Asymmetric catalysis is a major theme
of research in contemporary
synthetic organic chemistry. The discovery of general strategies for
highly enantioselective photochemical reactions, however, has been
a relatively recent development, and the variety of photoreactions
that can be conducted in a stereocontrolled manner is consequently
somewhat limited. Asymmetric photocatalysis is complicated by the
short lifetimes and high reactivities characteristic of photogenerated
reactive intermediates; the design of catalyst architectures that
can provide effective enantiodifferentiating environments for these
intermediates while minimizing the participation of uncontrolled racemic
background processes has proven to be a key challenge for progress
in this field. This review provides a summary of the chiral catalyst
structures that have been studied for solution-phase asymmetric photochemistry,
including chiral organic sensitizers, inorganic chromophores, and
soluble macromolecules. While some of these photocatalysts are derived
from privileged catalyst structures that are effective for both ground-state
and photochemical transformations, others are structural designs unique
to photocatalysis and offer insight into the logic required for highly
effective stereocontrolled photocatalysis.
Stereochemical control of electronically excited states is a long-standing challenge in photochemical synthesis, and few catalytic systems that produce high enantioselectivities in triplet-state photoreactions are known. We report herein an exceptionally effective chiral photocatalyst that recruits prochiral quinolones using a series of hydrogen-bonding and π–π interactions. The organization of these substrates within the chiral environment of the transition metal photosensitizer leads to efficient Dexter energy transfer and effective stereoinduction. The relative insensitivity of these organometallic chromophores towards ligand modification enables the optimization of this catalyst structure for high enantiomeric excess (ee) at catalyst loadings as much as 100-fold lower than the optimal conditions reported for analogous chiral organic photosensitizers.
Enantioselective
catalysis of excited-state photoreactions remains
a substantial challenge in synthetic chemistry, and intermolecular
photoreactions have proven especially difficult to conduct in a stereocontrolled
fashion. Herein, we report a highly enantioselective intermolecular
[2 + 2] cycloaddition of 3-alkoxyquinolones catalyzed by a chiral
hydrogen-bonding iridium photosensitizer. Enantioselectivities as
high as 99% ee were measured in reactions with a range of maleimides
and other electron-deficient alkene reaction partners. An array of
kinetic, spectroscopic, and computational studies supports a mechanism
in which the photocatalyst and quinolone form a hydrogen-bonded complex
to control selectivity, yet upon photoexcitation of this complex,
energy transfer sensitization of maleimide is preferred. The sensitized
maleimide then reacts with the hydrogen-bonded quinolone–photocatalyst
complex to afford a highly enantioenriched cycloadduct. This finding
contradicts a long-standing tenet of enantioselective photochemistry
that held that stereoselective photoreactions require strong preassociation
to the sensitized substrate in order to overcome the short lifetimes
of electronically excited organic molecules. This system therefore
suggests that a broader range of alternate design strategies for asymmetric
photocatalysis might be possible.
Cyclobutyl moieties in drug molecules are rare, and in general, they are minimally substituted and stereochemically simple. Methods to assemble structurally complex cyclobutane building blocks suitable for rapid diversification are thus highly desirable. We report herein a photosensitized [2 + 2] cycloaddition with vinyl boronate esters affording straightforward access to complex, densely functionalized cyclobutane scaffolds. Mechanistic studies suggest an activation mode involving energy transfer to the styrenyl alkene rather than the vinyl boronate ester. synthetic versatility of boronate ester chemistry suggests a flexible strategy to prepare novel compounds in an underexplored region of chemical space.
■ ASSOCIATED CONTENT* sı Supporting InformationThe Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.1c00938.Detailed experimental procedures, full spectroscopic data for all new compounds, and CV and SV data (PDF)
Functionalized tryptamines are targets of interest for development as small molecule therapeutics. The ring opening of aziridines with indoles is a powerful method for tryptamine synthesis if site selectivity can be controlled. 4-Nitrobenzyl carbamate (PNZ)-protected aziridines undergo regioselective ring opening to produce β-substituted tryptamines for a series of indoles. The PNZ-protected tryptamines can be further manipulated by PNZ removal under mild conditions.
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