Stimuli-responsive polymers that release small molecules under mechanical stress are appealing targets for applications ranging from drug delivery to sensing. Here, we describe a modular mechanophore design platform for molecular release via a mechanically triggered cascade reaction. Mechanochemical activation of a furan–maleimide Diels–Alder adduct reveals a latent furfuryl carbonate that subsequently decomposes under mild conditions to release a covalently bound cargo molecule. The computationally guided design of a reactive secondary furfuryl carbonate enables the decomposition and release to proceed quickly at room temperature after unmasking via mechanical force. This general strategy is demonstrated using ultrasound-induced mechanical activation to release a fluorogenic coumarin payload from a polymer incorporating a chain-centered mechanophore.

An intermolecular 1,2-carboamination of unactivated alkenes proceeding via a Pd(II)/Pd(IV) catalytic cycle has been developed. To realize this transformation, a cleavable bidentate directing group is used to control the regioselectivity of aminopalladation and stabilize the resulting organopalladium(II) intermediate, such that oxidative addition to a carbon electrophile outcompetes potential β-hydride elimination. Under the optimized reaction conditions, a broad range of nitrogen nucleophiles and carbon electrophiles are compatible coupling partners in this reaction, affording moderate to high yields. The products of this reaction can be easily converted to free γ-amino acids and γ-lactams, both of which are common structural motifs found in drug molecules and bioactive compounds. Reaction kinetics and DFT calculations shed light on the mechanism of the reaction and explain empirically observed reactivity trends.

We report the enhancement of photocatalytic performance by introduction of hydrogen-bonding interactions to a Re bipyridine catalyst and Ru photosensitizer system (ReDAC/RuDAC) by the addition of amide substituents, with carbon monoxide (CO) and carbonate/bicarbonate as products. This system demonstrates a more-than-3-fold increase in turnover number (TONCO = 100 ± 4) and quantum yield (ΦCO = 23.3 ± 0.8%) for CO formation compared to the control system using unsubstituted Ru photosensitizer (RuBPY) and ReDAC (TONCO = 28 ± 4 and ΦCO = 7 ± 1%) in acetonitrile (MeCN) with 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo­[d]­imidazole (BIH) as sacrificial reductant. In dimethylformamide (DMF), a solvent that disrupts hydrogen bonds, the ReDAC/RuDAC system showed a decrease in catalytic performance while the control system exhibited an increase, indicating the role of hydrogen bonding in enhancing the photocatalysis for CO2 reduction through supramolecular assembly. The similar properties of RuDAC and RuBPY demonstrated in lifetime measurements, spectroscopic analysis, and electrochemical and spectroelectrochemical studies revealed that the enhancement in photocatalysis is due not to differences in intrinsic properties of the catalyst or photosensitizer, but to hydrogen-bonding interactions between them.

A palladium(II)-catalyzed 1,2-dicarbofunctionalization reaction of unactivated alkenes has been developed, wherein a cleavable bidentate directing group is used to control the regioselectivity and stabilize the putative alkylpalladium(II) intermediate. Under the optimized reaction conditions, a broad range of nucleophiles and electrophiles were found to participate in this transformation, providing moderate to high yields. 3-Butenoic acid derivatives containing internal alkenes and α-substituents were reactive substrates, offering a powerful platform for preparing β,γ-substituted carbonyl compounds with multiple stereocenters.

Polymers that release small molecules in response to mechanical force are promising materials for a variety of applications ranging from sensing and catalysis to targeted drug delivery. Within the rapidly growing field of polymer mechanochemistry, stress-sensitive molecules known as mechanophores are particularly attractive for enabling the release of covalently bound payloads with excellent selectivity and control. Here, we review recent progress in the development of mechanophore-based molecular release platforms and provide an optimistic, yet critical perspective on the fundamental and technological advancements that are still required for this promising research area to achieve significant impact.

A palladium(II)-catalyzed alkene difunctionalization reaction has been developed, wherein Bpin is used to trap chelation-stabilized alkylpalladium(II) intermediates that are formed upon nucleopalladation. A range of carbon and nitrogen nucleophiles were found to be suitable coupling partners in this transformation, providing moderate to high yields. Both 3-butenoic and 4-pentenoic acid derivatives were reactive substrate classes, affording β,γ- and γ,δ-difunctionalized carboxylic acid derivatives. This work represents a new strategy to synthesize highly functionalized secondary boronates that complements existing methods.

Polymers that release functional small molecules in response to mechanical force are appealing targets for drug delivery, sensing, catalysis, and many other applications. Mechanically sensitive molecules called mechanophores are uniquely suited to enable molecular release with excellent selectivity and control, but mechanophore designs capable of releasing cargo with diverse chemical functionality are limited. Here, we describe a general and highly modular mechanophore platform based on masked 2-furylcarbinol derivatives that spontaneously decompose under mild conditions upon liberation via a mechanically triggered reaction, resulting in the release of a covalently installed molecular payload. We identify key structure–property relationships for the reactivity of 2-furylcarbinol derivatives that enable the mechanically triggered release of functionally diverse molecular cargo with release kinetics being tunable over several orders of magnitude. In particular, the incorporation of an electron-donating phenoxy group on the furan ring in combination with an α-methyl substituent dramatically lowers the activation barrier for fragmentation, providing a highly active substrate for molecular release. Moreover, we find that phenoxy substitution enhances the thermal stability of the mechanophore without adversely affecting its mechanochemical reactivity. The generality and efficacy of this molecular design platform are demonstrated using ultrasound-induced mechanical force to trigger the efficient release of a broad scope of cargo molecules, including those bearing alcohol, phenol, alkylamine, arylamine, carboxylic acid, and sulfonic acid functional groups.

During the past decade, many research groups have described catalytic methods for 1,2-carboboration, allowing access to structurally complex organoboronates from alkenes. Various transition metals, especially copper, palladium, and nickel, have been widely used in these reactions. This review summarizes advances in this field, with a special focus on the catalytic cycles involved in different metal-catalyzed carboboration reactions, as well as the regio-and stereochemical consequences of the underlying mechanisms. 1,2-Carboboration of other unsaturated systems, such as alkynes and allenes, is outside of the scope of this review. Scheme 1. General depiction of catalyst-controlled 1,2-carboboration. In this scheme and throughout the manuscript, nucleophilic reaction partners are drawn in blue, and electrophilic reaction partners are drawn in red. Scheme 4. Cu(I)-catalyzed borylative radical cyclization. Scheme 5. Cu(I)-catalyzed intramolecular carboboration involving an aldol cyclization. Scheme 6. Cu(I)-catalyzed intramolecular acylboration.Review Isr. J. Chem. 2020, 60, 219 -229 Scheme 7. Cu(I)-catalyzed divergent alkylboration of alkenes. Scheme 8. Cu(I)-catalyzed alkene carboboration with aldehydes as the electrophile. Scheme 9. Cu(I)-catalyzed three-component acylboration. Scheme 10. Cu(I)-catalyzed heteroarylboration of 1,3-dienes.