Modular Access to Substituted Azocanes via a Rhodium-Catalyzed Cycloaddition–Fragmentation Strategy

A short entry to substituted azocanes by a Rh-catalyzed cycloaddition–fragmentation process is described. Specifically, exposure of diverse N-cyclopropylacrylamides to phosphine-ligated cationic Rh(I) catalyst systems under a CO atmosphere enables the directed generation of rhodacyclopentanone intermediates. Subsequent insertion of the alkene component is followed by fragmentation to give the heterocyclic target. Stereochemical studies show, for the first time, that alkene insertion into rhodacyclopentanones can be reversible.


S5
The spectroscopic properties of this compound were consistent with the data available in the literature. 3
HCl (100 mL) were added, the layers were separated and the aqueous phase was further extracted with EtOAc (2 × 50 mL). The organic extracts were combined, dried over Na 2 SO 4 and concentrated in vacuo. The residue was purified by flash column chromatography (30% EtOAc/hexane) to afford the title compound (2.

2-(4-Methoxyphenyl)acrylic acid
A solution of methyl 2-(4-methoxyphenyl)acrylate (450 mg, 2.34 mmol) and KOH (656 mg, 11.7 mmol) in THF (3.9 mL) and water (2.3 mL) was heated to 70 °C for 12 h. The reaction mixture was cooled to r.t. and diluted with water (20 mL). The solution was extracted with Et 2 O (20 mL) and then the aqueous portion was adjusted to pH 12 by addition of 1 M aq.

S17
General procedure E: cis-4g (53.6 mg, 0.249 mmol) was employed and the reaction was stirred at 150 °C for 22 h. Flash column chromatography (30% EtOAc/hexane) afforded the title compound 7g (30.5 mg, 50%) as a colorless oil. The spectroscopic data for 7g was consistent with the data reported above.

Methyl-d 3 -triphenylphosphonium iodide
To a solution of triphenylphosphine ( To a solution of methyl-d 3 -triphenylphosphonium iodide (7.50 g, 18.4 mmol) in THF (75 mL) at -78 °C was added n-BuLi (12.1 mL, 18.4 mmol, 1.52 M in THF) dropwise over 5 minutes. The solution was stirred at -78 °C for 15 minutes and then warmed to r.t. and stirred for 30 minutes. The reaction mixture was cooled back down to -78 °C and 3-phenylpropanal (2.43 mL, 18.4 mmol) was added dropwise over 5 minutes. After 20 minutes, the solution was warmed to r.t. and stirred for 18 h. The reaction mixture was filtered through Celite ® and concentrated in vacuo. The residue was purified by flash column chromatography (100% hexane) to afford the title compound (1.93 g, 78%) as a colorless oil; ν max / cm