A novel silica catalysed stereoselective cyclic carbamate and carbonate rearrangement

Article abstract of DOI:10.1039/b303791f

Phenylsulfanyl-containing five- and six-membered lactones, cyclic carbamates and carbonates stereospecifically interconvert in the presence of silica gel via thiiranium ions.

Full text of DOI:10.1039/b303791f

A novel silica catalysed stereoselective cyclic carbamate and carbonate
rearrangement
Lorenzo Caggiano, John Davies, David J. Fox, David C. Moody and Stuart Warren*
University Chemistry Laboratory, Lensfield Road, Cambridge, UK CB2 1EW. E-mail: sw134@cam.ac.uk
Received (in Cambridge, UK) 4th April 2003, Accepted 30th May 2003
First published as an Advance Article on the web 12th June 2003
Phenylsulfanyl-containing five- and six-membered lactones,
cyclic carbamates and carbonates stereospecifically inter-
convert in the presence of silica gel via thiiranium ions.
carbamates are in equilibrium in these reaction conditions, and
even after prolonged heating, no other products are observed.
This isomerisation is similar to that observed for the non-cyclic
carbamate previously reported, but there a true equilibrium was
not established and both isomers ultimately reacted to form an
allylic sulfide.1
Pyrrolidines have been synthesised from six-membered-ring
carbamates with stereospecific migration of a PhS group and
loss of CO2.1,2 If a similar process were to occur with the five-
membered-ring carbamate 1, then the product would be either
an aziridine 2 or an azetidine 3, depending on the relative rates
of these two competing ring-closing reactions (Scheme 1).
Similar aziridine-forming reactions involve the opening of a
bromonium3 and iodonium ions.4,5 Azetidines6 and b-lactams
can be made by the opening of bromonium7,8 and sulfonium9,10
ions.
This reversible reaction was extended to more substituted
compounds. Aldol products11 6,7 and 8 (aldol of isobutyric acid
onto 1-phenylsulfanylcyclohexane carboxaldehyde11) were in-
dividually converted into oxazolidinones 9–11 which were
heated in the presence of silica gel until equilibria with the six-
membered-ring carbamates 12–14 were achieved (Table 1,
Scheme 3). The configurations of compounds 10 and 13,
confirmed by X-ray crystallographic analysis, are consistent
with the reaction occurring via a stereospecific episulfonium ion
rearrangement with inversion at the secondary centre (Fig. 1).†
In the least substituted case the oxazinone 5 is the more stable
compound and 4,5-cis-substitution destabilises the near-planar
oxazolidinones 10 and 11 with respect to their respective six-
membered-ring isomers even more. The trans-relationship in
carbamates 9 and 12 alone favours the five-membered-ring
compound. Cyclisation of alkyl carbamates onto episulfon-
ium,12 episelenonium,13,14 bromonium12 and iodonium13,14
ions also produce cyclic carbamates, but there is however no
evidence in these cases that the cyclisations are reversible. The
effect of changing the cyclohexane ring has not been investi-
gated.
Scheme 1
The synthesis of oxazolidinone 1 was achieved via an aldol
reaction and a modified Curtius rearrangement in which the
isocyanate is captured by the neighbouring hydroxyl group
(Scheme 2). Treatment of this carbamate with silica gel in
refluxing chloroform produced a 17 : 83 mixture of starting
material and new compound that was neither of the cyclic
amines 2 and 3, but the six-membered-ring carbamate 5. A
rearrangement of the five-membered-ring carbamate had oc-
curred without loss of CO2. If the reaction occurred via an
episulfonium ion intermediate 4 then the carbamate anion must
be stable enough to reopen the episulfonium ion without
decarboxylation and form the alternative carbamate 5 (Scheme
2). When the purified six-membered-ring carbamate 5 was
resubjected to the rearrangement reaction procedure, five-
membered-ring carbamate 1 was reformed, and after 32 hours,
a similar (1 : 5 12 : 88) mixture was observed. The two
Table 1 The synthesis of 4-substituted oxazolidinones and their silica
catalysed rearrangement to oxazinones (see Schemes 2 and 3)
Oxazolidinone
yield
from aldol
Rearrangement
equilibrium ratio
R1
R2
Oxazinone
H
CH3
H
H
H
CH3
CH3
1 (70%)
5
(1 : 5) 13 : 87
(9 : 12) 64 : 36
(10 : 13) 2 : 98
(11 : 14) 2 : 98
anti-9 (88%)
syn-10 (84%)
11 (32%a)
anti-12
syn-13
14
CH3
a Yield from isobutyric acid.
Scheme 2 Reagents and conditions: i, KOH, H2O, THF; ii, (PhO)2PON3, t-
BuOH, D, 70% (2 steps); iii, SiO2, CHCl3, D, see Table 1.
Scheme 3 Reagents and conditions: i, KOH, H2O, THF; ii, (PhO)2PON3, t-
BuOH, D; iii, SiO2, CHCl3, D; see Table 1 for yields.
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This journal is © The Royal Society of Chemistry 2003

