CO2-Mediated Formation of Chiral Carbamates from meso-Epoxides via Polycarbonate Intermediates

Article abstract of DOI:10.1021/acs.joc.6b01616

Carbon dioxide has attracted broad interest as a renewable C1 feedstock for efficient transformation into value-added organic chemicals; nevertheless, far less attention was paid to its stereochemically controlled catalytic fixation/conversion processes. Here, we report a new strategy for the selective synthesis of chiral carbamates from carbon dioxide via polycarbonate intermediates, which are formed by the desymmetric copolymerization of meso-epoxides using enantiopure dinuclear Co(III) catalyst systems with 99% enantioselectivity. Subsequent degradation reaction of the resultant polycarbonates with various primary or secondary amine nucleophiles can afford optically active carbamates, with the complete configuration retention of the two chiral carbon centers. Our accomplishment reported here opens up a new route to prepare a wide range of CO₂-based carbamate scaffolds with excellent yields and 99% enantiomeric excess.

Full text of DOI:10.1021/acs.joc.6b01616

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Article
CO2-Mediated Formation of Chiral Carbamates from
meso-Epoxides via Polycarbonate Intermediates
Ye Liu, Wei-Min Ren, Ke-Ke He, Wen-Zhen Zhang, Wen-Bing Li, Meng Wang, and Xiao-Bing Lu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01616 • Publication Date (Web): 14 Sep 2016
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CO2-Mediated Formation of Chiral Carbamates from meso-
Epoxides via Polycarbonate Intermediates
Ye Liu*, WeiꢀMin Ren, KeꢀKe He, WenꢀZhen Zhang, WenꢀBing Li, Meng Wang & XiaoꢀBing Lu*
6
State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 linggong road, Dalian 116024,
China
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Keywords: chiral carbamates • carbon dioxide • mesoꢀepoxides • tandem reaction • polycarbonates
________________________________________________________________________________
ABSTRACT: Carbon dioxide has attracted broad interest
as a renewable C1 feedstock for efficient transformation
into valueꢀadded organic chemicals, nevertheless, far less
attention was paid to its stereochemically controlled
catalytic fixation/conversion processes. Here we report a
new strategy for the selective synthesis of chiral carbamates
from carbon dioxide via polycarbonate intermediates, which
are formed by the desymmetric copolymerization of mesoꢀ
epoxides using enantiopure dinuclear Co(III) catalyst
systems with 99% enantioselectivity. Subsequent
degradation reaction of the resultant polycarbonates with
various primary or secondary amines nucleophiles can
afford optically active carbamates, with the complete configuration retention of the two chiral carbon centers. Our
accomplishment reported here opens up a new route to prepare a wide range of CO2ꢀbased carbamates scaffolds
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with excellent yields and 99% enantiomeric excess.
_________________________________________________________________________________________________________________________________________
conventional methods for the formation of carbamates
■
INTRODUCTION
usually concerned the toxic phosgene or isocyanates. The use
of CO2 as an alternative reagent for the direct synthesis of
organic carbamates is highly desirable.13ꢀ18 Recently, Jiang
and coworkers reported a baseꢀpromoted threeꢀcomponent
coupling of CO2, amines, and Nꢀtosylhydrazones to provide
organic carbamates and the reaction was suggested to
The efficient transformation of carbon dioxide (CO2) into
valueꢀadded organic compounds can contribute to a more
sustainable chemical industry, since CO2 is an abundant,
inexpensive and nonꢀtoxic renewable C1 resource.1ꢀ7 CO2 is a
thermodynamically stable molecule, the end product in any
carbonꢀbased combustion process, thus relatively highꢀenergy
reactants are often used to gain thermodynamic driving force
for facilitating its transformation. As a consequence, the
quantity of CO2 consumed in these transformation processes
is likely always to be a very small fraction of the total CO2
generated from the emissionꢀbased human activity. However,
this strategy potentially provides access to the more
environmentally benign routes to produce useful chemicals
otherwise made from the reagents detrimental to the
environment. Indeed, the majority of reactions using CO2 as a
feedstock concern the preparation of relatively simple achiral
chemicals, with an emphasis on CO2 incorporation efficiency,
while far less attention was paid to the stereochemically
controlled catalytic CO2 fixation/conversion processes.8ꢀ10
Carbamate derivatives scaffolds, the key structural
elements of various naturally occurring compounds, play
very important and ubiquitous roles in pharmaceutical,
agrochemical and material terrains.11,12 However, the
proceed via
a
carbocation intermediates.19 Also, the
aminolysis reaction of cyclic carbonates using simple
alkylamines is wellꢀdocumented under mild conditions.20ꢀ23
More recently, Kleij et al. succeeded in employing aromatic
amines as nucleophiles for the aminolysis in presence of
triazabicyclodecene.24 Nevertheless, rare examples were
reported regarding the synthesis of enantiopure carbamates,
and the processes in these limited reports generally suffered
from moderate product selectivity or/and very low
enantioselectivity.25,26
Previously, we have demonstrated that enantiopure
biphenolꢀlinked dinuclear Co(III) complex I was a rare
privileged chiral catalyst for the enantioselective
copolymerization of CO2 with mesoꢀepoxides, affording the
corresponding polycarbonates with complete alternating
structure and ≥98% enantioselectivity (Figure 1).27ꢀ29 Since
the mainꢀchain chirality originates from the two contiguous
chiral carbon atoms, the degradation of the optically active
O
R1
N
×
*
HNR1(R2)
O
R
O
R
R
S R
*
HO
O
R
R2
R
R
I
N
O
N
O
O
R
R
O
R
R
tBu
O
X
R
S
R
Polycarbonate
intermediates
(R,R,R,R)-I
(S,S,S,S)-I
X
R
But
Carbamate
O
N
O
N
R
R
Co
Ia: R = Me
Ib: R = H.
+
R1
N
*
HNR1(R2)
O
S
O
CO2
HO
O
*
R2
S
S
S
X = 2,4-dinitrophenoxide
O
×
R
O
O
R
R
R
R
S R
R
Privileged Chiral Catalysts
99% ee
Figure 1. Tandem desymmetric CO2/meso-epoxides copolymerization and nucleophilic depolymerization for preparing chiral
carbamates.
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polycarbonates into small molecule compounds by the
carbamates (Table 1, entries 13 and 14). This tandem
approach for the synthesis of carbamates from epoxides and
CO2 via polycarbonate intermediates demonstrated that this
methodology was very effective for various alkaloids.
nucleophilic attack at the carbonyl carbon atom should not
affect the configuration of the two stereogenic centers. With
this idea in mind, we are of great interest to systematically
explore the further transformation of these enantiopure
polycarbonates to chiral fine chemicals with high levels of
stereoretention. Herein, we present a tandem strategy for
selective synthesis of chiral carbamates from CO2 via
polycarbonate intermediates, using various amines
nucleophiles (Figure 1). Our accomplishment reported here
opens up a new route to prepare a wide range of CO2ꢀbased
carbamates scaffolds with excellent yields and 99%
enantiomeric excess.
