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

Stereodivergent Synthesis of Allenes with α,β‐Adjacent Central Chiralities Empowered by Synergistic Pd/Cu Catalysis DOI
Ling Zhao, Yicong Luo, Junzhe Xiao

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(9)

Published: Jan. 3, 2023

The stereodivergent synthesis of allene compounds bearing α,β-adjacent central chiralities has been realized via the Pd/Cu-catalyzed dynamic kinetic asymmetric alkylation racemic allenylic esters. matched reactivity bimetallic catalytic system enables challenging reaction aryl-substituted acetates with sterically crowded aldimine esters smoothly under mild conditions. Various chiral non-natural amino acids a terminal allenyl group are easily synthesized in high yields and excellent diastereo- enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers product can be readily accessed by switching configurations two metal catalysts. Furthermore, easy interconversion between uncommon η3 -butadienyl palladium intermediate featuring weak C=C/Pd coordination bond stable Csp2 -Pd is beneficial for transformation process (DyKAT).

Language: Английский

Citations

44
Dual-Catalyzed Stereodivergent Electrooxidative Homocoupling of Benzoxazolyl Acetate DOI
Jiayin Zhang,

Wangjie Zhu,

Ziting Chen

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(2), P. 1522 - 1531

Published: Jan. 3, 2024

The development of a reliable strategy for stereodivergent radical reactions that allows convenient access to all stereoisomers homocoupling adducts with multiple stereogenic centers remains an unmet goal in organic synthesis. Herein, we describe dual-catalyzed electrooxidative C(sp3)–H/C(sp3)–H complete absolute and relative stereocontrol the synthesis molecules contiguous quaternary stereocenters general predictable manner. reaction is achieved by synergistically utilizing two distinct chiral catalysts convert identical racemic substrates into inherently distinctive reactive intermediates, dictate enantioselective addition, allow full complement stereoisomeric products via simple catalyst permutation. successful execution dual-electrocatalytic programmed activation provides significant conceptual advantage will serve as useful foundation further research cooperative stereocontrolled transformations diversity-oriented

Language: Английский

Citations

36
Synergistic Pd/Cu-Catalyzed 1,5-Double Chiral Inductions DOI
Jiacheng Zhang, Yicong Luo, Zheng En

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9241 - 9251

Published: March 19, 2024

Much attention has been focused on the catalytic asymmetric creation of single chiral centers or two adjacent stereocenters. However, construction nonadjacent stereocenters is significant importance but challenging because lack remote induction models. Herein, based a C═C bond relay strategy, we report synergistic Pd/Cu-catalyzed 1,5-double model. All four stereoisomers target products bearing 1,5-nonadjacent involving both allenyl axial and central chirality could be obtained divergently by simply changing combination catalysts with different configurations. Control experiments DFT calculations reveal novel mechanism 1,5-oxidative addition, contra-thermodynamic η3-allyl palladium shift, conjugate nucleophilic substitution, which play crucial roles in control reactivity, regio-, enantio-, diastereoselectivity. It expected that this strategy may provide general protocol for synthesis structural motifs distant

Language: Английский

Citations

19
Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing both Axial and Central Chirality DOI Creative Commons
Shuang Yang,

Jia-Bo Huang,

Dahua Wang

et al.

Precision Chemistry, Journal Year: 2024, Volume and Issue: 2(5), P. 208 - 220

Published: April 23, 2024

The catalytic asymmetric diastereodivergent synthesis of axially chiral 2-alkenylindoles was established via phosphoric acid-catalyzed addition reactions C3-unsubstituted with

