One
of the most common reactions of diazo compounds with alkenes
is cyclopropanation, which occurs through metal carbene or free carbene
intermediates. Alternative functionalization of alkenes with diazo
compounds is limited, and a methodology for the addition of the elements
of Z-CHR2 (with Z = H or heteroatom, and CHR2 originates from N2CR2) across a carbon–carbon
double bond has not been reported. Here we report a novel reaction
of diazo compounds utilizing a radical-mediated addition strategy
to achieve difunctionalization of diverse alkenes. Diazo compounds
are transformed to carbon radicals with a photocatalyst or an iron
catalyst through PCET processes. The carbon radical selectively adds
to diverse alkenes, delivering new carbon radical species, and then
forms products through hydroalkylation by thiol-assisted hydrogen
atom transfer (HAT), or forms azidoalkylation products through an
iron catalytic cycle. These two processes are highly complementary,
proceed under mild reaction conditions, and show high functional group
tolerance. Furthermore, both transformations are successfully performed
on a gram-scale, and diverse γ-amino esters, γ-amino alcohols,
and complex spirolactams are easily prepared with commercially available
reagents. Mechanistic studies reveal the plausible pathways that link
the two processes and explain the unique advantages of each.
Reactions with the unstable and highly reactive zwitterionic intermediates generated in processes catalysed by transition metals are providing new opportunities for molecular constructions. Insertion reactions involve the collapse of zwitterionic intermediates, but trapping them would allow structural elaborations that are not currently available. To synthesize complex molecules in this manner, reactive electrophiles can be used to trap the zwitterionic intermediates. Here, we describe the use of imines, activated by chiral organocatalysts, and a highly efficient integrated rhodium and chiral Brønsted acid co-catalysed process to trap zwitterionic intermediates that have been proposed previously to undergo a formal C-H insertion reaction, allowing us to obtain polyfunctionalized indole and oxindole derivatives in a single step with excellent diastereoselectivity and enantioselectivity.
Based
on the strategy of polarity reversal in the generation of
free radicals derived from diazo compounds, photocatalyzed multicomponent
reactions (MCRs) of nitrogen aromatic heterocycles, alkenes, and diazo
compounds form functionalized derivatives in good to high yields and
exacting regioselectivities. The carbon radicals generated from the
acceptor diazo compounds are electrophilic, and their selective additions
with alkenes provide nucleophilic radicals, which enable the further
rapid assembly with various heteroarenes. A delicate balance has been
achieved between the activation of heteroarenes through protonation
and the decomposition of diazo compounds by the same acid. This multicomponent
Minisci reaction shows high functional group tolerance, especially
in the incorporation of biologically active molecules. Detailed mechanistic
studies that include photophysical measurements elaborate this radical
cascade reaction. Furthermore, this transformation provides new opportunities
for versatile reactions of diazo compounds in radical cascade multicomponent
coupling reactions.
The first experimental examples of Diels-Alder (DA) reactions of diazo compounds as heterodienophiles with dienes have been studied with density functional theory (DFT) using the M06-2X functional. For comparison, the reactivities of diazo esters as dienophiles or 1,3-dipoles with 1,3-dienes in intermolecular model systems have been analyzed by the distortion/interaction model. The 1,3-dipolar cycloaddition is strongly favored for the intermolecular system. The intramolecular example is unique because the tether strongly favors the (4 + 2) cycloaddition.
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