Chao Zhou

Chiral heterocyclic lactams have been kinetically resolved in a photochemical process that involves selective hydrogen abstraction by a chiral benzophenone catalyst. Recognition of one enantiomer is achieved by a two-point hydrogen bonding interaction that directs the reactive carbonyl group of the photocatalyst to the C-H bond at the stereogenic center within the lactam. The generated radical is converted to an oxidized product in a cobaloxime-catalyzed dehydrogenation reaction. The unreactive enantiomer is retained and isolated in enantiomerically enriched form (21 examples, 31-56% yield, 90-99% ee).

Cross-coupling acylation by direct aldehyde activation is ideal to construct a useful carbonyl motif. However, the strong C-H bond energy, short radical lifetime, and mismatched radical polarity render this reaction a huge challenge. Herein, the semiconductor quantum dots (QDs) interface is demonstrated to overcome the obstacles lying on the way to acylating alkene or alkylarene, directly activating the formyl C-H bond into an acyl radical. Further stabilization of the obtained radical species by the QD interface ensured their effective cross-coupling with the generated intermediate from the coupling partner. The interface of QDs was exemplified to execute photochemical transformation, showcasing a highly efficient and selective cross-coupling acylation reaction under extremely mild conditions.

Represented herein is a simple thiol identified as an effective precursor to photochemically form a carbocation. Thanks to the thiyl radical rapid transformation to disulfide, which serves not only to stabilize the generated thiyl radical but also to allow the second electron transfer to form a carbocation. The resulting carbocations, including primary benzylic, secondary, and tertiary carbocations, can smoothly couple with nitrogen, oxygen, and carbon nucleophilic coupling partners as well as complex drug molecules, accompanied by elemental sulfur formation in air.

Aromatic compounds are one of the most abundant feedstocks in chemical industry, which typically focuses on their functionalization or full reduction. Partial reduction through dearomative sequences has been considerably less explored but would uncover the true potential of aromatic compounds in providing rapid access to complex and higher-value three-dimensional scaffolds. Several dearomative strategies have been established; however, most of these methods either necessitate metal-mediated multistep manipulations or are highly limited in their scope. Herein, an alternative photocatalytic radical cascade approach is disclosed, which exploits dearomative difunctionalization through selective dearomative spirocyclization/imination of nonactivated arenes. Various bifunctional oxime esters and carbonates are utilized in single-step installation of a range of functional groups concomitant with formation of a spiro-center and introduction of an iminyl functionality to furnish dearomatized spiro-imine scaffolds through tandem N–O bond cleavage, hydrogen-atom transfer, radical addition, 5-exo-trig cyclization, and radical cross-coupling sequences. The disclosed methodology allows formation of three or four new chemical bonds, including C−O, C−C, C−N bonds, in a single synthetic step, affording highly decorated three-dimensional structures from readily available starting materials.

Diels-Alder cycloaddition of anthracene with olefin is achieved in a homogeneous solution via energy transfer under visible light. A series of substrates including electroneutral styrene derivatives can be successfully converted into the corresponding cycloadducts in a head-to-head orientation with high to excellent yields. The high ortho-regioselectivity, mild condition, and broad substrate scope enable promising advances in organic transformation.

Photo-mediated radical dearomatization involving 5-exo-trig cyclizations has proven to be an important route to accessing spirocyclic compounds, whereas 6-exo-trig spirocyclization has been much less explored. In this work, a dearomative annulation cascade is realized through photoredox-mediated C–O bond activation of aromatic carboxylic acids to produce two kinds of spirocyclic frameworks. Mechanistically, the acyl radical is formed through oxidation of triphenylphosphine and subsequent C–O bond cleavage, followed by a 6-exo-trig cyclization/SET/protonation sequence to generate the spiro-chromanone products in an intramolecular manner. Furthermore, the protocol was extended to more challenging intermolecular tandem sequences consisting of C–O bond cleavage, radical addition to an alkene substrate, and 5-exo-trig cyclization to yield complex spirocyclic lactams.

An aerobic metal-free, visible-light-induced regioselective thiolation of phenols with thiophenols is reported. The cross-coupling protocol exhibits great functional group tolerance and high regioselectivity. Mechanistic studies reveal that the disulfide radical cation plays a crucial role in the visible-light catalysis of aerobic thiolation. Simply controlling the equivalent ratio of substrates enables the selective formation of sulfide or sulfoxide products with high activity in a one-pot reaction.

Transition-metal catalyzed C-N bond-forming reactions have emerged as fundamental and powerful tools to construct arylamines, a common structure found in drug agents, natural products and fine chemicals. Reported herein is an alternative access to heteroarylamine via radical-radical cross-coupling pathway, powered by visible light catalysis without any aid of external oxidant and reductant. Only by visible light irradiation of a photocatalyst such as a metal-free photocatalyst, a cascade single electron transfer event of amines and heteroarylnitriles, manifested by steady-state and transient spectroscopic studies, results in amine radical cation and aryl radical anion in situ for the C-N bond formation. The metal-free and redox economic nature, high efficiency and site-selectivity of C-N cross-coupling of a range of available amines, hydroxylamines and hydrazines with heteroarylnitriles make this protocol promising in both academic and industrial settings.

Combining "N-chlorosuccinimide (NCS)" as the safe chlorine source with "Acr+-Mes" as the photocatalyst, we successfully achieved benzylic C-H bond chlorination under visible-light irradiation. Furthermore, benzylic chlorides could be converted to benzylic ethers smoothly in a one-pot manner by adding sodium methoxide. This mild and scalable chlorination method worked effectively for diverse toluene derivatives, especially for electron-deficient substrates. Careful mechanistic studies supported that NCS provided hydrogen abstractor "N-centered succinimidyl radical", which was responsible for the cleavage of benzylic C-H bond, relying on the reducing ability of Acr+-Mes.

Here is the first visible light catalytic intermolecular cross [2 + 2] cycloaddition of enynes with alkenes to alkynyl cyclobutanes established with good functional group tolerance and high reaction efficiency and selectivity. Detailed studies reveal that enynes, including nonaromatic ones, can be sensitized by fac-Ir(ppy)₃ via an energy transfer pathway. Addition of the Lewis acid PPh₃AuNTf₂ enables the cross photo[2 + 2] cycloaddition reaction to take place under both direct visible light irradiation or sensitization by Ru(bpy)₃(PF₆)₂.