Unveiling Extreme Photoreduction Potentials of Donor-Acceptor Cyanoarenes to Access Aryl Radicals from Aryl Chlorides.

Since the seminal work of Zhang in 2016, donor-acceptor cyanoarene-based fluorophores, such as 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), have been widely applied in photoredox catalysis and used as excellent metal-free alternatives to noble metal Ir- and Ru-based photocatalysts. However, all the reported photoredox reactions involving this chromophore family are based on harnessing the energy from a single visible light photon, with a limited range of redox potentials from -1.92 to +1.79 V vs SCE. Here, we document the unprecedented discovery that this family of fluorophores can undergo consecutive photoinduced electron transfer (ConPET) to achieve very high reduction potentials. One of the newly synthesized catalysts, 2,4,5-tri(9H-carbazol-9-yl)-6-(ethyl(phenyl)amino)isophthalonitrile (3CzEPAIPN), possesses a long-lived (12.95 ns) excited radical anion form, 3CzEPAIPN•-*, which can be used to activate reductively recalcitrant aryl chlorides (Ered ≈ -1.9 to -2.9 V vs SCE) under mild conditions. The resultant aryl radicals can be engaged in synthetically valuable aromatic C-B, C-P, and C-C bond formation to furnish arylboronates, arylphosphonium salts, arylphosphonates, and spirocyclic cyclohexadienes.

Olefin Metathesis in Continuous Flow Reactor Employing Polar Ruthenium Catalyst and Soluble Metal Scavenger for Instant Purification of Products of Pharmaceutical Interest.

In recent years, the development of continuous-flow reactors has attracted growing attention from the synthetic community. Moreover, findings in the precise control of the reaction parameters and improved mass/heat transfer have made the flow setup an attractive alternative to batch reactors, both in academia and industry, enabling safe and easy scaling-up of synthetic processes. Even though a majority of the pharmaceutical industry currently rely on batch reactors or semibatch reactors, many are integrating flow technology because of easier maintenance and lower risks. Herein, we demonstrate an operationally simple flow setup for homogeneous ring-closing metathesis, which is applicable to the synthesis of active pharmaceutical ingredients precursors or analogues with high efficiency, low residence time, and in a green solvent. Furthermore, through the addition of a soluble metal scavenger in the subsequent step within the flow system, the level of ruthenium contamination in the final product can be greatly reduced (to less than 5 ppm). To ensure that this method is applicable for industrial usage, an upscale process including a 24 h continuous-flow reaction for more than 60 g of a Sildenafil analogue was achieved in a continuous-flow fashion by adjusting the tubing size and flow rate accordingly.

Photo-mediated selective deconstructive geminal dihalogenation of trisubstituted alkenes.

Selective deconstructive functionalization of alkenes, other than the well-established olefin metathesis and ozonolysis, to produce densely functionalized molecular scaffolds is highly attractive but challenging. Here we report an efficient photo-mediated deconstructive germinal dihalogenation of carbon-carbon double bonds. A wide range of geminal diiodoalkanes and bromo(iodo)alkanes (>40 examples) are directly prepared from various trisubstituted alkenes, including both cyclic and acyclic olefins. This C=C cleavage is highly chemoselective and produces geminal dihalide ketones in good yields. Mechanistic investigations suggest a formation of alkyl hypoiodites from benzyl alcohols and N-iodoimides, which undergo light-induced homolytic cleavage to generate active oxygen radical species.

Metal-salen molecular cages as efficient and recyclable heterogeneous catalysts for cycloaddition of CO2 with epoxides under ambient conditions.

A salen based molecular cage, salen@cage, was synthesized and complexed with Co and Al to yield metal-salen molecular cages, Co(ii)@cage, Co(iii)@cage and Al(iii)@cage. These cages were demonstrated to be efficient heterogeneous catalysts for the cycloaddition of CO2 with styrene oxide, achieving full conversion at 25 °C and 1 atm CO2. Good to excellent yields of various cyclic carbonates were also achieved under mild conditions. Al(iii)@cage can be reused up to five times without any significant loss of its high catalytic activity. The capability to access a variety of heterogeneous organometallic catalysts with salen@cage offers new prospects for practical CO2 utilization and chemical manufacturing.

Utilization of Stop-flow Micro-tubing Reactors for the Development of Organic Transformations.

A new reaction screening technology for organic synthesis was recently demonstrated by combining elements from both continuous micro-flow and conventional batch reactors, coined stop-flow micro-tubing (SFMT) reactors. In SFMT, chemical reactions that require high pressure can be screened in parallel through a safer and convenient way. Cross-contamination, which is a common problem in reaction screening for continuous flow reactors, is avoided in SFMT. Moreover, the commercially available light-permeable micro-tubing can be incorporated into SFMT, serving as an excellent choice for light-mediated reactions due to a more effective uniform light exposure, compared to batch reactors. Overall, the SFMT reactor system is similar to continuous flow reactors and more superior than batch reactors for reactions that incorporate gas reagents and/or require light-illumination, which enables a simple but highly efficient reaction screening system. Furthermore, any successfully developed reaction in the SFMT reactor system can be conveniently translated to continuous-flow synthesis for large scale production.