Regioselective Beckmann rearrangements of furanoside and pyranoside-derived oximes

Article abstract of DOI:10.1016/j.tetasy.2010.11.031

The Beckmann rearrangement is a useful reaction employed to provide access to amides from oxime substrates. Applied to cyclic structures, the Beckmann rearrangement leads to ring expansion and allows access to cyclic lactams. Our investigations focused up

Full text of DOI:10.1016/j.tetasy.2010.11.031

Tetrahedron: Asymmetry 22 (2011) 109–116
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Regioselective Beckmann rearrangements of furanoside and
pyranoside-derived oximes
Rajdeep K. Benning a, Helen M. I. Osborn b, , Andrea Turkson a
⇑
a Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, United Kingdom
b Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, United Kingdom
a r t i c l e i n f o
a b s t r a c t
Article history:
The Beckmann rearrangement is a useful reaction employed to provide access to amides from oxime sub-
strates. Applied to cyclic structures, the Beckmann rearrangement leads to ring expansion and allows
access to cyclic lactams. Our investigations focused upon the synthesis of glycoside-derived lactams from
oxime precursors. In probing a range of conditions, we observed that 2,4,6-trichloro[1,3,5]triazine (TCT)
was an effective and mild promoter of the rearrangement affording pyrano- and heptanoside lactam
products with excellent regioselectivities.
Received 18 November 2010
Accepted 26 November 2010
Available online 14 January 2011
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
charide mimics,22 this programme has focused on investigating
the feasibility of the Beckmann rearrangement of carbohydrate-
The Beckmann rearrangement, first discovered in 1886, involves
the conversion of an oxime to an amide.1 Since it results in the
cleavage of a carbon–carbon bond and the formation of a car-
bon–nitrogen bond, the Beckmann rearrangement is a powerful
method in the synthesis of lactams, which have evident therapeu-
tic importance. Thus, lactam derivatives have been reported to be
derived oximes for furnishing functionalised lactam derivatives.
Beckmann rearrangements on carbohydrate derivatives have pre-
viously been reported, for example by Dongare et al.,23 using fura-
nose derivatives, en-route to precursors to azythromycin and
hydroxycyclic lactams. In addition, rearrangements of carbohy-
drate hydrazones have been reported by Tronchet et al.24 allowing
access to seven-membered aminolactams. Herein we have exam-
ined the Beckmann rearrangement of a wider range of furanoside
and pyranoside substrates to more fully explore the potential of
this approach for access to functionalised lactams.
micromolar inhibitors of
a
- and b-glycosidase enzymes2–4 and
have also been used to synthesise peptide mimics5,6 and ribofura-
nose systems.7 The synthesis of some key pharmaceuticals involves
a Beckmann rearrangement as an important step. For example an
efficient method towards the synthesis of benzazepines, as
reported by Cordero-Vargas et al.,8 employed a Beckmann rear-
rangement in order to obtain an intermediate precursor to tolvap-
tan. Whilst Brønsted or Lewis acids are the archetypal catalysts in
the Beckmann rearrangement,9–19 these reagents can often lead to
degradation of the starting materials, particularly under forcing
reaction conditions. Cyanuric chloride (TCT, 2,4,6-trichloro[1,3,
5]triazine)20 has been reported to be a milder activator that also
offers the advantage that it can be used on a large scale, without
functionalisation of the oxime hydroxyl group.21 Throughout the
literature, in examples where Beckmann rearrangements occur, it
is stated that the migrating group is that which is trans to the
oxime hydroxyl group. Identification of which isomer of the oxime
is the more stable, and hence present for the rearrangement, is the
key for predicting the structure of the amide product.
2. Results and discussion
In order to probe the feasibility of using oximes derived from
pyranosides and furanosides within the Beckmann rearrangement,
ketones 1a,25 2a,26 3a,27 4a28 and 5a29 were prepared according to
the literature procedures as precursors to the oximes (Fig. 1). Ke-
tones were specifically selected for study to probe the feasibility
of using both pyranoside and furanoside derived oximes, as well
as to allow the oxime functionality to be incorporated at differing
positions within the glycopyranoside, in order to ultimately access
different isomeric lactams. In addition, a range of protecting groups
was incorporated within the substrates to probe the compatibility
of the reagents required to effect the Beckmann rearrangement
with the substrates themselves.
Due to the instability of the ketones 1a, 2a, 3a, 4a and 5a to col-
umn chromatography, they were converted directly to their
respective oximes 1b, 2b, 3b, 4b and 5b (Fig. 2) by reaction with
hydroxylamine hydrochloride and sodium acetate, and were puri-
fied by column chromatography prior to attempting the Beckmann
With the growing interest in the potential use of functionalised
medium-large sized rings as glycosidase inhibitors and monosac-
⇑
Corresponding author. Fax: +44(0)118 378 4644.
E-mail address: h.m.i.osborn@rdg.ac.uk (H.M.I. Osborn).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.11.031

110
R. K. Benning et al. / Tetrahedron: Asymmetry 22 (2011) 109–116
O
O
SEt
NH
O
O
Ph
O
O
O
O
SEt
PivO
Ph
Ph
O
Ph
O
O
O
O
O
O
N
SEt
PivO
HO
O
O
PivO
O
O
O
1b
O
O
OMe
1c
O
2a26
3a27
1a25
O
O
O
O
O
O
OMe
OBn
O
MeO
O
O
O
O
Me
Me
HN
O
BnO
N
O
OH
O
N
BnO
Me
OMe
OMe
OH
2c
2b
4a28
5a29
Scheme 1. For reagents and conditions see Table 2.
Figure 1.
rearrangement. Oximes were isolated in excellent synthetic yields
as single isomers, whose configurations are as shown in Figure 2.
