RuPhosPdG3/RuPhos (c) 100 71 With optimal conditions in hands, the scope of Buchwald-Hartwig coupling on ex situ generated 3-arylazetidines was evaluated in the presence of diversely substituted aryl and heteroaryl bromides. 3-Phenylazetidines performed equally well with electron-rich and electron-poor aryl bromides, providing 1,3-bis-arylated azetidines 9a-g in excellent yields (82 to 99%). Worthy of note, a better yield was obtained through Bachwald-Hartwig coupling on 2-bromopyridines (9g, 99%) than under SNAr conditions . The introduction of a donor group (OCF3) at the para-position similarly led to compounds 9h-l in moderate to good yields (up to 86%). The reaction also proved highly functional group tolerant, as witnessed in the case of 9k containing an aldehyde (59%), and selective for bromides over chlorides (9i, 77%). Heterocyclic Grignard reagents such as 2-thiophenymagnesium and 3dibenzothiophenylmagnesium bromides were also engaged in bis-arylations (9m-o, 46 to 62%). The addition of an electronpoor Grignard reagent provided 9q in 79% yield. Analogs of drug compounds were finally synthesized following this rational design, to demonstrate the applicability of such method. Azetidine-analogs (9q-9t) of Adapalene and Tazarotene were obtained in a minimum of steps in very good yields through Buchwald-Hartwig couplings, in which the azetidine-moiety was employed to serve as isostere of either aryl-or alkynyl-groups.