Reactions of heterocumulenes with organometallic reagents: XVI. Quantum-chemical study on the mechanisms of formation of homo- and heteroannular azacycloheptadienes in reactions of 2-aza-1,3,5-trienes with potassium tert-butoxide

Abstract

Mechanisms of intramolecular transformations of carbanions generated from 2-aza-1,3,5-trienes by the action of potassium tert-butoxide, which could lead to homo-or heteroannular azacycloheptadienes, were studied by quantum-chemical methods in terms of the density functional theory. The corresponding gradient channels were localized for model 1-methylsulfanyl-1-(cyclopentylideneamino)-and 1-methylsulfanyl-1-(cyclohexylideneamino)buta-1,3-dien-2-ols. Analysis of the kinetic and thermodynamic parameters showed that carbanion generated from N-cyclopentylidenebuta-1,3-dien-1-amine undergoes rearrangement mainly into homoannular azacycloheptadiene and that analogous N-cyclohexylidene derivative gives rise to heteroannular isomer. The results of calculations were consistent with the experimental data. * For communication XV, see [1].Seven-membered nitrogen-containing heterocycles constitute structural fragments of many natural and synthetic biologically active compounds which have found wide applications in medicine and pharmacology [2]. Increased interest in these compounds stimulated search for rational ways of their synthesis, including the synthesis of new derivatives. We recently showed that 2-aza-1,3,5-trienes I available in one preparative step from α-lithiated allenes (e.g., methoxyallene or protected allenyl alcohol) and s-alkyl isothiocyanates (e.g., isopropyl isothiocyanate) (Scheme 1) [3] by the action of potassium tert-butoxide in tetrahydrofuran-dimethyl sulfoxide are readily (-30°C, 30 min) transformed into previously unknown 4,5-dihydro-3H-azepines II (Scheme 2); these results were briefly reported in [4,5].

Reactions of heterocumulenes with organometallic reagents: XVII. One-pot synthesis of alkoxy and (alkylsulfanyl)-substituted pyrroles and 2,3-dihydropyridines from aliphatic isothiocyanates and lithiated alkoxyallenes

“…The transition of 1-aza-1,3,4-triene VIg obtained by adding 1-lithio-1-methoxyallene (IIa) to cyclohexyl isothiocyanate with the subsequent S-alkylation of the adduct with ethyl iodide into a stable structural isomer VIIg (Scheme 1) occurs in keeping with calculation data (HF/6-31G**) [19] in a sigle stage by [1,5]-migration of hydrogen through the fl attening of the molecule skeleton (E act 141.9 kJ mol −1 ). Experimentally isolated 2-aza-1,3,5-triene VIIg contained an impurity of pyrrolea IIIg and 1-aza-1,3,4-triene VIg.…”

“…isothiocyanate, on the contrary, essentially facilitates the closure of 1-aza-1,3,4-triene VIi obtained therefrom into the pyrrole ring hence partially "inhibiting" the [1,5]-H shift. The presence in compounds IIIi, IVi, VIi of the highly reactive vinyloxy group essentially extends their synthetic potential [24], in particular as monomers (it is well known [25] that the most important application fi eld for vinyl ethers is the industry of synthetic polymers).…”

“…It turned out that after the alkylation of adduct Vh the formed 1-aza-1,3,4-triene VIh (Scheme 1) already under the conditions of the reaction at uncommonly low temperature (-70 × 0°C) for [1,5]sigmatropic rearrangements isomerized quantitatively into 2-aza-1,3,5-triene VIIh whose electrocyclization provided in high yield one more representative of previously unknown and unavailable 6-(alkylsulfanyl)-2,3-dihydropyridines, 2-methoxy-2,3-dihydropyridine IVh (see the table). The corresponding pyrrole IIIh was not identifi ed among the reaction products.…”

“…Inasmuch as 2-aza-1,3,5-trienes attract independent interest (as linear precursors both of 2,3-dihydropyridines [4] and, for example, of 3H-azepines and 4,5-dihydro-3H-azepines [7]) we with especial attention investigated the [1,5]-sigmatropic rearrangement of the synthesized 1-aza-1,3,4-trienes VI. The best result that was attained up till now by the variation of the isomerization conditions of N-ethyl-substituted azatriene was a mixture of 1-aza-1,3,4-triene VIb and 2-aza-1,3,5-triene VIIb (in the ratio ~3 : 2) containing traces of pyrrole IIIb and 2,3-dihydropyridine IVb.…”

“…Obviously the ratio of the heterocyclic reaction products, i.e., pyrrole III and 2,3-dihydropyridine IV, is governed by the ratio of the rates of two competing processes related to the thermally induced reorganization of 1-aza-1,3,4-triene VI: the intramolecular [1,5]-cyclization into pyrrole (with the formation of a new C-N bond) and the isomerization into 2-aza-1,3,5-triene VII (through [1,5]-H shift). It is also obvious that the kinetic parameters of the concurrent reactions alongside the thermodynamic characteristics of the reaction products should be or at least may be signifi cantly affected by the stereoelectronic effects of the substituents in the starting 1-aza-1,3,4-triene VI and in the long run by the structure of the initial reagents (allene, isothiocyanate, and alkyl halide).…”