Pyrimidine 2- stannyl

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). 

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>. 

The stannylation and silylation of heteroaryl halides has also been studied. The stannylation of 4-iodo pyrimidine was conducted with hexamethyl and hexa-ra-butyl ditin in the presence of fluoride ion and Pd(PPh3)2(OAc)2 as catalyst. The stannylation of 5-bromopyrimidine occurred in the highest yields in the presence of the ligandless catalyst bis(7r-allylpalladium chloride).175 The silylation of bromopyridines, bromopyrimidines, and bromoquinolines also occurred after 96 h at 160 °C with Pd(PPh3)4 as catalyst in HMPT solvent.162... 

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%... 

The yield of coupling products from 5-stannylated pyrimidines 151 is normally high (Scheme 62).i i Pyrimidines with the stannyl group in the electrophilic 4-position 152 also react weU.i i Carbosubstitution in the 4-position in the 2-pyrimidinone 153 proceeds under similar conditions. In the pyridine series, the coupling reaction is exemplified by the reaction of a 4-stannyl derivative with a triflate of a benzonaphthyridine for the preparation of a pyridinylbenzonaphthyridine 154.i i... 

Tin Reagents. The presence of a 3-methyl group in the 2-chloroquinoline 202 has a beneficial effect on reaction rates and efficiency in Stille-type alkenylations with terminal stannyl alkenes (Scheme 77). This was attributed to steric acceleration in the reductive elimination of Pd(0) from a Pd(II) complex. The purine 6-position is highly electrophilic. A chloro substituent is readily replaced under Stille conditions using tri(n-butyl)vinylstannane. The 6-vinylpurine product 203 from the coupling is reacted further in situ in Heck couphngs. These reactions proceed readily because of the electron-withdrawing effect from the ir-deficient pyrimidine moiety of the heterocycle.t ... 

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