Catalytic Asymmetric [3+2] Cycloadditions of C‐3 Unsubstituted 2‐Indolylmethanols: Regio‐, Diastereo‐ and Enantioselective Construction of the Cyclopenta[b]indole Framework

Abstract

Abstract:The first catalytic asymmetric [3+2] cycloaddition of 2-indolylmethanols with 3-vinylindoles has been established, which makes use of C-3 unsubstituted 2-indolylmethanol as a C 3 building block in the presence of a chiral phosphoric acid. By using this strategy, biologically important cyclopenta [b]indole frameworks were efficiently constructed with regiospecificity in high yields (up to 99%), excellent diastereo-and enantioselectivities (up to > 95:5 dr, 96:4 er). This reaction not only represents the first catalytic asymmetric [3+2] cycloaddition of C-3 unsubstituted 2-indolylmethanols, but also has confronted the great challenges in 2-indolylmethanol-involved enantioselective transformations.

New Perspectives in the Indole Ring Functionalization using 2‐Indolylmethanols

“…A complementary reaction leading to regioisomeric pyrroloindoles 71 can be achieved from C‐3 unsubstituted 2‐indolylmethanols 68 and 3‐alkenylindoles 69 in the presence of SPINOL‐derived chiral phosphoric acid 70a (Scheme ) . As previously observed in similar reactions, the intermediate carbocation generated upon dehydration of 68 undergoes a selective nucleophilic attack at C‐3 with subsequent ring closure of the resulting indoleninium ion intermediate.…”

Chiral Spirocyclic Phosphoric Acids and Their Growing Applications

“…The remarkable organocatalytic asymmetric [3+2] cycloaddition of 2‐indolylmethanols with 3‐vinylindoles catalyzed by chiral catalyst ( S )‐ SPA 4 has been established by Shi group (Scheme 34). [ 38 ] This protocol tolerates a broad substrate scope with high enantioselectivity.…”

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

“…Consequently,S hi and co-workersd emonstrated an asymmetric [3+ +2]-cycloaddition reaction of 2-indolylmethanols 68 with 3-vinylindoles 69 (Scheme16). [31] Densely functionalized cyclopenta [b]indoles 71 were constructed in excellent enantiopurity.…”

“…Whereas [3+2]‐cycloaddition reactions of 3‐indolylmethanols are well explored, the use of 2‐indolylmethanols is limited. Consequently, Shi and co‐workers demonstrated an asymmetric [3+2]‐cycloaddition reaction of 2‐indolylmethanols 68 with 3‐vinylindoles 69 (Scheme ) . Densely functionalized cyclopenta[ b ]indoles 71 were constructed in excellent enantiopurity.…”