DBU-promoted nucleophilic activation of carbonic acid diesters

Article abstract of DOI:10.1002/ejoc.201001725

The reactivity of carbonic acid diesters in the presence of the amidine base DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) has been investigated for the first time. Organic carbonates can be activated by DBU through the formation of N-alkoxycarbonyl ketene aminal 2 as the ultimate product. The latter species may form through deprotonation of the corresponding N-alkoxycarbonyl-amidinium cation 1⁺ by the amidine base. We have for the first time isolated and characterized, both in the solid state (X-ray crystal structure determination, IR) and in solution (NMR), a few 1⁺ chloride salts and studied their reactivity towards the organic base. The reactivity of both 1⁺ and 2 with methanol has also been explored. Ketene aminal 2 behaves as a "CO₂R" carrier, as it can selectively transfer the alkoxycarbonyl group to the alcohol and regenerate the amidine base. Carbonic acid diesters can be activated by the amidine base DBU to give N-alkoxycarbonyl ketene aminal 2. The latter species may form through deprotonation of N-alkoxycarbonyl-amidinium cations 1⁺ by the amidine base and behave as carriers of the -C(O)OR group. Copyright

Full text of DOI:10.1002/ejoc.201001725

FULL PAPER
DOI: 10.1002/ejoc.201001725
DBU-Promoted Nucleophilic Activation of Carbonic Acid Diesters
Marianna Carafa,[a] Ernesto Mesto,[b] and Eugenio Quaranta*[a]
Keywords: Organocatalysis / Reaction mechanisms / Amidine base / Carbonic acid ester
The reactivity of carbonic acid diesters in the presence of the
amidine base DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) has
been investigated for the first time. Organic carbonates can
be activated by DBU through the formation of N-alkoxy-
carbonyl ketene aminal 2 as the ultimate product. The latter
species may form through deprotonation of the correspond-
ing N-alkoxycarbonyl-amidinium cation 1+ by the amidine
base. We have for the first time isolated and characterized,
both in the solid state (X-ray crystal structure determination,
IR) and in solution (NMR), a few 1+ chloride salts and studied
their reactivity towards the organic base. The reactivity of
both 1+ and 2 with methanol has also been explored. Ketene
aminal 2 behaves as a “CO2R” carrier, as it can selectively
transfer the alkoxycarbonyl group to the alcohol and regen-
erate the amidine base.
Introduction
The ability of amidine bases, such as DBU (1,8-diazabi-
cyclo[5.4.0]undec-7-ene), to act as nucleophiles towards a
variety of electrophiles has been well established in the last
few years.[1,2] Recently, it has been proposed that DBU can
act as a nucleophile and react with electrophilic substrates,
such as carbonic acid diesters [dimethyl carbonate (DMC)
and dibenzyl carbonate], and activate them by forming the
cationic intermediate N-alkoxycarbonyl DBU derivative 1+
[Equation (1)].[3] It is proposed that the latter species plays
a key role in several important DBU-catalyzed synthetic
processes, such as esterification of carboxylic acids with
DMC, methylation of phenols, indoles, and benzimidazoles
with DMC, benzylation of the N, O, and S atoms with di-
benzyl carbonate,[3] and in perhaps some recently described
carbonylation processes.[4a,4c] However, the reactivity of car-
bonic acid diesters in the presence of DBU has never been
investigated. Direct evidence supporting equilibrium (1) is
still lacking. Furthermore, the chemistry of the 1+ adduct
is practically unknown, as 1+ salts have never been isolated
nor characterized.
(1)
devoted to exploring new ways to activate carbonic acid
diesters,[4] we also focus on the direct reaction of dialkyl,
diaryl, and aryl alkyl carbonates with DBU. We demon-
strate that ketene aminal 2 forms, as the ultimate product,
from the addition of DBU to carbonic acid diesters by an
equilibrium process likely involving intermediate 1+. The re-
activity of both 1+ and their conjugated bases 2 with meth-
anol is also described. The behavior of ketene aminal 2 as
a “CO2R” carrier is highlighted.
Herein, for the first time, we report the isolation and full
characterization, both in the solid state (X-ray crystal struc-
ture determination, IR) and in solution (NMR), of a few
1+ chloride salts (1a, R = Me; 1b, R = Ph), and the conver-
sion of the N-alkoxycarbonyl-amidinium adduct 1+
(Scheme 1) into the ketene aminal 2 (Scheme 1) in the pres-
ence of the amidine base DBU. As a part of our studies
Scheme 1. Numbering system in DBU, 1+, and 2.
Results and Discussion
[a] Dipartimento di Chimica, Università degli Studi di Bari “Aldo
Moro”, Campus Universitario,
Via E. Orabona 4, 70126 Bari, Italy
Isolation and Characterization of N-Alkoxycarbonyl-
Amidinium Chloride Salts 1a (R = Me) and 1b (R = Ph)
Fax: +39-080-5442129
E-mail: quaranta@chimica.uniba.it
[b] Dipartimento Geomineralogico, Università degli Studi di Bari
“Aldo Moro”, Campus Universitario,
Via E. Orabona 4, 70126 Bari, Italy
Chloride salts 1a and 1b were prepared by treating DBU
with the corresponding chloroformate [Equation (2)] at
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DBU-Promoted Nucleophilic Activation of Carbonates
293 K in ethereal solvents. Depending on the reaction con-
ditions, the product precipitated along with variable
amounts of DBU·HCl. Both compounds were hygroscopic,
and 1a was isolated as the monohydrate salt 1a·H2O.
