Rhodium-Catalyzed Asymmetric Transfer Hydrogenation/Dynamic Kinetic Resolution of 3-Benzylidene-Chromanones

Abstract

Straightforward access to enantiomerically enriched cis-3-benzyl-chromanols from (E)-3-benzylidene-chromanones was developed through Rh-catalyzed asymmetric transfer hydrogenation. This transformation allowed the reduction of both the CC and CO bonds and the formation of two stereocenters in high yields with excellent levels of diastereo- and enantioselectivities (up to >99:1 dr, up to >99% ee) in a single step through a dynamic kinetic resolution process using a low catalyst loading and HCO2H/DABCO as the hydrogen source.

Asymmetric hydrogenation and transfer hydrogenation in the enantioselective synthesis of flavonoids

“…Most recently, two other groups reported almost simultaneously more direct approaches toward the cis -3-benzyl-chroman-4-ols through the one-pot CC/CO bond reduction catalysed by Rh III (ref. 94) or Ru II (ref. 95) Noyori–Ikariya type complexes (Scheme 43).…”

“…Ratovelomanana-Vidal and co-workers reported Rh-catalysed one-pot CC/CO reduction of homoisoflavones 185 (Scheme 44). 94 After reaction optimization, fourteen ( R , R )- 186 alcohols were obtained selectively (>20 : 1 dr) in good to excellent yields (69–98%) with excellent enantioselectivities (97 to >99% ee) by using only 0.5 mol% of ( R , R )- CAT9 and HCO 2 H/DABCO (5 : 2.5 equiv.) as the hydrogen source in acetonitrile at 50 °C for 24 h. Within the reaction scope, the methoxy group at the B-ring was evaluated at the ortho , meta and para -positions, resulting in a slight decrease of the enantiomeric excess in the first case (97% ee).…”

Tethered Rh(III)-N-(p-Tolylsulfonyl)-1,2-Diphenylethylene-1,2-Diamine Complexes: Efficient Catalysts for Asymmetric Transfer Hydrogenation

“…This one-pot ATH cascade protocol allowed the reduction of the C=C and C=O bonds and the formation of two stereocenters in high yields with diastereo- and enantioselectivities up to >99:1 dr and >99% ee through a DKR process using a low catalyst loading and HCO 2 H/DABCO as the hydrogen source (Table 1 , H). 13 The kinetic resolution (KR) of 2-aryl tetrahydro-4-quinolone derivatives 21 was efficiently achieved through ATH using the previous catalytic system. The reaction afforded the enantiomerically enriched 2-aryl-2,3-dihydroquinolin-4(1 H )-ones 23 with excellent levels of enantioselectivity (up to >99% ee) as well as the corresponding synthetically useful enantiomerically enriched 2-aryl tetrahydro-4-quinolols 22 in high isolated yields and up to >99% enantioselectivity (Table 1 , I).…”

“…10 The ATH of -keto--acetal enamides 15 has been studied with complex (R,R)-B and the HCO 2 H/Et 3 N (5:2) azeotropic mixture delivering a wide range of enantioenriched -hydroxy--acetal enamides 16 with a high chemoselectivity observed toward the reduction of the carbonyl group over the C=C bond, yields up to quantitative and enantioselectivities up to 99% (Table 1, F). 11 The same catalytic system was used to access 1,2,3,4tetrahydroquinolin-4-ols 18 conveniently through ATH of 4-quinolone derivatives 17 with excellent enantioselectivi-(F) ATH of -keto--acetal enamides 11 -Access to -hydroxy--acetal enamides -Mild conditions -Low catalyst loading -Excellent chemo-and enantioselectivities (G) ATH of Quinolone Derivatives 12 -Efficient and practical access to 1,2,3,4-tetrahydroquinolin-4-ols -Catalytic ATH cascade reaction -Mild conditions -Excellent enantiofacial discrimination (H) ATH/DKR of 3-Benzylidene Chromanones 13 -One-pot ATH cascade protocol to access cis-benzyl-chromanols -Low catalyst loading -2 stereogenic centers controlled in a single step -Excellent diastereo-and enantioselectivities (I) ATH/KR of 2-Aryl-2,3-dihydroquinolin-4(1H)-ones 14 -Synthesis of 2-aryl-2,3-dihydroquinolin-4(1H)-ones and 2-aryl tetrahydro-4quinolols -Efficient kinetic resolution -Excellent enantioselectivities (J) ATH of -Aminoalkyl ′-Chloromethyl Ketones 15 -Access to both diastereomers of 3-amino-1-chloro-2-hydroxy-4-phenylbutanes -Low catalyst loading -Excellent yields and high diastereoselectivities -Key building blocks for pharmaceutical intermediates -Broad scope (K) ATH/DKR of -Substituted -Keto Carbonitriles 16 -Efficient access to -substituted -hydroxy carbonitriles -Building blocks for biologically active pharmaceuticals -Excellent yields -High diastereoselectivities and excellent enantioselectivities -Rationalization of the diastereoselectivity by DFT calculations -Wide substrate scope…”

Straightforward Access to Enantioenriched cis-3-Fluoro-dihydroquinolin-4-ols Derivatives via Ru(II)-Catalyzed-Asymmetric Transfer Hydrogenation/Dynamic Kinetic Resolution

“…Asymmetric transfer hydrogenation (ATH) has been reported by Lassaletta and co-workers [ 5 ] as a method to access enantiomerically enriched fluoro-tetralol via a dynamic kinetic resolution (DKR) process ( Scheme 1 a). Following the premise of the fluorine need and the previous works in the laboratory including the ATH/DKR of 3-fluoro-chromanone derivatives [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ] ( Scheme 1 b), we herein report an asymmetric transfer hydrogenation/dynamic kinetic resolution [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ] (ATH/DKR) of tert -butyl 3-fluoro-4-oxo-3,4-dihydroquinoline-1(2 H )-carboxylates into the corresponding enantioenriched cis -fluorohydrins ( Scheme 1 c).…”