Reversible Thiyl Radical Addition-Fragmentation Chain Transfer Polymerization.

Developing reversible-deactivation radical polymerization (RDRP) methods that could directly control the thiyl radical propagation is highly desirable yet remains challenging in modern polymer chemistry. Here, we reported the first reversible thiyl radical addition-fragmentation chain transfer (SRAFT) polymerization strategy, which utilizes allyl sulfides as chain transfer agents for reversibly deactivating the propagating thiyl radicals, thus allowing us to directly control a challenging thiyl radical chain polymerization to afford polymers with well-defined architectures. A linear dependence of molecular weight on conversion, high chain-end fidelity, and efficient chain extension proved good controllability of the polymerization. In addition, density functional theory calculations provided insight into the reversible deactivation ability of allyl sulfides. The SRAFT strategy developed in this work represents a promising platform for discovering new controlled polymerizations based on thiyl radical chemistry.

Mechanism-Guided Design of Chain-Growth Click Polymerization Based on a Thiol-Michael Reaction.

The development of chain-growth click polymerization is challenging yet desirable in modern polymer chemistry. In this work, we reported a novel chain-growth click polymerization based on the thiol-Michael reaction. This polymerization could be performed efficiently under ambient conditions and spatiotemporally regulated by ultraviolet light, allowing the synthesis of sulfur-containing polymers in excellent yields and high molecular weights. Density functional theory calculations indicated that the thiolate addition to the Michael acceptor is the rate-determining step, and introducing the phenyl group could facilitate the chain-growth process. This polymerization is a new type of chain-growth click polymerization, which will provide a unique approach to creating functional polymers.

A Strategy for Controlling the Polymerizations of Thiyl Radical Propagation by RAFT Agents.

The ability to extend the polymerizations of thiyl radical propagation to be regulated by existing controlled methods would be highly desirable, yet remained very challenging to achieve because the thiyl radicals still cannot be reversibly controlled by these methods. In this article, we reported a novel strategy that could enable the radical ring-opening polymerization of macrocyclic allylic sulfides, wherein propagating specie is thiyl radical, to be controlled by reversible addition-fragmentation chain transfer (RAFT) agents. The key to the success of this strategy is the propagating thiyl radical can undergo desulfurization with isocyanide and generate a stabilized alkyl radical for reversible control. Systematic optimization of the reaction conditions allowed good control over the polymerization, leading to the formation of polymers with well-defined architectures, exemplified by the radical block copolymerization of macrocyclic allylic sulfides and vinyl monomers and the incorporation of sequence-defined segments into the polymer backbone. This work represents a significant step toward directly enabling the polymerizations of heteroatom-centered radical propagation to be regulated by existing reversible-deactivation radical polymerization techniques.

Intermolecular Radical Addition to Ketoacids Enabled by Boron Activation.

The intermolecular radical addition to the carbonyl group is difficult due to the facile fragmentation of the resulting alkoxyl radical. To date, the intermolecular radical addition to ketones, a valuable approach to construct quaternary carbon centers, remains a formidable synthetic challenge. Here, we report the first visible-light-induced intermolecular alkyl boronic acid addition to α-ketoacids enabled by the Lewis acid activation. The in situ boron complex formation is confirmed by various spectroscopic measurements and mechanistic probing experiments, which facilitates various alkyl boronic acid addition to the carbonyl group and prevents the cleavage of the newly formed C-C bond. Diversely substituted lactates can be synthesized from readily available alkyl boronic acids and ketoacids at room temperature merely under visible light irradiation, without any additional reagent. This boron activation approach can be extended to alkyl dihydropyridines as radical precursors with external boron reagents for primary, secondary, and tertiary alkyl radical additions. The pharmaceutically useful anticholinergic precursors are easily scaled up in multigrams under metal-free conditions in flow reactors.

Radical Ring-Closing/Ring-Opening Cascade Polymerization.

A novel strategy for the synthesis of main-chain polymers through radical ring-closing/ring-opening cascade polymerization is reported. Efficient radical cyclopolymerization was achieved through systematic optimization of the electronic properties of 1,6-diene structures. Fusing 1,6-diene with allylic sulfide or allylic sulfone motifs enabled a ring-closing/ring-opening cascade reaction that provides a strong driving force for the ring-opening polymerization of large macrocyclic monomers. The ability of 1,6-diene-fused allylic sulfone to undergo efficient SO2 extrusion generated a propagating alkyl radical capable of reversible deactivation. This strategy provides a general platform for the synthesis of polymers incorporating complex main-chain structures and degradable functionalities.

Radical Cascade-Triggered Controlled Ring-Opening Polymerization of Macrocyclic Monomers.

A strategy for the controlled radical ring-opening polymerization of macrocyclic monomers is reported. Key to this approach is an allyl alkylsulfone-based ring-opening trigger that can undergo a radical cascade reaction to extrude sulfur dioxide and generate an alkyl radical for controlled chain propagation. A systematic study correlating reaction conditions with polymer molecular weight and molecular weight distribution allowed excellent control over polymerization. The versatility of this radical cascade-triggered ring-opening polymerization approach was further demonstrated through the first radical block copolymerization of macrocyclic monomers, and the incorporation of degradable functionality into the polymer backbone.

