Journal of Organic Chemistry最新文献

A trifluoromethylpyridylation of unactivated alkenes in aqueous solution under open air is reported. This process allows the incorporation of trifluoromethyl and the construction of pyridines annulated to saturated cycles via an intramolecular Minisci reaction using Langlois’ reagent (CF₃SO₂Na) as a trifluoromethyl source. Extrusion of air from the reaction is not required. A broad functional group tolerance is observed. A series of five-, six-, and seven-membered cycles are obtained, exhibiting great potential application in the preparation of diversified pyridines.

The irradiation of a series of 4-phenoxyphenol esters in a sustainable micellar environment has been studied from both preparative and mechanistic viewpoints, and the results were compared with those obtained in cyclohexane solutions. These esters underwent the photo-Fries rearrangement reaction, and the microheterogeneous media induced a noticeable selectivity in favor of the ortho-regioisomer formation with yields up to 96% yield. UV–visible and 1D and 2D NMR (DCS, NOESY, and DOSY) spectroscopies have been employed to determine the binding constant (K_b) and the location of the esters within the hydrophobic core of the spherical micelles. Furthermore, the diffusion coefficient (D) and hydrodynamic radius (r_s) were also measured. Application of the photo-Fries reaction of esters in microheterogeneous media as a key step in a multistep sequence has been carried out, leading to the preparation of (4-phenoxy)-(2-n-pentylcarbonyl)-phenoxyethyl selenocyanate (10), an interesting target molecule showing potential biological activity against Trypanosoma cruzi.

We have succeeded in constructing a trans-2,6-disubstituted piperidine (trans-2,6-DP) skeleton by treatment of allylsilane derivative 2 with TMSOTf. Our designed trans-2,6-DP 1 has oxygen functional groups at the 2- and 6-positions and an exo-methylene moiety at the 4-position and is expected to be applied not only to the synthesis of various natural products but also as an excellent chiral building block with pseudo-symmetry. To demonstrate the versatility of 1, the total synthesis of (−)-myrtin and trans-piperidine-type poison-frog alkaloid 213A and 213B was accomplished.

A palladium-catalyzed decarboxylative allylic sulfonylation reaction of vinyloxazolidine-2,4-diones with inexpensive and readily available sodium sulfinates as sulfonylation reagents has been developed. Under the catalysis of Pd(PPh₃)₄, a wide range of γ-sulfonyl-α,β-unsaturated amides can be synthesized in good to excellent yields. The developed protocol is characterized by exclusive regioselectivity, mild reaction conditions, broad substrate scope, good functional group tolerance, and suitable for gram-scale synthesis.

sp³-Rich molecular scaffolds incorporating nitrogen heterocycles represent important starting points for assembling compound screening libraries and drug discovery. Herein, we report a four-step synthesis of a conformationally well-defined sp³-rich scaffold incorporating two morpholine rings embedded within a spiroacetal framework. The synthesis involves the intermediacy of a 2-chloromethyl-substituted morpholine, accessed from epichlorohydrin and readily available β-aminoalcohols. Base-mediated dehydrochlorination affords an exocyclic enol ether, from which the second morpholine ring is constructed in two steps. Scaffold synthesis is high-yielding and can be performed on a large scale. The methodology allows ready substitution of one–or both– of the morpholine rings for 1,4-oxazepanes and the generation of 6,7- and 7,7-spiroacetal analogues, which are virtually unexplored in drug discovery. Substituted 6,6-systems can be prepared and, in some instances, undergo acid-mediated anomerization to deliver the scaffolds in high diastereoselectivity. The two amine functionalities embedded in the 6,6- and 6,7-spiroacetal scaffolds were sequentially functionalized to provide a diverse physical compound library. These library compounds occupy a similar chemical space to small-molecule drugs that have been approved for clinical application by the Food and Drug Administration yet are structurally dissimilar and may therefore act upon novel targets, representing attractive starting materials for drug discovery.