Pyridine reaction with methyl propiolate

Occasionally, [2.2.3]cyclazines have been obtained from pyridines in reasonable yields. Thus (251) is formed in a reaction of the 2-vinylpyridine (252) with methyl propiolate <71 JCS(C)3296>. Acylative cyclization of pyridine-2-carbaldehyde with a,/3-unsaturated carbonyl compounds provides a convenient route to l-acyl[2.2.3]cyclazines (Scheme 38) <74H(2)585). 

Crabtree, Johnson, and Tebby55 have studied the reaction of pyridine with methyl propiolate and found that the major product is 31, high-pressure hydrogenation of which resulted in loss of the acrylic ester side chain to give indolizidin-3-one, whereas treatment with piperidine gave a product (32) believed to be the indolizine [Eq. (8)]. 

Acheson and Robinson also investigated the reaction of methyl propiolate with pyridine and its 3-methyl, 4-methyl, and 3,5-dimethyl... 

Cyclic nitrones with substituents a to the nitrogen atom (38) undergo 1,3-dipolar cycloaddition with methyl propiolate to form isoxazolo[2,3-a]pyridines (39) and (40) with high regio- and stereo-specificity (Scheme 14).64 The chiral cyclic nitrones (41) undergo asymmetric 3 + 2-cycloaddition reaction with a, /i-unsaturated carbonyl compounds to form cycloadducts (42) with very high diastereomeric excess (>99%) (Scheme 15).65... 

Reaction of l-amino-3-benzyloxypyridinium mesitylenesulfonate 755 with methyl propiolate in the presence of potassium carbonate in DMF at room temperature gave a mixture of methyl 4-benzyloxy- 756 and 6-benzyloxypyr-azolo[l,5- ]pyridine-3-carboxylates 757 (Scheme 95) <1996H(43)2249>. Treatment of 756 and 757 with 48%... 

Furthermore, it has been shown that compounds of type 235 are versatile starting materials for addition and cyclization reactions employing reactive triple and double bonds. With methyl propiolate, syn addition takes place to aiford the adducts 240. In the presence of alcohols, compounds 240 are cyclized to give the imidazo[l,2-a]pyridines and pyrido[l,2-a]pyrimidines 241136 (Scheme 63). By treatment with methyl acrylate, the lactone derivatives 235 give the spiro compounds 242 in an addition and cyclocondensation sequence.137 With dimethyl acetylenedicarboxylate, 235 forms several condensed and unsaturated spiro compounds 243, similar to 242,137 as well as the tricyclic 5-lactone 244 (Scheme 64). 

Another example is the reaction of pyridine with methyl propiolate to give (65), which clearly arises by nucleophilic attack of the acetylenic... 

Methyl propiolate and pyridine give a rather unstable 2 1 molar adduct which is the 1,2-dihydropyridine (112). The reaction sequence proposed to account for its formation is identical in principle to a similar scheme proposed earlier in the acridine series (Section II,A,2) and is also supported by the observation that the 1-benzoyl-pyridinium cation with the phenylacetylide anion yields (113). ... 

Michael/Henry/dehydration/aromatisation reaction of 2-(2-oxoethyl) benzal-dehydes and nitroalkenes mediated by pyrrolidine to obtain polysubstituted naphthalene derivatives. DBU catalysed the conjugate additions of alcohols to ot,p-unsaturated nitriles, esters and ketones. Perhaps more important are the aza-Michael addition reactions of amines to a,p-unsaturated ketones, nitriles and esters. Recently, Costa, Vilarrasa and coworkers described the addition of lactams, imides, 2-pyridone, pyrimidine-2,4-diones and inosines to methyl propiolate and other similar compounds, DABCO and DMAP being the best catalysts. As mentioned before, tertiary amines give zwitterionic species with activated allynes. It was as early as 1932 when Diels and Alder used the reaction of pyridine with dimethyl acetylenedicarbojylate (DMAD) for the synthesis of heterocycles. The interception of the corresponding intermediate with Al-tosylimines and activated olefins provided access to l-azadienes ° and highly substituted butadienes (Scheme 2.6). When the quenching species of the zwitterionic intermediate is a 1,2-diketone, dibenzoyl maleates or cyclopentenedione derivatives could be obtained (Scheme 2.6). The interception of the zwitterionic species of N-methyl imidazole (NMI) and DMAD with ketenes to obtain unsaturated esters has also been shown. ... 

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