Table 1. Synthesis of enantiopure carbamate derivatives from
[a]
cis-2,3-epoxybutane and CO2
R1
O
*
Chiral Catalyst I
Amine
HO
O
O
O
*
R
N
R2
CO2
+
*
*
R
*
*
R
R
O
R
O
9
R
trans-polymer
trans-carbamate
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Entry
Product
Temp. Time Yield
ee
Specific rotation
(%)[b]
(%)[c]
(o)[d]
(oC)
25
40
60
80
(h)
1
2
3
4
2
2
2
2
68
87
97
99 (S,S)
99 (S,S)
99 (S,S)
8 (+)
8 (+)
8 (+)
8 (+)
■
RESULTS AND DISCUSSION
HO
O
N
Chiral carbamates synthesis. Since cisꢀ2,3ꢀepoxybutane
exhibits both high reactivity and enantioselectivity in
copolymerizing with CO2, it was chosen as a model
monomer of mesoꢀepoxides for testing the aminolysis of the
polycarbonate intermediate using various amines. Firstly, the
asymmetric copolymerization CO2 with cisꢀ2,3ꢀepoxybutane
mediated by enantiopure dinuclear Co(III) catalyst (S,S,S,S)ꢀ
Ia could realize the complete conversion of epoxides,
affording the highly enantiopure poly(transꢀ2ꢀbutene
carbonate) with (S,S)ꢀconfiguration. Without further
purification, piperidine was added to the reaction mixtures
and the aminolysis reaction could be carried out smoothly at
O
(S,S)-1a
98 (96) 99 (S,S)
HO
O
O
N
5[e]
60
60
2
4
96 (95) 99 (R,R)
8 (-)
(R,R)-1a
O
O
HO
N
6[f]
89
91
95
99 (S,S)
99 (S,S)
99 (S,S)
5 (+)
(S,S)-1b
HO
HO
HO
O
O
O
N
3 (+)
7
8
60
60
4
8
(S,S)-1c
O
O
O
O
N
room temperature within
2
hours, affording the
10 (+)
corresponding carbamate (S,S)ꢀ1a with 68% yield (Table 1,
entry 1). The enantiomeric excess (ee) of the resulting
carbamate was determined by chiral HPLC using AD column
to be 99% with an S,Sꢀconfiguration, which was in
accordance with that of poly(transꢀ2ꢀbutene carbonate). This
result suggests that the aminolysis process did not affect the
stereochemistry of the two contiguous chiral centers. It was
found that the presence of trace water was very important for
this aminolysis reaction. The yields were increased to 87% at
(S,S)-1d
H
N
9[g]
10
11
12
60
60
60
8
8
8
90
88
94
---[h]
11 (+)
9 (+)
9 (+)
(S,S)-1e
H
N
---[h]
HO
HO
O
O
(S,S)-1f
O
O
H
N
Ph
99 (S,S)
o
o
(S,S)-1g
40 C, and 97% at 60 C (Table 1, entries 2 and 3). Notably,
no change in product selectivity and enantioselectivity was
observed when the reaction was carried out at 80 oC (Table 1,
entry 4). The carbamate with (R,R)ꢀconfiguration was also
isolated with 95% yield from (R,R,R,R)ꢀIa mediated cisꢀ2,3ꢀ
epoxybutane/CO2 copolymerization (Table 1, entry 5).
Moreover, dimethylamine, diethylamine, morpholine,
ethylamine, nꢀbutylamine, and benzyl amine as nucleophiles
could also transform the polycarbonate intermediate into the
corresponding carbamates in high yields with a prolonged
H
HO
O
N
O
99 (S,S)
12 (+)
32 (+)
60
60
12
8
86
93
(S,S)-1h
NH
H
HO
O
N
Ph
13[e]
99 (R,R,R)
O
(R,R,R)-1i
H
HO
O
N
Ph
99 (R,S,S)
50 (+)
14
60
8
92
O
(R,S,S)-1i
o
time of 4–8 hours at 60 C (Table 1, entries 6–11). Because
aDetailed experimental procedure for polymerization and
aminolysis reaction, see EXPERIMENTAL SECTION,
amine/H2O/epoxide = 1/1/1, molar ratio. b1H NMR yield, and
isolated yield in brackets. Yield was calculated based on
meso-epoxides. cDetermined by chiral HPLC, and cis-
carbamate was not detected. dSpecific rotation was
determined by polarimeter in chloroform at 20 oC (c = 1).
eDinuclear Co(III) complex (R,R,R,R)-Ia was used.
fDimethylamine solution (40 wt. % in H2O, amine/epoxide =
the desymmetric ringꢀopening of mesoꢀepoxides was a
typical SN2 reaction, cisꢀcarbamate was not detected during
this transformation (see EXPERIMENTAL SECTION and
Figures S63ꢀS66 in Supporting Information). Of importance,
all resulting carbamates have 99% enantioselectivity,
suggesting the complete configuration retention during the
aminolysis process. It is worth while noting here
parenthetically that no change in yield and enantioselectivity
was observed in the aminolysis reaction of the purified
poly(transꢀ2ꢀbutene carbonate) after complete removal of
metal catalyst precursor. This implies that the presence of the
catalyst for CO2/epoxide copolymerization has no influence
on the subsequent aminolysis of the resultant polycarbonates.
We were delightedly to find that tryptamine (a common
alkaloid) could be also employed as a nucleophilic reagent
for the aminolysis reaction with chiral poly(transꢀ2ꢀbutene
carbonate). The yield of the corresponding carbamate (S,S)ꢀ
1h was 86%, and the enantioselectivity was up to 99% (Table
1, entry 12). Also, the chiral (R)ꢀαꢀphenylethylamine can be
employed as the nucleophilic reagent for the aminolysis of
(R,R)ꢀ or (S,S)ꢀpoly(transꢀ2ꢀbutene carbonate)s to prepare
optically active diastereoisomeric (R,R,R) or (R,S,S)ꢀ
g
10/1, molar ratio) was used. Ethylamine solution (70 wt. % in
H2O, amine/epoxide = 10/1, molar ratio) was used. hThe ee
value was not determined because of the low ultraviolet
response in HPLC analysis.
The scope of this tandem approach regarding mesoꢀ
epoxides was demonstrated by the reaction of various
polycarbonates with piperidine under the optimized
conditions (Table 2). In comparison with cisꢀ2,3ꢀepoxybutane,
the formation of the corresponding carbamate products from
alicyclic mesoꢀepoxides/CO2 copolymers proceeded very
slowly, especially for 2a, 2b and 2c (48–54% yields) from
cyclohexene oxide. However, the enantioselectivities of the
resultant carbamates were all ≥98% ee, the same as that of
the corresponding polycarbonates (Table 2, entries 1ꢀ4).
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Table 2. Tandem CO2/meso-epoxides copolymerization and aminolysis of polycarbonates to prepare Chiral carbamate.[a]
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aDetailed experimental procedure for polymerization and aminolysis reaction, see EXPERIMENTAL SECTION, amine/H2O/epoxide
= 5/5/1, molar ratio. bMolar ratio. cDetermined by using gel permeation chromatography in THF, calibrated with polystyrene.
dDetermined the resultant diol by chiral GC or the dibenzoate using benzoyl chloride by chiral HPLC, and cis-diol was not detected.
f
e1H NMR yield, and yield was calculated based on meso-epoxides. Determined by chiral HPLC, and cis-carbamate was not
detected. gSpecific rotation was determined by polarimeter in chloroform at 20 oC (c = 1). hDimethylamine solution (40 wt. % in H2O,
i
amine/epoxide = 10/1, molar ratio) was used. The ee value was not determined because of the low ultraviolet response in HPLC
analysis. jThe polymer with high molecular weight and isotacticity was not soluble in THF, chloroform or DMF, even in 1,2,4-Cl3C6H3,
the Mn and PDI could not be determined. kThe reaction was carried out in toluene solution (epoxide/toluene = 1/4, molar ratio).