Whilst the configurations of the oxime bonds for 1b, 2b, 3b, 4b
and 5b could not be deduced by NMR spectroscopic analysis at this
stage of the programme, they could be deduced after the
Beckmann rearrangements were subsequently performed, by con-
sidering the regioselectivity of the rearrangements (vide infra).
in these cases elimination also occurred from the intermediate lac-
tams introducing unsaturation within the products 3c, 4c and 5c.
Given the high degree of functionality, and the incorporation of
stereogenic centres, within these products, the success of these
rearrangements was particularly encouraging. Moreover, although
the yield of formation of 3c and 4c was moderate, that for 5c was
excellent.
To account for the regioselectivities observed, migration was
presumed to occur from the C-3,4 bond for oxime 3b, the C-4,5
bond for oxime 4b and the C-1,2 bond for oxime 5b. Whilst the
structures of 3c and 5c were unequivocally deduced from analysis
of a range of spectroscopic data, the structure of 4c was tentatively
assigned as that shown in Scheme 2 via analysis of 1H and 13C NMR
and IR spectroscopy; the material proved insufficiently stable for a
complete set of spectroscopic data to be collected. Thus the 1H
NMR spectrum obtained for 4c illustrated that the singlet peak
resulting from the methoxy group in oxime 4b, which was present
at 3.44 ppm, was no longer present. Moreover, peaks were now
present at 8.55 and 8.90 ppm and these could be accounted for
by the formation of the imine and aldehyde functional groups,
respectively, as proposed by structure 4c. The corresponding car-
bons for these functional groups were present at 162.3 and
151 ppm, respectively. Finally, IR spectroscopic data showed
stretches at 1774 and 1715 cmꢀ1, which could be accounted for
O
O
O
Ph
O
Ph
O
O
O
O
O
SEt
PivO
O
N
N
N
O
OMe
HO
OH
OH
1b 73%
2b 79%
3b 72%
OMe
MeO
OBn
HO
N
Me
Me
O
O
O
BnO
O
N
BnO
Me
OMe
OMe
OH
4b 80%
5b 74%
Figure 2.
by the a,b-unsaturated system and the aldehyde functional group,
respectively.
A range of activators are available for the Beckmann rearrange-
ment,9–20 and, therefore, a range of activators and conditions were
initially screened to probe their effectiveness for promoting rear-
rangement of one furanoside oxime 2b and one pyranoside oxime
1b. Optimum conditions from this initial screen were then applied
to the wider range of oximes. The conditions used to optimise the
Beckmann rearrangement are summarised within Table 1.
The results summarised in Table 1 and Schemes 1 and 2 illustrate
that oximes derived from a range of protected carbohydrate
monomers have potential for access to functionalised six and seven-
membered ring lactams. The oxime functionality has been incorpo-
rated at various positions within the carbohydrate framework, with
good effect, and a range of protecting groups and anomeric groups
have been tolerated within the reaction. In this way, access to a
range of funtionalised lactams has been achieved in moderate to
very good yield and the further manipulation of these to afford
targets of interest for the inhibition of glycosidase enzymes is
currently under investigation within our laboratories.
From the screening conditions the only activator that proved
effective was TCT. This was, therefore, utilised to effect the Beck-
mann rearrangement of the wider range of oximes, as exemplified
in Table 2. Where a rearrangement was successfully accomplished,
the equivalents of TCT used, and reaction conditions employed,
were altered in an attempt to optimise the yields further. The re-
sults portrayed in Table 2 represent the optimum results obtained.
For substrates 1b and 2b, the Beckmann rearrangement oc-
curred with migration of the bond trans-to the oxime OH (i.e. the
C-1,2 bond for 1b and the C-3,4 bond for 2b) to afford the lactam
products 1c and 2c as single regioisomers in synthetically useful
yields (Scheme 1). A thioethyl group was tolerated at C-1, to afford
1c which is of potential use as a donor in subsequent glycosidation
reactions. For oxime 2b, the excellent regiocontrol was in contrast
to that previously reported using a molybdenum catalyst, where
the rearrangement resulted in a mixture of regioisomers, and the
regioisomer 2c was formed as the minor component.23
3. Conclusion
Oximes derived from pyranosides and furanosides have been
prepared in excellent yields. The Beckmann rearrangement of
these has then occurred with migration of the C–C bond trans to
the oxime OH to afford lactams with excellent regioselectivities.
The method has been effective for the rearrangement of oximes
displaying a range of protecting groups and anomeric groups,
and excellent compatibility of the protecting groups with the acti-
vator, TCT, has been observed. Whilst the yields are generally mod-
erate, in some cases excellent conversion yields have been
obtained, highlighting the synthetic value of this reaction.
