Tandem Wittig Reaction–Ring Contraction of Cyclobutanes: A Route to Functionalized Cyclopropanecarbaldehydes

Abstract

An original tandem reaction consisting of a Wittig reaction−ring contraction process between α-hydroxycyclobutanone and phosphonium ylides has been developed. Highly functionalized cyclopropanecarbaldehydes are obtained in good to high yield.

Ring contraction in synthesis of functionalized carbocycles

“…133 (G) Tandem Wittig reaction/ring contraction. 134 (H) Oxidative and deformylative ring contraction gave cyclopentane 185 containing vicinal quaternary carbon centers. 135…”

Iodine(III)-Mediated Fluorination/Semipinacol Rearrangement Cascade of 2-Alkylidenecyclobutanol Derivatives: Access to β-Monofluorinated Cyclopropanecarbaldehydes

“…According to the known procedure, a solution of 2b (0.2 mmol, 47.2 mg) and (ethoxycarbonylmethylene)-triphenylphosphorane (0.3 mmol, 1.5 equiv) in toluene (0.5 mL) was stirred in a sealed tube reactor at 110 °C in a metal bath for 18 h. The crude mixture, without aqueous workup, was directly purified by flash column chromatography (petroleum ether/EtOAc = 20:1→15:1) to give compound 7 as a yellow oil in 66% yield (40.5 mg). 1 H NMR (400 MHz, chloroform- d ): δ 8.04 (d, J = 8.1 Hz, 2H), 7.43 (d, J = 8.1 Hz, 2H), 6.85 (d, J = 15.9 Hz, 1H), 5.69 (d, J = 15.9 Hz, 1H), 5.37 (d, J = 46.7 Hz, 1H), 4.13 (q, J = 7.1 Hz, 2H), 3.92 (s, 3H), 1.24 (t, J = 7.1 Hz, 3H), 1.20–1.16 (m, 1H), 1.10–0.98 (m, 3H).…”

“…Methyl 4-(Fluoro(1-(hydroxymethyl)cyclopropyl)-methyl)benzoate (4). According to the known procedure, 25 to a solution of 2b (0.2 mmol, 47.2 mg, 1.0 equiv) in MeOH (3 mL) was added NaBH 4 (15.1 mg, 0.4 mmol, 2.0 equiv) at 0 °C, and the reaction mixture was stirred at the same temperature for 15 min. The mixture was poured into H 2 O and extracted with EtOAc.…”

“…HRMS (ESI-TOF) m/z: [M + Na] + calcd for C 13 H 13 FO 4 Na,275.0690;found,cyclopropyl)-methyl)benzoate (6). According to the known procedure, 25 compound 2b (0.2 mmol, 47.2 mg) was dissolved in MeOH (3 mL). Oxone (245.0 mg, 0.8 mmol, 4.0 equiv) was added in one portion and stirred at room temperature for 48 h. 1 N HCl was used to dissolve the salts, and EtOAc was added to extract the products.…”

Stereoselective Synthesis of trans-Decalin-Based Spirocarbocycles via Photocyclization of 1,2-Diketones

“…Carbocyclic four-membered ring compounds are important building blocks in organic synthesis . In this aspect, α-hydroxyl cyclobutanone derivatives are particularly attractive because of their usefulness as starting materials for the preparation of structurally diverse molecules . Because of its high ring strain, synthesis of cyclobutanone is challenging.…”