Alkynes, furans from

When these cycloaddition reactions are carried out with alkynes, furan derivatives are formed. lodonium ylide 5, for instance, on photochemical reaction with alkynes 43, gives benzofurans 44 (86JOC3453) (Eq. 19). In a similar way, the iodonium ylide derived from 2-hydroxy-1,4-naphthoquinone undergoes a cycloaddition reaction with phenylacety-lene to yield benzofuran 45 (Scheme 16) (89LA167). 

A new strategy for the synthesis of highly substituted benzo[lr]furans from weta-substituted hydroxybenzenes and alkynes via a rhodium(III)-catalyzed activation of a sterically hindered C-H bond was demonstrated. A possible mechanism involving dual directing group-assisted ortho C—H bond activation was proposed (14OBC9105). 

This transformation was applied in the sequential one-pot synthesis of disubsti-tuted benzo[6]furan from dichlorophenol, terminal alkyne, and boronic acid [42]. In this case, water was used as the cosolvent to conduct successfully the SuzuM-Miyaura coupling reaction after chlorobenzo[(i]furan formation (Scheme 23). The use of two ligands, Cy-DHTP and XPhos, was necessary to promote the formation... 

Cao, H., Jiang, H. F., and Huang, H. W. 2011. Transition-metal-catalyzed domino reactions Efficient one-pot regiospecific synthesis of highly functionahzed polysubstituted furans from electron-deficient alkynes and 2-yn-l-ols. Synthesis. (7) 1019—1036. 

The above approaches can also be applied to a range of other aromatic heterocycles, including furans, thiophenes and oxazoles [2, 15]. While these protocols typically require the initial assembly of the precursor for cyclization, Trost has demonstrated that palladium catalysis can also be employed to assemble the en-yn-ol 8 for cyclization to furans. (Scheme 6.11) [16]. This reaction, that proceeds via the palladium-catalyzed regioselective addition of terminal alkynes to internal propargyl alcohols, provides a biomolecular method to build up furans from these two alkyne building blocks. 

Many research groups further investigated the scope of the Rh(II)-catalyzed synthesis of furans from alkynes and a-diazocarbonyl compounds [194, 209-221]. Some representative results are summarized in Scheme 8.70. Tri- and tetra-substi-tuted furans possessing a vast array of functional groups and diverse substitution patterns could be efficiently accessed via this methodology. 

Pang W, Zhu S, Xin Y, Jiang H, Zhu S (2010) Rh2(OAc)4 catalyzed formation of fluorine-containing polysubstituted furans from diazocompounds and aromatic alkynes. Tetrahedron... 

Reaction with Alkynes. Furane and naphthalene derivatives can be synthesized from 1,3-dicarbonyls and alkynes (eq 25). Large substituents on the alkyne can lower the reaction yield. 

Cao et al. [65] have reported that carbon nanotubes (CNT) supported copper oxide catalyzed S5mthesis of tetra-substituted furans from electron deficient alkynes and a-hydroxy ketones (Scheme 43). 

The furan ring is a common structural motif present in many biologically active molecules and pharmaceutical substances. Accordingly, the development of efficient synthetic routes to produce furans has been a major research field for over a century. Transition-metal-catalyzed transformations are probably the most powerful tools presently available for preparing furans from readily accessible starting materials [47-56]. Alkynes have been widely employed as building blocks for this end. In this context, the first metal-mediated synthetic approach to furocoumarins involving... 

The cyclic enol ether 255 from the functionalized 3-alkynoI 254 was converted into the furans 256 by the reaction of allyl chloride, and 257 by elimination of MeOH[132], The alkynes 258 and 260, which have two hydroxy groups at suitable positions, are converted into the cyclic acetals 259 and 261. Carcogran and frontalin have been prepared by this reaction[124]. 

Hydroxy-THISs react with electron-deficient alkynes to give nonisol-able adducts that extrude carbonyl sulfide, affording pyrroles (23). Compound 16 (X = 0) seems particularly reactive (Scheme 16) (25). The cycloaddition to benzyne yields isoindoles in low- yield. Further cyclo-addition between isoindole and benzyne leads to an iminoanthracene as the main product (Scheme 17). The cycloadducts derived from electron-deficient alkenes are stable (23, 25) unless highly strained. Thus the two adducts, 18a (R = H, R = COOMe) and 18b (R = COOMe, R = H), formed from 7, both extrude furan and COS under the reaction conditions producing the pyrroles (19. R = H or COOMe) (Scheme 18). Similarly, the cycloadduct formed between 16 (X = 0) and dimethylfumarate... 

Cyclotrithiazyl chloride is also a useful reagent in organic chemistry in the fusion of 1,2,5-thiadiazoles to quinones as well as the synthesis of (a) isothiazoles from 2,5-disubstituted furans and (b) bis-1,2,5-thiadiazoles from A-alkylpyrroles (Scheme 8.4). Alkenes and alkynes react readily with (NSC1)3 to give 1,2,5-thiadiazoles, while 1,4-diphenyl-1,3-butadiene gives a variety of heterocyclic products including a bis(l, 2,5-thiadiazole). ... 

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). 

Snieckus and his group members [104] used the known domino Sonogashira/ Castro-Stephens reaction [105, 106] for the synthesis of the natural product pli-cadin (6/1-209), this having been isolated from Psorelia plicata in 1991 [107]. In this synthesis, Pd°-catalyzed reaction of the alkyne 6/1-210 and the iodobenzene derivative 6/1-211 in the presence of Cul led to the furan 6/1-212, which was transformed into 6/1-209 via 6/1-213 (Scheme 6/1.54). There are some discrepancies of the physical data of the natural and the synthetic product thus, it might be possible that the natural product has a different structure. It should also be mentioned that the... 

Diterpenoids related to lambertianic acid were prepared by intramolecular cyclization of either an alkene or an alkyne with a furan ring <2005RJ01145>. On heating amine 101 with allyl bromide, the intermediate ammonium ion 102 was formed which then underwent [4+2] cycloadditions in situ to give the spiroazonium bromides 103 and 104 (Scheme 13). These isomers arose from either endo- or co-transition states. The analogous reaction was also carried out with the same amine 101 and propargyl bromide. The products 105 and 106 contain an additional double bond and were isolated in 58% yield. The product ratios of 103 104 and 105 106 were not presented. 

Ethyl diazopyruvate, under copper catalysis, reacts with alkynes to give furane-2-carboxylates rather than cyclopropenes u3) (Scheme 30). What looks like a [3 + 2] cycloaddition product of a ketocarbenoid, may actually have arisen from a primarily formed cyclopropene by subsequent copper-catalyzed ring enlargement. Such a sequence has been established for the reaction of diazoacetic esters with acetylenes in the presence of certain copper catalysts, but metallic copper, in these cases, was not able to bring about the ring enlargement14). Conversely, no cyclopropene derivative was detected in the diazopyruvate reaction. 

The Pd-catalysed cyclisation of ( >3-alkyny]-3-tnfluoromethyl allylic alcohols 2, derived from a cross coupling reaction between terminal alkynes and the 3-iodo alcohols 1, yields the pyrans 3 rather than the expected furan derivatives (Scheme 1). It appears that the electron-withdrawing properties of the CF3 group assist the 6-endo-dig cyclisation . 

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... 

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