Pyridine 2-sulfonamides, rearrangement

However, studies on the scope of this sequence revealed that the substrate has to be an N-tosyl sulfonamide and that certain boronic acids are not trans-metallated but rather give rise to the formation of the pyrrole 21 or a pyridine derivative 22 (Scheme 7). The peculiar outcome as a carbopalladation-Suzuki sequence is rationalized by co or dinative stabilization of the insertion intermediate 18 by the sulfonyl oxygen atom, as represented in structure 19, now suppressing the usual /3-hydride elimination. If the transmetallation is rapid the Suzuki pathway is entered leading to product 17. However, if the transmetallation is slow, as for furyl or ferrocenyl boronic acid, either /i-hydride elimination or a subsequent cyclic carbopalladation occurs. The former leads to the formation of the diene 20 that is isomerized to the pyrrole 21. The latter furnishes the cyclopropylmethyl Pd species 23, which rearranges with concomitant ring expansion to furnish piperidyl-Pd intermediate 24 that suffers a -hydride elimination to give the methylene tetrahydro pyridine 22. 

The formation of nicotinic acid derivatives by base-mediated nitrogen to carbon rearrangement of -substituted pyridine 2-sulfonamides (Scheme 189) has been reported. ... 

An illustration of the essential steps in inhibition of acid secretion by PPIs with pantoprazole as an example. The drug is administered in a gastroprotected formulation and is absorbed in the duodenum or is administered in a reconstituted IV formulation. The acidic, membrane-enclosed space of the active parietal cell s secretory canaliculus accumulates the PPI approximately 1,000-fold (pH 1.0, pKa of drug approximately 4.0) due to protonation of the pyridine. After intramolecular transfer to the N of the benzimidazole, rearrangement of the molecule occurs to form first the cationic thiophilic sulfenic acid and then the sulfonamide, either of which reacts rapidly with cysteines on the luminal face of the pump. 

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