Transition Metal-Catalyzed Hetero-[5 + 2] Cycloadditions of Cyclopropyl Imines and Alkynes:  Dihydroazepines from Simple, Readily Available Starting Materials

Abstract

The first example of a transition metal-catalyzed hetero-[5 + 2] cycloaddition reaction is described. Use of cyclopropyl imines as five-atom components, an alkyne as a two-carbon component, and a Rh(I) catalyst enables a new route to dihydroazepines. This new hetero-[5 + 2] cycloaddition works well with aldimines, ketimines, and with substituted cyclopropanes and affords the desired dihydroazepines in excellent yields as single regioisomers. Use of serial imine formation/aza-[5 + 2] cycloaddition generates the desired dihydroazepines in one operation from three commercially available starting materials. The reaction has been scaled to give gram quantities of dihydroazepine.

Recent Developments in the [5+2] Cycloaddition

“…[33] These results reported in 2002 are illustrated in Scheme 19. In this area, Cabaleiro-Lago et al have reported a density functional theory study of these reactions.…”

Palladium‐Catalyzed and Hybrid Acids‐Assisted Synthesis of [60]Fulleroazepines in One Pot under Mild Conditions: Annulation of N‐Sulfonyl‐2‐aminobiaryls with [60]Fullerene through Sequential C‐H Bond Activation, C‐C and C‐N Bond Formation

“…To our surprise, substrates bearing electronwithdrawing chloro groups, 1h and 1i, produced their products 2h and 2i in excellent isolated yields (40 and 51%; 66 and 68% based on converted C 60 ; entries 8 and 9). We isolated the monofunctionalized products 2j-l in lower chemical yields (19-22%) due to the formation of bis-and multi-addition products (entries [10][11][12]; this notion was ascribed to the presence Yield [%] [c]…”

Catalyst‐Dependent Divergent Synthesis of Pyrroles from 3‐Alkynyl Imine Derivatives: A Noncarbonylative and Carbonylative Approach

“…[11] Intramolecular nucleophilic attack of the imine on the activated alkyne and the subsequent rearrangement forms rhodium-containing pyrrole intermediate B.…”

“…The reactions proceeded smoothly when the R 2 substituent was changed from a simple alkyl group to a benzyl, PMB, or 2-phenylethyl group to afford the desired products in moderate to good yields (Table 3, entries [1][2][3][4][5]. The substituent on the alkyne functionality could also tolerate a substituted phenyl group or thienyl, which provided the desired products in yields ranging from moderate to good (Table 3, entries [6][7][8][9][10][11]. In this reaction, irrespective of whether an electron-donating group or electron-withdrawing group was introduced on the phenyl ring, the corresponding product was obtained in a relatively low yield.…”

“…The difficulties mainly lie in the regioselectivity [10] (Scheme 2, this work). On the other hand, cyclopropylimines [11] are very useful five-atom synthons in organic chemistry and their reactivities are quite similar to vinylcyclopropanes (VCPs). [12] In 2000 and 2002, Murai and co-workers [11a] and Wender et al [11b] independently reported the [5+1] and [5+2] cycloaddition of cyclopropylimines (Scheme 2 b).…”