(2)
Figures 1 and 2 show the crystal structures of 1a·H2O
and 1b as determined by X-ray single crystal analysis. As
expected, atoms C12, O1, O2, and N8 lie in the same plane
[root-mean-square deviations: 0.006 Å (for 1b), 0.003 Å (for
1a·H2O)]. The plane is rotated with respect to that of C7,
N8, N1, C6, C11, and C2 and with a rotation angle reversed
in the two adducts [1b: –47.68(4), 1a·H2O: 42.79(6)]. Conse-
quently, in 1b the C12–O1 bond is almost perpendicular to
the mean plane individuated by C6, C5, C3, and C2, but is
parallel to the above plane in 1a·H2O. The root-mean-
Figure 2. ORTEP view of the salt 1b (displacement ellipsoids are
set at 50%). The hydrogen labels are omitted for clarity. Selected
bond lengths [Å] and angles [°]: O1–C12 1.1900(14), O2–C12
1.3379(14), O2–C13 1.4080(13), N8–C9 1.4799(15), N8–C7
1.3642(14), N8–C12 1.4162(14), N1–C11 1.4776(16), N1–C7
1.3036(14), N1–C2 1.4868(15), C12–O2–C13 119.39(9), N8–C12–
O2 107.19(9), N8–C12–O1 125.91(10), O2–C12–O1 126.87(10),
C9–N8–C7 119.55(9), C9–N8–C12 119.03(9), C7–N8–C12
121.13(9), C11–N1–C7 124.26(10), C11–N1–C2 114.0(1), C7–N1–
C2 121.57(10), O1–C12–N8–C7 –30.19(17), C9–N8–C7–N1
–13.94(16), N8–C7–N1–C11 –1.38(17), C6–C7–N1–C2 3.06(13),
O2–C12–N8–C9 –34.67(13), O1–C12–N8–C9 143.58(12), O2–C12–
N8–C7 151.56(98), O1–C12–N8–C7 –30.19(17).
square deviation from the mean plane of C7, N8, C12, and
C9 is only 0.022 Å in 1b and 0.033 Å in 1a·H2O, showing
that N8 retains a noteworthy sp2-hybridized character in
both adducts. The plane is twiddled [20.51(5)° in 1b,
17.90(5)° in 1a·H2O] with respect to that of C7, N8, N1,
C6, C11, and C2 but is rotated [32.19(5)° in 1b, 29.79(6)°
in 1a·H2O] with respect to the plane containing the car-
bonyl bond (N8, C12, O1, and O2). The latter feature is
intriguing as it suggests in both salts that the N8 atom con-
jugates preferentially with the atoms C7 and N1 of the ami-
dine moiety rather than with the carbonyl group. Accord-
ingly, in both salts, the N8–C12 bond length is longer than
usually reported in the literature for carbamate com-
Figure 1. ORTEP view of the salt 1a·H2O (displacement ellipsoids
are set at 50%). The hydrogen labels are omitted for clarity. Se- pounds,[5,6] but the N8–C7 bond is shorter than expected
for a CN single bond.[7]
lected bond lengths [Å] and angles [°]: O1–C12 1.192(2), O2–C12
1.327(2), O2–C13 1.454(2), N8–C9 1.486(2), N8–C7 1.359(2), N8–
In both structures the C=O bond is slightly shorter than
C12 1.414(2), N1–C11 1.477(3), N1–C7 1.309(2), N1–C2 1.484(2),
found in related systems.[5,8] Accordingly, the C=O IR fre-
C12–O2–C13 114.39(16), N8–C12–O2 109.37(15), N8–C12–O1
quency (Table 1) is higher than normally observed for car-
124.49(16), O2–C12–O1 126.15(17), C9–N8–C7 119.19(14), C9–
N8–C12 120.12(14), C7–N8–C12 120.60(14), C11–N1–C7
124.36(16), C11–N1–C2 114.61(15), C7–N1–C2 121.03(16), O1–
C12–N8–C7 27.60(26), C9–N8–C7–N1 13.91(22), N8–C7–N1–C11
5.51(24), C6–C7–N1–C2 2.69(23), O2–C12–N8–C9 31.89(21), O1–
C12–N8–C9 –148.95(18), O2–C12–N8–C7 –151.55(15), O1–C12–
N8–C7 27.60(26).
bamate esters.[8]
In addition, both salts were characterized in solution by
NMR spectroscopy (Table 1 and Exp. Section). The reso-
nance of the iminium C7 is characteristic and located at
approximately 172 ppm. The value measured for C7 in 1a
Table 1. Selected IR[a] and NMR[b] spectoscopy data for the salts 1a–b and ketene aminals 2a–b.
ν(C=O)
ν(C=N)
ν(C=C)
δH(H6)
δH(H5)
δC(CO2)
δC(C6)
δC(C7)
[d]
1a[c]
1b[c]
2a[e]
2b
1748
1764
1639
1633
–
–
–
3.29
3.31
152.80
150.89
155.43
153.18
33.77
34.04
172.62
172.69
143.19
142.83
[d]
1701, 1716[f]
1663
4.71[g]
1.98
2.01
105.27[h]
1709[i]
–
4.89[g]
106.04[h]
[j]
3
[a] ν [cm–1]. [b] In CDCl3. δ [ppm]. [c] IR done in Nujol. [d] See Exp. Section. [e] IR done neat. [f] Shoulder. [g] br. t, JH,H = 6 Hz, 1 H.
1
[h] dm, JC,H = 159–160 Hz. [i] In CDCl3. [j] Masked.
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M. Carafa, E. Mesto, E. Quaranta
FULL PAPER
(172.62 ppm) is close to that (171.5 ppm) reported by
For instance, at room temperature the alkyl aryl carbon-
Shieh,[3a] who obtained 1a in situ by reacting MeOC(O)Cl ates MeOC(O)OPh (3a) or tBuOC(O)OPh (3c), or the di-
with an excess amount of DBU.[9]
aryl carbonate (PhO)2CO (3b), were treated with the amid-
ine base to afford ketene aminals 2a, 2c, and 2b, respectively
(Table 2).
Conversion of Amidinium Cation 1+ into Ketene Aminal 2
(2a, R = Me; 2b, R = Ph)
Table 2. Reaction of DBU with ROC(O)OPh (3; 3a, R = Me; 3b,
R = Ph; 3c, R = tBu) at 293 K, and selected IR[a] spectroscopy
data and yields for products 2.
By using the reaction of DBU with MeOC(O)Cl, we were
able to isolate and fully characterize the unprecedented ke-
tene aminal 2a (Table 1).
