Complementary reactions of allylic carbamates using palladium(II): Formation of oxazolidinones or allylic amides from a common precursor

Article abstract of DOI:10.1055/s-0028-1083282

The use of palladium to effect two different reactions on a common starting material is presented. With a copper oxidant, an aminohalogenation is achieved to produce oxazolidinones. When the copper is absent, a [3,3]-sigmatropic rearrangement takes place

Full text of DOI:10.1055/s-0028-1083282

148
PAPER
Complementary Reactions of Allylic Carbamates Using Palladium(II):
Formation of Oxazolidinones or Allylic Amides from a Common Precursor
Formationof
O
t
xazol
e
v
A
llylic
A
mid
e
es from
a
Cn
ommonPrecursorD. R. Christie,*a Adam D. Warrington,a Christopher J. Lunnissb
a
Departmentt of Chemistry, Loughborough University, Loughborough, LE11 3RF, UK
Fax +44(1509)223925; E-mail: s.d.christie@lboro.ac.uk
b
GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG1 2NY, UK
Received 24 October 2008
O
O
O
Abstract: The use of palladium to effect two different reactions on
a common starting material is presented. With a copper oxidant, an
aminohalogenation is achieved to produce oxazolidinones. When
the copper is absent, a [3,3]-sigmatropic rearrangement takes place
to produce allylic amides.
O
O
NHR2
[Pd]
[Os]
O
NR2
NR2
R1
R1
R1
OR1
X
Key words: palladium, rearrangement, halogenation, amines,
amides
Scheme 1 Metal-mediated activation of a tethered alkene
with palladium by Stahl2 and Sorenson.3 We have initially
investigated aminohalogenation reactions of tethered sys-
tems. Lu5 and Chemler6 have reported on this type of re-
action, however, both groups utilized tosyl protecting
groups on the nitrogen. More recently, Michael has illus-
trated a related reaction employing a tridentate palladium
catalyst.7
The progress of research into organometallic reagents in
the last 40 years is perhaps epitomized by looking at the
entries for ‘palladium’ in Synthesis since its inception in
1969. In the 1970s there are a few mentions of palladium
– notable mostly as palladium(II) reactions. However, the
frequency of articles using the transition metal increases
in the 1980s and 1990s, and most dramatically in the late
1990s and 2000s, with a bias towards palladium(0)-medi-
ated processes. There is obviously still an increasing use
of transition-metal mediated reactions and, of these, palla-
dium is among the most common. As such, we wish to
present our results on two palladium-mediated reactions.
Of particular note is the versatility of the catalyst to effect
different reactions on the same substrate through judi-
cious choice of reaction conditions.
We were keen to avoid the use of tosylate as it can present
difficulties in removal, and we were also interested in the
possibility of combining several reactions into one pot.
We therefore chose the trichloroacetyl group, which ap-
peared to fit the profile of providing the necessary protec-
tion and reactivity for the nitrogen, whilst also being
relatively straightforward to remove by several different
methods. We started by preparing the requisite carbam-
ates simply by reaction of the appropriate allylic alcohol
with trichloroacetyl isocyanate. Subsequent reaction of
this with palladium acetate, in the presence of a copper
salt and lithium chloride, gave the cyclised products in
good yields and excellent diastereoselectivity. The copper
salt is required to oxidize the palladium(0) back to palla-
dium(II). We were delighted to find that during the work-
up, the trichloroacetyl group was suitably labile, and all
the products were isolated as the free oxazolidinones
(Scheme 2).
We were initially looking at a means through which to
activate alkenes towards functionalisation with hetero-
atoms, principally oxygen and nitrogen. For the most part,
dihydroxylation and aminohydroxylation reactions have
been the domain of osmium, but we recently highlighted
that there is a complementary role played by palladium in
related reactions.1 Most notable on this front is the recent
work by Stahl2 and Sorensen3 who have shown that palla-
dium can produce highly functionalised aminohydroxyla-
tion products from alkenes. We were keen to look at the
use of tethered systems, which would provide a means to
control regiochemistry and perhaps also stereochemistry.
To this end, we started with systems such as those shown
in Scheme 1. Here, we were concerned with the palladi-
um(II)-mediated reaction of carbamates with pendant ole-
fins to produce the corresponding heterocycles. This type
of reaction has been achieved by Donohoe4 with osmium
in an aminohydroxylation reaction and, more recently,
O
O
O
Pd(OAc)2 (5 mol%)
CuCl2 (4 equiv)
LiCl (2 equiv)
O
O
N
H
CCl3
NH
R
THF, 25 °C
R
Cl
2
1
Scheme 2 Palladium-mediated cyclisation
Attempting the reaction without the trichloroacetyl group
did not allow the reaction to proceed, so we assume the
group stays on under the reaction conditions, but is
cleaved on work-up. One other point is worthy of note: the
order of addition of the copper, lithium and palladium is
crucial to the reaction. If the reagents are added simulta-
SYNTHESIS 2009, No. 1, pp 0148–0154
0
2
.
