Kimpe
and co-workers from Ghent University, Belgium and Kaunas University
of Technology, Lithuania reported an unknown and intersting
spirocyclic diamine compound 1,5-diazaspiro[2.3]hexanes (Fig. 1).
Their approach to the synthesis of the target spiro-compound began
with ethyl 2-(bromomethyl)-1-tosylaziridine-2-carboxylate (marked in
red in scheme 1). This key intermediate was prepared from the hydroxy
deri. 2 in overall 79% yield following the reaction sequence as
depicted in scheme 1 as against the reported 17% yield from
corresponding bromo compound 3.
First
the hydroxy deri. was treated under Mitsunobu condition with BocNHTs
to deliver the product in 91% yield. The Boc-group is derprotected
and the tosyl deri. thus obtained was brominated to give the dibromo
compoundd that was cyclized by treating with pot. Carbonate in
acetonitrile to give the key intermediate.
After
condition optimziation, the key intermediate was further reduced
using LAH at -78 °C to deliver the corresponding aldehyde which was
treated with various amines to give respective imines. This imines
when reduced with sodium borohydride, an unexpcted rearraged product
was isolated in 80-90 yield and the same were cyclized after
treatment with potasium carbonate to give the protected targeted
spirocyclic diamine derivatives. The aurthors tried deprotection of
strained spirocyclic compound and succeeded in the isolation of the
free amine compound without ring-opening. The free amine was fully
characterized and the analytical data supported the structure.
However, the authors failed to get the analytically pure amino-compd
via column purification or the oxalate salt formation.
Overall, a very good synthesis has been reported for the preparation of highly strained
spirocylic diamine compounds with excellent yields at each stage.
This
report will deinitely boost the confidence of synthetic organic chemists to
prepare and synthesise various strained diamino derivatives.
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