Highly Efficient Kinetic Resolution of Aryl-Alkenyl Alcohols by Ru-Catalyzed Hydrogen Transfer

Abstract

No matter through asymmetric reduction of ketones or kinetic resolution of secondary alcohols, enantioselective synthesis of the corresponding secondary alcohols is challenging when the two groups attached to the prochiral or chiral centers are spatially or electronically similar. For examples, dialkyl (sp³ vs. sp³), diaryl (sp² vs. sp²), and aryl-alkenyl (sp² vs. sp²) alcohols are difficult to produce with high enantioselectivities. By exploiting our recently developed Ru-catalysts of minimal stereogenicity, we reported herein a highly efficient kinetic resolution of aryl-alkenyl alcohols through hydrogen transfer. This method enabled such versatile chiral building blocks for organic synthesis as allylic alcohols, to be readily accessed with excellent enantiomeric excesses at practically useful conversions.

Keywords: Ru-catalyst; aryl-alkenyl alcohols; asymmetric transfer hydrogenation; kinetic resolution; selectivity factor.

Figure 1

Kinetic resolution of racemic aryl-alkenyl alcohols via a Ru-catalyzed hydrogen transfer.

Scheme 1

Optimization of Conditions ^a.

Figure 2

Kinetic resolution of allylic alcohols via hydrogen transfer. General conditions: racemic allylic alcohol (0.2 mmol), Ru-(S)-ⁱPrPyme-catalyst (0.1–0.25 mol%), KO^tBu (15 mol%), toluene or CH₂Cl₂ (2.0 mL), 23 °C. ^aAn amine nucleophile (2d or 2e, 0.12 mmol) was added. ^b No external nucleophile was added. Conversion (c) was calculated by the following formula: c = 1− (¹H NMR yield_{(recovered alcohols)})%. Yields were determined by ¹H NMR using 1,4-dinitrobenzene as the internal standard. s = In[(1 − c)(1 − ee)]/In[(1 − c)(1 + ee)].