Development of a Robust Procedure for the Copper-catalyzed Ring-Opening of Epoxides with Grignard Reagents

Abstract

A general procedure for the copper-catalyzed regioselective ring-opening of epoxides with Grignard reagents is described. The procedure developed provides robust reaction conditions which limit the formation of impurities and has been applied successfully using a series of epoxides and Grignard reagents to provide the desired products in >90% yield with excellent regioselectivity and purity.

Total Synthesis of a Mycolic Acid from Mycobacterium tuberculosis

“…Acid hydrolysis of the acetal, followed by a one‐pot tosylation of the primary alcohol and intramolecular S N 2 reaction went smoothly, and yielded the corresponding epoxide 25 in excellent yield over two steps. Epoxide opening with Grignard reagent 26 using catalytic CuCl minimized the formation of halohydrin by‐products and afforded the secondary alcohol 27 in good yield. Finally, methylation of the secondary hydroxyl using an excess of MeI and NaH resulted in both enantiomers of fragment C in nearly quantitative yields.…”

An alternative synthesis of the CNS stimulant Prolintane

“…Next, the epoxide 3 was subjected to a regioselective ring opening using vinyl magnesium bromide in presence of CuI to afford the required key intermediate 1-Phenylpent-4-en-2-ol 4 in 85% yield. 9 Installation of succinimide moiety on 1-Phenylpent-4-en-2-ol 4 was accomplished using Mitsunobu protocol 10 to furnish succinimido derivative 5 in 80% yield. Subsequently, amide reduction of compound 5 was performed using lithium aluminium hydride (LiAlH4) in THF under reflux condition to obtain pyrrolidine 6 in 76% yield.…”

Substrate stereocontrol in bromine-induced intermolecular cyclization: asymmetric synthesis of pitavastatin calcium

“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 5 2927, 2863, 1643, 1488, 1099, 1068MS (ESI): m/z 293 (M + Na + ). 10 Obtained ( 4, 134.1, 133.5, 129.0, 128.6, 117.8, 73.9, 72.5, 69.6, 37.9; HRMS (ESI-TOF) m/z calcd for C12H16ClO2 (M + H + ) 227.0839, found 227.0833.…”