Enantioselective Construction of Cyclopenta[b]indole Scaffolds via the Catalytic Asymmetric [3 + 2] Cycloaddition of 2-Indolylmethanols with p-Hydroxystyrenes

Abstract

The catalytic asymmetric [3 + 2] cycloaddition of 2-indolylmethanols to p-hydroxystyrenes was established in the presence of a chiral phosphoramide, and this reaction provided chiral cyclopenta[b]indole scaffolds in generally high yields and with good enantioselectivities (up to 98% yield, 99:1 er). The control experiments demonstrated that the dual hydrogen-bonding activation mode of the chiral catalyst toward the two substrates played an important role in the reaction. In addition, the large-scale reaction indicated that this catalytic asymmetric [3 + 2] cycloaddition could be scaled up for the synthesis of chiral cyclopenta[b]indole derivatives.

N-Triflylphosphoramides: highly acidic catalysts for asymmetric transformations

“…Further developing ionic (3 + 2) cycloadditions, the group of Shi, envisaged one such reaction using 2-indolylmethanols 2.37 as suitable carbocationic precursors for a (3 + 2) cycloaddition with hydroxystyrenes 2.38 (Scheme 15a). 98 Several PA were tried unsuccessfully, affording either no reaction or low enantioselectivity. Regarding (R)-S-PA-7, (R)-[H 8 ]-PA-7 and (R)-PA-7, it is noticeable, yet not obvious, how subtle differences in the catalyst's backbone can lead to dramatic, dissimilar outputs (Scheme 15b).…”

Organocatalytic Strategies for the Synthesis of Cyclopenta‐Fused Arenes and Heteroarenes

“…Furthermore, control experiments revealed the crucial role of free N−H groups in enantioinduction through hydrogen bonding. The authors also have extended this concept for the enantioselective synthesis of cyclopenta[ b ]indoles by employing p ‐hydroxystyrenes and chiral phophoramides …”

“…The authors also have extendedt his concept for the enantioselective synthesis of cyclopenta[b]indoles by employing p-hydroxystyrenes and chiral phophoramides. [32] In 2012, Guo and co-workersr eporteda na symmetrico nepot multicatalytic cascade reactiono f3 -indolylmethanols 74 (Scheme 17). [33] In this approach, aw ide variety of cyclopenta [b]indoles 80 were accessed in high diastereo-and enantioselectivity.T he proposed reactionp athway involves an initial aalkylation of aldehydes 75 and3 -indolylmethanols 74,c atalyzed by aminothiourea 76,t og enerate 77.I nt he presence of an ucleophile (such as 79), aldehyde 77 undergoes chiral Brønsted acid (78)-catalyzed sequential inter-a nd intramolecular Friedel-Crafts alkylations that lead to the formation of complex pentannulated indoles 80.…”

Chemodivergent Tandem Cyclizations of 2-Indolylmethanols with Tryptophols: C–N versus C–C Bond Formation

“…Recently, indolylmethanols have emerged as versatile synthons in organic synthesis. , Especially, 2-indolylmethanol-involved reactions have been widely employed in the synthesis of indole derivatives or indole-fused cyclic frameworks. , However, the investigations on 2-indolymethannols are only limited to substitutions or cyclizations (Scheme ). To the best of our knowledge, there is no report on the chemodivergent reactions of 2-indolymethannols.…”