Redox-triggered dearomative [5 + 1] annulation of indoles with O-alkyl ortho-oxybenzaldehydes for the synthesis of spirochromanes

Abstract

The dearomative [5 + 1] annulation of 2-methylindoles with new five-membered synthon was developed through cascade [1,5]-hydride transfer/dearomative cyclization in HFIP for the synthesis of spirochromanes bearing the 2-methylindolenine skeleton.

Merging dearomatization with redox-neutral C(sp3)–H functionalization via hydride transfer/cyclization: recent advances and perspectives

“…In this context, in 2022, our group realized the dearomative [5 + 1] annulation of O -alkyl ortho -oxybenzaldehydes 36 with 2-methylindoles 37 through HFIP-mediated, hydride transfer-involved dearomative cyclization for the synthesis of spirocyclic 2-methylindolenines 38 carrying a chromane skeleton (Scheme 8). 15 Notably, a dramatic reactivity difference was observed between O -alkyl ortho -oxybenzaldehydes and tertiary aminobenzaldehydes. When O -benzyl salicylaldehyde was used, the intermolecular nucleophilic addition overwhelmed the intramolecular hydride transfer and delivered the diarylated product 41 .…”

“…9 Recently, a conceptually new hydride transfer-involved dearomatization, which combines two hot research fields of dearomatization and direct C(sp 3 )-H functionalization in a single reaction, has drawn much attention from chemists. [10][11][12][13][14][15][16][17][18][19] This "two-birds-with-one-stone" strat- egy opens a powerful avenue to not only streamline the synthesis of previously challenging target molecules but also prepare unreported structurally novel skeletons. In the past few years, with an ever-growing understanding of this rising area, our group have dedicated and made contributions to the hydride transfer-involved dearomatization reactions.…”

Visible-light-induced cyclization of 2-alkenyl-1,1′-biphenyls

“…4 In the past decades, related 1,5-shifts of a hydride in C–C bond-forming cyclization reactions have also been reported by other groups, 5 and recent examples include various cyclization reactions using ethers, amines, and acetals as hydride donors. 6 In 2019, Wang and co-workers developed a B(C 6 F 5 ) 3 -catalyzed hydride-transfer-induced cyclization reaction of vinyl-substituted N , N -dialkyl arylamines without using a transition metal (Scheme 1b). 7 Subsequently, Paradies et al have showed that the borane-catalyzed reaction can be extended to induce a [1,7]-H shift, enabling the synthesis of 2,3-disubstituted dihydroquinoline-4-ones in high yields with excellent diastereoselectivity (Scheme 1c).…”

Controllable Synthesis of N-Heterocycles via Hydride Transfer Strategy-Enabled Formal [5 + 1] and [5 + 2] Cyclizations

“…Analysis reveals that 59% of U.S. FDA approved unique small-molecule drugs contain an Nheterocycle. 1 Tetrahydroquinolines and benzazepines are the two important representatives of N-heterocycles, which have been widely distributed in bioactive molecules (Figure 1). 2,3 Therefore, many methods were disclosed to construct two such skeletons.…”