No abstract

Various 2-(6-substituted 3(Z)-hexen-1,5-diynyl)anilines 1a-g were treated with potassium tert-butoxide or potassium 3-ethylpentanoxide in NMP at 60 degrees C for 2 h to give the corresponding 5-substituted carbazoles 2a-g in 36-65% yields together with indoles 9a-g in 21-40% yields, respectively. Exposing the trifluoroacetamide analogues 10h-k under the same reaction conditions gave the carbazoles 2b-e in 37-57% yields and indoles 9b-e in 15-27% yields. Subsequent cyclizations of acetamide analogues 10a-g gave carbazoles 2a-g in 53-86% yields.

Treatment of 2-(1-aryl-3-propynoyl) anisoles 1 with N-chlorosuccinimide (NCS) or N-bromosuccinimide (NBS) gave the 3-halogenated flavones and their related molecules in moderate yields.Keywords: Electrophiclic cyclization; Flavonoids.Flavonoids are a series of the earliest discovered natural products, which occur in most families of higher plant kingdom. As a major class of plant components, over 4000 flavonoid compounds have been identified 1 that exhibit a variety of pharmacological activities, including antiflammatic, antioxidant, antithrombogentic, antiviral, anticarcinogenic and antiproliferative effects. 2 Some flavonoids have also been demonstrated to possess the binding affinities for the estrogen receptor.3 Despite an abundance of flavonoids from natural sources, it is still of interest to obtain them by synthesis since novel biological activities are continuously discovered for these compounds and their derivatives. 4 Herein, we report a new synthetic method to obtain 3-halogenated flavonoids 2 by electrophile-promoted cyclization of 2-(3-substituted 2-propynonyl)anisoles 1 (Eq. 1), and which had no investigation about the route.(1)The synthesis of flavone precursor 1a is summarized in Scheme I. Treatment of salicyclic aldehyde (3) with methyl iodide in DMF for 12 h produced 2-methoxybenzaldehyde (4) in 92% yield. Compound 4 was reacted with lithium phenylacetylide (from treatment of 1.0 eq. phenylacetylene with 1.2 eq. n-BuLi in THF) at 0°C for 2 h to yield the alcohol 5a in 85% yield. Oxidation of 3a with MnO 2 afforded the 2-(3-phenyl-2-propynonyl)anisoles 1a in 96% yield.Several sets of conditions for the cyclization reaction have been tested and the results are summarized in Table 1.Compound 1a was first treated with 3 equivalents of iodine, N-iodosuccinimide (NIS), NBS, or NCS in refluxing CH 2Cl2. No product was isolated in all reactions even after the reaction time was extended to 24 h. Only the starting materials were recovered. When the solvent CH 2Cl2 was replaced by DMF, reaction of 1a with NIS at 100°C for 2 h gave the undesired product 7aa in 50% yield. Treatment of 1a with NBS under the same reaction conditions gave 3-bromoflavone 6ab in 36% yield together with addition product 7ab in 30% yield. Reaction of 1a with NCS gave 3-chloroflavone 6ac in 57% yield along with the addition adduct 7ac in 15% yield. The structure of compound 6ac was unambiguously determined by X-ray crystallography (Fig. 1). The results confirmed that the electrophilic cyclization of 2-(3-phenyl-2-propynoyl)anisole takes a 6-endo pathway instead of a 5-exo pathway to generate 3-chloroflavone (6ac). Under the same reaction conditions, reaction of 1a with iodine gave neither addition adduct nor the cyclization adduct. Moreover, DMSO

Ring closure reactions Ring closure reactions O 0130Substituent Effects on the Cyclization Mode of 7-Sulfonyl-3-hepten-1,5-diynes and 11-Sulfonylundeca-3,7-dien-1,5,9-triynes. -It is found that the substituent on the alkyne terminus in 7-sulfonyl-3-hepten-1,5-diynes has no influence on the cyclization mode. However, substituents on the alkene terminus play an important role. In the presence of hydrogen substituents, Myers-type cyclization takes place, while starting from benzene analogues like (VII), considerable amounts of Schmittel-type cyclization products are obtained. The cyclization mode of 11-sulfonylundeca-3,7-dien-1,5,9-triynes, however, is strongly dependent on substituents on the alkyne terminus.

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