Synthesis of Chiral 2-Substituted 1,4-Benzoxazin-3-ones via Iridium-Catalyzed Enantioselective Hydrogenation of Benzoxazinones

Abstract

An efficient iridium-catalyzed enantioselective hydrogenation of 2-alkylidene 1,4-benzoxazin-3-ones using our developed iPr-BiphPHOX as a ligand is reported. This method showed good functional group compatibility and delivered the corresponding reduced products in excellent yields (up to 99%) with excellent enantioselectivities (up to 99% ee). The reaction proceeded very well on a gram scale with low catalyst loadings (0.1 mol %), providing the product with no erosion in enantioselectivity. Additionally, three bioactive molecules can be easily obtained from the reduced products.Letter pubs.acs.org/OrgLett

Cu‐Catalyzed Asymmetric Kinetic Boron Conjugate Addition of γ‐Substituted α,β‐Unsaturated γ‐Lactams

“…( R )‐ 1 a could be reduced to N ‐heterocycle compound 4 in 45 % yield by employing LiAlH 4 /ZnCl 2 . Additionally, ( R )‐ 1 a could also be hydrogenated in the presence of an Ir/ rac ‐In‐BiphPHOX catalyst, providing 5 in 88 % yield [11] . Moreover, the synthetic utility of chiral saturated β‐hydroxy γ‐lactams 2 was also demonstrated (Scheme 2, c).…”

“…Additionally, (R)-1 a could also be hydrogenated in the presence of an Ir/rac-In-BiphPHOX catalyst, providing 5 in 88 % yield. [11] Moreover, the synthetic utility of chiral saturated β-hydroxy γ-lactams 2 Table 1: Optimization of the reaction conditions. [a] ligand C.…”

Transition Metal‐Catalyzed Enantioselective Synthesis of Chiral Five‐ and Six‐Membered Benzo O‐heterocycles

“…Very recently, Zhang and Yuan reported Ir-catalyzed asymmetric hydrogenation of 2-alkylidene 1,4-benzoxazin-3ones 13 by i Pr-BiphPHOX ligand (TMC5), which is derived from biphenylphosphineoxazolines (BiphPHOX) with axis unfixed skeleton. [34] Various substituted substrates could be applied, affording the products with excellent yields and enantioselectivities (Scheme 4). However, the substrate without protecting group on the nitrogen atom led to trace amount of product.…”

Axis‐Unfixed Biphenylphosphine‐Oxazoline Ligands: Design and Applications in Asymmetric Catalytic Reactions

“…In order to further expand the scope of the application of the BiphPHOX ligand in asymmetric hydrogenation reactions, we developed an efficient Ir/BiphPHOX complex catalyzed asymmetric hydrogenation of 2‐alkylidene 1,4‐benzoxazin‐3‐ones 39 (six‐membered ring substrates bearing exocyclic C=C bonds) (Scheme 16). [32] Under the optimized reaction conditions, the scope of the substrates was examined. The reaction showed good functional group compatibility and delivered a variety of chiral 2‐substituted 1,4‐benzoxain‐3‐ones 40 a – 40 w in excellent yields (up to 99 %) and with excellent enantioselectivities (up to 99 %).…”