Various chiral carbamates with 99% ee can be produced from
CO2ꢀbased polycarbonates from cyclopentene oxide, 3,4ꢀ
(Figure 2). The Xꢀray single crystal study revealed the
absolute configuration of the resulting carbamate derivative
was the same as that of the corresponding polycarbonate,
suggesting the aminolysis reaction only concerns the
nucleophilic addition of amine to carbonyl group of the CO2ꢀ
based polycarbonates, rather than the two chiral carbon
centers.
epoxytetrahydrofuran,
3,5ꢀdioxaꢀepoxides,
1,4ꢀ
dihydronaphthalene oxide and 1,2ꢀepoxyꢀ4ꢀcyclohexene
(Table 2, entries 5ꢀ14) (For NMR and HPLC spectrum of
various carbamates, see Figures S1ꢀS60 in Supporting
Information). Furthermore,
a
chiral (S,S)ꢀcarbamate
derivative possessing one heavy bromine atom, which was
prepared by treatment of (S,S)ꢀ2a with 4ꢀbromobenzoic acid
(for detailed synthesis procedure, see EXPERIMENTAL
SECTION), was succeeded in isolating in crystal state
Mechanism understanding: It is worth noting here that the
reaction of poly(transꢀ2ꢀbutene carbonate) with piperidine
was finished only within 2 hours, while the aminolysis of the
CO2ꢀbased polycarbonates from alicyclic mesoꢀepoxides
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(such as cyclohexene oxide and cyclopentene oxide)
In order to better assess the mechanistic aspects of the
aminolysis process, in situ FTIR spectroscopy was used to
monitor the reaction (detailed experimental procedure, see
EXPERIMENTAL SECTION). As is easily observed, the
intense absorbance for the asymmetric v(C=O) vibration of
polycarbonates appears at ～ 1750 cm−1, while that of
carbamate derivatives usually finds at 1698 cmꢀ1. For the
aminolysis reaction of poly(transꢀ2ꢀbutene carbonate) with
piperidine, we clearly observed not only the decrease in
absorbance at 1747 cmꢀ1 (for polycarbonate) and the
continuous increase in peak intensity at 1698 cmꢀ1 (for
carbamate derivatives), but also a new species at 1813 cmꢀ1,
which increased at first, and disappeared gradually as a
function of time. The absorbance at 1813 cmꢀ1 was originated
from transꢀ2ꢀbutene carbonate, a cyclic carbonate (Figure 3,
Plotsꢀ(a) and (b)). This result indicates that the aminolysis
reaction using piperidine as a nucleophilic reagent underwent
the cyclic carbonate intermediate, which was formed from the
degradation of poly(transꢀ2ꢀbutene carbonate) by a backꢀ
biting mechanism, starting from the copolymer chain end
(Figure 4, route A). Another degradation route is the random
depolymerization caused by the nucleophilic attack of amine
or water to the carbonyl group of CO2ꢀbased polycarbonates
(Figure 4, route B).
proceeded very slowly for the formation of the corresponding
carbamate products, giving relatively low yields even at a
prolonged time of 24–72 hours, together with the formation
of 1,2ꢀdiol byproducts to a certain extent. The unexpected
results prompted us to consider the different aminolysis
routes for the two kinds of polycarbonates.
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Figure 2. X-Ray molecular structures of (S,S)-carbamate
derivative. The substrate was prepared by treatment of (S,S)-
2a with 4-bromobenzoic acid (hydrogen atoms and
uncoordinated solvent omitted for clarity). Thermal ellipsoids
are at the 30% probability level.
Interestingly,
for
the
aminolysis
reaction
of
poly(cyclopentene carbonate) with piperidine, we did not
Figure 3. IR spectra of the aminolysis reaction of various CO2-polymers and piperidine. Plots-(a) and (c): Three-dimensional stack
plot of the IR spectra collected every 1 min during reaction; Plots-(b) and (d): Reaction profiles for the aminolysis reaction as a
function of time. Plots-(a) and (b) are aminolysis reaction of poly(trans-2-butene carbonate) and Plots-(c) and (d) are aminolysis
reaction of poly(cyclopentene carbonate), respectively. Peak at 1698 cm-1 for carbamates derivatives, peak at ～1750 cm-1 for CO2-
polymers, and peak at 1813 cm-1 for trans-2-butene carbonate.
R1
O
*
HNR1(R2)
route A
O
R
O
O
R
O
HO O
S S
N
R2
O
O
S
S
S
S
S
S
O
O
m-1
O
R
R
R
R
R
R
R1
N
*
O
R
O
O
S
HO
R2
S
S
S
*
*
*
O
R
O
O
R
OH
O
O
R
R
S
S
S
S
S
S
S
R
O
R
OH
S
HO
O
m
S
S
S
S
HNR1(R2)
O
O
O
n
R
R
+
route B
O
R
R
R
or
H2O
HNR1(R2)
OH
S
HO
+
S
+
R1
N
O
R
O
O
R
OH
O
R
R
HO
S
R2
S
O
R
R
O
R
R
m-n-2
Figure 4. Two routes for the formation of chiral carbamates from the aminolysis reaction of enantiopure CO2-based polycarbonates
using amines as nucleophiles. Route A underwent the cyclic carbonate intermediate for poly(trans-2-butene carbonate). Route B was
the random depolymerization for poly(cyclopentene carbonate).
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observe the formation of cyclopentene carbonate (the
absorbance peak at ～1800 cm−1), and only discovered the
consecutive decrease in absorbance at 1751 cmꢀ1 (for
poly(cyclopentene carbonate)) and the continuous increase in
peak intensity at 1698 cmꢀ1 (for carbamate derivatives)
(Figure 3, Plotsꢀ(c) and (d)). This implies that the aminolysis
reaction did not concern the cyclic carbonate intermediate,
probably due to the ring strain placed on the fiveꢀmembered
carbonate ring in order to accommodate the conformational
requirements of the alicyclic cyclopentenyl ring.30,31
Furthermore, we succeeded in isolating an intermediate, 2,2'ꢀ
carbonyldioxydicyclohexanol, which should be formed in the
random depolymerization (Figure 4, route B).32
Representative procedure for aminolysis reaction
monitored by in situ FTIR spectroscopy: In a typical
experiment, a 100 mL stainless steel autoclave reactor,
modified with a ZnSeW AR window to allow for the use of
an ASI ReactIR 45 system equipped with a MCT detector
and 30 bounce DiCOMP in situ probe, is heated to the
desired temperature. In this manner, a single 256ꢀscan
background spectrum was collected. The poly(transꢀ2ꢀbutene
carbonate) (1.0 g, 8.6 mmol) and piperidine (8.6 mmol, 1
equiv to per carbonate unit) was dissolved in THF (20 mL),
and then the mixture solution was injected into the reactor via
the injection port at 60 oC and the FTIR probe began
collecting scans. The infrared spectrometer was set up to
collect one spectrum every 1 min over a certain period.
