Polysubstituted pyrimidine synthesis

Polysubstituted pyrimidines 39 can be obtained from a,P-unsaturated imines 38 and amidines or guanidines in a one-pot procedure [270]. The imines 38 are generated in situ in a sequential three-component process from methyl phosphonate, nitriles, and aldehydes (both preferentially aromatic for the utihty of 38 in pyridine synthesis, cf p. 373) ... 

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. ... 

The high selectivity in sequential nucleophilic substitution in perfluorodiazines made them attractive scaffolds for the synthesis of a diverse array of polysubstituted diazines. These approaches were recently developed by Stanford group. Thus, tetra-fluoropyritnidine may be used as a scaffold for the synthesis of a range of 2,4,6-trisubstituted pyrimidine derivatives upon sequential displacement of the fluorine atoms attached to the strongly activated 4-, 6- and 2-positions (Table 9) [158]. The first two substitutions proceed in very mild conditioned (0 °C or room temperature). The last nucleophilic substitution of fluorine at 2-position proceeds in harsh conditions and needs MW heating. 

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