Bimetallic aluminum(salen) catalyzed synthesis of oxazolidinones from epoxides and isocyanates

Article abstract of DOI:10.1021/cs4001046

The bimetallic aluminum(salen) complex [Al(salen)]₂O is shown to catalyze the synthesis of oxazolidinones from epoxides and isocyanates. The reaction is demonstrated to proceed with overall retention of epoxide stereochemistry, and both aromati

Full text of DOI:10.1021/cs4001046

Research Article
pubs.acs.org/acscatalysis
Bimetallic Aluminum(salen) Catalyzed Synthesis of Oxazolidinones
from Epoxides and Isocyanates
Thilo Baronsky, Christopher Beattie, Ross W. Harrington, Reyhan Irfan, Michael North,*
Javier G. Osende, and Carl Young
School of Chemistry and University Research Centre in Catalysis and Intensified Processing, Newcastle University, Bedson Building,
Newcastle upon Tyne, NE1 7RU, U.K.
S
* Supporting Information
ABSTRACT: The bimetallic aluminum(salen) complex [Al-
(salen)]2O is shown to catalyze the synthesis of oxazolidinones
from epoxides and isocyanates. The reaction is demonstrated
to proceed with overall retention of epoxide stereochemistry,
and both aromatic and aliphatic isocyanates can be used as
substrates. In contrast to the corresponding reactions between
epoxides and carbon dioxide or carbon disulfide which are also
catalyzed by [Al(salen)]2O, no cocatalyst is needed in the
reactions with isocyanates. A mechanism is proposed which involves breaking and reforming of the Al−O−Al unit during the
catalytic cycle, and this is supported by results obtained using monometallic catalysts.
KEYWORDS: oxazolidinone, aluminum, salen, epoxide, isocyanate
Scheme 1. Synthesis of Oxazolidinones Using Catalyst 1
INTRODUCTION
■
Aluminum(salen) complex 1 was first introduced by Jacobsen
as a catalyst for asymmetric Michael additions.1−7 The same
complex was subsequently shown by Zhu to catalyze Passerini-
type reactions,8 and we have previously shown that complex 1
will catalyze: the asymmetric addition of trimethylsilyl cyanide
to aldehydes;9,10 the synthesis of cyclic carbonates from
epoxides and carbon dioxide;11−15 and the synthesis of di- or
trithiocarbonates from epoxides and carbon disulfide.16,17 Both
of the latter two reactions involve the reaction between an
epoxide and a heterocumulene. We therefore decided to
investigate the use of complex 1 to catalyze the reaction
between epoxides and isocyanates leading to oxazolidinones as
shown in Scheme 1. Oxazolidinones are of medicinal chemistry
interest in their own right18−26 and are also useful synthetic
intermediates, for example, as precursors of β-aminoalcohols.27
Related mononuclear, aluminum(salen) complexes have also
been used for cyclic carbonate synthesis28 and polycarbonate
synthesis by direct reaction of carbon dioxide with epoxides,29
oxetanes,30 or ring-opening polymerization of cyclic carbo-
nates.31
The reaction shown in Scheme 1 has previous been shown to
be catalyzed by species including: ammonium salts,32
lanthanide salts,33−35 lithium halides,36−40 magnesium hal-
ides,41 tetraphenylantimony iodide,42−44 and trialkyltin hal-
ides.45−48 However, both the regiochemistry (formation of 4
versus 5) and stereochemistry of the reaction (retention or
inversion of epoxide 2 stereochemistry) should be controlled,
and the reaction should accommodate a wide range of epoxides
2 and isocyanates 3. In this respect it is notable that previous
work has largely been restricted to mono-substituted epoxides
and arylisocyanates and has often employed toxic catalysts. In
contrast, complex 1 is derived from an abundant, inexpensive,
and relatively non-toxic metal. There is only one previous
example of an aluminum catalyst for the synthesis of
oxazolidinones from epoxides and isocyanates and that involved
the use of aluminum trichloride in refluxing DMF.49
Oxazolidinones have also been prepared by related chemistry
involving the reaction between epoxides and ethyl carbamate
catalyzed by a cobalt(salen) complex.50
Received: February 7, 2013
Revised: March 11, 2013
Published: March 15, 2013
© 2013 American Chemical Society
790
dx.doi.org/10.1021/cs4001046 | ACS Catal. 2013, 3, 790−797

ACS Catalysis
Research Article
conversion of styrene oxide into a 2:1 ratio of oxazolidinones
4a and 5a after a reaction time of 24 h (Table 1, entry 13).
The conditions of Table 1, entry 13 were taken as optimal
and applied to seven other epoxides to give oxazolidinones 4b−
h and 5b−h as detailed in Table 2. The results in entries 2−6 of
RESULTS AND DISCUSSION
■
Screening studies were carried out using equimolar amounts of
styrene oxide and phenyl isocyanate under various conditions
with the results being shown in Table 1. Initial experiments
Table 1. Reaction of Styrene Oxide with Phenylisocyanate
Table 2. Reaction of Epoxides with Phenylisocyanate
a
a
b
b
entry
1
Bu4NBr
solv.
t (h) T (°C) conv. (%) 4a:5a
epoxide 2
1
2
2.5
2.5
5
2.5
2.5
5
18
18
18
18
18
20
20
20
40
20
20
40
24
18
80
80
120
80
80
80
80
80
80
80
80
80
0
18
17
0
a
b
entry 1 (mol %)
R1
R2
conv. (%)
4:5
0:1
1
2
3
4
5
6
7
8
5
5
Ph
H
H
H
H
H
H
H
100
100
100
100
91
1.9:1 (61, 32)
1:10 (0, 48)
0:1 (82)
3
0:1
Me
4
5
5
5
CH2Cl
nBu
nOct
5
0
0
0
5
1:6.1 (12, 62)
1:6.6 (13, 65)
0:1 (94)
6
2.5
0
0
50
37
68
85
59
64
72
100
1.5:1
7
2.5
0
1:1.8
5
8
5
1.4:1
1.4:1
1.3:1
1.9:1
1.8:1
1.9:1
5
CH2OPh
CH2OH
100
71
9
5
0
5
1:0 (62)
c
c
10
11
12
13
2.5
5
0
EC
10
(CH2)4
63
(44)
d
a
Conversion of epoxide 2 into 4+5 determined by 1H NMR
0
DCB
DCB
d
b
5
0
spectroscopy of the reaction mixture. Ratio of 4:5 determined by
1H NMR spectroscopy prior to chromatographic separation. Figures in
brackets are isolated chemical yields after separation by column
5
0
MePh
a
b
mol %. Conversion of epoxide 2 into 4a+5a and ratio of 4a:5a
c
c
1
chromatography. Reaction time 48 h.
determined by H NMR spectroscopy of the reaction mixture. EC =
ethylene carbonate. DCB = 1,2-dichlorobenzene.
d
Table 2 show that styrene oxide was exceptional in giving 3,4-
isomer 4a as the major product since the 3,5−isomer of
oxazolidinones 4/5b−f was the major product with other
monosubstituted epoxides. Thus, in general, epoxide ring-
opening occurs at the less hindered carbon atom, but for
styrene oxide, this sterically driven trend is overridden by the
electronic preference for ring-opening to occur at the benzylic
position.54 All of the reactions proceeded readily beyond 50%,
and no kinetic resolution of the racemic epoxides occurred,
consistent with previous results obtained for cyclic carbonate
synthesis using catalyst 1.11−15
Glycidol also underwent epoxide ring-opening selectively at
the more hindered carbon atom (Table 2, entry 7). However, it
is well-known55−59 that this epoxide reacts with isocyanates by
a different mechanism in which the isocyanate first reacts with
the alcohol to form an intermediate carbamate which then
reacts intramolecularly with the epoxide to form 3,4-
oxazolidinone 4g. Notably however, this mechanism is known
to require a base (sodium hydride55,56 or triethylamine58,59 are
commonly used), and this was the first indication that complex
1 might have significant basicity, presumably associated with its
bridging oxygen atom.
Cyclohexene oxide also underwent reaction, to form
oxazolidinone 4h. In this case, the amount of catalyst was
increased to 10 mol % and the reaction time extended to 48 h
(Table 2, entry 8) to ensure that a good yield of compound 4h
was obtained as a single diastereomer by NMR spectroscopy.
