Brønsted acid catalyzed intramolecular benzylic cyclizations of alkylpyridines

Abstract

Aldehyde and ketone electrophiles incorporated into the side chains of 2- and 4-alkylpyridines participate in intramolecular aldol-like condensations with pyridine benzylic carbons in the presence of Brønsted acid catalysts. Pyridines featuring β-ketoamide side chains undergo cyclization in the presence of 10 mol% TfOH to afford pyridyl-substituted hydroxy lactams in good yield. These products were found to be resistant to further dehydration under a variety of conditions, however treatment with thionyl chloride elicited an unusual dehydration/oxidation reaction sequence. In contrast, acid-catalyzed cyclization of pyridines tethered to aliphatic aldehydes with amine linkers gives pyridyl-substituted dehydro-piperidine products. Similarly, intramolecular condensation of salicylaldehyde- and salicylketone-substituted pyridines affords pyridyl-substituted benzofurans.

Construction of 1,2,4-Triazole Derivatives via Cyclocondensation of Alkylidene Dihydropyridines and Aryldiazonium Salts

“…4 We have initiated studies examining the reactivity of 4substituted alkylidene dihydropyridines and have reported intramolecular aldol-like reactions with attached carbonyl electrophiles. 5 More recently, we have demonstrated the use of anhydrobases as alkene partners in intramolecular Mizoroki− Heck cyclizations (Scheme 1A). 6 During attempts to develop intermolecular versions of this reaction, we screened aryldiazonium salts as organic electrophiles with the expectation that the high reactivity of aryldiazonium cations in Pd-catalyzed couplings would facilitate the desired Heck−Matsuda reaction.…”

Strategies To Access γ-Hydroxy-γ-butyrolactams

“…Pigge and co-workers treated 4-hydroxypyrrolidin-2ones with excess thionyl chloride in the presence of a base to generate γ-hydroxy-γ-butyrolactams. 102 Indeed, by taking advantage of the dehydration properties of SOCl 2 , the reaction first produces 1,5-dihydro-2H-pyrrol-2-one intermediate A. A further reaction of A with SOCl 2 in the pres-ence of base affords species B and/or C, which then undergoes a nucleophilic addition reaction with H 2 O to form the γ-hydroxy-γ-butyrolactam (Scheme 54).…”

Direct Access to Fused Salicylaldehydes and Salicylketones from Tetraynes

“…[1] Salicylaldehyde has mainly been obtained through the Reimer-Tiemannr eaction; [2] however, the yield of salicylaldehyde obtained by this method is low,a nd it is difficult to recover and recycle the large quantity of chloroform used with phenol in this reaction. [1] Salicylaldehyde has mainly been obtained through the Reimer-Tiemannr eaction; [2] however, the yield of salicylaldehyde obtained by this method is low,a nd it is difficult to recover and recycle the large quantity of chloroform used with phenol in this reaction.…”

“…Salicylaldehydes and salicylketones are importanti ntermediates in the productiono fp erfumes,d yes, plastics, agricultural materials, and drugs such as aspirin. [1] Salicylaldehyde has mainly been obtained through the Reimer-Tiemannr eaction; [2] however, the yield of salicylaldehyde obtained by this method is low,a nd it is difficult to recover and recycle the large quantity of chloroform used with phenol in this reaction. [3] The construction of benzene rings from acyclicb uilding blocks is av ersatile approachf or the preparation of functionalized arenes, and various synthetic methods have been documented in the literature.…”