Blaise reaction intermediate

Exanqile 4, Chemoselective tandem acylation of a Blaise reaction intermediate ... 

A tandem one-pot method for the construction of highly substituted pyridine derivatives from nitriles, Reformatsky reagents, and 1,3-enynes was developed by Lee and coworkers in 2011 [64], The reaction sequential consisted of the reaction of nitrile with a Reformatsky reagent and then selective addition of the Blaise reaction intermediate to 1,3-enyne, followed by isomerization, cyclization, and an aromatiza-tion cascade to give the final pyridines in moderate to excellent yields. 

Blaise reaction. Formation of (i-oxocsters by treatment of a-bromocarboxylic esters with zinc in the presence of nitriles. The intermediate organo-zinc compound reacts with the nitrile, and the complex is hydrolyzed with 30% potassium hydroxide. 

Hannick and Kishi cyclized an intermediate bromozinc enamino ester (41 Scheme 21) to obtain the heterocycle (42), used for the synthesis of saxitoxins. The Kishi procedure for the Blaise reaction has been applied to a facile synthesis of p-keto-S-butyrolactones (43), or tetronic acids (44 Scheme 22). 

An improved Blaise reaction provides a simple access to enaminones 34. Treatment of nitriles 32 with three to five molar equivalents of a-bromo esters 33 and activated zinc dust in refluxing THF gives the enaminones in high yield, Scheme 10. The value of the method was demonstrated by the conversion of the nitrile 35 to the pyrrolidine derivative 36, a key intermediate in the synthesis of the alkaloid saxitontn (83JOC3833). 

A modified Blaise reaction (the imine intermediate is converted to an enamine moiety rather than hydrolyzed to a carbonyl) can be used for the preparation of... 

Non-stabilized zinc ester enolates (463) (Reformatsky enolates) have been reported to add to terminal alkynes (465) in the presence of nitriles RC=N, affording (467). The reaction is initiated by the Blaise reaction of (463) with the nitrile, which generates the zinc chelate (464). The latter species then adds to the alkyne (465) in a Markovnikov manner, and the resulting intermediate (466) undergoes a retro-Blaise fragmentation to afford the zinc enolate (467) and the original nitrile. When combined with aDiels-Alder reaction partner and subsequent oxidative aromatization, this sequence can serve as a one-pot de novo construction of a-arylated alkanoates. " ... 

Tetronic acids (Scheme 18) are of great interest because their derivatives are widespread in nature. The Blaise reaction (addition of the zinc derivative of an a-bromo ester to a nitrile) has been applied to optically active 0-protected cyanohydrins. Isolation of the tetronic acids was achieved, in moderate yields, by acid hydrolysis and cyclization of the intermediate imines [94]. Better results were obtained in an optimized reaction sequence [141] (Scheme 18). 

A partial reduction of O-protected chiral cyanohydrins is also possible by reaction with Reformatsky reagents (Blaise reaction). The primarily formed imino intermediates can be hydrolyzed under very mild conditions to give the enamines ( )-15, which yield by treatment with strong acids the tetronic acids (R)-16 (Scheme 9) [39,40]. 

Simple esters of monocarbosylie acids apparently do not react rith form aldehyde. HoweA er, alpha halogenated esters undergo the Reformatskj reaction- with diy paraformaldeh t de or polyoxymethylene and zinc, gi nng hydrox> esters ns products. These reactions were studied by Blaise and co-workers The reaction mechaimm probably invob es the formation of an organcanetallic intermediate a indicated below in the case of ethyl alpha-bromoisobutyrate ... 

---