2-Stannylpyrimidines, reactions

Thermal decarboxylation of pyrimidylcarboxylic organotin esters is another means to prepare the corresponding stannylpyrimidines [33]. This method obviates the intermediacy of lithiated pyrimidine species that would undergo undesired reactions at higher temperatures. The decarboxylation occurs at the activated positions. Therefore, thermal decarboxylation of tributyltin carboxylate 62, derived from refluxing carboxylic acid 61 with bis(tributyltin) oxide, provided 4-stannylpyrimidine 63. Addition of certain Pd(II) complexes such as bis(acetonitrile)palladium(II) dichloride improved the yields, whereas AIBN and illumination failed to significantly affect the yield. 

Stannylpyrimidines have been prepared from the reaction of halogenopyrimidines with stannylhthium or stannylsodium reagents (e.g. equation 7-27),96 and again, by analogy with the homoarylstannanes, the heteroarylstannanes can be made from the heteroaryl halide and a distannane with a palladium catalyst (equation 7-28).97... 

A range of stannylpyrimidines and pyrazines can be prepared by reaction of the halodiazines with a lithiostannane, however attempts to prepare 3-stannylpyridazines fail. Their Stille reactions are consistently successful. 

Pyrimidines stannylated in the 4-position are active in coupling reactions. 5-Chloro-4-stannylpyrimidines, either as 2-sulfide or 2-one, are coupled with alkenyl or aryl halides to form 208, 210, and 212. With an acid chloride, ketone 213 is formed in the absence of catalyst, which has an otherwise deleterious effect on the reaction. The reaction between thiophene-2-carbonyl chloride and the 4-stannylpyrimidine is run at -78°C (94T275). 

Stannylpyrimidines also react with acid chlorides to form ketones (214) without a catalyst (Scheme 46). The reaction with furoyl chloride is almost instantaneous at -78°C the yield of ketone is 52%. 2-Thienylcarbonyl chloride provides the ketone in 62% yield. On the other... 

Stannylpyrimidines react readily with organohalides and -triflates under the influence of Pd catalysis (Scheme 34). 2-Methylthio-5-trimethyl- or tributyl-stannylpyrimidine reacts with bromo-styrene or propenyl bromide to yield (216) <88ACS(B)455,89JCS(P1)255>. 5-Pyrimidinyl biheteroarenes are accessible from bromofurans, bromothiophenes or bromopyridines and stannylated pyrimidines <89ACS684>. 5-Stannylated 2-pyrimidinones (217) are good substrates for coupling reactions (218). 

Stannylpyrimidines react similarly. This reaction has been applied to pyrimidine nucleosides for substitution at C6. Initially LDA in THF at — 78°C was used for the regioselective metallation at C6 in uridine. The lithiated species was quenched with a stannyl chloride to form the stannane to be used in the coupling with an aryl iodide. The optimal conditions in most cases involve 10 mole%... 

Pyrimidines stannylated in the 4-position are highly active in coupling reactions at low temperature and will couple with an acid chloride to form ketones such as (233) in the absence of catalyst (Scheme 38). 2-Stannylpyrimidines also react rapidly with acid chlorides to form the ketones (234) in the absence of catalyst <94T275>. 

A-Alkylation is the favored reaction path in competition with (9-alkylation. A -Alkylation is further favored by using (9-silyl or (9-stannylpyrimidines as substrates. Simple alkoxypyrimidines... 

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