R
3/DBU
[mol/mol]
DBU
[μL]
THF[b]
[mL]
2
ν(C=O)
2[c]
[%]
To the best of our knowledge, the literature reports only
Me
4
1
150
300
–
–
2a
2a
1701 (vw)
1701 (m)
17
18
a few examples of N-alkoxycarbonyl-substituted ketene am- Me
1716 (m)[d]
inals.[10] In the 13C NMR spectrum of 2a the imine C7 atom
[e]
tBu
tBu
tBu
4
1
0.25
120
300
640
–
–
–
2c
2c
2c
6
8
25
resonates at 143.19 ppm, while the doublet of multiplets at
1705 (w)
1694 (m)
105.27 ppm (1JC,H = 159 Hz) is due to the sp2-hybridized
1701 (m)[d]
C6 with only one H atom directly bound. The attached H6
[f]
3
Ph
Ph
3
1
140
190
2
0.3
2b
2b
20
25
proton absorbs at 4.71 ppm (br. t, JH,H = 6 Hz, 1 H) and
is coupled with the vicinal H5 protons, which produce a
pseudo-quartet at higher fields (δ =1.98 ppm).
1716 (m)
1732 (m)[d]
1717 (ms)
1732 (ms)[d]
Ph
0.25
870
–
2b
70
Equilibrium (3) may offer a plausible rationale for the
formation of 2a. Accordingly, the addition of DBU
(0.2 equiv.) to a CDCl3 solution of 1a prompted the rapid
formation of 2a, with easily identifiable 1H NMR reso-
nances in the spectrum of the reaction mixture. At 293 K
in CDCl3, 1b was also treated with DBU to readily give
2b according to Equation (3). The NMR spectrum of the
reaction mixture (DBU/1b, 0.5 mol/mol) showed the ap-
pearance of new signals from DBU·HCl and ketene aminal
2b (R = Ph). The spectroscopic features of 2b agreed fully
with those exhibited by 2a (Table 1 and Exp. Section). Equi-
librium (3) lies to the right. In fact, the addition of more
DBU (overall DBU/1b molar ratio: 1) favored the pro-
duction of 2b and DBU·HCl, and resulted in the disappear-
ance of the resonances due to 1b. Accordingly, in the IR
spectrum of the solution, the carbonyl absorption of 1b at
1760 cm–1 was replaced by that of 2b, centered at 1709 cm–1.
These findings clearly show that 1+ is not a stable species
in the presence of free DBU, which can act as an effective
base to the cation and abstract one of the acidic H6 pro-
tons.[2c,11,12]
[a] Liquid film, ν [cm–1]. [b] Used as solvent. [c] NMR yields, based
on the limiting reagent. Normally, yields of 2 were measured after
a reaction time of 4–8 h and did not change significantly after 20–
24 h. [d] Poor or unresolved. [e] Not observed. [f] Not measured.
Besides the signals from the carbonate and DBU, the IR
spectra of the reaction mixtures showed new weak to me-
dium absorptions between 1700 and 1730 cm–1, consistent
with the formation of 2. NMR spectroscopy was much
1
more informative. H NMR decoupling experiments of the
solutions, and analysis in those regions of the spectra not
obscured by other resonances (3, DBU, PhOH), allowed us
to locate most of ketene aminal resonances, such as the very
characteristic ones due to H6 and H5 (see Exp. Section). In
the 13C NMR spectra of the mixtures, all the signals for
2a–c were easily identifiable, and the diagnostic resonances
due to C6, C7, and CO2 were found in the expected ranges
(see Exp. Section).
As a whole, the spectroscopic data support the establish-
ment of equilibrium (4). Equilibrium (4) lies to the left and
its position depends on the nature of R and the molar ratio
of carbonate/DBU (Table 2).
(3)
(4)
Ketene aminals 2a–c may form from the intermediate
ionic species (1+)–OPh (R = Ph, Me, tBu), ensuing from
Reaction of DBU with Carbonic Acid Diesters
The above data provide the key for rationalizing the the nucleophilic attack of DBU on the carbonyl group of 3
chemistry of organic carbonates in the presence of [Scheme 2, Equation (4a)].[3a] However, the NMR spectra
DBU.[3,4a,4c] Herein, we show that DBU can interact with did not show any detectable amount of (1+)–OPh, in ac-
carbonic acid diesters to give ketene aminal 2 as the ulti- cordance with the fact that once 1+ formed, it easily con-
mate product.
verted into 2 in the presence of free DBU.
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DBU-Promoted Nucleophilic Activation of Carbonates
rium (4), because of the tendency of the alcohol, ROH, to
react with 2 and give back DBU and (RO)2CO, as we have
ascertained in the case for the reaction of 2a with MeOH
(see below).
(5)
Scheme 2. Plausible reaction pathway to ketene aminal 2.
Reactivity of 1+ and 2 Towards Methanol
Moreover, in experiments with 3a or 3c, no evidence for
the formation of 2b was found. This suggests that the nucleo-
philic attack of DBU on an unsymmetrical carbonate
ROC(O)OPh results in the selective expulsion of PhO–. In
accordance with the selective formation of intermediate A
with respect to B (Scheme 3), we found that, at a higher
temperature (393 K, 24 h) and with 0.25 equiv. of DBU, 3a
was decarboxylated to anisole,[4c] but we did not observe
the disproportionation of 3a to dimethyl carbonate and di-
phenyl carbonate (3b).
In principle, both the amidinium cation 1+ and its respec-
tive ketene aminal 2 are potential carbonylating substrates.
This fact prompted us to explore their reactivity as carbon-
ylating agents[4,14] and ascertain if 1+ and/or 2 formed by
reaction of the carbonate with DBU are really activated
forms of that original organic carbonate. In this study we
focused on methanol, a relatively weak nucleophilic species,
as the reference nucleophile.
We found that after a long time period (17 h) at 293 K
in CDCl3, neither 1b nor 3b showed any significant reactiv-
ity with a 2-fold molar excess amount of MeOH. However,
a drastic change in reactivity was observed when, under the
same reaction conditions, 1b was treated with 2 molar
equiv. of MeOH in the presence of a catalytic amount of
DBU (approximately 20 mol-% relative to 1b+). As a matter
of fact, the amidine base promoted the smooth formation
of DBU·HCl and 3a; see Equation (6). The conversion of
1b was complete within about 1 h.
Scheme 3.