0
1
.2
0
0
9
Advanced online publication: 12.12.2008
DOI: 10.1055/s-0028-1083282; Art ID: C05408SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Formation of Oxazolidinones or Allylic Amides from a Common Precursor
149
Table 1 Aminochlorination with Palladium(II)a
Table 2 One-Pot Protection, Aminochlorination/Deprotectiona
Entry
R
Product
2a
Yield (%) dr (trans/cis)
Entry
R
Product
2a
Yield (%)
1
2
3
4
5
6
Et
70
70
73
75
69
67
>25:1
>25:1
>25:1
>25:1
12:1
1
2
3
4
5
6
Et
69
66
73
73
65
62
Ph
2b
Ph
2b
i-Pr
2c
i-Pr
2c
PhCH2CH2
H2C=CH
H2C=CHCH2
2d
PhCH2CH2
H2C=CH
H2C=CHCH2
2d
2e
2e
2f
>25:1
2f
a Reaction conditions: see Scheme 2, and the experimental section.
a Reaction conditions: see Scheme 3, and the experimental section.
neously, or the palladium is added first, no reaction oc-
curs. However, we found that if the copper and lithium
salts are added first and stirred with the substrate then, af-
ter ten minutes, the palladium is added, the reaction pro-
ceeds as shown. The reasons for the different behaviour
are unclear, but the results are reproducible.
The yields of the one-pot procedure were comparable to
the two-step process outlined above. The diastereomeric
ratios were also the same, with only one isomer visible in
most cases.
As mentioned above, the requirement for the protecting
group is definite since the reaction did not proceed with
the primary carbamate. However, we found a different
product was produced under slightly elevated tempera-
tures. The rearranged carbamate was similar to that re-
ported by Lu,8 who suggested the reaction may operate by
a palladium(II) aminopalladation/b-heteroatom elimina-
tion. This is related to the Overman [3,3]-sigmatropic
rearrangement of allylic trichloroacetimidates, which pro-
duce allylic trichloroamides.9 When using the free car-
bamate, we produced the rearranged products where the
Of note in the results presented in Table 1 is the consis-
tently good yield of products obtained with a range of
alkyl, alkenyl and aromatic groups. In addition, the reac-
tion was regioselective for five-membered ring formation
when presented with the opportunity to form the six-
membered ring (entry 6). None of the six-membered rings
were isolated. Also of note is the high degree of stereose-
lectivity in favour of the trans-isomer, which we attribute
to 1,3-allylic strain in the transition state.
With this success in hand, we next sought to extend the re- reaction proceeded through the carbonyl group
action and telescope the activation step and the cyclisation (Scheme 4).10
into one pot. Thus, the isocyanate was reacted with the al-
cohol in situ. After this had been achieved, we simply add-
ed the copper and lithium salts, followed by the palladium
source (Scheme 3). The overall yields are presented in
Table 2; again the free amide was produced, negating the
requirement for any deprotection step. An attempt to add
the allylic formation step (vinylmagnesium bromide onto
the requisite aldehyde) into the one-pot protocol was un-
successful.
O
O
Pd(OAc)2 (5 mol%)
LiCl (2 equiv)
O
NH2
Ph
O
NH2
Ph
THF, 40 °C
60%
4
3
Scheme 4 Palladium-mediated rearrangement
However, when the trichloroacetyl protecting group was
used, which effectively increased the acidity of the N–H
moiety, this allowed the reaction to proceed through the
central nitrogen. This produced the allylic amides with the
protecting group still attached. Initial studies looked at op-
timisation of the reaction conditions and showed that tet-
rahydrofuran at 60 °C with 5 mol% palladium(II) acetate
and two equivalents of lithium chloride were optimal
(Scheme 5). If the lithium salt was omitted, no reaction
took place. It is notable that, except for the absence of the
copper oxidant, these conditions are almost identical to
those used in the aminochlorination reaction. With the op-
timisation studies in hand, we proceeded to address the
scope of the reaction using a range of substrates.
O
O
OH
Cl3CCONCO
O
N
CCl3
H
R
THF, 0 °C to 25 °C
R
3
1
Pd(OAc)2 (5 mol%)
CuCl2 (4 equiv)
LiCl (2 equiv)
then
O
one-pot
procedure
THF, 25 °C
O
NH
R
2
The yields in Table 3 are all excellent but in an effort to
increase the utility of the reaction, we again sought to
combine the activation and rearrangement steps into a
Cl
Scheme 3 One-pot palladium-mediated cyclisation
Synthesis 2009, No. 1, 148–154 © Thieme Stuttgart · New York

150
S. D. R. Christie et al.
PAPER
Table 4 One-Pot Protection/Activation, Rearrangementa
O
O
Pd(OAc)2 (5 mol%)
O
LiCl (2 equiv)
O
N
CCl3
Entry
R
Product
5a
Yield (%)
H
THF, 60 °C
R
N
CCl3
H
R
1
2
3
4
5
6
7
8
Et
80
84
81
78
78
92
80
76
1
5
Ph
5b
Scheme 5 Palladium-mediated rearrangement
i-Pr
5c
PhCH2CH2
PhCH2
CH2=CH
H
5d
Table 3 Scope of the Palladium-Mediated Rearrangementa
5e
Entry
R
Product
5a
Yield (%)
5f
1
2
3
4
5
6
7
8
Et
82
87
84
80
82
85
85
85
5g
Ph
5b
p-NO2C6H4
5h
i-Pr
5c
a Reaction conditions: see Scheme 6, and the experimental section.
