ORGANIC
LETTERS
1999
Vol. 1, No. 9
1395-1397
Oxidative Deprotection of
Diphenylmethylamines
Peter B. Sampson and John F. Honek*
Department of Chemistry, UniVersity of Waterloo, Waterloo,
Ontario, Canada N2L 3G1
Received August 18, 1999
ABSTRACT
The diphenylmethyl amino protecting group can be efficiently removed by initial oxidation of the amine to an imine by 2,3-dichloro-5,6-
dicyanobenzoquinone. The resulting imine can then be easily hydrolyzed under mildly acidic conditions. This method is particularly well
suited for the preparation of r-amino phosphinates and r-amino phosphonates.
The benzhydryl or diphenylmethyl (Dpm) group has been
used as a protecting group for carboxylic acids,1 alcohols,2
and amines.3 As a protecting group for the amine functional-
ity, it offers an alternative to the trityl group by its relative
stability to strong acid conditions.4 Traditionally, removal
of the diphenylmethyl protecting group from an amine
functionality has been achieved via hydrogenation,5a using
triethylsilane/TFA,5b or under vigorous acidic conditions.3a
We describe an oxidative approach to release of the protect-
ing group in which the secondary amine is oxidized to an
imine, which can be hydrolyzed under mildly acidic condi-
tions. Moreover, this method of imine formation has synthetic
applications in the Schiff base mediated preparation of
R-amino acids,6 R-amino phosphinates,7 and R-amino phos-
phonates.8
extensive use of this compound as a dehydrogenating agent
in organic synthesis.9 Despite this, examples of the quinone-
mediated oxidation of amines are limited. In general, primary
and secondary aliphatic amines undergo nucleophilic dis-
placement reactions with halogen-containing quinone oxi-
dants, whereas aliphatic tertiary amines are known to react
by way of a charge transfer complex to give enamines.10
Recently, however, DDQ has been reported to effect the
oxidative removal of the p-methoxybenzyl protecting group
of an indole nitrogen11 and the oxidative fragmentation of
the alkaloid catharanthine.12
The Dpm protecting group was removed through initial
oxidation of the secondary amine to an imine as outlined in
Scheme 1. The Dpm-amine was dissolved in anhydrous
The high oxidation potential (E0 ) 1000 mV)9 of 2,3-
dichloro-5,6-dicyanobenzoquinone (DDQ) has resulted in the
Scheme 1a
(1) Lapatsanis, L.; Milias, G.; Paraskewas, S. Synthesis 1985, 513-15.
(2) Jackson, G.; Jones, H. F.; Petursson, S.; Webber, J. M. Carbohydr.
Res. 1982, 102, 147-57.
(3) (a) Baylis, E. K.; Campbell, C. D.; Dingwall, J. G. J. Chem. Soc.,
Perkin Trans. 1 1984, 2845-53. (b) Corey, E. J.; Grogan, M. J. Org. Lett.
1999, 1, 157-60.
(4) Pless, J. HelV. Chim. Acta 1976, 59, 499-512.
(5) (a) Ryglowski, A.; Kafarski, P. Tetrahedron 1996, 52, 10685-92.
(b) Neumann, W. L.; Rogic, M. M.; Dunn, T. J. Tetrahedron Lett. 1991,
42, 5865-68.
(6) O’Donnell, M. J.; Polt, R. J. Org. Chem. 1982, 47, 2663-66.
(7) McCleary, P. P.; Tuck, B. J. Chem. Soc., Perkin Trans. 1 1989, 1319-
29.
a Reagents: (i) DDQ, benzene, crushed 4A molecular sieves, 60
°C, 1 h.; (ii) 0.1 N HCl, diethyl ether, 6 h.
(8) (a) Genet, J. P.; Uziel, J.; Touzin, A. M.; Juge, S. Synthesis 1990,
41-43. (b) Genet, J. P.; Uziel, J.; Port, M.; Touzin, A. M.; Roland, S.;
Thorimbert; S., Tanier, S. Tetrahedron Lett. 1992, 33, 77-80.
benzene in the presence of crushed 4A molecular sieves at
60 °C.13 Addition of DDQ (1 equiv) gave quantitative
10.1021/ol990956i CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/25/1999