For substrates 3b, 4b and 5b the rearrangements again pro-
ceeded to form in each case a single regioisomer of product, but

R. K. Benning et al. / Tetrahedron: Asymmetry 22 (2011) 109–116
111
Table 1
Substrate
Activation protocol
Result
O
O
O
p-TsOH or PPA, MeCN or DMF, rt to reflux
p-TsOH or PPA, MeCN or DMF, rt to reflux
P2O5 (1 or 2 equiv)/CF3SO3H (1 or 2 equiv), DMF, reflux
P2O5 (1 or 2 equiv)/CF3SO3H (1 or 2 equiv), DMF, reflux
p-TsCl, DMAP, pyr., rt then heat to 50 °C
p-TsCl, DMAP, pyr., rt then heat to 50 °C
TCT (1.2 equiv), DMF, rt o/n
Decomposition
O
O
O
O
N
O
O
OH
2b
Ph
Ph
Ph
Ph
O
O
SEt
SEt
SEt
SEt
PivO
N
Decomposition
HO
1b
O
O
O
Decomposition
N
O
OH
2b
O
O
O
PivO
N
Decomposition
HO
1b
O
O
O
Starting material returned in quantitative yield
N
O
OH
2b
O
O
Ph
O
O
O
O
SEt
PivO
PivO
Tosylated oxime 6 82% plus oxime 1b
N
N
HO
1b
TsO
6
O
O
O
O
O
O
O
O
Desired product formed, 62%
HN
N
O
OH
O
2c
2b
O
O
SEt
NH
O
O
O
PivO
Ph
O
N
Desired product formed, 42%
TCT (1.2 equiv), DMF, rt o/n
HO
1b
PivO
O
1c
O
O
O
NCS/PPh3, DCM rt to reflux
Starting material returned in quantitative yield
O
N
O
OH
2b
(continued on next page)

112
R. K. Benning et al. / Tetrahedron: Asymmetry 22 (2011) 109–116
Table 1 (continued)
Substrate
Activation protocol
Result
O
Ph
O
O
SEt
PivO
N
NCS/PPh3, DCM rt to reflux
Starting material returned in quantitative yield
HO
1b
O
O
O
O
O
O
Oxime carbonate 7 formed in 54% yield but no
rearrangement occurred
O
O
ClCO2Et, pyr., DCM, 2.5 h then BF3ꢂOEt2, DCM, rt, 20 h
N
N
O
O
OH
OCO2Et
7
2b
O
O
Ph
O
SEt
PivO
N
ClCO2Et, pyr., DCM, 2.5 h then BF3ꢂOEt2, DCM, rt, 69 h
Decomposition
HO
1b
O
O
O
Microwave irradiation with or without BiCl3 at
temperatures ranging from 30 to 120 °C
for up to 10 min
Starting material returned
O
N
O
OH
2b
O
O
Ph
O
SEt
PivO
Microwave irradiation with or without BiCl3
at temperatures ranging from 30 to 120 °C for
up to 10 min
N
Starting material returned
HO
1b
acid reagent (25:1 EtOH/H2SO4). Flash chromatography was car-
ried out using Merck silica gel 60 (40–63 m particle size) using
4. Experimental
l
1H NMR spectra were recorded in either chloroform-d or MeOH-
d at 250 MHz on a Bruker DPX-250 FT-NMR spectrometer or at
400 MHz on a Bruker AMX-400 FT-NMR spectrometer. Chemical
shifts (d) are quoted in parts per million (ppm) using the following
abbreviations: s (singlet); d (doublet); t (triplet); q (quartet); sxt
(sextet); app. t (apparent triplet); m (multiplet); bs (broad singlet);
bm (broad multiplet). Coupling constants (J values) are expressed
in Hertz to the nearest 0.5 Hz. 13C NMR spectra were recorded on
the same spectrometers described above at 63 MHz or 100 MHz
in chloroform-d or MeOH-d. Chemical shifts are reported in parts
per million (ppm). Infrared spectra were recorded as thin films
between sodium chloride plates on a Perkin–Elmer Paragon 1000
FT-IR spectrometer. The absorptions are stated in wavenumbers
(cmꢀ1) and the abbreviations used to depict the degree of absorp-
tion are: w (weak); m (medium); s (strong); br (broad). Melting
points were determined using an electrothermal digital heated
metal block apparatus and are uncorrected. Mass spectrometry
data were recorded using a Fisons VG Autospec mass spectrometer
using chemical ionisation (C.I.). Molecular ions and fragment ions
are reported as mass/charge (m/z) ratios. Optical rotation measure-
ments were recorded using a Perkin–Elmer 341 polarimeter at the
sodium D line (589 nm) in CHCl3 or MeOH and are quoted in units
of 10ꢀ1 deg cm2 gꢀ1. Thin layer chromatography (TLC) was per-
formed on Merck aluminium backed plates coated with 0.2 mm
Silica Gel 60 F254. The spots were visualised using UV light
(254 nm) or by spray-head development using an ethanol–sulfuric
head pressure by means of bellows. Beckmann rearrangement
investigations under microwave conditions were performed using
a CEM Discover 100 W microwave reactor. Anhydrous conditions
for reactions were achieved using oven-dried glassware prior to
use, anhydrous solvents and using an atmosphere of nitrogen or ar-
gon. Anhydrous solvents (acetonitrile, dichloromethane, diethyl
ether, N,N-dimethylformamide, dimethyl sulfoxide, methanol and
pyridine) were bought from Aldrich as sure-sealed bottles. Anhy-
drous THF was obtained by distillation over Na metal. All chemi-
cals were obtained from Sigma–Aldrich, Acros, Fluka or Lancaster
chemical suppliers.