Determination of carbamate derivatives:
1: (2S,3S)ꢀ3ꢀhydroxybutanꢀ2ꢀyl piperidineꢀ1ꢀcarboxylate
((S,S)ꢀ1a) was obtained after purification by column
chromatography on silica gel (petroleum ether/ethyl acetate =
1:1) in 96% yield as a light yellow oil (1.93 g, 9.60 mmol)
(Table 1, entry 4). 1H NMR (400 MHz, CDCl3): δ 4.69ꢀ4.63
(m, 1H), 3.76ꢀ3.71 (m, 1H), 3.42 (s, 4H), 2.48 (br, 1H), 1.60ꢀ
1.52 (m, 6H), 1.22 (d, J = 6.6 Hz, 3H), 1.18 (d, J = 6.6 Hz,
3H). 13C NMR (100 MHz, CDCl3): δ 155.5, 75.8, 70.4, 44.8,
25.6, 25.5, 24.3, 19.0, 16.5. HRMS (m/z): Calcd. for
[C10H20NO3]+ ([M+H]+): 202.1443, found: 202.1445.
2: (2S,3S)ꢀ3ꢀhydroxybutanꢀ2ꢀyl dimethylcarbamate ((S,S)ꢀ
1b) was obtained after purification by column
chromatography on silica gel (petroleum ether/ethyl acetate
= 1:1) in 86% yield as a light yellow oil (1.38 g, 8.57 mmol).
1H NMR (400 MHz, CDCl3): δ 4.70ꢀ4.64 (m, 1H), 3.77ꢀ3.71
(m, 1H), 2.94 (s, 6H), 1.25 (d, J = 6.8 Hz, 3H), 1.20 (d, J =
6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 156.5, 75.8,
70.1, 36.3, 35.7, 18.7, 16.3. HRMS (m/z): Calcd. for
[C7H16NO3]+ ([M+H]+): 162.1130, found: 162.1135.
3: (2S,3S)ꢀ3ꢀhydroxybutanꢀ2ꢀyl diethylcarbamate ((S,S)ꢀ1c)
was obtained after purification by column chromatography
on silica gel (petroleum ether/ethyl acetate = 1:1) in 87%
yield as a light yellow oil (1.64 g, 8.68 mmol). 1H NMR
(400 MHz, CDCl3): δ 4.72ꢀ4.65 (m, 1H), 3.78ꢀ3.72 (m, 1H),
3.29 (s, 4H), 1.24 (d, J = 6.8 Hz, 3H), 1.19 (d, J = 6.8 Hz,
3H), 1.13 (t, J = 6.8 Hz, 6H). 13C NMR (100 MHz, CDCl3):
δ 155.7, 75.5, 70.4, 41.8, 41.2, 18.9, 16.3, 14.0, 13.4. HRMS
(m/z): Calcd. for [C9H20NO3]+ ([M+H]+): 190.1443, found:
190.1442.
4: (2S,3S)ꢀ3ꢀhydroxybutanꢀ2ꢀyl morpholineꢀ4ꢀcarboxylate
((S,S)ꢀ1d) was obtained after purification by column
chromatography on silica gel (petroleum ether/ethyl acetate =
1:1) in 90% yield as a light yellow oil (1.83 g, 9.01 mmol).
1H NMR (400 MHz, CDCl3): δ 4.74ꢀ4.68 (m, 1H), 3.79ꢀ3.73
(m, 1H), 3.67 (s, 4H), 3.49ꢀ3.48 (m, 4H), 1.25 (d, J = 6.4 Hz,
3H), 1.19 (d, J = 6.4 Hz, 3H). 13C NMR (100 MHz, CDCl3):
δ 155.2, 75.6, 69.5, 66.2, 43.9, 43.7, 18.5, 15.9. HRMS (m/z):
Calcd. for [C9H18NO4]+ ([M+H]+): 204.1236, found:
204.1234.
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■
CONCLUSION
In summary, we have developed an effective methodology for
the highly enantioselective synthesis of various chiral
carbamates from CO2 via enantiopure polycarbonate
intermediates formed by dinuclear Co(III) complex mediated
desymmetric copolymerization of CO2 and mesoꢀepoxides at
mild conditions. This methodology showed broad substrate
scope for both amine nucleophiles and mesoꢀepoxides,
predominantly affording the corresponding optically active
products in high isolated yields and up to 99%
enantioselectivity. The mechanistic study showed that two
degradation routes are responsible for the formation of chiral
carbamates from the aminolysis reaction of amines with
enantiopure CO2ꢀbased polycarbonates. This study is
expected to open up a new route to prepare a wide range of
chiral CO2ꢀbased chemicals with excellent enantioselectivity.
■
EXPERIMENTAL SECTION
General information: All manipulations involving airꢀ
and/or waterꢀsensitive compounds were carried out in a glove
box or with the standard Schlenk techniques under dry
nitrogen. The asymmetric copolymerization of CO2 with
various mesoꢀepoxides mediated by enantiopure dinuclear
cobalt complexes was according to the literature methods.27ꢀ
29,33 Epoxides were distilled over calcium hydride.
Mass Spectrometry. A Micromass QꢀTof mass spectrometer
equipped with an orthogonal electrospray source (Zꢀspray)
used for the cobalt complexes in positive ion mode (Capillary
= 2000 V, Sample cone = 20 V).
Representative procedure for copolymerization/aminolysis
reaction: In a predried 20 mL autoclave equipped with a
magnetic stirrer, dinuclear Co(III) complex (S,S,S,S)ꢀIa (0.01
mmol,
0.001
equiv),
PPNꢀDNP
(PPN
=
bis(triphenylphosphine)iminium, DNP = 2,4ꢀdinitrophenoxide,
0.02 mmol, 0.002 equiv) as cocatalyst and mesoꢀepoxide (10
mmol,
1
equiv) were dissolved in toluene (mesoꢀ
epoxide/toluene = 1/2 (volume ratio)) in an argon atmosphere.
After CO2 was introduced, the reaction mixture was stirred at
a desired temperature for an appropriate time. Then CO2 was
released, a small amount of the resultant mixture was removed
from the autoclave for 1H NMR analysis to quantitatively give
the conversion of mesoꢀepoxide, the selectivity of
polycarbonate to cyclic carbonate, as well as carbonate
linkages. Then GPC analysis to give the polymer molecular
weight (Mn) and molecular weight distribution (PDI). Then
the piperidine (10 mmol, 1 equiv) and water (10 mmol, 1
equiv) in 10 mL THF were added the polymerization mixture.
The resultant mixture was stirred for a desired time at a
designed temperature. Then water (10 mL) was added and the
organic layer was extracted with ethyl acetate (20 mL × 3).
The combined organic phase was washed with brine and dried
over Na2SO4. After removal of the solvent, the residue was
purified by column chromatography on silica gel eluted with
petrol ether/ethyl acetate to give the corresponding carbamate
derivatives.
