Though the properties of N-heterocyclic carbenes (NHCs) are generally dominated by the very strong σ donating character, electronic activation has emerged as an effective method to cooperate with typical carbon-framework steric optimization for highly enantioselective chiral NHC–transition-metal catalysis in recent years. NHC electronic changes associated with structural variations are now better understood by quantitative analysis using various methods. Here we highlighted and correlated some interesting chiral induction improvement methods, which were brought by electronic and steric cooperation on chiral NHC–transition-metal catalysis.1 Introduction2 Hemilabile Sidechains on NHC Ligands3 Electronic and Bond Angle Changes Brought by NHC Core Size Variations4 Electronic Activators on the NHC Core5 Conjugated Systems and Fused Ring Structures6 Remote Electronic Activators on the N-Aryl Ring7 Summary and Outlook

Diastereodivergent heterocycle synthesis has been recognized as an important tool for drug discovery in recent years, yet strategies based on nickelacycle formation have not been established. Here, we report a NHC-Ni catalyzed highly 1,3- and 1,4-diastereodivergent heterocycle synthesis from enyne, which is achieved by manipulating the enyne N-substituent (allowing switching of selectivity from up to 2:98 to 98:2). The key to success is the efficient diastereodivergent formation of a nickelacyclopentene, with broad enyne scope at mild conditions, which subsequently provides reductive hydroalkenylation, acylation and silylation products on demand. Diastereoisomers which are sterically hard to distinguish or difficult to access by conventional routes are now accessible easily, including those with very similar 4°, contiguous and skipped stereocenters.

N-Heterocyclic carbenes | Enynes | Diastereodivergent synthesis | Hydrosilylation | HydroalkenylationCatalytic diastereodivergent hydrosilylative enyne cyclization with high generality and broad scope was achieved using electronic activated N-heterocyclic carbene-Ni(0) as a catalyst and R 3 SiH as silane (IPr Cl , syn-: anti-selectivity from up to 98 : 2 to 7 : 93 by Z = O, NH vs. NMs, R 1 = n-pentyl). Heterocycles bearing homoallylsilane rather than vinylsilane was obtained chemoselectively. The undesired yet highly competitive reactivity was suppressed, like direct hydrosilylation of alkene and alkyne concurrently. Optionally, the homoallylsilane products could be reduced further in one-pot using IPrMe as ligand and (EtO) 3 SiH as silane under otherwise the same standard condition as the above, offering practical access to additional stereocenters and more diverse product structures from enynes.

NHC-Nickel(0) catalyzed 1,3-and 1,4diastereodivergent hydroacylative heteroenyne cyclization with aldehydes was achieved (Syn-:Anti-, switchable from up to 1:99 to 98:2). Both sets of heterocyclic diastereomers are accessible via this route, with a high γ-:α-enone structure ratio. Preliminary DFT investigations indicated that the manipulation of the N-substituent exerts a direct influence on the diastereoselectivity of NHC-nickelacyclopentene formation. The energy differences associated with the endocyclic bond angle (CÀ ZÀ C) changes noted in the calculations, might possibly account for the broad scope and high diastereodivergent selectivity observed.

Isocyanides are common compounds in fine and bulk chemical syntheses. However, the direct addition of isocyanide to simple unactivated cyclopropene via transition metal catalysis is challenging. Most of the current approaches focus on 1,1-insertion of isocyanide to M-R or nucleophilc insertion. That is often complicated by the competitive homo-oligomerization reactivity occurring at room temperature, such as isocyanide 1,1-insertion by Ni(II). Here we show a (N-heterocyclic carbene)Ni(II) catalyst that enables cyclopropene-isocyanide [5 + 1] benzannulation. As shown in the broad substrate scope and a [trans-(N-heterocyclic carbene)Ni(isocyanide)Br2] crystal structure, the desired cross-reactivity is cooperatively controlled by the high reactivity of the cyclopropene, the sterically bulky N-heterocyclic carbene, and the strong coordination ability of the isocyanide. This direct addition strategy offers aromatic amine derivatives and complements the Dötz benzannulation and Semmelhack/Wulff 1,4-hydroquinone synthesis. Several sterically bulky, fused, and multi-substituted anilines and unsymmetric functionalized spiro-ring structures are prepared from those easily accessible starting materials expediently.

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