Chiral Phosphoric‐Acid‐Catalyzed Transfer Hydrogenation of Ethyl Ketimine Derivatives by Using Benzothiazoline

Abstract

Chiral phosphoric acid catalyzed transfer hydrogenation of ketimines derived from propiophenone derivatives and reductive amination of alkyl ethyl ketone derivatives were extensively examined in the presence of two representative hydrogen donors. The excellent enantioselective transfer hydrogenation was achieved by use of benzothiazoline as a hydrogen donor. The theoretical studies elucidated that the unsymmetrical structure of benzothiazoline plays an important role in high enantioselective hydrogenation.

Selecting Chiral BINOL‐Derived Phosphoric Acid Catalysts: General Model To Identify Steric Features Essential for Enantioselectivity

“…For Type I  Z reactions the correct catalyst is dependent on the nature of the imine and nucleophile. Reactions involving acyclic imines require a catalyst that has large proximal sterics to disfavor Type II pathways and small AREA(θ) to disfavor competing Type I  E pathway 6, 7, 14b, 23, 54, 55, 56, 57, 58, 59, 60. If the imine is cyclic, the optimal catalyst is dependent on the nature of the nucleophile.…”

Enantiodivergent Atroposelective Synthesis of Chiral Biaryls by Asymmetric Transfer Hydrogenation: Chiral Phosphoric Acid Catalyzed Dynamic Kinetic Resolution

“…We selected 1 as as ubstrate for three reasons (Figure 1): 1) ease of ring opening to form the biaryl imine 2;2 )high affinity of the resulting 2 to chiral phosphoric acids (CPA); and 3) ease of modification of the aromatic ring of the aniline moiety,af eature which would strongly affect both reactivity and enantioselectivity.T he selection of the transformation from 2 was also important to achieve the high selectivity.W e envisaged that the transfer hydrogenation was suited for this purpose because of the high reliability of the chiral phosphoric acid catalysis. [15][16][17] An initial trial was conducted under reductive amination conditions starting with the lactol 5a,n ot 1a,f or streamline the screening of reaction conditions (catalysts and anilines): asolution of 5a in toluene was treated with 1.1 equivalents of o-hydroxyaniline (8a)a nd 1.5 equivalents of the Hantzsch ester 9a in the presence of 4 M.S.a nd 10 mol %o f ap hosphoric acid (Table 1). When TRIP (6a), which showed excellent catalytic performance in the asymmetric transfer hydrogenation of imines, [16,17] was employed, the transfer hydrogenation reaction proceeded smoothly to afford the biaryl 3aa in 75 %y ield with 33 % ee (entry 1).…”

“…[15][16][17] An initial trial was conducted under reductive amination conditions starting with the lactol 5a,n ot 1a,f or streamline the screening of reaction conditions (catalysts and anilines): asolution of 5a in toluene was treated with 1.1 equivalents of o-hydroxyaniline (8a)a nd 1.5 equivalents of the Hantzsch ester 9a in the presence of 4 M.S.a nd 10 mol %o f ap hosphoric acid (Table 1). When TRIP (6a), which showed excellent catalytic performance in the asymmetric transfer hydrogenation of imines, [16,17] was employed, the transfer hydrogenation reaction proceeded smoothly to afford the biaryl 3aa in 75 %y ield with 33 % ee (entry 1). Catalysts bearing 9-anthryl groups (6b)a nd 2,4-(CF 3 ) 2 C 6 H 3 groups (6c)r esulted in moderate selectivities (entries 2a nd 3).…”

Chiral Brønsted acid-catalyzed enantioselective Friedel–Crafts reaction of 2-methoxyfuran with aliphatic ketimines generated in situ

“… 4 From a mechanistic viewpoint of the chiral phosphoric acid-catalyzed reaction, the origin of the stereochemical outcome in the carbon–carbon (C–C) bond-forming reaction of the aliphatic ketimine has scarcely been investigated 5 despite conducting detailed studies of the enantioselective reduction of ketimines. 6 To establish the enantioselective Friedel–Crafts reaction of aliphatic ketimines followed by the acquisition of mechanistic insight into the stereo-determining step, we designed the reaction system shown in Scheme 1 .…”