5- Bromo-2-chloropyrimidine, coupling with

Since chloro substituents in the benzenoid pyrimidine 5-position will not normally react with a stannane, the reaction between 2,5-dichloropyrimidine and styryltributylstannane is specific for the activated 2-position 5-bromo-2-chloropyrimidine is coupled with selective substitution of bromine in the 5-position (108). The 2-chlorine can subsequently be substituted [89ACSA(B)62]. In reactions of 2,4-dichloropyrimidine with /3-styryl- or phenyltributylstannane the carbosubstituent is selectively introduced into the 4-position (110) [89ACSA(B)62]. The same regioselectiv-ity is observed for Ni-catalyzed coupling with organomagnesium reagents (see below), and the regioselectivity corresponds to the relative reactivity... 

Couplings in 5-bromo-2-chloropyrimidine would be expected to proceed preferentially in the 5-bromo position (Scheme 75). This order of preference has been changed by an initial exchange of the chloro with an iodo substituent. The prodnct from the halogen exchange, 5-bromo-2-iodopyrimidine, is selectively conpled in the 2-position with a wide... 

Bromo-2-chloropyrimidine, however, is coupled selectively at the 5-position to form the product 207. Phenylation by phenylstannanes takes place in the same regioselective manner (yide supra). In reactions of 2,4-dichloropyrimidine with p-styryl- or phenyl(tri-n-butyl)stannane, the carbosubstituent goes selectively into the 4-position 209. A second carbosubstituent can subsequently be introduced into the 2-position. The regioselectivity corresponds to the relative reactivity of pyrimidine toward heteronucleophiles. In 2,4,6-trichloropyrimidine one chlorine in the 4/6-position is replaced selectively 210 under conditions for monocoupling. 

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