(6)
No spectroscopic (IR, NMR) evidence has been ob-
tained for the formation of ketene aminal 2 when dialkyl
carbonates, such as dimethyl, dibenzyl, or diethyl carbon-
ate, were treated with DBU at 293 K. Moreover, no reso-
We cannot exclude that the catalytic effect observed upon
nances attributed to 2a were observed when DMC/DBU addition of DBU may be ascribed to the formation of meth-
mixtures (1 mol/2 mol) were monitored by 1H NMR at tem- oxide ion, which even in low concentrations (as the pKa
peratures between 293 and 343 K.[13] Nevertheless, on the values of MeOH and DBU suggest),[15,16] is a stronger
basis of the reactivity exhibited by diaryl and aryl alkyl car- nucleophile than MeOH. However, soon after adding the
bonates, we cannot exclude in the latter cases the presence base to the CDCl3 solution of 1b and MeOH, we also noted
of the (1+)–OR and/or 2 species in the reaction mixture at that the NMR spectrum of the reaction mixture showed the
very low concentrations. There may be a twofold explana- presence of ketene aminal 2b. The signals of both 2b and
tion for the behavior observed with dialkyl carbonates. Di- 1b rapidly quenched within about 1 h, because of the for-
alkyl carbonates are much less reactive species than 3a–c,[14] mation of the products. This fact suggests that the ketene
and reversible formation of the (1+)–OR salt from the com- aminal may be a catalytically active intermediate in the
bination of DBU and (RO)2CO [see Equation (1), R = carbonylation process shown in Equation (6), which may
alkyl] may suffer from a higher energy barrier. Moreover, involve the reaction of 2b (R = Ph) with the alcohol as the
equilibrium (5) may lie to the left more than equilib- final step; see Equation (7).
Eur. J. Org. Chem. 2011, 2458–2465
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M. Carafa, E. Mesto, E. Quaranta
FULL PAPER
chloride salts, and studying their reactivity towards the or-
ganic base. Upon treatment with DBU, organic carbonates
are activated towards nucleophilic attack by the formation
of ketene aminal 2, which can act as a carrier of the CO2R
group. These findings are of interest for their implications
in catalysis and open the way to a more accurate under-
standing of the role played by the amidine base in DBU-
catalyzed acylation reactions.[3,4a,4c]
(7)
Further support of this hypothesis was obtained by in-
vestigating the reactivity of 1a and 2a with MeOH.
Likewise 1b, even after reaction times as long as 16 h and
with 7 molar equiv. of MeOH in CDCl3, 1a·H2O did not
exhibit any appreciable reactivity towards the alcohol. In
addition, under comparable conditions (293 K; CDCl3;
MeOH/3a, 1.8 mol/mol; 20 h), 3a did not react significantly
with MeOH.
Experimental Section
General Methods: Unless otherwise stated, all reactions and manip-
ulations were conducted under an inert gas atmosphere by using
vacuum line techniques. All solvents were dried according to con-
ventional methods (P2O5, Na/benzophenone)[17] and stored under
N2. Carbonate 3a was prepared according to the literature.[18] Car-
bonate 3b was recrystallized from diethyl ether at 253 K before use.
DBU, ROC(O)Cl (R = Me, Ph), and the other organic carbonates
were used as received. DBU was stored under an inert atmosphere.
IR spectra were recorded with a Shimadzu FTIR Prestige 21 spec-
trophotometer or a Perkin–Elmer FTIR 1710 instrument. NMR
spectra were recorded with a Varian Inova 400 spectrometer.
Chemical shifts are in δ (ppm) and measured relative to residual
solvent peaks. GC analyses were recorded with a HP 5890 Series
II gas chromatograph (capillary column: Heliflex AT-5,
30 mϫ0.25 mm, 0.25 μm film thickness). GC–MS analyses were
recorded with a Shimadzu GC-17A linked to a Shimadzu GC–MS
QP5050 selective mass detector (capillary column: Supelco MDN-
5S, 30 mϫ0.25 mm, 0.25 μm film thickness). Analyses of gases
were performed with a Dani 8610 GC equipped with a TCD 866.
Single-crystal X-ray analyses were carried out with a Bruker X8
Apex II diffractometer equipped with an APEX-II CCD detector.
Compared to amidinium cation 1a+ and carbonate 3a,
the corresponding ketene aminal 2a was a more reactive
species and a more active carbonylating agent. At 293 K in
CDCl3 (MeOH/2a, 1.7 mol/mol), 2a readily transferred the
methoxycarbonyl group to the alcohol producing DMC
and the regenerated amidine base; see Equation (7), R =
Me. Under the working conditions, the methoxycarbon-
ylation reaction shown in Equation (7), R = Me, was rela-
tively fast (2a conversion as high as 77%, after only 2 h)
and quantitative (Figure 3). The process was also very selec-
tive, as no side products were detected in the reaction mix-
ture.
Isolation and Characterization of 8-Methoxycarbonyl-1,8-diazabicy-
clo[5.4.0]undec-7-enium Chloride Monohydrate (1a·H2O): DBU
(1 mL, 6.7 mmol) in diethyl ether (15 mL) was added dropwise to
an excess amount of MeOC(O)Cl (3 mL, 38.7 mmol) dissolved in
the same solvent (5 mL). The solution was stirred for 1 h. The re-
sulting solid precipitate was filtered, washed with diethyl ether, and
redissolved in CH2Cl2. The CH2Cl2 solution was treated with THF
(tetrahydrofuran) and cooled to 253 K. The resulting suspension
was filtered, and the solid DBU·HCl, the major component, was
removed. After addition of diethyl ether and more THF to the
solution, a white solid was obtained which was recrystallized re-
peatedly from CH2Cl2/THF to give 1a·H2O (170 mg, 10%). 1H
NMR (400 MHz, CDCl3, 293 K): δ = 1.72–1.86 (br. m, 6 H, 3-H,
Figure 3. Reaction of 2a (153.0 mg, 0.73 mmol) with methanol
(0.050 mL, 1.23 mmol; MeOH/2a, 1.7 mol/mol) in CDCl3 (1 mL)
1
at 293 K. Conversion of 2a (determined by H NMR) versus time.
The above results are very enlightening and demonstrate
clearly that DBU can activate carbonic acid diesters
through the formation of N-alkoxycarbonyl ketene aminal
2 which can behave as a carrier of the CO2R group.
