Indoles with conjugated carbonyl compounds

In terms of Michael additions at the indole C-3-position, montmorillonite KIO has been shown to be effective in promoting the conjugate addition of indoles to a,p-unsaturated carbonyl compounds <99MC929>. In what is also a Michael process, microwave irradiation has been shown to be effective in promoting the trimolecular condensation of substituted indoles 111 with... 

An efficient method for the construction of bis(indolyl)methanes and bis(indolyl) glycol conjugates from carbonyl compounds with indoles in the presence of a catalytic amount of iron(III) fluoride under solvent-free conditions has been reported by Kamble et al. (2006) (Scheme 2.4). The desired products were obtained in high yields with a simple and environmentally benign procedure. The use of iron(III) fluoride is feasible because of its stability, easy handling, easy recovery, reusability, and good activity. 

The generation of an iminium ion of a, 3-unsaturated carbonyl compounds lowers the LUMO energy. As a result, the cx-CH acidity increases as well as the ability to participate in conjugate additions. The first organocatalyzed 1,4-addition to a,j3-unsaturated aldehydes was reported by the MacMillan group [78]. For theoretical explorations of the configurative outcome of Michael additions of pyrroles and indoles to crotonaldehyde see Reference [79]. This transformation has been widely used in Friedel-Crafts alkylations of a,(5-unsaturated carbonyl compounds (see Reference [lb] and reports cited therein). Comparable examples of this transformation with ( )-crotonaldehyde in the intermolecular series were found in aryl alkylation with trifluoroborate (58 and 60) [80], indole alkylation (62) [81], Friedel-Crafts alkylation of electron-rich benzenes (64) [82], and Friedel-Crafts alkylation with phosphonates (65) [83] (Scheme 4.21). 

Conjugate addition has also been carried out with l-(3-indolyl) enones. The reactivity of these compounds might be expected to be attenuated somewhat by the donor character of the indole ring, relative to the carbonyl group. Good results were obtained using InBrs-TMS-Cl, both at 10 mol % [261]. These conditions were also successful with A-protected (f-Boc, TIPS, PhS02) 3-indolyl enones. 

---