Cu-Catalyzed Asymmetric Conjugate Addition of Dialkylzincs to Enones Using a (±)-trans-1,2-Cyclohexanediamine-Based Bis(NHC) Derived from l-Leucinol

Abstract

A hydroxyamide-functionalized azolium salt as the precursor of a (±)-trans-1,2-cyclohexanediamine-based bis(NHC) ­ligand was designed and synthesized from readily accessible l-leucinol. The combination of a Cu salt with this chiral ligand precursor promoted the asymmetric conjugate addition of Et₂Zn to 2-cyclohexen-1-one at room temperature without the need for temperature control to afford the corresponding 1,4-adduct with up to 95% ee.

Key words

asymmetric catalysis - carbene complexes - copper - ­Michael addition - ligands

• References and Notes


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• 13 Analytical and Spectral Data of L1: ¹H NMR (400 MHz, DMSO-d ₆): δ = 10.58 (br, 2 H), 8.54 (d, J = 8.2 Hz, 2 H), 7.90 (br, 2 H), 7.68–7.66 (m, 2 H), 7.42–7.33 (m, 4 H), 5.76 (br, 2 H), 5.30–5.18 (m, 4 H), 4.65–4.62 (m, 2 H), 3.81 (br, 2 H), 3.41–3.37 (m, 4 H), 2.58 (br, 2 H), 2.49–2.43 (m, 2 H), 2.05 (br, 2 H), 1.83 (br, 2 H), 1.66–1.58 (m, 2 H), 1.36 (t, J = 6.9 Hz, 4 H), 0.89–0.86 (m, 6 H), 0.84–0.81 (m, 6 H). HRMS (ESI²⁺): m/z calcd for C₃₆H₅₂N₆O₄ ²⁺: 316.2019; found: 316.2014.
• 14 General Procedure for the ACA Reaction: To a solution of azolium salt (0.045 mmol) in THF (9 mL) were added Cu salt (0.06 mmol) and enone (1 mmol). After the mixture was cooled to 0 °C, Et₂Zn (1 M in hexanes, 3 mmol, 3 mL) was added to the reaction vessel. The color immediately changed from yellow to dark-brown. After stirring at room temperature for 3 h, the reaction was quenched with 10% HCl aq. The resulting mixture was extracted with i-Pr₂O (3 × 10 mL) and dried over Na₂SO₄. The product was purified by silica gel column chromatography (hexane–Et₂O).