Synthesis of 2 , 4-disubstituted furans and 4 , 6-diaryl-substituted 2 , 3-benzo-1 , 3 a , 6 a-triazapentalenes

Reactions of acylacetylenes 1a–h with benzotriazole 2 give intermediates 3a–h. The treatment of 3a–h with trimethylsulfonium iodide in the presence of base give intermediate oxiranes 4a–h and 2,3-benzo-1,3a,6a-triazapentalenes 7d–g depending on substituent. Acid-catalyzed rearrangement of crude 4a–h give 2,4-disubstituted furans 5a–h.


Introduction
The furan ring is an important structural unit in many biologically active and naturally occurring compounds. 1Furan syntheses and their applications have been reviewed in detail.1d,2 The available strategies for the preparation of 2,4-disubstituted furans (Scheme 1) utilize ring construction via: (i) acid-catalyzed rearrangement of oxiranyl ketones, 1c,3 and (ii) their enol (or thioenol) ethers; 1a,1e-g,4 (iii) thermal annulation of 3,4-dihaloketones; 5 (iv) radical cyclizationreductive demethoxylation of bromoketals; 6 palladium-catalyzed cyclization of (v) 2-methoxyor 2-unsaturated pent-4-yn-1-ol, 7 and (vi) allenyl aldehydes; 8 (vii) base-catalyzed cyclization of γ-alkynyl ketones, 9 (viii) carbon insertion into cyclic enol -metal complexes; 10 To develop a procedure for regioselective preparation of unsymmetrical 2,4-disubstituted furans, we have investigated the reactivity of 2-oxiranyl-vinyl benzotriazoles 4 (Scheme 2) toward rearrangement followed by elimination of benzotriazole to afford furans 5. We now disclose the preparation of 2,4-disubstituted furans 5a-h in two steps from acylacetylenes 1a-h in methodology that utilizes the leaving capability of the benzotriazole group 12 and thus compliments the Garst-Spencer furan synthesis.1a In the course of our investigation we also have found and now report the preparation of heteropentalenes 7d-g from benzoylacetylenes 1d-g via a mechanism which may involve intermediates 6d-g.

Result and Discussion
Acylacetylenes 1a-h and benzotriazole 2 (Scheme 2) react in the presence of catalytic amounts of t-BuOK in toluene under reflux to give β-benzotriazolyl unsaturated ketones 3a-h as mixtures of cis/trans-isomers in good yields.Structures 3a-h were supported by their 1 H and 13 C NMR spectra.Compounds 3a-h were converted to oxiranes 4a-h by treatment with trimethylsulfonium iodide (1.3-2.0 equivalents) in methylene chloride -50% aqueous NaOH two-phase system in the presence of tetrabutylammonium iodide at 20-40 °C for 12-48 h. 13 Crude oxiranes 4a-h rearranged in the presence of p-toluenesulfonic acid in THF solution at 50-60 °C to afford furans 5a-h.To support the reaction pathway proposed, intermediate 4a was isolated, but because of its instability only 1 H and 13 C NMR spectra of 4a were acquired and used to deduce its structure.The The structures of furans 5a-h were supported by their 1 H and 13 C NMR spectra.Their 1 H NMR spectra no longer show signals in the range 7.0-8.2ppm corresponding to the benzotriazolyl group in 3a-h and 4a, nor signals for oxirane ring protons as for intermediate 4a.
In the 13 C NMR spectra of 5a-h, the signals around 181-204 ppm corresponding to the carbonyl group in 3a-h, as well as signals around 111 ppm, 120 ppm, 133 ppm, and 146 ppm assigned to benzotriazolyl groups in 3a-h are no longer present.New signals in the 13 C NMR spectra of 5a-h in the ranges 103.3-107.7 ppm, 137.1-139.0ppm, and 153.8-155.8ppm are distinctive for 2,4-disubstituted furans 10b,14 and were assigned to the carbon atoms of the furan ring formed.
The treatment of 3d-g with trimethylsulfonium iodide in the presence of base gave, in addition to compounds 5d-g, isolable byproducts.The 1 H NMR spectra of these byproducts no longer appear to be typical for N-substituted benzotriazoles with 1 H signals around 8.0-8.2 ppm as in 3a-h.However, the 13 C NMR spectra of the byproducts show signals near 111 ppm, 120 ppm and 147 ppm, which together with elemental analyses suggested the presence of a benzotriazole moiety.The 13 C NMR spectra also show two new signals in the range 105.0-105.5 ppm and 113.1-113.7 ppm.A single crystal X-ray structure determination for the product obtained from 3e unambiguously demonstrated it to be the 2,3-benzo-1,3a,6a-triazapentalene 7e (Figure 1).The bonding geometry within the molecule is similar to that in the only other reported X-ray structure containing this heterocyclic ring system. 15Heteropentalenes of this type cannot be represented by a single valence bond description.Based on the fact that the 4-chlorophenyl ring is approximately coplanar with the benzopentalene system [angle between meanplanes = 5.9(1)º] whereas the phenyl ring is twisted out of this plane [by 45.2(1)º] it is probable that the atom labelled C3 carries significant charge.In accord with this proposal is the observation that the C3-C10 bond is significantly shorter than the C1-C16 bond.The 1 H and 13 C NMR spectra of these byproducts also support the heteropentalene structures 7d-g.The reaction mechanism for the formation of 7d-g probably involves nucleophilic attack on the epoxide in 4d-g from the 2-position benzotriazole nitrogen to give intermediate 6d-g.Intermediates 6d-g then eliminate formaldehyde with the formation of 4,6-diarylsubstituted 2,3benzo-1,3a,6a-triazapentalenes 7d-g in 8-71 % yields.Interestingly, for compound 3e, the corresponding heteropentalene 5e was obtained only in 8 % yield while the formation of 7h was not detected.
To examine the possible differences in the reactivity of individual isomers of intermediates 3, we separated mixtures of cis/trans-isomers 3a,c,e-h.However, subsequent reactions of the individual cis and trans isomers of 3 with trimethylsulfonium iodide and p-toluenesulfonic acid gave the same final product composition in all cases.

