Tunable Titanocene Lewis Acid Catalysts for Selective Friedel–Crafts Reaction of Indoles and N‐Sulfonyl­aldimines. Issue 3 (30th November 2015)

• Record Type: Journal Article
• Authors: Xiu, Wang; Zhenhua, Wang; Zhang, Guofang; Zhang, Weiqiang; Wu, Ya; Gao, Ziwei
• Is Part Of: European journal of organic chemistry. Issue 3(2016)
• Page Start: 502
• Page End: 507
• Publication Date: 2015-11-30
• Subjects: Chemoselectivity -- Titanium -- Lewis acids -- Cooperative catalysis -- Friedel–Crafts reaction; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201501122
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: A new strategy to control the selective Friedel–Crafts reaction of indoles and imines under mild conditions was developed. Phenol derivatives were established as efficient ligands to finely tune the activity of titanocene dichloride. Cp2 TiCl2 and phenol catalyzed the mono‐Friedel–Crafts reaction of indoles and N ‐sulfonyl aldimines with good yields (91 %), whereas o ‐aminophenol significantly enhanced the activity of the titanocene catalyst and promoted the synthesis of bisindole with excellent yields (98 %). The new organometallic Lewis acid catalysts are air‐tolerant, can be used with low catalyst loading (3 mmol‐%) and are compatible with –NO2, –F, –Cl, –Br, and –OMe (30 examples with yields from good to excellent). The titanocene catalysts were fully characterized by NMR and HRMS analysis. The results suggest that Cp2 TiCl(OC6 H5 ) (I ) and Cp2 TiCl(OC6 H4 NH3 + Cl – ) (II ) were catalytic species for the mono‐ and double‐Friedel–Crafts reactions, respectively. Distinguished from single functional acid catalystsI, catalystII showed a catalytic cooperative effect of two acid components, which led to a fine tuning of the reactivity as well as to the selectivity of the desired reaction pathways. Abstract : A Ti‐catalyzed, highly selective Friedel–Crafts reaction of indoles and imines has been developed. Cp2 TiCl2 and phenol, with a single Lewis acid site, catalyzed the mono‐Friedel–Crafts reaction of indoles and N ‐sulfonylaldimines, whereas o ‐aminophenol enhanced the acidity of titancene catalyst, enabling both Lewis and Brønsted acid sites to promote the synthesis of bisindole.