Enantioselective 1,4-Borylamination Enabled by Copper Catalysis DOI
Bo Su, Yu‐Jie Zhu

Synlett, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Abstract Compounds bearing both boryl and amino groups are highly valuable synthons in organic synthesis. However, while enantioselective 1,1- 1,2-borylamination reactions have been developed, processes enabling distal borylamination rarely investigated. Here, we present an 1,4-borylamination reaction, achieved through a copper-catalyzed cascade hydroborylation hydroamination of arylidenecyclopropanes. This four-component reaction provides direct access to enantioenriched 4-aminoalkylboronate products with high chemo-, site-, enantioselectivity. The versatility these was demonstrated their broad transformations extensive applications the synthesis various drug core structures. Additionally, preliminary mechanistic studies were conducted investigate pathway, intermediates, chemo- site-selectivity.

Language: Английский

Cu-Catalyzed Asymmetric Dicarboxylation of 1,3-Dienes with CO2 DOI
Yong‐Yuan Gui, Xiao‐Wang Chen,

Xiao-Yan Mo

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 2919 - 2927

Published: Jan. 26, 2024

Dicarboxylic acids and derivatives are important building blocks in organic synthesis, biochemistry, the polymer industry. Although catalytic dicarboxylation with CO2 represents a straightforward sustainable route to dicarboxylic acids, it is still highly challenging limited generation of achiral or racemic acids. To date, asymmetric give chiral has not been reported. Herein, we report first 1,3-dienes via Cu catalysis. This strategy provides an efficient environmentally benign high regio-, chemo-, enantioselectivities. The copper self-relay catalysis, that is, Cu-catalyzed boracarboxylation carboxylated allyl boronic ester intermediates subsequent carboxylation C–B bonds dicarboxylates, key success this dicarboxylation. Moreover, protocol exhibits broad substrate scope, good functional group tolerance, easy product derivatizations, facile synthesis liquid crystalline polyester drug-like scaffolds.

Language: Английский

Citations

29
Copper-Catalyzed Regiodivergent and Enantioselective Hydrosilylation of Allenes DOI

Jian‐Lin Xu,

Zheyuan Xu,

Zi‐Lu Wang

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(12), P. 5535 - 5542

Published: March 17, 2022

A copper-catalyzed regiodivergent hydrosilylation of a wide range simple allenes is reported. Linear and branched allylsilanes were formed by judicious choice solvents. Furthermore, obtained with high enantioselectivity (up to 97% enantiomeric excess) the aid C2-symmetric bisphosphine ligand in unprecedented asymmetric allene hydrosilylation.

Language: Английский

Citations

60
Confronting the Challenging Asymmetric Carbonyl 1,2-Addition Using Vinyl Heteroarene Pronucleophiles: Ligand-Controlled Regiodivergent Processes through a Dearomatized Allyl–Cu Species DOI
Yuyang Dong, Alexander W. Schuppe, Binh Khanh

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(13), P. 5985 - 5995

Published: March 26, 2022

The selective reductive coupling of vinyl heteroarenes with aldehydes and ketones represents a versatile approach for the rapid construction enantiomerically enriched secondary tertiary alcohols, respectively. Herein, we demonstrate CuH-catalyzed regiodivergent carbonyl-containing electrophiles, in which selectivity is controlled by ancillary ligand. This leverages an situ generated benzyl- or dearomatized allyl-Cu intermediate, yielding either exocyclic addition products, method exhibits excellent regio-, diastereo-, enantioselectivity tolerates range common functional groups heterocycles. dearomative pathway allows direct access to variety functionalized saturated heterocyclic structures. reaction mechanism was probed using combination experimental computational approach. Density theory studies suggest that ligand-controlled regioselectivity results from C-H/π interaction steric repulsion transition states, leading major minor regioisomers, Hydrocupration heteroarene pronucleophile enantiodetermining step, whereas diastereoselectivity enforced interactions between benzylic intermediate substrates six-membered cyclic state.

Language: Английский

Citations

44
Dearomative Addition-Hydrogen Autotransfer for Branch-Selective N-Heteroaryl C–H Functionalization via Ruthenium-Catalyzed C–C Couplings of Diene Pronucleophiles DOI
Jonathan Z. Shezaf, S. H. Lee,

Yhin Sarah Teoh

et al.

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

Published: Jan. 6, 2025

A novel mechanism for N-heteroaryl C–H functionalization via dearomative addition-hydrogen autotransfer is described. Upon exposure to the catalyst derived from RuHCl(CO)(PPh3)3 and Xantphos, dienes 1a–1g suffer hydroruthenation form allylruthenium nucleophiles that engage in addition-β-hydride elimination furnish branched products of C–C coupling 3a–3s 4a–4f. Oxidative cleavage isoprene adducts 3j, 3k, 3l, 3n followed by ruthenium-catalyzed dynamic kinetic asymmetric ketone reduction provides enantiomerically enriched N-heteroarylethyl alcohols 6a–6d and, therefrom, amines 7a–7d. Density functional theory calculations correlate experimentally observed regioselectivities with magnitude LUMO coefficients corroborate rate-determining addition. In presence 2-propanol trifluoroethanol, dearomatized pyrimidine 2a quinazoline 2n were isolated characterized.