3
4-H, and 5-H), 2.23 (quint, JH,H = 6 Hz, 2 H, 10-H), 3.29 (br. m,
3
2 H, 6-H), 3.87 (s, 3 H, OMe), 3.95 (t, JH,H = 6.2 Hz, 2 H, 9-H
or 11-H), 4.08 (pseudo-t overlapped with the signal of 2-H, 2 H,
9-H or 11-H), 4.10 (br. m, 2 H, 2-H) ppm.[19] 13C{1H} NMR
(100 MHz, CDCl3, 293 K): δ = 20.87, 21.93, 25.12, 28.06, 33.77
(C-6), 44.08, 52.04, 55.41 (OMe), 57.64, 152.80 (CO2), 172.62 (C-
Conclusions
7) ppm. IR (Nujol): ν = 1748 (s, C=O), 1639 (s, C=N), 1219, 1200,
˜
This study sheds light on the reactivity of carbonic acid
diesters in the presence of an amidine base such as DBU.
We have demonstrated unambiguously that DBU, by re-
acting as a nucleophile with organic carbonates, can gener-
ate through an equilibrium process reactive ketene aminal
2 as the ultimate product. The latter species may reasonably
form by deprotonation of a N-alkoxycarbonyl-amidinium
cation 1+ with the amidine base. We have shown this by
1155 cm–1. C11H21ClN2O3 (264.74): calcd. Cl 13.39; found Cl 13.24.
Isolation and Characterization of 8-Phenoxycarbonyl-1,8-diazabicy-
clo[5.4.0]undec-7-enium Chloride (1b): A solution of DBU (2 mL,
13.4 mmol) in THF (10 mL) was added dropwise to PhOC(O)Cl
(1.7 mL, 13.6 mmol) which was dissolved in the same solvent
(10 mL). The solution was stirred for 1 h at ambient temperature.
The resulting white precipitate was filtered, washed with THF, and
recrystallized from CH2Cl2/diethyl ether to give 1b (2.48 g, 60%).
isolating and characterizing, for the first time, a few 1+ 1H NMR (400 MHz, CDCl3, 293 K): δ = 1.73 (unresolved br., 6
2462
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2458–2465

DBU-Promoted Nucleophilic Activation of Carbonates
H, 3-H, 4-H, and 5-H), 2.29 (quint, 3JH,H = 6 Hz, 2 H, 10-H), 3.31 capillary tube) as an external reference, and FTIR. For more de-
3
(br. m, 2 H, 6-H), 3.97 (t, JH,H = 6.2 Hz, 2 H, 9-H or 11-H), 4.08 tails, see Table 2. Besides NMR signals from the reactants 3a and
3
(br. m, 2 H, 2-H), 4.18 (pseudo-t, JH,H = 6 Hz, 2 H, 9-H or 11-
DBU, there were also signals in the spectra from the products 2a
H), 7.08 (dm, 2 H, ortho-H), 7.19 (m, 1 H, para-H), 7.31 (m, 2 H, and phenol (see below). Herein, we report in detail the spectro-
meta-H) ppm.[19] 13C{1H} NMR (100 MHz, CDCl3, 293 K): δ = scopic characterization of the equimolar mixture of 3a (260 μL,
20.85, 21.54, 24.86, 27.85, 34.04 (C-6), 44.56, 52.36, 57.84, 120.72
(C-ortho), 126.88 (C-para), 129.64 (C-meta), 149.61 (C-ipso), 150.89 is for the reaction solution. H NMR (400 MHz, 293 K, 3a): δ =
(CO ), 172.62 (C-7) ppm. IR (Nujol): ν = 1764 (s, C=O), 1633 (s, 3.25 (s, OMe), 6.66–6.70 (overlapped m, para-H and ortho-H), 6.83
C=N), 1277, 1221, 1192 cm–1. C16H21ClN2O2 (308.79): calcd. Cl (m, meta-H) ppm. 1H NMR (400 MHz, 293 K, DBU): δ = 0.92 (br.
2.07 mmol)/DBU (300 μL, 2.01 mmol). The characterization data
1
˜
2
11.48; found Cl 11.35.
m, 3-H), 1.03 (br. m, 4-H and 5-H), 1.15 (quint, 10-H), 1.84 (br.
m, 6-H), 2.53 (m, 2-H), 2.56 (t, 9-H or 11-H), 2.71 (t, 9-H or 11-
Isolation and Characterization of Methyl 1,8-Diazabicyclo[5.4.0]-
undec-6-ene-8-carboxylate (2a):
1
3
H) ppm. H NMR (400 MHz, 293 K, 2a): δ = 4.36 (br. t, JH,H
=
A solution of DBU (2.0 mL,
3
6 Hz, 6-H), 3.09 (s, OMe), 2.99 (t, JH,H = 6.8 Hz, 9-H or 11-H),
13.4 mmol) in THF (10 mL) was added dropwise to MeOC(O)Cl
(1.05 mL, 13.6 mmol) which was dissolved in the same solvent
(10 mL). The reaction mixture was stirred for 1 h, cooled to 253 K
for 3 h, and then filtered. Evaporation in vacuo of the solution
gave ketene aminal 2a (0.710 g) as a colorless viscous oil. 1H NMR
(400 MHz, CDCl3, 293 K): δ = 1.44 (m, 3J4-H,3-H = 6.2 Hz, 2 H, 4-
3
2.46 (m, 2-H), 2.34 (t, JH,H = 6 Hz, 9-H or 11-H), 1.58 (pseudo-
3
3
q, J5-H,4-H = 6.2 Hz, 5-H), 1.20 (quint, JH,H = 6 Hz, 10-H) ppm.
