3890
P. W. H. Chan et al. / Tetrahedron: Asymmetry 10 (1999) 3887–3891
Figure 1.
Since the partially deprotected adducts 14 and 15 were readily available, the configurational stability of
1
both derivatives (1:1 C6D6/D2O, 24 h, rt) was therefore examined. By careful H NMR spectroscopic
analysis, no change in the epimeric ratio of the amino product 15 was detected, but the ratio of the
major product 14a to that of the minor compound 14b was found to have changed from 8:1 to 2:1,
suggesting that epimerisation could indeed take place at an intermediate stage once cleavage of one of
the benzylcarbamate protecting groups had occurred.
In summary, the development of a route to conformationally restricted diamino functionalised pyrroli-
dines, obtained in excellent yields and with a high degree of diastereocontrol, was shown to be possible
through the electrophilic amination at C-7 of the β-amino chiral template 6. Subsequent elaboration
of these compounds provided an efficient route to the 3,4-diaminopyroglutaminol 12 in excellent yield,
albeit with some loss of chiral integrity at C-4. Although the stereochemistry of some of the intermediates
generated could not be directly determined by conventional analytical protocol, the chemoselective
hydrogenolysis of compound 9 allowed the assignment of the absolute configuration of the major isomers
obtained as well as revealing the source of the observed epimerisation.
Acknowledgements
The authors are grateful to the Engineering and Physical Sciences Research Council and Merck Sharp
and Dohme for providing financial funding to P.C. We wish to acknowledge the use of the EPSRC
Chemical Database Service at Daresbury17 and the EPSRC National Mass Spectrometric Service Centre
at Swansea.
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