A one-pot Synthesis of Functionalized Azadienes from 2-hydroxypyridine , Activated Acetylenes and Alkyl Isocyanides

A one-pot synthesis of dialkyl 2-[(alkylimino)(2-oxopyridin-1(2H)-yl)methyl]but-2-enedioate from alkyl isocyanides, dialkyl acetylenedicarboxylates, and 2-hydroxypyridine, in good yields, is described.


INTRODUCTION
Isocyanides are known to form zwitterions with activated acetylenic compounds such as dimethyl acetylenedicarboxylate 1 .Reaction between isocyanides, electron-deficient acetylenes and nucleophiles was first documented by Oakes in 1969 and 1973 2,3 .Such interesting and promising transformation was nearly forgotten until Yavari in 1996 extended its application to dibenzoylmethane as NuH 4 .Later on, more publications on such a reaction were published differing mostly in the nature of NuH used [5][6][7][8][9][10] .

General procedure for the preparation of compounds 4
To a stirred mixture of 3 (1 mmol) and acetylenic ester 2 (1 mmol) in CH 2 Cl 2 (5 mL), was slowly added 1 (

RESULTS AND DISCUSSION
Thus, reaction of isocyanides 1, acetylenic esters 2, and 2-hydroxypyridine 3 proceeded spontaneously in CH 2 Cl 2 , and was completed within a few hours.The 1 H-and 13   compounds 4a-4e were deduced from their IR, 1 H-NMR, and 13 C-NMR spectra.The 1 H-NMR spectrum of 4a in CDCl 3 showed a singlet for the two methyl of 2,6-dimethylphenyl (δ(H) 2.24), along with three singlets for methoxy (δ(H) 3.65 and 3.83) and methine (δ(H) 5.79) H-atoms.Characteristic multiplets for the Ph H-atoms were observed at ä(H) 6.02-7.97.The 13 C-NMR spectrum of 4a exhibited 17 resonances in agreement with the proposed structure.The mass spectrum of 4a displayed the molecular ion peak at m/z 368.The NMR spectra of 4b-4e were similar to those of 4a except for the substituents.
A possible mechanism for these transformations is proposed in Scheme 2. It is conceivable that the reaction involves the initial formation of the 1:1 zwitterionic intermediate 5 between the isocyanide 1 and acetylenic ester 2 (Scheme 1).Protonation of 5 by the acidic compound 3 leads to intermediate 6. Subsequent attack of the resulting nucleophile 7 on the positively charged ion 6 affords azadiene derivatives 4.
In conclusion, the three-component reaction of alkyl isocyanides, dialkyl acetylene dicarboxylates, and 2-hydroxypyridine provides a simple one-pot synthesis of stable functionalized azadienes.This procedure has the advantages of high yields and mild reaction conditions.

Scheme 2 :
Scheme 2: A Plausible Mechanism for the Formation of Products 4.