Selectivity in the electrochemical deprotection of cinnamyl groups from oxygen and nitrogen functionalities: Carbonates versus carbamates

Article abstract of DOI:10.1016/j.tetlet.2005.08.020

Several cinnamyloxy carbamates and carbonates were subjected to electrochemical reduction, and the reductive fate of the cinnamyl group was investigated. Complete selectivity was observed in the removal of the cinnamyl group from oxygen versus nitrogen.

Full text of DOI:10.1016/j.tetlet.2005.08.020

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 6851–6854
Selectivity in the electrochemical deprotection of cinnamyl
groups from oxygen and nitrogen functionalities:
carbonates versus carbamates
Petr Cankarˇ,a Diane Dubas,b Scott C. Banfield,b
MÕhamed Chahmab and Tomas Hudlickyb,*
aDepartment of Chemistry, Palacky University, Olomouc, Czech Republic
bDepartment of Chemistry, Brock University, St. Catharines, Ont., Canada L2S 3A1
Received 6 July 2005; revised 29 July 2005; accepted 2 August 2005
Available online 19 August 2005
Abstract—Several cinnamyloxy carbamates and carbonates were subjected to electrochemical reduction, and the reductive fate of
the cinnamyl group was investigated. Complete selectivity was observed in the removal of the cinnamyl group from oxygen versus
nitrogen.
Ó 2005 Elsevier Ltd. All rights reserved.
1. Introduction
O
O
O
O
O
O
N
N
N
The cinnamyl group has been shown to be easily and
selectively removed by electrochemical reduction from
oxygen and nitrogen atoms in preference to all other
allylic systems.1 We have shown that such reductions
are also selective toward removal of cinnamyl groups
in which the double bond is not further substituted or
contained within a ring. Such selectivity is unusual com-
pared to other methods of reduction (dissolved metal,
and palladium-2–5 or ruthenium-6mediated processes).
Further study led to investigations of selectivity in elec-
trochemical reductions of cinnamyl groups from ethers
versus esters, ethers versus amines, cinnamyl ethers ver-
sus benzyl ethers, and cinnamyl versus allyl carba-
mates.7 We have shown that reduction of cinnamyl
groups from oxygen occurs in preference to their
removal from nitrogen and that the cinnamyloxycar-
bonyl (COC) is reduced with complete selectivity in
preference to allyloxycarbonyl (Alloc), which is usu-
ally removed via palladium catalysis, as shown in
Figure 1.
-2.45 V, Hg
N
H
CH3CN
79 %
Ph
1
2
Figure 1. Electrochemical reduction of cinnamyl versus allyl
carbamates.
In this letter, we report the outcome of electrochemical
reductions of cinnamyl carbamates and cinnamyl car-
bonates and note the difference in the mechanism of
reduction of the cinnamyl groups from these two func-
tionalities, as opposed to the fate of their removal from
esters and ethers.
2. Results and discussion
In an earlier letter,7 we reported the electrochemical
behavior of 3, the linear sweep voltammogram (LSV)
of which exhibited three waves (À2.30, À2.73, and
À2.93 V vs AgCl/Ag). Reduction at À2.30 V furnished
aminoalcohol 4 with apparent lack of selectivity, as
shown in Figure 2. Reinvestigation of these results un-
der slightly different conditions (absence of phenol as
proton source) revealed three waves at À2.68, À2.79,
Keywords: Electrochemical reduction; Cinnamyloxy carbonate reduc-
tive deprotection; Cinnamyloxy carbamate reductive deprotection.
Corresponding author. Tel.: +1 905 688 5550x4956; fax: +1 905 984
4841; e-mail addresses: banfield_scott@yahoo.ca; thudlicky@
brocku.ca
*
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.08.020