5: (2S,3S)ꢀ3ꢀhydroxybutanꢀ2ꢀyl ethylcarbamate ((S,S)ꢀ1e)
was obtained after purification by column chromatography
on silica gel (petroleum ether/ethyl acetate = 1:2) in 85%
yield as a light yellow oil (1.37 g, 8.51 mmol). 1H NMR
(400 MHz, CDCl3): δ 4.70ꢀ4.62 (m, 2H), 3.75ꢀ3.68 (m, 1H),
3.27ꢀ3.20 (m, 2H), 1.22 (d, J = 6.4 Hz, 3H), 1.19 (d, J = 6.4
Hz, 3H), 1.15 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 156.4, 75.0, 70.1, 35.7, 18.9, 16.4, 15.0. HRMS
(m/z): Calcd. for [C7H16NO3]+ ([M+H]+): 162.1130, found:
162.1138.
6: (2S,3S)ꢀ3ꢀhydroxybutanꢀ2ꢀyl butylcarbamate ((S,S)ꢀ1f)
was obtained after purification by column chromatography
on silica gel (petroleum ether/ethyl acetate = 1:1) in 84%
yield as a colorless oil (1.59 g, 8.41 mmol). 1H NMR (400
MHz, CDCl3): δ 4.79 (br, 1H), 4.68ꢀ4.62 (m, 1H), 3.75ꢀ3.68
(m, 1H), 3.21ꢀ3.16 (m, 2H), 1.53ꢀ1.45 (m, 2H), 1.40ꢀ1.31 (m,
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2H), 1.22 (d, J = 6.4 Hz, 3H), 1.19 (d, J = 6.4 Hz, 3H), 0.93
13: (1S,2S)ꢀ2ꢀhydroxycyclohexyl diethylcarbamate ((S,S)ꢀ2c)
was obtained after purification by column chromatography
on silica gel (petroleum ether/ethyl acetate = 1:1) in 46%
yield as a light yellow oil (0.99 g, 4.60 mmol). 1H NMR (400
MHz, CDCl3): δ 4.52ꢀ4.45 (m, 1H), 3.56ꢀ3.49 (m, 1H), 3.30
(m, 5H), 2.08ꢀ2.00 (m, 2H), 1.72ꢀ1.70 (m, 2H), 1.40ꢀ1.25 (m,
4H), 1.13 (t, J = 6.8 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ
156.9, 79.0, 73.7, 42.0, 41.5, 33.5, 30.6, 24.0, 23.7, 14.1, 13.5.
HRMS (m/z): Calcd. for [C11H22NO3]+ ([M+H]+): 216.1600,
found: 216.1602.
14: (1S,2S)ꢀ2ꢀhydroxycyclopentyl piperidineꢀ1ꢀcarboxylate
((S,S)ꢀ3a) was obtained after purification by column
chromatography on silica gel (petroleum ether/ethyl acetate =
1:1) in 62% yield as a light yellow solid (1.33 g, 6.24 mmol).
1H NMR (400 MHz, CDCl3): δ 4.69ꢀ4.65 (m, 1H), 4.08ꢀ4.03
(m, 1H), 3.78 (br, 1H), 3.40 (s, 4H), 2.10ꢀ2.00 (m, 2H), 1.76ꢀ
1.53 (m, 10H). 13C NMR (100 MHz, CDCl3): δ 156.4, 84.6,
78.4, 45.0, 44.8, 32.4, 30.0, 25.6, 24.3, 21.3. HRMS (m/z):
Calcd. for [C11H20NO3]+ ([M+H]+): 214.1443, found:
214.1445.
15: (1S,2S)ꢀ2ꢀhydroxycyclopentyl butylcarbamate ((S,S)ꢀ3b)
was obtained after purification by column chromatography
on silica gel (petroleum ether/ethyl acetate = 1:1) in 77%
yield as a light yellow oil (1.55 g, 7.71 mmol). 1H NMR (400
MHz, CDCl3): δ 4.73ꢀ4.67 (m, 2H), 4.09ꢀ4.08 (m, 1H), 3.49
(br, 1H), 3.20ꢀ3.15 (m, 2H), 2.07ꢀ2.03 (m, 2H), 1.72ꢀ1.65 (m,
4H), 1.51ꢀ1.46 (m, 2H), 1.39ꢀ1.31 (m, 2H), 0.94 (t, J = 7.2
Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 157.5, 84.2, 78.3,
40.7, 32.3, 31.9, 30.0, 21.2, 19.9, 13.7. HRMS (m/z): Calcd.
for [C10H20NO3]+ ([M+H]+): 202.1443, found: 202.1441.
16: (1S,2S)ꢀ2ꢀhydroxycyclopentyl benzylcarbamate ((S,S)ꢀ3c)
was obtained after purification by column chromatography
on silica gel (petroleum ether/ethyl acetate = 2:1) in 66%
yield as a light yellow solid (1.54 g, 6.55 mmol).1H NMR
(400 MHz, CDCl3): δ 7.37ꢀ7.29 (m, 5H), 5.06 (s, 1H), 4.73 (s,
1H), 4.38 (d, J = 5.6 Hz, 2H), 4.11 (s, 1H), 3.43 (s, 1H), 2.11ꢀ
2.05 (m, 2H), 1.74ꢀ1.62 (m, 4H). 13C NMR (100 MHz,
CDCl3): δ 157.5, 138.2, 128.7, 127.6, 127.5, 84.5, 78.3, 45.1,
32.3, 30.1, 21.3. HRMS (m/z): Calcd. for [C13H18NO3]+
([M+H]+): 236.1287, found: 236.1281.
(t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 156.6,
74.9, 69.9, 40.5, 31.8, 19.7, 18.8, 16.3, 13.5. HRMS (m/z):
Calcd. for [C9H20NO3]+ ([M+H]+): 190.1443, found:
190.1449.
7: (2S,3S)ꢀ3ꢀhydroxybutanꢀ2ꢀyl benzylcarbamate ((S,S)ꢀ1g)
was obtained after purification by column chromatography
on silica gel (petroleum ether/ethyl acetate = 2:1) in 90%
1
yield as a light yellow oil (2.01 g, 9.01 mmol). H NMR
9
(400 MHz, CDCl3): δ 7.36ꢀ7.27 (m, 5H), 5.08 (br, 1H),
4.73ꢀ4.67 (m, 1H), 4.38 (d, J = 5.6 Hz, 2H), 3.76ꢀ3.69 (m,
1H), 1.24 (d, J = 6.4 Hz, 3H), 1.19 (d, J = 6.4 Hz, 3H). 13C
NMR (100 MHz, CDCl3): δ 156.6, 138.4, 128.3, 127.1,
127.0, 75.0, 69.6, 44.6, 18.6, 16.2. HRMS (m/z): Calcd. for
[C12H18NO3]+ ([M+H]+): 224.1287, found: 224.1290.
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8:
(2S,3S)ꢀ3ꢀhydroxybutanꢀ2ꢀyl
(2ꢀ(1Hꢀindolꢀ3ꢀ
yl)ethyl)carbamate ((S,S)ꢀ1h) was obtained after purification
by column chromatography on silica gel (petroleum
ether/ethyl acetate = 1:2) in 80% yield as a brown oil (2.21 g,
1
8.00 mmol). H NMR (400 MHz, CDCl3): δ 8.13 (s, 1H),
7.59 (d, J = 7.6 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.21 (t, J =
8.0 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 7.02 (s, 1H), 4.81 (br,
1H), 4.68ꢀ4.62 (m, 1H), 3.69ꢀ3.66 (m, 1H), 3.54ꢀ3.50 (m,
2H), 2.99ꢀ2.96 (m, 2H), 2.23 (br, 1H), 1.20 (d, J = 6.8 Hz,
3H), 1.16 (d, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3):
δ 156.6, 136.4, 127.2, 122.2, 122.0, 119.3, 118.6, 112.5,
111.3, 75.3, 70.2, 41.2, 25.5, 18.9, 16.6. HRMS (m/z): Calcd.
for [C15H21N2O3]+ ([M+H]+): 277.1552, found: 277.1554.
