posted on 2013-12-06, 00:00authored byRachel Aranha Potter, Amy M. Bowser, Yanbo Yang, José S. Madalengoitia, Joseph
W. Ziller
Bridged bicyclic tertiary allylic
amines aza-norbornene 1 and isoquinuclidene 2 add to isocyanates, isothiocyanates,
and in situ-generated carbodiimides to form zwitterionic intermediates
that undergo 1,3-diaza-Claisen rearrangements to afford highly substituted
ureas, thioureas, and guanidines, respectively. Aza-norbornene 1 is significantly more reactive toward 1,3-diaza-Claisen
rearrangements than isoquinuclidene 2. This reactivity
difference is most likely due to the inherent ring strain in the aza-bicyclo[2.2.1]heptene
ring system of aza-norbornene 1. The most apparent reactivity
trend of the heterocumulenes is that the most electron-deficient heterocumulenes
are more reactive toward 1,3-diaza-Claisen rearrangements. The introduction
of a new stereocenter α- to the nucleophilic nitrogen in aza-norbornene 1 and isoquinuclidine 2 decreases the reactivity
toward 1,3-diaza-Claisen rearrangements, while the exodiastereomers 3b and 4b are less reactive than the corresponding
endodiastereomers 3a and 4a. Isocyanates
that bear an electron-withdrawing group react with allylic amines 1–3b to afford mixtures of ureas and isoureas;
however, with excess isocyanate and heat, thermodynamic equilibration
is possible affording ureas. Inspired by this observation, a one-pot
reaction of isocyanates with amines 1, 2, and 3b followed by BF3·OEt2-catalyzed isomerization of the urea/isourea mixture was developed
that affords the corresponding ureas in excellent yields.