Copper -catalyzed furan synthesis

Propose a mechanism for the following copper-catalyzed furan synthesis involving a tandem propargylation/cycloisomerization step. ... 

As demonstrated below, a Lewis acid-mediated reaction was utilized in the synthesis of dihydro[b furan-based chromen-2-one derivatives from l-cyclopropyl-2-arylethanones and allenic esters <070L4017>. The TiCh-catalyzed anti-Markovnikov hydration of alkynes, followed by a copper-catalyzed O-arylation was applied to the synthesis of 2-substituted benzo[6]furan <07JOC6149>. In addition, benzo[6]furan-based heterocycles could be made from chloromethylcoumarins <07SL1951>, substituted cyclopropanes <07AGE1726>, as well as benzyne and styrene oxide <07SL1308>. On the other hand, DBU-mediated dehydroiodination of 2-iodomethyl-2,3-dihydrobenzo[6]furans was also useful in the synthesis of 2-methylbenzo[Z>]furans <07TL6628>. 

Furane synthesis. Copper-catalyzed deco iposition of ethyl diazopyruvate (1) in the presence of cnol ethers or of alkynes provide a useful route to ethyl a-furoates. 

The copper catalyzed Diels-Alder reactions of a variety of dienes have been elegantly exploited by Evans as a key step in the synthesis of natural products (Sch. 49). The synthesis of tetrahydrocannabinol (219) [92] employs the acyclic diene 217 furan is used as a diene in the synthesis of shikimic acid (222) [93]. Although the methodology uses the very reactive catalyst 188, the reactions are still slow, suggesting that less reactive dienes require longer reaction times and higher temperatures for completion. A copper Lewis acid-mediated intramolecular Diels-Alder reaction has served as a key step in the total synthesis of isopulo upone [94]. 

In 2011, a palladium-catalyzed ring opening of furans as a source of a,p-unsaturated aldehydes was developed.In the presence of a palladium catalyst, heterocyclic compounds can be produced. In this procedure, furans may be ring-opened via pallado-catalyzed reactions leading to a,p-unsaturated aldehydes and ketones tethered to indole and isoquinoline moieties. Fu and co-workers developed a simple and efficient copper-catalyzed one-pot tandem method for the synthesis of benzimidazo[l,2-Z>]isoquinolin-ll-one derivatives... 

B.M. Aquila, A new synthesis of 8-methylpsoralen utilizing a palladium-copper catalyzed reaction to generate the furan ring and thus allowing for the generation of novel analogs in the 5 -position, Tetrahedron Lett. 38 (1997) 2795-2798. 

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>. 

A catalytic, enantioselective approach towards the synthesis of polyol chains has recently been reported by Carreira et al. and has been applied in a synthesis of the polyol subunit of amphotericin B (Scheme 5) [13]. Aldol addition of the silyl dienolate 26 to furfural (27) catalyzed by the Tol-BlNAP-CuF -complex (2 mol-%) gives rise to the addition product 28 in 95 % yield and >99 % ee after one recrystallization. Spectroscopic evidence indicates that a copper dienolate is formed in situ from the silyl dienolate 26 and is actually the active nucleophile [14], Standard transformations including a j-yw-selective reduction of the ft-hydroxy ketone by the method of Prasad and the oxidative conversion of the furan ring to the car-... 

A carboxyl group is removed from a heterocyclic nucleus in much the same way as from an aromatic nucleus (method 13), i.e., by thermal decomposition. The pyrolysis is catalyzed by copper or copper salts and is frequently carried out in quinoline solution. The reaction is important in the synthesis of various alkyl and halo furans. Furoic acid loses carbon dioxide at its boiling point (205°) to give furan (85%). A series of halo furans have been made in 20-97% yields by pyrolysis of the corresponding halofuroic acids. The 5-iodo acid decarboxylates at a temperature of 140°, whereas the 3- and 5-chloro acids requite copper-bronze catalyst at 250°. ... 

A new method for the synthesis of furan-substituted allenes via Cu(I)-catalyzed coupling of conjugated ene-yne-ketones with terminal alkynes was developed. A copper carbene migratory insertion was proposed as the key step in this transformation, with conjugated ene-yne-ketones as carbene precursors (14OL4082). 

Copper-mediated synthesis of 1,4-diaryl-l,2,3-triazoles 97 from iV-tosylhydrazones 96 and aniline was reported (13AG(E) 13324). Cu(ll)-catalyzed domino reactions of 2ff-azirines with diazotetramic and diazotet-ronic acids yielded synthesis of 2-substituted-2H-l,2,3-triazoles (130BC5535). Photooxygenation of azidoalkyl furans provided an endo-peroxide intermediate which underwent [3+ 2] cydoaddition to give... 

---