PhCH2CH2
PhCH2
CH2=CH
H
5d
5e
ene. In this case, the rearranged product was isolated in
excellent yield.
5f
In addition, we also looked at microwave irradiation as a
means of accelerating the reaction. To this end, a general
screening of solvents again found that tetrahydrofuran
was the best medium for the reaction, this time with a tem-
perature of 100 °C, controlled by the microwave reactor.
In general, the yields from these reactions were higher
than those obtained under the thermal conditions listed in
Table 3, and showed excellent conversion into the desired
products (Table 5).
5g
p-NO2C6H4
5h
a Reaction conditions: see Scheme 5, and the experimental section.
one-pot protocol. As shown in Scheme 6, reaction with
the isocyanate in tetrahydrofuran was followed by addi-
tion of the palladium and lithium salts. This protocol al-
lowed the allylic alcohols to be converted into allylic
amides in a one-pot, two-step reaction (Table 4).
O
O
Pd(OAc)2 (5 mol%)
LiCl (2 equiv)
O
O
N
CCl3
O
O
H
OH
N
CCl3
THF
MW, 100 °C
95%
Cl3CCONCO
O
N
CCl3
H
H
R
THF, 0 °C to 25 °C
5i
R
1
3
Scheme 7 Palladium-mediated rearrangement of cyclohexenyl-
substituted substrate
Pd(OAc)2 (5 mol%)
LiCl (2 equiv)
THF, 60 °C
then
one-pot
procedure
Table 5 Microwave-Accelerated Rearrangementa
O
Entry
R
Product
5a
Yield (%)
R
N
CCl3
H
1
2
3
4
5
6
7
8
Et
98
92
95
90
90
92
89
80
5
Ph
5b
Scheme 6 One-pot palladium-mediated rearrangement
i-Pr
5c
We next attempted the rearrangement of substrates with
internal double bonds. These reactions are of interest
since the rearranged products would then contain an
asymmetric centre. However, using trans-substituted alk-
enes in the reaction gave no products. The reactions were
assessed under the standard conditions given in Scheme 5,
under higher reaction temperatures, and under microwave
conditions. Unfortunately, only very small amounts of
products were ever isolated. Using a cyclohexenyl-substi-
tuted substrate was more successful (Scheme 7), perhaps
because this compound contains a more accessible cis alk-
PhCH2CH2
PhCH2
CH2=CH
H
5d
5e
5f
5g
p-NO2C6H4
5h
a Reaction conditions: see the experimental section.
Synthesis 2009, No. 1, 148–154 © Thieme Stuttgart · New York

PAPER
Formation of Oxazolidinones or Allylic Amides from a Common Precursor
151
Palladium(II)-Catalysed Chloroamination Cyclisation; Gener-
al Procedure
Finally, although the rearrangement reaction did not facil-
itate removal of the protecting group on work-up as in the
case of the oxazolidinone, we have confirmed that the
trichloroacetyl group can be removed by reaction with a
zinc/copper couple (as an alternative to the more well-
known zinc dust deprotection method14) in excellent yield
(>86% in all cases). This, then, represents a method for
the conversion of allylic alcohols into the corresponding
allyl amines in a three-step, two-pot protocol in excellent
overall yield.
To a solution of allylic alcohol (1 equiv) in anhydrous THF (10 mL)
cooled to 0 °C in an ice bath was added, dropwise, trichloroacetyl
isocyanate (1.1 equiv). The reaction was warmed slowly to r.t. with
stirring and the reaction was monitored by TLC. Upon consumption
of the starting material, LiCl (2 equiv) and CuCl2 (4 equiv) were
added in a single portion and the reaction was stirred for 5 min.
Pd(OAc)2 (0.05 equiv) was then added and stirring was maintained
for 12 h. The reaction mixture was concentrated in vacuo and the
crude product was purified by flash silica chromatography as indi-
cated.
In summary, we have developed a method of synthesizing
either oxazolidinones or allylic amines from a common
starting material simply by addition or omission of a cop-
per oxidant. In addition, we have been able to use a more
labile protecting group that is easily removed, sometimes
on workup.
Palladium-Catalysed [3,3]-Sigmatropic Rearrangement;
General Procedure
(2,2,2-Trichloroacetyl)carbamic acid (1 equiv), PdCl2 (0.05 equiv),
and LiCl (2 equiv) in anhydrous THF (10 mL) were combined, and
stirring was maintained for 12 h at 60 °C. The reaction mixture was
concentrated in vacuo and the crude product was purified by flash
silica chromatography as indicated.
Commercial anhydrous solvents were used in all reactions except
for light petroleum (PE) 40–60 °C, and EtOAc, which were distilled
from CaCl2. THF was distilled from sodium and benzophenone,
CH2Cl2 was distilled from phosphorous pentoxide or CaCl2. NaH
was used as a 60% dispersion oil. DMF, benzene and toluene were
bought as anhydrous solvents in Sure-Seal® bottles.
