Reduction of Aliphatic Nitro Groups

Published by MatTodd on 26 June 2007 - 9:52am

Subject 

Request for Help

We have been working for a little while on the aza-Henry route to PZQ. We're going to submit a paper to an open access journal on some of this work, but I thought we should post on something we're looking at now, since we've come up against an unexpectedly difficult step and need some help.
We've been trying to reduce an aliphatic nitro group (picture is below). The compound is a model case for PZQ that we've been looking at. This reduction looks to be a very simple reaction, and we did not expect problems.
Aliphatic nitro reductionAliphatic nitro reduction
Shibasaki has reported on the reduction of aza-Henry beta-nitroamines like this.1 The literature contains few reliable procedures for aliphatic nitro reduction2 – aromatic nitro groups are no problem. We've tried regular hydrogenation, Raney Nickel, SmI2 and LiAlH4. Jim Anderson at Nottingham recently published a very nice paper resurrecting Al-Hg amalgam as a reagent for this transformation, and we are having luck with it.3 This post is a very overdue appeal to the community at large:
a) Does anyone know of any other good reaction conditions for this reaction?
b) Does anyone have any advice on good ways to isolate the resulting diamines?
Cheers,
Mat
 
1. K. Yamada, S. J. Harwood, H. Groger and M. Shibasaki, Angew. Chem. Int. Ed. 1999, 38, 3504-3506.
2. S. L. Ioffe, V. A. Tartakovskii and S. S. Novikov, Russ. Chem. Rev. 1966, 35, 19-32.
3. J. C. Anderson and H. A. Chapman, Synthesis 2006, 3309-3315.