Homoallenyl azines and proton sponges
Juraj Galeta
Allenyl synthon is nowadays used for the preparation of a large variety of organic compounds exhibiting
various biological activities. Synthesis of non-symmetrical allenyl azines 1 and their chemical
transformations are extensively studied at our laboratories. It was found that azines 1 reacted thermally
with various dipolarophiles in combined intra-intermolecular criss-cross cycloaddition. The first project of
my Thesis is based on the reactions of 1 with various alkynes in boiling xylene affording a mixture of three
possible products. We isolated expected substituted 1,10-diazatricyclo[5.2.14,7
.01,10
]deca-2,6-dienes 2 but
in some cases new pyrrolo[1,2-b]pyrazoles 3 and 4 were obtained as well. This reaction was found to be
diastereoselective with high atom economy. The influence of dipolarophile nature as well as the
substitution at 1 is discussed on the basis of the proposed mechanisms. It is worth noting that pyrrolo[1,2b]pyrazoles
might show interesting biological activity as their skeleton is very similar to that of
Withasomnine alkaloid.
The second project deals with the preparation and basicity investigation of new structural types of proton
sponges (PS). The general feature of all PS is the presence of two basic nitrogen centers in the molecule,
which have an orientation that allows the uptake of one proton to yield a stabilized intramolecular
hydrogen bond. Herein, we report a molecular framework design differing significantly from the traditional
topology of proton sponges. We developed a suitable synthetic approach to the preparation of
compounds 6 by intramolecular criss-cross cycloaddition reactions of symmetrical homoallenyl azines 5.
The acid-catalyzed rearrangement of cycloadducts 6 afforded bidentate caged secondary amines 7 in
quantitative yields and following alkylation reactions led to air nonsensitive highly stable substituted
diazatetracyclo[4.4.0.13,10
.15,8
]dodecanes 8 with rare alicyclic scaffolding. Their pKBH+ values were
determined by 1
H NMR transprotonation experiments as well as their sensitivity toward nucleophiles,
acids and bases. The molecular structures of free base and monoprotonated form of 8 were proved by Xray
structure analysis.
References:
Galeta J., Man S., Bouillon J.-P., Potáček M. Eur. J. Org. Chem. 2011, 392.
Galeta J., Potáček M. J. Org. Chem. 2012, 77, 1010.