4.1. Ethyl 2-deoxy-2-hydroxylimine-3-O-pivaloyl-4,6-O-
benzylidene-1-thio-a-D
-glucopyranoside 1b25
Ketone 1a25 (2.77 g, 7.01 mmol) was solubilised in ethanol
(10 mL). This was added to a solution of sodium acetate (1.73 g,
21.0 mmol) and hydroxylamine hydrochloride (1.46 g, 21.1 mmol)
in water (10 mL) at 54 °C. The reaction mixture was stirred at
approximately this temperature for a total of 2 h and then the reac-
tion mixture was left to stir at room temperature overnight. The
reaction mixture was washed with distilled water (30 mL) and ex-
tracted with DCM (3 ꢁ 30 mL). The organic layers were combined,
dried over MgSO4, filtered and concentrated in vacuo. The crude
product was then purified by column chromatography (5.5:1
hexane/ethyl acetate, with 1% NEt3) to give pure 1b as a white

R. K. Benning et al. / Tetrahedron: Asymmetry 22 (2011) 109–116
113
Table 2
Oxime Substrate
Product
Activator
Conversion yield (%)
Ph
O
SEt
NH
O
O
O
O
SEt
PivO
Ph
N
O
TCT (1.2 equiv), DMF, rt o/n
45
62
HO
PivO
O
1b
1c
O
O
O
O
O
O
O
O
TCT (1.2 equiv), DMF, rt o/n
HN
O
N
O
O
OH
O
2c
2b
Ph
O
O
O
O
Ph
O
TCT (1.2 equiv), DMF, rt o/n
42
39
N
OMe
HN
OH
O
3c
3b
OBn
O
OBn
HO
N
BnO
N
BnO
TCT (8.4 equiv), DMF, rt o/n
O
O
OMe
4b
BnO
OBn
4c
OMe
H
O
MeO
O
Me
Me
N
O
O
TCT (2.04 equiv), DMF, 50 °C, 2 h
78
O
Me
N
O
O
MeO
OMe
OH
MeO
5c
5b
OMe
O
O
O
O
Ph
O
O
O
Ph
Ph
O
O
HN
3c
N
HN
OMe
O
OH
3b
O
OBn
OBn
OBn
HO
OBn
O
OBn
O
N
N
HO
N
HN
- MeOH
OMe
O
O
OMe
O
O
BnO
BnO
BnO
OMe
BnO
OBn
BnO
OBn
4b
4c
H
O
OMe
NH
O
OMe
MeO
O
N
O
- MeOH
O
Me
O
Me
O
O
O
MeO
MeO
N
O
O
MeO
Me
MeO
OMe
OH
5c
5b
Scheme 2. For reagents and conditions see Table 2.
foam (2.17 g, 73%). ½a D20
ꢃ
¼ þ88:4 (c 1.0, CHCl3) {lit.25
½
a 2D0
ꢃ
¼ þ137:6
1097 s (C–O), 1004 m (C@N), 913 s, 867 m, 799 w, 733 s, 698 s
(Ar), 649 s (C–S); 1H NMR (CDCl3): d 1.16 (9H, s, (CH3)3CO), 1.26
(3H, t, J 7.5, SCH2CH3), 2.60–2.77 (2H, m, SCH2CH3), 3.53–3.74
(2H, m, H-6, H-4), 4.27–4.34 (1H, m, H-6), 4.42–4.49 (1H, m,
(c 0.5, CHCl3)}; IR (thin film): m
(cmꢀ1): 3367 br (O–H), 3068 w,
2974 s (C–H), 2931 w, 2873 w, 2252 m, 1739 s (C@O), 1480 s,
1457 s, 1398 s, 1370 s, 1313 m (C–H), 1278 s, 1216 m, 1136 s,

114
R. K. Benning et al. / Tetrahedron: Asymmetry 22 (2011) 109–116
H-5), 5.50 (1H, s, PhCH), 5.75 (1H, d, J 6.5, H-3), 6.24 (1H, s, H-1),
7.27–7.39 (5H, m, Ar-H); 13C NMR (CDCl3): d 15.09 (SCH2CH3),
21.48 (SCH2CH3), 26.84 ((CH3)3CCO), 39.23 (CH3)3CCO), 60.86
(C-5), 65.31 (C-6), 66.67 (C-3), 66.86, 69.89, 69.97, 70.55, 74.37
(C-1), 80.42 (C-4), 101.38 (PhCH), 126.40 (2 ꢁ Ar-C), 128.68
(2 ꢁ Ar-C), 129.39 (Ar-C), 137.41 (Ar-C), 151.24 (C-2), 152.35,
176.83 ((CH3)3CCO); m/z (CI): 409 ([M]+, 8%), 38 (100), 307 (25),
242 (18), 149 (12). Found [M]+, 409.1543 C20H27O6NS requires
[M]+, 409.1559.
216 (56), 140 (14), 101 (76). Found [M+H]+, 274.1291. C12H20NO6
requires [M+H]+, 274.1291.
4.4. (2R, 5S, 6S, 7R) 5,6:7,8-Di-O-isopropylidene-[1,3]oxazinan-4-
one 2c
2,4,6-Trichloro[1,3,5]triazine (0.224 g, 1.21 mmol) was solubi-
lised in anhydrous DMF (0.8 mL). The complete disappearance of
triazine was followed by TLC. Then a solution of 1,2:5,6-di-O-isopro-
pylidene-a-D-ribo-hexofuranos-3-ulose 2b (0.318 g, 1.16 mmol) in
4.2. (2S, 5S, 6S, 7R) 2-Thioethyl-5-O-pivaloyl-6,8-O-benzylidene-
[1,3]oxazepan-4-one 1c
anhydrous DMF (8 mL) was added and the reaction stirred under
N2 at rt for 44 h. The DMF was removed azeotropically using toluene
and to the resulting residue were added H2O (30 mL) and DCM
(30 mL). The two phases were separated and the organic phase
was washed successively with satd NaHCO3 (20 mL), 1% HCl
(20 mL) and brine (20 mL). The organic phase was dried over MgSO4,
filtered and concentrated in vacuo. The crude product was purified
by column chromatography (2:1 v/v hexane/EtOAc) to yield pure
2,4,6-Trichloro[1,3,5]triazine (45.9 mg, 0.249 mmol) was solubi-
lised in anhydrous DMF (0.5 mL) and the mixture was stirred for
30 min. Then ethyl 2-deoxy-2-hydroxylimine-3-O-pivaloyl-4,6-O-
benzylidene-1-thio-a-D-glucopyranoside 1b (0.100 g, 0.244 mmol)
in anhydrous DMF (1.5 mL) was added and the reaction stirred at
rt under N2 for 16 h. The solvent was removed azeotropically in va-
cuo using toluene. To the residue was added DCM (30 mL), H2O
(10 mL) and satd NaHCO3 (15 mL). The two phases were separated
and the aqueous phase re-extracted with DCM (3 ꢁ 20 mL). The
combined organic phases were dried over MgSO4, filtered and con-
centrated in vacuo. The crude product was purified by column chro-
matography (100:4 v/v DCM/MeOH) to give pure oxazepan-4-one
2c as a yellow oil (0.197 g, 62%). ½a D20
¼ þ1:2 (c 0.53, CHCl3); IR (thin
ꢃ
film): m
(cmꢀ1): 3384 br (N–H), 2940 m (C–H), 2506 m, 1736 w, 1654
w (C@O), 1457 w, 1377 w, 1255 w, 1164 w, 1074 s, 1035 s, 886 w; 1H
NMR (CDCl3): d 1.32 (3H, s, CH3), 1.35 (3H, s, CH3), 1.42 (3H, s, CH3),
1.53 (3H, s, CH3), 4.01–4.14 (2H, m, 2 ꢁ H-8), 4.17–4.28 (1H, m, H-7),
4.54 (1H, d, J 3.5, H-5), 5.36 (1H, d, J 2.5, H-2), 5.90 (1H, d, J 3.5, H-6),
8.11 (1H, s, NH); 13C NMR (CDCl3): d 25.56 (CH3), 26.58 (CH3), 27.08
(CH3), 27.30 (CH3), 67.73 (C-8), 72.62 (C-7), 76.20 (C-2), 83.56 (C-5),
105.44 (C-6), 109.90 (C(CH3)2), 112.84 (C(CH3)2), 159.96 (C-3).
