Allylic Substitution of Esters Derived from 2-Bromocyclohex-2-enol with Aryl Copper Reagents and Synthetic Utilization of the Derived anti S_N2′ Products

Abstract

Allylic substitution of esters derived from 2-bromocyclohex-2-enol with PhMgBr-based copper reagent was investigated to find high anti S_N2′ selectivity with the diethyl phosphate, whereas other esters such as picolinate, acetate, and mesylate resulted in partial racemization or recovery of the starting esters. This protocol was applied to the copper reagent derived from 2-Me-4-MeOC₆H₃MgBr and CuBr·SMe₂ and the olefin part of the anti S_N2′ product was cleaved for a synthesis of patchouli alcohol.

Key words

allylic substitution - bromocyclohex-2-enol - copper - Grignard reagent - patchouli alcohol

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• 16 General Procedure To an ice-cold suspension of CuBr·SMe₂ (114 mg, 0.555 mmol) in THF (4 mL) was added PhMgBr (0.68 mL, 0.703 M in THF, 0.48 mmol) dropwise. The mixture was stirred at 0 °C for 30 min and cooled to –40 °C. A solution of phosphate 2E (95% ee, 49.7 mg, 0.159 mmol) in THF (4 mL) was added to the mixture dropwise. After 3 h at 0 °C the reaction was quenched by addition of sat. NH₄Cl and purification of the crude product by chromatography afforded 3a (34.9 mg, 93%): 89% ee by HPLC; 94% CT. ¹H NMR (400 MHz, CDCl₃): δ = 1.50–1.68 (m, 2 H), 1.76–1.85 (m, 1 H), 2.09–2.27 (m, 3 H), 3.66–3.76 (m, 1 H), 6.35 (dt, J = 1, 4 Hz, 1 H), 7.21–7.27 (m, 3 H), 7.30–7.36 (m, 2 H). ¹³C-APT NMR (100 MHz, CDCl₃): δ = 17.9 (–), 27.8 (–), 33.9 (–), 49.8 (+), 124.4 (–), 126.7 (+), 128.3 (+), 128.4 (+), 132.0 (+), 143.4 (–).