Palladium-Catalysed [3,3]-Sigmatropic Rearrangement under
Microwave Conditions; General Procedure
(2,2,2-Trichloroacetyl)carbamic acid (1 equiv), PdCl2 (0.05 equiv),
and LiCl (2 equiv) were weighed into a microwave vial and anhy-
drous THF (2 mL) was added. The vessel was subjected to micro-
wave irradiation in a Biotage Initiator 8 system, and the reaction
was monitored by TLC. The reaction mixture was concentrated in
vacuo and the crude product was purified by flash silica chromatog-
raphy as indicated.
The reagents used were obtained from Sigma–Aldrich Chemical
Co. Ltd, Lancaster Synthesis Ltd and Strem Chemical Co. Ltd.
Melting points were determined on a Leica Galen III hot stage melt-
ing point apparatus and are uncorrected. Infrared spectra were re-
corded on a Perkin–Elmer Paragon 1000 FT-IR spectrophotometer
on NaCl plates as thin films of pure liquid, CDCl3 solution or
Nujol® mulls.
1H (400.15 MHz) and 13C (100.62 MHz) NMR spectra were record-
ed using a Bruker AC-400 spectrometer; 1H (250.15 MHz) spectra
were recorded using a Bruker AC-250 spectrometer.
4-Chloromethyl-5-ethyloxazolidin-2-one (2a)
Pent-1-en-3-ol (0.0345 g, 0.401 mmol) was subjected to the general
palladium(II)-catalysed chloroamination cyclisation. The crude
product was purified by flash silica chromatography (EtOAc–PE,
1:2) to yield the product.
Yield: 0.0453 g (69%); yellow oil.
IR (neat): 3295 (NH), 1749 (C=O), 1024 (CO) cm–1.
1H NMR (400 MHz, CDCl3): d = 6.96 (1 H, br s), 4.38–4.31 (1 H,
m), 3.77–3.72 (1 H, m), 3.61–3.51 (2 H, m), 1.85–1.69 (2 H, m),
1.04 (3 H, t, J = 7.4 Hz).
High-resolution mass spectrometry was carried out on a Jeol SX
102 machine, using the fast atom bombardment (FAB) ionisation
technique. For FAB spectroscopy, a matrix of 1,3-nitrobenzylalco-
hol (NOBA) or octadecane was used to dissolve the compounds un-
der investigation prior to ionisation.
13C NMR (100 MHz, CDCl3): d = 159.2 (q), 81.5 (CH), 58.0 (CH),
45.7 (CH2), 28.0 (CH2), 8.7 (CH3).
TLC using silica gel as absorbent was carried out with aluminium
backed plates coated with silica gel (Merck Kieselgel 60 F254), and
TLC using alumina as absorbent was carried out with aluminium
MS (FAB): m/z (%) = 166 (33), 164 (100), 106 (16).
HRMS (FAB): m/z [M+] calcd for C6H10NO2Cl: 164.0400; found:
backed plates coated with neutral aluminium oxide (Merck 150 F254
,
TypeT). The plates were analysed under UV light or stained with io-
dine or potassium permanganate. Silica gel (Merck Kieselgel 60 H
silica) was used for column chromatography unless otherwise spec-
ified. Samples were applied either as liquids, saturated solutions of
the appropriate solvent system, or pre-adsorbed onto flash silica gel.
Column chromatography using alumina was carried out with Ald-
rich aluminium oxide, activated neutral, Brockmann 1, STD Grade,
150 mesh size. Preparative TLC was carried out using aluminium
oxide (Merck 60 PF254, Type E).
164.0400.
4-Chloromethyl-5-phenyloxazolidin-2-one (2b)
a-Vinylbenzyl alcohol (0.0541 g, 0.403 mmol) was subjected to the
general palladium(II)-catalysed chloroamination cyclisation. The
crude product was purified by flash silica chromatography (EtOAc–
PE, 1:2) to yield the product.
Yield: 0.0563 g (66%); off-white powder; mp 125.1–128.4 °C.
IR (Nujol): 3285 (NH), 1751 (C=O), 1023 (CO) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.44–7.35 (5 H, m), 7.10 (1 H, br
s), 5.37 (1 H, d, J = 4.8 Hz), 4.02–3.98 (1 H, m), 3.67 (2 H, d, J =
5.6 Hz).
13C NMR (100 MHz, CDCl3): d = 159.1 (q), 137.9 (q), 129.2 (CH),
129.1 (2 × CH), 125.6 (2 × CH), 80.8 (CH), 61.2 (CH), 45.4 (CH2).
(2,2,2-Trichloroacetyl)carbamic Acid; General Procedure
To a solution of an allylic alcohol (1 equiv) in CH2Cl2 (20 mL)
cooled to 0 °C in an ice bath was added, dropwise, trichloroacetyl
isocyanate (1.1 equiv). The mixture was stirred for 4 h until con-
sumption of the starting material was observed (reaction monitored
by TLC ). The solvent was removed by evaporation to afford the
crude product, which was purified by flash silica chromatography if
required.
MS (FAB): m/z (%) = 214 (33), 212 (100).
HRMS (FAB): m/z [M+] calcd for C10H10NO2Cl: 212.0478; found:
212.0479.
