Current Organic Chemistry - Volume 13, Issue 15, 2009

During the past decades, great progress has been made on the direct asymmetric addition of terminal alkynes to carbonyl compounds (aldehydes and ketones) and imines. The present issue is focused on the recent development of novel chiral catalysts for such enantioselective alkynylation reactions. Asymmetric alkynylation of imines is reviewed by Prof. Pedro. Diastereoselective procedures are involved in the addition of metal alkynylides to chiral nonracemic imines derived from chiral amines or chiral carbonyl compounds. Enantioselective non-catalytic procedures have been achieved with the use of stoichiometric additives or alkynylboron reagents. In addition, catalytic addition of terminal alkynes or zinc acetylides has been carried out in the presence of chiral metal complexes, especially copper complexes as catalysts. The second review has been provided by Dr. Tyrrell on the topic of asymmetric alkynylation reaction of aldehydes by a Zn(OTf)2-chiral ligand-base system. It demonstrates the synthetic utility of effective Carreira’s protocol in an array of natural product synthesis. In the past several years, various combinations of novel chiral ligands and transition metal sources have been employed as catalysts in organozinc reagents mediated asymmetric alkynylation reaction. In the review by Prof. Mao and et al., they highlight the recent advances in this field and try to compare the methods available for this transformation.

This review deals with the asymmetric alkynylation of imines (and iminium ions) to give chiral nonracemic propargylamines. Diastereoselective procedures involved the addition of metal alkynylides to chiral nonracemic imines derived from chiral amines or chiral carbonyl compounds. Enantioselective non-catalytic procedures have been achieved with the use of stoichiometric additives or alkynylboron reagents. Finally, catalytic addition of terminal alkynes or zinc acetylides has been carried out in the presence of chiral metal complexes, especially copper complexes as catalysts.

Optically active propargylic alcohols serve as an important building block in asymmetric synthesis. The customised synthesis of chiral ligands and transition metal activators as catalysts, to effect asymmetric alkynylation reactions, continue to feature in the literature. This review article focuses upon the use of Zn(OTf)2, in conjunction with 2-point chiral ligands, for effecting asymmetric alkynylation reactions to aldehydes.

There is growing interest in enantioselective synthesis of optically active propargylic alcohols. One of the most effective and straightforward ways for their synthesis is asymmetric addition of terminal alkynes to aldehydes. In the past several years, various combinations of novel chiral ligands and transition metal sources have been employed as catalysts in this asymmetric alkynylation reaction. In this review, we highlight the recent advances in this field and try to compare the methods available for this transformation.

Asymmetric alkynylation of ketones can provide versatile chiral tertiary propargylic alcohols. A series of strategies have been achieved in the past few years. Relative optimal reaction conditions for obtaining the highest enantioselectivities and yields, as well as the practical scope of different types of catalytic systems are reviewed.

β-ketoesters namely, ethyl acetoacetate (1a) or ethyl benzoylacetate (1b) reacted with1,3-binucleophilic reagents to yield 1,2,3,6-tetrahydropyridine-3-carbonitrile (3a-d) derivatives. Each of 3a,b coupled with a proper arenediazonium or heteroarenediazonium salts to produce 5-aryl-(heteroaryl)azo-6-hydroxy-4-methyl-2-oxo(thioxo)-2,3- dihydropyridine-3-carbonitriles 5a-f. Heating under reflux each of 5c,e with acetic anhydride in pyridine led to cyclization and formation of pyrazolo[5,1-c]pyrido[2,3-e][1,2,4] triazine-3-carboxylate derivatives 6a,b. Compounds 3a,b added to 4- chloro-α-cyanocinammonitriles (7) in refluxing pyridine afforded pyrano[2,3-b]pyridines 8a,b. Treatment of 3b with bromomalononitrile in ethanolic potassium hydroxide solution gave directly 3-amino-8-cyano-7-methyl-5-oxothiazolo[ 3,2-a]pyridine-2-carboxamide(18). Heating compound 18 with either formic acid alone or in the presence of formamide yielded pyrido[2/,3/:2,3]thiazolo[4,5-d]pyrimidine derivatives 19,20 respectively.