Studies On The Three-component Reactions Of Terminal Alkynes,Aldehydes,and Amines

One important goal in modern synthetic organic chemistry is the development of simple and efficient methods for the construction of complex compounds from readily available simple starting materials. In recent years, multi-component reactions, in which three or more than three components could be introduced into target molecules in one-pot, have attracted attention from chemists. Among them, the transition metal-catalyzed three-component reaction of terminal alkynes, aldehydes, and amines has become a typical and useful example. The propargylic amines synthesized by this method are often important building blocks, playing an important role in synthesizing complex natural products and pharmaceuticals. Furthermore, the cascade three-component reactions of terminal alkynes, aldehydes, and amines could also be used for constructing various nitrogen-containing heterocycles and allenes. I have focused on the three-component reactions of terminal alkynes, aldehydes, and amines during my Ph.D. study:Part Ⅰ:Asymmetric Synthesis of Chiral Propargylic Amines and Axially Chiral Allenoates1. We have established a highly enantioselective general synthesis of chiral propargylic amines using 2-methylbut-3-yn-2-ol, aldehydes, and pyrrolidine in the presence of CuBr and (R,Ra)-N-PINAP ligand. After removing the dimethylcarbinol unit in the 2-methylbut-3-yn-2-ol, the useful terminal propargylic amines obtained could be further functionalized to give different non-terminal 2-alkynylic amines.2. We have developed a silver(Ⅰ)-mediated highly enantioselective synthesis of axially chiral allenoates from optically active propargylic amines with efficient central-to-axial chirality transfer.Part Ⅱ:Copper(Ⅰ)-Catalyzed Cascade Three-Component Reaction of Terminal Alkynes, Aldehydes, and Amines1. We have developed a copper(I)-catalyzed three-component reaction for the efficient synthesis of pyrones and 2,5-dihydrofurans from terminal propargylic alcohols, electron-poor aldehydes, and amines. The reaction would afford pyrones in case of using ethyl glyoxalate as the aldehyde and secondary terminal propargylic alcohols as the terminal alkynes. The 2,5-dihydrofurans could also be converted into 2,5-disubsituted furans upon treating with CH3I. This method has several advantages such as mild reaction conditions, broad substrate scope, and easily available materials, extending the scope of copper-catalyzed three-component reactions of terminal alkynes, aldehydes and amines.2. We have developed a copper(I)-catalyzed three-component reaction of the terminal alkynes, aldehydes, and 3-pyrroline for the synthesis of N-allyl pyrroles. This novel reaction is simple and atom economic, affording N-allyl pyrroles with exclusive E-stereoselectivity under exceptionally mild conditions. Moreover, it could provide a highly attractive and convergent approach toward optically active N-allyl pyrroles by employing the CuBr and (R,Ra)-N-PINAP catalytic system. The mechanism of the reaction has also been investigated.