Asymmetric Hydrogenation of 2-Arylated Cycloalkanones through Dynamic Kinetic Resolution

Abstract

Asymmetric hydrogenation of 2-arylcycloalkanones with trans-RuCl₂(binap)(1,2-diamine) and t-C₄H₉OK in 2-propanol selectively gives the corresponding cis-2-arylcycloalkanols in excellent enantiomeric purity and high yield. Two synthetic intermediates of biologically active compounds have been prepared by this method.

Key words

2-arylcycloalkanones - asymmetric hydrogenation - ­BINAP - dynamic kinetic resolution - ruthenium complexes

References

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  BINAP = 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl. TolBINAP = 2,2′-bis(di-4-tolylphosphino)-1,1′-binaphthyl. XylBINAP = 2,2′-bis(di-3,5-xylylphosphino)-1,1′-binaphthyl. DAIPEN = 1,1-di(4-anisyl)-2-isopropyl-1,2-ethylenediamine. DPEN = 1,2-diphenylethylene diamine.

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  Experimental Procedure of the Hydrogenation of 2a with Ketone:Ru = 100,000:1. Solid (R,RR)-7a (0.5 mg, 0.47 µmol), t-C₄H₉OK (180 mg, 1.73 mmol), and 2a (9.12 g, 51.2 mmol) were placed in a 500 mL glass autoclave equipped with a Teflon-coated magnetic stirring bar. Air present in the autoclave was replaced by argon. 2-Propanol (100 mL), which had been degassed by three freeze-thaw cycles, was added to the autoclave. The vessel was pressurized to 8 atm of hydrogen. The reaction mixture was vigorously stirred at 25 °C for 48 h, during which time the hydrogen cylinder was kept connected. After carefully venting the hydrogen gas in the apparatus, the solvent was removed under reduced pressure. The yield determined by GC was 100%. Subsequently, the residue was passed through a silica gel pad, eluted with a 1:4 EtOAc-hexane mixture giving (1S,2S)-5a (8.61 g, 93% yield, cis:trans = 100:0, 99.6% ee), [α]_D ²³ +103.6 (c 2.02, CH₃OH) {lit. [α]_D ²⁷ -106 (c 0.20, CH₃OH)},

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15

Absolute configuration of (2S,3S)-10 was determined after removal of the N-benzyl group by hydrogenolysis. [15]