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A photochemically induced nickel-catalyzed radical cross-coupling of phthalimido trifluoroethanol with aryl bromides to furnish α-aryl-α-trifluoromethyl alcohols is reported. This reaction proceeds via a photoinduced charge transfer of an electron donor-acceptor complex between Hantzsch ester and phthalimido trifluoroethanol, followed by 1,2-hydrogen atom transfer, to generate the α-hydroxytrifluoroethyl radical for the cross-coupling of aryl bromides. No exogenous photocatalysts or stoichiometric metal reductants are required in this mild and operationally simple protocol. Broad substrate compatibility and excellent functional group tolerance are observed.

An iron-catalyzed coupling reaction of difluoroenol silyl ethers and cyclobutanone oxime esters is described. This protocol provides a convenient access to various previously unknown and potentially useful gem-difluoromethylenated ketonitriles inmoderate to good yields. The transformations of resulting products to other fluorinecontaining products is also documented.

The first C–H trifluoroethylamination of heteroarenes with N-trifluoroethyl hydroxylamine reagents under photoredox catalysis has been described.

The regioselective C–H heptafluoroisopropylation of heteroarenes with heptafluoroisopropyl silver provided convenient access to a wide range of CF(CF3)2-containing heteroarenes.

A metallaphotoredox-catalyzed strategy for the selective and divergent aminocarbonylation of alkynes with amines and 1 atm of CO is reported. This synergistic protocol not only enables the Markovnikov-selective hydroaminocarbonylation of alkynes to afford α,β-unsaturated amides, but also facilitates a sequential four-component hydroaminocarbonylation/radical alkylation in the presence of tertiary and secondary alkyl boronate esters, which allows for straightforward conversion of alkynes into corresponding amides. Preliminary mechanistic studies disclose that a photoinduced oxidative insertion of aniline and CO into nickel followed by a migratory insertion of (carbamoyl)nickel species could be involved.

A photochemically induced selective and divergent cyanation reaction of alkynes, enabled by phosphorus radicals, is described. With the use of simple triarylphosphine as a co-catalyst, three cyanation reactions, including di-hydrocyanation, anti-Markovnikov hydrocyanation, and domino hydrocyanation/reduction, can be divergently achieved, furnishing a wide array of alkyl dinitriles, alkenyl nitriles, and alkyl nitriles under mild conditions. Terminal and internal alkynes are applicable with high efficiency and excellent selectivity. Synthetic applications for biologically active agents and preliminary experimental and computational mechanistic studies are reported.

The heptafluoroisopropyl group (CF(CF3 )2 ) is prevalent in pharmaceuticals and agrichemicals. However, heptafluoroisopropoxylated (OCF(CF3 )2 ) compounds remain largely underexplored, presumably due to the lack of efficient access to these compounds. Herein, we disclose the practical and efficient heptafluoroisopropoxylation reactions through the invention of a series of redox-active N-OCF(CF3 )2 reagents. These reagents were readily prepared from the oxidative heptafluoroisopropylation of hydroxylamines with AgCF(CF3 )2 . The substitutions on the nitrogen atom significantly affected the properties and reactivities of N-OCF(CF3 )2 reagents. Accordingly, two types of N-OCF(CF3 )2 reagents including N-OCF(CF3 )2 phthalimide A and N-OCF(CF3 )2 benzotriazolium salt O' were used as OCF(CF3 )2 anion and radical precursors, respectively. This protocol enables the direct heptafluoroisopropoxylation of a range of substrates, delivering the corresponding products in moderate to excellent yields.

Pentafluorosulfanyl chloride (SF5 Cl) is the most prevalent reagent for the incorporation of SF5 group into organic compounds. However, the preparation of SF5 Cl often relies on hazardous reagents and specialized apparatus. Herein, we described a safe and practical synthesis of a bench-stable and easy-to-handle solution of SF5 Cl in n-hexane under gas-reagent-free conditions. The synthetic application of SF5 Cl was demonstrated through the unprecedented reaction with diazo compounds. The chemoselective hydro- and chloropentafluorosulfanylations of α-diazo carbonyl compounds were developed in the presence of K3 PO4 or copper catalyst, respectively. These reactions provide a direct and efficient access to various α-pentafluorosulfanyl carbonyl compounds of high value for potential applications.

