Iridium-Catalyzed Asymmetric Difunctionalization of C–C σ-Bonds Enabled by Ring-Strained Boronate Complexes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(30), P. 16508 - 16516

Published: July 20, 2023

Enantioenriched organoboron intermediates are important building blocks in organic synthesis and drug discovery. Recently, transition metal-catalyzed enantioselective 1,2-metalate rearrangements of alkenylboronates have emerged as an attractive protocol to access these valuable reagents by installing two different carbon fragments across C═C π-bonds. Herein, we report the development iridium-catalyzed asymmetric allylation-induced rearrangement bicyclo[1.1.0]butyl (BCB) boronate complexes enabled strain release, which allows difunctionalization C-C σ-bonds, including dicarbonation carboboration. This provides a variety enantioenriched three-dimensional 1,1,3-trisubstituted cyclobutane products bearing boronic ester that can be readily derivatized. Notably, reaction gives trans diastereoisomers result from anti-addition σ-bond, is contrast syn-additions observed for reactions promoted PdII-aryl other electrophiles our previous works. The diastereoselectivity has been rationalized based on combination experimental data density functional theory calculations, suggest BCB highly nucleophilic react via early states with low activation barriers.

Language: Английский

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Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(9), P. 6078 - 6144

Published: April 17, 2024

Alcohols are abundant and attractive feedstock molecules for organic synthesis. Many methods their functionalization require them to first be converted into a more activated derivative, while recent years have seen vast increase in the number of complexity-building transformations that directly harness unprotected alcohols. This Review discusses how transition metal catalysis can used toward this goal. These broadly classified three categories. Deoxygenative functionalizations, representing derivatization C–O bond, enable alcohol act as leaving group formation new C–C bonds. Etherifications, characterized by O–H represent classical reactivity has been modernized include mild reaction conditions, diverse partners, high selectivities. Lastly, chain reactions described, wherein acts mediator formal C–H alkyl backbone. Each these classes transformation will discussed context intermolecular arylation, alkylation, related reactions, illustrating alcohols harnessed

Language: Английский

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Stereodivergent Construction of 1,3‐Chiral Centers via Tandem Asymmetric Conjugate Addition and Allylic Substitution Reaction

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(10)

Published: Jan. 4, 2023

Herein, we report a synthesis of cyclohexanones bearing multi-continuous stereocenters by combining copper-catalyzed asymmetric conjugate addition dialkylzinc reagents to cyclic enones with iridium-catalyzed allylic substitution reaction. Good excellent yields, diastereoselectivity and enantioselectivity can be obtained. Unlike the stereodivergent construction adjacent (1,2-position) reported in literature, current reaction achieve nonadjacent (1,3-position) proper combination two chiral catalysts different enantiomers.

Language: Английский

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Asymmetric Synthesis of Chiral 1,2‐Bis(Boronic) Esters Featuring Acyclic, Non‐Adjacent 1,3‐Stereocenters

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(5)

Published: Dec. 15, 2023

The construction of acyclic, non-adjacent 1,3-stereogenic centers, prevalent motifs in drugs and bioactive molecules, has been a long-standing synthetic challenge due to acyclic nucleophiles being distant from the chiral environment. In this study, we successfully synthesized highly valuable 1,2-bis(boronic) esters featuring nonadjacent 1,3-stereocenters. Notably, reaction selectively produces migratory coupling products rather than alternative deborylative allylation or direct byproducts. This approach introduces new activation mode for selective transformations gem-diborylmethane asymmetric catalysis. Additionally, found that other gem-diborylalkanes, previously challenging steric hindrance, also participated reaction. incorporation 1,2-bis(boryl)alkenes facilitated diversification alkenyl two boron moieties our target compounds, thereby enabling access broad array versatile molecules. DFT calculations were performed elucidate mechanism shed light on factors responsible observed excellent enantioselectivity diastereoselectivity. These determined arise ligand-substrate repulsions syn-addition transition state.

Language: Английский

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Enantioselective Synthesis of Cyclobutane Derivatives via Cascade Asymmetric Allylic Etherification/[2 + 2] Photocycloaddition

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(40), P. 21752 - 21759

Published: Sept. 28, 2023

Chiral cyclobutane presents as a popular motif in natural products and biologically active molecules, its derivatives have been extensively used key synthons organic synthesis. Herein, we report an efficient synthetic method toward enantioenriched derivatives. The reaction proceeds cascade fashion involving Ir-catalyzed asymmetric allylic etherification visible-light induced [2 + 2] cycloaddition. Readily available branched allyl acetates cinnamyl alcohols are directly the substrates under mild conditions, providing broad range of chiral cyclobutanes good yields with excellent diastereo- enantioselectivities (up to 12:1 dr, >99% ee). It is worth noting that all catalysts were simultaneously added without any separated step this approach. gram-scale diverse transformations product further enhance potential utility method.

