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Umpolung is an old and important concept in organic chemistry, which significantly expands the chemical space and provides unique structures. While, previous research focused on carbonyls or imine derivatives, the umpolung reactivity of polarized C–C σ-bonds still needs to explore. Herein, we report an umpolung reaction of bicyclo[1.1.0]butanes (BCBs) with electron-deficient alkenes to construct the C(sp3)-C(sp3) bond at the electrophilic position of C–C σ-bonds in BCBs without any transition-metal catalysis. Specifically, this transformation relies on the strain-release driven bridging σ-bonds in bicyclo[1.1.0]butanes (BCBs), which are emerged as ene components, providing an efficient and straightforward synthesis route of various functionalized cyclobutenes and conjugated dienes, respectively. The synthetic utilities of this protocol are performed by several transformations. Preliminary mechanistic studies including density functional theory (DFT) calculation support the concerted Alder-ene type process of C–C σ-bond cleavage with hydrogen transfer. This work extends the umpolung reaction to C–C σ-bonds and provides high-value structural motifs. Umpolung reactions typically focus on carbonyls or imine derivatives. Here, the authors report the umpolung reaction of C–C σ-bonds in bicyclo[1.1.0]butanes (BCBs) with electrophilic alkenes, yielding various cyclobutenes or conjugated dienes. [ABSTRACT FROM AUTHOR]

Hydrogen atom transfer (HAT) process is a powerful and effective strategy for activating C-H bonds followed by further functionalization. Intramolecular 1,n (n = 5 or 6)-HATs are common and frequently encountered in organic synthesis. However, intramolecular 1,n (n = 2 or 3)-HAT is very challenging due to slow kinetics. Compared to proton-shuttle process, which is well established for organic synthesis, hydrogen radical-shuttle (HRS) is unexplored. In this work, a HRS-enabled decarboxylative annulation of carbonyl compounds via photoredox catalysis for the synthesis of indanones is developed. This protocol features broad substrate scope, excellent functional group tolerance, internal hydrogen radical transfer, atom- and step-economy. Critical to the success of this process is the introduction of water, acting as both HRS and hydrogen source, which was demonstrated by mechanistic experiments and density functional theory (DFT) calculations. Importantly, this mechanistically distinctive HAT provides a complement to that of typical proton-shuttle-promoted, representing a breakthrough in hydrogen radical transfer, especially in the inherently challenging 1,2- or 1,3-HAT. Although hydrogen atom transfer is widely observed in synthetic organic chemistry, intramolecular hydrogen atom transfer between atoms separated by fewer than four bonds is kinetically slow. Here the authors show a method to form indanones, with hydrogen atoms shuttled across short distances by water. [ABSTRACT FROM AUTHOR]

The development of enantiodivergent catalysis for the preparation of both enantiomers of a chiral compound is of importance in pharmaceutical and bioorganic chemistry. With the design of a class of reactive and stereoselective organocatalysts, acyclic chiral secondary amines, a method for achieving the enantiodivergence is developed simply by changing the secondary N-i-Bu- to N-Me-group within the catalyst architecture while maintaining the same absolute configuration of the catalysts, which modulates the catalyst conformation. This catalyst-controlled enantiodivergent method not only enables challenging asymmetric transformations to occur in an enantiodivergent manner but also features a high level of stereocontrol and broad scope that is demonstrated in eight different reactions (90 examples), all delivering both enantiomers of a range of structurally diverse products including hitherto less accessible, yet important, compounds in good yields with high stereoselectivities. Enantiodivergent methods, which to access both enantiomers of the same compound, are of importance in drug synthesis. Here, the authors show that by simply changing a NiBu- to a NMe-group in readily available amine organocatalysts, high stereocontrol and broad scope are achieved in eight asymmetric reactions. [ABSTRACT FROM AUTHOR]

Higher-order cycloadditions are a powerful strategy for the construction of polycycles in one step. However, an efficient and concise version for the induction of asymmetry is lacking. N-heterocyclic carbenes are widely used organocatalysts for asymmetric synthesis and could be an ideal choice for enantioselective higher-order cycloadditions. Here, we report an enantioselective [10 + 2] annulation between catalytically formed aza-benzofulvene intermediates and trifluoromethyl ketone derivatives. This protocol exhibits a wide scope, high yields, and good ee values, reflecting a robust and efficient higher-order cycloaddition. Density functional theory calculations provide an accurate prediction of the reaction enantioselectivity, and in-depth insight to the origins of stereocontrol. High-order cycloaddition reactions are useful for the construction of polycycles in a single step, but versions that induce asymmetry are limited. Here the authors report the construction of asymmetric polycycles via N-heterocyclic carbene-catalyzed hetero-[10 + 2] cycloaddition of indole-2-carbaldehydes with trifluoromethyl ketone derivatives. [ABSTRACT FROM AUTHOR]

Unlike the well-reported 1,2-difunctionalization of alkenes that is directed by classic pyridine and imine-containing directing groups, oxo-palladacycle intermediates featuring weak Pd-O coordination have been less demonstrated in C-H activated cascade transformations. Here we report a quadruple C-H activation cascade as well as hydro-functionalization, C-H silylation/borylation sequence based on weakly coordinated palladium catalyst. The hydroxyl group modulates the intrinsic direction of the Heck reaction, and then acts as an interrupter that biases the reaction away from the classic β-H elimination and toward C-H functionalization. Mechanistically, density functional theory calculation provides important insights into the key six-membered oxo-palladacycle intermediates, and indicates that the β-H elimination is unfavorable both thermodynamically and kinetically. In this article, we focus on the versatility of this approach, which is a strategic expansion of the Heck reaction. Combining the Heck reaction with other transformations provides a powerful strategy to access diverse, complex compounds. Here, the authors report a weak coordination dominated Pd(0)-catalyzed quadruple C-H activation followed by hydro-functionalization, C-H silylation, and C-H borylation. [ABSTRACT FROM AUTHOR]