Tandem free-radical addition/substitution chemistry and its application to the preparation of novel AT1 receptor antagonistsDedicated to Professor Athel Beckwith and in recognition of his many contributions to free radical chemistry; he was an exceptional scientist, a gentleman and a scholar. The world has lost a scientific treasure.Electronic supplementary information (ESI) available: 1H and 13C NMR spectra of compounds 3 (Y = Se), 4 (Y = S), 4 (Y = Se), 5 (Y = Se), 9, 10, 12 (Y = Se), 13 (Y =

Benzothiophene and benzoselenophene analogues of the thiophene-containing antihypertensives milfasartan and eprosartan were prepared and tested for AT 1 receptor antagonist properties. While the sulfur-containing systems were prepared following existing methodology, the selenium-containing analogues required the development of novel, tandem free-radical chemistry involving addition of aryl radicals to alkynes, followed by intramolecular homolytic substitution at the higher heteroatom. All four compounds prepared proved to be excellent AT 1 receptor antagonists, with p K B estimates of 7.2-9.5. Homolytic addition/substitution chemistry has been used to prepare benzoselenophene analogues of the antihypertensive compounds milfasartan and eprosartan. Benzothiophenes were also prepared.