2.4- Disubstituted furans, formation

The addition of trithiazyl trichloride (NSC1)3 to 2,5-disubstituted furans and to N-2,5-trisubstituted pyrroles has led to the formation of isothiazole derivatives <96JHC1419>. 

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

In 1985, Tsuji s group carried out a Pd-catalyzed reaction of propargyl carbonate with methyl acetoacetate as a soft carbonucleophile under neutral conditions to afford 4,5-dihydrofuran 109 [89-91]. The resulting unstable 109 readily isomerized to furan 110 under acidic conditions. In addition, they also reported formation of disubstituted furan 112 via a Pd-catalyzed heteroannulation of hydroxy propargylic carbonate 111 [92], Presumably, an allenylpalladium complex (c/. 114) was the key intermediate. 

Furthermore, intercepting the furylpalladium(II) species 130 with an electrophile would result in a carbodepalladation in place of protodepalladation. Therefore, a tandem intramolecular alkoxylation of p.y-acetylenic ketone 127 was realized to afford trisubstituted furan 131 when allyl chloride was added to the original recipe [103]. 2,2-Dimethyloxirane was used as a proton scavenger, ensuring exclusive formation of 3-allylated 2,5-disubstituted furan 131 without contamination by protonated furans. 

The application of immobilized heterobimetallic cobalt-rhodium in nanoparticles has also been reported. In the presence of water, CO, and amine, internal acetylenes 119 were converted to 3,4-disubstituted furan-2(5H)-ones 120 and 121 in high yields, in which an amine was necessary for the formation of furanone and a higher CO pressure was required for good yield (Equation (8)). It is important to notice that the catalyst has been easily recovered without loss of activity or formation of hydrogenated side-products. The reaction proceeded in good yield for the symmetric substrates (entries 1 and 2) while it always gave two regioisomers for asymmetric alkyne substrates (entries 3-8). The isomer ratio was dependent on the steric and electronic nature of the substituents. 

Treatment of lithiated (41) with aldehydes (42a-c) at -78 °C and then at room temperature gives the corresponding alcohols (43a-c) in yields up to 80%. When (43a-c) were refluxed in benzene containing a catalytic amount of p-toluenesulfonic acid the 2-substituted furans (44a-c) were formed in good yields. Various 2,3-disubstituted furans were readily prepared by combination of the synthetic methods for 2- and 3-substituted furans (Scheme 9). The synthetic utility of this route is illustrated by the preparation of 2-(3,7-dimethyl-2,6-heptadienyl-3-methylfuran (47), which is a typical 2,3-disubstituted furan occurring in nature, starting from the aldehyde (46) and the acetal (45) (Scheme 10). Table 1 summarizes the 2,3-disubstituted furans synthesized by this route. However, attempts to extend the method to the preparation of 3-acylfurans (48) was unsuccessful because of the formation of the vinyl sulfone (49) via deacylation. 

A more detailed view of the selectivities (Table 12.5) reveals a selective formation of the 2,4-disubstituted furan with the copper(I) catalysts (entries 1 and 2), a low... 

Two sequential electrochemical annulations of an electron-rich 3,4-disubstituted furan ring were employed to generate the fused tricyclic ring system of arteannuins. The second reaction, as depicted below, represented the formation of a quaternary carbon center by a formal 6-endo cyclization under these anodic oxidation conditions <07OL4599>. 

Migration of the phenylsulfanyl group was suggested as a key step in formation of 2,5-disubstituted furans 243 and 244 from ketopropargyl sulfides 245, by heating them at 130 °C in the presence of catalytic amounts of Cul... 

Although less common than conversions of a,3-, and of p,Y-acetylenic ketones, Y,5-alkynones can also lead to formation of furans. The Y,8-acetylenic ketone 227 undergoes a Pd-catalyzed cyclization to furnish 2,5-disubstituted furan 228 (no yield provided) [180]. 

A novel organophosphine-mediated protocol for the construction of substituted furans with different substitution patterns was disclosed, in which a variety of y-aroyloxy butynoates were converted to 2,3- and 2,4-disubstituted furans as well as 2,3,5-trisubstituted furans as shown below <04JA4118>. Another phosphine-initiated reaction leading to the formation of vinylfurans with substituents on the furan ring using 2-penten-4-ynones and a various aldehydes was also published <04T1913>. 

The diastereoselective [4 + 3] cycloaddition between 2,5-disubstituted furans and vinylthionium ions was achieved (140L4476). The vinylthio-nium ion was generated either from a ort/io-phenylethynylbenzoyl allylic ester in the presence of a gold catalyst or from the allylic alcohol with a Bronsted acid. However, using 2-substituted furans led predominantly to the formation of Friedel-Crafts alkylated products. 

The same researchers also reported a very facile cycloisomerization reaction of allenyl ketones 15 into furans 16 in the presence of gold(III) catalyst (Scheme 8.7) [46, 103-112]. Furthermore, the authors extended this reaction to the cydoisomeriza-tion-addition cascade process of allenyl ketones 15 with enones 17 to produce 2,5-disubstituted furans 18 (Scheme 8.8) [111]. Formation of the latter products was rationalized via two proposed pathways. According to path A, fiiran intermediate 16 undergoes an auration with Au(III)-catalyst to produce the furyl-gold species, which, upon subsequent 1,4-addition to the Michael acceptor 17, generates intermediate 19... 

---