1c as a colourless oil (44.5 mg, 45%). ½a D20
¼ þ55:4 (c 0.55, CHCl3);
ꢃ
IR (thin film):
m
(cmꢀ1): 3348 br (N–H), 2974 m (C–H), 1740 s
(C@O), 1648 m (C@O), 1594 m, 1480 m, 1456 m, 1370 m, 1282 m,
1178 m, 1154 m, 1098 s, 1077 m, 979 m, 752 m, 698 m; 1H NMR
(CDCl3): d 1.29 (9H, s, (CH3)3CO), 1.30–1.38 (3H, m, SCH2CH3),
2.71–2.78 (2H, m, SCH2CH3), 3.81 (1H, t, J 10.0, H-8), 3.97 (1H, app.
t, J 10.0, H-6), 4.28–4.41 (2H, m, H-8, H-7), 5.58 (1H, s, PhCH), 5.86
(1H, d, J 9.5, H-5), 6.50 (1H, s, H-2), 7.33–7.39 (3H, m, Ar-H), 7.43
(2H, m, Ar-H), 8.50 (1H, s, NH); 13C NMR (CDCl3): d 15.55 (SCH2CH3),
26.47 (SCH2CH3), 27.49 ((CH3)3CCO), 39.26 (CH3)3CCO), 64.35 (C-7),
68.96 (C-8), 69.06 (C-5), 76.20 (C-2), 79.84 (C-6), 101.58 (PhCH),
126.35 (Ar-C), 126.42 (Ar-C), 128.62 (2 ꢁ Ar-C), 129.43 (Ar-C),
137.34 (Ar-C), 163.93 (C-4), 177.52 ((CH3)3CCO); m/z (CI): 410
([M+H]+, 18%), 348 (100), 307 (44), 242 (41). Found [M+H]+,
410.1625. C20H28O6NS requires [M+H]+, 410.1637.
4.5. Methyl 4,6-O-benzylidene-2-deoxy-a-D-erythro-hexopyran-
oside-3-ulose oxime 3b32
A solution of hydroxylamineꢂHCl (52.1 mg, 0.764 mmol) and
NaOAc (56.3 mg, 0.686 mmol) in distilled H2O (0.5 mL) was heated
to 54 °C. To this was added methyl 4,6-O-benzylidene-2-deoxy-
a-D-erythro-hexopyranosid-3-ulose 3a (60.1 mg, 0.227 mmol) in
ethanol (4.5 mL) and the reaction heated at 54 °C for 7.5 h. The eth-
anol was removed in vacuo and to the residue was added DCM
(20 mL) and H2O (20 mL). The two phases were separated and
the aqueous phase was re-extracted with DCM (3 ꢁ 20 mL). The
combined organic phases were dried over MgSO4, filtered and con-
centrated in vacuo. The crude product was purified by column
chromatography (7:1 v/v DCM/EtOAc + 1% NEt3) to yield pure
oxime 3b as a white solid (45.9 mg, 72%). Mp 208.6–209.7 (lit.33
4.3. 1,2:5,6-Di-O-isopropylidene-a-D-ribo-hexofuranos-3-ulose
oxime 2b30
208 °C); ½a 2D0
ꢃ
¼ þ86:8 (c 0.5, CHCl3) (lit.33
½
a 2D3
ꢃ
¼ þ202 (c 1.0,
HydroxylamineꢂHCl (0.781 g, 11.2 mmol) and NaOH (0.420 g,
10.5 mmol) were dissolved in EtOH (25 mL) and the resulting NaCl
filtered off. To this prepared solution was added ketone 2a
(0.4473 g, 1.73 mmol) and the reaction was stirred under N2 at
room temperature for 70 h. The reaction was then concentrated
in vacuo. To the resulting white solid was added H2O (6 mL) and
DCM (30 mL). The two phases were separated and the aqueous
phase re-extracted with DCM (5 ꢁ 30 mL). The combined organic
phases were dried over MgSO4, filtered and concentrated in vacuo.
