Furo pyridines, formation

The total synthesis of the furo[3,2-a]carbazole alkaloid furostifoline is achieved in a highly convergent manner by successive formation of the car-bazole nucleus and annulation of the furan ring (Scheme 15). Electrophilic substitution of the arylamine 30 using the complex salt 6a provides complex 31. In this case, iodine in pyridine was the superior reagent for the oxidative cyclization to the carbazole 32. Finally, annulation of the furan ring by an Amberlyst 15-catalyzed cyclization affords furostifoline 33 [97]. 

Disilylation of furo[3,4-r-]pyridine followed by dialkylation leads to the formation of a-disubstituted derivatives in good yields (61-70%). This methodology provides a key step in the synthesis of the pyridone alkaloid cerpegin, 54 <2004OL2925>. 

A [2+2+2] cyclization reaction of acetylenes and nitriles leads to the formation of furo[3,4-r]pyridines under cobalt-catalyzed conditions (Scheme 11) <2005SL1188>. 

A photocyclization of 3-(2-pyrrolyl)-3-amino-2-alkeneimines under acidic reaction conditions leads to the formation of pyrrolo[3,2-3]pyridine as shown in Equation (22) <1999T14079>. When oxygen or sulfur heteroatoms are substituted for the pyrrole ring nitrogen, the corresponding furo- and thieno[3,2-3]pyridines are formed. All of the photocyclizations require lengthy reaction times and the yields tend to be low, especially for the furopyridine derivatives. 

The palladium/copper-catalyzed coupling reaction of 2-iodo-3-methoxy-6-methylpyridine and terminal alkynes leads to the formation of o-methoxyalkynylpyridines which undergo electrophilic cyclization reactions to afford furo[3,2-3]pyridines in moderate yields <2005JOC10292>. A similar Pd/Cu-catalyzed reaction with hydroxypyridines and trimethylsilyl (TMS)-acetylene leads to the formation of alkynyl pyridines which cyclize to form furo[2,3- ]-pyridines in good yields <1998JME1357>. 

The copper(l) iodide-promoted ring closure of the pyridyl bromophenyl ketone 106 leads to the formation of 2-(3 -bromophenyl)furo[2,3-r-]pyridine as shown in Equation (46) <2005JOC6964>. 

Scope of this synthetic strategy is not limited to benzofiirans. The reaction of 2-iodo-3-hydroxypyridine and 1,1 -diethoxy-2-propync under Sonogashira coupling conditions (palladium-copper catalyst system) leads to the formation of the substituted furo[3,2-6]pyridine shown in 3.56.72... 

A one-step synthesis of furo[3,2-c]- and furo[3,2-6]-pyridines has been realized using a cycloaddition reaction of an alkynic compound with 3,5-dichloropyridine 1-oxide (Scheme 15) (75JA3227). Formation of (75) probably proceeds through a 1,2-dihydropyridine (73) with a subsequent 1,5-sigmatropic shift to (74) elimination of hydrogen chloride yields... 

A wealth of literature has been amassed concerning the synthesis and utility of the furo-1,3,2-dioxathiole ring system, particularly in the area of carbohydrate synthesis. The furo[3,4-d]-1,3,2-dioxathiole system may be conveniently prepared by treatment of a tetrahydrofuran-3,4-diol species with SOCl2 in the presence of pyridine cw-diols favor the formation of the desired cyclic sulfite... 

The synthesis of heterocycles via rDA processes includes the preparation of heterocycles with two different heteroatoms. Furo[3,4-c]pyridine (218), a previously unknown polyheterocyclic, has beat achieved by FVP of adduct (217) (equation 98). The heteropentalene Aieno[3,4-6]fuian (220) has been synthesized by a reaction pathway based upon rDA formation of polyheterocycle (219) (equation 99). Other heterocycles prepared via rDA reactions that contain two differoit heteroatoms include 6H-l,3-oxazin-6-one (221) and 3-arylisoxazoles (222). ... 

Much work has been done on the photochemical ring-expansion of pyridine A -imides to 1,2-diazepines, but it has previously not proved possible to extend this reaction to the formation of 2,3-benzodiazepines (58) from isoquinoline A -imides (57). Now, however, it has been shown that this reaction can be effected in 30-50% yield if it is done in the presence of base. Full reports have now been published on the photolysis of thieno-, furo-, and pyrrolo-[ ]- and -[c]-pyridine A -imides. These reactions give both 1,2-and 1,3-diazepines fused to the heteroaromatic rings (see these Reports, Volumes 2 and 3). 

Reaction of the arylamine 62 with the complex salt 52 in acetonitrile at room temperature afforded complex 64 in 87% yield (Scheme 17) [125]. Subsequent oxidative cyclization, aromatization and demetalation using iodine in pyridine provided carbazole 65 in 71% yield. Heating of compound 65 in chlorobenzene in the presence of the acidic cation exchange resin amberlyst 15 led to ring closure with formation of the furo[3,2-a]carbazole 66. Oxidation of the methyl group at C-3 to a formyl group using 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ)... 

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]. 

Cyclization of iodopyiidinyl aUyl ethers derived fom dihalopyridines and sodium aUyUc oxides leads to formation of furo[2,3-fc]pyridines 292, furo[3,2-c]pyiidines 293, and furo[2,3-c]pyridines 294 by a Heck mode of reaction (Scheme 101). In the reaction sequences, the initial step in the preparation of iodopyridine aUyl ethers involves regioselective lithiation of 3-fluoro, 2-fluoro-, and 4-chloropyridines with LDA. Subsequently, the lithiated species are treated with iodine as electrophile. A variety of iodopyiidinyl ethers have been prepared from dihalopyridines and sodium aUyhc oxides and subjected to the Pd-catalyzed cyclization reactions with formation of the furoannulated pyridine products. When the allyl groups carry a 2-substituent as in stracture 295, hydridopaUadium elimination is prevented. Instead, sodium formate reductive elimination of the palladium substituent gives the product 296. The isomeric structures 297 and 298 are available similarly. ... 

Later, Tu and coworkers [57] reported domino synthesis of furo[3,4-h][l, Sjnaphthyridines 93 through three-component reactions of aldehydes 69, 2-aminoprop-l-ene-l,l,3-tricarbonitrile 29, and N-substituted 4-aminofuran-2(5H)-ones 57 in EtOH using EtONa as a base (Scheme 12.36). N-substituted 3-aminocyclohex-2-enones were also suitable for this domino reaction, affording 21 examples of benzo[h][l,8]naphthyridines in 69-84% chemical yield, with the concomitant formation of two new pyridine rings. 

---