Benzofuran reaction with carbenes

Nitrogen [186], oxygen [187], and sulfur nucleophiles [170] also act as nice Michael donors in the tandem MCI reactions [Eq. (106)]. The a-oxyalkylidene carbene 116, generated by the reaction with phenoxide anion, shows a high selectivity for 1,5-insertion to the aromatic over the aliphatic C-H bonds to give the benzofuran. 

The only known reaction of a furan with a dihalocarbene is that recently reported between benzofuran and dichlorocarbene in hexane at 0°. The initial adduct (7) could not be isolated but on hydrolysis gave the ring-expanded product 8, possibly via 9, in 15% yield. Benzothiophene was recovered in 92% yield under the same conditions. 2,5-Dihydrofuran reacted with dichloro- and dibromo-carbene to give the products of allylic insertion, 2-dihalogenomethyl-2,5-dihydrofuran, as well as the normal addition products. ... 

A plausible pathway is that the aromatisation of the cyclohexadienone 92 by a proton shift is accelerated in the presence of Ac20 under formation of acetate 93. The simultaneously generated acetic acid then cleaves the acetate to form the free phenol 94 (Scheme 44). This effect was observed for the first time during studies towards the total synthesis of the lipid-alternating and anti-atherosclerotic furochromone khellin 99 [64].The furanyl carbene chromium complex 96 was supposed to react with alkoxyalkyne 95 in a benzannulation reaction to give the densely substituted benzofuran derivative 97 (Scheme 45). Upon warming the reaction mixture in tetrahydrofuran to 65 °C the reaction was completed in 4 h, but only a dimerisation product could be isolated. This... 

Benzannulation reactions of Fischer carbene complexes have proved a useful route for the synthesis of benzene rings fused to one furan ring and one additional heteroaromatic ring (Equation 96) <2005TL2211>. Thus, reaction of chromium carbene complex 168 with the conjugated dienyne systems produces benzofuran derivatives (Table 7). 

Reaction of alkynylbisiodonium ditriflates (48) with sodium phenoxide gave rise to good yields of benzofurans by 1,5-CH insertion of the intermediate alkylidenecarbene (49).61 The selectivity of 1,5-CH insertion of carbene (50) was observed to be highly dependent on the method of carbene generation.62... 

Various 2-substituted benzofurans 165 are obtained by the interaction of iodo-nium salts 164 with sodium phenoxide in methanol (Scheme 63) [126, 127]. This reaction proceeds via the intramolecular alkylidene carbene insertion into the ortho-CH bond of the phenoxy ring. Furopyridine derivatives 167 can be prepared similarly by the intramolecular aromatic C-H insertion of the alkylidenecarbenes generated by the reaction of alkynyliodonium tosylates 166 with potassium salts of 4- or 3-hydroxypyridines [128]. 

Finally, the a,/ -unsaturated carbene complex may be generated in situ by alkyne insertion into a chromium-carbene bond of a saturated chromium carbene leading to a chromium vinyl carbene (equivalent to intermediate (f )-D in the mechanism of the benzannulation reaction, see Section 8.2.1, Scheme 3), which may undergo subsequent benzannulation with a second equivalent of the alkyne [43a]. This strategy was subsequently applied to the synthesis of (Z)-enediynes and related compounds [43b], and to that of substituted benzofurans (see also Section 8.5) [43c, 43d]. 

Phenoxide ion, unlike alkoxides, interacts favorably with alkynyliodonium species. Reaction of two equivalents of lithium phenoxide with the [bis(phenyliodonium)ethyne, 30, results in diphenoxyacetylene, 79 [24] [Eq. (36)]. Benzofurans, 81, are obtained in the reaction of 23 with PhONa in methanol [Eq. (37)] [64]. As indicated, these products arise via insertion of the intermediate carbene, 80, into the ortho-C-H bond. 

Recently, the Ye group found the [3 -I- 4] annulation of enals with aurones in the presence of a bifunctional N-heterocyclic carbene catalyst. The reaction gave the corresponding benzofuran-fused s-lactones 130 in good yields with good diastereoselectivities and excellent enantioselectivities (Scheme 20.55). 

Unsubstituted benzofuran-3-carboxylates are formed as the major products by the reaction of f-butyl (o-methoxyphenyl) (oxo)acetates with TMSC(MgBr)N2 (eq 26). Alkylidene carbenes are first formed from a-ketoesters, which cyclize to oxonium ylides. Elimination of methylene affords benzofurans. 

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