octanol. It was engaged in the directed γ-C(sp
3 )–H arylation with iodobenzene to
afford the desired arylated product 29 in excellent yield. Compound 29 was then
treated with NIS and HBF 4 to provide the corresponding ortho-iodinated product in
mono-selective fashion, which was subsequently engaged in the Cu-catalyzed
cyclization to give THQ 30 in 81% yield over two steps. Finally, removal of the
PA group from the cyclized compound 30 under reductive conditions followed by
N-methylation furnished (+)-angustureine in good overall yield.
Despite significant improvements of palladium-catalyzed directed C(sp
3 )–H
arylation, including the use of less reactive but more cost-attractive aryl bromides
[56] or open-air, room-temperature conditions [57], only sporadic examples of
Scheme 6 Formal synthesis of (+)-obafluorin via Pd-catalyzed directed γ-C–H arylation of a
threonine derivative
Scheme 7 Synthesis of (+)-angustureine involving Pd-catalyzed directed γ-C–H arylation
Applications of Catalytic Organometallic C(sp
3
)–H Bond Functionalization
141