Leveraging the Stereochemical Complexity of Octahedral Diastereomeric-at-Metal Catalysts to Unlock Regio-, Diastereo-, and Enantioselectivity in Alcohol-Mediated C–C Couplings via Hydrogen Transfer DOI
Jonathan Z. Shezaf, Catherine G. Santana, Eliezer Ortiz

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(12), P. 7905 - 7914

Published: March 13, 2024

Experimental and computational studies illuminating the factors that guide metal-centered stereogenicity and, therefrom, selectivity in transfer hydrogenative carbonyl additions of alcohol proelectrophiles catalyzed by chiral-at-metal-and-ligand octahedral d6 metal ions, iridium(III) ruthenium(II), are described. To augment or invert regio-, diastereo-, enantioselectivity, predominantly one from among as many 15 diastereomeric-at-metal complexes is required. For catalysts, cyclometalation assists defining stereocenter, for ruthenium(II) iodide counterions play a key role. Whereas classical strategies to promote catalysis aim high-symmetry transition states, well-defined low-symmetry states can unlock selectivities otherwise difficult achieve inaccessible.

Language: Английский

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

Adam Cook,

Stephen G. Newman

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

Citations

39
Carbonyl umpolung as an organometallic reagent surrogate DOI
Xi‐Jie Dai, Chenchen Li, Chao‐Jun Li

et al.

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(19), P. 10733 - 10742

Published: Jan. 1, 2021

Carbonyls can serve as surrogates for organometallic reagents via hydrazones.

Language: Английский

Citations

80
Allenes and Dienes as Chiral Allylmetal Pronucleophiles in Catalytic Enantioselective C=X Addition: Historical Perspective and State‐of‐The‐Art Survey DOI
Ming Xiang, Dana E. Pfaffinger, Michael J. Krische

et al.

Chemistry - A European Journal, Journal Year: 2021, Volume and Issue: 27(52), P. 13107 - 13116

Published: June 29, 2021

Abstract The use of allenes and 1,3‐dienes as chiral allylmetal pronucleophiles in intermolecular catalytic enantioselective reductive additions to aldehydes, ketones, imines, carbon dioxide other C=X electrophiles is exhaustively catalogued together with redox‐neutral hydrogen auto‐transfer processes. Coverage limited processes that result both C−H C−C bond formation. alkynes latent multicomponent allylations involving dienes not covered. As illustrated this review, the ability serve tractable non‐metallic has evoked many useful transformations have no counterpart traditional chemistry.

Language: Английский

Citations

67
The Chosen Few: Parallel Library Reaction Methodologies for Drug Discovery DOI

Amanda W. Dombrowski,

Ana L. Aguirre,

Anurupa Shrestha

et al.

The Journal of Organic Chemistry, Journal Year: 2021, Volume and Issue: 87(4), P. 1880 - 1897

Published: Nov. 15, 2021

Parallel library synthesis is an important tool for drug discovery because it enables the of closely related analogues in parallel via robust and general synthetic transformations. In this perspective, we analyzed methodologies used >5000 libraries representing 15 prevalent The data set contains complex substrates diverse arrays building blocks over last 14 years at AbbVie. that have demonstrated robustness generality with proven success are described along their substrate scopes. evolution past decade discussed. We also highlight combination high-throughput experimentation will continue to facilitate library-amenable discovery.

Language: Английский

Citations

66
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
Enantioselective Metal-Catalyzed Reductive Coupling of Alkynes with Carbonyl Compounds and Imines: Convergent Construction of Allylic Alcohols and Amines DOI
Eliezer Ortiz, Jonathan Z. Shezaf, Yu-Hsiang Chang

et al.

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(14), P. 8164 - 8174

Published: June 23, 2022

The use of alkynes as vinylmetal pronucleophiles in intermolecular enantioselective metal-catalyzed carbonyl and imine reductive couplings to form allylic alcohols amines is surveyed. Related hydrogen auto-transfer processes, wherein or serve dually reductants proelectrophiles, also are cataloged, applications target-oriented synthesis. These processes represent an emerging alternative the stoichiometric reagents Nozaki-Hiyama-Kishi (NHK) reactions alkenylation.

Language: Английский

Citations

41
Manganese(I)-catalyzed asymmetric (transfer) hydrogenation of ketones: An insight into the effect of chiral PNN and NN ligands DOI
Jitao Yang,

Lijun Yao,

Zheng Wang

et al.

Journal of Catalysis, Journal Year: 2023, Volume and Issue: 418, P. 40 - 50

Published: Jan. 7, 2023

Language: Английский

Citations

26
Dynamic Kinetic Resolution of 2‐(Quinolin‐8‐yl)Benzaldehydes: Atroposelective Iridium‐Catalyzed Transfer Hydrogenative Allylation DOI Creative Commons
José A. Carmona, Patricia Rodríguez‐Salamanca, Rosario Fernández

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(35)

Published: June 30, 2023

An atroposelective Ir-catalyzed dynamic kinetic resolution (DKR) of 2-(quinolin-8-yl)benzaldehydes/1-naphthaldehydes by transfer hydrogenative coupling allyl acetate is disclosed. The allylation reaction takes place with simultaneous installation central and axial chirality, reaching high diastereoselectivities excellent enantiomeric excesses when ortho-cyclometalated iridium-DM-BINAP used as the catalyst. racemization substrates occurs through a designed transient Lewis acid-base interaction between quinoline nitrogen atom aldehyde carbonyl group.

Language: Английский

Citations

24
Organometallic Mn(I) Complexes in Asymmetric Catalytic (Transfer) Hydrogenation and Related Transformations DOI Creative Commons
Dexin Fu, Zheng Wang, Qingbin Liu

et al.

ChemCatChem, Journal Year: 2024, Volume and Issue: 16(14)

Published: March 7, 2024

Abstract Direct asymmetric hydrogenation (AH) and transfer (ATH) are among the most efficient approaches to produce chiral building blocks. Recently, these types of transformations have witnessed a shift towards use molecular catalysts based on earth‐abundant transition metals due their ready availability, economic advantage, novel properties. With particular regard manganese, catalyst development has seen both efficiency substrate scope in AH ATH greatly improved, with emergence large number well‐defined Mn‐complexes employed this field. The reaction includes C=O bonds, reduction C=N bonds reductive C=C bonds. Herein, our survey area focuses catalytic activity such complexes, versatility routes convert substrates target molecules. We consider collected findings article will be helpful reader by providing an insight into ligand design, thereby aiding future development. Moreover, review is aimed at highlighting remarkable progress made last seven years manganese complexes for enantioselective reduction.

Language: Английский

Citations

11
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

2