General procedure for the preparation of 3a-h
catalytic amount of potassium tert-butoxide (5-10 mg) was added to a solution of acylacetylene 1a-h (10 mmol) and benzotriazole (2) (1.55 g, 13 mmol) in toluene and the reaction mixture was refluxed for 3-5 h under a nitrogen atmosphere.Then the reaction mixture was cooled down to room temperature and washed with saturated aqueous solution of sodium carbonate to remove excess benzotriazole.The organic layer was dried over magnesium sulfate, and the solvent was evaporated in vacuum.The crude product (mixture of cis/trans-isomers) was purified by column chromatography to give 3a-h (the crude product may be used on the next step without additional purification).4 Hz, 1H, minor), 2.54 (q, J = 14.5, 7.3 Hz, 2H, minor), 2.34 (q, J = 14.5, 7.3 Hz, 2H, major), 1.07 (t, J = 7.3 Hz, 3H, minor), 0.99 (t, J = 7.3 Hz, 3H, major); 13

General procedure for the preparation of 5a-h and 7d-g
A vigorously stirred mixture of 3a-h (4 mmol) with trimethylsulfonium iodide (1.06 g, 5.2 mmol) in the presence of tetrabutylammonium iodide (50 mg, 0.13 mmol) in dichloromethane (15 mL) and 50% aqueous NaOH (15 mL) was refluxed under nitrogen atmosphere for 6−36 h (the reaction progress was monitored by TLC; the addition of extra trimethylsulfonium iodide (1.0-2.0 mmol) may be required).When 3a-h was consumed, the product was extracted with dichloromethane.The extract was dried over magnesium sulfate and the solvent was evaporated to give the crude intermediate 4a-c,h or a mixture of 4d-g and 7d-g.
The residue was dissolved in anhydrous THF, a catalytic amount of p-toluenesulfonic acid (10-20 mg) was added and the reaction mixture was refluxed for 0.5-1 h under nitrogen atmosphere.Then the reaction mixture was concentrated in vacuum and the residue was subjected to column chromatography on silica gel to give 5a-h and 7d-g.

11 Issue
and (ix) an oxidative ring transformation of pyrylium salts.