The team led by Professor Tong Xiaofeng has published their latest research results “Domino Sequences Involving Stereoselective Hydrazone-type Heck Reaction and Denitrogenative [1,5]-Sigmatropic Rearrangement” in a top international journal ----Journal of the American Chemical Society (JACS).

Traditional Heck reactions realized by C-C coupling of halogenated hydrocarbon and alkene provide a powerful tool to construct C−C bonds, for which scientists have shared the Nobel Prize in Chemistry in 2010. Compared with mature C-C Heck reactions, carbon═heteroatom Heck reactions are rather few. The introduction of heteroatom has made fundamental changes in coordination, causing great difficulty in migratory insertion (as seen in Scheme 1).

(1) Alkene generally adopts η2-bound mode to form a π-complex such as species A1 and complex A1 is prone to develop a tight [2π +2σ] transition state TS, which in turn facilitates the alkene insertion step to generate alkyl−Pd(II) intermediate B1. For example, the C=NR unit may prefer a η1-imino-Pd(II) type coordination (A2). Since this type of coordination cannot form similar transition state, it may hamper the formation of the η2-Pd(II) complex with the C=N double bonds.

(2) In addition, the N-Pd(II) bond formed by migratory insertion of C=N is weaker than that of C-Pd. Therefore, C=N bond migratory insertion is endothermic, which is also unfavorable in thermodynamics.

To address these problems, the research started a new path to explore Hydrazone-type Heck Reaction by drawing inspirations from studies on metal-catalyzed hydrazone (C=N-NH2) and C=heteroatom double bonds. After reasonable design and repeated optimization of the reaction substrate and catalytic system, a Pd(0)-catalyzed hydrazone-type Heck reaction was realized and asymmetric catalysis was also achieved through conventional PHOX chiral ligand. The research obtains Heck reaction products by the insertion of hydrazone and the elimination of highly selective β-H. Then through coupling conversion of [1,5]- rearrangement of azene, it constructs 3-substituted tetrahydropyridines with degrees of optical purity up to 99% (as seen in Scheme 2).