Synthesis 2009, No. 1, 148–154 © Thieme Stuttgart · New York

152
S. D. R. Christie et al.
PAPER
4-Chloromethyl-5-isopropyloxazolidin-2-one (2c)11
4-Methylpent-1-en-3-ol (0.0416 g, 0.416 mmol) was subjected to
the general palladium(II)-catalysed chloroamination cyclisation.
The crude product was purified by flash silica chromatography
(EtOAc–PE, 1:2) to yield the product.
Yield: 0.0539 g (73%); colourless solid; mp 66–70 °C (Lit.11 65–
67 °C).
IR (Nujol): 3300 (NH), 1751 (C=O), 1240 (CO) cm–1.
1H NMR (400 MHz, CDCl3): d = 6.70 (1 H, br s), 5.82–5.71 (1 H,
m), 5.26–5.19 (2 H, m), 4.50–4.45 (1 H, m), 3.82 (1 H, q, J = 6.0
Hz), 3.54 (2 H, d, J = 6.0 Hz), 2.58–2.46 (2 H, m).
13C NMR (100 MHz, CDCl3): d = 159.4 (q), 130.5 (CH), 120.4
(CH2), 79.4 (CH), 57.4 (CH), 45.5 (CH2), 38.8 (CH2).
MS (FAB): m/z (%) = 178 (33), 176 (100), 124 (5), 122 (15).
HRMS (FAB): m/z [M+] calcd for C7H10NO2Cl: 176.0478; found:
176.0477.
IR (Nujol): 3279 (NH), 1735 (C=O), 1240 (CO) cm–1.
1H NMR (400 MHz, CDCl3): d = 6.92 (1 H, br s), 4.16 (1 H, dd, J =
6.4, 4.4 Hz), 3.86–3.82 (1 H, m), 3.55 (2 H, d, J = 5.6 Hz), 2.01–
1.87 (1 H, m), 1.01 (6 H, d, J = 7.2 Hz).
13C NMR (100 MHz, CDCl3): d = 159.6 (q), 84.8 (CH), 56.0 (CH),
46.3 (CH2), 32.2 (CH), 17.3 (CH3), 16.7 (CH3).
Carbamic Acid 3-Phenylallyl Ester (4)4
To a solution of carbamic acid 1-phenylallyl ester (0.200 g, 1.13
mmol) in anhydrous THF was added Pd(OAc)2 (0.0127 g, 0.0564
mmol) and LiCl (0.958 g, 2.26 mmol) in a single portion. Stirring
was started and the reaction was monitored by TLC. Upon con-
sumption of the starting material, the solvent was removed via rota-
ry evaporation and the crude product was purified by flash silica
chromatography (EtOAc–PE, 2:1) to yield the product.
4-Chloromethyl-5-phenethyloxazolidin-2-one (2d)11
5-Phenylpent-1-en-3-ol (0.100 g, 0.616 mmol) was subjected to the
general palladium(II)-catalysed chloroamination cyclisation. The
crude product was purified by flash silica chromatography (EtOAc–
PE, 1:2) to yield the product.
Yield: 0.120 g (60%); clear oil.
Yield: 0.108 g (73%); colourless oil.
IR (neat): 3278 (NH), 1750 (C=O) cm–1.
IR (Nujol): 3409 (NH2), 3331 (NH2), 1682 (C=O), 1608 (C=C)
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.25–7.12 (5 H, m), 6.66 (1 H, br
s), 4.33–4.26 (1 H, m), 3.70–3.65 (1 H, m), 3.51–3.39 (2 H, m),
2.83–2.62 (2 H, m), 2.09–1.85 (2 H, m).
1H NMR (400 MHz, CDCl3): d = 7.33–7.16 (5 H, m), 6.58 (1 H, d,
J = 16.0 Hz), 6.22 (1 H, dt, J = 16.0, 6.4 Hz), 4.71 (2 H, br s), (2 H,
dd, J = 6.4, 1.6 Hz).
13C NMR (100 MHz, CDCl3): d = 140.2 (q), 128.6 (2 × CH), 128.5
(2 × CH), 126.4 (CH), 79.6 (CH), 58.5 (CH), 45.6 (CH2), 36.8
(CH2), 30.8 (CH2).
13C NMR (100 MHz, CDCl3): d = 156.7 (q), 136.2 (q), 133.9 (CH),
128.6 (2 × CH), 128.1 (CH), 126.6 (2 × CH), 123.5 (CH), 65.7
(CH2).
MS (FAB): m/z (%) = 242 (34), 240 (100), 122 (7), 120 (10).
MS (FB): m/z (%) = 177 (55), 117 (100), 115 (27).
HRMS (FAB): m/z [M+] calcd for C12H14NO2Cl: 240.0791; found:
HRMS (FAB): m/z [M+] calcd for C10H11NO2: 177.0790; found:
240.0791.
177.0792.
4-Chloromethyl-5-vinyloxazolidin-2-one (2e)
2,2,2-Trichloro-N-pent-2-enylacetamide (5a)
1,4-Pentadien-3-ol (0.0309 g, 0.367 mmol) was subjected to the
general palladium(II)-catalysed chloroamination cyclisation. The
crude product was purified by flash silica chromatography (EtOAc–
PE, 1:2) to yield the product.
