α- and γ-Regiocontrol and Enantiospecificity in the Copper-Catalyzed Substitution Reaction of Propargylic Phosphates with Grignard Reagents.

Abstract

The regioselectivity (r.s.) and enantiospecificity (e.s.) of the substitution reactions of secondary propargylic alcohol derivatives using reagents derived from ArMgBr and Cu salts were studied. First, the picolinate, 3-methylpicolinate, and diethylphosphonate derivatives of Ph(CH2 )2 CH(OH)C≡CTMS were reacted with PhMgBr/CuCN in ratios of 2.5:2.7-2.5:0.25. The use of 2.5:0.25 ratio in THF/DME (6:1) at 0 °C for 1 h afforded the α-substitution product from the phosphate with ≥98 % r.s. and 99 % e.s. CuBr⋅Me2 S gave similar selectivity. The reaction system was then applied to phosphates derived from R1 CH(OH)C≡CR2 and ArMgBr to obtain synthetically sufficient r.s. and e.s. values with R2 =TMS, Ph, whereas iPr was borderline in terms of size as an R1 substituent. The presence of a substituent at the o-position of Ar marginally affected the selectivity. We also found that the use of PhMgBr/Cu(acac)2 in a 2:1 ratio in THF produced the γ-substitution products (allenes) with high r.s. and e.s.