Scheme 6 Reagents and conditions: i, SiO2, PhCH3, D.
carbonate 20 the PhS group is adjacent to two similarly acylated
carbons and the new product is the result of a further
rearrangement to another five-membered-ring carbonate 21
(Scheme 6). This reaction is the first example of a PhS double
migration in this type of rearrangement process.
We thank the EPSRC for financial assistance towards the
purchase of the Nonius CCD diffractometer, and a studentship
(L. C.).
Fig. 1 Molecular structure of syn-carbamates 10 and 13 determined by X-
ray analysis. Pictured is only one of the two enantiomers of 13 in the unit
cell, each with a slightly different conformation.
Notes and references
†
Crystal data for 10: C16H21NO2S, M = 291.40, orthorhombic, space
group P212121 (no. 19), a = 6.7248(2), b = 13.1339(8), c = 16.6976(9) Å,
U = 1474.8(2) Å3, Z = 4, µ(Mo-Ka) = 0.221 mm21, 6257 reflections
measured at 180(2) K using an Oxford Cryosystems Cryostream cooling
apparatus, 2568 unique (Rint = 0.041); R1 = 0.037, wR2 = 0.085. Absolute
structure parameter 0.04(8). The structure was solved with SHELXS-9723
and refined with SHELXL-97.23 CCDC 207751.
For 13: C16H21NO2S, M = 291.40, monoclinic, space group P21/c (no.
14), a = 10.8413(3), b = 14.7036(9), c = 19.2137(11) Å, b = 90.201(3)°,
U = 3062.8(3) Å3, Z = 8, µ(Mo-Ka) = 0.213 mm21, 18109 reflections
measured at 180(2) K using an Oxford Cryosystems Cryostream cooling
apparatus, 5375 unique (Rint = 0.097); R1 = 0.052, wR2 = 0.095. The
structure was solved with SHELXS-9723 and refined with SHELXL-97.23
CCDC 207752. See http://www.rsc.org/suppdata/cc/b3/b303791f/ for crys-
tallographic data in CIF or other electronic format.
Scheme 4 Reagents and conditions: i, LDA, THF, 278 °C; BrCH2CO2Et,
HMPA, 73%; ii, NaBH4, THF, 0 °C, 18%; iii, SiO2, CHCl3, D.
Silica gel also catalyses the generation of episulfonium ions
from esters and carbonates,1 and we were interested to see
whether this occurred with related lactones and cyclic carbon-
ates. Five-membered-ring compounds 16 (Scheme 4) and 19
(Scheme 5) were made from known intermediates ketone15 15
and olefin16 18 respectively, and were treated with silica gel. In
refluxing chloroform both compounds formed equilibrium
mixtures with their six-membered-ring isomers 17 and 20 (16 :
17 75 : 25 and 19 : 20 91 : 9), again without any loss of CO2
from the carbonate. The position of equilibrium for the lactone
favours the five-membered ring, a result in sharp contrast to the
equivalent cyclic ethers where the THP is the only product in a
thermodynamically controlled isomerisation,17 so the inclusion
of a carbonyl group stabilises the five-membered ring with
respect to the six-membered ring. The additional oxygen atom
in the carbonates 19 and 20 favours the five-membered ring
even more. Five- and six-membered phenylseleno-lactones18
have been shown to interconvert with strong acid or Lewis acid
catalysis,19 or on standing.20 Silica gel also isomerises b- to g-
lactones via episulfonium21 and episelenonium21 ions. Phenyl-
seleno-containing cyclic carbonates similar to compounds 19
and 20 also interconvert during silica column chromatog-
raphy.22
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Scheme 5 Reagents and conditions: i, OsCl3, K3Fe(CN)6, K2CO3,
quinuclidine, t-BuOH, H2O; ii, CDI, CH3CN, 40% (2 steps), iii, SiO2,
CHCl3, D.
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