The assignment of the diazo site in products of the reaction of p-toluenesulfonylhydrazine with beta-lapachone, 3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione, and other 1,2-naphthoquinones in methanol solution at room temperature has been accomplished using 1H,13C HMBC and 1H,15N HMBC NMR experiments. Only one diazo-naphthalenone product was isolated in yields ranging from 50-100% from each reaction. The site of diazo substitution of beta-lapachone and derivatives is the 1-position, in contrast to substitution at the 2-position in 4-MeO-1,2-naphthoquinone. Steric factors, rather than electronic factors, control the reaction site. Along with 2-diazo-1(2H)-naphthalenone, an additional product isolated from the reaction of p-toluenesulfonylhydrazide with 1,2-naphthoquinone was 2-diazo-4-hydroxy-1(2H)-naphthalenone. Confirmation of the formation of 6-diazo-2,2-dimethyl-2,3,4,6-tetrahydro-2H-benzo[h]cromen-5-one, obtained from beta-lapachone, was achieved using single crystal X-ray diffraction.
Derivatives 6a and 6b, have been obtained in a chemoselective manner by a two step synthesis from β-lapachone (3a) and nor-β-lapachone (3b), respectively, using CH 2 N 2 in ether, which provided the lapachone-epoxide derivatives, 5a and 5b, followed by treatment with BF 3 .Et 2 O/CH 2 Cl 2 . Basic work-up of the reaction mixture of 5a or 5b with BF 3 .Et 2 O/CH 2 Cl 2 led instead to isolation of the rearranged derivatives 7a and 7b, respectively. An ab initio theoretical study [B3LYP/6-311+G(d)] on 3a indicated that the carbon atom, C6, carries a higher positive charge than that at C5 and hence predicts a greater reactivity towards nucleophiles at C6. Another important factor controlling the chemoselectivity in the reaction of 3a with CH 2 N 2 is the steric hindrance of the CH 2 groups of the pyran ring.
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