Scheme 16 Solvent effect on the reaction site of 1-methoxy-3-(2-nitrovinyl)indole

The substrate (123a) is available by the nitroaldol reaction of 1-methoxy-indole-3-carbaldehyde (10a). Employing THF as a solvent, the reaction of 123a with NaOMe or NaOn-Pr at 0 °C provides the Michael addition products, 1-methoxy-3-(1-methoxy-2-nitroethyl)indole (124a, 90%) and 1-methoxy-3-(2-nitro-1-«-propyloxyethyl)indole (124b, 92%), respectively. Similar reactions of 123a with sodium allyl oxide, potassium 1,1-dimethylallyl oxide, and sodium 3-butyn-1-oxide in THF produce 124c (58%), 124d (81%), and 124e (95%), respectively. It is interesting to note that the reaction of 123a with potassium 1,1-dimethylallyl oxide at reflux instead of 0 °C generates a novel cyclic product (125,55%) probably through the expected intermediate (124d). The structure of 125 is proved by X-ray single-crystal analysis of its derivative [36].

We know in some reactions the employment of a different base results in a different product from the original one. The reaction of 123a with 1,1-dimethylpropargyl alcohol in THF, employing KOi-Bu as the base, forms a novel cyclic product (126, 35%). A similar reaction using NaH as the base in THF affords a conjugate addition product (127, 75%). The fact that the treatment of 127 with KOi-Bu provides 126 (60%) clearly shows 126 is formed through 127 [36].

In dipolar aprotic solvents, 123a reacts with nucleophiles regioselectively at the 2-position with concomitant liberation of the 1-methoxy group. Treatment of 123a with either NaOMe or NaO«-Pr in DMF generates 128a (85%) and 128b (45%), respectively. In these reactions, formation of conjugate addition products to the ^-carbon atom of the nitrovinyl side chain is not observed at all. In addition, it should be noted that the N(1)-H compound (123b) does not undergo a nucleophilic substitution reaction even under forcing reaction conditions [36].

The reaction of 123a with allyl alcohol/NaH in DMF produces 2-allyloxy-3-(2-nitrovinyl)indole (128c, 65%) and (d/)-3-allyl-3-(2-nitrovinyl)-2-oxindole (129, 6%) as expected. Alternatively, compound (129) can be obtained by heating 128c at 144 °C on celite by the Claisen-type rearrangement (95%). Unexpectedly, the reaction of 123a with sodium allyl oxide in N-me-thylformamide or DMF at around 105 °C gives rise to 128d (58%) and 128e (49%), respectively. In both cases, formation of 129 is not observed at all [36].

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