9:
(2R,3R)ꢀ3ꢀhydroxybutanꢀ2ꢀyl
((R)ꢀ1ꢀ
phenylethyl)carbamate ((R,R,R)ꢀ1i) was obtained after
purification by column chromatography on silica gel
(petroleum ether/ethyl acetate = 2:1) in 88% yield as a white
solid (2.09 g, 8.82 mmol). 1H NMR (400 MHz, CDCl3): δ
7.42ꢀ7.31 (m, 5H), 5.02 (s, 1H), 4.90 (s, 1H), 4.67 (s, 1H),
3.74 (s, 1H), 2.16 (s, 1H), 1.53 (m, 3H), 1.24 (d, J = 6.8 Hz,
6H). 13C NMR (100 MHz, CDCl3): δ 155.7, 143.4, 128.7,
127.5, 126.0, 75.6, 70.6, 50.8, 22.5, 19.3, 16.8. HRMS (m/z):
Calcd. for [C13H20NO3]+ ([M+H]+): 238.1443, found:
238.1449.
10:
(2S,3S)ꢀ3ꢀhydroxybutanꢀ2ꢀyl
((R)ꢀ1ꢀ
phenylethyl)carbamate ((R,S,S)ꢀ1i) was obtained after
purification by column chromatography on silica gel
(petroleum ether/ethyl acetate = 2:1) in 85% yield as a light
yellow oil (2.02 g, 8.52 mmol). 1H NMR (400 MHz, CDCl3):
δ 7.36ꢀ7.24 (m, 5H), 5.04 (s, 1H), 4.83 (s, 1H), 4.65ꢀ4.62 (m,
1H), 3.70ꢀ3.67 (m, 1H), 2.19 (s, 1H), 1.48 (d, J = 6.8 Hz, 3H),
1.22 (s, 3H), 1.15 (d, J = 6.8 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 155.7, 143.5, 128.7, 127.3, 125.9, 75.4, 70.3, 50.7,
22.5, 19.1, 16.6. HRMS (m/z): Calcd. for [C13H20NO3]+
([M+H]+): 238.1443, found: 238.1447.
11: (1S,2S)ꢀ2ꢀhydroxycyclohexyl piperidineꢀ1ꢀcarboxylate
((S,S)ꢀ2a) was obtained after purification by column
chromatography on silica gel (petroleum ether/ethyl acetate =
1:1) in 50% yield as a light yellow powder solid (1.14 g, 5.02
mmol). 1H NMR (400 MHz, CDCl3): δ 4.50ꢀ4.44 (m, 1H),
3.55ꢀ3.49 (m, 1H), 3.43 (s, 4H), 3.28 (br, 1H), 2.08ꢀ2.00 (m,
2H), 1.72ꢀ1.69 (m, 2H), 1.62ꢀ1.54 (m, 6H), 1.39ꢀ1.22 (m,
4H). 13C NMR (100 MHz, CDCl3): δ 156.3, 79.2, 73.7, 44.9,
33.4, 30.5, 25.7, 25.6, 24.3, 24.0, 23.7. HRMS (m/z): Calcd.
for [C12H22NO3]+ ([M+H]+): 228.1600, found: 228.1605.
12: (1S,2S)ꢀ2ꢀhydroxycyclohexyl dimethylcarbamate ((S,S)ꢀ
2b) was obtained after purification by column
chromatography on silica gel (petroleum ether/ethyl acetate =
1:1) in 41% yield as a white powder solid (0.77 g, 4.12
mmol). 1H NMR (400 MHz, CDCl3): δ 4.50ꢀ4.44 (m, 1H),
3.56ꢀ3.50 (m, 1H), 3.20 (br, 1H), 2.93 (s, 6H), 2.08ꢀ2.00 (m,
2H), 1.72ꢀ1.70 (m, 2H), 1.39ꢀ1.23 (m, 4H). 13C NMR (100
MHz, CDCl3): δ 157.4, 79.3, 73.6, 36.5, 36.0, 33.4, 30.6,
24.0, 23.7. HRMS (m/z): Calcd. for [C9H18NO3]+ ([M+H]+):
188.1287, found: 188.1285.
17:
(5S,6S)ꢀ6ꢀhydroxyꢀ2,2ꢀdimethylꢀ1,3ꢀdioxepanꢀ5ꢀyl
piperidineꢀ1ꢀcarboxylate ((S,S)ꢀ4a) was obtained after
purification by column chromatography on silica gel
(petroleum ether/ethyl acetate = 1:1) in 81% yield as a white
powder solid (2.21 g, 8.10 mmol). 1H NMR (400 MHz,
CDCl3): δ 4.64ꢀ4.60 (m, 1H), 3.82 (d, J = 12.0 Hz, 1H), 3.77ꢀ
3.76 (m, 2H), 3.69ꢀ3.60 (m, 2H), 3.44ꢀ3.41 (m, 5H), 1.61ꢀ
1.54 (m, 6H), 1.35 (s, 6H). 13C NMR (100 MHz, CDCl3): δ
155.1, 101.5, 76.0, 71.4, 61.2, 59.4, 44.9, 25.7, 25.5, 24.7,
24.3, 24.2. HRMS (m/z): Calcd. for [C13H23NNaO5]+
([M+Na]+): 296.1474, found: 296.1471.
18: (9S,10S)ꢀ10ꢀhydroxyꢀ7,12ꢀdioxaspiro[5.6]dodecanꢀ9ꢀyl
piperidineꢀ1ꢀcarboxylate ((S,S)ꢀ4b) was obtained after
purification by column chromatography on silica gel
(petroleum ether/ethyl acetate = 1:1) in 80% yield as a white
1
solid (2.51 g, 8.02 mmol). H NMR (400 MHz, CDCl3): δ
4.60ꢀ4.57 (m, 1H), 3.79 (dd, J = 12.0, 2.0 Hz, 1H), 3.74ꢀ3.73
(m, 2H), 3.67ꢀ3.58 (m, 2H), 3.45ꢀ3.38 (m, 5H), 1.60ꢀ1.48 (m,
14H), 1.40ꢀ1.35 (m, 2H) 13C NMR (100 MHz, CDCl3): δ
155.1, 101.6, 76.2, 71.5, 60.5, 58.6, 45.0, 33.6, 33.3, 25.7,
25.5, 24.3, 22.9. HRMS (m/z): Calcd. for [C16H27NNaO5]+
([M+Na]+): 336.1787, found: 336.1789.
