Furan with carbenes

Furan and thiophene undergo addition reactions with carbenes. Thus cyclopropane derivatives are obtained from these heterocycles on copper(I) bromide-catalyzed reaction with diazomethane and light-promoted reaction with diazoacetic acid ester (Scheme 41). The copper-catalyzed reaction of pyrrole with diazoacetic acid ester, however, gives a 2-substituted product (Scheme 42). 

The only known reaction of a furan with a dihalocarbene is that recently reported between benzofuran and dichlorocarbene in hexane at 0°. The initial adduct (7) could not be isolated but on hydrolysis gave the ring-expanded product 8, possibly via 9, in 15% yield. Benzothiophene was recovered in 92% yield under the same conditions. 2,5-Dihydrofuran reacted with dichloro- and dibromo-carbene to give the products of allylic insertion, 2-dihalogenomethyl-2,5-dihydrofuran, as well as the normal addition products. ... 

Thus photolysis of the tosylhydrazone sodium salt of 5//-dibenzo[a,c]cyclohepten-5-one (14) at — 60 °C in the presence of cyclopentadiene or furan with tetrahydrofuran as cosolvent gave the cyclopropene Diels-Alder adducts 17 and 18 in 73 and 47% yields, respectively. If the photolysis was stopped shortly after all the tosylhydrazone salt had decomposed, adduct 17 was the only isomer found in the cyclopentadiene reaction. In the formation of the furan adduct 18, the reaction was not so clean and a number of unidentified products were also formed. Unfortunately, adduct 18 is thermally unstable at the temperature necessary for thermal formation of carbene 15. No trace of adduct 18 was detected when the arylcarbene 19 was generated directly from its tosylhydrazone salt in the presence of furan. ... 

Homothiophene and homofuran (10, X = S, O) are the most reactive substrates. They are easily prepared by carbene addition (using diazomethane as carbene precursor) to thiophene and furan, respectively. Since carbene insertion into the a-carbon-hydrogen bond of diethyl ether (which is usually used as a solvent) competes with carbene addition to the aromatic system, the diazomethane solution for carbene generation is most conveniently prepared using the reactant as solvent. ... 

Treatment of ) -hydroxyketones or j8-trimethylsilyloxyketones with trimethylsilyldiazomethyl-lithium yields 2,3-dihydrof urans, which can be dehydrogenated to furans with mangenese dioxide (Scheme 18) <94SL46i>. Obviously a carbene is an intermediate in the first step of the reaction. 

Previously, only a handftil of reports have demonstrated asymmetric hydrogenation of mono-substituted furans, with limited scope and enantioselectivities. In a new study (14AGE8751), a Ru(II) complex bearing the chiral N-heterocyclic carbene ligand SINpEt was employed to successfully hydrogenate disubstituted furans to chiral tetrahydrofu-rans. In the case of 2,4-disubstituted furans, products were obtained with excellent enantio- and diastereoselectivity.The cis isomer was the major product. 

Gold(I)-catalyzed intermolecular cyclization of furans with alkynes produced phenols. Under the same conditions, 1,3-diphenylisobenzofuran reacted with alkynes forming 2,3-disubstituted indenes via a cyclopropyl gold carbene (13CEJ6581). 

Computational methods used to evaluate practical application of biomass-derived furanic compounds indicate that in pyrolysis of 2-methylfuran ketene generation occurs by 1,5-hydrogen migration with carbene formation followed by concerted ring opening to form ketene and propyne with a barrier of 287.3 kj mol, as computed at the CBS-QB3 level of theory (Scheme 4.25). Routes to vinylketene and aUenylketene were also found. 

The insertion of alkynes into a chromium-carbon double bond is not restricted to Fischer alkenylcarbene complexes. Numerous transformations of this kind have been performed with simple alkylcarbene complexes, from which unstable a,/J-unsaturated carbene complexes were formed in situ, and in turn underwent further reactions in several different ways. For example, reaction of the 1-me-thoxyethylidene complex 6a with the conjugated enyne-ketimines and -ketones 131 afforded pyrrole [92] and furan 134 derivatives [93], respectively. The alkyne-inserted intermediate 132 apparently undergoes 671-electrocyclization and reductive elimination to afford enol ether 133, which yields the cycloaddition product 134 via a subsequent hydrolysis (Scheme 28). This transformation also demonstrates that Fischer carbene complexes are highly selective in their reactivity toward alkynes in the presence of other multiple bonds (Table 6). 

