Direct conversion of azides and benzyl carbamates to t-butyl carbamates using polymethylhydrosiloxane and Pd-C

Article abstract of DOI:10.1246/cl.2000.780

One step direct conversion of azides and benzyl carbamates to t-butyl carbamales is achieved using inexpensive and safe hydride source namely polymethylhydrosiloxane (PMHS) under Pd-C catalysis.

Full text of DOI:10.1246/cl.2000.780

780
Chemistry Letters 2000
Direct Conversion of Azides and Benzyl Carbamates to t-Butyl Carbamates Using
Polymethylhydrosiloxane and Pd-C
S. Chandrasekhar,* L. Chandraiah, Ch. Raji Reddy, and M. Venkat Reddy
Indian Institute of Chemical Technology, Hyderabad 500 007, India
(Received April 13, 2000; CL-000351)
One step direct conversion of azides and benzyl carba-
mates to t-butyl carbamates is achieved using inexpensive and
safe hydride source namely polymethylhydrosiloxane (PMHS)
under Pd-C catalysis.
N-(t-Butoxycarbonyl) functionality plays a major role as
the protective group for amines in the synthesis of unusual
amino acids and also in peptide chemistry.1 This is due to its
reasonable stability and easy removal under mild conditions. In
the former case an amino group is generally introduced through
azide and then reduced to amine followed by blocking prefer-
ably as t-butyl carbamate. A few attempts have been made
recently to achieve this transformation in “one-pot”.2 Similarly
interconversion of one protective group to other especially
direct conversion of benzyl carbamates to t-butyl carbamates
has been gaining prominence.3 The activity of clinically used
anticancer compound Taxotere® is attributed to t-Boc present in
side chain amino acid of Taxol.4 This back ground of N-Boc in
organic and medicinal chemistry and also our own interest in
making amino containing clinically useful compounds has
prompted us to develop a new and efficient “one pot” protocol
for direct conversion of azides and benzyl carbamates to t-butyl
carbamtes (Equations 1 and 2). Our efforts in this direction
have resulted in identifying PMHS as an efficient reagent5
under Pd-C catalysis. The findings are documented herein.
PMHS is gaining prominence in the recent times especially as a
safe, economic alternative in reductions.6
and entry 6 of Table 2) is however noted as a minor limitation
of this reaction.
A typical experimental procedure for both the transforma-
tions is as follows: To a solution of substrate (1.0 mmol) in
ethyl alcohol (10 mL) was added 10% Pd-C (~15 mg), PMHS
(0.180 g, 3 mmol) and di-t-butyl dicarbonate (0.240 g, 1.1
mmol). After stirring for given time (see Tables), the reaction
mixture was filtered and filtrate was evaporated in vacuo. The
residue was chromatographed on silica gel to the corresponding
N-Boc products in excellent yields8 (see tables).
In conclusion, we have developed a convenient method for
direct conversion of azides and N-Cbz protected amines to more
useful N-Boc protected amines. We believe that the reagent
system described here has tremendous potential for use in
organic synthesis due to its high chemoselectivity, efficiency,
economy, simplicity, and safety. The application of the present
methodology to the natural product synthesis is currently under-
way.
The results pertaining to both these transformations are
summerized in Tables 1 and 2 respectively. Interestingly,
hydrogenation sensitive substrates (entries 3 and 7 of Table 1
and entries 3, 4, 5 and 6 of Table 2) underwent smooth chemos-
elective conversions. Also other protective groups viz.,
TBDMS ether (entry 8 of Table 2), ester substrates (entries 5, 6,
8 and 10 of Table 2) and acetal group (entry 9 of Table 2) were
unaffected. Entry 8 (Table 1) demonstrates smooth reductive
protection to generate a Sertraline intermediate,7 a powerful
clinically used antidepressant. The halo aromatics (entries 2
and 8 of Table 1) were also stable to present protocol.
Reduction of double bond in the substrate (entry 4 of Table 1
We thank INSA (New Delhi) for research grant and CSIR,
New Delhi for fellowship to three of us (LC, CRR and MVR).
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
781
(1991). (b) G. M. Coppola and H. F. Schuster,
“Construction of Chiral Molecules using Amino Acids,”
John Wiley & Sons, New York (1987).
2
3
a) H. Kotsuki, T. Ohishi, and T. Araki, Tetrahedron Lett.,
38, 2129 (1997). see also: T. J. Woltering, G. Weitz-
Schmidt and C. H. Wong, Tetrahedron Lett., 37, 9033
(1996). b) C. A. M. Afonso, Tetrahedron Lett., 36, 8857
(1995) and references cited therein.
a) J. S. Bajwa, Tetrahedron Lett., 33, 2955 (1992). b) M.
Sakaitani, K. Hori, and Y. Ohfune, Tetrahedron Lett., 29,
2983 (1988).
4
5
F. Gueritte, D. Guenard, F. Lavelle, M. T. LeGoff, L.
Mangatal, and P. Polier, J. Med. Chem., 34, 992 (1991).
a) S. Chandrasekhar and M. Ahmed, Tetrahedron Lett., 40,
9325 (1999). b) S. Chandrasekhar, M. Venkat Reddy, and
L. Chandraiah, Synth. Commun., 29, 3981 (1999). c) S.
Chandrasekhar, Y. Ravindra Reddy, and Ch. Raji Reddy,
Chem. Lett., 1998, 1273. d) S. Chandrasekhar, Y. Ravindra
Reddy, and C. Rama Rao, Synth. Commun., 27, 2251
(1997).
6
a) H. Mimoun, J. Y. S. Laumer, L. Giannini, R. Scopelliti,
and C. Floriani, J. Am. Chem. Soc., 121, 6158 (1999). b) X.
Verdaguer, U. E. W. Lange, and S. L. Buchward, Angew.
Chem., Int. Ed. Engl., 37, 1103 (1998). c) D. S. Hays and
G. C. Fu, J. Org. Chem., 63, 2796 (1998) and references
cited therein. d) M. D. Drew, N. Lawrence, D. Fontaine,
and L. Sehkri, Synlett, 1997, 989.
7
8
S. Chandrasekhar and M. Venkat Reddy, Tetrahedron, 56,
1111 (2000).
All the products were characterized after chromatography
by IR, 1H NMR and mass spectroscopy.
References and Notes
IICT Communication No. 4401.
1
a) T. W. Greene and P. G. M. Wuts, “Protective Groups in
Organic Chemistry,” John Wiley & Sons, New York