Details

Autor(en) / Beteiligte

• Shen, Haigen
• Zhang, Zheng
• Shi, Zhaoxin
• Gao, Ke
• Wang, Zhaobin

Titel

A modular approach to stereoselective homoaldol reaction via photoredox/Cr/Co triple catalysis

Ist Teil von

• Chem, 2024-03, Vol.10 (3), p.998-1014

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Stereoselective homoaldol reactions offer an efficient route to valuable γ-hydroxy carbonyl compounds, which widely occur in natural products and bioactive molecules. However, achieving catalytic asymmetric homoaldol additions remains a significant challenge due to homoenolate’s amphoteric nature. Herein, we present a modular approach for stereoselective homoaldol reactions utilizing photoredox/Cr/Co triple catalysis, granting precise control over quadruple selectivity. Our method employs easily accessible acyloxy- and amide-substituted 1,3-dienes as homoenolate precursors, operating through a radical-polar crossover mechanism under mild conditions. This obviates the need for strong bases and stoichiometric chiral reagents, characteristic of classical approaches. The robustness and practicality of this method were demonstrated through late-stage modifications and the formal synthesis of bioactive compounds and natural products. Our preliminary mechanistic investigations encompassing radical trapping, control experiments, UV-vis spectroscopy, Stern-Volmer quenching, and deuterium-labeling provide valuable insights into the reaction pathway. [Display omitted] •Catalytic asymmetric homoaldol addition in a radical-involved approach•Quadruple selectivity controls photoredox/Cr/Co triple catalysis•Regioselective MHAT of internal 1,3-dienes•Quick access to related natural products and bioactive molecules Efficient methods for stereoselective homoaldol reactions are pivotal in synthetic chemistry due to the prevalence of γ-hydroxy carbonyl compounds in natural products and bioactive molecules. These compounds possess significant biological activities and are crucial synthetic intermediates. Despite advances in asymmetric aldol reactions, achieving selective homoaldol additions remains intricate due to homoenolate’s intricate behavior. The innovative modular approach using photoredox/Cr/Co triple catalysis marks a paradigm shift. By leveraging synergistic catalytic cycles, this method eliminates traditional limitations, obviating strong bases and stoichiometric chiral reagents. This innovation not only advances the synthetic chemistry toolbox but also underscores the potential of cooperative catalytic systems to revolutionize asymmetric transformations, making a lasting impact on synthetic methodology and enabling the creation of diverse and complex molecular architectures. Stereoselective homoaldol reactions remain a prominent challenge with limited success. In this work, we describe a photoredox/Cr/Co triple-catalyzed regio- and stereoselective homoaldol reaction using internal 1,3-dienes as a homoenolate equivalent. This protocol obviates the need for strong bases and stoichiometric chiral reagents, characteristic of classical approaches. Robustness and practicality are demonstrated via application in late-stage modification and the formal synthesis of bioactive compounds and natural products.