New transformations of 2-Aza-1,3,5-trienes by the action of t-BuOK-THF-DMSO

Abstract

2-Aza-1,3,5-trienes have become readily accessible due to discovery and systematic studies of reactions of allenic and acetylenic carbanions with isothiocyanates [1, 2]. These compounds are universal precursors of new 2,3-dihydropyridines [3–7], pyridines [5], 5,6-dihydropyridin-2(1H)and -3(4H)-ones [6], pyridine2(1H)-thiones [7], cyclobuta[1,2-b]pyrroles [4, 7, 8], and seven-membered nitrogen-containing heterocycles [9–11]. In particular, we found that 2-aza-1,3,5-trienes obtained from, e.g., methoxyor 1-(1-ethoxyethoxy)allene and isopropyl isothiocyanate undergo fast transformation in t-BuOK–THF (0°C, 10 min) or t-BuOK– THF–DMSO (–30°C, 30 min) into previously inaccessible 3(6)-methoxy[9] and 3(6)-(1-ethoxyethoxy)substituted [10] 7-methyl-2-methylsulfanyl-4,5-dihydro-3H-azepines and 2-methyl-3H-azepines whose ratio depends on the nature of substituent in position 3 (6), as well as on the reaction conditions. On the other hand, conjugated 2-aza-1,3,5-triene synthesized from dilithium derivative of 2-methyl-5-(prop-2-yn-1-yl)thiophene and isopropyl isothiocyanate reacted with potassium tert-butoxide in THF–DMSO to give exclusively 2-methyl-6-(5-methylthiophen-2-yl)-3H-azepine [11]. Analogous reaction of 2-aza-1,3,5-trienes derived from allenes or acetylenes and unbranched alkyl isothiocyanates could open the way to previously unknown 6(3)-alkyl-substituted dihydroazepines and/or azepines. However, deprotonation of such aza trienes has not been reported so far, and the result of this transformation is difficult to predict. While continuing studies in this field, we were the first to react α-lithiated methoxyallene with butyl isothiocyanate with a view to obtain previously unknown N-(but-1-ylidene)-2-methoxy-1-methylsulfanylbuta-1,3-dien-1amine (I, 2-aza-1,3,5-triene) (Scheme 1) and convert it into 6(3)-ethylazacycloheptadienes and -trienes (Scheme 2). It is known that 1-aza-1,3,4-trienes derived from branched sec-alkyl isothiocyanates undergo smooth isomerization (via [1,5]-H shift) into the corresponding 2-aza-1,3,5-trienes at room or moderately elevated temperature (~60°C, 10–20 min) [1, 9– 11]. Analogous sigmatropic rearrangement of 1-azaISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 1, pp. 141–145. © Pleiades Publishing, Ltd., 2011. Original Russian Text © N.A. Nedolya, O.G. Volostnykh, O.A. Tarasova, A.I. Albanov, B.A. Trofimov, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 1, pp. 141–145.