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

Xia‐Min Jiang,

Chong‐Lei Ji,

Jianfei Ge

et al.

Angewandte Chemie, Journal Year: 2023, Volume and Issue: 136(5)

Published: Dec. 15, 2023

Abstract 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 ‐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

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

Hong‐Cheng Shen,

Mihai V. Popescu, Ze‐Shu Wang

et al.

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

Citations

45
Ni-catalysed assembly of axially chiral alkenes from alkynyl tetracoordinate borons via 1,3-metallate shift DOI

Xingxing Ma,

Mengwei Tan,

Luo Li

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(1), P. 42 - 53

Published: Jan. 1, 2024

Language: Английский

Citations

27
Asymmetric C3-Allylation of Pyridines DOI
Zhong Liu,

Zhu-Jun Shi,

Lu Liu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: unknown

Published: May 17, 2023

Asymmetric intermolecular C–H functionalization of pyridines at C3 is unprecedented. Herein, we report the first examples such transformations: specifically, C3-allylation via tandem borane and iridium catalysis. First, borane-catalyzed pyridine hydroboration generates nucleophilic dihydropyridines; then, dihydropyridine undergoes enantioselective iridium-catalyzed allylation; finally, oxidative aromatization with air as oxidant gives C3-allylated pyridine. This protocol provides direct access to excellent enantioselectivity (up >99% ee) suitable for late-stage pyridine-containing drugs.

Language: Английский

Citations

39
Ir‐Catalyzed Enantioselective Synthesis of gem‐Diborylalkenes Enabled by 1,2‐Boron Shift DOI

Jianfei Ge,

Xi‐Zhang Zou,

Xinru Liu

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(32)

Published: June 15, 2023

Abstract Asymmetric cross‐couplings based on 1,2‐carbon migration from B‐ate complexes have been developed efficiently to access valuable organoboronates. However, enantioselective reactions triggered by 1,2‐boron shift remained be unaddressed synthetic challenge. Here, Ir‐catalyzed asymmetric allylic alkylation enabled was developed. In this reaction, we disclosed that excellent enantioselectivities were achieved through an interesting dynamic kinetic resolution (DKR) process of carbonates at the elevated temperature. Notably, highly (bis‐boryl)alkenes array diversifications versatile molecules. Extensive experimental and computational studies conducted elucidate reaction mechanism DKR clarify origin enantioselectivities.

Language: Английский

Citations

27
Asymmetric Synthesis of Chiral 1,2‐Bis(Boronic) Esters Featuring Acyclic, Non‐Adjacent 1,3‐Stereocenters DOI

Xia‐Min Jiang,

Chong‐Lei Ji,

Jianfei Ge

et al.

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

Citations

22
Simultaneous Stereoinvertive and Stereoselective C(sp3)–C(sp3) Cross-Coupling of Boronic Esters and Allylic Carbonates DOI Creative Commons

Hong‐Cheng Shen,

Ze‐Shu Wang, Adam Noble

et al.

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

Citations

5
Iridium-Catalyzed Stereocontrolled C(sp3)–C(sp3) Cross-Coupling of Boronic Esters and Allylic Carbonates Enabled by Boron-to-Zinc Transmetalation DOI Creative Commons

Hong‐Cheng Shen,

Varinder K. Aggarwal

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

Published: Feb. 6, 2025

The stereocontrolled C(sp3)–C(sp3) cross-coupling represents a considerable challenge of great contemporary interest. While this has been achieved through the reactions boronate complexes with π-allyl iridium complexes, such suffered from limited substrate scope. We now report that following transmetalation to organozinc reagents enables previously unreactive substrates engage in cross-coupling. broader scope enabled their application synthesis biologically active molecules. react stereoinvertive coupling pathway contrast other electrophiles occur retention stereochemistry. reaction uniquely combines enantiospecific reactivity an enantioenriched organometallic nucleophile enantioselective engagement racemic electrophile, enabling access all stereoisomers.

Language: Английский

Citations

0
Chemoselective and Stereoselective Allylation of Bis(alkenyl)boronates DOI

Minh‐Khoa Tran,

Joseph M. Ready

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(36)

Published: May 23, 2024

Bis(alkenyl)boronates react with optically active Ir(π-allyl) species in a process that involves allylation of the more substituted olefin and 1,2-metalate shift less olefin. The method constructs valuable enantioenriched tertiary allylic boronic esters high chemoselectivity, enantioselectivity diastereoselectivity. Allylic functionalization reactions transform 1,3-stereodiad to 1,5- 1,6-stereochemical relationships.

Language: Английский

Citations

3
Recent Advances in Catalytic Asymmetric Synthesis of Chiral 1,2-Bis(boronic) Esters DOI Open Access
Chong‐Lei Ji, De‐Wei Gao

Chinese Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 44(5), P. 1385 - 1385

Published: Jan. 1, 2024

Chiral 1,2-bis(boronic) esters are essential building blocks in the field of synthetic chemistry, and their catalytic asymmetric synthesis has attracted significant interest chemists.Recently, diboration olefins, using transition metals chiral diols, emerged as straightforward atom-economical methods for producing highly valuable esters.Asymmetric hydrogenation vinyl bis(boronic) can be a complementary approach to synthesizing these products.Additionally, borofunctionalization alkenes or alkynes represents another effective strategy constructing scaffolds.A recent innovation involves migratory coupling reactions with gem-diborylalkanes, offering new avenues esters.The latest developements challenges moleculeshis summarized, potential future research directions this prospected.

Language: Английский

Citations

3
Merging Organocatalysis with 1,2-Boronate Rearrangement: A Lewis Base-Catalyzed Asymmetric Multicomponent Reaction DOI Creative Commons

Hong‐Cheng Shen,

Varinder K. Aggarwal

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(40), P. 27305 - 27311

Published: Sept. 24, 2024

Catalytic asymmetric multicomponent 1,2-boronate rearrangements provide a practical approach for synthesizing highly valuable enantioenriched boronic esters. When applied to alkenyl or heteroaryl boronates, these reactions have relied mainly on transition-metal catalysis. Herein, we present an organocatalytic, Lewis base-catalyzed rearrangement, involving indoles, esters, and Morita-Baylis-Hillman carbonates, leading enantioenriched, substituted indole indoline derivatives. Using cinchona alkaloid-based catalysts, high selectivity has been achieved, enabling expansion of the chemical space around pharmaceutically relevant

Language: Английский

Citations

3