(2,2,2-Trichloroacetyl)carbamic acid 1-ethylallyl ester (0.050 g,
0.182 mmol) was subjected to the general [3,3]-sigmatropic rear-
rangement conditions using microwave irradiation at 100 °C for 20
min. The crude product was purified by flash silica chromatography
(cyclohexane–EtOAc, 1:2) to yield the product.
Yield: 0.0385 g (65%); yellow oil; dr = 12:1.
Yield: 0.0412 g (98%); white powdery solid; mp 49.3–51.4 °C.
IR (neat): 3233 (NH), 1696 (C=O) cm–1.
1H NMR (400 MHz, CDCl3): d = 6.69 (1 H, br s), 5.83–5.73 (1 H,
m), 5.53–5.44 (1 H, m), 3.94 (2 H, d, J = 5.8 Hz), 2.14–2.03 (2 H,
m), 1.02 (3 H, t, J = 7.4 Hz).
IR (Nujol): 3286 (NH), 1751 (C=O), 1240 (CO) cm–1.
1H NMR (400 MHz, CDCl3): d (major isomer) = 6.63 (1 H, br s),
5.97–5.89 (1 H, m), 5.48 (1 H, dt, J = 16.8, 1.2 Hz), 5.36 (1 H, dt,
J = 10.4, 1.2 Hz), 4.83–4.79 (1 H, m), 3.84 (1 H, q, J = 5.6 Hz), 3.60
(2 H, d, J = 5.6 Hz); d (minor isomer) = 6.63 (1 H, br s), 5.97–5.89
(1 H, m), 5.56 (1 H, dt, J = 16.8, 1.2 Hz), 5.44 (1 H, dt, J = 10.4, 1.2
Hz), 5.19–5.14 (1 H, m), 4.17–4.11 (1 H, m), 3.60 (2 H, d, J = 5.6
Hz).
13C NMR (100 MHz, CDCl3): d (major isomer) = 158.6 (q), 133.7
(CH), 119.3 (CH2), 80.2 (CH), 58.8 (CH), 45.2 (CH2); d (minor iso-
mer) = 158.6 (q), 129.23 (CH), 121.3 (CH2), 79.1 (CH), 56.8 (CH),
43.9 (CH2).
13C NMR (100 MHz, CDCl3): d = 160.6 (q), 138.8 (CH), 126.1
(CH), 44.6 (CH2), 25.8 (CH2), 14.0 (CH3).
MS (FAB): m/z (%) = 232 (53), 230 (92), 228 (31), 162 (21), 145
(100).
HRMS (FAB): m/z [M+] calcd for C7H10NOCl3: 229.9828; found:
229.9828.
MS (FAB): m/z (%) = 164 (33), 162 (100), 149 (21), 120 (5), 118
(10).
HRMS (FAB): m/z [M+] calcd for C6H8NO2Cl: 162.0322; found:
162.0321.
2,2,2-Trichloro-N-(3-phenylallyl)acetamide (5b)12
(2,2,2-Trichloroacetyl)carbamic acid 1-phenylallyl ester (0.050 g,
0.155 mmol) was subjected to the general [3,3]-sigmatropic rear-
rangement conditions. The crude product was purified by flash sil-
ica chromatography (cyclohexane–EtOAc, 1:2) to yield the product.
5-Allyl-4-chloromethyloxazolidin-2-one (2f)11
Yield: 0.0397 g (92%); yellow oil.
IR (Nujol): 3230 (NH), 1691 (C=O) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.34–7.19 (5 H, m), 6.54 (1 H, d,
J = 15.9 Hz), 6.28 (1 H, dt, J = 15.9, 5.8 Hz), 4.92 (1 H, br s), 4.24
(2 H, d, J = 5.8 Hz).
1,5-Hexadiene-3,4-diol (0.0377 g, 0.384 mmol) was subjected to
the general palladium(II)-catalysed chloroamination cyclisation.
The crude product was purified by flash silica chromatography
(EtOAc–PE, 1:2) to yield the product.
Yield: 0.0674 g (62%); yellow oil.
Synthesis 2009, No. 1, 148–154 © Thieme Stuttgart · New York

PAPER
Formation of Oxazolidinones or Allylic Amides from a Common Precursor
153
13C NMR (100 MHz, CDCl3): d = 136.7 (q), 131.5 (CH), 128.5
(2 × CH), 128.2 (CH), 127.8 (CH), 126.8 (2 × CH), 63.4 (CH2).
2,2,2-Trichloro-N-penta-2,4-dienylacetamide (5f)
(2,2,2-Trichloroacetyl)carbamic acid 1-vinylallyl ester (0.0500 g,
0.183 mmol) was subjected to the general [3,3]-sigmatropic rear-
rangement conditions using microwave irradiation at 100 °C for 20
min. The crude product was purified by flash silica chromatography
(cyclohexane–EtOAc, 1:2) to yield the product.
2,2,2-Trichloro-N-(4-methylpent-2-enyl)acetamide (5c)
(2,2,2-Trichloroacetyl)carbamic acid 1-isopropylallyl ester (0.050
g, 0.173 mmol) was subjected to the general [3,3]-sigmatropic rear-
rangement conditions using microwave irradiation at 100 °C for 10
min. The crude product was purified by flash silica chromatography
(cyclohexane–EtOAc, 1:2) to yield the product.