The 3-H and 4-H resonances of 2a were masked by the signals at
1.15 ppm and 1.03 ppm for DBU, respectively, as ascertained by
1
decoupling experiments. H NMR (400 MHz, 293 K, PhOH): δ =
6.16 (m, para-H), 6.35 (dm, ortho-H), 6.62 (m, meta-H), 13.56 (br.,
OH) ppm. 13C{1H} NMR (100 MHz, 293 K, 2a): δ = 23.10, 24.36,
25.82, 28.27, 42.87, 48.35, 51.51 (OMe), 52.51, 103.73 (C-6), 143.51
(C-7), 154.60 (CO2) ppm. 13C{1H} NMR (100 MHz, 293 K, 3a): δ
= 54.36 (OMe), 120.47 (C-ortho), 125.25 (C-para), 128.84 (C-meta),
150.84 (C-ipso), 153.36 (CO2) ppm. 13C{1H} NMR (100 MHz,
293 K, DBU): δ = 22.17, 25.57, 27.94, 29.05, 35.95, 43.27, 47.43,
51.72, 159.55 ppm. 13C{1H} NMR (100 MHz, 293 K, PhOH): δ =
115.49 and 116.04 (C-ortho and C-para), 128.44 (C-meta), 160.43
(C-ipso) ppm. In the proton-coupled spectrum the 2a resonances
assigned to C-6 and OMe were, respectively, a doublet of multiplets
(1JC,H = 158 Hz) and a quartet (1JC,H = 146 Hz). The FTIR spec-
trum (liquid film) of the reaction solution showed, besides the sig-
nals of 3a (1767 cm–1, C=O) and DBU (1620 cm–1, C=N), new po-
orly resolved medium absorptions at 1701 and 1716 cm–1 (C=O)
due to 2a.
3
3
H), 1.61 (m, J3-H,4-H = 6 Hz, 2 H, 3-H), 1.69 (m, JH,H = 6 Hz, 2
3
H, 10-H), 1.98 (pseudo-q, J5-H,6-H = 6.2 Hz, 2 H, 5-H), 2.82 (m,
2 H, 9-H or 11-H), 2.91 (m, 2 H, 2-H), 3.41 (t, JH,H = 6.6 Hz, 2
H, 9-H or 11-H), 3.54 (s, 3 H, OMe), 4.71 (br. t, J6-H,5-H = 6 Hz,
3
3
1 H, 6-H) ppm.[19] 13C{1H} NMR (100 MHz, CDCl3, 293 K): δ =
23.43, 24.46, 26.03, 28.33, 43.34, 49.00, 52.40 (OMe), 52.91, 105.27
(C-6), 143.19 (C-7), 155.44 (CO2) ppm. In the proton-coupled spec-
trum, the signals at 52.40 ppm (OMe) and 105.27 ppm (C-6) split,
respectively, into a quartet (1JC,H = 145 Hz) and a doublet of mul-
tiplets (1JC,H = 159 Hz). IR (neat): ν = 1717 (shoulder), 1701 (s,
˜
C=O), 1663 (ms, C=C), 1273, 1213, 1184, 1167, 1122 cm–1. MS
(70 eV): m/z (%) = 210 [M]+, 195 [M – CH3]+, 181, 179 [M –
OCH3]+, 151 [M – CO2CH3]+, 123, 98, 68, 54, 41. C11H18N2O2
(210.26): calcd. C 62.83, H 8.63, N 13.32; found C 62.63, H 8.84,
N 13.15.
Reaction of 1b with DBU in CDCl3: The addition of DBU
(0.030 mL, 1 equiv.) to a solution of 1b (0.0583 g, 0.189 mmol) in
CDCl3 resulted in disappearance of the NMR resonances of the
salt and the appearance of the new signals corresponding to 2b
(phenyl 1,8-diazabicyclo[5.4.0]undec-6-ene-8-carboxylate) and
General Procedure for Reaction of 3c with DBU: To the organic
carbonate a measured volume of the amidine base (Table 2) was
added. The reaction mixture was stirred at ambient temperature
for a given time (5–8 h) and analyzed by NMR (1H and 13C), using
[D6]DMSO (contained in a coaxial capillary tube) as an external
reference, and FTIR. For more details, see Table 2. Besides NMR
signals from the reactants 3c and DBU, there were also signals in
the spectra from the products 2c (8-tert-butyl 1,8-diazabicy-
clo[5.4.0]undec-6-ene-8-carboxylate) and phenol (see below).
Herein, we report in detail the spectroscopic characterization of
the 1:4 (mol/mol) mixture of 3c (200 μL, 1.08 mmol)/DBU (640 μL,
4.28 mmol). The characterization data is for the reaction solution.
1H NMR (400 MHz, 293 K, 3c): δ = 1.12 (s, Me), 6.78 (dm, ortho-
H), 6.81 (m, para-H), 6.98 (m, meta-H) ppm. 1H NMR (400 MHz,
293 K, DBU): δ = 1.01 and 1.18 (br. m, 3-H, 4-H, and 5-H), 1.28
(quint, 10-H), 1.91 (m, 6-H), 2.72–2.79 (overlapped signals, 2-H, 9-
DBU·HCl. The characterization data is for the reaction mixture.
3
1H NMR (400 MHz, CDCl3, 293 K, 2b): δ = 1.46 (m, J4-H,3-H
=
3
6 Hz, 2 H, 4-H), 1.64 (m, J3-H,4-H = 6 Hz, 2 H, 3-H), 1.77 (quint,
3JH,H = 6 Hz, 2 H, 10-H), 2.01 (pseudo-q, J5-H,6-H = 6.2 Hz, 2 H,
3
5-H), 2.90 (m, 2 H, 9-H or 11-H), 2.96 (m, 2 H, 2-H), 3.52 (br. t,
3
3JH,H = 6.2 Hz, 2 H, 9-H or 11-H), 4.89 (br. t, J6-H,5-H = 6 Hz, 1
H, 6-H), 6.98 (dm, 2 H, ortho-H), 7.03 (m, 1 H, para-H), 7.20 (m,
2
H, meta-H) ppm.[19] 1H NMR (400 MHz, CDCl3, 293 K,
DBU·HCl): δ = 1.52–1.59 (unresolved m, 3-H, 4-H, and 5-H), 1.83
3
3
(quint, JH,H = 6 Hz, 10-H), 2.69 (m, 6-H), 3.23 (t, JH,H = 6 Hz,
3
9-H), 3.31 (t, JH,H = 6 Hz, 11-H), 3.32 (m, 2-H partially over-
lapped with the signal of 11-H), 11.22 (br. s, NH) ppm.[19] 13C{1H}
NMR (100 MHz, CDCl3, 293 K, 2b): δ = 23.38, 24.46, 25.88, 28.26,
43.75, 48.97, 52.88, 106.04 (C-6), 121.31 (C-ortho), 124.71 (C-para),
128.76 (C-meta), 142.83 (C-7), 151.25 (C-ipso), 153.18 (CO2) ppm.
