2.3- Dihydro-2-substituted-benzofurans

A study of 5 to A alkyl migration of substituted 5-(l(3//)-isobenzofuranon-3-yl)isothiuronium bromide to A,A -dimethyl-A-(3-oxo-l,3-dihydro-2-benzofuran-l-yl)thiourea involves two consecutive back-side 5 2 reactions, where a carboxylate anion has a role as a leaving group as well as an internal nucleophile (Scheme 194). °... 

Bromomethyl-3,4-dibromo-3,4-dihydrocoumarin 1 (Fig. 11.4) and its chloro-methylated analogue 2b rapidly and progressively inactivate a-chymotrypsin and also the activities of a series of trypsin-like proteases. A benzyl substituent characteristic of good substrates of a-chymotrypsin was introduced at the 3-position to make inhibition more selective. This substituted dihydrocoumarin 3 irreversibly inhibited a-chymotrypsin and other proteases. These functionalized six-membered aromatic lactones, and their five- and seven-membered counterparts, 3//-benzofuran-2-ones 2a26 and 4,5-dihydro-3//-benzo[b]oxepin-2-ones 2c,27 were the first efficient suicide inhibitors of serine proteases. Their postulated mechanism of action is shown in Scheme 11.2. 

Treatment of the dibromides with sodium ethoxide gives 2-bromo-methyl-2,3-dihydrobenzofurans (170) o- (2,3-dibromopropyl)phenyl acetate (188, X = OAc, R = H) gives 2-bromomethyl-2,3-dihydro-benzofuran (170, R = R1 = H).447 The following substituted 2-bromo-methyl-2,3-dihydrobenzofurans have been prepared by this method ... 

Bcnzofuran-4,7-dioncs have been synthesized regioselectively by [3 + 2] photoaddition of 2-hydroxy-1,4-benzoquinones with a range of alkenes (equation 185)664. The reaction occurs in 30-60% yield and is a useful method for the synthesis of the benzofuran ring system, which is important in natural products like acamelin665. Substituted naphthoquinones may also be used in this reaction666,667 and this has lead to a very simple two-step synthesis of maturinone. In a similar reaction, a [3 + 2] photoaddition reaction of 2-amino-1,4-naphthoquinones with electron-rich alkenes gave 13-82% yields of 2,3-dihydro-177-bcn/ /]indole-4,9-diones in a single-step process which involved photolysis followed by oxidation (equation 186)668,669. 

Formation of the methylcarbamate of 2,3-dihydro-2,2- dimethyl-4-hydroxy benzofuran in 57% yield has been reported from the N-methylamido derivative of saccharin through nucleophilic substitution by the addition of triethylamine in aqueous acetone (1 2) at ambient temperature over 2 hours (ref.29). 

A number of instances can be cited from the literature wherein the isosteres had similar transformations. Bacterial dioxygenase-catalyzed ci5-dihydroxylation of the tetracyclic arene benzo[c]phenanthrene was found to occur exclusively at fjord region (cavity region) bonds. The isosteric compounds benzo[b]naphthol [l,2-d]furan and benzo[b]naphthol[l,2-d]thiophene were also similarly ci5-dihydroxylated at the fjord region bonds by bacterial dioxygenases (Boyd et al., 2001) (see Fig. 4.3). The isosteres 1,2-dihydronaphthalene, 2,3-dihydrobenzothiophene, and 2,3-dihydro-benzofuran gave similar corresponding diol products on incubation with Pseudomonas putida UV4. Microbes that possess the metabolic pathways to metabolize benzene, when substituted by... 

S. Parekh, D. Bhavsar, M. Savant, S. Thakrar, A. Bavishi, M. Parmar, H. Vala, A. Radadiya, N. Pandya, J. Serly, J. Molnar, A. Shah, Synthesis of some novel benzofuran-2-yl(4,5-dihydro-3,5-substituted diphenylp)frazol-l-yl)methanones and studies on the antiproliferative effects and reversal of multidrug resistance of human MDRl-gene transfected mouse l)fmphoma cells in vitro, Eur. J. Med. Chem. 46 (2011) 1942-1948. 

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