Coupling by Hydrogen Substitution

A variety of arenes and heteroarenes react with alkenes in the presence of palladium(II) derivatives to produce alkenyl substitution products. Three methods are commonly employed for the in situ preparation of palladium derivatives (i) direct metallation of an arene or heteroarene with a Pd(II) salt (ii) exchange of the organic group from a main-group organometallic to a Pd(II) compound (iii) oxidative addition of an organic halide, an acetate, or triflate salt to Pd(0) or a Pd(0) complex. For catalytic reactions Cu(II) chloride or p-benzoquinone is usually used to reoxidize Pd(0) to Pd(II). 

If two hydrogens on a /3-carbon are available, elimination to ( /-alkenes is strongly preferred. If only one hydrogen is present on the /3-carbon, the stereochemistry can be predicted on the basis of syn-addition of the organopalladium group to the double bond, followed by syn-elimination of a palladium hydride (91MI1). 

The fused pyridines, 3-bromoquinoline and 4-bromoisoquinoline, are both alkenylated by ethyl acrylate or styrene (3, 4). The reaction with acrylonitrile was less satisfactory, especially in the 4-position in isoquinoline (78JOC2947 79CPB193). 

Allylic alcohols react differently. The coupling product has a saturated carbon chain in which the hydroxyl group has been oxidized to a formyl or keto group (7). The yields from 3-bromopyridine were generally high a methyl group on an olefinic carbon in the alcohol retards the reaction (78JOC3396). 

Methoxy- or methylthio-5-iodopyrimidines (9) are effectively coupled with methyl acrylate to form the product (10). Reaction of the 5-bromo analog is slower, and is sensitive to vicinal interaction in 4,6-disubstituted pyrimidines, most of the substrate was unreacted (only a 10% yield) (86S555). A free amino group in the 4-position (11) is tolerated in the preparation of the alkenylated product (12) (82CPB2410). 

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