Kondrat’eva pyridine synthesis

Kondrat eva pyridine synthesis. This methodology to pyridine rings continues to be applied in total synthesis. An approach to the antitumor compound ellipticine 34 ° makes use of a Diels-Alder reaction of acrylonitrile and oxazole 32 to form pyridiyl derivative 33. Addition of methyllithium and hydrolysis transforms 33 into 34. 

The azaphenanthrene alkaloid eupolauramine appeared to be an ideal target for exploring the applicability of an intramolecular Kondrat eva pyridine synthesis in the construction of natural products. Despite the fact that 2-phenyloxazoles are unreactive in intermolecular cycloadditions, the Diels-Alder reaction of oxazole-olefin 97 was expected to provide the tricyclic framework of eupolauramine... 

Pyridines can be achieved by the [4 + 2] hetero Diels-Alder cycloaddition of i) an alkene dienophile and an 3-azadiene such as 1,2,4-triazine (the Boger reaction), oxazole (Kondrat eva pyridine synthesis), oxazinone, pyrimidine, or ii) an alkene and a 4-azadiene or iii) a butadiene and an azadienophile. 

This reaction was first reported by Kondrat eva in 1957. It is a general method for synthesizing pyridine derivatives involving an inverse demand Diels-Alder Cycloaddition between an azadiene (especially the oxazoles) and a dienophile followed by an extmsion of the resulting bridge of the bicyclic intermediate. Thus this reaction is known as the Kondrat eva pyridine synthesis, Kondrat eva reaction, Kondrat eva cycloaddition,or Kondrat eva approach. " ... 

Other references related to the Kondrat eva pyridine synthesis are cited in the literature. 

Iwase and Aoki reported a very efficient synthesis of 3- or 4-substitufed pyridines via high-pressure Diels-Alder reaction of oxazole 1. For example, 1 reacted with acrylonitrile at 1.1 Mpa to produce 3-cyanopyridine 1652 in 95% yield (Scheme 1.425). Kondrat eva and co-workers described cycloaddition reactions of 2-aminoox-azoles 1653 with maleimide (Scheme 1.425). The authors isolated several different... 

Intramolecular Kondrat eva synthesis was also developed in the synthesis of several pyridine-containing natural products. ... 

Oxazoles were used in the Kondrat eva reaction for the synthesis of pyridine-based compounds (13OL2530, 13OL3550). A continuous flow procedure was reported for a scalable synthesis of benzoxazoles 137 starting form 3-halo-N-acyl anilines 136 (130L5546). The reaction proceeded via a base-mediated elimination of the 3-halo substituents to give an aryne intermediate that underwent intramolecular cyclization to provide lithiated benzoxazoles that were quenched in-line by addition of electrophiles (E ). 

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