19: (3S,4S)ꢀ4ꢀhydroxytetrahydrofuranꢀ3ꢀyl piperidineꢀ1ꢀ
carboxylate ((S,S)ꢀ5a) was obtained after purification by
column chromatography on silica gel (petroleum ether/ethyl
acetate = 1:1) in 77% yield as a light yellow solid (1.65 g,
1
7.67 mmol). H NMR (400 MHz, CDCl3): δ 4.90ꢀ4.83 (m,
1H), 4.31 (m, 1H), 4.16ꢀ4.05 (m, 2H), 3.86ꢀ3.83 (m, 1H),
3.73ꢀ3.69 (m, 1H), 3.40 (m, 4H), 3.09 (s, 1H), 1.61ꢀ1.53 (m,
6H). 13C NMR (100 MHz, CDCl3): δ 155.2, 81.8, 76.5, 73.3,
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71.1, 45.0, 44.8, 25.7, 25.4, 24.2. HRMS (m/z): Calcd. for
[C10H18NO4]+ ([M+H]+): 216.1236, found: 216.1233.
20: (2S,3S)ꢀ3ꢀhydroxyꢀ1,2,3,4ꢀtetrahydronaphthalenꢀ2ꢀyl
The retention time of cisꢀcarbamate was completely different
from transꢀisomer, which confirmed that cisꢀisomer wasn't
produced during the aminolysis reaction (Figures S65 and
S66 in Supporting Information).
2. Determination of the cyclic carbonates intermediates
for the aminolysis reaction of poly(trans-2-butene
carbonate):
piperidineꢀ1ꢀcarboxylate ((S,S)ꢀ6a) was obtained after
purification by column chromatography on silica gel
(petroleum ether/ethyl acetate = 1:1) in 75% yield as a white
powder solid (2.05 g, 7.45 mmol).1H NMR (400 MHz,
CDCl3): δ 7.18ꢀ7.09 (m, 4H), 4.98ꢀ4.92 (m, 1H), 4.09ꢀ4.03
(m, 1H), 3.45 (s, 4H), 3.31ꢀ3.20 (m, 3H), 2.95ꢀ2.86 (m, 2H),
1.67ꢀ1.57 (m, 6H). 13C NMR (100 MHz, CDCl3): δ 155.9,
133.8, 133.4, 128.7, 128.4, 126.33, 126.26, 75.8, 70.4, 44.9,
36.6, 33.9, 25.6, 24.3. HRMS (m/z): Calcd. for [C16H22NO3]+
([M+H]+): 276.1600, found: 276.1602.
Synthesis procedure for transꢀ2ꢀbutene carbonate (Scheme
S3 in Supporting Information):
9
(S,S)ꢀCO2 copolymer from cisꢀ2,3ꢀepoxybutane (100 mg,
0.86 mmol) and DBU (1.3 mg, 0.0086 mmol) were
transferred into a flask and 5 mL THF was added. After the
polymer was dissolved completely, the resultant mixture was
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o
21:
(1S,6S)ꢀ6ꢀhydroxycyclohexꢀ3ꢀenꢀ1ꢀyl
piperidineꢀ1ꢀ
stirred for 12 h at 60 C. The conversion of the polymer was
carboxylate ((S,S)ꢀ7a) was obtained after purification by
column chromatography on silica gel (petroleum ether/ethyl
acetate = 1:1) in 81% yield as a light yellow solid (1.83 g,
>99% based on 1H NMR analysis. After cooling to room
temperature, hydrochloric acid (1 M, 10 mL) was added to
the reaction mixture. The organic layer was extracted with
ethyl acetate (10 mL × 3). The combined organic phase was
washed with water, brine and dried over Na2SO4. After
removal of the solvent, the residue was purified by column
chromatography on silica gel eluted with petrol ether/ethyl
acetate (1/1) to give transꢀ(S,S)ꢀcarbonate as a light yellow
oil (95 mg, yield 95%). 1H NMR (400 MHz, CDCl3): δ 4.39–
4.28 (m, 2H), 1.45 (d, J = 6.0 Hz, 6H). 13C NMR (100 MHz,
CDCl3): δ 154.6, 80.0, 18.4. HRMS (m/z): Calcd for
[C5H8NaO3]+ ([M+Na]+): 139.0371; found: 139.0372.
1
8.13 mmol). H NMR (400 MHz, CDCl3): δ 5.60ꢀ5.51 (m,
2H), 4.83ꢀ4.77 (m, 1H), 3.90ꢀ3.83 (m, 1H), 3.45ꢀ3.43 (m,
4H), 2.98ꢀ2.97 (br, 1H), 2.60ꢀ2.51 (m, 2H), 2.20ꢀ2.11 (m,
2H), 1.61ꢀ1.54 (m, 6H). 13C NMR (100 MHz, CDCl3): δ
155.9, 124.4, 123.8, 75.2, 69.8, 44.9, 33.6, 30.8, 25.6, 24.3.
HRMS (m/z): Calcd. for [C12H20NO3]+ ([M+H]+): 226.1443,
found: 226.1445.
Mechanistic understanding of ammonolysis reaction:
1. Synthesis of cis-carbamates and carbamates: In order
to confirm that the diastereoisomer, cisꢀcarbamates were not
produced in the aminolysis process, the cisꢀcarbamates with
(R,S)ꢀ or (S,R)ꢀconfiguration were synthesized (Scheme S1 in
Supporting Information).
Representative procedures for the synthesis of cisꢀ
cyclopentene carbonate: In a predried 20 mL autoclave
equipped with a magnetic stirrer, Cr(III)ꢀSalen catalyst (0.02
mmol, 1 equiv), PPNꢀCl (0.40 mmol, 20 equiv) and
cyclopentene oxide (20 mmol, 1000 equiv) were dissolved in
toluene (epoxide/toluene = 1/1, volume ratio) in an argon
atmosphere. After CO2 was introduced, the reaction mixture
was stirred at 100 oC for 24 hours. After the reaction mixture
was cooled to room temperature, then CO2 was released, a
small amount of the resultant mixture was removed from the
autoclave for 1H NMR analysis, the results showed that
cyclopentene oxide were all converted to cisꢀcyclopentene
carbonate as the sole product. The crude product was purified
by vacuum distillation as a white solid (2.51 g, 98% yield).
1H NMR (400 MHz, CDCl3): δ 5.12ꢀ5.11 (m, 2H), 2.20ꢀ2.14
(m, 2H), 1.83ꢀ1.64 (m, 4H). 13C NMR (100 MHz, CDCl3): δ
155.4, 81.8, 33.0, 21.4 (Figures S61 and S62 in Supporting
Information). HRMS (m/z): Calcd for [C6H8NaO3]+
([M+Na]+): 151.0371; found: 151.0377.
From PlotꢀA, Figure S67 in Supporting Information, we
discovered that transꢀ2ꢀbutene carbonate was detected during
the aminolysis reaction of poly(transꢀ2ꢀbutene carbonate) in
absence of water. This phenomenon was in accordance with
the in situ FTIR experiments (Figure 3, plotsꢀ(a) and (b)).
However, when the reaction was performed in presence of
water (PlotꢀB, Figure S67 in Supporting Information), the
transꢀ2ꢀbutene carbonate was not detected because the
reaction proceeded very quickly. The addition of water can
accelerate the reaction, and this phenomenon has been
frequently observed in ringꢀopening of epoxides using amine
nunucleophiles.34ꢀ37 Moreover, we also isolated the transꢀ2ꢀ
butene carbonate in a different method, it can react with
piperidine, the product was same as the aminolysis reaction
of poly(transꢀ2ꢀbutene carbonate) directly (Figure S68 in
Supporting Information). This results also indicated that the
aminolysis reaction of poly(transꢀ2ꢀbutene carbonate)
underwent the cyclic carbonate intermediate, which was
formed from the degradation of poly(transꢀ2ꢀbutene
carbonate) by a backꢀbiting mechanism, starting from the
copolymer chain end (Figure 4, route A). So the aminolysis
reaction of poly(transꢀ2ꢀbutene carbonate) show excellent
selectivities (>99%) and yields (>90%), without 1,2ꢀdiol
byproducts.
