Bis-heteroannulation

J. Marco-Contelles, The Paulson-Khand reaction on carbohydrate templates I. Synthesis of bis-heteroannulated-phyranosides, Tetrahedron Lett. 55 5059 (1994). 

A very neat method for the synthesis of furanoeremophilanes has been devised which incorporates a so-called bis-heteroannulation process.318 This is achieved by an intramolecular Diels-Alder reaction between an oxazole and an acetylenic grouping and is nicely demonstrated by the synthesis of ligularone (711) and petasalbine (712) (Scheme 67).319 A number of straightforward syntheses of... 

Jacobi has used intramolecular oxazole-alkyne Diels-Alder reactions, elegantly and with great success, to prepare a number of natural products containing fruan, lactone, and butenolide rings. These syntheses and the methodology based on the oxazole Diels-Alder reaction, termed bis-heteroannulation, have been reviewed in detaU. ... 

The first natural product synthesized using the bis-heteroannulation strategy was evodone, a structurally simple member of the naturally occurring furanoterpenes. The synthesis began with commercially available 4-methyl-8-valerolactone 170, which was converted to the cycloaddition precursor 171 in fom steps (Fig. 3.52). 

Hassner and Fischer " also studied the intramolecular bis-heteroannulation of oxazoles tethered to a variety of heterodienophiles. The azo-compounds 258 n = 3 ), prepared in situ via (diacetoxyiodo)benzene oxidation of the corresponding hydrazide in refluxing benzene, gave a 40% yield of 259 (n = 1-2) (Fig. 3.76). 

Many examples of the use of chiral Ca-symmetric bis(oxazoline) hgands have been presented here. Other examples include their use in various heteroannulations, one of which is shown in Figure 9.69. Here, the vinyl iodide, (Z)-3-iodo-2-methyl-2-propen-l-ol, 235 is condensed with 1,2-undecadiene to form the 3-methylene-2//-pyran derivative 237. " When this reaction was mn in the presence of 10 mol% of bis(oxazoline) Ugand 236 complexed with palladium(ll), 237 was produced in 70% yield with 79% ee. 

Metal-mediated electrophilic cyclizations of o-ethynylanilines leading to indoles have also been reported. For example, the gold(III)-catalyzed heteroannulation of bis-aniline 119 produced 2,2 -biindole 120 <04S610>. A similar heteroannulation reaction was reported utilizing copper triflate as the catalyst <04JOC1126>. 

Sbderberg et al. have developed a sequence of Stille coupling followed by palladium (O)-catalyzed reductive N-heteroannulation for the synthesis of tetrahydrocarbazo-lones 238 (Scheme 57) [216, 217]. Palladium(0)-catalyzed coupling of 2-nitroar-ylstannanes 236 with 2-iodo-2-cyclohexenones 235 afforded the 2-(2-nitrophenyl)-2-cyclohexenones 237. Cyclization with carbon monoxide in the presence of catalytic amounts of bis(dibenzylideneacetone)palladium, l,3-bis(diphenylphos-phino)propane (dppp), and 1,10-phenanthroline led to the corresponding tetrahy-drocarbazolones 238 which can be transformed to the carbazoles 32 by Wolff-Kishner reduction and subsequent aromatization. This approach has been applied to the formal synthesis of murrayaquinone A [216]. 

In 2008, this group reported the synthesis of quinoxalines [41], The reactions were performed using bis(dibenzylideneacetone)palladium(0), l,3-bis(diphenyl-phosphino)propane, and 1,10-phenanthroline in DMF under 6 bar of carbon monoxide at 70 °C. A -Heteroannulation of enamines derived from 2-nitroben-zenamines forming mixtures of 1,2-dihydroquinoxalines and 3,4-dihydroquinox-alin-2-ones in moderate to good yields (Table 9.4). Some mechanistic insights lent support for nitrosoarene/nitrene intermediates. 

In 1997, a detailed study of the heteroannulation of o-iodophenol with acetylenic substrates through palladium-copper catalysis leading to the synthesis of 2-substituted benzofurans was reported by Kundu and coworkers. Using bis(triphenylphosphine)palladium(ii) chloride-copper iodide as the catalytic system and triethylamine as the base and dimethyl-formamide as the solvent, the desired benzofurans were isolated in good yields (Scheme 2.53). An acyclic compound was isolated and proved to be the intermediate in the synthesis of the benzofurans. Some of the benzofurans have been transformed into biologically active compounds. In this... 

A novel palladium-catalyzed N-heteroannulation of enamines, formed by condensation of 2-nitrobenzenamines with aldehydes, to afford readily separafed 1,2-dihydroquinoxalines and 3,4-dihydroquinoxalinones (Scheme 69) has been developed by Soderberg ef al. [100]. The reaction catalyzed by bis(dibenzylideneacetone)palladium(0). 

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