6852
P. Cankarˇ et al. / Tetrahedron Letters 46 (2005) 6851–6854
O
OH
OH
O
O
O
Ph
Ph
-2.3 V, Hg
CH3CN
-2.53 V, Hg
CH3CN
Ph
OH
+
O
Ph
N
90 %
NH2
HN
O
27 %
O
4
3
5
6
Figure 2. Electrochemical reduction of carbonate versus carbamate.
Table 1. Substrate reduction peak potentials with CH3CN
zation. This result supported previously observed selec-
tivity in the removal of the cinnamyl group from oxygen
in preference to nitrogen but at the same time raised two
additional questions: (1) Why did the carbonate yield
cinnamyl alcohol and not 1-phenylpropene as in the
reductions of esters (ethers)? (2) Is the secondary carba-
mate less prone to reductive cleavage than the more
substituted case of 1? To answer the first question we
analyzed the products from the reduction of ether 7,
ester 8, and carbonate 9. Ether 7 was reduced at a mer-
cury cathode at À2.82 V to afford 1,2,3,4-tetrahydro-2-
naphthol (10) and 1-phenylpropene (11), which was
detected by GC–MS. No cinnamyl alcohol (6) was
detected. The electrochemical reduction of ester 8 affor-
ded cyclohexanecarboxylic acid and a mixture of cinn-
amyl alcohol (6) and 1-phenylpropene (11) in a 1:2
ratio. The electrochemical reduction of carbonate 9 fur-
nished tetrahydronaphthol 10 and cinnamyl alcohol (6),
as shown in Figure 3. These results indicate that the first
reductive event in cinnamyloxycarbonyl substrates
occurs at the carbonyl group and not at the cinnamyl
moiety. The observation that carbonates are reduced
to yield only cinnamyl alcohol (and carbon monoxide)
is consistent with the greater stability of radical anions
derived from carbonate compared to those originating
in esters. In esters such as 8, the tendency to form an
radical anion at the carbonyl versus the styrene unit is
similar, and therefore both reduction products are
observed.
Substrate
Ep1(V)a
Ep2(V)a
Ep3(V)a
3
À2.680
—
À2.790
À2.950
—
À3.080
À3.080
À3.080
À3.020
À3.100
À3.080
À3.080
6
9
À2.690
11
13
14
19
—
—
À2.680
—
—
À2.770
À2.780
À2.760
a Versus AgNO3/Ag.
and À3.09 V versus AgNO3 (0.1 M MeCN)/Ag (Table
1).8 By the comparison of the cyclic voltammogram
(CV) of 3 with that of substrates 6, 9, and 19, the first
wave was shown to correspond to the reduction of the
carbonate, the second resulted from the reduction of
the carbamate, and the third wave was due to cinnamyl
alcohol, produced in the electrochemical reductions that
occurred at the first and second waves. Accordingly, in
the LSV of compound 3 the reductive cleavage of the
carbonate group should occur at À2.68 V. As the reduc-
tion waves of the carbonate and carbamate are so close,
the electrochemical reduction was performed at À2.53 V
potential with 2 F/mol delivered. Surprisingly, alcohol 5
was isolated along with an equivalent of cinnamyl alco-
hol 6. Thus, the previously reported7 non-selective
reduction of 3 to 4 was proven to be erroneous.
The reductive cleavage of the carbonate group clearly
occurred selectively in preference to the carbamate
whose further reduction led to the intramolecular cycli-
We also investigated the reduction of 13 and 14 to deter-
mine the influence of substitution on the reduction of
O
Ph
OH
-2.82 V, Hg
CH3CN
Ph
+
44 %
10
detected by GC-MS
7
11
O
COOH
O
Ph
-2.6 V, Hg
CH3CN
Ph
Ph
OH
OH
Ph
+
+
8
9
12
6
(1:2)
11
OH
O
O
Ph
-2.45 V, Hg
CH3CN
+
O
64 %
6
81 %
10
Figure 3. Reductive fate of cinnamyl ether, ester, and carbonate.

P. Cankarˇ et al. / Tetrahedron Letters 46 (2005) 6851–6854
6853
carbamates. Compound 13 was prepared directly from
4-hydroxypiperidine and cinnamyloxycarbonylimidaz-
ole in the presence of sodium hydride in dry dioxane.
The preparation of the bis-protected 4-aminopiperidine
14 was performed in a similar way by treatment of 4-
aminopiperidine with cinnamyloxycarbonylimidazole
in dichloromethane. The LSV of compound 13 revealed
three waves at À2.55, À2.90 and À3.05 V. Electrochem-
ical reduction at a mercury cathode at À2.55 V fur-
nished alcohol 15 and cinnamyl alcohol (6) in high
yield reflecting full selectivity of the reduction. When
carbamate 15 was subjected to identical reduction condi-
tions in the presence of 2 equivof phenol as a proton
source, complete deprotection was observed to provide
4-hydroxypiperidine (16). Compound 14 showed two
waves at À2.62 and À3.05 V. After the electrochemical
reduction at À2.62 V at the mercury cathode (with and
without the 2 equivof phenol as a proton source) the
cyclic carbamate 17 was isolated in a low yield and a
mixture of 1-phenylpropene (11) and cinnamyl alcohol
(6) were detected by GC–MS in a ratio 2.5/1. When
the cyclic carbamate 17 was subjected to an additional
4 F/mol in the presence of phenol, complete deprotec-
tion was observed to the secondary amine 18 and 1-phe-
nylpropene (11). The isolated yields reported for the
reductions have not been optimized.9 In the case of
O
OH
N
OH
O
N
O
Ph
-2.52 V, Hg
CH3CN
+
-2.55 V, Hg
CH3CN
Ph
OH
Ph
+
N
H
+
82%
11
PhOH, 2 eq.
6
O
O
Ph
100%
conversion
16
79%
15
O
O
O
Ph
13
O
Conditions:
A) -2.62 V, Hg
CH3CN
O
Ph
+
N
N
O
HN
N
O
Ph
Ph
N
O
or
-2.51 V, Hg
OH
Ph
Ph
Ph
+
+
B) -2.62 V, Hg
CH3CN
PhOH, 2eq.
PhOH, 2 eq.
CH3CN
A: 10%
B: 2.3%
6
11
11
N
H
O
O
Ph
O
O
Ph
20%
18
A: 38%
B: 1.5%
17
14
Ph
N
-2.65 V, Hg
CH3CN
O
HN
O
Ph
O
O
32%
20
19
Figure 4. Results of the reductions of carbonate versus tertiary carbamate (in 13), secondary versus tertiary carbamate (in 14), and a secondary
carbamate 19.
A. Initial reduction at styrene site
O
O
O
R
R
R
O
N
O
N
O
N
O
e-
A
H
H
RN
Ph
O
Ph
B
Ph
6-endo-trig
21
Ph
-e-
e-
O
O
O
O
R
R
R
O
N
O
N
O
N
O
O
O
RN
Ph
RHN
Ph
H
H
H
22
Ph
Ph
Ph
B. Initial reduction at carbamate site
Figure 5. Proposed mechanistic options for electrocyclization of secondary carbamates.