Crystals of compound 4h suitable for X-ray analysis were grown
from diethyl ether, and the resulting crystal structure (Figure 1)
clearly showed that the two rings were cis-fused to one another.
Both the cis-60,61 and trans-isomers62 of compound 4h are
known compounds, and the formation of cis-fused product was
unexpected as it implies that the conversion of cyclohexene
oxide into oxazolidinone 4h occurs by a double inversion
mechanism. Such a mechanism and stereochemical outcome
has previously been observed during the reaction of 1,2-
disubstituted epoxides with carbon dioxide catalyzed by
complex 1 and tetrabutylammonium bromide.63 In this case,
the epoxide initially undergoes ring-opening by bromide to
were based around the use of 2.5 mol % of complex 1 and
tetrabutylammonium bromide as a cocatalyst in the absence of
a solvent, conditions which were optimal for the addition of
carbon dioxide to epoxides.11−15 However, at room temper-
ature this resulted in no reaction occurring (Table 1, entry 1)
and even at 80 °C, only 18% conversion of styrene oxide into
oxazolidinone 5a was observed (Table 1, entry 2). Increasing
the catalyst loadings to 5 mol % (Table 1, entry 3) was not
beneficial, and further increase of the reaction temperature to
120 °C resulted in decomposition (Table 1, entry 4).
Control experiments at 80 °C proved to be informative. In
the absence of catalyst 1 or tetrabutylammonium bromide, no
reaction occurred (Table 1, entry 5). Both complex 1 and
tetrabutylammonium bromide were found to be catalytically
active in their own right (Table 1, entries 6 and 7), but
catalyzed the preferential formation of opposite regioisomers of
oxazolidinones 4/5a. Furthermore, comparison of Table 1,
entries 2,6 and 7 shows that complex 1 and tetrabutylammo-
nium bromide actually inhibit each others catalytic activity, a
result which is in marked contrast to the reactions of epoxides
with carbon dioxide and carbon disulfide where a cooperative
effect between these two catalytic species was observed.11−17
Subsequent reaction optimization experiments therefore
focused on the use of complex 1 alone, and by increasing the
catalyst loading to 5 mol %, the conversion could be increased
to 68% after 20 h (Table 1, entry 8) or 85% after 40 h (Table 1,
entry 9). Finally, the influence of a solvent was investigated
through the use of three high boiling point solvents with very
different polarities. Ethylene carbonate is a green polar aprotic
solvent which can be used as a replacement for dimethylforma-
mide (DMF) and dimethylsulfoxide (DMSO).51−53 It gave
only a slight improvement in conversion compared to solvent
free conditions (compare Table 1, entries 6 and 10). The
chlorinated solvent 1,2-dichlorobenzene of intermediate polar-
ity gave no improvement in conversion, but a minor increase in
regioselectivity compared to the use of no solvent (compare
Table 1, entries 8 and 9 with 11 and 12). Finally, the use of a
nonpolar solvent, toluene proved to be optimal, giving 100%
791
dx.doi.org/10.1021/cs4001046 | ACS Catal. 2013, 3, 790−797

ACS Catalysis
Research Article
a
Table 3. Reaction of Epoxides with Aromatic Isocyanates
b
c
entry epoxide 2, R1 isocyanate 3, R2 conv. (%)
4:5
1
Ph
4-O2NC6H4
4-MeOC6H4
4-MeC6H4
4-FC6H4
34
62
69
68
38
39
41
88
100
79
46
40
33
2.8:1 (14, 6)
1.8:1 (38, 17)
1.9:1 (38, 7)
2.2:1 (40, 22)
3.5:1 (28, 8)
2.5:1 (27, 11)
0:1 (36)
2
Ph
3
Ph
4
Ph
5
Ph
4-ClC6H4
4-BrC6H4
4-O2NC6H4
4-MeOC6H4
4-MeC6H4
4-FC6H4
6
Ph
7
CH2Cl
CH2Cl
CH2Cl
CH2Cl
CH2Cl
CH2Cl
CH2Cl
8
0:1 (80)
9
0:1 (89)
10
11
12
13
0:1 (44)
4-ClC6H4
4-BrC6H4
Cy
0:1 (43)
0:1 (40)
Figure 1. X-ray structure of compound 4h.
0:1 (21)
a
All reactions carried out at 80 °C in toluene for 24 h using 5 mol % of
b
catalyst 1. Conversion of epoxide 2 into 4+5 determined by 1H NMR
form an aluminum bound bromo alkoxide which can react with
carbon dioxide to form an aluminum bound bromo carbonate
which can then undergo ring closure, eliminating the bromide
to form the cyclic carbonate product.12,13 However, for the
synthesis of oxazolidinone 4h, no tetrabutylammonium bro-
mide or other nucleophilic cocatalyst was present, so the
formation of a trans-fused product was anticipated as had been
observed for the reaction between cyclohexene oxide and
carbon disulfide catalyzed by complex 1 and tributylamine.16,17
Having shown that the synthesis was compatible with a range
of epoxides, its compatibility with various isocyanates was
investigated. Styrene oxide and epichlorohydrin were selected
as representative examples of aromatic and aliphatic epoxides,
and they were each reacted with six aromatic isocyanates to give
oxazolidinones 4/5i−t as shown in Scheme 2. The results are
c
1
spectroscopy of the reaction mixture. Ratio of 4:5 determined by H
NMR spectroscopy. Figures in brackets are isolated chemical yields
after separation by column chromatography.
to react with the isocyanate, converting it into a more reactive
acylating agent. The reaction between styrene oxide and 4-
chlorophenylisocyanate was selected as a test reaction.
However, triethylamine, N,N-dimethylaminopyridine, triphe-
nylphosphine, triphenylphsophine oxide, pyridine N-oxide,
hexamethylphosphoramide, and trimethylammonium oxide
were all found to be catalytically inactive in their own right
and acted as inhibitors of reactions when used with complex 1.
A catalytic cycle which accounts for the observed regio- and
stereochemistry is shown in Scheme 3. In this mechanism, the
Scheme 3. Proposed Catalytic Cycle
Scheme 2. Synthesis of Oxazolidinones 4/5i−t
presented in Table 3. For reactions involving styrene oxide, the
3,4-oxazolidinone (4i−n) was always the major product formed
in around a 2:1 ratio relative to 3,5-oxazolidinone 5i−n (Table
3, entries 1−6). In contrast, for reactions involving epichlor-
ohydrin, only the 3,5-oxazolidinone (5o−t) was formed from
any of the isocyanates (Table 3, entries 7−12). The electronic
properties of the isocyanate affected the yield of oxazolidinones
4/5i−t with the highest yields obtained using electron-rich
isocyanates (Table 3, entries 2−4 and 8−10) while electron
deficient isocyanates gave lower yields and the 4-nitro-
phenylisocyanate gave particularly low yields with both
epoxides (Table 3, entries 1 and 7). The reaction was not
restricted to aromatic isocyanates as shown by the formation of
product 5u from epichlorohydrin and cyclohexylisocyanate
(Table 3, entry 13).
Lewis-basic bridging oxygen of complex 1 first reacts with the
isocyanate to form adduct 6. This increases the Lewis acidity of
the aluminum ions, one of which can coordinate to the epoxide,
forming adduct 7 in which the epoxide ring is activated toward
ring-opening. In most cases for monosubstituted epoxides, the
epoxide ring-opening occurs at the terminal carbon by an SN2
type mechanism (and hence with inversion of configuration in
the case of cyclohexene oxide). However, in the case of styrene
oxide the electronic stabilization available from the aromatic
ring favors ring-opening at the benzylic position. In either case,
ring-opening forms adduct 8 in which the bimetallic Al−O−Al
unit within the catalyst has been broken. Ring closure of adduct
8 as shown involves a second substitution reaction which will
proceed with inversion of configuration and forms oxazolidi-
nones 4/5 as well as reforming bimetallic catalyst 1.
