Tetrahedron Letters
Low-valent titanium-catalyzed deprotection of allyl- and
propargyl-carbamates to amines
⇑
Suchithra Madhavan, Hiromasa Takagi, Shunpei Fukuda, Sentaro Okamoto
Department of Materials and Life Chemistry, Kanagawa-University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
In the presence of Me3SiCl, Ti(O-i-Pr)4/Mg and CpTiCl3/Mg reagents effectively catalyzed the deprotection
of allyloxycarbonyl (alloc)- and propargyloxycarbonyl (poc)-protected amines in THF at around room
temperature to produce parent amines in good yields. Alloc- and poc-protected secondary amines were
smoothly deprotected to parent amines by a reaction catalyzed by a Ti(O-i-Pr)4/Me3SiCl/Mg reagent. The
deprotection of alloc- and poc-protected primary amines was successfully catalyzed by a CpTiCl3/
Me3SiCl/Mg reagent.
Received 19 February 2016
Revised 24 March 2016
Accepted 29 March 2016
Available online 29 March 2016
Keywords:
Deprotection
Ó 2016 Elsevier Ltd. All rights reserved.
Low-valent titanium
Allyloxycarbonyl
Propargyloxycarbonyl
Amines
The protection/deprotection of organic functional groups is of
great importance in organic synthesis.1 Mild conditions that
achieve high functional group compatibility and selectivity are
desired for the introduction and removal of protective groups.
Groups that protect amine functionalities are of significant interest
for the synthesis of nitrogen-containing molecules. The allyloxy-
carbonyl (alloc) group has been a useful protecting group for ami-
nes, and allyl carbamates are readily formed by reacting with alloc
chloride under mild conditions. The removal of an alloc moiety
from allyl carbamates to give the parent amine has conventionally
been accomplished under neutral, mild conditions through
reactions catalyzed by transition metals such as Pd and Ni in the
presence of a suitable nucleophile or hydride source, e.g., amines,
thiols, HCO2H, tin hydrides, and silyl hydrides.1 However, there
are drawbacks associated with heavy-metal-based deprotection
reactions: the high cost of reagents, reagent toxicity, and/or the
competitive formation of allylamine.2,3
We recently developed facile, selective C–O cleavage reactions
of allyl and propargyl ethers that were catalyzed by a low-valent
titanium Ti(O-i-Pr)4 (1a)/Me3SiCl/Mg reagent.6,7 In addition, we
found that a titanatrane complex 1b8 (Scheme 1) in the presence
of Me3SiCl and Mg powder selectively generated a Ti(III) species,
which catalyzed the deallylation and depropargylation of allyl
and propargyl ethers, respectively (Eq. 1 in Scheme 1).7d On the
basis of these results, we conducted an extensive investigation of
the deprotection of allyl and propargyl carbamates by low-valent
titanium reagents. Consequently, we found that allyl carbamates
2 and propargyl carbamates 3 were efficiently deprotected to the
parent amines 4 through a reaction catalyzed by low-valent
titanium reagents generated from Ti(O-i-Pr)4 (1a), the titanatrane
complex 1b, or CpTiCl3 (1c)9,10 in the presence of Me3SiCl and
Mg (Eqs. 2 and 3, respectively).
First, we investigated the reactions of the allyl carbamate 2a
and 2b derived from dibenzylamine and 2-phenylethylamine,
respectively, with Ti complex (1)/Me3SiCl/Mg reagents (Equation
in Table 1). Thus, to a mixture of allyl carbamate 2, a Ti complex,
and Mg powder in THF, Me3SiCl was added at room temperature.
The yields of 4 were determined by 1H NMR analyses using an
internal standard. The results are summarized in Table 1.
The propargyloxycarbonyl (poc) group is stable at various acidic
and basic conditions and is considered a protective group for
alcohols and amines.4 Deprotection of poc-protected alcohols and
amines is conventionally conducted by reaction with a stoichio-
metric amount of benzyltriethylammonium tetrathiomolybdate
(BnNEt3)2MoS4.4,5 The development of
a
milder, inexpensive
The allyl carbamate of secondary amine 2a was successfully
deprotected to its parent dibenzylamine by the reaction with
Me3SiCl/Mg in the presence of a catalytic amount of 1a, 1b, or 1c
in THF at room temperature (runs 1–6). Note that the presence
of Me3SiCl was essential for catalysis. However, deprotection of the
alloc derivative of primary amine 2b was problematic (runs 7–13).
deprotection method of poc-protected groups is desired.
⇑
Corresponding author.
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.