Yield: 0.0386 g (92%); white powdery solid; mp 46.7–48.2 °C.
IR (neat): 3296 (NH), 1700 (C=O) cm–1.
1H NMR (400 MHz, CDCl3): d = 6.30–6.19 (2 H, m), 5.75–5.68
(1 H, m), 5.21–5.17 (1 H, m), 5.10–5.06 (1 H, m), 4.58 (1 H, br s),
4.53 (2 H, d, J = 6.8 Hz).
13C NMR (100 MHz, CDCl3): d = 161.8 (q), 135.9 (CH), 134.4
(CH), 127.4 (CH), 118.6 (CH2), 46.2 (CH2).
Yield: 0.0400 g (95%); white powdery solid; mp 45.1–47.3 °C.
IR (neat): 3228 (NH), 1693 (C=O) cm–1.
1H NMR (400 MHz, CDCl3): d = 6.72 (1 H, br s), 5.69 (1 H, dd, J =
15.4, 5.4 Hz), 5.43 (1 H, dt, J = 15.4, 6.0 Hz), 3.93 (2 H, d, J = 6.0
Hz), 2.38–2.24 (1 H, m), 1.00 (6 H, d, J = 7.2 Hz).
13C NMR (100 MHz, CDCl3): d = 162.0 (q), 142.5 (CH), 120.7
(CH), 43.4 (CH2), 30.8 (CH), 22.1 (2 × CH3).
N-Allyl-2,2,2-trichloroacetamide (5g)13
(2,2,2-Trichloroacetyl)carbamic acid allyl ester (0.050 g, 0.203
mmol) was subjected to the general [3,3]-sigmatropic rearrange-
ment conditions using microwave irradiation at 100 °C for 20 min.
The crude product was purified by flash silica chromatography (cy-
clohexane–EtOAc, 1:2) to yield the product.
Yield: 0.0366 g (89%); white powdery solid; mp 29–31 °C (Lit.13
28–31 °C).
IR (Nujol): 3396 (NH), 1724 (C=O) cm–1.
1H NMR (400 MHz, CDCl3): d = 6.87 (1 H, br s), 5.85–5.63 (1 H,
m), 5.47–5.06 (2 H, m), 3.95 (2 H, d, J = 5.5 Hz).
MS (FAB): m/z (%) = 246 (64), 244 (90), 242 (37), 167 (25), 149
(100), 113 (19).
HRMS (FAB): m/z [M+] calcd for C8H12NOCl3: 243.9985; found:
243.9990.
2,2,2-Trichloro-N-(5-phenylpent-2-enyl)acetamide (5d)
(2,2,2-Trichloroacetyl)carbamic acid 1-(3-phenylethane)allyl ester
(0.050 g, 0.143 mmol) was subjected to the general [3,3]-sigmatro-
pic rearrangement conditions using microwave irradiation at 100 °C
for 20 min. The crude product was purified by flash silica chroma-
tography (cyclohexane–EtOAc, 1:2) to yield the product.
13C NMR (100 MHz, CDCl3): d = 160.5 (q), 132.1 (CH), 116.7
(CH2), 44.0 (CH2).
Yield: 0.0393 g (90%); white/yellow solid; mp 121.3–124.0 °C.
IR (neat): 3230 (NH), 1689 (C=O) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.31–7.23 (2 H, m), 7.22–7.12
(3 H, m), 6.61 (1 H, br s), 5.79–5.69 (1 H, m), 5.53–5.43 (1 H, m),
3.90 (2 H, d, J = 6.0 Hz), 2.70 (2 H, t, J = 7.6 Hz), 2.38 (2 H, q, J =
7.6 Hz).
13C NMR (100 MHz, CDCl3): d = 161.1 (q), 140.8 (q), 134.0 (CH),
128.0 (2 × CH), 127.9 (2 × CH), 125.5 (CH), 124.0 (CH), 42.7
(CH2), 34.8 (CH2), 33.4 (CH2).
2,2,2-Trichloro-N-[3-(4-nitrophenyl)allyl]acetamide (5h)
(2,2,2-Trichloroacetyl)carbamic acid 1-(4-nitrophenyl)allyl ester
(0.050 g, 0.136 mmol) was subjected to the general [3,3]-sigmatro-
pic rearrangement conditions using microwave irradiation at 100 °C
for 20 min. The crude product was purified by flash silica chroma-
tography (cyclohexane–EtOAc, 1:2) to yield the product.
Yield: 0.0352 g (80%); orange oil.
IR (Nujol): 3236 (NH), 1697 (C=O) cm–1.
MS (FAB): m/z (%) = 308 (46), 306 (49), 289 (14), 253 (13), 251
(14).
HRMS (FAB): m/z [M+] calcd for C13H14NOCl3: 306.0219; found:
306.0225.
1H NMR (400 MHz, CDCl3): d = 8.18 (2 H, d, J = 7.6 Hz), 7.51
(2 H, d, J = 8.2 Hz), 7.04 (1 H, br s), 6.67 (1 H, d, J = 15.8 Hz), 6.41
(1 H, dt, J = 15.8, 5.8 Hz), 4.22 (2 H, d, J = 5.8 Hz).
