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important compounds such as alafosfalin and (R)-phospho-
A Simple and Efficient Access to r-Amino
Phosphonates from N-Benzyloxycarbonylamino
Sulfones Using Indium(III) Chloride†
tyrosin possess an R-amino phosphonate moiety as their
structural unit.5 In addition, R-amino phosphonates have
been employed as insecticides,6a herbicides,6b,6c and fungi-
cides.6d Due to their interesting biological properties, various
methods have been developed for the synthesis of these
compounds.7 The optically active forms of these molecules
have also been synthesized.3a,5,8 Generally, the carbonyl
compound and amines or directly the imines have been
utilized in these synthetic methods. However, many of these
methods are associated with different drawbacks such as
high temperature, long reaction time, application of costly
reagents, and tedious experimental procedure. Recently,
Biswanath Das,* Kongara Damodar, and Nisith Bhunia
Organic Chemistry Division-I, Indian Institute of Chemical
Technology, Hyderabad 500 007, India
Received March 16, 2009
ZrOCl2 8H2O has been introduced as an efficient catalyst
3
for one-pot reaction of amines, aldehydes, and diethyl
phosphite to form R-amino phosphonates in excellent yields
under solvent-free conditions.9 The three-component reac-
tion of aldehydes, 2-aminophenol, and diphenyl phosphite
catalyzed by chiral scandium(III)-N,N0-dioxide complexes
afforded the corresponding R-amino phosphonates with
high diastereoselectivity.10 A four-component reaction for the
preparation of R-amino phosphonates has also been developed
by treatment of methyleneaziridines with Grignard reagents,
alkyl halides, and dialkyl phosphites.11 Herein, we wish to
report the application of N-benyloxycarboxylamino sulfones
for a simple and efficient synthesis of R-amino phosphonates.
Treatment of N-benzyloxycarbonylamino sulfones with
triethyl phosphite catalyzed by InCl3 produces the corre-
sponding protected R-amino phosphonates in high yields
(71-92%).
SCHEME 1. N-Benzyloxycarbonylamino Sulfones as Precursors
of N-Acyliminium Ions
R-Amino phosphonic acids and their derivatives exhibit
various important biological properties1 and can serve as
structural analogues of the corresponding R-amino acids.2
They are used as antibacterial,3a,3b anticancer,3c and anti-
HIV agents.3d These compounds are also utilized as peptide
mimics4a and enzyme inhibitors.4b-4d Several medicinally
† Studies on Novel Synthetic Methodologies. 188.
N-Benyloxycarbonylamino sulfones, generally referred to
as R-amido sulfones, can be conveniently prepared12 from
aldehydes and are generally stable solids which can be stored
for prolonged times. It is known that they can be converted
into the corresponding protected imines (N-acyliminium ions)
on treatment with an appropriate Lewis acid (Scheme 1).13
These imine derivatives contain a positively charged nitrogen
atom and are thus highly suitable for nucleophilic addition.
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DOI: 10.1021/jo900558d
r
Published on Web 07/02/2009
J. Org. Chem. 2009, 74, 5607–5609 5607
2009 American Chemical Society