Allenyl Azide Cycloaddition Chemistry. Synthesis of Pyrrolidine-Containing Bicycles and Tricycles via the Possible Intermediacy of Azatrimethylenemethane Species

Abstract

Thermolysis of 5-azidoallenes bearing a C(1) methyl group and either an aryl ring or an alkene on C(1) furnishes tricyclic (from the aryl substrates) or bicyclic (from the alkenyl substrates) pyrrolidine products following formal H-CN addition across an intermediate imine. High levels of diastereoselectivity are observed in all cases studied. This reaction cascade presumably passes through unobserved triazoline and azatrimethylenemethane diyl intermediates en route to product.

Cyclization Cascade of Allenyl Azides: A Dual Mechanism

“…The diyls that are formed from the non-conjugated substrates cyclize with complete stereochemical control through a 5-electron conrotatory process resembling the familiar 4n-type W-H electrocyclizations. Finally, the competition between electrocyclization and [1,7]-hydrogen shift within the conjugated system-derived indolidene depends on the nature of the terminal unsaturation; if an alkene is present, electrocyclization is preferred energetically and tricyclic product is formed, whereas if the terminal unsaturation is an arene ring, disrupting its aromaticity is too penalizing, and the [1,7] H-shift predominates. Overall, these results point to the value of computational approaches in disentangling complex reaction sequences that may feature bis allylic diradicals.…”

“…The trade-off between the gain in indolic aromatic resonance energy upon C-C (or C-N) bond formation and the loss of same at the arene fragment must influence the product distribution. This competition can be resolved by the intervention of a second, independent pathway by which the indole can recapture its aromaticity, but at no expense to the arene unit; formal [1,7] hydrogen shift from the methyl group to either the indolidene's C(3) position (from (E)-18 Ph or to it's nitrogen (from (Z)-18 Ph ) to furnish 14 Ph or it's tautomer, tau-14 Ph , respectively. Tau-14 Ph , if formed, then could proceed to the observed product 14 by simple proton shift.…”

“…The energy barrier for the final C-C bond forming cyclization of ((E)-18 Ph into 21 Ph suffers a severe penalty when compared to its vinyl counterpart (from 14-15 kcal/mol (vinyl) to 25-26 kcal/mol (phenyl)). The increase in the electrocyclic ring closure barrier heights for the phenyl-substituted series allows the alternative [1,7]-H shifts to be expressed. The calculated barrier height for the C-H bond forming shift of (E)-18 Ph into 14 Ph at 26.8 kcal/mol is only slightly higher than the calculated (E)-18 Ph →21 Ph electrocyclization barrier, but the related [1,7] C-H-to-N-H shift extending from (Z)-18 Ph , at over 40 kcal/mol, is unlikely to be expressed experimentally.…”

“…The increase in the electrocyclic ring closure barrier heights for the phenyl-substituted series allows the alternative [1,7]-H shifts to be expressed. The calculated barrier height for the C-H bond forming shift of (E)-18 Ph into 14 Ph at 26.8 kcal/mol is only slightly higher than the calculated (E)-18 Ph →21 Ph electrocyclization barrier, but the related [1,7] C-H-to-N-H shift extending from (Z)-18 Ph , at over 40 kcal/mol, is unlikely to be expressed experimentally. However, the calculated barrier to interconversion of (Z)-18 Ph into (E)-18 Ph (26.1 kcal/mol) is likely to render this isomerization process facile under the experimental conditions.…”

Regioselective Intramolecular [3+2] Annulation of Allene-Nitrones

“…[5][6][7][8][9][10][11][12][13][14][15] In contrast to the intermolecular reaction, there are very few examples of the intramolecular 1,3-diploar cycloaddition between the nitrone and allene groups. [16][17][18][19][20][21][22] Of particular interest among them is the reaction of the nitrone 1 16) derived from the reaction of 5,6-heptadien-2-one with Nmethylhydroxylamine (Chart 1). The in situ formed 1 (n=1) furnished the bicyclic isoxazolidine 2 in 45% yield via the cycloaddition with the distal double bond of the allenyl group, while the nonselective formation of the two bicyclic cycloadducts 3 (36%, two diastereoisomers in a ratio of 26 to 10) and 4 (29%) was observed when the one carbon-elongated nitrone 1 (n=2) was employed.…”