摘要：

Ti-mediated reductive cross-coupling of imines with unactivated alkenes and alkynes for the synthesis of nitrogen-containing heterocycles is described. A two-step, three-component process for the stereoselective synthesis of substituted piperidines was developed. Alkoxide-directed cross-coupling of imines with conjugated alkynes proceeds in a highly regioselective manner to deliver coupled products with C-C bond formation occurring α- to the conjugated systems. Subsequent condensation of the coupled products with aldehydes followed by cationic annulation (i.e. Pictet-Spengler-like cyclization and aza-Prins cyclization) affords highly substituted piperidines with typically very high levels of stereoselection. Next, studies toward the synthesis of the common intermediate of macroline and sarpagine-related indole alkaloids employing our recently developed Ti-mediated cross-coupling of imines with allylic alcohols as a key step were reported. An azabicyclo[3.3.1]nonane ring, which could be advanced to the proposed common intermediate in future studies, was prepared. This study also led to the development of a double asymmetric cross-coupling of chiral imines with chiral allylic alcohols for the stereoselective synthesis of ( )-disubstituted homoallylic amines. A three-component coupling sequence for the regiospecific synthesis of substituted pyridines was also developed. Substituted pyridines were prepared from functionalized primary homoallylic amines via Hg (II) or Ag (I)-promoted cyclization followed by oxidation. The homoallylic amines were in turns prepared from Ti-mediated cross-coupling of generated -TMS imines with dithiane-substituted allylic alcohols, which were synthesized via selective 1,2-addition of dithiane anions to α,β-unsaturated carbonyl compounds.

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