Catalytic 1,3‐Difunctionalisation of Organic Backbones through a Highly Stereoselective, One‐Pot, Boron Conjugate‐Addition/Reduction/Oxidation Process

Abstract

A simple one-pot, three-step synthetic route to chiral 1,3-amino alcohols and 1,3-diols has been established. Considering the overall stereocontrol of the synthetic protocol, the first and key step is an enantioselective β-boration of α,β-unsaturated imines and ketones, respectively. The enantioselectivity provided by the Cu(I) catalyst modified with Josiphos- and Mandyphos-type ligands has been examined. The oxidative substitution of the boryl unit with a hydroxyl group proceeds with complete retention of configuration at the C(β)-atom. In parallel, the stoichiometric reduction of the imino or carbonyl group provides a second stereogenic centre. Depending on the nature of the reducing reagent, exceptionally high diastereoselectivity is achieved, especially for syn-1,3-amino alcohols and 1,3-diols.

Recent Advances in Metal-Catalyzed Asymmetric 1,4-Conjugate Addition (ACA) of Nonorganometallic Nucleophiles

“…In 2011, Fernańdez and co-workers successfully developed a one-pot three-step borylation/reduction/oxidation of α,βunsaturated imine starting materials using Cu(I) complexes based on chiral phosphorus ligands, providing an efficient route for the synthesis of γ-amino alcohols, valuable synthetic intermediates, in good yields with up to 99% ee (Scheme ). 311,312 Most recently, Whiting and co-workers disclosed the synthesis of chiral homoallylic boronates with high ee's by an efficient one-pot methodology (the imine is formed in situ from its respective α,β-unsaturated aldehyde, followed by catalytic borylation in the presence of complex L85−Cu(I) and workup). The unstable borylation products could easily be transformed to stable compounds by either a subsequent Wittig olefination to give homoallylic boronates or subsequent CN reduction and C−B oxidation reactions to yield γ-amino alcohols (Scheme 76b).…”

Zeolite Immobilized Copper Catalyzed Conjugate Borylation of α,β-Unsaturated Compounds in Aqueous Media

“…[21] Notably, after pioneering works of Hosomi [22] and Miyaura, [23] Cu-catalyzed β-borylations have been widely explored because copper is green, cheap and abundant. Based on Cu(I) catalysis, conjugate β-borylation of α,β-unsaturated olefins was reported by groups of Yun, [24] Hoveyda, [25] Fernández, [26] and others. [27] However, Cu(I)-catalyzed procedures must be performed in anhydrous organic solvents.…”