6854
P. Cankarˇ et al. / Tetrahedron Letters 46 (2005) 6851–6854
secondary carbamate 19, electrochemical reduction at
À2.65 V at the mercury cathode afforded the cyclic car-
bamate 20 without any formation of cinnamyl alcohol
or 1-phenylpropene (Fig. 4).
(CFI), Ontario Innovation Trust (OIT), TDC Research
Foundation Fellowship to S.C.B., and the Canada Re-
search Chair Foundation.
References and notes
3. Conclusions
1. Solis-Oba, A.; Hudlicky, T.; Koroniak, L.; Frey, D.
Tetrahedron Lett. 2001, 42, 1241.
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3. Oshima, M.; Sakamoto, T.; Maruyama, Y.; Ozawa, F.;
Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. Jpn. 2000, 73,
453.
4. Lautens, M.; Paquin, J. Org. Lett. 2003, 5, 3391.
5. Yoshida, A.; Hanamoto, T.; Inanaga, J.; Mikami, K.
Tetrahedron Lett. 1998, 39, 1777.
6. Maruyama, Y.; Sezaki, T.; Tekawa, M.; Sakamoto, T.;
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7. Hansen, J.; Freeman, S.; Hudlicky, T. Tetrahedron Lett.
2003, 44, 1575.
8. Experimental procedure: Cyclic voltammetry experiments
were performed with 15–30 mg of substrate in 30 mL of
CH3CN containing 0.15 M Et4NBr (or 0.1 M n-Bu4NPF6
for values reported in Table 1). Glassy carbon was used as
the working electrode. Platinum and AgNO3/Ag (0.1 M
CH3CN) were used as counter and references electrodes,
respectively. The working and counter electrodes were
polished on alumina before use. iR compensations were
applied for all experiments for potential measurements.
Sweep rates were typically 100 mV/s. The reported poten-
tials are for peak maxima. The electrolyses were performed
at controlled potential in a cell with two compartments. The
cathode was a mercury pool and the anode was platinum.
The reactions were monitored by observing the drop in the
current and by TLC. The solution was decanted into ether
and filtered to remove the electrolyte. The filtrate was
concentrated and the products isolated by column
chromatography.
The electrochemical reduction of carbonates versus car-
bamates proceeds with complete selectivity with the car-
bonate moiety reduced in preference to carbamate. In
the absence of a proton source, tertiary carbamates are
not reduced and secondary carbamates cyclize via one
of the possible pathways proposed in Figure 5. In carba-
mates, the tendency to form the ketyl versus styryl
radical anion may be similar (as in esters). We offer an
initial speculation regarding two options that may be
possible: one involving the proton transfer as in path-
way A (Fig. 5), the other proceeding through the ketyl
cyclization as in pathway B. Both pathways would lead
to the same product, 22, after a loss of an electron from
ketyl 21.
In the presence of a proton source, tertiary carbamates
are fully reduced to amines and cinnamyl alcohol.
Secondary carbamates are prone to cyclization follow-
ing the first electron transfer and are not further
reduced. The selectivity of removal of the cinnamyl
group favors the less basic atom (oxygen), in agreement
with previously reported observations for ethers versus
amines.7 The mechanism of the observed electrocycliza-
tion will be investigated in detail, and the results as well
as potential applications in synthesis will be reported in
due course.
Acknowledgements
9. The conversions of substrates to products were complete
(vide TLC analysis). Isolation and purification of products
at the scale at which the initial experiments were performed
(0.2–0.7 mM) were complicated by the large amount of
electrolyte used. Optimized larger scale procedures will
obviate these problems.
This work was funded by National Science and Engi-
neering Research Council (NSERC) of Canada,
NSERC-PDF to S.C.B., Petroleum Research Fund
administered by the American Chemical Society (PRF-
38075-AC), Canadian Foundation for Innovation