Language: Английский

Citations

1
Recent Advances in Catalytic Asymmetric Ketone Allylations and Their Applications DOI

Lie Wang,

Ruoshi Jin, Yiyuan Peng

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: 15(3), P. 1487 - 1513

Published: Jan. 9, 2025

Due to the wide applications of resulting chiral tertiary homoallylic alcohols in organic synthesis, catalytic asymmetric ketone allylations have attracted continuous attention from synthetic chemists. Despite inherent difficulty enantiofacial differentiation and low reactivity ketones, past two decades witnessed rapid progress allylation ketones. Many efficient methods been reported, with discovery unprecedented catalysts reagents. The current Review aims give a summary achievements this area 2011 date is divided into six parts according reagents that were applied. Special paid scope application each method brief introduction corresponding mechanisms.

Language: Английский

Citations

1
Dual Cobalt/Organophotoredox Catalysis for Diastereo- and Regioselective 1,2-Difunctionalization of 1,3-Diene Surrogates Creating Quaternary Carbon Centers DOI

Sijing Xue,

Àlex Cristòfol, Bart Limburg

et al.

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(6), P. 3651 - 3659

Published: March 7, 2022

The synthesis of compounds having quaternary carbon centers through a catalytic stereo- and regioselective difunctionalization 2-substituted 1,3-dienes remains elusive. Here, we present dual Co/photoredox-catalyzed cascade approach that addresses this challenge using modular vinyl cyclic carbonates functioning as masked 2-aryl-1,3-diene surrogates. latter species are conveniently prepared in situ converted into nucleophilic Co(allyl) intermediates intercepted by aldehydes to afford homoallylic alcohols with ample scope reaction partners. developed protocol marks significant step forward the use structurally versatile their 1,2-hydroalkylation 1,2-dicarbofunctionalization.

Language: Английский

Citations

35
Organophotoredox/Ni-Cocatalyzed Allylation of Allenes: Regio- and Diastereoselective Access to Homoallylic Alcohols DOI
Hui Xie, Bernhard Breit

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(5), P. 3249 - 3255

Published: Feb. 24, 2022

A dual organophotoredox/nickel-catalyzed reductive coupling of allenes with aldehydes has been developed for the rapid assembly anti-homoallylic alcohols high levels regioselectivities (>20:1), diastereoselectivities (up to >20:1), and yields 91%). The allylation was realized through a crucial π-allylnickel intermediate, which obtained via insertion Ni–H intermediate. Moreover, γ,γ-disubstituted homoallylic quaternary stereocenter can also be prepared by this protocol.

Language: Английский

Citations

33
Cobalt‐Catalyzed Regiodivergent and Enantioselective Intermolecular Coupling of 1,1‐Disubstituted Allenes and Aldehydes DOI
Wei Huang,

Jiahui Bai,

Yinlong Guo

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(19)

Published: March 3, 2023

Catalytic enantioselective coupling of 1,1-disubstituted allenes and aldehydes through regiodivergent oxidative cyclization followed by stereoselective protonation or reductive elimination promoted chiral phosphine-Co complexes is presented. Such processes represent unprecedented unique reaction pathways for Co catalysis that enable catalytic generation metallacycles with divergent regioselectivity accurately controlled ligands, affording a wide range allylic alcohols homoallylic are otherwise difficult to access without the need pre-formation stoichiometric amounts alkenyl- allyl-metal reagents in up 92 % yield, >98 : 2 regioselectivity, dr >99.5 0.5 er.

Language: Английский

Citations

21
Dual‐Catalysed Intermolecular Reductive Coupling of Dienes and Ketones** DOI Creative Commons

Victor J. Mayerhofer,

Martina Lippolis, Christopher J. Teskey

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(2)

Published: Nov. 10, 2023

Abstract We report a mild, catalytic method for the intermolecular reductive coupling of feedstock dienes and styrenes with ketones. Our conditions allow concomitant formation cobalt hydride species single‐electron reduction Subsequent selective hydrogen‐atom transfer from generates an allylic radical which can selectively couple persistent radical‐anion ketone. This radical‐radical negates unfavourable steric interactions ionic pathways avoids unstable alkoxy previous olefin‐carbonyl couplings, were limited, as result, to aldehydes. Applications this novel straightforward approach include efficient synthesis drug molecules, key intermediates in site‐selective late‐stage functionalisation.

Language: Английский

Citations

20
Asymmetric Synthesis of Trisubstituted Vicinal Diols through Copper(I)‐Catalyzed Diastereoselective and Enantioselective Allylation of Ketones with Siloxypropadienes DOI
Nan Jiang,

Pei‐Zhi Liu,

Zhi‐Zhou Pan

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(21)

Published: Feb. 27, 2024

Chiral trisubstituted vicinal diols are a type of important organic compounds, serving as both common structure units in bioactive natural products and chiral auxiliaries asymmetric synthesis. Herein, by using siloxypropadienes the precursors allyl copper(I) species, copper(I)-catalyzed diastereoselective enantioselective reductive allylation ketones was achieved, providing syn-diols anti-diols good to excellent enantioselectivity. DFT calculations show that cis-γ-siloxy-allyl copper species generated favorably with either 1-TBSO-propadiene or 1-TIPSO-propadiene. Moreover, steric difference TBS group TIPS distinguishes face selectivity acetophenone, leading syn-selectivity for anti-selectivity Easy transformations were performed, demonstrating synthetic utility present method. one diol prepared above used suitable organocatalyst catalytic self-coupling aldimines situ B

Language: Английский

Citations

8