Alkoxy(carbene)iron(0) and amino(carbene)iron(0) complexes usually react with alkynes to give rj4-pyrone iron complexes and furans, respectively [54]. Nevertheless the chemoselective formation of naphthols was reported for alkoxy(carbene)iron(0) complexes with the electron-poor alkyne dimethyl... 

Silylfiirans are available from acylsilane dicarbonyl confounds <96JOC1140>. Fhotocycloaddition of 35 with aUcenes leads cleanly to tetrasubstituted furans 38 in yields of 85%. A mechanism is proposed involving an alkyl propargyl biradical (as 36) that closes first to a vinyl carbene (as 37) and than to 38 <96JOC3388>. 

An interesting variation appears when furan reacts with the allenic carbene generated by the action of potassium ter-butoxide upon l-bromo-3,3-dimethylallene. Though the yield is only 9%, one product is reasonably assigned a structure (Scheme 52) that could hardly be approached by way of a cyclopropane intermediate. The authors comment that in an allenic carbene in the singlet state two electrons will be accommodated in the sp... 

Unexpectedly, some diazoesters seem to react by way of carbene intermediates even in highly ionic media at room temperature.276 With acetic acid alone 2-furyldiazoacetic ester supplies two products retaining the furan ring. But if the acetic acid is mixed with ether or dichloromethane then a Z-alkenyne (Scheme 53) appears just as if a carbene had been formed. The... 

Reaction of a tungsten carbene complex with alkynyllithium followed by treatment of aldehyde in the presence of Et3Al afforded trisubstituted furans in good to excellent yields <06AG(I)6874>. Dienes were the products without Ft,AI. 

Etherification using a metal vinylidene has also been combined with G-G bond formation through the reaction of an alkynyl tungsten complex with benzaldehyde (Scheme 14). The addition of an internal alcohol to the incipient /3,/Udialkylvinylidene that is generated leads to dehydration and the formation of a Fischer-type alkylidene complex. Further reactions of this carbene with a range of nucleophiles have provided access to various furan derivatives.374,375... 

Furans. Reaction of a,a-dimethoxy ketones with 1 affords a dihydrofuran (2) presumably via a carbene (a) that inserts intramolecularly into a C—H of an adjacent methoxy group. The reaction often results directly in a furan, since the elimination of methanol from 2 is facile. 

The 774-vinylketene complex (85) could be oxidatively decomplexed with Ce(IV) to afford the lactone (87). Although no reaction was observed with methanol (unlike a postulated chromium analogue16,18 26), treatment with sodium methoxide produced the expected /3, y-unsaturated ester (88). Thermolysis of complex 85 afforded no trace of the naphthol that one would expect33 from a proposed chromium vinylketene complex with the same syn relationship between the phenyl group and the ketene moiety. Instead, only the furan (89.a) was seen. Indeed, upon exhaustive reaction of tricarbon-ylcobalt carbenes (84 and 90) with different alkynes, the furans (89.a-d) were isolated as the exclusive products in moderate to excellent yields. 

The intermediate vinylketene complexes can undergo several other types or reaction, depending primarily on the substitution pattern, the metal and the solvent used (Figure 2.27). More than 15 different types of product have been obtained from the reaction of aryl(alkoxy)carbene chromium complexes with alkynes [333,334]. In addition to the formation of indenes [337], some arylcarbene complexes yield cyclobutenones [338], lactones, or furans [91] (e.g. Entry 4, Table 2.19) upon reaction with alkynes. Cyclobutenones can also be obtained by reaction of alkoxy(alkyl)carbene complexes with alkynes [339]. 

Depending on the types of substituents and the precise reaction conditions (l,3-butadien-l-yl)carbene complexes can undergo direct cyclization to yield cyclo-pentadienes [337,350]. As mentioned in Section 2.2.5.1, cyclopentadiene formation occurs particularly easily with aminocarbene complexes [351]. Alternatively, in particular at higher reaction temperatures, CO-insertion can lead to the formation of a vinylketene complex, which, again depending on the electronic properties of the substituents and the reaction conditions, can cyclize to yield cyclobutenones, furans [91,352], cyclopentenones, furanones [91], or phenols (Dotz benzannulation) [207,251,353]. 

Fig. 4.24. Reaction of electrophilic carbene complexes with furans and pyrroles leading to ring-opening of the heterocycle [1429].

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