Furans preparation from dicarbonyl

Pyrans 342 were prepared from furan derivatives 241, readily accessible by the reaction of glucose with /J-dicarbonyl compounds.328 The reaction was accomplished under acidic conditions and probably proceeds according to Eq. (16). 

Radical cyclization of divinyl ethers prepared from the reaction of 1,3-dicarbonyl compounds and ethyl propynoate gave rise to trisubstituted furans as shown in Ae following example <03TL2125>. 

Synthetically, compound 152 was prepared by the Friedel-Crafts procedure from furan-3,4-dicarbonyl chloride and a tetralin derivative (85JCR (S)338). 1,4-Dihydro-l,4-epoxy-5,8-naphthoquinone, when treated with 3,6-di(2-pyridyl)-l,2,4,5-tetrazine, yielded the quinone 153 (75JCS(P1)1339) derivatives of 153 are also known (74CC1034). The parent compound (153) is a stable derivative of the unstable isobenzofuran. Finally, 3-acetyl-2-furyl-1,4-benzo- (or -naphtho-) quinones are isomerized photochemically in aprotic solvents into the quionones 154 (66HCA1806). 

The ring synthesis of five-membered heterocycles has been extensively investigated, and many and subtle methods have been devised. Each of these three heterocyclic systems can be prepared from 1,4-dicarbonyl-compounds, for furans by acid-catalysed cyclising dehydration, and for pyrroles and thiophenes by interaction with ammonia or a primary amine, or a source of sulfur, respectively. 

Other interesting methods can generate furans. One method treats an allylic diol such as 125 with pyridinium chlorochromate (PCC see Chapter 17, Section 17.2.3), in an oxidative-cyclization process, to give 3-ethylfuran, 126. Thiophene derivatives can also be prepared from 1,4-dicarbonyl compounds. A Paal-Knorr thiophene synthesis reacts 2,4-hexanedione (115) with phosphorus pentasulfide (P4S10) to give 2,5-dimethylthiophene, 127. 

Pyrroles furans and thiophenes are prepared from y-dicarbonyl compounds... 

A 4% sodium amalgam is prepared from the careful addition of sodium (3 g, 130 mmol), in small portions, to mercury (650 g, 3.25 mol), which is rapidly stirred. The amalgam is allowed to return to room temperature over 1 h, and then a tetrahydro-furan (100 mL) solution of tetracarbonyl(dicyclopentadienyl)diiron (10.62 g, 30 mmol) is added in one portion and is efficiently stirred for 2 h. The amber tetrahydrofuran solution of sodium dicarbonyl(cyclopentadienyl)ferrate is separated from the amalgam and transferred to a new flask via syringe. This solution is cooled to 0 °C and l-bromo-2,2-di-methoxypropane (llg, 60 mmol) in tetrahydrofuran (10 mL) is added dropwise over 30 min. The yellow-brown solution is stirred at 0 °C for a further 30 min and then at room temperature for 3 h. The solvent is removed, and the residue is extracted with pentane (ca. 

Aside from alcohols, other oxygen nucleophiles have also participated in hydroalkoxylation reactions with alkynes. The most common of these are 1,3-dicarbonyl compounds, whose enol oxygens are readily available to add to alkynes. Cyclization reactions of this type have been carried out under Pd(0) catalysis with various aryl or vinyl iodides or triflates, often in the presence of CO, affording the corresponding furan derivatives (Equation (95)).337-340 A similar approach employing cyclic 1,3-diketones has also been reported to prepare THFs and dihydropyrans under Pd, Pt, or W catalysis.341 Simple l-alkyn-5-ones have also been isomerized to furans under the influence of Hg(OTf)2.342... 

The acid fission of furans, to yield 1,4-dicarbonyl compounds, is not satisfactory from the preparative point of view. This fission reaction has recently been restudied.169, 287-292 It is preferable to use the route involving 2,5-dialkoxy-2,5-dihydrofurans, which on hydrogenation and acid hydrolysis give the desired 1,4-dicarbonyl compounds. 

As illustrations of the variety of methods available, the three processes below show (i) the addition of isonitrile anions to a,P-unsaturated nitro-compounds, with loss of nitrous acid to bring about aromatisation, (ii) the interaction of thioglycolates with 1,3-dicarbonyl-compounds, for the synthesis of thiophene 2-esters, and (iii) the cycloaddition/cycloreversion preparation of furans from oxazoles. 

Furan Dlcarbonyl Chloride. Kelly s procedure was followed, with modification to prepare 2,3-furan dicarbonyl chloride. A mixture of 5.30 g (0.034 mole) of 2,3-furan dicarboxylic acid (purified by recrystallization from a small volume of acetic acid) in 250 ml of anhydrous ether was stirred magnetically in a flask cooled in an ice-water bath and equipped with an efficient condenser and a drying tube containing calcium chloride. 

Fluorinated 1,4-dicarbonyl compounds of the type 987, which carbonyl groups are mounted on an aromatic core, are common starting materials for the preparation of chain-fluorinated phthalazines and their analogues. Apart from benzene derivatives 1003 [605] and 1005 [606] (Scheme 214), derivatives of azulene [607], indene [608] and furane [609] were introduced into these transformations. 

Consider the Johnson synthesis of progesterone. The q clization precursor (102) was derived from cyclopentenone 101, which was prepared by an intramolecular aldol-dehydration of 1,4-diketone 100. Johnson did not construct the 1,4-difunctional relationship present in 100. It was purchased in the form of 2-methylfuran (96). This simple heterocyclic compound is at the same oxidation state as the 1,4-dicarbonyl compound, released by hydrolysis of the furan, first in a protected form (98 and 99) and finally ready for use in the aldol dehydration (99 — 100). 

---