In view of the moderate yields obtained with electron
deficient isocyanates, the effect of nucleophilic cocatalysts was
investigated in the hope that that the cocatalyst might be able
792
dx.doi.org/10.1021/cs4001046 | ACS Catal. 2013, 3, 790−797

ACS Catalysis
Research Article
The mechanism shown in Scheme 3 requires that the catalyst
initially possesses an Al−X−Al unit, but that this is capable of
being broken during the catalytic cycle. To investigate this, the
use of the monometallic aluminum(salen) complexes17 9−11
(Figure 2) as catalysts for the reaction between phenyl-
isocyanates. In contrast to the corresponding reactions between
epoxides and either carbon dioxide or carbon disulfide which
are also catalyzed by complex 1, no cocatalyst is needed for the
reaction with isocyanates, and cocatalysts including tetrabuty-
lammonium bromide were found to inhibit the reaction.
Compared to previously reported catalysts for the synthesis of
oxazolidinones from epoxides and isocyanates,32−49 the use of
complex 1 allows the use of aliphatic as well as aromatic
isocyanates. Reactions can be carried out at lower temperatures
than literature procedures which require the use of refluxing
DMF,39 refluxing xylene,37 or a sealed system at 200 °C.32 The
use of highly toxic catalysts based on tin45−48 and/or
antimony42−44,46 is avoided as is the use of lanthanide based
catalysts.33,34 Finally, only 5 mol % catalyst is required
compared with the 10 mol %42−44,46 or even 50 mol %41
required by some other catalyst systems.
Figure 2. Monometallic aluminum(salen) complexes 9−11.
isocyanate and styrene oxide, 1-decene oxide or 3-chloropro-
pylene oxide to form oxazolidinones 4/5a,c,e was investigated
with the results being presented in Table 4.
Use of cyclohexene oxide as substrate resulted in the
exclusive formation of cis-fused oxazolidinone 4h, the structure
of which was proven by X-ray crystallography. This is the same
stereochemistry as seen in the reaction between epoxides and
carbon dioxide catalyzed by complex 1, but the opposite
stereochemistry to that seen in the reaction between epoxides
and carbon disulfide catalyzed by complex 1. The stereo-
chemistry of compound 4h implies that the reaction
mechanism involves a double inversion of configuration.
Additional mechanistic studies to elucidate the catalytic cycle
and provide a coherent mechanistic analysis for the reactions
between epoxides and heterocumulenes catalyzed by complex 1
are underway and will be reported in due course.
Table 4. Oxazolidinone Synthesis Using Monometallic
a
Complexes 9−11
b
catalyst
epoxide 2,
R1
9
10
11
1
Ph
0
0
53 (2.4:1
100 (1.9:1
4a:5a)
4a:5a)
nOct
6 (all 5e) 7 (all 5e) 35 (1:5.4
4e:5e)
91 (1:6.6 4e:5e)
ClCH2
57 (all 5c) 49 (all 5c) 66 (all 5c)
100 (all 5c)
EXPERIMENTAL SECTION
a
■
All reactions carried out at 80 °C in toluene for 24 h using 5 mol % of
1
b
General Procedures. H NMR spectra were recorded at
catalyst. Conversion of epoxide 2 into 4+5 and in brackets, ratio of
400 or 300 MHz, 13C NMR spectra were recorded at 100 or 75
MHz, and 19F NMR spectra were recorded at 376 MHz. All
1
4:5 determined by H NMR spectroscopy of the reaction mixture.
spectra were recorded at ambient temperature. H and 13C
1
NMR spectra were referenced to the residual solvent peak, 19F
Monomometallic complexes 9 and 10 had essentially no
catalytic activity for the synthesis of oxazolidinones 4/5a,e.
However, chloride containing complex 11 was catalytically
active, had about half the activity of complex 1, and gave a
similar 4:5 ratio to complex 1. In all cases, 5 mol % of catalyst
was used, but since complex 1 is bimetallic it contains twice as
many aluminum(salen) units as complex 11. This may account
for the difference in catalytic activity between complexes 1 and
11. It is known that chlorine can bridge between aluminum
atoms,64−71 which would result in the formation of oligomeric
species analogous to complex 1 and provide the bimetallic
assembly required for the mechanism shown in Scheme 3. In
contrast, this is not possible for complex 9 and sterically
retarded in complex 10.
In contrast, all of the monometallic complexes catalyzed the
addition of phenylisocyanate to 3-chloropropylene oxide, and
all displayed a level of catalytic activity which was about half
that displayed by complex 1 (Table 4). It appears that 3-
chloropropylene oxide can act as a source of chloride during the
reactions and that this can convert monometallic complexes 9
and 10 into chloro complex 11. The chloride may be generated
by nucleophilic substitution using either the ethoxide ligand
present in complex 10 or the adventitious moisture in the
reactions.
1
NMR spectra were externally referenced to CFCl3. For H
NMR spectra, multiplicities are reported as s (singlet), d
(doublet), t (triplet), q (quartet), m (multiplet), br (broad), or
a combination of these. GCMS were recorded on a FactorFour
(VF-5 ms) capillary column (30 m × 0.25 mm) with helium as
the carrier gas. The conditions used were as follows: initial
temperature 60 °C, hold at initial temperature for 3 min, then
ramp rate 15 °C/min to 270 °C; hold at final temperature for 5
min. For the first 3.50 min, the eluent was routed away from
the mass detector. Subsequently, the detector was operated in
full EI or CI scan mode.
General Procedure for the Synthesis of Oxazolidi-
nones. To a stirred solution of complex 1 (0−0.087 mmol)
and a cocatalyst (0−0.087 mmol) in toluene (2 mL) was added
an epoxide (0.874 mmol) and isocyanate (0.874 mmol). The
reaction was then heated to 80 °C and stirred for 18−48 h. The
reaction was cooled to room temperature and solvent removed
in vacuo. CH2Cl2 (5 mL) was added to the residue and the
mixture filtered through silica, washing with additional CH2Cl2
(5 mL), and the solvent was removed in vacuo. The conversion
and ratio of regioisiomeric oxazolidinones was determined by
1H NMR spectroscopy; then the residue was purified as
described for each compound below.
3,4-Diphenyloxazolidin-2-one72 4a. Purification by flash
chromatography (CH2Cl2:EtOAc 98:2) gave compound 4a
(0.128 g, 61%) as a white solid. mp 128−130 °C (lit.61 128−
129 °C); υmax(ATR) 3065, 2976, 1744 cm−1; δH(300 MHz,
CONCLUSIONS
Bimetallic aluminum(salen) complex 1 catalyzes the synthesis
of oxazolidinones from epoxides and aromatic or aliphatic
■
793
dx.doi.org/10.1021/cs4001046 | ACS Catal. 2013, 3, 790−797

ACS Catalysis
Research Article
CDCl3) 7.5−7.2 (9H, m), 7.10 (1H, tt J 7.4, 1.3 Hz), 5.43 (1H,
dd J 8.8, 6.0 Hz), 4.80 (1H, t J 8.7 Hz), 4.22 (1H, dd J 8.6, 6.0
Hz); δC(75 MHz, CDCl3) 155.8, 138.6, 137.3, 129.3, 128.9,
128.8, 126.3, 124.7, 121.0, 69.8, 60.9; GCMS TR 15.76 min; m/
z(CI) 240 (MH+, 100), 195 (50).
276 (MH+, 10); Found (ESI) 276.1958, C17H26NO2 (MH+)
requires 276.1964.
3-Phenyl-5-octyloxazolidin-2-one73 5e. Purification by
flash chromatography (CH2Cl2:EtOAc 98:2) gave compound
5d (0.300 g, 65%) as a beige colored solid. mp 70−71 °C (lit.73
69−70 °C); υmax(ATR) 2917, 2850, 1721 cm−1; δH(300 MHz,
CDCl3) 7.6−7.5 (2H, m), 7.5−7.3 (2H, m), 7.14 (1H, tt J 7.3,
1.2 Hz), 4.7−4.6 (1H, m), 4.08 (1H, t J 8.5 Hz), 3.66 (1H, dd J
8.7, 7.2 Hz), 2.0−1.8 (1H, m), 1.8−1.6 (1H, m), 1.6−1.2 (12H,
m), 0.89 (3H, t J 6.9 Hz); δC(75 MHz, CDCl3) 154.9, 138.7,
129.0, 123.9, 118.4, 73.1, 50.7, 35.1, 31.8, 29.4, 29.3, 29.1, 24.6,
22.6, 13.9; m/z(ESI) 573 (2M+Na+, 100), 298 (M+Na+, 95),
276 (MH+, 10).