Language: Английский

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Asymmetric Allylic Substitution‐Isomerization for the Modular Synthesis of Axially Chiral N‐Vinylquinazolinones

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(40)

Published: Aug. 16, 2023

Abstract Axially chiral N ‐substituted quinazolinones are important bioactive molecules, which presented in many synthetic drugs. However, most strategies toward their atroposelective synthesis mainly limited to the axially arylquinazolinone frameworks. The development of modular methods access diverse quinazolinone‐based atropisomers remains scarce and challenging. Herein, we report regio‐ ‐vinylquinazolinones via strategy asymmetric allylic substitution‐isomerization. catalysis system utilized both transition‐metal organocatalysis efficiently afford trisubstituted tetrasubstituted ‐vinylquinazolinone atropisomers, respectively. With meticulous design β‐substituted substrates, Z ‐ E ‐tetrasubstituted were obtained good yields high enantioselectivities.

Language: Английский

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Simultaneous Stereoinvertive and Stereoselective C(sp³)–C(sp³) Cross-Coupling of Boronic Esters and Allylic Carbonates

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(20), P. 13719 - 13726

Published: May 9, 2024

With increasing interest in constructing more three-dimensional entities, there has been growing cross-coupling reactions that forge C(sp3)–C(sp3) bonds, which leads to additional challenges as it is not just a difficult bond construct but issues of stereocontrol also arise. Herein, we report the stereocontrolled enantioenriched boronic esters with racemic allylic carbonates enabled by iridium catalysis, leading formation bonds single or vicinal stereogenic centers. The method shows broad substrate scope, enabling primary, secondary, and even tertiary be employed, can used prepare any four possible stereoisomers coupled product chiral new method, combines simultaneous enantiospecific reaction nucleophile enantioselective electrophile process, offers solution for stereodivergent two C(sp3) fragments.

Language: Английский

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Iridium-Catalyzed Enantioselective Allylic Substitution of Vinylcyclopropanes by Carboxylic Acids

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(9), P. 6261 - 6267

Published: April 21, 2023

An efficient method for a highly regio- and enantioselective allylic substitution of vinylcyclopropanes using carboxylic acids as oxygen nucleophile via iridium catalysis has been developed. This represents atom-economic approach the synthesis synthetically useful chiral building blocks in high yields. The practical utility this is demonstrated by application products transformations.

Language: Английский

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Ir-Catalyzed Asymmetric Cascade Allylation/Spiroketalization Reaction for Stereoselective Synthesis of Oxazoline-Spiroketals

Organic Letters, Journal Year: 2023, Volume and Issue: 25(2), P. 325 - 330

Published: Jan. 6, 2023

An asymmetric cascade allylation/spiroketalization reaction between 2-(1-hydroxyallyl)phenols and 5-methyleneoxazolines is accomplished by using a chiral Ir(I) catalyst derived from commercially available iridium precursor the Carreira ligand. This protocol furnishes class of structurally novel unique oxazoline-spiroketals in up to 86% yield, >99% ee >20:1 dr. Moreover, control experiments reveal that 4,4-disubstitution on necessary avoid aromatization for spiroketalization occur. On basis this, plausible mechanism illustrated.

Language: Английский

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Catalytic Asymmetric Ring Opening Reactions of Vinylcyclopropanes

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 27(19)

Published: Jan. 11, 2024

Abstract Vinylcyclopropanes (VCPs) are important building blocks with multifaceted reactivity. Catalytic asymmetric ring opening of vinylcyclopropanes is a highly efficient process to access valuable chiral molecules diverse functionalities that can be further functionalized for series synthetic purposes. VCPs very well‐known substrates cycloaddition reactions and this chemistry has been widely explored. On the contrary, despite enormous potential, development new innovative strategies catalytic, somewhat underdeveloped. Recently, several significant examples have emerged in literature various both activated unactivated involve transition metal catalysis. These developments relevant additions vinylcyclopropane chemistry. In review, we aim summarize all catalytic transformations reported till date provide comprehensive analysis these research outcomes.

Language: Английский

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