Remote C-H alkylation and C-C bond cleavage enabled by an in situ generated palladacycle.
The direct and selective functionalization of C-H bonds of arenes is one of the most challenging yet valuable aims in organic synthesis. Despite notable recent achievements, a pre-installed directing group proved to be essential in most of the methodologies reported so far. In this context, the use of a transient directing group that can be generated in situ has attracted attention and demonstrated the great potential of this strategy. Here we report the use of an in situ generated palladacycle to accomplish remote-selective C-H alkylation reactions of arenes. Following the C-H functionalization event, the alkylated aryl ring undergoes a formal migration to provide diversely substituted benzofuran and indole scaffolds. Computational studies revealed that a palladium(IV) intermediate is not involved in the alkylation step. The aryl migration was found to proceed through a sequential C-C bond cleavage, insertion and β-hydride-elimination process. The increasing steric bulk that builds up during the C-H functionalization step drives the unusual C-C bond cleavage in a non-strained system.
Davenport Laboratories, Department of Chemistry, University of Toronto, 80 St George Street, Toronto, Ontario M5S 3H6, Canada.
Juntao
J
Ye
Davenport Laboratories, Department of Chemistry, University of Toronto, 80 St George Street, Toronto, Ontario M5S 3H6, Canada.
Zhihao
Z
Shi
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany.
Theresa
T
Sperger
Davenport Laboratories, Department of Chemistry, University of Toronto, 80 St George Street, Toronto, Ontario M5S 3H6, Canada.
Yoshifumi
Y
Yasukawa
Davenport Laboratories, Department of Chemistry, University of Toronto, 80 St George Street, Toronto, Ontario M5S 3H6, Canada.
Cian
C
Kingston
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany.
Franziska
F
Schoenebeck
Davenport Laboratories, Department of Chemistry, University of Toronto, 80 St George Street, Toronto, Ontario M5S 3H6, Canada.
Mark
M
Lautens