We report herein the three-component radical addition reaction of SF

Reported herein is a direct and efficient route to 1-bromo-1-fluoroalkanes through the reaction of unactivated alkenes with dibromofluoromethane under photoredox catalysis. The key to the success of these addition reactions is the employment of a suitable photoredox catalyst. In particular, hydro- and bromo-bromofluoromethylated products were chemoselectively formed using THF and DMF/H2O as solvents, respectively. Furthermore, the synthetic application of the prepared 1-bromo-1-fluoroalkanes has been demonstrated by their transformation into a variety of fluorine-containing compounds.

A silver-mediated oxidative difluoromethylation of styrenes and vinyl trifluoroborates with TMSCF2 H is reported for the first time. This method enables direct and facile access to CF2 H-alkenes from abundant alkenes with excellent functional-group compatibility. Moreover, this Ag/TMSCF2 H protocol could further enable a series of radical difluoromethylation reactions of a wide array of substrates, offering a generic and complementary platform for the construction of diversified C-CF2 H bonds.

The increasing pharmaceutical importance of trifluoromethylarenes has stimulated the development of more efficient trifluoromethylation reactions. Tremendous efforts have focused on copper- and palladium-mediated/catalyzed trifluoromethylation of aryl halides. In contrast, no general method exists for the conversion of widely available inert electrophiles, such as phenol derivatives, into the corresponding trifluoromethylated arenes. Reported herein is a practical nickel-mediated trifluoromethylation of phenol derivatives with readily available trimethyl(trifluoromethyl)silane (TMSCF3 ). The strategy relies on PMe3 -promoted oxidative addition and transmetalation, and CCl3 CN-induced reductive elimination. The broad utility of this transformation has been demonstrated through the direct incorporation of trifluoromethyl into aromatic and heteroaromatic systems, including biorelevant compounds.

A nickel-catalyzed, enantioselective, three-component fluoroalkylarylation of unactivated alkenes with aryl halides and perfluoroalkyl iodides has been described. This cross-electrophile coupling protocol utilizes a chiral nickel/BiOx system as well as a pendant chelating group to facilitate the challenging three-component, asymmetric difunctionalization of unactivated alkenes, providing direct access to valuable chiral β-fluoroalkyl arylalkanes with high efficiency and excellent enantioselectivity. The mild conditions allow for a broad substrate scope as well as good functional group toleration.

A cascade oxidative trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles with AgSCF3 is described. This protocol allows for the synthesis of novel bis(trifluoromethylthiolated) or trifluoromethylthiolated pyrrolo[1,2-a]indol-3-ones in moderate to good yields. Mechanistic investigations indicated that radical processes were probably involved in these transformations.

Catalytic, intermolecular difunctionalization of alkenes represents an efficient and diverse protocol for the buildup of molecular complexity from abundant materials by forging two chemical bonds in a single operation. Despite important progress in this area, transition-metal-catalyzed three-component difunctionalization of unactivated alkenes remains underdeveloped, mainly because of the low reactivity, reduced polarization, and high tendency toward β-hydride elimination of these compounds. In this context, nickel-catalyzed, selective, intermolecular difunctionalization methods that generally proceed via two distinct reaction pathways, migratory insertion of nickel species into alkenes and radical addition to alkenes, have been developed. This short review highlights recent advances in this area.1 Introduction2 Nickel-Catalyzed Three-Component Difunctionalization of Unactivated­ Alkenes via Migratory Insertion Processes3 Nickel-Catalyzed Three-Component Difunctionalization of Unactivated­ Alkenes via Radical Processes4 Conclusions and Perspectives

A photoredox/nickel dual catalyzed reductive hydrobenzylation of alkynes and benzyl chlorides by employing alkyl amines as a stoichiometric reductant is described. This synergistic protocol proceeds

