substrates, high yields and enantioselectivities.
View Article and Find Full Text PDFJ Am Chem Soc
August 2024
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Enantiopure -stereogenic organosilanes are highly valued in the fields of organic synthesis, development of advanced materials, and drug discovery. However, they are not naturally occurring, and their synthesis has been largely confined to resolution of racemic silanes or desymmetrization of symmetric silanes. In contrast, the dynamic kinetic asymmetric transformation (DYKAT) of racemic organosilanes offers a mechanistically distinct approach and would broaden the accessibility of -stereogenic silanes in an enantioconvergent manner.
View Article and Find Full Text PDFNat Commun
July 2024
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, Germany.
A strong and confined Brønsted acid catalyzed enantioselective cyclization of bis(methallyl)silanes provides enantioenriched Si-stereogenic silacycles. High enantioselectivities of up to 96.5:3.
View Article and Find Full Text PDFJ Am Chem Soc
March 2023
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany.
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