Benzo furans, alkyl

A palladium-catalyzed one-step synthesis of dihydrobenzo[fc]furan-based fused aromatic heterocycles from bifunctional bromoenoates or bromoalkyl indoles and iodoarenes was reported, and an example is provided in the scheme below <060L3601>. 2-Alkyl- or 2-aryl-substituted benzo[ >]furans were synthesized by a copper-TMEDA catalyzed intramolecular annulation from the corresponding ketones <06OL1467>. 

Benzofuran-3(2/f)-ones (396) exist in the keto form but undergo ready enolization. Acetylation with acetic anhydride and sodium acetate affords 3-acetoxybenzo[6]furans, but reaction under acidic conditions usually supplies these products admixed with 3-acetoxy-2-acetylbenzo[6]furans. Alkylation usually furnishes a mixture of O- and C-alkylated products. 3-Acetoxy-6-methoxy-4-methylbenzo[6]furan, on Vilsmeier reaction, supplies the 3-chlorobenzo[6]furan-2-carbaldehyde, the product expected from an enolizable ketone (72AJC545). Benzofuran-3(2//)-ones react normally with carbonyl reagents. Grignard reagents react in the expected way and dehydration of the intermediate affords a 3-substituted benzo[6]furan. The methylene group is reactive so that self condensation, condensation with aldehydes and ketones and reaction with Michael acceptors all occur readily. 

Benzo[6]furan may be alkylated with t- butyl chloride and zinc chloride, the products being the 2- and 3-substituted compounds in the ratio 1 2. Benzo[6]furan is chloromethylated at the 2-position. 2-Methyl- and 2-phenyl-benzo[ ]furan are chloromethylated in the 3-position. 

Photocyclization of A -alkylfuran-2-carboxyanilides conducted in inclusion crystals with optically active tartaric acid-derived hosts led to the formation of tricyclic /ra r-dihydrofuran compounds with up to 99% ee <1996JOC6490, 1999JOC2096>. 2-(/>-Alkoxystyryl)furans underwent photocyclization to give 5-(3-oxo-(/ )-butenyl)benzo[ ]furans as the predominant isomers in undehydrated dichloromethane as shown in Equation (59). The intermediate alkyl enol ether could be obtained by performing the reaction in anhydrous benzene <1999OL1039>. 

Both benzo[ >]thiophenes and benzo[ >]furans can be obtained from the thiophenol or phenol respectively, by S-/0-alkylation with bromoacetaldehyde acetal and then acid-catalysed ring closure involving intramolecular electrophilic attack on the ring. 

We decided to investigate one final substrate that contained our desired side chain for the intramolecular Diels-Alder cycloaddition as well as a small and removable cyano group. Our synthesis is outlined in Scheme 11. Phenol 53 was alkylated with chloroacetonitrile, then condensed to form 2-cyano benzo-furan 54. Subsequent quatemarization to 56 was accomplished with sodium hydride and a bromocrotcMiate (55) electrophile. Following phenol ether deprotection and reduction of the benzylic ketone with sodium borohydride, we were in a position to evaluate the dearomatization step. Unfortunately, all attempts to access the quinone epoxide 58 under classic or modified Adler-Becker reaction conditions failed. With these results, we closed the book on the second chapter in our vinigrol saga and went back to the drawing board. 

Other parameters of the palladium(n)-catalysed benzofuran synthesis were explored. Ultimately, it was found that the ideal system employed a 2 1 ligand/palladium ratio (10mol% Pd(OAc)2 and 20mol% ethyl nicotinate) and a substoichiometric amount (20mol%) of NaOAc at 100 °C. With this system in hand, a variety of substituted benzo-furans were accessed (Figure 9.7). The reaction was limited to electron-rich aryl systems the palladation event required a sufficiently nucleophilic arene in order to occur. The aryl subunit, however, tolerated an array of alkyl and alkoxy substitution patterns within the... 

The gold-catalyzed conversion of arylynamides provided benzo[(>]furans with amine fianctionality at the 2-position and alkyl groups at the 3-position (13CEJ12504). 6,7-Dihydrobenzo[fc]furan-4(5fJ)-ones and benzo[l>]furans could be obtained via gold(I)-catalyzed transformations (13CEJ12512). 

The mass spectrum of 2-pyrone shows an abundant molecular ion and a very prominent ion due to loss of CO and formation of the furan radical cation. Loss of CO from 4-pyrone, on the other hand, is almost negligible, and the retro-Diels-Alder fragmentation pathway dominates. In alkyl-substituted 2-pyrones loss of CO is followed by loss of a hydrogen atom from the alkyl substituent and ring expansion of the resultant cation to the very stable pyrylium cation. Similar trends are observed with the benzo analogues of the pyrones, although in some cases both modes of fragmentation are observed. Thus, coumarins. 

Benzo[b]furan, 2-alkyl-2,3-dihydro-synthesis, 4, 680 Benzo[b]furan, 2-amino-synthesis, 4, 710 Benzo[b]furan, 3-amino-tautomerism, 4, 38 Benzo[b]furan, 2-amino-2,3-dihydro-applications, 4, 708... 

Synthesis of 2-alkyl- or 2-aryl-substituted benzo[b]furans has been reported, involving a CuITMEDA complex which catalyzes the transformation of readily available ketone derivatives into the corresponding benzofurans in good-to-excellent yields in water (Eq. 6.13).29... 

Rhodococcus sp. Strain WU-K2R A Rhodococcus strain capable of sulfur-specific desulfurization of benzothiophene, naphthothiophene (NT), and some of their alkyl derivatives was reported [35]. The metabolites of BT desulfurization were BT sulfone, benzo[c][l,2]oxanthiin S-oxide, benzo[c][l,2]oxanthiin S,S-dioxide, o-hydroxystyrene, 2,(2 -hydroxyphenyl)ethan-l-al, and benzofuran. The NT metabolites were NT sulfone, 2 -hydroxynaphthyl ethene, and naphtho[2,l-b]furan [35], The exact biochemical pathway was not determined, however, part of the pathway for BT desulfurization was speculated to be similar to Paenibacillus All-2. 

Ebel s method is an adaptation of the Stoermer synthesis of benzo-[h]furans and involves the 0-alkylation of a phenolate anion (229, Scheme 58) with a 2-halocyclohexanone (230). The resultant 2-phenoxycyclo-hexanone 231 is then cyclized by poly phosphoric acid, usually at 100°C, or sometimes by concentrated sulfuric acid, to afford a 1,2,3,4-tetrahydrodi-benzofuran (232). Dehydrogenation to the dibenzofuran is often effected with palladized charcoal, but 2,3-dichloro-5,6-dicyano-l,4-benzoquinone ... 

III. Benzo[f]furan and Its Alkyl- and Monoaryl-Substituted Derivatives.142... 

AHC(18)337>. The 3-alkylbenzo[6 ]furans result from cyclodehydration of aryloxyacetones the most common dehydrating agents are sulfuric acid, phosphorus oxychloride and poly-phosphoric acid. The allyl ethers of phenols can be converted to 2-alkyl-2,3-dihydro-benzo[6]furan by heating with polyphosphoric acid, pyridine hydrochloride or magnesium chloride at 180 °C the intermediate o-allylphenol is not isolated. 

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