Asymmetric Transfer Hydrogenation of Arylidene-Substituted Chromanones and Tetralones Catalyzed by Noyori–Ikariya Ru(II) Complexes: One-Pot Reduction of C═C and C═O bonds

Abstract

3-Arylidenechroman-4-ones and 2-arylidene-1-tetralones are hydrogenated to cis-benzylic alcohols in dr’s and er’s up to 99:1 via a CC and CO one-pot reduction in the presence of 2–5 mol % Noyori–Ikariya-type RuII chiral complexes and HCO2Na as a hydrogen source under asymmetric transfer hydrogenation–dynamic kinetic resolution (ATH-DKR) conditions. The oxidation of theses substrates resulted in the enantioselective synthesis of the natural homoisoflavanone dihydrobonducellin and its carba-analogues.

Enantioselective Synthesis of Isoflavanones and Pterocarpans through a RuII‐Catalyzed ATH‐DKR of Isoflavones

“…Moreover, the saturated alcohol 10 a was obtained with very poor stereoselectivity (6 : 4 dr, 87 : 13 er). On the other hand, ( R , R )‐ 10 a had been obtained under mild conditions (2 mol% of ( R , R )‐ 1 b at rt) in excellent stereoselectivity (>20 : 1 dr, >99 : 1 er) through the one‐pot reduction of the isomer 9 a’ in our previous report [11] (Scheme 4b). These data indicate a considerably greater difficulty for the C=C bond to be reduced by these Ru II ‐complexes 1 in substrates with higher conformational freedom at 3‐position [benzyl ( 9 ) versus phenyl ( 6 )] as well as for endocyclic C=C bonds ( 9 ) versus exocyclic C=C bonds ( 9’ ).…”

“…of HCO 2 Na reduction of 6 k led only to 56 % conversion. Finally, the use of 10 mol% of Cu(OTf) 2 as additive [11] allowed the obtention of the cis ‐alcohol 8 k , substituted with the bulky bromine atom at 2’‐position, in 85 % yield and 98 : 2 er by using 5 mol% of ( R , R )‐ 1 b at 70 °C (Scheme 3, method C).…”

“…These optically active products are especially sensitive to epimerization, requiring a mild oxidation protocol to avoid erosion of the enantiomeric purity. In this context, the Dess‐Martin periodinane (DMP) oxidation [11,26] stands out as a useful metal‐free alternative to the already reported metal‐based protocol [8] …”

“…Taking into account our group‘s continuous interest in the synthesis of isoflavonoids and their modified carba‐analogues [10] for biological evaluation, we are now focusing on developing practical methodologies based on ATH‐DKR to obtain these compounds in their enantiomerically enriched forms. Very recently, we reported the one‐pot reduction of C=C and C=O bonds of homoisoflavones and carba‐analogues under ATH‐DKR (Scheme 1c) [11] . The cis ‐alcohols were obtained in enantioselectivities up to >99 % ee by using ( R , R )‐ 1 b and HCO 2 Na as the hydrogen source in a biphasic aqueous media.…”

Base-Catalyzed Traceless Silylation and Deoxygenative Cyclization of Chalcones to Cyclopropanes

“…The precipitate was dried to obtain the desired products. The pure product was obtained by recrystallization …”