Premium
α‐ and γ‐Regiocontrol and Enantiospecificity in the Copper‐Catalyzed Substitution Reaction of Propargylic Phosphates with Grignard Reagents
Author(s) -
Kobayashi Yuichi,
Takashima Yuji,
Motoyama Yuuya,
Isogawa Yukari,
Katagiri Kyosuke,
Tsuboi Atsuki,
Ogawa Narihito
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202004413
Subject(s) - chemistry , substituent , regioselectivity , reagent , selectivity , medicinal chemistry , grignard reaction , substitution reaction , copper , alcohol , catalysis , grignard reagent , stereochemistry , organic chemistry
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(CH 2 ) 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⋅Me 2 S gave similar selectivity. The reaction system was then applied to phosphates derived from R 1 CH(OH)C≡CR 2 and ArMgBr to obtain synthetically sufficient r.s. and e.s. values with R 2 =TMS, Ph, whereas i Pr was borderline in terms of size as an R 1 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.