Iridium‐Catalyzed Asymmetric Allylic Dearomatization by a Desymmetrization Strategy

Abstract

A desymmetrization strategy was developed involving iridium-catalyzed allylic dearomatization of indoles. The six-membered-ring spiroindolenines contain three contiguous stereogenic centers, including an all-carbon quaternary center, and were obtained in up to 99 % yield with 99 % ee and >95:5 d.r. When treated with a catalytic amount of tosylic acid, six-membered spiroindolenine undergoes an unprecedented six-to-seven-membered ring expansion, affording the corresponding hexahydroazepino[4,5-b]indole.

Highly Diastereo‐ and Enantioselective Synthesis of Cyclohepta[b]indoles by Chiral‐Phosphoric‐Acid‐Catalyzed (4+3) Cycloaddition

“…Although their prominence in natural and non‐natural bioactive molecules has stimulated considerable synthetic efforts in this area, the construction of cyclohepta[ b ]indoles in a stereodefined way remains challenging, and very few methods enable the asymmetric formation of such molecules . Multistep syntheses have been reported by the groups of Gaich and Zheng and You in which the cyclohepta[ b ]indole moiety was delivered by a diastereoselective cyclization of an enantiomerically enriched preformed precursor. In 2011, Enders and co‐workers reported the first enantioselective synthesis of the corresponding seven‐membered ring on the basis of two consecutive Friedel–Crafts reactions catalyzed by a chiral thioamide and Au I sequentially .…”

Stereoselective Construction of Spiro‐Indolenine Frameworks through a Prins/Friedel–Crafts Cyclization Cascade Reaction

“…A similar strategy has been reported for the preparation of hexahydro‐1 H ‐spiro[isoquinoline‐4,4′‐pyran] derivatives from benzylamine‐derived homoallylic alcohols . A strategy for the preferential attack of electrophiles at the 3‐position of the indole ring has also been reported …”

Metal‐Free Dearomatization: Direct Access to Spiroindol(en)ines in Batch and Continuous‐Flow

“…The synthesis of spiroindol(en)ines and related spirocarbocycles through dearomatization of indole and substituted phenols has captured the close attention of chemist due to their widespread presence in various natural products and biologically relevant molecules . Henceforth, greener and atom economical syntheses of these structures have become imperative for synthetic chemists (Scheme a–c) . Several simple Lewis or π‐acidic catalysts were employed in the last decades for the synthesis of spiroindolenines through dearomatization of indole at the C‐3 position, including nano‐metal catalysts .…”

“…[2,3] Henceforth,g reener and atom economicals yntheses of these structures have become imperative for synthetic chemists (Scheme 1a-c). [4][5][6][7][8] Several simple Lewis or p-acidic catalysts weree mployed in the last decades for the synthesis of spiroindolenines through dearomatization of indole at the C-3 position,i ncluding nano-metal catalysts. [9] In addition, an umber of alternative methodsf or the synthesis of spiroindolenines has also been developed in the last decade, viz.…”