Practical synthesis of hex-5-ynoic acid from cyclohexanone

Abstract

Hex-5-ynoic acid, a mult.ipurpose synth0n, was synthesized in three steps starting from cyclohexanone by bromination--dehydrobr6mination of the intermediate hex-5-enoic acid.

Enantioselective Organocatalyzed Bromolactonizations: Applications in Natural Product Synthesis

“…Yield: 26.9 g (82%). The spectroscopic data were in accord with literature values . TLC (heptane/EtOAc 85:15): R f = 0.47, visualized with KMnO 4 stain.…”

“…The combined organic extracts were washed with brine, dried (Na 2 SO 4 ), and filtered, and the solvent was evaporated in vacuo. The residue was purified by flash chromatography on silica (hexanes/EtOAc in various proportions) to afford the corresponding methyl 5-arylhex-5-enoates 11d , 11f , and 11j with physical and spectral data in accord with literature values . The chemical yields for 11d , 11f , and 11j were 78 mg (96%), 144 mg (96%), and 82 mg (50%), respectively.…”

“…The resulting solution was allowed to warm to room temperature over 3 h. Glacial acetic acid (16 mL) was carefully added to the mixture and stirred for 1 h. This mixture was quenched with water, extracted with CH 2 Cl 2 (2 × 45 mL), and dried (MgSO 4 ). The residue was purified by flash chromatography on silica (10% EtOAc in hexane) to afford the corresponding methyl 5-bromohex-5-enoate ( 10 ) with physical and spectral data in accord with literature values . Step 2: Methyl 5-bromohex-5-enoate ( 10 , 100 mg, 0.48 mmol, 1.0 equiv), the specific 4-arylboronic acid (0.58 mmol.…”

Synthesis of carboxylated derivatives of poly(isobutylene-co-isoprene) by azide–alkyne “click” chemistry

“…The acetylenic acids were synthesized by modifying the procedure of Starostin et al 45 The synthesis of 5-hexynoic acid (6-COOH) is described in Scheme 2. Cyclohexanone was first treated with 30% H2O2 to form cyclohexanone peroxide, which upon reaction with FeSO4/CuSO4 CuBr (eq) PMDETA (eq) Alkyne (eq) Solvent (50 mL for 0.5 g of IIR) promotes migration of the acetylenic bond to the center of the chain.…”

“…Cyclohexanone was first treated with 30% H2O2 to form cyclohexanone peroxide, which upon reaction with FeSO4/CuSO4 CuBr (eq) PMDETA (eq) Alkyne (eq) Solvent (50 mL for 0.5 g of IIR) promotes migration of the acetylenic bond to the center of the chain. 45,46 Consequently we preferred using NaOH, with PEG-200 acting as a phase transfer catalyst. This method was found to favor the formation of 5-hexynoic acid as compared with an aqueous NaOH solution (Figure S3).…”