Benzo furans, alkyl synthesis

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>. 

Benzo[6]furan, 2-(3-alkoxypropylaminomethyl)-2,3-dihydro-properties, 4, 708 Benzo[6]furan, 2-alkyl-acylation, 4, 606 Benzo[6]furan, 3-alkyl-synthesis, 4, 680... 

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... 

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... 

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 ... 

A Ni-catalyzed cyclization cross-coupling reaction of iodoalkenes with alkyl zinc halides has been employed for the synthesis of various tetrahydrofuran derivatives <2007AGE-ASAP>. The TiCU-catalyzed anti-Markovnikov hydration of alkynes has been applied to the synthesis of various benzo[3]furans <2007JOC6149>. 

Condensation of salicylaldehyde and its derivatives with a variety of esters of chloroacetic acids in the presence of TBAB led to the synthesis of benzo[b]furans by means of a solid-liquid PTC reaction under the action of microwave irradiation [39]. This was a modification of one of the most popular routes to substituted benzo[b]furans, i.e. O-alkylation of O-hydroxylated aromatic carbonyl compounds with a-halogenated carbonyl compounds then intramolecular condensation. The mixture of aldehydes and chloroacetic acid esters were absorbed on potassium carbonate then irradiated in an open vessel in a domestic MW oven for 8-10 min (Eq. 26). 

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