13C{1H} NMR (100 MHz, CDCl3, 293 K, DBU·HCl): δ = 19.89,
24.20, 26.87, 28.82, 33.05, 39.11, 48.26, 53.66, 164.58 (C-7) ppm.
In both the 1H NMR and 13C NMR spectra of DBU·HCl, the
chemical shifts were sensitive to the used DBU/1b molar ratio.
1
H, and 11-H) ppm. H NMR (400 MHz, 293 K, 2c): δ = 4.38 (br.
3
3
t, JH,H = 6 Hz, 6-H), 3.04 (t, JH,H = 6.8 Hz, 9-H or 11-H), 2.56
3
(m, 2-H), 2.48 (t, JH,H = 6 Hz, 9-H or 11-H), 1.68 (pseudo-q,
3J5-H,6-H = 6.6 Hz, 5-H), 1.35 (quint, JH,H = 6 Hz, 10-H), 1.03 (s,
3
Me) ppm. The 4-H resonance was masked by the signal at
1.10 ppm, as ascertained by decoupling experiments, and the reso-
nance due to 3-H was obscured by the signals of DBU around
1
1.18 ppm. H NMR (400 MHz, 293 K, PhOH): δ = 6.22 (m, para-
General Procedure for the Reaction of 3a with DBU: To the organic
carbonate a measured volume of the amidine base (Table 2) was
added. The reaction mixture was stirred at ambient temperature
for a given time (4–5 h) and analyzed by NMR (1H and 13C), using
[D6]DMSO (deuterated dimethyl sulfoxide, contained in a coaxial
H), 6.34 (dm, ortho-H), 6.68 (m, meta-H), 11.5 (v br., OH) ppm.
13C{1H} NMR (100 MHz, 293 K, 2c): δ = 23.37, 24.76, 27.56 (Me),
27.88, 29.09, 42.34, 48.58, 52.88, 78.05 (CMe3), 103.94 (C-6),
3
144.12 (C-7), 153.44 (CO2) ppm. C{1H} NMR (100 MHz, 293 K,
3c): δ = 26.82 (Me), 81.95 (CMe3), 120.74 (C-ortho), 125.02 (C-
Eur. J. Org. Chem. 2011, 2458–2465
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2463

M. Carafa, E. Mesto, E. Quaranta
FULL PAPER
para), 128.85 (C-meta), 150.95 (C-ipso), 151.05 (CO2) ppm.
13C{1H} NMR (100 MHz, 293 K, DBU): δ = 22.58, 25.92, 28.33,
29.34, 36.48, 43.81, 47.68, 51.90, 158.91 ppm. 13C{1H} NMR
(100 MHz, 293 K, PhOH): δ = 115.30 and 116.45 (C-ortho and C-
para), 128.44 (C-meta), 159.99 (C-ipso) ppm. In the proton-coupled
spectrum the 2c resonance assigned to C-6 was a doublet of mul-
tiplets (1JC,H = 158 Hz). In the region of 2000–1600 cm–1, the FTIR
spectrum of this mixture showed the signals of 3c (1759 cm–1,
C=O) and DBU (1620 cm–1, C=N), as well as new medium absorp-
tions at 1694 and 1701 cm–1 (shoulder), consistent with the forma-
tion of 2c.
spectroscopy. The NMR spectra showed complete conversion of
1b. In the 13C NMR spectrum, the generated organic carbonate 3a
produced a characteristic quartet at 153.83 ppm (3JC,H = 4 Hz)
which was assigned to the carbonyl C atom. Minor amounts of
DMC and phenol were slowly formed by further reaction of 3a
with an excess amount of methanol. The GC-MS analysis of the
reaction solution further confirmed the formation of all the above
products.
Reaction of 2a with MeOH: Methanol (0.050 mL; 1.23 mmol) was
added to a solution of 2a (153.0 mg; 0.73 mmol) in CDCl3 (1 mL),
and the mixture was stirred at ambient temperature. The quantita-
tive conversion of 2a into DMC and DBU was monitored by 1H
(400 MHz) and 13C (100 MHz) NMR spectroscopy (see also Fig-
ure 3). In the 13C NMR spectrum the organic carbonate (DMC)
produced a characteristic septuplet at 155.59 ppm (3JC,H = 4 Hz)
which was assigned to the carbonyl C atom. The formation of the
products was further confirmed by GC analysis. In the range of
2000–1600 cm–1, the FTIR spectrum of the solution showed the
characteristic absorptions of DMC and DBU at 1755 (C=O) and
1612 cm–1 (C=N), respectively.
General Procedure of Reaction of 3b with DBU: To the mixture of
the organic carbonate and the amidine base (Table 2) a minimum
volume of THF was added, in cases where the mixture was hetero-
geneous at ambient temperature (Table 2). The solution was stirred
at ambient temperature for 5 h and analyzed by NMR (1H and
13C), using [D6]DMSO (contained in a coaxial capillary tube) as an
external reference, and FTIR. For more details, see Table 2. Besides
NMR signals from the reactants 3b, DBU, and THF, if used, there
were also signals in the spectra from the products 2b and phenol
(see below). Herein, we report in detail the spectroscopic charac-
terization of the equimolar mixture of 3b (0.2700 g, 1.26 mmol)/
DBU (190 μL, 1.27 mmol) and THF (0.3 mL). The characteriza-
X-ray Crystallographic Analyses[20–22]
Salt 1a·H2O: C11H21Cl1N2O3, Mr = 264.75, T = 293 K, mono-
clinic, space group P21/c, scan type: ω – φ, a = 6.6506(4) Å, b =
15.5432(10) Å, c = 13.2041(10) Å, α = γ = 90°, β = 90.237(5)°, V
1
tion data is for the reaction solution. H NMR (400 MHz, 293 K,
THF): δ = 3.05, 1.11 ppm. 1H NMR (400 MHz, 293 K, DBU): δ
= 0.83 (m, 3-H), 0.89–1.02 (overlapped m, 4-H and 5-H), 1.08
(quint, 10-H), 1.81 (m, 6-H), 2.43 (m, 2-H), 2.46 (t, 9-H or 11-H),
=
1364.92(16) Å3,
Z
=
4, ρcalcd.
