Modular Access to Azepines by Directed Carbonylative C–C Bond Activation of Aminocyclopropanes

A modular Rh-catalyzed entry to azepines is outlined. Under a CO atmosphere, protecting group directed C–C bond activation of aminocyclopropanes provides rhodacyclopentanones. These intermediates are effective for intramolecular C–H metalation of either an N-aryl or N-vinyl unit en route to azepine ring systems. Thus, byproduct-free heterocyclizations are enabled by sequential C–C activation and C–H functionalization steps.

The mixture was cooled to r.t and the contents of the four tubes were combined and diluted with ether (20.0 mL). The mixture was filtered through a pad of Celite, the filtrate was   129.7, 126.4, 124.9, 118.9, 77.2, 35.3, 28.3, 15.6, 14.3, 12.8.
The residue was purified by flash column chromatography (10% EtOAc/hexane) to yield the S23 title compound (S,S) trans-1m (55.5 mg, 31%, >99:1 e.r.) as a colorless oil. The enantiopurity of this compound was confirmed after the subsequent step.
The mixture was stirred at -78 °C for 1 h and then allyl bromide (10.4 uL, 0.12 mmol) was added to the mixture. The mixture was warmed to r.t. and stirred for 36 h. The mixture was then concentrated in vacuo and the residue was purified by column chromatography (10% EtOAc/Hex) to yield the title compound 8a (25.6 mg, 75%) as a colorless oil. A mixture of diastereomers A and B were obtained in a 8:1 (A:B) ratio.
The reaction mixture was stirred at r.t. for 4 h before concentrating in vacuo. The residue was dissolved in toluene (5.00 mL), then triethylamine (0.85 mL, 6.00 mmol) and benzyl chloroformate (1.00 mL, 3.00 mmol) were added. The reaction mixture was heated at 80 °C for 6 h. The suspension was cooled to r.t. and water (10.0 mL) was added. The mixture was extracted with EtOAc (3 × 10.0 mL) and the organic extracts were combined, dried over Na2-SO4 and concentrated in vacuo. The residue was purified by column chromatography (10% [α]D 23 +26.33 (c = 0.81, CHCl3).
The enantiopurity of this compound was determined by chiral SFC (Chiralpak IC, isocratic