An ongoing challenge in trifluoromethylthiolation reactions is the use of less expensive and easily available trifluoromethylthio sources. Herein, we disclose an unprecedented usage of trifluoromethanesulfonic anhydride (Tf2 O) as a radical trifluoromethylthiolating reagent. Hydrotrifluoromethylthiolation of unactivated alkenes and alkynes with Tf2 O in the presence of PMePh2 and H2 O under visible-light photoredox catalysis gave the addition products. The trifluoromethylthio radical (. SCF3 ) was first formed from Tf2 O through a photoredox radical processes and deoxygenative reduction of PMePh2 , and H2 O serves as the H-atom donor for the hydrotrifluoromethylthiolation reaction. This reaction provides a new strategy for radical trifluoromethylthiolation.

For the surgical treatment of coronary artery disease, renal artery stenosis and other peripheral vascular diseases, there is significant demand for small diameter (inner diameter6 mm) vascular grafts. However, autologous grafts are not always available when the substitute vascular grafts are severely diseased. In our previous work, hybrid small-diameter vascular grafts were successfully fabricated by combining electrospun polycaprolactone (PCL) and decellularized rat aorta (DRA). However, histological assessments of these grafts revealed the development of intimal hyperplasia, indicating potential negative impacts on the long-term patency of these grafts. To address this challenge, PCL nanofibers blended with rapamycin (RM) were electrospun outside the decellularized vascular graft to fabricate a RM-loaded hybrid tissue-engineered vascular graft (RM-HTEV), endowing the graft with a drug delivery function to prevent intimal hyperplasia. RM-HTEV possessed superior mechanical properties compared to DRA and exhibited a sustained drug release profile. To evaluate the applicability of RM-HTEV in vivo, abdominal aorta transplantation was performed on rats. Doppler sonography showed that the grafts were functional for up to 8 weeks in vivo. Moreover, histological analysis of explanted grafts 12 weeks postimplantation demonstrated that RM-HTEV significantly decreased neo-intimal hyperplasia compared with HTEV, without impairing reendothelialization and M2 macrophage polarization. Overall, RM-HTEV represents a promising strategy for developing small-diameter vascular grafts with great clinical translational potential. STATEMENT OF SIGNIFICANCE: In this study, a new type of rapamycin-loaded hybrid tissue-engineered vascular graft (RM-HTEV) was fabricated using electrospinning technology. The unique hybrid bi-layer structure endowed the RM-HTEV with multi-functionality: the exterior rapamycin-loaded electrospun PCL nanofibrous layer enhanced the mechanical properties of the graft and possessed drug releasing property; the interior decellularized aorta layer with porous structure could facilitate cell proliferation and migration. In in vivo implantation experiment, RM-HTEV exhibited satisfying long-term patency rate and significantly inhibited intimal hyperplasia without impairing re-endothelialization and M2 macrophage polarization. This strategy is expected to be a promising strategy for developing bioactive small-diameter vascular grafts with great clinical translational potential.

Long-segment defects remain a major problem in clinical treatment of tubular tissue reconstruction. The design of tubular scaffold with desired structure and functional properties suitable for tubular tissue regeneration remains a great challenge in regenerative medicine. Here, we present a reliable method to rapidly fabricate tissue- engineered tubular scaffold with hierarchical structure via 4-axis printing system. The fabrication process can be adapted to various biomaterials including hydrogels, thermoplastic materials and thermosetting materials. Using polycaprolactone (PCL) as an example, we successfully fabricated the scaffolds with tunable tubular architecture, controllable mesh structure, radial elasticity, good flexibility, and luminal patency. As a preliminary demonstration of the applications of this technology, we prepared a hybrid tubular scaffold via the combination of the 4-axis printed elastic poly(glycerol sebacate) (PGS) bio-spring and electrospun gelatin nanofibers. The scaffolds seeded with chondrocytes formed tubular mature cartilage-like tissue both via in vitro culture and subcutaneous implantation in the nude mouse, which showed great potential for tracheal cartilage reconstruction.

