Enantioselective Bromination of Silyl Enol Ethers with Chiral Pentacarboxycyclopentadienyl Bromide

Dedicated to Professor Hisashi Yamamoto on the occasion of his 80^th birthday

Abstract

Chiral pentacarboxycyclopentadienyl bromide reagents were synthesized to accomplish enantioselective bromination of silyl enol ethers to give corresponding α-bromoketone products in good yields and up to 77% ee. A catalytic version of this reaction was also demonstrated through the combination of Lewis acid activators and diethyl 2,2-dibromomalonate as stoichiometric achiral bromine source.

Key words

enantioselectivity - asymmetric synthesis - bromine - silyl enol ethers - α-bromoketones - chiral pentacarboxycyclopentadienyl bromide

Publication History

Received: 17 April 2023

Accepted after revision: 08 May 2023

Accepted Manuscript online:
08 May 2023

Article published online:
14 June 2023

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• 17 Typical Procedure for Synthesizing Product 3a To a solution of PCCP-Br 1a (88 mg, 0.083 mmol, 1.0 equiv) in dry DCM (1.5 mL) was added dropwise silyl enol ether (0.1 mmol, 1.2 equiv) at –78 °C. After 22 h, the reaction was quenched by the addition of saturated aqueous NaHCO₃ (2 mL) and then extracted with dichloromethane (3 × 2 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (petroleum ether/ethyl acetate, 175:1 to 20:1) on silica gel to give 18.1 mg of 3a as colorless liquid (97% yield). The enantioselectivity was 69% ee, [α]_D ²⁵ +23.2 (c 0.19, CH₂Cl₂). HPLC conditions: Chiralpak AS-H column [hexanes/2-propanol = 98:2, flow rate = 1.0 mL/min), λ = 254 nm, t _R (major) = 9.0 min, t _R (minor) = 10.8 min. ¹H NMR (400 MHz, CDCl₃): δ = 8.09 (d, J = 7.7 Hz, 1 H), 7.54–7.50 (m, 1 H), 7.35 (t, J = 7.6 Hz, 1 H), 7.28 (d, J = 7.7 Hz, 1 H), 4,73 (t, J = 4.3 Hz, 1 H), 3.35–3.27 (m, 1 H), 2.92 (td, J = 17.2, 4.6 Hz, 1 H), 2.57–2.42 (m, 2 H) ppm. ¹³C NMR (101 MHz, CDCl₃): δ = 190.5, 142.9, 134.1, 129.9, 128.7, 128.6, 127.1, 50.4, 31.9, 26.1 ppm.