Rhodium-Catalyzed Regio- and Enantioselective Direct Allylation of Methyl Ketones

Abstract

We report a highly branch-selective and enantioselective allylic alkylation of simple ketones with racemic aliphatic allylic carbonates under mild conditions. By using a Rh–bisoxazolinephosphine system and catalytic amounts of a base in THF, a series of chiral β-branched γ,δ-unsaturated ketones were obtained with excellent regio- and enantioselectivities. An outer-sphere nucleophilic substitution C–C bond-formation process is proposed on the basis of mechanistic studies.

Key words

rhodium catalysis - bisoxazolinephosphines - ketones - allylic substitution - asymmetric catalysis

Publication History

Received: 05 May 2022

Accepted after revision: 05 July 2022

Accepted Manuscript online:
05 July 2022

Article published online:
30 September 2022

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• 12 Chiral β-Branched γ,δ-Unsaturated Ketones 3; General ProcedureIn a N₂-filled glovebox, a pressure tube equipped with a magnetic stirrer bar was charged with [Rh(cod)Cl]₂ (1.3 mg, 1.25 mol%), NPN^Ph, ^iPr (3.0 mg, 3.0 mol%), and THF (1.0 mL), and the mixture was stirred at rt for 15 min. rac-1 (0.2 mmol, 1.0 equiv), 2 (0.3 mmol, 1.5 equiv), and a 1.0 M solution of LiHMDS in THF (20 μL; 10.0 mol%) were added to the solution and the tube was tightly capped, transferred out of the glovebox, and heated at 80 °C for 12 h. The mixture was then cooled, filtered through a short pad of silica gel (with elution by EtOAc), and concentrated under reduced pressure. The residue was purified by column chromatography.(3S)-1-(4-Methoxyphenyl)-3-propylpent-4-en-1-one (3aa)Synthesized from 1a and 2a by following the general procedure on a 0.2 mmol scale as a colorless viscous oil; yield: 44.1 mg, (96%; 95% ee, b/l = 15:1), [α]_D ²⁵ –14.0 (c = 0.8, CHCl₃).HPLC [Shimadzu LC-2030; Chiralpak IG, ⁱ PrOH–hexane (1.0:99.0), 1.0 mL/min, 40 °C, λ = 254 nm]: t _R = 22.660 min (major), 26.555 min (minor). ¹H NMR (400 MHz, CDCl₃): δ = 7.85 (d, J = 8.9 Hz, 2 H), 6.85 (d, J = 8.9 Hz, 2 H), 5.60 (ddd, J = 17.2, 10.3, 8.3 Hz, 1 H), 4.95–4.85 (m, 2 H), 3.79 (s, 3 H), 2.84 (d, J = 7.1 Hz, 2 H), 2.72–2.62 (m, 1 H), 1.38–1.19 (m, 4 H), 0.82 (t, J = 8.0 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 198.1, 163.4, 141.7, 130.5, 130.4, 114.6, 113.7, 55.4, 43.6, 39.8, 36.9, 20.2, 14.1. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₂₁O₂: 233.1536; found: 233.1532.