3,5-Diphenyloxazolidin-2-one72 5a. Purification by flash
chromatography (CH2Cl2:EtOAc 98:2) gave compound 5a
(0.067 g, 32%) as a white solid. mp 76−78 °C (lit.61 78−79
°C); υmax(ATR) 3062, 2975, 1734 cm−1; δH(300 MHz, CDCl3)
7.6−7.3 (9H, m), 7.16 (1H, tt J 7.4, 1.1 Hz), 5.66 (1H, dd, J
8.8, 7.6 Hz), 4.40 (1H, t J 8.8 Hz), 3.98 (1H, dd J 8.9, 7.6 Hz);
δC(75 MHz, CDCl3) 154.7, 138.4, 138.3, 129.1, 129.0, 125.7,
124.2, 118.6, 74.1, 52.8; GCMS TR 16.33 min; m/z(CI) 240
(MH+, 100), 194 (80).
3-Phenyl-5-phenoxymethyloxazolidin-2-one41,43 5f.
Purification by flash chromatography (CH2Cl2:EtOAc 98:2)
gave compound 5f (0.420 g, 94%) as a white solid. mp 139−
140 °C (lit.41,43 138−139 °C); υmax(ATR) 3061, 2960, 1737
cm−1; δH(300 MHz, CDCl3) 7.60 (2H, d J 7.7 Hz), 7.41 (2H, t
J 8.5 Hz), 7.33 (2H, t J 7.3 Hz), 7.18 (1H, t J 7.3 Hz), 7.02
(1H, t J 7.3 Hz), 6.93 (2H, d J 7.6 Hz), 5.1−4.9 (1H, m), 4.3−
4.2 (3H, m), 4.10 (1H, dd J 8.9, 5.9 Hz); δC(75 MHz, CDCl3)
158.3, 154.3, 138.4, 129.7, 129.1, 124.3, 122.0, 118.6, 115.0,
70.5, 68.4, 47.7; m/z(ESI) 561 (2M+Na+, 100), 292 (M+Na+,
100), 270 (MH+, 10).
3-Phenyl-5-methyloxazolidin-2-one32 5b. Purification
by flash chromatography (CH2Cl2:EtOAc 98:2) gave com-
pound 5b (0.074 g, 48%) as a white solid. mp 79−82 °C (lit.32
79−82 °C); υmax(ATR) 3036, 2938, 2877, 1742 cm−1; δH(300
MHz, CDCl3) 7.54 (2H, d J 8.7 Hz), 7.38 (2H, t J 8.1 Hz), 7.14
(1H, t J 7.4 Hz), 4.80 (1H, sex J 6.5 Hz), 4.13 (1H, t J 8.5 Hz),
3.63 (1H, dd J 8.9, 7.1 Hz), 1.54 (3H, d J 6.3 Hz); δC(75 MHz,
CDCl3) 154.9, 138.6, 129.1, 124.1, 118.5, 69.5, 52.1, 20.7; m/
z(ESI) 200 (M+Na+, 100), 178 (MH+, 30).
3-Phenyl-5-chloromethyloxazolidin-2-one41 5c. Purifi-
cation by washing with hexane and Et2O gave compound 5c
(0.221 g, 82%) as a white solid. mp 101−103 °C (lit.41 104−
105 °C); υmax(ATR) 3065, 2962, 1735 cm−1; δH(300 MHz,
CDCl3) 7.6−7.3 (4H, m), 7.17 (1H, tt J 7.4, 1.1 Hz), 4.88 (1H,
dddd, J 8.7, 6.5, 5.6, 4.1 Hz), 4.19 (1H, t, J 8.9 Hz, 1H), 3.98
(1H, dd, J 9.1, 5.7 Hz), 3.75 (1H, dd J 11.6, 6.6 Hz); δC(75
MHz, CDCl3) 153.9, 138.0, 129.1, 124.4, 118.6, 70.9, 48.3,
44.5; GCMS TR 13.87 min; m/z(CI) 214 (M(37Cl)H+, 30);
212 (M(35Cl)H+, 100), 132 (72).
3-Phenyl-4-butyloxazolidin-2-one 4d. Purification by
flash chromatography (CH2Cl2:EtOAc 98:2) gave compound
4d (0.045 g, 12%) as a cream colored solid. mp 122−123 °C;
υmax(ATR) 3064, 2954, 1740 cm−1; δH(300 MHz, CDCl3) 7.6−
7.3 (4H, m), 7.20 (1H, tt J 6.9, 1.7 Hz), 4.52 (1H, t J 8.4 Hz),
4.5−4.3 (1H, m), 4.13 (1H, dd J 8.3, 5.2 Hz), 1.8−1.6 (1H, m),
1.6−1.5 (1H, m), 1.4−1.1 (4H, m), 0.88 (3H, t J 6.7 Hz);
δC(75 MHz, CDCl3) 155.7, 137.1, 128.5, 125.2, 122.1, 66.9,
56.5, 31.7, 26.1, 22.4, 13.7; m/z(ESI) 461 (2M+Na+, 100), 242
(M+Na+, 20), 220 (MH+, 5); Found (ESI) 220.1331,
C13H18NO2 (MH+) requires 220.1338.
3-Phenyl-4-hydroxymethyloxazolidin-2-one57 4g. Pu-
rification by flash chromatography (CH2Cl2:EtOAc 98:2) gave
compound 4g (0.201 g, 62%) as a white solid. mp 109−111 °C
(lit.57 112−115 °C); υmax(ATR) 3271, 1737 cm−1; δH(300
MHz, CDCl3) 7.5−7.2 (4H, m), 7.10 (1H, tt J 7.2, 1.4 Hz),
6.76 (1H, br s), 4.57 (1H, dd J 12.2, 2.9 Hz), 4.00 (1H, dd J
12.2, 6.5 Hz), 3.29 (1H, ddt J 6.7, 4.1, 2.7 Hz), 2.90 (1H, t J 4.4
Hz), 2.71 (1H, dd J 4.9, 2.6 Hz); δC(75 MHz, CDCl3) 153.1,
137.7, 129.1, 123.8, 119.1, 65.8, 49.5, 44.6; m/z(ESI) 409 (2M
+Na+, 100), 216 (M+Na+, 35).
Cis-3-Phenylhexahydrobenzooxazolidin-2-one60,61
4h. Purification by crystallization from Et2O gave compound
4h (0.160 g, 44%) as a white solid. mp 88−89 °C (lit.45 93−94
°C); υmax(ATR) 3065, 2936, 2864, 1734 cm−1; δH(300 MHz,
CDCl3) 7.6−7.4 (2H, m), 7.4−7.3 (2H, m), 7.16 (1H, tt J 7.3,
1.2 Hz), 4.69 (1H, dt J 6.5, 4.4 Hz), 4.28 (1H, q J 6.3 Hz), 2.2−
2.1 (1H, m), 2.1−2.0 (1H, m), 1.9−1.7 (1H, m), 1.7−1.5 (4H,
m), 1.4−1.2 (1H, m); δC(75 MHz, CDCl3) 155.8, 137.5, 129.1,
124.7, 121.3, 73.2, 56.1, 26.7, 26.1, 19.9, 19.1; m/z(ESI) 457
(2M+Na+, 100), 240 (M+Na+, 32), 218 (MH+, 5). X-ray data is
given in the Supporting Information.
3-(4-Nitrophenyl)-4-phenyloxazolidin-2-one 4i. Purifi-
cation by flash chromatography (CH2Cl2:EtOAc 98:2) gave
compound 4i (0.026 g, 14%) as a yellow syrup. υmax(ATR)
3033, 2883, 1773 cm−1; δH(300 MHz, CDCl3) 8.01 (2H, d J 9.0
Hz), 7.52 (2H, d J 9.1 Hz), 7.4−7.2 (5H, m), 5.35 (1H, dd J
8.7, 5.4 Hz), 4.74 (1H, t J 8.6 Hz), 4.15 (1H, dd J 8.7, 5.5 Hz);
δC(75 MHz, CDCl3) 155.0, 143.0, 137.6, 129.8, 129.4, 125.9,
125.6, 124.6, 119.6, 69.9, 60.5; GCMS TR 18.72 min; m/z(EI)
284 (M+, 100), 225 (25), 179 (20), 149 (40), 91 (30); Found
(ESI) 285.0883, C15H13N2O4 (MH+) requires 285.0875.
