Highly Enantioselective SPINOL‐Derived Phosphoric Acid Catalyzed Transfer Hydrogenation of Diverse C=N‐Containing Heterocycles

Abstract

A highly efficient and enantioselective hydrogenation of diversely substituted C=N‐containing heterocyclic compounds such as 3‐aryl‐1,4‐benzoxazines and 2‐arylquinolines was experimentally explored by using 1,1′‐spirobiindane‐7,7′‐diol‐derived chiral phosphoric acids as the catalyst. This method provides straightforward access to the corresponding tetrahydroquinolines and dihydro‐2H‐1,4‐benzothiazines in high yields (85–99 %) with excellent enantioselectivities (91–99 %). The attractive features of this procedure, which include mild reaction conditions, operational simplicity, relatively low catalyst loading (1 mol‐%), and high levels of enantioselectivities, make it a useful approach for the practical synthesis of optically active nitrogen‐containing aromatic heterocycles.

Chiral and Regenerable NAD(P)H Models Enabled Biomimetic Asymmetric Reduction: Design, Synthesis, Scope, and Mechanistic Studies

“…On the basis of density functional theory calculations [see the Supporting Information (SI) for more details] and aforementioned experimental data, a plausible mechanism 21 and optimized stationary points together with their relative energies are illustrated in Scheme 11. 22 The optimized stationary points and relative energies mainly involved in the chiral and regenerable NAD(P)H model-facilitated biomimetic asymmetric reduction of CN and CC bonds. At first, the chiral NAD(P)H model (R)-1f could be reduced to (R)-1f-H in situ by the ruthenium complex and hydrogen gas.…”

S‐Benzyl‐N,N′‐diphenyl Isothiouronium Iodide as an Efficient Organocatalyst for the Transfer Hydrogenation of 1,4‐Benzoxazines

“…Metal‐free catalysts for the transfer hydrogenation have been rarely developed. Hitherto, metal‐free catalysts, such as, phosphonic acid derivatives, [5a–e] B(C 6 F 5 ) 3 , [5f] and thiourea dioxide [5g] have been reported. There is need for an upgraded metal‐free catalyzed protocol (Scheme 1).…”

Chiral Phosphoric Acids as Versatile Tools for Organocatalytic Asymmetric Transfer Hydrogenations

“…Serving as a benchmark reactions, various procedures were reported for the asymmetric reduction of 2-phenylquinoline (49), relying on classical CPA catalysis in alternative reaction media, [55] bitetralone-modified CPAs, [56] cyclophane-and cathenane-based CPAs, [57][58][59] bisphosphoric acids, [60,61] as well as using BIFOL- [62] and SPINOL-derivatives (Scheme 19). [63] Tang et al explored a novel, AOX-mediated (AOX: aza-oxylene) methodology to access dihydroquinolines (Scheme 20). [64] In the presence of a Brønsted acid, the 1,2dihydroquinoline substrate ( 52) undergoes dearomatization forming a reactive and highly electrophilic aza-o-xylene (AOX) intermediate which then readily reacts with the HE 3 reductant.…”

“…In 2015, Shi et al successfully applied SPINOL-derived phosphoric acids for the ATH of 1,4-benzoxazines. [63] Using (S)-CPA 8, a broad range of 2-aryl substituted substrates (65 a-l) could be reduced in 85-99 % yield and in excellent enantioselectivities (91-> 99 % ee) with very low catalyst loading (Scheme 24). Notably, this method was also suitable for the ATH of diverse N-heterocycles including quinolines (49), 1,4-benzothiazolines (67), and benzoxazinanones (69) resulting in similarly high catalytic efficiency for all substrate classes.…”

“…Serving as a benchmark reactions, various procedures were reported for the asymmetric reduction of 2‐phenylquinoline ( 49 ), relying on classical CPA catalysis in alternative reaction media, [55] bitetralone‐modified CPAs, [56] cyclophane‐ and cathenane‐based CPAs,[ 57 , 58 , 59 ] bisphosphoric acids,[ 60 , 61 ] as well as using BIFOL‐ [62] and SPINOL‐derivatives (Scheme 19 ). [63] …”