The crude product was purified by column chromatography (3:2 v/v
hexane/EtOAc) to yield pure oxime 2b as a white solid (0.3760 g,
CHCl3)); IR (thin film): m
(cmꢀ1): 3243 m (O–H), 2906 m (C–H),
2361 m, 2343 m, 1452 w, 1403 w, 1379 w, 1278 w, 1210 m,
1128 s, 1094 s, 1054 s, 988 s, 915 m, 852 w, 748 m, 697 m, 643
m; 1H NMR (CDCl3): d 2.25 (1H, dd, J 4.5, 15.0, H-2, eq.), 3.37
(3H, s, OCH3), 3.57 (1H, d, J 15.0, H-2, ax.), 3.84 (1H, t, J 10.0, H-
6), 3.99–4.13 (1H, m, H-5), 4.23 (1H, d, J 9.5, H-4), 4.31 (1H, dd, J
4.5, 10.0, H-6), 4.92 (1H, d, J 4.5, H-1), 5.62 (1H, s, PhCH), 7.32–
7.38 (3H, m, Ar-H), 7.40–7.52 (2H, m, Ar-H), 8.77 (1H, br s,
NOH); 13C NMR (CDCl3): d 30.64 (C-2), 55.30 (OCH3), 65.17 (C-5),
69.85 (C-6), 78.42 (C-4), 98.95 (C-1), 102.62 (PhCH), 126.78
(2 ꢁ Ar-C), 128.67 (2 ꢁ Ar-C), 129.51 (Ar-C), 137.31 (Ar-C),
149.59 (C-3); m/z (CI): 280 ([M+H]+, 11%), 247 (24), 181 (12), 149
(100). Found [M+H]+, 280.1174. C14H18NO5 requires [M+H]+,
280.1185.
79%). Mp 97.2–101.0; (lit.31 103–104 °C); ½a 2D0
ꢃ
¼ þ173:3 (c 0.9,
CHCl3) {lit.31
½
a 2D1
ꢃ
¼ þ183 (c 0.6, CHCl3)}; IR (thin film):
m
(cmꢀ1):
3370 br (OH), 2988 s (C–H), 2938 m (C–H), 1457 m (C–N), 1374
s (CH3), 1215 s, 1158 s, 1071 s (C–O), 1023 s, 951 s, 877 s, 732
w; 1H NMR (CDCl3): d 1.37 (3H, s, CH3), 1.42 (3H, s, CH3), 1.44
(3H, s, CH3), 1.52 (3H, s, CH3), 3.99–4.07 (2H, m, 2 ꢁ H-6), 4.29–
4.36 (1H, m, H-5), 4.77 (1H, d, J 3.0, H-4), 5.29 (1H, d, J 4.5, H-2),
6.02 (1H, d, J 4.5, H-1); 13C NMR (CDCl3): d 25.58 (CH3), 26.40
(CH3), 27.70 (CH3), 27.92 (CH3), 65.80 (C-6), 74.57 (C-2), 77.08
(C-5), 77.69 (C-4), 105.10 (C-1), 110.68 (C(CH3)2), 114.16
(C(CH3)2), 157.98 (C-3); m/z (CI): 274 ([M+H]+, 100%), 258 (59),
4.6. (2R, 3R) 3,8-O-Benzylidene-[1,4]oxazepin-4-one 3c
2,4,6-Trichloro[1,3,5]triazine (31.0 mg, 0.168 mmol) was added
to anhydrous DMF (0.5 mL). After the formation of a white solid,
the reaction was monitored by TLC until complete disappearance
of the triazine starting material. Then a solution of methyl 4,6-O-
benzylidene-2-deoxy-a-D-erythro-hexopyranoside-3-ulose oxime

R. K. Benning et al. / Tetrahedron: Asymmetry 22 (2011) 109–116
115
3b (45.9 mg, 0.164 mmol) in anhydrous DMF (1 mL) was added
and the reaction was stirred under N2 at rt for 20 h. The DMF
was azeotropically removed in vacuo using toluene. Next, DCM
(20 mL) and H2O (7 mL) were added to the residue and the two
phases separated. The organic phase was washed successively with
satd NaHCO3 (7 mL), 1% HCl (7 mL) and then with brine (7 mL). The
organic phase was dried over MgSO4, filtered and concentrated in
vacuo. The crude product was purified by column chromatography
(3:2 v/v hexane/EtOAc) to yield pure rearranged product 3c as a
(250 MHz, CDCl3): 1.22 (3H, d, J 6.5, C(6)H), 1.24 (3H, s, CH3),
1.29 (3H, s, CH3), 3.17 (3H, s, OCH3), 3.21 (3H, s, OCH3), 3.36
(3H, s, OCH3), 3.40 (1H, app. t, J 10.0, C(4)H), 3.87–3.98 (1H, m,
C(5)H), 4.59 (1H, d, J 10.0, C(3)H), 5.72 (1H, s, C(1)H), 8.31 (1H,
br. s, N@OH); dC (63 MHz, CDCl3): 16.8 (CH3), 18.0 (CH3), 18.1
(CH3), 48.1 (OCH3), 48.8 (OCH3), 55.4 (OCH3), 66.6 (C5), 67.6 (C3),
74.1 (C4), 91.5 (C1), 100.1 (C), 100.4 (C), 150.9 (C2); m/z (ESI)
328 ([M+Na]+, 100%). Found [M+Na]+ 328.1361, C13H23N1Na1O7
requires 328.1367.
