(Hive Addict)
05-23-03 20:50
No 435002
      Transfer Hydrog. Nitro to amine keep configuration
(Rated as: excellent)

Transfer Hydrogenation: A Stereospecific Method for the Conversion of Nitro Alkanes into Amines
Anthony G. M. Barrett* and Christopher D. Spilling
Tetrahedron Letters, Vol. 29, No. 45, 5733-34, (1988) (../rhodium/chemistry /nitro2amine.cth.pd-af.html)

A series of nitroalkanes were converted into the corresponding amines with retention of configuration by transfer hydrogenation using ammonium formate and Pd/C.

Recently we needed a mild, rapid procedure for the conversion of beta-nitroalcohols into the corresponding hydroxy amines with retention of the configuration.  Usually such reductions are carried out by hydrogenations over Raney nickel or platinum1.  However, these procedures frequently require elevated temperatures and pressures.  In 1984, Ram and Ehrenkaufer reported that nitro compounds could be easily converted into the corresponding amines by transfer hydrogenation using ammonium formate catalyzed by Pd/C.2  The authors however did not determine the stereochemical outcome of the reaction.  Herein we report our observation on this reduction protocol which clearly demonstrate that the method is stereospecific and proceeds with retention of configuration.  As such we consider that it is the method of choice for the production of amines from funtionalized nitro alkanes.

Thus transfer hydrogenation of the pure racemic syn3 nitro alcohol is in methanol solution gave the amino alcohol (2a) in 80% yield.  None of the anti isomer was detected in the product by NMR spectroscopy.  In the same way the nitro alcohols4 (1b) [syn: anti ; 1:8.1], (3a) [syn:anti ; 1:2.9], (3b) [syn:anti ; 1:3.2], (5a) [anti only], and (6a) [syn: anti ; 1:8.1] were converted into the corresponding beta-aminoalcohols (2b) [44%, syn: anti ; 6:1], (4a)5 [61%, syn:anti ; 1:2.8], (4b) [87%, syn:anti ; 1.3.2], (5b) [73%, anti], and (6b) [58%, only anti observed].


A typical procedure is as follows: to a solution of the nitro alcohol (3b) [0.219g, 1.1mmol] in THF and methanol (50:50, 10ml) was added 10% Pd/C (50mg) followed by ammonium formate (0.35g, 5 eq).  The mixture was stirred at RT until all the starting nitro alcohol had been consumed. (TLC).  The mixture was diluted with Et2O (100ml), filtered, and the filtrate was evaporated in vacuo to yield the crude amine.  Flash column chromatography [SiO2, methanol/chloroform ; 2:98 ; v/v] gave the amine (4b) [0.16g, 87%].


1. F.G. Bordwell, E.W. Garbisch Jr. JOC, (1963), 28, 1765. 
F.G. Bordwell and R.L. Arnold, Ibid., (1962), 27, 4426
A.T. Nielson, Ibid., (1962), 27, 1998.
Bordwell and J.B. Biranowski, Ibid., (1967), 32, 629
R.J. Sundberg and P.A. Bukowick, Ibid., (1968), 33, 4098
D. Seebach, A.K. Beck, T. Mukhopadhyay and E. Thomas, Helv. Chim. Acta, (1982), 65, 1101

2. S. Ram and R.E. Ehrenkaufer, Tetrahedron Lett., (1984), 25, 3415
S. Ram and R.E. Ehrenkaufer, Synthesis, (1986), 133

3. M. Eyer and D. Seebach, JACS, (1985), 107, 3601

4. A.G.M. Barrett and C.D. Spilling, submitted to JOC

5. F. W. Hoover and H.B. Hass, JOC, (1947), 12, 506
M. Baudet and M. Gelbcke, Anal. Lett., (1979), 12, 6412.