The transformation of a large-volume industrial by-product and stable greenhouse gas fluoroform (HCF3 ) to useful products has recently received significant attention. Now, a simple and scalable preparation of AgCF3 by treatment of HCF3 with t-BuOK and AgOAc is disclosed. The reactivity of the HCF3 -derived AgCF3 has been demonstrated by hydrotrifluoromethylation of alkenes and C-H trifluoromethylation of (hetero)arenes. This work not only provides a new avenue for the utilization of HCF3 , but also presents a reliable and easy-to-execute synthesis of the relatively stable AgCF3 solution.

A copper-catalyzed borylfluoromethylation of alkenes with fluoromethyl iodide and diboron reagents was disclosed. This protocol afforded the previously unknown and synthetically useful borylfluorom...

The reaction of easily available Morita–Baylis–Hillman (MBH) alcohols with AgSCF3 in the presence of n-Bu4NI and KI affords primary allylic SCF3 products in high yields and excellent regioselectivities. This regioselective dehydroxytrifluoromethylthiolation protocol could also be extended to propargylic alcohols for the preparation of the primary propargylic SCF3 products.

Shape memory polymers are of great interest for biomedical applications. However, most stimuli used to trigger shape memory processes, including heat, light, electricity, magnetism, and pH are inconvenient and maybe harmful to the body. Here, we designed and fabricated a new shape memory porous scaffold using biocompatible and readily available water as the trigger. This scaffold was based on poly(fumaricacid-co-1,7-octadiene diepoxide-co-terephthalic acid) (PFOT) synthesized via epoxide ring-opening polymerization in one step. The PFOT scaffold promoted the adhesion, spreading, proliferation and function of cardiomyoblast H9C2 cells in a manner comparable to that for the poly(lactic-co-glycolic acid) scaffold. It exhibited an excellent water-responsive shape memory effect with a fixity and recovery ratio >97% and a shape-recovery process of several minutes, suitable for surgery. In addition, the PFOT scaffold presented good in vitro biodegradation. More importantly, PFOT contains extensive free hydroxyl ...

Three-dimensional (3D) printing offers great potential to customize sophisticated constructs for a myriad of applications. However, many thermosets require long-term curing under harsh conditions, which is not compatible with rapid 3D printing processing. 3D printing of these thermosets remains a challenge. Here, we report a new strategy for direct 3D printing of various thermosets via readily available extrusion-based technology using sacrificial sodium chloride particles as a removable thickener for printing and a reinforcer for curing, exemplified by crosslinked polyester, polyurethane and epoxy resins. Specifically, the 3D constructs exhibited hierarchical and porous architectures, which are highly desired for many applications, including regenerative medicine, sensors, actuators, catalyst supports, and energy absorbers. As a proof-of-concept demonstration, we 3D printed vapomechanical sensors and actuators featuring fast, large, robust, and gradient responsiveness, in addition to biodegradable scaffolds to promote vascularization and tissue ingrowth in vivo and elastic myocardial patches to efficiently treat myocardial infarction. We expect that this study will pave a new way to tailor sophisticated 3D structures of thermosets and will be very useful for diverse applications.

One of the pivotal factors that limits the clinical applications of tissue engineering is the inability to create complex three-dimensional (3D) tissues due to the lack of a long-range mass transport capability. Here we present a simple versatile strategy to fabricate perfusable and permeable hierarchical microchannel-networks (PHMs) via the combination of one-pot 3D printed sacrificial caramel templates and polymer coating with integrated phase separation. The patterned PHMs possess a biomimetic three level vascular structure including a custom-made scalable 3D framework, interconnected microchannels and permeable walls with controllable micropores. The fabrication process can be adapted to various polymers and integrated with diverse matrices including hydrogels, particle leached porous scaffolds, electrospun nanofibers, and bacterial cellulose. We demonstrated the power of PHMs to facilitate mass exchange in tissue engineering constructs by showing that the PHMs could maintain the metabolic functions of heart cells in vitro, facilitate in vivo angiogenesis and tissue integration, and efficiently treat myocardial infarction.