Furo furans. preparation

Condensed benzo[i>]furan molecules can be prepared by inter- or intra-molecular Diels-Alder reactions from furo[3,4-b]benzofurans, and some interesting intermolecular examples are listed below. As can be seen, the furo[3,4-i>]benzofuran 60 underegoes Diels-Alder reactions with naphtho-l,4-quinone in the presence of Znl2 as a Lewis acid to form the aromatized cycloadduct. When the diene precursor reacts with benzo-l,4-quinone in the absence of Znl2, the product is obtained as an endo-exo mixture <00JCS(P1)1387>. 

The l-oxa-2,4,5-cycloheptatrienes 602 and 603 were postulated to be intermediates in the rearrangement of certain (ethynylfuryl)oxiranes to furo[3,4-b]furans [251]. The replacement of the methylene groups of 1,2-cycloheptadiene (465) by SiMe2 groups and the introduction of substituents at the allene moiety allowed the preparation of isolable seven-membered ring allenes. Thus, Barton et ah [177] obtained 604 and Ando et al. [178] 605. A few reactions of these systems have also been studied [177, 252]. Both groups [178, 253] synthesized the [4.4]betweenallene 606 and determined its structure by X-ray diffraction. 

A series of a,a-dimethoxysilyl enol ethers has been prepared and shown to undergo diastereoselective [4+3]-cycloaddition with furan and cyclopentadiene in the presence of catalytic amounts of trimethylsilyl triflate <99SL213>. Furo[3,4-d]oxazoles and furo[3,4-d]thiazo-les react with 13-dimethyloxyallyl to give [4+3]-cycloadducts. The ring opening reaction of these compounds with H2S04Mt20 yields armulated hydroxytropones <99H(51)1225>. 

An alternative, but effective, method for preparing furo[2,3-r/ pyrimidines with the potential for polysubstitution in the furan ring is shown in Equation (108). Here -dimethylbarbituric acid 299 is treated with a variety of alkenes in MeCN containing cerium(iv) ammonium nitrate to produce 300 with complete regioselectivity (Equation 108) <2000SC4277>. 

While the synthesis of benzofuran derivatives from suitable furan derivatives has been comparatively little investigated, the synthesis of fused two-ring and three-ring compounds containing a pyridine nucleus from furan derivatives has been more successful furo[3,2-c]pyridines (345),752>753 2,3-dihydrofuro[2,3-a ]quinolines (from 4,5-dihydro-3-furoic acid),754 acrophyllin (346), and 7-hydroxydictamnine (347) (from ethyl 2-ethoxy-4-oxo-4,5-dihydrofuran-3-carboxylate),755 are examples of compounds in this class which have been prepared. 

Several routes are available for the preparation of furo[3,2-c]pyridine itself starting both from furan (Scheme 12) (71BSF1727, 71JHC57, 74BSF515) and from pyridine derivatives (Scheme 13) (71CR(C)(272)2197, 72BSF1442). The latter synthesis gives (8) in an overall yield of 12%. 

Furo[3,4-c]pyridin-4-one derivatives have been prepared from 3,4-disubstituted furans (Scheme 20). Thus Michael addition of acetoacetic esters to /rans-3-hexene-2,5-dione gives adducts with a cyclohemiacetal structure (90) which easily dehydrates to furan derivatives (91) by treatment with acid. These compounds are suitable intermediates for the preparation of furo[3,4-c]pyridin-4-ones and furo[3,4-c]pyranones (Section 3.17.2.2.1) (78JHC993). These latter compounds are far more stable than the previously described furo[3,4-c]-pyridine itself. 

An appropriately substituted furan derivative (206 X,Y = Br, Cl), prepared from the corresponding ketone and a hydrazine, can undergo cyclization by displacing a halogen to give a furo[3,2-c]pyridazine (207) (Equation (72)) <86MI 707-05). 

Condensation of benzo[fr]furan-3(2H)-one with 1 in acetic acid in the presence of triethylamine afforded 2-(3-benzo[fr]furyl)dimedone 481, which upon acylation with acid anhydrides in the presence of 70% perchloric acid led to the corresponding tetrahydrobenzo[t>]furo[2,3-cJ-pyrylium perchlorate 482 (94CHE283). Similarly, benzo[fr]thieno[2,3-c]-pyrylium perchlorate 484 (94CHE283) and benzo[t>]seleno[2,3-cJpyrylium salt 485 were prepared (94CHE283). 

Furan derivatives are prepared by reaction of o-iodophenols. 2-Phenylbenzo-[ >]furan was prepared by the reaction of o-iodophenol (64) with 1-alkyne in one step [40]. It should be noted that similar 2-arylbenzo[i>]furan formation occurred by the use of Pd-free, copper-phosphine complex [41]. Similarly 2-substituted furo[3.2-i ]pyridine 66 was prepared from 2-iodo-3-pyridinol (65) in a one-pot reaction [42]. Naturally occurring ailanthoidol was synthesized by the reaction of 67 and 68 to give the cyclized product 69 [43]. 

Rhodium(lll)-catalyzed redox—neutral coupling of N-phenoxyacet-amides and alkynes led to benzo[l)]furan derivatives (13AGE6033). Furo[2,3-l)]pyran-6-one derivatives were prepared via rhodium(II)-catalyzed reactions of diazo compounds and ethynyl compounds (13T9294). Copper-mediated oxidative annulation of phenols and unactivated internal alkynes afforded benzo[l ]furan derivatives (13CS3706). E t-kaurane maoecrystalV was produced via C-H functionalization (13JA14552). Rhodium-catalyzed intramolecular C-H... 

---