13C NMR (100 MHz, CDCl3): d = 161.6 (q), 146.8 (q), 142.0 (q),
130.6 (CH), 127.9 (CH), 126.6 (2 × CH), 123.6 (2 × CH), 42.6
(CH2).
2,2,2-Trichloro-N-(4-phenylbut-2-enyl)acetamide (5e)
(2,2,2-Trichloroacetyl)carbamic acid 1-phenylbut-3-allyl ester
(0.050 g, 0.149 mmol) was subjected to the general [3,3]-sigmatro-
pic rearrangement conditions using microwave irradiation at 100 °C
for 15 min. The crude product was purified by flash silica chroma-
tography (cyclohexane–EtOAc, 1:2) to yield the product.
MS (FAB): m/z (%) = 323 (69), 321 (86), 163 (35), 144 (100).
HRMS (FAB): m/z [M+] calcd for C11H9N2O3Cl3: 322.9679; found:
322.9680.
2,2,2-Trichloro-N-cyclohex-2-enylacetamide (5i)13
Yield: 0.0391 g (90%); white powdery solid; mp 119.7–122.1 °C.
IR (neat): 3335 (NH), 1696 (C=O) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.38–7.17 (5 H, m), 6.72 (1 H, br
s), 5.93–5.86 (1 H, m), 5.60–5.54 (1 H, m), 3.97 (2 H, t, J = 6.0 Hz),
3.40 (2 H, d, J = 6.4 Hz).
13C NMR (100 MHz, CDCl3): d = 162.1 (q), 139.4 (q), 133.9
(2 × CH), 128.6 (3 × CH), 126.3 (CH), 125.0 (CH), 43.1 (CH2),
38.6 (CH2).
(2,2,2-Trichloroacetyl)carbamic acid cyclohex-2-enyl ester (0.050
g, 0.175 mmol) was subjected to the general [3,3]-sigmatropic rear-
rangement conditions using microwave irradiation at 100 °C for 15
min. The crude product was purified by flash silica chromatography
(cyclohexane–EtOAc, 1:2) to yield the product.
Yield: 0.161 g (95%); white powdery solid; mp 84.2–87.0 °C (Lit.13
85.5–87 °C).
IR (neat): 3226 (NH), 1689 (C=O) cm–1.
MS (FAB): m/z (%) = 294 (54), 292 (92), 147 (34), 144 (100), 132
(15).
HRMS (FAB): m/z [M+] calcd for C12H12NOCl3: 291.9985; found:
291.9985.
1H NMR (400 MHz, CDCl3): d = 6.59 (1 H, br s), 6.02–5.94 (1 H,
m), 5.68–5.62 (1 H, m), 4.51–4.41 (1 H, m), 2.11–2.03 (2 H, m),
2.02–1.92 (1 H, m), 1.75–1.61 (3 H, m).
13C NMR (100 MHz, CDCl3): d = 160.6 (q), 132.2 (CH), 125.2
(CH), 46.2 (CH), 26.3 (CH2), 21.4 (CH2), 18.8 (CH2).
Synthesis 2009, No. 1, 148–154 © Thieme Stuttgart · New York

154
S. D. R. Christie et al.
PAPER
MS (FAB): m/z (%) = 242 (6), 167 (26), 149 (100), 113 (21), 95
(11).
HRMS (FAB): m/z [M+] calcd for C8H10NOCl3: 241.9906; found:
241.9901.
(5) Lei, A.; Lu, X.; Liu, G. Tetrahedron Lett. 2004, 45, 1785.
(6) Manzoni, M. R.; Zabawa, T. P.; Kasi, D.; Chemler, S. R.
Organometallics 2004, 23, 5618.
(7) Michael, F. E.; Sibbald, P. A.; Cochran, B. M. Org. Lett.
2008, 10, 793.
(8) Lei, A.; Lu, X. Org. Lett. 2000, 2, 2357.
(9) (a) Overman, L. E. Acc. Chem. Res. 1980, 13, 218.
(b) Nubbemeyer, N. Synthesis 2003, 961.
Acknowledgment
We would like to thank GlaxoSmithKline and Loughborough Uni-
versity for funding.
(10) For a related example, see: Garner, P.; Park, J. M. J. Org.
Chem. 1988, 53, 2979.
(11) Bach, T.; Eckhardt, M.; Furlong, M.; Knoess, H. P.; Berger,
S.; Knochel, P. Tetrahedron 1994, 50, 2415.
(12) Ali, I. A. I.; El Ashry, E. S. H.; Schmidt, R. R. Tetrahedron
2004, 60, 4773.
(13) Overman, L. E. J. Am. Chem. Soc. 1976, 98, 2901.
(14) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd ed.; John Wiley and Sons: New
York, 1999.
References
(1) Christie, S. D. R.; Warrington, A. D. Synthesis 2008, 1325.
(2) Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 7179.
(3) Alexanian, E. J.; Lee, C.; Sorensen, E. J. J. Am. Chem. Soc.
2005, 127, 7690.
(4) Donohoe, T. J.; Johnson, P. D.; Helliwell, M.; Keenan, M.
Chem. Commun. 2001, 2078.
Synthesis 2009, No. 1, 148–154 © Thieme Stuttgart · New York