Single-step conversion of N-benzyl, N-trityl and N-diphenylmethyl amines to t-butyl carbamates using polymethylhydrosiloxane

Article abstract of DOI:10.1016/S0040-4039(03)00172-2

t-Butyl carbamates were obtained efficiently in high yields from the corresponding N-benzyl, N-trityl and N-diphenylmethyl precursors in a single-step reductive transformation employing polymethylhydrosiloxane and di-t-butyl dicarbonate under Pd(OH)₂/C catalysis.

Full text of DOI:10.1016/S0040-4039(03)00172-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2057–2059
Single-step conversion of N-benzyl, N-trityl and
N-diphenylmethyl amines to t-butyl carbamates using
polymethylhydrosiloxaneꢀ
S. Chandrasekhar,* B. Nagendra Babu and Ch. Raji Reddy
Indian Institute of Chemical Technology, 500007 Hyderabad, India
Received 12 December 2002; revised 7 January 2003; accepted 17 January 2003
Abstract—t-Butyl carbamates were obtained efficiently in high yields from the corresponding N-benzyl, N-trityl and N-diphenyl-
methyl precursors in a single-step reductive transformation employing polymethylhydrosiloxane and di-t-butyl dicarbonate under
Pd(OH)2/C catalysis. © 2003 Elsevier Science Ltd. All rights reserved.
The protection, deprotection and interconversion of
protecting groups form an integral part of multistep
organic synthesis. A direct method for interconversion
of one protecting group to another is often a desired
transformation as it increases synthetic efficiency by
avoiding the intermediate steps.1 Amines are an impor-
tant part of many bio-active natural products and they
are useful intermediates both in protected as well as
unprotected forms, in basic as well as in applied
research.2 Among various N-protecting groups, the t-
butyloxycarbonyl group is one of the most commonly
and frequently used protecting groups due to its reason-
able stability and ease of cleavage under mild condi-
tions. Besides this, the presence of Boc protection in the
Taxol side chain (Taxotere®) is important.
organic synthesis.5,6 In continuation of these studies,
herein we wish to report a new and efficient protocol
for the one-pot reductive transformation of N-benzyl,
N-trityl and N-diphenylmethyl amines to the corre-
sponding t-butylcarbamates using polymethylhy-
drosiloxane and di-t-butyl dicarbonate in the presence
of Pd(OH)2/C catalysis (Scheme 1).
The scope and generality of this reagent system is
illustrated with several examples and the results are
summarized in Tables 1 and 2. Initially, N,N-dibenzyl
phenyl glycine methyl ester was treated with PMHS
and (Boc)2O in the presence of Pd(OH)2/C in absolute
ethanol at room temperature to afford the correspond-
ing t-butyl carbamate in 90% isolated yield, with the
ester functionality being unaffected (entry 1, Table 1).7
Interestingly, it was found that the transformation pro-
ceeded smoothly without affecting the commonly used
hydroxyl protecting groups MPM, MOM and TBS
ethers (entries 3, 4 and 6, Table 1). This conversion is
also effective in the presence of a free hydroxyl group
(entry 5, Table 1). We have observed that when a
benzyl ester is present within the substrate, the resultant
product was devoid of it affording the corresponding
acid (entry 7, Table 1). As a minor limitation, we found
that double bond reduction occurred in the case of the
A literature search showed that, there are few examples
of the conversion of N-benzyl and N-trityl amines to
t-butyl carbamates.3 There are, to our knowledge, no
reports presenting the direct conversion of N-diphenyl-
methyl amines to t-butyl carbamates. Consequently, the
development of new and general methods for these
purposes is being pursued. In our development of new
reduction procedures for the synthesis of t-butyl carba-
mates,4 we were especially interested in exploring the
potential use of polymethylhydrosiloxane (PMHS)
which has gained prominence as a safe and economic
reagent in recent times as a versatile reductant in
Keywords: polymethylhydrosiloxane; di-tert-butyl dicarbonate.
ꢀ IICT Communication No. 020909.
* Corresponding author. Tel.: +91-40-7193434; fax: +91-40-7160512;
e-mail: srivaric@iict.ap.nic.in
Scheme 1.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00172-2

2058
S. Chandrasekhar et al. / Tetrahedron Letters 44 (2003) 2057–2059
Table 1. Conversion of -NBn2 and NBn to -NHBoc and
NBoc protected amines
Table 2. Conversion of trityl (Tr) and diphenylmethane
(DPM) protected amines to Boc protected amines
N-allyl substituted amines (entry 8, Table 1). The sta-
bility of the aromatic ring and aliphatic ketone is an
added advantage of this protocol (entries 9 and 10,
Table 1).
Encouraged by these findings we have extended the
reaction conditions to N-trityl and N-diphenylmethyl
amine substrates and it was found that this protocol
holds equally well with respect to aliphatic as well as
aromatic substrates (entries 1–10, Table 2). It is worth
mentioning that the halo functionality was also stable
to the present reaction conditions (entry 6, Table 2).
(ꢀ15 mg). Di-t-butyl dicarbonate (240 mg, 1.1 mmol)
was added and the reaction mixture was stirred at room
temperature for the given time (see Tables 1 and 2).
After completion of the reaction, the mixture was
filtered and the filtrate was evaporated in vacuo. The
residue was purified by column chromatography on
silica gel to give the corresponding NH-Boc or N-Boc
products in excellent yields.8
In conclusion, we have developed a new and convenient
method for the direct conversion of N-benzyl, N-trityl
and N-diphenylmethyl amines to t-butyl carbamates.
We firmly believe that the present protocol has poten-
tial utility in organic synthesis due to its chemoselectiv-
ity, efficiency, economy, simplicity and safety.
Acknowledgements
Typical experimental procedure: To a stirred solution of
the substrate (1 mmol) in ethyl alcohol (10 mL) was
added PMHS (180 mg, 3 mmol) and 10% Pd(OH)2/C
B.N.B. and C.R.R. thank the CSIR, New Delhi, for
financial assistance.

S. Chandrasekhar et al. / Tetrahedron Letters 44 (2003) 2057–2059
2059
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1
8. Spectroscopic data of the products: (entry 3, Table 1): H
NMR (CDCl3): l 7.2 (d, J=8.6 Hz, 2H), 6.82 (d, J=8.6
Hz, 2H), 4.4 (s, 2H), 3.78 (s, 3H), 3.47 (t, J=4.8 Hz, 2H),
3.27 (m, 2H), 1.43 (s, 9H); EIMS (m/z): 137 (M+−144).
1
(Entry 4, Table 1): H NMR (CDCl3): l 4.61 (s, 2H), 3.59
(t, J = 4.4 Hz, 2H), 3.36–3.28 (m, 5H), 1.46 (s, 9H); EIMS
1
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l 3.6 (broad s, 1H), 1.59–1.49 (m, 14H), 1.43 (s, 9H);
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