3-(4-Nitrophenyl)-5-phenyloxazolidin-2-one 5i. Purifi-
cation by flash chromatography (CH2Cl2:EtOAc 98:2) gave
compound 5i (0.016 g, 9%) as a yellow solid. mp 151−153 °C;
υmax(ATR) 3050, 2917, 1743 cm−1; δH(300 MHz, CDCl3) 8.25
(2H, d J 9.3 Hz), 7.74 (2H, d J 9.3 Hz), 7.5−7.4 (5H, m), 5.72
(1H, dd J 8.7, 7.5 Hz), 4.48 (1H, t J 8.9 Hz), 4.04 (1H, dd J 9.1,
7.5 Hz); δC(75 MHz, CDCl3) 154.0, 143.8, 137.4, 129.5, 129.2,
125.8, 125.6, 124.9, 117.7, 74.3, 52.4; m/z(ESI) 307 (M+Na+,
3-Phenyl-5-butyloxazolidin-2-one19 5d. Purification by
flash chromatography (CH2Cl2:EtOAc 98:2) gave compound
5d (0.227 g, 62%) as a cream colored solid. mp 65−66 °C;
υmax(ATR) 2958, 2927, 2872, 1737 cm−1; δH(300 MHz,
CDCl3) 7.6−7.5 (2H, m), 7.5−7.3 (2H, m), 7.15 (1H, tt J
7.4, 1.2 Hz), 4.7−4.6 (1H, m), 4.10 (1H, t J 8.5 Hz), 3.68 (1H,
dd J 8.8, 7.2 Hz), 2.0−1.8 (1H, m), 1.8−1.6 (1H, m), 1.6−1.3
(4H, m), 0.96 (3H, t J 7.2 Hz); δC(75 MHz, CDCl3) 154.9,
138.7, 129.0, 124.0, 118.4, 73.1, 50.7, 34.8, 26.7, 22.4, 13.8; m/
z(ESI) 461 (2M+Na+, 100), 242 (M+Na+, 20), 220 (MH+, 5).
3-Phenyl-4-octyloxazolidin-2-one 4e. Purification by
flash chromatography (CH2Cl2:EtOAc 98:2) gave compound
4e (0.06 g, 13%) as a yellow oil; υmax(ATR) 3180, 3056, 1706
cm−1; δH(300 MHz, CDCl3) 7.6−7.3 (3H, m), 7.3−7.1 (2H,
m), 4.55 (1H, t J 8.4 Hz), 4.5−4.3 (1H, m), 4.15 (1H, dd J =
8.3, 5.3 Hz), 1.8−1.7 (1H, m), 1.7−1.5 (1H, m), 1.4−1.2 (12H,
m), 0.88 (3H, t J 6.2 Hz); δC(75 MHz, CDCl3) 155.7, 137.1,
129.2, 125.2, 122.1, 66.9, 56.5, 32.0, 31.7, 29.3, 29.2, 29.0, 23.9,
22.5, 13.9; m/z(ESI) 573 (2M+Na+, 100), 298 (M+Na+, 95),
794
dx.doi.org/10.1021/cs4001046 | ACS Catal. 2013, 3, 790−797

ACS Catalysis
Research Article
100), 285 (MH+, 50), 259 (70); Found (ESI) 285.0887,
C15H13N2O4 (MH+) requires 285.0875.
3-(4-Chlorophenyl)-4-phenyloxazolidin-2-one76,77
4m. Purification by flash chromatography (CH2Cl2:EtOAc
98:2) gave compound 4m (0.058 g, 28%) as a white solid. mp
126−128 °C (lit.76 131 °C); υmax(ATR) 3030, 2967, 2908,
1736 cm−1; δH(300 MHz, CDCl3) 7.4−7.1 (9H, m), 5.30 (1H,
dd J 8.7, 6.1 Hz), 4.73 (1H, t J 8.7 Hz), 4.15 (1H, dd, J 8.5, 6.0
Hz); δC(100 MHz, CDCl3) 155.7, 137.7, 135.5, 129.8, 129.4,
129.0, 128.9, 126.1, 121.8, 69.7, 60.5; m/z(ESI) 298 (M-
(37Cl)+Na+, 30), 296 (M(35Cl)+Na+, 100).
3-(4-Chlorophenyl)-5-phenyloxazolidin-2-one 5m. Pu-
rification by flash chromatography (CH2Cl2:EtOAc 98:2) gave
compound 5m (0.017 g, 8%) as a white solid. mp 113−117 °C;
υmax(ATR) 2922, 1750 cm−1; δH(300 MHz, CDCl3) 7.6−7.3
(9H, m), 5.67 (1H, t J 8.1 Hz), 4.38 (1H, t J 8.8 Hz), 3.95 (1H,
dd, J 9.0, 7.5 Hz); δC(100 MHz, CDCl3) 147.3, 137.8, 136.7,
129.7, 129.2, 129.1, 129.0, 125.6, 119.4, 74.0, 52.6; m/z(ESI)
298 (M(37Cl)+Na+, 30), 296 (M(35Cl)+Na+, 100); Found
(ESI) 274.0620, C15H13NO235Cl (MH+) requires 274.0635.
3-(4-Bromophenyl)-4-phenyloxazolidin-2-one 4n. Pu-
rification by flash chromatography (CH2Cl2:EtOAc 98:2) gave
compound 4n (0.075 g, 27%) as a yellow solid. mp 134−137
°C; υmax(ATR) 3010, 2922, 1739 cm−1; δH(300 MHz, CDCl3)
7.4−7.2 (9H, m), 5.33 (1H, dd J 8.7, 6.0 Hz), 4.75 (1H, t J 8.7
Hz), 4.17 (1H, dd, J 8.6, 6.0 Hz); δC(75 MHz, CDCl3) 155.5,
138.1, 136.5, 131.9, 129.5, 129.0, 126.2, 122.4, 117.7, 69.8, 60.8;
GCMS TR 17.47 min; m/z(CI) 319 (M(81Br)H+, 100), 317
(M(79Br)H+, 95); Found (ESI) 318.0112, C15H13NO279Br
(MH+) requires 318.0130.
3-(4-Methoxyphenyl)-4-phenyloxazolidin-2-one74 4j.
Purification by flash chromatography (CH2Cl2:EtOAc 98:2)
gave compound 4j (0.089 g, 38%) as a cream colored solid. mp
131−133 °C (lit.57 137−138 °C); υmax(ATR) 2923, 1734 cm−1;
δH(300 MHz, CDCl3) 7.3−7.1 (7H, m), 6.68 (2H, d J 9.1 Hz),
5.22 (1H, dd J 8.8, 6.4 Hz), 4.66 (1H, t J 8.7 Hz), 4.09 (1H, dd
J 8.6, 6.4 Hz), 3.61 (3H, s); δC(75 MHz, CDCl3) 157.0, 156.2,
138.5, 130.2, 129.2, 128.7, 126.5, 123.3, 114.3, 69.6, 61.4, 55.3;
GCMS TR 18.15 min; m/z(EI) 269 (M+, 100), 224 (25).
3-(4-Methoxyphenyl)-5-phenyloxazolidin-2-one75 5j.
Purification by flash chromatography (CH2Cl2:EtOAc 98:2)
gave compound 5j (0.040 g, 17%) as a cream colored solid. mp
105−107 °C; υmax(ATR) 2925, 2853, 1738 cm−1; δH(300 MHz,
CDCl3) 7.5−7.3 (7H, m), 6.91 (2H, d J 9.1 Hz), 5.62 (1H, dd J
8.7, 7.5 Hz), 4.34 (1H, t J 8.8 Hz), 3.94 (1H, dd J 8.8, 7.5 Hz),
3.80 (3H, s); δC(75 MHz, CDCl3) 156.8, 155.0, 138.5, 131.6,
129.0, 125.7, 120.6, 114.5, 74.0, 55.6, 53.3; GCMS TR 17.05
min; m/z(EI) 269 (M+, 100).
3-(4-Methylphenyl)-4-phenyloxazolidin-2-one39 4k.
