The palladium-catalysed cross-coupling reaction between alkenes and aryl halides (Mizoroki-Heck reaction) is a powerful methodology to construct new carbon-carbon bonds 1 . However, the success of this reaction is in part hampered by an extremely marked regioselectivity on the double bond, which dictates that electron-poor alkenes react exclusively on the beta carbon 2 . Here, we show that ligand-free, few-atom palladium clusters in solution catalyse the α-selective intramolecular Mizoroki-Heck coupling of iodoaryl cinnamates, and mechanistic studies support the formation of a sterically-encumbered cinnamate-palladium cluster intermediate. Following this rationale, the α-selective intermolecular coupling of aryl iodides with styrenes is also achieved with palladium clusters encapsulated within fine-tuned and stericallyrestricted zeolite cavities, to produce 1,1-bisarylethylenes which are further engaged with aryl halides by a metal-free photoredox catalysed coupling.These ligand-free methodologies significantly expand the chemical space of the Mizoroki-Heck coupling. INTRODUCTION.The regioselectivity of the intra-and intermolecular Mizoroki-Heck coupling 3 is basically dictated by the chemical nature of the alkene coupling partner. Electron-poor alkenes, perhaps the most used starting alkenes for the reaction (i.e. acrylates and styrenes), give E-1,2-alkenes (β coupling) as major reaction products, since the neutrally charged Pd intermediate inserts the alkene in such a way that the electron withdrawing group (EWG) points away from the coupling position. This stereochemical outcome, shown in Figures 1a and 1b, is switched in the cationic mechanism, where alkenes with electron donor groups (EDG), i.e. vinyl ethers, give the 1,1-alkene product (α coupling) 4 . Coherently, neutral alkenes, i.e. alkyl alkenes, give mixtures of β and α products, and it is difficult to find in the open literature any example which clearly contradicts the regioselective rules shown in Figure 3 1b. Reported alternatives consist in the use of sterically encumbered stoichiometric Pd complexes 5 or aryl pseudohalides, such as aryl sulfonates 6 , triflates 7 , carboxylates 8 and diazocompounds 9 , which also trigger a cationic pathway to give the α product regardless of the alkene partner used. While these strategies are remarkable, the complex Pd catalyst and the aryl pseudo-halide are much more laborious to prepare and expensive than typical palladium catalysts and aryl halides for conventional Mizoroki-Heck reactions. An additional issue of the intermolecular coupling is the lack of reactivity of polysubstituted alkenes, as shown in Figure 1c, which is severely restricted by the prohibitive steric hindrance generated during alkene insertion into nearly planar alkene-Pd intermediates 10 . Together, these limitations explain why more than the half of the theoretical possible couplings are, in principle, not feasible yet in reasonable yields, as illustrated in Figure 1d, and why the Mizoroki-Heck reaction is still underrepresented in indu...

Organic synthesis mediated by biphotonic processes has gained great momentum in the last five years. Herein, an overview of the existing examples is reported.

The regioselectivity in non-polar [3+2] cycloaddition (32CA) reactions has been studied within the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311G(d,p) level. To this end, the 32CA reactions of nine simplest three-atom-components (TACs) with 2-methylpropene were selected. The electronic structure of the reagents has been characterized through the Electron Localisation Function (ELF) and the Conceptual DFT. The energy profiles of the two regioisomeric reaction paths and ELF topology of the transition state structures are studied to understand the origin of the regioselectivity in these 32CA reactions. This MEDT study permits to conclude that the least electronegative X1 end atom of these TACs controls the asynchronicity in the C−X (X=C, N, O) single bond formation, and consequently, the regioselectivity. This behaviour is a consequence of the fact that the creation of the non-bonding electron density required for the formation of the new single bonds has a lower energy demand at the least electronegative X1 atom than at the Z3 one.

In this work, the feasibility of triplet fusion upconversion (TFU, also named triplet–triplet annihilation upconversion) technology for the functionalization (arylation) of furans and thiophenes has been successfully proven. Activation of aryl halides by TFU leads to generation of aryl radical intermediates; trapping of the latter by the corresponding heteroarenes, which act as nucleophiles, affords the final coupling products. Advantages of this photoredox catalytic method include the use of very mild conditions (visible light, standard conditions), employment of commercially available reactants and low-loading metal-free photocatalysts, absence of any sacrificial agent (additive) in the medium and short irradiation times. The involvement of the high energetic delayed fluorescence in the reaction mechanism has been evidenced by quenching studies, whereas the two-photon nature of this photoredox arylation of furans and thiophenes has been manifested by the dependence on the energy source power. Finally, the scaling-up conditions have been gratifyingly afforded by a continuous-flow device. Graphical abstract

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