0.150ϫ0.600ϫ0.750 mm3, F(000) = 464, μ(Mo-Kα) = 0.280 mm–1,
min. transmission 0.8702, max. transmission: 1.000, 2θmax.
=
1.29 gcm–3, crystal size:
=
1
2.67 (t, 9-H or 11-H) ppm. H NMR (400 MHz, 293 K, PhOH): δ
61.12°, 11826/3855 measured/independent reflections [R(int) =
0.027], 2457/154 reflection used/number of parameters, refinement
against |F|, GOF = 1.017, final R indices were R1 = 0.042 [IϾ3σ(I)]
and wR2 = 0.047 [IϾ3σ(I)], H atoms isotropically refined, residual
electron density 0.25/–0.16 eÅ3. Mo-Kα radiation (λ = 0.71073).
Structure solution obtained by charge flipping method with
SUPERFLIP.[20] Least-squares refinement was carried out by
CRYSTAL.[21]
= 6.14 (m, para-H), 6.33 (dm, ortho-H), 6.57 (m, meta-H), 13.32
(br., OH) ppm. 1H NMR (400 MHz, 293 K, 2b): δ = 4.48 (t, br,
3JH,H = 6 Hz, 6-H), 3.03 [9-H or 11-H, masked by the THF signal
at 3.05 ppm; when irradiating at 3.03 ppm, the quintet at 1.18 ppm,
due to 10-H (see below), converted into a triplet with 3JH,H = 6 Hz],
3
3
2.33 (t, JH,H = 5.9 Hz, 9-H or 11-H), 1.56 (pseudo-q, J5-H,6-H
=
3
6.2 Hz, 5-H), 1.18 (quint, JH,H = 6 Hz, 10-H), 0.98 (4-H, masked
by DBU multiplet between 0.89 and 1.02 ppm; when irradiating at
0.98 ppm, the pseudo-quartet at 1.56 ppm, due to 5-H, converted
into a doublet with 3J5-H,6-H = 6.2 Hz) ppm. The 2-H and 3-H reso-
nances could not be assigned, as they were masked, respectively, by
the DBU signals at approximately 2.3–2.4 ppm and between 0.8–
1.0 ppm. The resonances for the ortho-H and meta-H overlapped
with those of 3b at 6.61 ppm (para-H) and 6.70–6.80 ppm (ortho-
H and meta-H). 13C{1H} NMR (100 MHz, 293 K, 2b): δ = 23.07,
24.28, 25.69, 28.14, 43.32, 48.36, 52.42, 104.67 (C-6), 120.97 (C-
ortho), 124.12 (C-para), 128.32 (C-meta), 143.19 (C-7), 151.45 (C-
ipso), 152.27 (CO2) ppm. 13C{1H} NMR (100 MHz, 293 K, 3b): δ
= 120.27 (C-ortho), 125.50 (C-para), 128.88 (C-meta), 150.63 (C-
ipso), 151.13 (CO2) ppm. 13C{1H} NMR (100 MHz, 293 K, DBU):
Salt 1b: C16H21Cl1N2O2, Mr = 308.81, T = 293 K, monoclinic,
space group P21/c, scan type: ω – φ, a = 10.1805(2) Å, b =
14.5849(4) Å, c = 10.3843(2) Å, α = γ = 90°, β = 100.4040(10)°, V
=
1516.53(6) Å3,
Z
=
4, ρcalcd.
0.265ϫ0.400ϫ0.900 mm3, F(000) = 604, μ(Mo-Kα) = 0.258 mm–1,
min. transmission: 0.9054, max. transmission: 1.000, 2θmax.
=
1.35 gcm–3, crystal size:
=
62.06°, 39738/4837 measured/independent reflections [R(int) =
0.026], 3285/190 reflection used/number of parameters, refinement
against |F|, GOF = 1.046, final R indices were R1 = 0.034 [IϾ3σ(I)]
and wR2 = 0.042 [IϾ3σ(I)], H atoms isotropically refined, residual
electron density 0.26/–0.13 eÅ3. Mo-Kα radiation (λ = 0.71073).
Structure solution obtained by charge flipping method with
SUPERFLIP.[20] Least-squares refinement was carried out by
CRYSTAL.[21]
δ
= 21.95, 25.40, 27.77, 28.93, 35.50, 42.84, 47.35, 51.65,
160.02 ppm. 13C{1H} NMR (100 MHz, 293 K, PhOH): δ = 115.39
and 116.39 (C-ortho and C-para), 128.39 (C-meta), 160.09 (C-
ipso) ppm. 13C{1H} NMR (100 MHz, 293 K, THF): δ = 66.81,
24.91 ppm. In the proton-coupled spectrum the resonance assigned
to C-6 of 2b was a doublet of multiplets (1JC,H = 160 Hz). In the
region of 2000–1600 cm–1, the FTIR spectrum (liquid film) of the
solution showed the signals of 3b (1782 cm–1, C=O) and DBU
(1620 cm–1, C=N), as well as medium poorly resolved new absorp-
tions at 1716 and 1732 cm–1 (C=O), assigned to 2b.
Acknowledgments
Università degli Studi di Bari (Fondi di Ateneo) and Ministero
dell’Istruzione, dell’Università e della Ricerca (MIUR) (PRIN
2008A7P7YJ_002) are acknowledged for financial support.
[1] T. Ishikawa, T. Kumamoto, Amidines in Organic Synthesis, in:
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of DBU: To a solution of 1b (99.1 mg, 0.321 mmol) and MeOH
(26 μL, 0.642 mmol) in CDCl3 (1 mL), DBU (10 μL, 0.067 mmol)
was added. The reaction mixture was stirred for about 1 h at 293 K
and then analyzed by 1H (400 MHz) and 13C (100 MHz) NMR
2464
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Eur. J. Org. Chem. 2011, 2458–2465

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[20] SUPERFLIP is a computer program for the solution of crystal
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[22] CCDC-788115 (for 1a·H2O) and -788114 (for 1b) contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Received: December 24, 2010
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Published Online: March 16, 2011
Eur. J. Org. Chem. 2011, 2458–2465
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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