white solid (16 mg, 42%). Mp 180.7–183.3; ½a D20
¼ þ49:9 (c 0.3,
ꢃ
CHCl3); IR (thin film):
m
(cmꢀ1): 3170 s (N–H), 3055 m, 2891 s (C–
4.9. (20S,30S,7R)-Methyl 2,3-O-(20,30-dimethoxybutane-20,30-diyl)-
H), 2252 w, 1645 m (C@O), 1603 s, 1469 m, 1452 m, 1407 m,
1379 m, 1262 s, 1229 s, 1137 s, 1096 s, 1059 m, 1030 m, 987 s,
923 m, 784 m, 751 s, 731 s, 714 s, 696 s, 642 s, 502 m; 1H NMR
(CDCl3): d 3.94 (1H, t, J 10.5, H-8), 4.13 (1H, sxt, J 4.8, H-2), 4.45
(1H, dd, J 4.8, 10.5, H-8), 4.55 (1H, d, J 11.0, H-3), 5.66 (1H, s, PhCH),
6.00 (1H, d, J 6.0, H-6), 6.71 (1H, d, J 6.0, H-7), 7.32–7.41 (3H, m, Ar-
H), 7.48–7.54 (2H, m, Ar-H); 13C NMR (CDCl3): d 68.67 (C-8), 71.73
(C-2), 74.60 (C-3), 94.72 (C-6), 102.25 (PhCH), 126. 73 (2 ꢁ Ar-C),
128.70 (2 ꢁ Ar-C), 129.62 (Ar-C), 137.01 (Ar-C), 146.26 (C-5),
151.23 (C-7); m/z (CI): 247 ([M]+, 100%), 181 (69), 131 (55). Found
[M]+, 247.0856. C13H13O4N requires [M]+, 247.0845.
[1,3]-oxazepin-4-one 5c
At first, TCT (123 mg, 0.669 mmol) was stirred in anhydrous
DMF (0.5 mL) for 2.5 h. A solution of 5b (108 mg, 0.334 mmol) in
anhydrous DMF (1.5 mL) was added and the reaction was heated
to 45–50 °C for 2 h. The solution was stirred for 21 h at room tem-
perature and then the contents were partitioned between CH2Cl2
(20 mL) and water (20 mL). The aqueous phase was further ex-
tracted with CH2Cl2 (2 ꢁ 20 mL). The combined organic phases
were dried (MgSO4), filtered and concentrated in vacuo. Flash col-
umn chromatography on silica gel (2:1 Petroleum ether (40–60°)/
Et2O) allowed the isolation of 5c as a colourless syrup (71.6 mg,
4.7. Methyl 2,3,6-tri-O-benzyl-
a-D
-xylo-pyranoside-4-ulose
78%). ½a 2D0
ꢃ
¼ ꢀ362 (c 0.87, CHCl3); mmax (NaCl disc/cmꢀ1) 2950 (s,
oxime 4b
CH), 1731 (s, C@O), 1453 (s, C@N), 1379 (s, CH3), 1177 (s, C–O),
1146 (s, C–N), 1036 (s, C–O); dH (250 MHz, CDCl3): 1.21 (3H, s,
CH3), 1.26 (3H, s, CH3), 1.34 (3H, d, J 6.5, OCH3), 3.20 (3H, s,
OCH3), 3.23 (3H, s, OCH3), 3.92 (1H, dd, J 10.0, 5.0, C(6)H), 4.44
(1H, d, J 10.0, C(5)H), 5.09 (1H, quin, J 5.0, C(7)H), 8.01 (1H, s,
C(2)H); dC (63 MHz, CDCl3): 16.5 (C8), 17.4 (CH3), 17.7 (CH3),
48.7 (OCH3), 49.2 (OCH3), 59.6 (C5), 69.4 (C7), 70.4 (C6), 99.6 (C),
99.8 (C), 116.3 (C4), 160.5 (C2); m/z (ESI) 296 ([M+Na]+, 100%).
Found [M+Na]+ 296.1089, C12H19N1NaO6 requires 296.1105.
At first, NaOAc (537 mg, 6.55 mmol) was solubilised in distilled
water (20 mL) and hydroxylamine hydrochloride (457 mg,
6.57 mmol) was added. The contents were heated to 54 °C and
4a (1.01 g, 2.18 mmol) in EtOH (20 mL) was added. The solution
was stirred under argon for 2 h at 77 °C, then at room temperature
overnight. The contents were then partitioned between water
(40 mL) and CH2Cl2 (40 mL). The aqueous phase was further ex-
tracted with CH2Cl2 (2 ꢁ 40 mL). The organic phase was dried
(MgSO4), filtered and concentrated in vacuo. Flash column chroma-
tography on silica gel (5:1 toluene/EtOAc) yielded 4b as a colour-
4.10. Ethyl 2-deoxy-2-hydroxylimine tosyl-3-O-pivaloyl-4,6-O-
benzylidene-1-thio-a-D-glucopyranoside 6
less oil (834 mg, 80%).½a D20
¼ þ59:7 (c 1.04, CHCl3); mmax (NaCl
ꢃ
disc/cmꢀ1) 3366 (br s, OH), 3030 (m, CH), 2916 (s, CH), 1497 (s,
C@C (arom)), 1454 (s, C@C (arom)), 1200 (s, C@N), 1123 (s, C–O),
1071 (s, C–O), 737 (s, CH (arom)), 698 (s, CH (arom)); dH
(400 MHz, CDCl3): 3.44 (3H, s, OCH3), 3.70 (1H, dd, J 10.5, 3.0,
C(6)H), 3.80 (1H, dd, J 10.5, 8.0, C(60)H), 3.87 (1H, t, J 3.5, C(2)H),
4.12 (1H, d, J 3.5, C(3)H), 4.31 (1H, d, J 12.0, OCH2Ph), 4.54 (1H,
d, J 11.5, OCH2Ph), 4.59–4.64 (4H, m, OCH2Ph), 4.87 (1H, d, J 4.0,
C(1)H), 5.26 (1H, dd, J 8.0, 2.5, C(5)H), 7.21–7.34 (15H, m, Ph),
8.82 (1H, s, NOH); dC (101 MHz, CDCl3): 56.5 (OCH3), 67.1 (C5),
69.2 (C6), 70.1 (OCH2Ph), 72.0 (OCH2Ph), 73.1 (OCH2Ph), 76.6
(C3), 78.8 (C2), 96.9 (C1), 127.5–128.3 (ArC), 137.4–138.0 (ArC),
152.9 (C@NOH); m/z (CI) 478 ([M+H]+, 77%), 477 ([M]+, 6%), 446
(100), 400 (36). Found [M]+ 477.2172, C28H31NO6 requires
477.2151.
