Controlling the selectivity of synthetically useful reactions has been a longstanding objective of organic chemistry. We report a regiodivergent synthetic protocol allowing access to diverse fluorinated 1,5-dienes through Pd/NHC-catalyzed ring-opening allylation of gem-difluorocyclopropanes. Density functional theory (DFT) calculations on regioselectivity-determining transition states provided critical insight into the design of the NHC ligand for switching regioselectivity. Consistent with the DFT predictions, N-heterocyclic carbene (NHC) ligands with bulky ortho substituents favored branched allylation, with the IHept ligand providing > 20:1 branched/linear regioselectivity. NHC ligands with less hindered ortho substituents such as IMes favored the thermodynamically more stable linear products. We were able to carry out late-stage modification of various complex molecules using this protocol. Our ligand-controlled approach provides efficient access to regioisomeric fluorinated 1,5-dienes from the same starting materials and constitutes a valuable addition to the toolbox of diversity-oriented synthesis.
The
concurrent incorporation of a germyl fragment and another functional
group (beyond the hydrogen atom) across the CC double bond
is a highly appealing yet challenging task. Herein we demonstrate
the efficient germyl peroxidation of alkenes with germanium hydrides
and tert-butyl hydroperoxide via a copper-catalyzed
three-component radical relay strategy. This protocol exhibits excellent
functional group tolerance and exquisite chemo- and regioselectivity
under mild conditions and represents a rare example of constructing
synthetically challenging metal-embedded organic peroxides.
The incorporation of a germyl group and another functional
fragment
across the CC bond is a challenging task due to the prevailing
hydrogermylation reaction. Herein, an efficient copper-catalyzed three-component
reaction of alkenes, germanium hydrides, and trimethylsilyl azide
has been disclosed. This transformation allows the concomitant introduction
of germyl and azide groups across the double bonds in a highly regioselective
manner with tert-butyl hydroperoxides as the bystanding
oxidant. The resulting β-germyl azides could be easily converted
into β-germyl amine and 1,2,3-triazoles of significant value.
The light-promoted regioselective germylation of aryl propiolamides/alkynoates with germanium hydrides is reported. The germyl-containing spiro[4.5]trienones were obtained when N-arylpropiolamides were used via sequential CÀ Ge and CÀ C bond formation, while aryl alkynoates delivered the vinylgermanes with radical Smiles rearrangement and CO 2 release.
An
efficient and selective protocol for the synthesis of perfluoroalkyl-group-substituted
benzo[4,5]imidazo[1,2-a]pyridines has been developed
in which β-perfluoroalkyl peroxides act as novel fluorinated
C3-building blocks to implement regioselective [3 + 3] annulation
with 2-cyanomethyl benzimidazole under metal-free conditions. The
application of the synthesized perfluoroalkylated BIPs as potent anticancer
reagents versus the nonfluorinated ones demonstrated the biological
utility of this method.
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