Cu(I)‐Catalyzed Asymmetric Cross‐Coupling of N‐Tosylhydrazones and Trialkylsilylethynes: Enantioselective Construction of C(sp)—C(sp³) Bonds

Abstract

The first catalytic enantioselective C(sp)―C(sp3) cross‐coupling reaction between N‐tosylhydrazones and trialkylsilylethynes in the presence of Cu(I) salts and chiral phosphoramidite ligands was developed. A series of synthetically interesting, functionalized alkynes were obtained with moderate to good enantioselectivities (up to 83% ee). Cu(II) carbene migratory insertion is proposed to be the enantio‐determining step.

Transition-Metal-Catalyzed Cross-Coupling with Ketones or Aldehydes via N-Tosylhydrazones

“…Mechanistically, a regioselective protonation occurs on the ipso position of the propargyl copper species influenced by the silyl moiety, which is supported by a following DFT study . Later, we attempted the asymmetric catalytic version of this coupling; however, only moderate enantio­selectivities can be achieved by using phosphor­amidite as the chiral ligand (Scheme b) . Similar asymmetric catalysis was also explored by Uozumi and co-workers…”

“…87 Later, we attempted the asymmetric catalytic version of this coupling; however, only moderate enantioselectivities can be achieved by using phosphoramidite as the chiral ligand (Scheme 17b). 88 Similar asymmetric catalysis was also explored by Uozumi and co-workers. 89 In addition to terminal alkynes, a wide range of arenes can also react with N-tosylhydrazones, in which they serve as alkyl electrophiles to produce the corresponding aromatic C−H alkylation products.…”

Fluoroalkyl N-sulfonyl hydrazones: An efficient reagent for the synthesis of fluoroalkylated compounds

“…Fluoroalkyl N-sulfonyl hydrazones have been developed and used as operationally safe diazo surrogates in carbene transfer reactions in this context. Nonetheless, due to the relatively high temperature (>50 °C) required for decomposition into diazo species, their use in the asymmetric reaction has not been reported [86][87][88][89][90][91][92][93]. Bi and co-workers [94] Despite recent considerable breakthroughs, we believe that the fluoroalkyl N-sulfonyl hydrazones have yet to reach their full potential.…”

Cu(i)- and Pd(ii)-catalyzed decarboxylative cross-couplings of alkynyl carboxylic acids with N-tosylhydrazones: access to trisubstituted allenes and conjugated enynes

“…9 Therefore, it is of great significance to explore novel strategies for synthesizing allenes and 1,3-enynes. 12 Based on our previous work on the synthesis of allenes and 1,3-enynes with metal carbene chemistry, 13,14 we have conceived that it would be highly desirable to explore alkynyl carboxylic acids as the cross-coupling partners in this type of transformations.…”