Dialkylzinc Promoted Asymmetric Addition Of Terminal Alkynes To Imines

The catalytic addition of terminal alkynes to C=O and C=N double bond is one of the major research endevors in synthetic chemistry over the past decades. In this paper, we mainly discuss the design and synthesis of some new C2-symmetric bis(β-hydroxy amide) ligands and their applications in the enantioselective addition of alkynylzinc to aldehydes, and dialkylzinc promoted asymmetric addition of alkynes to chiral N-tert-butylsulfinylimines and N-tosylaldimines. This thesis is composed of four parts as below:1. Propargylic amines are highly useful building blocks in organic synthesis. This part provides an overview of the most significant advances in the preparation of propargylic amines via the direct addition of alkynes to imines and carbon nitrogen electrophiles in the presence of metal catalysts or promoters.2. A series of chiral C2-symmetric bis(β-hydroxy amide) ligands was synthesized via the reaction of isophthaloyl dichloride and amino alcohols derived from L-amino acids. The amount of ZnEt2, Ti(O'Pr)4 and solvents had a strong effect on the asymmetric alkynylation of aldehydes, and the propargyl alcohols were obtained in high yields (82-94% yield) and high enantiomeric excesses (52-98% ee) under optimized conditions.3. The first direct approach for the asymmetric synthesis of (E)-2-arylidene-1,4-diphenylbut-3-yn-l-amines by addition of alkynylzinc to chiral N-tert-butyl-sulfinylimines was reported. The alkynylzinc was formed in situ from dialkylzinc and terminal alkynes reacted with imines under reflux conditions affording the disired products. Following this methodology, a number combination of various alkynes and imines to give the products with excellent diastereoselectivitis and good yields (up to 92% yield and up to>99:1 dr). The stereochemistry of the compounds was determined by X-ray crystallography. On the basis of a number of experimental observations, we gave an explanation for the new reaction mechanism. 4. We have reported the first procedure for the catalytic enantioselective additon of terminal alkynes to N-tosylaldimines to give N-tosyl-(E)-(2-en-3-ynyl)-amines by using dimethylzinc and BINOL-type ligands. The reaction works with a variety of aromatic and heteroaromatic N-tosylaldimines, and with different alkynes, providing the expected products with good yields (51-92% yield) and high enantiomeric excesses (82-99% ee). In particular, this method could be used to deal with two different alkynes to give diversified products successfully.