Journal
ACS CATALYSIS
Volume 8, Issue 5, Pages 4516-4527Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acscatal.8b01116
Keywords
C-H functionalization; Pd catalysis; alkynes; palladacycles; regioselectivity; beta-effects
Categories
Funding
- National Science Foundation under the CCI Center for Selective C-H Functionalization [CHE-1700982]
- NSF MRI-R2 grant [CHE-0958205]
- NIH Shared Instrumentation Grant [S10-RR027172]
- NIH [SRR023679A, 1S10RR016634-01]
- NSF [CHE-9633007, CHE-0130862]
Ask authors/readers for more resources
Although C-H functionalization is now established as a powerful tool for chemical synthesis, achieving site selectivity can be challenging, especially in complex systems. Here, we report regiodivergence in a Pd(II)-mediated C(sp(2))-H alkynylation of substrates with beta-carbolinamide and picolinamide as N,N-bidentate chelating groups on the basis of the identity of the TIPS alkyne halide coupling partner: TIPS alkyne bromides give delta-C(sp(2))-H alkynylation products while TIPS alkyne iodides give gamma-C(sp(2))-H alkynylation products. Using an integrated experimental and computational approach, we examine the C-H alkynylation mechanism and determine the factors leading to the observed selectivity in great detail. We show that delta-palladation is kinetically favored over gamma-palladation, whereas the latter is thermodynamically favored. However, equilibration of the palladacycles makes them both accessible as reactive intermediates. TIPS alkyne bromides react selectively with the six-membered palladacycle (from delta-palladation) through a migratory insertion pathway. The observed delta-selectivity in this case is attributed to decreased ring strain in the migratory insertion transition state with the six-membered palladacycle. We demonstrate that the gamma-selectivity observed with TIPS alkyne iodides arises from a switch in mechanism, from migratory insertion to Pd(II)/Pd(IV) oxidative addition. Finally, an in-depth mechanistic study uncovered a beta-Pd effect, which is analogous to the well-established beta-Si effect, that promotes delta-C-H alkynylated product formation through an unusual vinyl beta-halo elimination.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available