Stereodivergent Construction of 1,4‐Nonadjacent Stereocenters via Hydroalkylation of Racemic Allylic Alcohols Enabled by Copper/Ruthenium Relay Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(36)

Published: June 28, 2022

An unprecedented hydroalkylation of racemic allylic alcohols and ketimine esters enabled by Cu/Ru relay catalysis has been developed via merging the ruthenium-catalyzed asymmetric borrowing-hydrogen reaction with a copper-catalyzed Michael addition in one-pot procedure. The current method enables efficient preparation highly functionalized δ-hydroxyesters bearing 1,4-nonadjacent stereocenters good yields high levels diastereoselectivity excellent enantioselectivity under mild conditions. full complement four stereoisomers products could be readily accessed orthogonal permutations two chiral metal catalysts. work highlights power for stereodivergent construction that were otherwise inaccessible.

Language: Английский

---

Enantioselective Metal-Catalyzed Reductive Coupling of Alkynes with Carbonyl Compounds and Imines: Convergent Construction of Allylic Alcohols and Amines

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

---

Dearomative Addition-Hydrogen Autotransfer for Branch-Selective N-Heteroaryl C–H Functionalization via Ruthenium-Catalyzed C–C Couplings of Diene Pronucleophiles

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

---

Cobalt‐Catalyzed Regiodivergent and Enantioselective Intermolecular Coupling of 1,1‐Disubstituted Allenes and Aldehydes

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

---

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

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

---

Stereo‐ and Site‐Selective Crotylation of Alcohol Proelectrophiles via Ruthenium‐Catalyzed Hydrogen Auto‐Transfer Mediated by Methylallene and Butadiene

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(49)

Published: Oct. 6, 2022

Iodide-bound ruthenium-JOSIPHOS complexes catalyze the redox-neutral C-C coupling of primary alcohols with methylallene (1,2-butadiene) or 1,3-butadiene to form products anti-crotylation good excellent levels diastereo- and enantioselectivity. Distinct from other methods, direct crotylation in presence unprotected secondary is possible, enabling generation spirastrellolide B (C9-C15) leucascandrolide A substructures significantly fewer steps than previously possible.

Language: Английский

---

Historical perspective on ruthenium-catalyzed hydrogen transfer and survey of enantioselective hydrogen auto-transfer processes for the conversion of lower alcohols to higher alcohols

Chemical Science, Journal Year: 2022, Volume and Issue: 13(43), P. 12625 - 12633

Published: Jan. 1, 2022

Ruthenium-catalyzed hydrogen auto-transfer reactions for the direct enantioselective conversion of lower alcohols to higher are surveyed. A brief historical perspective on ruthenium-catalyzed transfer is given.

Language: Английский

---

Stereo- and Site-Selective Conversion of Primary Alcohols to Allylic Alcohols via Ruthenium-Catalyzed Hydrogen Auto-Transfer Mediated by 2-Butyne

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(19), P. 8861 - 8869

Published: May 3, 2022

The first enantioselective ruthenium-catalyzed carbonyl vinylations via hydrogen autotransfer are described. Using a ruthenium-JOSIPHOS catalyst, primary alcohols 2a–2m and 2-butyne 1a converted to chiral allylic 3a–3m with excellent levels of absolute stereocontrol. Notably, 1°,2°-1,3-diols participate in site-selective C–C coupling, enabling asymmetric vinylation beyond premetalated reagents, exogenous reductants, or hydroxyl protecting groups. 2-propanol as reductant, aldehydes dehydro-2a, 2l highly 2-butyne-mediated under otherwise identical reaction conditions. Regio-, stereo-, mediated by 2-pentyne 1b form adducts 3n, 3o, epi-3o also tiglyl alcohol motif obtained upon butyne-mediated vinylation, which is itself found diverse secondary metabolites, may be commonly encountered polyketide stereodiads, -triads, -tetrads, demonstrated the formation 4a–4d. collective mechanistic studies, including deuterium labeling experiments, corroborate catalytic cycle involving dehydrogenation transient aldehyde ruthenium hydride, engages alkyne hydrometalation nucleophilic vinylruthenium species that enacts addition. A stereochemical model for addition invoking formyl CH···I[Ru] CH···O≡C[Ru] bonds proposed based on prior calculations crystallographic data.

Language: Английский

---

Carbonyl Allylation and Crotylation: Historical Perspective, Relevance to Polyketide Synthesis, and Evolution of Enantioselective Ruthenium-Catalyzed Hydrogen Auto-Transfer Processes

Synthesis, Journal Year: 2023, Volume and Issue: 55(10), P. 1487 - 1496

Published: Feb. 20, 2023

Abstract The evolution of methods for carbonyl allylation and crotylation alcohol proelectrophiles culminating in the design iodide-bound ruthenium-JOSIPHOS catalysts is prefaced by a brief historical perspective on asymmetric its relevance to polyketide construction. Using gaseous allene or butadiene as precursors allyl- crotylruthenium nucleophiles, respectively, new capabilities have been unlocked, including stereo- site-selective 1,3-diols related polyols. 1 Introduction Historical Perspective 2 Ruthenium-Catalyzed Conversion Lower Alcohols into Higher 3 Conclusion Future Outlook

Language: Английский

---

Asymmetric Ruthenium-Catalyzed Carbonyl Allylations by Gaseous Allene via Hydrogen Auto-Transfer: 1° versus 2° Alcohol Dehydrogenation for Streamlined Polyketide Construction

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(3), P. 1662 - 1668

Published: Jan. 12, 2023

Iodide-bound ruthenium–JOSIPHOS complexes catalyze the redox-neutral C–C coupling of primary alcohols 2a–2r with gaseous allene (propadiene) 1a to form enantiomerically enriched homoallylic 3a–3r complete atom efficiency. Using formic acid as reductant, aldehydes dehydro-2a and dehydro-2c participate in reductive deliver adducts 3a 3c comparable levels asymmetric induction. Deuterium labeling studies corroborate a mechanism which alcohol dehydrogenation triggers hydroruthenation transient allylruthenium–aldehyde pairs that carbonyl addition. Notably, due kinetic preference for dehydrogenation, chemoselective 1°,2°-1,3-diols occurs absence protecting groups. As illustrated by synthesis C7–C15 spirastrellolide B F (7 vs 17 steps), C3–C10 cryptocarya diacetate (three seven or nine steps) fragment common C8′–C14′ mycolactone (one four C22–C28 marinomycin A this capability streamlines type I polyketide construction.

Language: Английский

---