Iridium-Catalyzed Branch-Selective Hydroalkylation of Simple Alkenes with Malonic Amides and Malonic Esters

We report the iridium-catalyzed branch-selective hydroalkylation
of simple alkenes such as aliphatic alkenes and aromatic alkenes with
malonic amides and malonic esters under neutral reaction conditions.
A variety of aliphatic alkenes and aromatic alkenes bearing bromine,
chlorine, ester, 2-thienylcarboxylate, silyl, and phthalimide groups
were all found to be suitable for this hydroalkylation. The combination
of this method with Krapcho dealkoxycarbonylation realized a one-pot
synthesis of β-substituted amide and ester from β-amide
ester and malonic ester. The hydroalkylated products derived from
malonic amides are suitable for further transformation. The finely
tuned reaction conditions realized the selective transformation of
hydroalkylated products to 1,3-diamines or monoamides with the same
reagent. Deuterium labeling experiments and measurement of the kinetic
isotope effect indicated that the catalytic cycle involves a reversible
step and cleavage of the C–H bond is not a rate-determining
step. Density functional theory calculations provided insight into
the reaction mechanism, where the carboiridation step is followed
by C–H reductive elimination.