Furan Ring Construction

Common methods for the furan ring construction were applied to preparation of trifluoromethyl-substituted benzofurans starting from the substrates bearing appropriately located CFs-group. Thus, 2-(trifluoropropynyl)-phenol 170 was cyclized into trifluoromethylbenzofuran 171 by heating with pyridine [118]. 

In another variation, the intermediate aldol product 64, with an extra hydroxy group in the y-position, was used to construct the furan ring of rosefuran (65), a trace component of rose oil (Scheme 6.56) (285). Here, the reaction of the nitropentene derivative 61 with crotyl acetate (62) afforded the 3,4,5-trisubstituted isoxazoline (63) in moderate yield. Removal of the acetyl group by saponification of the cycloadduct, subsequent demasking of the aldol moiety using Mo(CO)6, and exposure of the ketodiol (64) to acid gave the target compound 65 (285). 

Reactions of this type have been used in the construction of the pyrrolylfuran derivatives (309) (R = H, 57% and R = C1, 24%) using nitrile ylides generated by the imidoyl chloride-KOf-Bu method (191). This reaction was a key step en route to simplified analogues of roseophilin, however, the reaction failed for the derivative with a methoxy group at the 4 position of the furan ring. 

The intramolecular Diels-Alder reaction has long been a powerful method for polycyclic ring construction. A1 Padwa of Emory University reports (J. Org. Chem. 68 227, 12003) that on Rh catalysis, a diazoalkyne such as 1 is smoothly converted into the reactive furan 2. Cyclization of 2 leads via 3 to the angularly-arylated product 4. 

The construction of the furan ring in a Feist-Benary type reaction starting from 4-hydroxy-6-methylpyran-2-one (66) has also proved to be useful for the synthesis of furo[3,2-c]pyridines (Scheme 14) (75JHC461, cf. 71BSF4041). Quite recently the synthesis of the hitherto unknown furo[3,2-c]pyridin-3-ols has been described (79LA371). 4-Hydroxypyridine-3-carboxylates (e.g. 69), which are available from diketene and /3-aminocrotonic esters, react with a-halogenoketones in the presence of potassium carbonate to give compounds of type 70. 

The furo[3,4-c]furan ring system of lignan, ( )-paulownin (51) was constructed stereoselectively by Kraus et al. [16] by the photocyclization of 50, as shown in Scheme 8.15... 

In the following scheme, the benzo[Z>]furan core of ( )-frondosin B was built up by the palladium-catalyzed quinone reduction, followed by Lewis acid-mediated benzo[Z>]furan formation <07OL3837>. In the total synthesis of bisabosquals, the core structure of benzo[ ]furan was constructed by an epoxide-ring opening reaction <07T10018>. 

Alternative suggestions for the construction of the furan ring have been made by Wenkert 154), who invokes a condensation of anthranilic acid with erythrose, and by Ghosal 159), who utilizes anthranilic acid and ornithine as precursors (see p. 262),... 

Palladium catalysis in the construction of the furan rings from alkynes and organic halides or triflates 02H(56)613. 

Construction of the suitably substituted geranic acid for making the furan ring has been effected too. For example, Poulter et al. have prepared the substituted geranate 865 by reaction of 4-methyl-3-pentenylcopper with the acetylenic ester 866. The ester 865 then underwent cyclization in the presence of acid to the lactone 867, related to scobinolide (161), and the action of acid on the lactol produced from 867 with diisobutylaluminum hydride gave perillene (849). The lactone 867 has also been prepared by a slightly different method the C9 alcohol 868 was made (in poor yield) from isobutenol and prenyl chloride with butyllithium. The extra carbon atom was introduced by the action of sodium cyanide on the epoxide of 868, and hydrolysis of the cyano group followed by dehydration yielded the lactone 867. The dimethylthioacetal of 867 has been used to synthesize perillene (849). This thioacetal was made from the suitably substituted ketene thioacetal 869 and dimethylsulfonium methylide. Thus the ketene thioacetal 870 (readily prepared from acetone, carbon disulfide, and sodium amylate, followed by methylation °) can be prenylated with lithium... 

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