Blaise reactions

Blaise, E. E. C. If. Hebd. Seances Acad. Sci. 1901, 132, 478, 978. Blaise was at Insti-tut Chimique de Nancy, France. 

P-Ketoesters from nitriles, a-haloesters and Zn. Cf. Reformatsky reaction. 

The Zn enolate itself is a C-enolate (in the crystal form), but for the reaction to occur, it equilibrates back into an 0-enolate 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 24, Springer-Verlag Berlin Heidelberg 2009 

Example 4, The first chemoselective tandem acylation of the Blaise reaction in- 

Ring opening of oxiranes using azide followed by PPh3-reduction of the intermediate azido-aleohol to give the eorresponding aziridines. 

P-Ketoesters from nitriles, a-haloesters and Zn. Cf. Reformatsky reaction. R-CN. Br CO.R 1 Zn, THP. m8ux  

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 28, Springer International Publishing Switzerland 2014 

Exanqile 4, Chemoselective tandem acylation of a Blaise reaction intermediate  

Example 5, Chemoselective intramolecular alkylation of Blaise reaction intermediate  

---

The reaction of a nitrile with a Reformatsky reagent is known as the Blaise reaction and when applied to (9-trimethylsilyl cyanohydrins leads to the formation of tetronic acids with high ee [79]. By working-up the Blaise reaction with ammonium chloride it is possible to isolate... 

Duffield, J.J. and Regan, A.C. (1996) Asymmetric synthesis of tetronic acids by Blaise reaction of protected optically active cyanohydrins. Tetrahedron Asymmetry, 7, 663-666. 

Syed, J., Forster, S. and Effenberger, F. (1998) Application of the Blaise reaction stereoselective synthesis of (4R)-tert-butyl 3-amino-4-trimethylsilyloxy-2-alkenoates from (R)-cyanohydrins. Tetrahedron Asymmetry, 9, 805-815. 

Allylic zinc reagents are highly reactive and add to acid chlorides and anhydrides. A double addition of the allylic moiety usually occurs, leading to tertiary alcohols . The double addition can be avoided by using a nitrile as substrate (Blaise reaction). By... 

Usually, after hydrolysis, the alcohol is the product, but sometimes (especially with aryl aldehydes) elimination follows directly and the product is an olefin. By the use of Bu,P along with Zn, the olefin can be made the main product,454 making this an alternative to the Wittig reaction (6-47). Since Grignard reagents cannot be formed from a-halo esters, the method is quite useful, though there are competing reactions and yields are sometimes low. A similar reaction (called the Blaise reaction) has been carried out on nitriles 455... 

Reformatsky first introduced electron-withdrawing substituents on the a-carbon of an organozinc halide, leading to the more reactive and thermally stable a-(alkoxycarbonyl)alkylzinc halides (123).107 Typically these reagents react with aldehydes or ketones to afford 3-hydroxy esters while nitriles afford 3-keto esters (Blaise reaction),l07b>c but 1,4-conjugate additions to select a,3 unsaturated ketones are precedented (Section 1.2.2.2.2). 

Based on this process, which is sometimes referred to as the Blaise reaction ,20,21 a straightforward entry into the saxitoxin and gonyautoxin series has been devised (Scheme 14.4) which relies upon the selective alkylation of the ambident zinc enamide 9 initially formed at its soft or hard site according to the HSAB principle.22 Specifically, a terminal halide group in substrate 8 (X = Br) affords the carbocyclic product 10 via C-alkylation, whereas a terminal sulfonate entity (X = 0S02Me) leads to the pyrrolidine derivative 11 via the N-alkylation pathway. 

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. 

This chapter summarizes studies on the nature of the Reformatsky reagent as well as other, related, zinc enolates and outlines the synthetic aspects of the reaction with aldehydes and ketones. In addition, reactions of the Reformatsky reagent with imines and nitriles (the Blaise reaction) are described. 

---