Cu-catalyzed Asymmetric Dearomative [3 + 2] Cycloaddition Reaction of Benzazoles with Aminocyclopropanes

Abstract

The enantioselective dearomative [3 + 2] cycloaddition reaction of benzazoles with aminocyclopropanes has been successfully developed. In the presence of a copper complex, derived from Cu(OTf) 2 and bisoxazoline, a series of hydropyrrolo-benzazole derivatives containing quaternary stereogenic centers were obtained in high yields with excellent enantioselectivity. This method could also provide 2-amino cyclopropanes with high enantiomeric purity by an efficient kinetic resolution. In addition, products could be transformed to pyrrolobenzothiazines and 1,5-benzothiazepines.

Catalytic Asymmetric Dearomative 1,3-Dipolar Cycloaddition of 2-Nitrobenzothiophenes and Isatin-Derived Azomethine Ylides

“…Tremendous efforts have been devoted to exploring innovative methods in this research area. , In particular, the CADA reaction of heteroarenes is regarded as one of the significant transformations for the construction of chiral heterocyclic architectures, which play an important role as pharmaceuticals in medicinal chemistry and as lead compounds for drug discovery . However, compared with the great progress on the CADA reaction of electron-rich heteroarenes, ,, research with respect to electron-deficient heteroarenes lags behind, presumably due to the high-energy barriers that must be overcome in the dearomative process. Therefore, the development of creative and efficient method for the CADA of electron-deficient heteroarenes remains an important goal in asymmetric synthesis.…”

Catalytic Enantioselective Ring-Opening Reactions of Cyclopropanes

“…The same group published later a dearomative (3 + 2) annulation reaction of benzazoles with aminocyclopropanes (Scheme 7A). 47 Enantioenriched hydropyrrolo-benzazoles containing quaternary stereocenters were obtained via kinetic resolution using Cu(OTf) 2 as the copper source and the tBuBOX ligand. The use of succinimidyl cyclopropane 27 in excess (4 equiv) was crucial to reach good yields and excellent enantioselectivities.…”

Asymmetric Catalytic Reactions of Donor–Acceptor Cyclopropanes

“…Thus, this process underwent kinetic resolution even when highly reactive aminocyclopropanes were used (Scheme 9 b). [20] …”

“…Thus,t his process underwent kinetic resolution even when highly reactive aminocyclopropanes were used (Scheme 9b). [20] ForC = Cd ouble bonds as dipolarophiles,s trongly polarized congeners are often required to undergo [3+ +2] cycloadditions with cyclopropanes to yield five-membered carbocycles.T ang et al described enantioselective annulations of cyclopropyl diesters with cyclic silyl enol ethers catalyzed by the chiral L8/Cu(ClO 4 ) 2 catalyst. [21] Theu se of the TBDPS protecting group was crucial to suppress the ring-opening side reaction and yield the desired annulated products 18.T his [3+ +2] cycloaddition was indeed as tepwise nucleophilic ringopening and intramolecular cyclization sequence (Scheme 10 a).…”