Purification by flash chromatography (CH2Cl2:EtOAc 98:2)
gave compound 4k (0.089 g, 38%) as a cream colored solid. mp
105−107 °C (lit.39 107−109 °C); υmax(ATR) 3036, 2971, 1741
cm−1; δH(300 MHz, CDCl3) 7.4−7.2 (7H, m), 7.08 (2H, d J
8.3 Hz), 5.39 (1H, dd J 8.9, 6.2 Hz), 4.77 (1H, t J 8.7 Hz), 4.19
(1H, dd J 8.5, 6.0 Hz), 2.27 (3H, s); δC(75 MHz, CDCl3)
155.9, 138.6, 134.7, 134.4, 129.4, 129.2, 128.6, 126.2, 121.2,
69.7, 60.9, 20.6; GCMS TR 16.21 min; m/z(EI) 253 (M+, 100).
3-(4-Methylphenyl)-5-phenyloxazolidin-2-one39 5k.
Purification by flash chromatography (CH2Cl2:EtOAc 98:2)
gave compound 5k (0.015 g, 7%) as a cream colored solid. mp
98−100 °C (lit.39 95−97 °C); υmax(ATR) 2963, 1734 cm−1;
δH(300 MHz, CDCl3) 7.5−7.4 (7H, m), 7.19 (2H, d J 8.1 Hz),
5.63 (1H, t J 8.1 Hz), 4.36 (1H, t J 8.8 Hz), 3.95 (1H, dd, J 9.0,
7.6 Hz), 2.34 (3H, s); δC(100 MHz, CDCl3) 154.8, 138.2,
135.6, 133.8, 129.6, 129.0, 128.9, 125.6, 118.4, 74.0, 52.8, 20.7;
GCMS TR 16.93 min; m/z(EI) 253 (M+, 35), 208 (100), 118
(65), 91 (35).
3-(4-Fluorophenyl)-4-phenyloxazolidin-2-one 4l. Puri-
fication by flash chromatography (CH2Cl2:EtOAc 98:2) gave
compound 4l (0.091 g, 40%) as a cream colored solid. mp 94−
97 °C; υmax(ATR) 2976, 1737 cm−1; δH(300 MHz, CDCl3)
7.4−7.2 (7H, m),), 6.94 (2H, dd J 9.2, 8.3 Hz), 5.34 (1H, dd J
8.8, 6.3 Hz), 4.78 (1H, t J 8.7 Hz), 4.21 (1H, dd J 8.7, 6.3 Hz);
δC(75 MHz, CDCl3) 159.9 (d J 243 Hz), 156.0, 138.2, 130.3,
129.5, 126.4, 123.1 (d J 8 Hz), 115.8 (d J 22 Hz), 69.8, 61.3;
δF(CDCl3) −117.2 (s); GCMS TR 15.48 min; m/z(EI) 257
(M+, 100); Found (ESI) 258.0908, C15H13NO2F (MH+)
requires 258.0930.
3-(4-Bromophenyl)-5-phenyloxazolidin-2-one75 5n.
Purification by flash chromatography (CH2Cl2:EtOAc 98:2)
gave compound 5n (0.030 g, 11%) as a yellow solid. mp 100−
103 °C; υmax(ATR) 2963, 1745 cm−1; δH(400 MHz, CDCl3)
7.7−7.4 (9H, m), 5.66 (1H, t J 7.9 Hz), 4.37 (1H, t J 8.8 Hz),
3.95 (1H, dd, J 8.8, 7.5 Hz); δC(100 MHz, CDCl3) 154.4,
138.0, 137.5, 132.1, 129.2, 129.1, 125.6, 119.9, 117.1, 74.1, 52.6;
GCMS TR 18.46 min; m/z(CI) 319 (M(81Br)H+, 70), 317
(M(79Br)H+, 70), 274 (100), 272 (75).
3-(4-Nitrophenyl)-5-chloromethyloxazolidin-2-
one41,78 5o. Purification by washing with hexane and Et2O
gave compound 5o (0.021 g, 6%) as a yellow solid. mp 157−
160 °C (lit.74 155−157 °C); υmax(ATR) 3138, 1756 cm−1;
δH(300 MHz, CDCl3) 8.28 (2H, d J 9.3 Hz), 7.76 (2H, d J 9.3
Hz), 5.1−4.9 (1H, m), 4.26 (1H, t J 9.1 Hz), 4.05 (1H, dd J 9.2,
5.7 Hz), 3.9−3.8 (2H, m); δC(75 MHz, CDCl3) 153.2, 143.9,
143.4, 125.0, 117.7, 71.1, 48.0, 44.4; GCMS TR 17.29 min; m/
z(EI) 258 (M(37Cl)+, 25), 256 (M(35Cl)+, 75), 177 (100).
3-(4-Methoxyphenyl)-5-chloromethyloxazolidin-2-
one79 5p. Purification by washing with hexane and Et2O gave
compound 5p (0.250 g, 80%) as a white solid. mp 105−107 °C
(lit.75 105−106 °C); υmax(ATR) 3020, 2970, 1731 cm−1;
δH(300 MHz, CDCl3) 7.41 (2H, d J 9.1 Hz), 6.89 (2H, d J 9.1
Hz), 4.82 (1H, dq J 8.8, 5.2 Hz), 4.09 (1H, t J 9.0 Hz), 3.87
(1H, dd J 9.1, 5.7 Hz), 3.78 (3H, s), 3.74 (2H, d J 5.1); δC(75
MHz, CDCl3) 156.7, 154.1, 131.1, 120.6, 114.4, 70.9, 55.5,
48.7, 44.7; GCMS TR 15.58 min; m/z(CI) 244 (M(37Cl)H+,
25), 242 (M(35Cl)H+, 75), 161 (100), 120 (25).
3-(4-Fluorophenyl)-5-phenyloxazolidin-2-one 5l. Puri-
fication by flash chromatography (CH2Cl2:EtOAc 98:2) gave
compound 5l (0.044 g, 22%) as a cream colored solid. mp 78−
81 °C; υmax(ATR) 3026, 2976, 1726 cm−1; δH(300 MHz,
CDCl3) 7.53 (2H, dd J 9.1, 4.6 Hz), 7.5−7.4 (5H, m), 7.09
(2H, dd J 9.3, 8.1 Hz), 5.66 (1H, t J 8.2 Hz), 4.37 (1H, t J 8.8
Hz), 3.96 (1H, dd J 8.9, 7.6 Hz); δC(100 MHz, CDCl3) 159.3
(d J 243 Hz), 154.8, 137.9, 134.2, 129.2, 129.1, 125.6, 120.1 (d J
7 Hz), 115.8 (d J 23 Hz), 74.0, 53.0; δF(CDCl3) −118.2 (s);
GCMS TR 16.26 min; m/z(CI) 258 (MH+, 100), 213 (60);
Found (ESI) 258.0915, C15H13NO2F (MH+) requires
258.0930.
3-(4-Methylphenyl)-5-chloromethyloxazolidin-2-one
5q. Purification by washing with hexane and Et2O gave
compound 5q (0.129 g, 45%) as a cream colored solid. mp
104−107 °C; υmax(ATR) 3033, 2963, 2920, 1734 cm−1; δH(300
MHz, CDCl3) 7.43 (2H, d J 8.5 Hz), 7.20 (2H, d J 8.1 Hz),
4.86 (1H, dddd, J 8.7, 6.6, 5.7, 4.2 Hz), 4.16 (1H, t J 9.0 Hz),
3.95 (1H, dd, J 9.2, 5.7 Hz), 3.80 (1H, dd, J 11.6, 4.2 Hz), 3.74
795
dx.doi.org/10.1021/cs4001046 | ACS Catal. 2013, 3, 790−797

ACS Catalysis
Research Article
Notes
(1H, dd, J 11.5, 6.6 Hz), 2.34 (3H, s); δC(75 MHz, CDCl3)
154.0, 135.6, 134.3, 129.7, 118.8, 71.0, 48.6, 44.5, 20.7; GCMS
TR 14.59 min; m/z(CI) 228 (M(37Cl)H+, 7), 226 (M(35Cl)H+,
20), 146 (100), 118 (45), 91 (35); Found (ESI) 226.0627,
C11H13NO235Cl (MH+) requires 226.0635.
The authors declare no competing financial interest.
