Regioselective Photocycloaddition of Pyridine Derivatives to Electron-Rich Alkenes

Abstract

Irradiation of a benzene solution of 3-cyano-2,6-dimethoxypyridine in the presence of ethyl vinyl ether (EVE) gave 1:1 photoadducts, 3-cyano-5-ethoxy-2,8-dimethoxy-4,5-dihydroazocine, in good yields, whose structure was established by X-ray single-crystal analysis. The photoadduct was produced via cycloaddition between the C3-C4 position of the pyridine derivatives and an alkene chromophore. On the other hand, 3-cyano-2,6-dimethoxy-4-methylpyridine cycloadds to EVE at the C2-C3 position of the pyridine ring upon irradiation. The difference is explained on the basis of the steric effect.

Photoaddition Reactions of Acetylpyridines with Silyl Ketene Acetals: SET vs [2 + 2]-Cycloaddition Pathways

“…An interesting feature of photoreactions of 13 – 15 with 16 – 18 is that both the SET and [2 + 2]-cycloaddition processes take place at the ketone carbonyl rather than pyridine ring center. The highly regioselective nature of these excited state processes is somewhat surprising because electron withdrawing group substituted pyridines were known to participate in [2 + 2]-cycloaddition and SET-promoted reactions, which occur in the pyridine ring centers (Scheme ). , One possible reason for the high selectivity of photochemical reactions of acetylpyridines could be associated with the magnitudes of charge coefficients in the n –π triplet excited states of these substrates (T 1 ), which could govern the sites of energetically most favored interactions with 16 – 18 . To gain information about this proposal, density functional theory (DFT) calculations using a B3LYP hybrid exchange correlation function employing 6-31G** (for ground states (S 0 ) and anion radicals of acetylpyridines) and CIS (for triplet states of acetylpyridines T 1 ) were carried out.…”

“…For example, it is well-known that the ketones serve as electron acceptors in photochemical C–C bond forming processes as well as participants in Paterno–Buchi reactions that generate oxetanes. In addition, pyridines, especially those possessing electron-withdrawing groups (e.g., cyano) have been observed to participate in both the SET and [2 + 2]-cycloaddition reactions , (Scheme ). The results of the current studies show that acetylpyridines react with an electron rich, dimethyl-substituted silyl ketene acetal via a pathway promoted by excited state SET that produces β-hydroxyesters in high yields.…”

Oxidative Dearomatization of Pyridines

“…Noting that this strategy could deliver elusive piperidine scaffolds functionalized with heteroatoms, we wished to extend this work to pyridines. Importantly, dearomative cycloadditions with pyridines are exceedingly rare and the first practical [4 + 2] cycloaddition was only recently demonstrated in intramolecular settings . Herein, we show that pyridines are viable substrates for arenophile-mediated para -cycloaddition and that the resulting cycloadducts are amenable to in situ oxidations.…”

Discovery of Potent, Highly Selective, and Orally Bioavailable Pyridine Carboxamide c-Jun NH2-Terminal Kinase Inhibitors

“…Selective chlorination of the 5-position of the known picolinic acid ester 9 16 followed by saponification of the ester provided acid 10 . The ethoxy group in 10 was cleaved in 6 N aqueous HCl solution, and the resulting hydroxy acid was treated with 2 equiv of 2-iodopropane and Ag 2 CO 3 followed by saponification of the resulting ester to yield acid 11 . Amides 12 and 13 were obtained by a TBTU mediated amide coupling reaction as described above.…”