Visible-Light-Induced Alkoxyl Radical Generation Enables Selective C(sp(3))-C(sp(3)) Bond Cleavage and Functionalizations.

The alkoxyl radical is an important reactive intermediate in mechanistic studies and organic synthesis; however, its current generation from alcohol oxidation heavily relies on transition metal activation under strong oxidative conditions. Here we report the first visible-light-induced alcohol oxidation to generate alkoxyl radicals by cyclic iodine(III) reagent catalysis under mild reaction conditions. The ß-fragmentation of alkoxyl radicals enables selective C(sp(3))-C(sp(3)) bond cleavage and alkynylation/alkenylation reactions with various strained cycloalkanols, and for the first time with linear alcohols.

Dual Hypervalent Iodine(III) Reagents and Photoredox Catalysis Enable Decarboxylative Ynonylation under Mild Conditions.

A combination of hypervalent iodine(III) reagents (HIR) and photoredox catalysis with visible light has enabled chemoselective decarboxylative ynonylation to construct ynones, ynamides, and ynoates. This ynonylation occurs effectively under mild reaction conditions at room temperature and on substrates with various sensitive and reactive functional groups. The reaction represents the first HIR/photoredox dual catalysis to form acyl radicals from α-ketoacids, followed by an unprecedented acyl radical addition to HIR-bound alkynes. Its efficient construction of an mGlu5 receptor inhibitor under neutral aqueous conditions suggests future visible-light-induced biological applications.

Hypervalent iodine reagents enable chemoselective deboronative/decarboxylative alkenylation by photoredox catalysis.

Chemoselective C(sp(3))-C(sp(2)) coupling reactions under mild reaction conditions are useful for synthesizing alkyl-substituted alkenes having sensitive functional groups. Reported here is a visible-light-induced chemoselective alkenylation through a deboronation/decarboxylation sequence under neutral aqueous reaction conditions at room temperature. This reaction represents the first hypervalent-iodine-enabled radical decarboxylative alkenylation reaction, and a novel benziodoxole-vinyl carboxylic acid reaction intermediate was isolated. This C(sp(3))-C(sp(2)) coupling reaction leads to aryl-and acyl-substituted alkenes containing various sensitive functional groups. The excellent chemoselectivity, stable reactants, and neutral aqueous reaction conditions of the reaction suggest future biomolecule applications.

Visible-light-induced chemoselective deboronative alkynylation under biomolecule-compatible conditions.

Here, we report a visible-light-induced deboronative alkynylation reaction, which is redox-neutral and works with primary, secondary and tertiary alkyl trifluoroborates or boronic acids to generate aryl, alkyl and silyl substituted alkynes. This reaction is highly chemoselective and performs well on substrates containing alkenes, alkynes, aldehydes, ketones, esters, nitriles, azides, aryl halides, alkyl halides, alcohols, and indoles, with no detectable occurrence of side reactions. The mechanism of this novel C(sp(3))-C(sp) bond coupling reaction was investigated by luminescence quenching, radical trapping, on-off light, and (13)C-isotopic-labeling experiments. This reaction can be performed in neutral aqueous conditions, and it is compatible with amino acids, nucleosides, oligosaccharides, nucleic acids, proteins, and cell lysates.

Hypervalent Iodine Reagents Enable C-H Alkynylation with Iminophenylacetic Acids via Alkoxyl Radicals.

Here we report δ-C-H alkynylation to synthesize various δ-alkynols from iminophenylacetic acids. The hypervalent iodine-coordinated benziodoxole-alkoxyl-iminophenylacetic acid complex was the key intermediate and was characterized by X-ray crystallography for the first time. δ-C-H alkynylation is compatible with sensitive functional groups, including azides, aldehydes, and free alcohols, for the synthesis of δ-alkynols with diversified substituents in excellent regioselectivity. This reaction extends to δ-hydroxylalkene and δ-hydroxylnitrile synthesis, and the δ-alkynol products are easily derivatized to other valuable bifunctional building blocks.

Synthesis of Functional Poly(propargyl imine)s by Multicomponent Polymerizations of Bromoarenes, Isonitriles, and Alkynes.

Here we reported a versatile and multicomponent polymerization (MCP) approach that enabled the synthesis of functional poly(propargyl imine)s with well-defined structures and high molecular weight (Mw up to 38 200) in excellent yields (up to 93%) from readily accessible monomers of dibromoarenes, isonitriles, and diynes. This MCP had the advantages of simple operation, wide substrate scope, and mild reaction conditions. The resulting polymers possessed good solubility and showed high thermal stability and refractive indices. The tetraphenylethene-containing polymer displayed a phenomenon of aggregation-induced emission and could respond to various acidic vapors.