ABBREVIATIONS
■
Salen, (1R,2R)-N,N′-bis(3,5-di-tert-butyl-salicylidene)cyclo-
3-(4-Fluorophenyl)-5-chloromethyloxazolidin-2-one
5r. Purification by washing with hexane and Et2O gave
compound 5r (0.128 g, 44%) as a white solid. mp 101−104
°C; υmax(ATR) 2946, 1737 cm−1; δH(300 MHz, CDCl3) 7.48
(2H, dd J 9.2, 4.6 Hz), 7.05 (2H, dd J 9.2, 8.2 Hz), 5.0−4.8
(1H, m), 4.13 (1H, t J 9.0 Hz), 3.91 (1H, dd J 9.1, 5.7 Hz), 3.76
(2H, d J 5.0 Hz); δC(75 MHz, CDCl3) 160.9, 154.0, 133.8 (d J
5.2 Hz), 120.2, 115.7 (d J 22.3 Hz), 70.4, 48.1, 44.7; δF(CDCl3)
−117.4 (s); GCMS TR 13.90 min; m/z(CI) 232 (M(37Cl)H+,
7), 230 (M(35Cl)H+, 20), 150 (100), 122 (75), 95 (35); Found
(ESI) 230.0376, C10H10NO2F35Cl (MH+) requires 230.0384.
3-(4-Chlorophenyl)-5-chloromethyloxazolidin-2-
one41 5s. Purification by washing with hexane and Et2O gave
compound 5s (0.216 g, 40%) as a white solid. mp 130−133 °C
(lit.41 131−133 °C); υmax(ATR) 2938, 1738 cm−1; δH(300
MHz, CDCl3) 7.49 (2H, d J 9.0 Hz), 7.33 (2H, d J 9.0 Hz),
5.0−4.8 (1H, m), 4.14 (1H, t J 9.0 Hz), 3.93 (1H, dd J 9.1, 5.6
Hz), 3.8−3.7 (2H, m); δC(75 MHz, CDCl3) 153.7, 136.5,
129.6, 129.0, 119.6, 71.0, 48.1, 44.6; GCMS TR 15.34 min; m/
z(CI) 250 (M(2× 37Cl)H+, 6), 248 (M(35Cl+37Cl)H+, 50), 246
(M(2× 35Cl)H+, 80), 166 (100), 130 (50), 63 (30).
3-(4-Bromophenyl)-5-chloromethyloxazolidin-2-
one80 5t. Purification by washing with hexane and Et2O gave
compound 5t (0.147 g, 40%) as a white solid. mp 125−128 °C
(lit.76 125−127 °C); υmax(ATR) 2961, 1733 cm−1; δH(300
MHz, CDCl3) 7.48 (2H, d J 9.1 Hz), 7.42 (2H, d J 9.1 Hz),
5.0−4.8 (1H, m), 4.13 (1H, t J 9.0 Hz), 3.91 (1H, dd J 9.1, 5.7
Hz), 3.8−3.7 (2H, m); δC(75 MHz, CDCl3) 153.6, 137.0,
132.0, 119.9, 117.2, 70.9, 48.0, 44.5; GCMS TR 16.27 min; m/
z(EI) 293 (M(81Br+37Cl)H+, 10), 291 (M(81Br+35Cl or 79Br
+37Cl)H+, 100), 289 (M(79Br+35Cl)H+, 80), 210 (25), 130
(25).
hexane-1,2-diamine
REFERENCES
■
(1) Taylor, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2003, 125,
11204−11205.
(2) Raheem, I. T.; Goodman, S. N.; Jacobsen, E. N. J. Am. Chem. Soc.
2004, 126, 706−707.
(3) Balskus, E. P.; Jacobsen, E. N. J. Am. Chem. Soc. 2006, 128, 6810−
6812.
(4) Taylor, M. S.; Zaltan, D. N.; Lerchner, A. M.; Jacobsen, E. N. J.
Am. Chem. Soc. 2005, 127, 1313−1317.
(5) Sammis, G. M.; Danjo, H.; Jacobsen, E. N. J. Am. Chem. Soc.
2004, 126, 9928−9929.
(6) Vanderwal, C. D.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126,
14724−14725.
(7) Gandelman, M.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2005, 44,
2393−2397.
(8) Yue, T.; Wang, M.-X.; Wang, D.-X.; Zhu, J. Angew. Chem., Int. Ed.
2008, 47, 9454−9457.
(9) North, M.; Williamson, C. Tetrahedron Lett. 2009, 50, 3249−
3252.
(10) North, M.; Villuendas, P.; Williamson, C. Tetrahedron 2010, 66,
1915−1924.
(11) Melen
́
dez, J.; North, M.; Pasquale, R. Eur. J. Inorg. Chem. 2007,
3323−3326.
(12) North, M.; Pasquale, R. Angew. Chem., Int. Ed. 2009, 48, 2946−
2948.
(13) Clegg, W.; Harrington, R. W.; North, M.; Pasquale, R. Chem.
Eur. J. 2010, 16, 6828−6843.
(14) Metcalfe, I. S.; North, M.; Pasquale, R.; Thursfield, A. Energy
Environ. Sci. 2010, 3, 212−215.
(15) North, M.; Young, C. ChemSusChem 2011, 4, 1685−1693.
(16) North, M.; Villuendas, P. Synlett 2010, 623−627.
(17) Clegg, W.; Harrington, R. W.; North, M.; Villuendas, P. J. Org.
Chem. 2010, 75, 6201−6207.
3-Cyclohexyl-5-chloromethyloxazolidin-2-one 5u. Pu-
rification by washing with hexane and Et2O gave compound 5u
(0.040 g, 21%) as a white solid. mp 94−97 °C; υmax(ATR)
2930, 2856, 1729 cm−1; δH(300 MHz, CDCl3) 4.8−4.6 (1H,
m), 3.8−3.6 (4H, m), 3.42 (1H, dd J 9.0, 5.6 Hz), 1.9−1.7 (4H,
m), 1.7−1.6 (1H, m), 1.5−1.3 (4H, m), 1.2−1.0 (1H, m);
δC(75 MHz, CDCl3) 156.3, 71.6, 52.9, 44.7, 44.0, 30.4, 30.3,
25.4; m/z(ESI) 220 (M(37Cl)H+, 35), 218 (M(35Cl)H+, 35);
Found (ESI) 218.0929, C10H17NO235Cl (MH+) requires
218.0948.
(18) Demaray, J. A.; Thuener, J. E.; Dawson, M. N.; Sucheck, S. J.
Bioorg. Med. Chem. Lett. 2008, 18, 4868−4871.
(19) Brnardic, E. J.; Fraley, M. E.; Garbaccio, R. M.; Layton, M. E.;
Sanders, J. M.; Culberson, C.; Jacobson, M. A.; Magliaro, B. C.;
Hutson, P. H.; O’Brien, J. A.; Huszar, S. L.; Uslaner, J. M.; Fillgrove, K.
L.; Tang, C.; Kuo, Y.; Sur, S. M.; Hartman, G. D. Bioorg. Med. Chem.
Lett. 2010, 20, 3129−3133.
(20) Ohno, T.; Ogawa, K.; Yano, S.; Fukushima, M.; Suzuki, N.;
Asao, T. Arch. Pharm. Life Sci. 2005, 338, 147−158.
(21) Barbachyn, M. R.; Toops, D. S.; Grega, K. C.; Hendges, S. K.;
Ford, C. W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.;
Yagi, B. H.; Buysse, J. M.; Demyan, W. F.; Kilburn, J. O.; Glickman, S.
E. Bioorg. Med. Chem. Lett. 1996, 6, 1009−1014.
(22) Gregory, W. A.; Brittelli, D. R.; Wang, C.-L. J.; Wuonola, M. A.;
McRipley, R. J.; Eustice, D. C.; Eberly, V. S.; Bartholomew, P. T.; Slee,
A. M.; Forbes, M. J. Med. Chem. 1989, 32, 1673−1681.
(23) Park, C.-H.; Brittelli, D. R.; Wang, C.-L. J.; Marsh, F. D.;
Gregory, W. A.; Wuonola, M. A.; McRipley, R. J.; Eberly, V. S.; Slee, A.
M.; Forbes, M. J. Med. Chem. 1992, 35, 1156−1165.