Representative procedures for synthesis of cisꢀcarbamate
(Scheme S2 in Supporting Information):
3. Determination of the intermediates for the aminolysis
reaction of poly(cyclopentene carbonate): From the
aminolysis reaction of poly(cyclopentene carbonate), except
for the 1,2ꢀdiols, carbamates and polymers, we also
discovered a new series of peaks, then we isolated this new
intermediate (Figure S69 in Supporting Information). After
cooling the reaction mixture to room temperature,
hydrochloric acid (1 M, 10 mL) was added. The organic layer
was extracted with ethyl acetate (20 mL × 3). The combined
organic phase was washed with water, brine and dried over
Na2SO4. After removal of the solvent, the residue was
purified by column chromatography on silica gel eluted with
petrol ether/ethyl acetate (2/1). Except for the carbamates, a
new intermediate was also separated. Based on NMR and
HRMS analysis, it was 2,2'ꢀcarbonyldioxydicyclohexanol
The cisꢀcyclopentene carbonate (512 mg, 4.0 mmol) was
transferred into a flask and 10 mL THF was added. After the
carbonate was dissolved completely, piperidine (4.0 mmol, 1
equiv to per carbonate unit) and water (4.0 mmol, 1 equiv to
per carbonate unit) were added. The resultant mixture was
o
stirred for 2 h at 60 C. After cooling to room temperature,
hydrochloric acid (1 M, 10 mL) was added to the reaction
mixture. The organic layer was extracted with ethyl acetate
(20 mL × 3). The combined organic phase was washed with
water, brine and dried over Na2SO4. After removal of the
solvent, the residue was purified by column chromatography
on silica gel eluted with petrol ether/ethyl acetate (2/1) to
give the cisꢀcarbamates as a light yellow oil (790 mg, yield
93%). 1H NMR (400 MHz, CDCl3): δ 4.95ꢀ4.91 (m, 1H),
4.20ꢀ4.15 (m, 1H), 3.44ꢀ3.42 (m, 4H), 2.37 (br, 1H), 1.99ꢀ
1.52 (m, 12H). 13C NMR (100 MHz, CDCl3): δ 154.6, 76.6,
72.4, 46.1, 43.9, 29.7, 27.4, 24.6, 23.4, 18.4 (Figures S63 and
S64 in Supporting Information). HRMS (m/z): Calcd. for
[C11H20NO3]+ ([M+H]+): 214.1443, found: 214.1445.
1
(Figures S70 and S71 in Supporting Information). H NMR
(400 MHz, CDCl3): δ 4.79ꢀ4.74 (m, 2H), 4.21ꢀ4.18 (m, 2H),
2.93 (s, 2H), 2.18ꢀ2.01 (m, 4H), 1.79ꢀ1.63 (m, 8H). 13C NMR
(100 MHz, CDCl3): δ 156.4, 87.0, 78.1, 32.6, 30.1, 21.7.
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HRMS (m/z): Calcd. for [C11H18NaO5]+: 253.1052, found:
253.1056.
5. Yu, D.; Teong, S. P.; Zhang Y. 2014, 293–294, 279−291.
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The aminolysis reaction of 2,2'ꢀcarbonyldioxydicyclohexanol
with piperidine was described in Figure S72 in Supporting
Information. Formation of 2,2'ꢀcarbonyldioxydicyclohexanol
not only accelerates the reaction, but also results in the
formation of 1,2ꢀdiols byproducts. Furthermore, water has a
positive effect on the reaction rate, the addition of water can
accelerate the reaction, however, it can also result in the
formation of 1,2ꢀdiols byproducts at the same time. However,
for the reaction of 2,2'ꢀcarbonyldioxydicyclohexanol with
piperidine in absence of water, the carbamate wasn't
discovered (PlotꢀA, Figure S72 in Supporting Information).
Because the aminolysis of poly(cyclopentene carbonate)
underwent a random fashion (Figure 4, route B), rather than a
cyclic carbonate intermediate, this reaction suffered from
relatively low product selectivities and yields compared with
poly(transꢀ2ꢀbutene carbonate).
8
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Synthesis procedure for (S,S)-carbamate derivative for X-
Ray analysis (Scheme S4 in Supporting Information):
A roundꢀbottom flask containing magnetic stirring bar was
charged with 4ꢀbromobenzoic acid (200 mg, 1.0 mmol),
15. Hooker, J. M.; Reibel, A. T.; Hill, S. M.; Schueller, M.
J.; Fowler, J. S. Angew. Chem. Int. Ed. 2009, 48, 3482–
3485.
(S,S)ꢀ2a (227 mg,
1 mmol), 4ꢀ(dimethylamino)pyridine
(DMAP, 134 mg, 1.1 mmol), and dichloromethane (4 mL).
N,N'ꢀDicyclohexylcarbodiimide (206 mg, 1.0 mmol) in
dichloromethane (1 mL) was added, and the mixture was
stirred at room temperature for 12 h. The resulting suspension
was filtrated and concentrated under reduced pressure. After
removal of the solvent, the residue was purified by column
chromatography on silica gel eluted with petrol ether/ethyl
acetate (10/1) to give (S,S)ꢀcarbamate derivative as a white
solid (377 mg, yield 92%). 1H NMR (400 MHz, CDCl3): δ
7.89 (d, J = 8.8 Hz, 2H), 7.57 (d, J = 8.8 Hz, 2H), 5.08ꢀ5.02
(m, 1H), 4.90ꢀ4.84 (m, 1H), 3.25 (s, 4H), 2.17ꢀ2.12 (m, 2H),
1.78ꢀ1.76 (m, 2H), 1.24ꢀ1.25 (m, 10H). 13C NMR (100 MHz,
CDCl3): δ 164.3, 153.8, 130.6, 130.2, 128.3, 127.0, 74.3, 73.5,
43.7, 29.7, 29.3, 24.5, 23.3, 22.64, 22.60 (Figures S73 and
S74 in Supporting Information). HRMS (m/z): Calcd. for
[C19H25BrNO4]+: 410.0967, found: 410.0968.
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Supporting Information.
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■
ASSOCIATED CONTENT
Supporting Information. NMR and HPLC spectrum of
various carbamates derivatives, and Xꢀray data. This material
is available free of charge via the Internet at
http://pubs.acs.org.
■
AUTHOR INFORMATION
Corresponding Author
* Eꢀmail: liuye@dlut.edu.cn
* Eꢀmail: xblu@dlut.edu.cn
Notes
The authors declare no competing financial interest
■
ACKNOWLEDGMENTS
This work is supported by the National Natural Science
Foundation of China (NSFC, Grant 21134002, 21504011),
and the Specialized Research Fund for the Doctoral Program
of Higher Education (SREDP) (Grant 20130041130004). X.ꢀ
B. Lu gratefully acknowledges the Chang Jiang Scholars
Program (T2011056) from the Ministry of Education of
China.
■
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