Addition of Indoles to Oxyallyl Cations for Facile Access to α-Indole Carbonyl Compounds

Abstract

A direct coupling of unprotected indoles and α-halo ketones via in situ generated oxyallyl cation intermediates is described. The reactions efficiently afford α-indole carbonyl compounds with good to quantitative yields.

PTSA‐Catalyzed Reaction of Indoles with 2‐Oxoaldehydes: Synthesis of α,α‐Bis(indol‐3‐yl) Ketones

“…The only two described catalytic methodologies involve the use of non easily available catalysts such as boron sulfonic acid or Ag nanoparticles (Scheme ) . In addition, no examples with α‐oxoaldehydes apart from arylglyoxals have been reported . Therefore, the development of robust, yet practical, synthetic methods for preparing α,α‐bis(indol‐3‐yl) ketones remains an important goal in this field.…”

Brønsted Acid Catalyzed α′‐Functionalization of Silylenol Ethers with Indoles

“…However, examples on the intermolecular direct trapping of oxyallyl cations with nucleophiles remain scarce 9. In fact, there are only a handful of contemporary examples which illustrate the use of carbon nucleophiles, in particular indoles, in this chemistry 9f,g. This advancement is, however, significant, as such strategies have also empowered the concise syntheses of various biologically active indole‐containing alkaloids, enabled by the crucial carbon(sp 2 )–carbon(sp 3 ) bond formation at the α‐position of carbonyl compounds 10…”

“…Not only would such reaction conditions require protection of the indole ring, but complete discrimination of the two similarly acidic and sterically hindered hydrogen atoms at the α‐ versus α′‐positions towards selective deprotonation would be very difficult. Equally as important, our chemistry also successfully addressed the challenging issue concerning the control of regioselectivity in the direct nucleophilic addition to unsymmetrical oxyallyl cations 9f,g. We discovered that an introduction of a silyl ether group to the oxyallyl cation moiety enabled the capture of this putative cationic species by indole with complete control of regioselectivity, predictably at the less substituted carbon center.…”

A Brønsted Acid Catalyzed Cascade Reaction for the Conversion of Indoles to α‐(3‐Indolyl) Ketones by Using 2‐Benzyloxy Aldehydes

“…and Chi et al. independently developed the addition of indole to ketone through formation of an oxo‐allyl cation intermediate; however, it is mostly effective for symmetric ketones, and for unsymmetric ketones a regioisomeric mixture of products was isolated . You et al.…”