Microwave-Assisted Diels-Alder Approach to 4-Substituted Indoles

Significance

Wipf and co-workers report a versatile synthesis of 4-substituted indoles 3 initiated by addition of an α-lithiated alkylaminofuran to carbonyl compounds followed by microwave-­accelerated intramolecular Diels-Alder (IMDA) reaction and aromatization. The starting stannane 1 is easily prepared by alkylation of Boc-protected 2-aminofuran. Transmetalation of stannane 1 with n-BuLi gives a lithium species which is trapped with an aldehyde to give the expected allylic alcohols 2. Heating furans 2 at reflux in toluene leads to gradual decomposition; however, the IMDA reaction proceeds smoothly with concomitant Boc deprotection at high temperature in o-DCB under microwave irradiation, presumably via the mechanism shown. This method exhibits moderate functional group tolerance, with aromatic groups clearly favored over alkyl groups. One example of the preparation of a 3,4-disubstituted indole is also presented.