Three-Component Photochemical 1,2,5-Trifunctionalizations of Alkenes toward Densely Functionalized Lynchpins.

Radical remote 1,n-difunctionalization reactions (n > 2) of alkenes are powerful tools to efficiently introduce functional groups with selected distances into target molecules. Among these reactions, 1,5-difunctionalizations are an important subclass, leading to sought-after scaffolds, but typically suffer from tailored starting materials and strict limitations for the formed functional group in 2-position. Seeking to address these issues and to make radical 1,5-difunctionalizations of alkenes more applicable, we report a novel three-component 1,2,5-trifunctionalization reaction between imine-based bifunctional reagents and two distinct alkenes, driven by visible light energy transfer-catalysis. Key to achieving this selective one-step installation of three different functional groups via the choreographed formation of four bonds was the utilization of a 1,2-boron shift and the rigorous capitalization of radical polarities and stabilities. Thorough mechanistic studies were carried out, and the synthetic utility of the obtained products was demonstrated by various downstream modifications. Notably, in addition to the functionalization of individual functional groups, their interplay gave rise to a unique array of cyclic products.

Catalytic Formal [2π+2σ] Cycloaddition of Aldehydes with Bicyclobutanes: Expedient Access to Polysubstituted 2-Oxabicyclo[2.1.1]hexanes.

Synthesis of bicyclic scaffolds has attracted tremendous attention because they are playing an important role as saturated bioisosteres of benzenoids in modern drug discovery. Here, we report a BF3 -catalyzed [2π+2σ] cycloaddition of aldehydes with bicyclo[1.1.0]butanes (BCBs) to access polysubstituted 2-oxabicyclo[2.1.1]hexanes. A new kind of BCB containing an acyl pyrazole group was invented, which not only significantly facilitates the reactions, but can also serve as a handle for diverse downstream transformations. Furthermore, aryl and vinyl epoxides can also be utilized as substrates which undergo cycloaddition with BCBs after in situ rearrangement to aldehydes. We anticipate that our results will promote access to challenging sp3 -rich bicyclic frameworks and the exploration of BCB-based cycloaddition chemistry.

Highly Selective Radical Relay 1,4-Oxyimination of Two Electronically Differentiated Olefins.

Radical addition reactions of olefins have emerged as an attractive tool for the rapid assembly of complex structures, and have plentiful applications in organic synthesis, however, such reactions are often limited to polymerization or 1,2-difunctionalization. Herein, we disclose an unprecedented radical relay 1,4-oxyimination of two electronically differentiated olefins with a class of bifunctional oxime carbonate reagents via an energy transfer strategy. The protocol is highly chemo- and regioselective, and three different chemical bonds (C-O, C-C, and C-N bonds) were formed in a single operation in an orchestrated manner. Notably, this reaction provides rapid access to a large variety of structurally diverse 1,4-oxyimination products, and the obtained products could be easily converted into valuable biologically relevant δ-hydroxyl-α-amino acids. With a combination of experimental and theoretical methods, the mechanism for this 1,4-oxyimination reaction has been investigated. Theoretical calculations reveal that a radical chain mechanism might operate in the reaction.

Visible-Light Photocatalyzed peri-(3 + 2) Cycloadditions of Quinolines.

Cycloaddition reactions─epitomized by the Diels-Alder reaction─offer an arguably unmatched springboard for achieving chemical complexity, often with excellent selectivity, in a modular single step. We report the synthesis of aza-acenaphthenes in a single step by an unprecedented formal peri-(3 + 2) cycloaddition of simple quinolines with alkynes. A commercially available iridium complex exerts a dual role of photosensitizer and photoredox catalyst, fostering a cyclization/rearomatization cascade. The initial energy-transfer phase leads to the acenaphthene skeleton, while the ensuing redox shuttling step leads to aromatization. We applied this technology to 8-substituted quinolines and phenanthrolines, which smoothly reacted with both terminal and internal alkynes with excellent levels of regio- and diastereoselectivity. Density functional theory calculations revealed the intertwined EnT/SET nature of the process and offered guiding design principles for the synthesis of new aza-acenaphthenes.

Vinyl Thianthrenium Tetrafluoroborate: A Practical and Versatile Vinylating Reagent Made from Ethylene.

The use of vinyl electrophiles in synthesis has been hampered by the lack of access to a suitable reagent that is practical and of appropriate reactivity. In this work we introduce a vinyl thianthrenium salt as an effective vinylating reagent. The bench-stable, crystalline reagent can be readily prepared from ethylene gas at atmospheric pressure in one step and is broadly useful in the annulation chemistry of (hetero)cycles, N-vinylation of heterocyclic compounds, and palladium-catalyzed cross-coupling reactions. The structural features of the thianthrene core enable a distinct synthesis and reactivity profile, unprecedented for other vinyl sulfonium derivatives.

Merging Pd0 /PdII Redox and PdII /PdII Non-redox Catalytic Cycles for the Allylarylation of Electron-Deficient Alkenes.

An allylarylation of electron-deficient alkenes with aryl boronates and allylic carbonates has been developed. This method allows access to a wide variety of carbon skeletons from readily available starting materials. Mechanistic studies indicate that this reaction is enabled by a cooperative catalysis based on merging Pd0 /PdII redox and PdII /PdII non-redox catalytic cycles.

Metal-free photosensitized radical relay 1,4-carboimination across two distinct olefins.

Intermolecular carboamination of olefins offers a powerful platform for the rapid construction of structurally complex amines from abundant feedstocks. However, these reactions often require transition-metal catalysis, and are mainly limited to 1,2-carboamination. Herein, we report a novel radical relay 1,4-carboimination across two distinct olefins with alkyl carboxylic acid-derived bifunctional oxime esters via energy transfer catalysis. The reaction is highly chemo- and regioselective, and multiple C-C and C-N bonds were formed in a single orchestrated operation. This mild and metal-free method features a remarkably broad substrate scope with excellent tolerance of sensitive functional groups, therefore providing easy access to structurally diverse 1,4-carboiminated products. Moreover, the obtained imines could be easily converted into valuable biologically relevant free γ-amino acids.