One-Step Synthesis of Hydropyrrolo[3,2-b]indoles via Cascade Reactions of Oxindole-Derived Nitrones with Allenoates

Abstract

Hydropyrrolo[2,3-b]indole is a privileged indoline motif, while its analogue, hydropyrrolo[3,2-b]indole, has been much less explored. Herein, we developed a cascade reaction of oxindole-derived nitrones with allenoates, providing straightforward access to the tetracyclic hydropyrrolo[3,2-b]indole scaffolds. Formation of multiple C–C/C–X bonds and cleavage could be achieved within one synthetic step using a simple catalyst (Gimeracil) under mild conditions. The reaction pathway may involve the generation of spiro-hydroazepinone as the key intermediate.

Highlighting the Rich Chemistry of the Allenone Moiety

“…[161] More specific investigations involving the formation of five-membered rings from allenones include DFT calculations on the generation of indole rings, [162] and examples of tricyclic indolizines, [163] benzo[d][1,3]dioxoles [164] and hydropyrrolo[3,2b]indoles. [165]…”

“…Thus, Michael addition of trimethyl phosphite onto α‐allenones and further oxycyclization has provided oxaphospholenes in moderate yields [161] . More specific investigations involving the formation of five‐membered rings from allenones include DFT calculations on the generation of indole rings, [162] and examples of tricyclic indolizines, [163] benzo[ d ][1,3]dioxoles [164] and hydropyrrolo[3,2‐ b ]indoles [165] …”

Catalyst-Controlled Switchable (5 + 4)/(3 + 4) Cycloadditions for the Divergent Synthesis of Pyrazole-Fused Seven- and Nine-Membered Heterocycles

“…The (3 + 2) cycloadditions delivering various spiro[4.4] systems were developed by the Guo group, the Wang group, and our group . Based on our previous works and interest in synthesizing medicinally relevant scaffolds through organocatalytic strategies, we propose to control the chemoselectivity of the cycloaddition reaction of MBH carbonate derived from 1,2-diketone using tunable 4-aminopyridine Lewis base catalysts . When a small catalyst is used, it will participate in a (3 + n ) cycloaddition as an allylic ylide.…”

Iron(iii)/quinoxaline-derived N,N-ligand catalyzed oxygen transfer reaction of N-vinyl nitrones through selective 4π-electrocyclization and N–O bond cleavage

“…7 Recently, N -vinyl nitrones have gained much attention in organic synthesis owing to their rich chemical transformations of the double bond on the N-atom, such as [3 + 2], [3 + 3], [4 + 1], [4 + 2], or [5 + 2] cycloadditions and intramolecular cyclization. 8 For example, Anderson's group developed a 4π-electrocyclization of malonoate-derived N -alkenyl nitrones or 6π-electrocyclization of β-keto ester-derived N -alkenyl nitrones to afford azetide nitrones and unsaturated morpholines, respectively (Scheme 1A). 9 Nakamura's group pioneered a copper( i )-catalyzed 2,3-rearrangement of ( E )- O -propargylic oximes to provide N -allenyl nitrone intermediates and sequential 4π- or 6π-azaelectrocyclization to access various heterocycles (Scheme 1B).…”