Language: Английский

Citations

17
Interrupting Associative π–σ–π Isomerization Enables Z-Retentive Asymmetric Tsuji–Trost Reaction DOI
Jiandong Liu,

Z. X. Dong,

Wenbin Cao

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(3), P. 2776 - 2785

Published: Jan. 8, 2025

The asymmetric Tsuji-Trost reaction has been extensively studied due to its importance in establishing stereogenic centers, often adjacent an E-olefin moiety organic molecules. generally preferential formation of chiral products is believed result from the thermodynamically more stable syn-π-allylpalladium intermediate. rapid associative π-σ-π isomerization makes it challenging synthesize Z-olefin via transient anti-π-allylpalladium Herein, we report a strategy for regulating by tuning steric bulkiness ligands, allylic leaving groups, and counteranions. utilization Pd catalyst derived phosphoramidite ligands interrupts isomerization, enabling highly efficient Z-retentive toward array α-amino acid derivatives bearing motif high yields (up 95%) excellent stereoselectivity 99% ee >19:1 Z/E) with low loading (0.1 mol %). mechanistic insights design reported this work pave way rational developments Tsuji-Trost-type reactions.

Language: Английский

Citations

3
Stereodivergent Construction of 3,3′-Disubstituted Oxindoles via One-Pot Sequential Allylation/Alkylation and Its Application to the Total Synthesis of Trigolute B and D DOI

Bin Qing,

Zhuang Yang, Zhenwei Wu

et al.

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

Published: Jan. 27, 2025

The absolute and relative configurations of bioactive chiral molecules are typically relevant to their biological properties. It is thus highly important desirable construct all possible stereoisomers a lead candidate or given natural compound. Synergistic dual catalysis has been recognized as reliable synthetic strategy for variety predictable stereodivergent transformations. Despite the impressive progress made in this field, carbon-carbon bond-formation reactions involving stabilized nucleophiles remain elusive. Herein, we report an iridium- magnesium-catalyzed one-pot sequential allylic alkylation/nucleophilic alkylation cascade process synthesis four 3,3'-disubstituted oxindoles through three-component reaction. A diverse array products readily prepared with high functional group compatibility good yields excellent diastereo- enantioselectivities. Subsequently, total spirooxindole alkaloid trigolutes B D accomplished concise unified route using same set starting materials.

Language: Английский

Citations

2
Stereodivergent Construction of Csp3−Csp3Bonds Bearing Vicinal Stereocenters by Synergistic Palladium and Phase‐Transfer Catalysis DOI

Jingqiang Han,

Rixin Liu,

Zitong Lin

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(2)

Published: Nov. 16, 2022

Abstract Synergistic catalysis has emerged as one of the most powerful tools for stereodivergent formation Csp 3 −Csp bonds bearing vicinal stereocenters. Despite many successes that have been achieved in this field, coupling reactions involving stabilized nucleophiles remain challenging because competing single‐catalysis pathway. Herein, we report a synergistic palladium/phase‐transfer catalyst system enables diastereodivergent 1,3‐dienes with nucleophile oxindoles. Both syn and anti products, quaternary tertiary stereocenters, could be selectively produced good yields high enantio‐ diastereoselectivities. Non‐covalent activation via chiral ion pair biphasic is crucial success factor achieving diastereodivergence.

Language: Английский

Citations

40
Stereodivergent Construction of 1,3‐Chiral Centers via Tandem Asymmetric Conjugate Addition and Allylic Substitution Reaction DOI
Jia‐Hao Xie,

Yi‐Ming Hou,

Zuolijun Feng

et al.

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

Citations

34
Simultaneous Dual Cu/Ir Catalysis: Stereodivergent Synthesis of Chiral β-Lactams with Adjacent Tertiary/Quaternary/Tertiary Stereocenters DOI
Jialin Qi, Tingting Song,

Zhenning Yang

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(4), P. 2555 - 2564

Published: Feb. 6, 2023

A stereodivergent synthesis of chiral β-lactams with contiguous tertiary/quaternary/tertiary stereocenters has been achieved by a Cu/Ir-catalyzed three-component interrupted Kinugasa allylic alkylation reaction. The two catalysts independently exert high local stereocontrol, providing access to four the eight possible stereoisomers in yields >99% ee. features this strategy are asymmetric simultaneous dual metal-catalyzed cascade reactions stereoselective coupling highly transient organometallic intermediates.

Language: Английский

Citations

27
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