Dialkylbiaryl phosphines are a valuable class of ligand for Pd-catalyzed amination reactions and have been applied in a range of contexts. This perspective attempts to aid the reader in the selection of the best choice of reaction conditions and ligand of this class for the most commonly encountered and practically important substrate combinations.

Dialkylbiaryl phosphines in Pd-catalyzed amination: a user's guide

Visible-light photocatalysis is a rapidly developing and powerful strategy to initiate organic transformations, as it closely adheres to the tenants of green and sustainable chemistry. Generally, most visible-light-induced photochemical reactions occur through single-electron transfer (SET) pathways. Recently, visible-light-induced energy-transfer (EnT) reactions have received considerable attentions from the synthetic community as this strategy provides a distinct reaction pathway, and remarkable achievements have been made in this field. In this Review, we highlight the most recent advances in visible-light-induced EnT reactions.

Visible-Light-Induced Organic Photochemical Reactions through Energy-Transfer Pathways.

Recent Developments in Organoboron Chemistry: Old Dogs, New Tricks

We report an investigation of the Chan–Lam amination reaction. A combination of spectroscopy, computational modeling, and crystallography has identified the structures of key intermediates and allowed a complete mechanistic description to be presented, including off-cycle inhibitory processes, the source of amine and organoboron reactivity issues, and the origin of competing oxidation/protodeboronation side reactions. Identification of key mechanistic events has allowed the development of a simple solution to these issues: manipulating Cu(I) → Cu(II) oxidation and exploiting three synergistic roles of boric acid has allowed the development of a general catalytic Chan–Lam amination, overcoming long-standing and unsolved amine and organoboron limitations of this valuable transformation.

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Spectroscopic Studies of the Chan–Lam Amination: A Mechanism-Inspired Solution to Boronic Ester Reactivity

Triplet Energy Transfer Photocatalysis: Unlocking the Next Level

Strategies to achieve spatiotemporal regulation of pre-existing alkenes via external stimuli are essential given the ubiquity of feedstock olefins in chemistry and their downstream applications. Mirroring the 1-0 switch that underpins mammalian vision through selective geometric isomerisation in retinal, strategies to manipulate 2D space by both geometric and positional isomerisation of alkenes via chemical, thermal and light-driven processes are being intensively pursued. This minireview highlights the current state of the art in activating and achieving directionality in these fundamental chemical transformations.

Positional and Geometrical Isomerisation of Alkenes: The Pinnacle of Atom Economy.

Geometrical E → Z alkene isomerization is intimately entwined in the historical fabric of organic photochemistry and is enjoying a renaissance (Roth et al. Angew. Chem., Int. Ed. Engl.198928, 1193-1207). This is a consequence of the fundamental stereochemical importance of Z-alkenes, juxtaposed with frustrations in thermal reactivity that are rooted in microscopic reversibility. Accessing excited state reactivity paradigms allow this latter obstacle to be circumnavigated by exploiting subtle differences in the photophysical behavior of the substrate and product chromophores: this provides a molecular basis for directionality. While direct irradiation is operationally simple, photosensitization via selective energy transfer enables augmentation of the alkene repertoire to include substrates that are not directly excited by photons. Through sustained innovation, an impressive portfolio of tailored small molecule catalysts with a range of triplet energies are now widely available to facilitate contra-thermodynamic and thermo-neutral isomerization reactions to generate Z-alkene fragments. This review is intended to serve as a practical guide covering the geometric isomerization of alkenes enabled by energy transfer catalysis from 2000 to 2020, and as a logical sequel to the excellent treatment by Dugave and Demange (Chem. Rev. 2003103, 2475-2532). The mechanistic foundations underpinning isomerization selectivity are discussed together with induction models and rationales to explain the counterintuitive directionality of these processes in which very small energy differences distinguish substrate from product. Implications for subsequent stereospecific transformations, application in total synthesis, regioselective polyene isomerization, and spatiotemporal control of pre-existing alkene configuration in a broader sense are discussed.

Advances in the E → Z Isomerization of Alkenes Using Small Molecule Photocatalysts.

The enantioselective, catalytic vicinal difluorination of alkenes is reported by II /IIII catalysis using a novel, C2 -symmetric resorcinol derivative. Catalyst turnover via in situ generation of an ArIIII F2 species is enabled by Selectfluor oxidation and addition of an inexpensive HF-amine complex. The HF:amine ratio employed in this process provides a handle for regioselective orthogonality as a function of Bronsted acidity. Selectivity reversal from the 1,1-difluorination pathway (geminal) to the desired 1,2-difluorination (vicinal) is disclosed (>20:1 in both directions). Validation with electron deficient styrenes facilitates generation of chiral bioisosteres of the venerable CF3 unit that is pervasive in drug discovery (20 examples, up to 94:06 e.r.). An achiral variant of the reaction is also presented using p-TolI (up to >95 % yield).

Enantioselective, Catalytic Vicinal Difluorination of Alkenes

Designing strategies to access stereodefined olefinic organoboron species is an important synthetic challenge. Despite significant advances, there is a striking paucity of routes to Z-α-substituted styrenyl organoborons. Herein, this strategic imbalance is redressed by exploiting the polarity of the C(sp2 )-B bond to activate the neighboring π system, thus enabling a mild, traceless photocatalytic isomerization of readily accessible E-α-substituted styrenyl BPins to generate the corresponding Z-isomers with high fidelity. Preliminary validation of this contra-thermodynamic E→Z isomerization is demonstrated in a series of stereoretentive transformations to generate Z-configured trisubstituted alkenes, as well as in a concise synthesis of the anti-tumor agent Combretastatin A4.

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Contra-Thermodynamic, Photocatalytic E→Z Isomerization of Styrenyl Boron Species: Vectors to Facilitate Exploration of Two-Dimensional Chemical Space

Isomerization-based strategies to enable the stereodivergent construction of complex polyenes from geometrically defined alkene linchpins remain conspicuously underdeveloped. Mitigating the thermodynamic constraints inherent to isomerization is further frustrated by the considerations of atom efficiency in idealized low–molecular weight precursors. In this work, we report a general ambiphilic C3 scaffold that can be isomerized and bidirectionally extended. Predicated on highly efficient triplet energy transfer, the selective isomerization of β-borylacrylates is contingent on the participation of the boron p orbital in the substrate chromophore. Rotation of the C(sp2)–B bond by 90° in the product renders re-excitation inefficient and endows directionality. This subtle stereoelectronic gating mechanism enables the stereocontrolled syntheses of well-defined retinoic acid derivatives.

John J. Molloy

Papers

Positional and Geometrical Isomerisation of Alkenes: The Pinnacle of Atom Economy.

Advances in the E → Z Isomerization of Alkenes Using Small Molecule Photocatalysts.

Enantioselective, Catalytic Vicinal Difluorination of Alkenes

Contra-Thermodynamic, Photocatalytic E→Z Isomerization of Styrenyl Boron Species: Vectors to Facilitate Exploration of Two-Dimensional Chemical Space

Boron-enabled geometric isomerization of alkenes via selective energy-transfer catalysis.