Synthesis of Indolyl-Tethered Spiro[cyclobutane-1,1′-indenes] through Cascade Reactions of 1-(Pyridin-2-yl)-1H-indoles with Alkynyl Cyclobutanols

Abstract

Presented herein is an efficient and unprecedented synthesis of indolyl-tethered spiro­[cyclobutane-1,1′-indenes] through the cascade reaction of 1-(pyridin-2-yl)-1H-indoles with alkynyl cyclobutanols. Mechanistic experiments implicate a sequential process in which 1-(pyridin-2-yl)-1H-indole first undergoes an alkenylation with alkynyl cyclobutanol followed by an intramolecular Friedel–Crafts reaction to give the title products. The utility of this novel protocol was reflected by the ample substrate scope, high chemo- and regioselectivity, removable directing group, and scalable preparation. In addition, the product thus obtained can be further derivatized quite efficiently.

Cascade Alkenylation/Intramolecular Friedel–Crafts Alkylation: High Selectivity at the C7-Position of BINOL

“…Based on the above experimental results and related studies, , we propose that this tandem C–H bond activation pathway starts with the formation of the activated cyclometalated complex I , derived from substrate 1a and the cobalt catalyst (Scheme ). Then, propargyl cycloalkanol 2a coordinates with the Co complex I to form intermediate II , followed by the insertion of the triple bond into the C–Co bond.…”

“…The other pathway has been extensively studied, which is sequential C–H activation/ring-opening of the strained cyclobutyl moiety affording the product containing the carbonyl functional group . Recently, a new C–H activation/Friedel–Crafts alkylation mode from alkynyl cycloalkanols was reported by Fan’s group with the high-priced iridium metal as a catalyst . Enlightened by these advancements, we envisage that the methodology undergoes an intramolecular cyclization process to introduce a high steric aryl substituent at the remote position of the BINOL backbone using pyrazole as DGs, which is a very common nitrogen-containing induction group in the field of C–H activation .…”

“…13 Recently, a new C− H activation/Friedel−Crafts alkylation mode from alkynyl cycloalkanols was reported by Fan's group with the high-priced iridium metal as a catalyst. 14 Enlightened by these advancements, we envisage that the methodology undergoes an intramolecular cyclization process to introduce a high steric aryl substituent at the remote position of the BINOL backbone using pyrazole as DGs, which is a very common nitrogencontaining induction group in the field of C−H activation. 15 Herein, we develop a pyrazole-directed C7-H alkenylation/ spirocyclization protocol of BINOL derivatives with alkynyl cycloalkanols under cost-effective, stable cobalt(III) catalysis 16 (eq 4).…”

Ruthenium(II)-Catalyzed Sterically Hindered C–H Acyloxylation to Synthesize Biaryl Isoquinoline Derivatives via Peresters

“…As one of the most significant classes of organic molecules, featuring in a large number of natural products and medicinally relevant compounds, esters have undoubtedly attracted much attention. Direct esterification of C–H bonds has prompted chemists to investigate the novel and practical synthetic approaches .…”

Synthesis of indene-fused spiro-dibenz(ox)azepines via Rh(iii)-catalyzed cascade regioselective C–H activation/annulation

“…Therefore, we hypothesized that by inducing structural modifications on the dibenzo[ b , f ][1,4]oxazepines at the C11-position and leveraging the imine functional group we could mimic the C–H activation/spiroannulation cascade reaction with ynones, suitable and relatively less explored coupling partners (Scheme 1d), which might provide a robust route to the synthesis of dihydrodibenzo[ b , f ][1,4]oxazepane containing spirocycles. Although, alkynes and other unsaturated coupling partners are the frequent go-to partners in C–H annulation reactions, 3,4 ynones remain as common electrophilic coupling partners in non-metallic reactions 5 and have thus far remained underutilized in C–H activation reactions. 6 Ynones as a potential coupling partner could directly give access to tetra-substituted spirocyclic indenes on coupling with appropriate substrates.…”