(24) Wang, C.-L.; Gregory, W. A.; Wuonola, M. A. Tetrahedron 1989,
45, 1323−1326.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H, 13C, and 19F NMR spectra of oxazolidinones 4/5a−u. X-ray
data for compound 4h. This material is available free of charge
via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
(25) Fugitt, R. B.; Martinelli, L. C. J. Pharm. Sci. 1973, 62, 1013−
1016.
(26) Zhang, X.; Chen, W.; Li, C.; Wu, X. J. Chem. Res. 2009, 739−
740.
(27) Roush, W. R.; James, R. A. Aust. J. Chem. 2002, 55, 141−146.
(28) Tian, D.; Liu, B.; Gan, Q.; Li, H.; Darensbourg, D. J. ACS Catal.
2012, 2, 2029−2035.
*E-mail: Michael.north@ncl.ac.uk.
Author Contributions
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
796
dx.doi.org/10.1021/cs4001046 | ACS Catal. 2013, 3, 790−797

ACS Catalysis
Research Article
(29) Darensbourg, D. J.; Billodeaux, D. R. Inorg. Chem. 2005, 44,
1433−1442.
(65) Cottone, A., III; Scott, M. J. Organometallics 2000, 19, 5254−
5256.
(66) Cottone, A., III; Scott, M. J. Organometallics 2002, 21, 3610−
3627.
(30) Darensbourg, D. J.; Ganguly, P.; Choi, W. Inorg. Chem. 2006,
45, 3831−3833.
(67) Scott, J.; Gambarotta, S.; Korobkov, I.; Knijnenburg, Q.; de
Bruin, B.; Budzelaar, P. H. M. J. Am. Chem. Soc. 2005, 127, 17204−
17206.
(68) Zhang, D. Eur. J. Inorg. Chem. 2007, 3077−3082.
(69) Vidyaratne, I.; Scott, J.; Gambarotta, S.; Duchateau, R.
Organometallics 2007, 26, 3201−3211.
(70) Jabri, A.; Mason, C. B.; Sim, Y.; Gambarotta, S.; Burchell, T. J.;
Duchateau, R. Angew. Chem., Int. Ed. 2008, 47, 9717−9721.
(71) Del Grosso, A.; Pritchard, R. G.; Muryn, C. A.; Ingleson, M. J.
Organometallics 2010, 29, 241−249.
(72) Irwin, W. J.; Wheeler, D. L. J. Chem. Soc. A 1971, 3166−3167.
(73) Dyen, M. E.; Swern, D. J. Am. Oil Chem. Soc. 1968, 45, 325−
330.
(31) Darensbourg, D. J.; Ganguly, P.; Billodeaux, D. R. Macro-
molecules 2005, 38, 5406−5410.
(32) Speranza, G. P.; Peppel, W. J. J. Org. Chem. 1958, 23, 1922−
1924.
(33) Qian, C.; Zhu, D. Synlett 1994, 129−130.
(34) Wu, H.-Y.; Ding, J.-C.; Liu, Y.-K. J. Indian Chem. Soc. 2003, 80,
36−37.
(35) Barros, M. T.; Phillips, A. M. F. Tetrahedron: Asymmetry 2010,
21, 2746−2752.
(36) Aroua, L.; Baklouti, A. Synth. Commun. 2007, 37, 1935−1942.
(37) Herweh, J. E.; Kauffman, W. J. Tetrahedron Lett. 1971, 12, 809−
812.
(38) Herweh, J. E. J. Heterocycl. Chem. 1968, 5, 687−690.
(39) Herweh, J. E.; Foglia, T. A.; Swern, D. J. Org. Chem. 1968, 33,
4029−4033.
(40) Siegel, H.; Wittmann, H. Monatsh. Chem. 1982, 113, 1005−
1017.
(74) Mallesham, B.; Rajesh, B. M.; Reddy, P. R.; Srinivas, R. D.;
Trehan, S. Org. Lett. 2003, 5, 963−965.
(75) Takiguchi, T.; Iwaki, T.; Togano, T.; Kosaka, Y.; Nakamura, S.
U.S. Patent US5624600A1, 1997.
(76) Jones, J. I. J. Chem. Soc. 1957, 2735−2743.
(77) Irwin, W. J.; Wheeler, D. L. J. Chem. Soc. C 1971, 3166−3167.
(78) Lukasiewicz, Z.; Urbanski, T. Org. Prep. Proc. Int. 1971, 3, 1−4.
(79) Gates, K. S.; Silverman, R. B. J. Am. Chem. Soc. 1989, 111,
8891−8895.
(80) Zhang, X.; Li, C.; Chen, W.; Wu, X. Lett. Org. Chem. 2010, 7,
226−228.
(41) Zhang, X.; Chen, W.; Zhao, C.; Li, C.; Wu, X.; Chen, W. Z.
Synth. Commun. 2010, 40, 3654−3659.
(42) Baba, A.; Fujiwara, M.; Matsuda, H. Tetrahedron Lett. 1986, 27,
77−80.
(43) Fujiwara, M.; Baba, A.; Matsuda, H. J. Heterocycl. Chem. 1988,
25, 1351−1357.
(44) Fujiwara, M.; Baba, A.; Matsuda, H. Bull. Chem. Soc. Jpn. 1990,
63, 1069−1073.
(45) Shibata, I.; Baba, A.; Iwasaki, H.; Matsuda, H. J. Org. Chem.
1986, 51, 2177−2184.
(46) Fujiwara, M.; Baba, A.; Tomohisa, Y.; Matsuda, H. Chem. Lett.
1986, 1963−1966.
(47) Baba, A.; Seki, K.; Matsuda, H. J. Heterocycl. Chem. 1990, 27,
1925−1930.
(48) Yano, K.; Amishiro, N.; Baba, A.; Matsuda, H. Bull. Chem. Soc.
Jpn. 1991, 64, 2661−2667.
(49) Javni, I.; Guo, A.; Petrovic, Z. S. J. Am. Oil Chem. Soc. 2002, 80,
595−600.
(50) Bartoli, G.; Bosco, M.; Carlone, A.; Locatelli, M.; Melchiorre, P.;
Sambri, L. Org. Lett. 2005, 7, 1983−1985.
(51) North, M.; Pizzato, F.; Villuendas, P. ChemSusChem 2009, 2,
862−865.
(52) Clegg, W.; Harrington, R. W.; North, M.; Pizzato, F.; Villuendas,
P. Tetrahedron: Asymmetry 2010, 21, 1262−1271.
(53) Morcillo, M.; North, M.; Villuendas, P. Synthesis 2011, 1918−
1925.
(54) Wu, G.-P.; Wei, S.-W.; Lu, X.-B.; Ren, W.-M.; Darensbourg, D.
J. Macromolecules 2010, 43, 9202−9204.
(55) Wang, H.; Kozekov, I. D.; Harris, T. M.; Rizzo, C. J. J. Am.
Chem. Soc. 2003, 125, 5687−5700.
(56) Roush, W. R.; Adam, M. A. J. Org. Chem. 1985, 50, 3752−3757.
(57) Farrissey, W. J., Jr.; Nashu, A. M. J. Heterocycl. Chem. 1970, 7,
331−333.
(58) Carlsen, P. H. J.; Gautun, H. S. H. Tetrahedron: Asymmetry
1995, 6, 1667−1674.
́
(59) Routier, J.; Calancea, M.; David, M.; Vallee, Y.; Denis, J.-N. Eur.
J. Org. Chem. 2008, 5687−5691.
(60) Nicolaou, K. C.; Zhong, Y.-L.; Baran, P. S. Angew. Chem., Int. Ed.
2000, 39, 625−628.
(61) Nicolaou, K. C.; Baran, P. S.; Zhong, Y.-L.; Barluenga, S.; Hunt,
K. W.; Kranich, R.; Vega, J. A. J. Am. Chem. Soc. 2002, 124, 2233−
2244.
(62) Baba, A.; Seki, K.; Matsuda, H. J. Org. Chem. 1991, 56, 2684−
2688.
(63) Beattie, C.; North, M.; Villuendas, P.; Young, C. J. Org. Chem.
2013, 78, 419−426.
(64) Healy, M. D.; Ziller, J. W.; Barron, A. R. Organometallics 1992,
11, 3041−3049.
797
dx.doi.org/10.1021/cs4001046 | ACS Catal. 2013, 3, 790−797