Transition
metal-catalyzed selective C–H bond functionalization enabled by transient
ligands has become an extremely attractive topic due to its economical and
greener characteristics. However, catalytic pathways of this reaction process
on unactivated sp<sup>3</sup> carbons of reactants have not been well studied
yet. Herein, detailed mechanistic investigation on Pd-catalyzed C(sp<sup>3</sup>)–H
bond activation with amino acids as transient ligands has been systematically
conducted. The theoretical calculations showed
that
higher angle
distortion of C(sp2)-H
bond
over C(sp3)-H
bond
and stronger
nucleophilicity of benzylic anion over its aromatic counterpart, leading to
higher reactivity of corresponding C(sp<sup>3</sup>)–H bonds; the angle strain
of the directing rings of key intermediates determines the site-selectivity of
aliphatic ketone substrates; replacement of glycine with β-alanine as the
transient ligand can decrease the angle tension of the directing rings. Synthetic experiments have confirmed that
β-alanine is indeed a more efficient transient ligand for arylation of
β-secondary carbons of linear aliphatic ketones than its glycine counterpart.<br><br>
Synthesis of Saturated Heterocycles via Metal-Catalyzed Formal Cycloaddition Reactions That Generate a C–N or C–O Bond