Ethyl
dene-1-thio-
2-deoxy-2-hydroxylimine-3-O-pivaloyl-4,6-O-benzyli-
-glucopyranoside 1b (97.0 mg, 0.237 mmol) was
a-D
solubilised in anhydrous pyridine (0.8 mL). p-Toluenesulfonyl
chloride (0.116 g, 0.608 mmol) and DMAP (1.8 mg, 0.015 mmol)
were added and the reaction stirred under N2 at rt for 20 h. The
pyridine was azeotropically removed in vacuo using toluene. The
crude product was purified by column chromatography (100:1 v/v
DCM/EtOAc) to yield pure tosylated oxime 6 as a white foam
(0.1096 g, 82%).
m
½
a 2D0
ꢃ
¼ þ1:9 (c 0.1, MeOH); IR (thin film):
(cmꢀ1): 2924 s (C–H), 2856 s (C–H), 1720 w (C@O), 1462 m,
1403 w, 1377 w, 1174 m, 1126 m, 1034 m, 1012 m, 684 m; 1H
NMR (CDCl3): d 1.20 (9H, s, (CH3)3CO), 1.33 (3H, t, J 7.5, SCH2CH3),
2.44 (1H, s, CH3), 2.65–2.77 (2H, m, SCH2CH3), 3.82–3.93 (2H, m, H-
6, H-4), 4.27–4.35 (2H, m, H-6, H-5), 5.55 (1H, s, PhCH), 5.72 (1H, d,
J 9.5, H-3), 6.30 (1H, s, H-1), 7.30–7.44 (7H, m, Ar-H), 7.75–7.79
(2H, m, Ar-H); 13C NMR (CDCl3): d 15.45 (SCH2CH3), 22.15 (CH3),
26.66 (SCH2CH3), 27.40 ((CH3)3CCO), 39.14 (CH3)3CCO), 64.33 (C-
5), 68.63 (C-3), 68.66 (C-6), 76.94 (C-1), 79.35 (C-4), 101.57 (PhCH),
126.28 (2 ꢁ Ar-C), 128.64 (2 ꢁ Ar-C), 129.22 (2 ꢁ Ar-C), 129.49 (Ar-
C), 130.05 (2 ꢁ Ar-C), 132.32 (Ar-C), 137.06 (Ar-C), 145.90 (Ar-C),
158.57 (C-2), 176.81 ((CH3)3CCO).
4.8. (20S,30S)-Methyl 2,3-O-(20,30-dimethoxybutane-20,30-diyl)-
L-lyxo-hexopyranoside-2-ulose oxime 5b
a-
At first, NH2OHꢂHCl (400 mg, 5.75 mmol) was added to NaOH
(92.2 mg, 2.30 mmol) in EtOH (10 mL). Distilled water (2 mL) was
then added followed by 5a (275 mg, 0.897 mmol). The reaction
was stirred at room temperature for 20 h, then it was partitioned
between water (30 mL) and CH2Cl2 (30 mL). The aqueous phase
was further extracted with CH2Cl2 (2 ꢁ 30 mL) and the organic
phase was dried (MgSO4), filtered and concentrated in vacuo to
yield crude 5b as a colourless solid (215 mg, 74%) which was used
4.11. 1,2:5,6-Di-O-isopropylidene-a-D-ribo-hexofuranos-3-(O-
ethyl methanoate)ulose 7
1,2:5,6-Di-O-isopropylidene-a-D-ribo-hexofuranos-3-ulose 2b
without further purification. ½a D20
ꢃ
¼ ꢀ212:9 (c 1.03, CHCl3); mmax
(0.688 g, 2.52 mmol) was solubilised in anhydrous DCM (10 mL).
To this was added anhydrous pyridine (0.20 mL, 2.52 mmol) fol-
lowed by the dropwise addition of ethyl chloroformate (0.24 mL,
(NaCl disc/cmꢀ1) 3291 (br m, OH), 2944 (s, CH), 1450 (m, C@N),
1376 (s, CH3), 1141 (s, C–O), 1111 (s, C–O), 1037 (s, C–O); dH

116
R. K. Benning et al. / Tetrahedron: Asymmetry 22 (2011) 109–116
5. Trabocchi, A.; Menchi, G.; Guarna, F.; Machetti, F.; Scarpi, D.; Guarna, A. Synlett
2006, 331.
6. Westermann, B.; Diedrichs, N.; Krelaus, R.; Walter, A.; Gedrath, I. Tetrahedron
2.52 mmol). The reaction was stirred at rt under N2 for 3.5 h. TLC
analysis showed the reaction to be complete. The reaction was di-
luted with DCM (30 mL) and H2O (35 mL). The two phases were
separated and the aqueous phase was re-extracted with DCM
(3 ꢁ 35 mL). The combined organic phases were dried over MgSO4,
filtered and concentrated in vacuo. The crude product was purified
by column chromatography (3:2 v/v hexane/EtOAc) to yield pure
Lett. 2004, 45, 5983.
7. Abramski, W.; Urban´ czky-Lipkowska, Z.; Chmielewski, M. J. Carbohydr. Chem.
1997, 16, 63.
8. Cordero-Vargas, A.; Quiclet-Sire, B.; Zard, S. Z. Bioorg. Med. Chem. 2006, 14,
6165.
9. Savarin, C. G.; Grisé, C.; Murry, J. A.; Reamer, R. A.; Hughes, D. L. Org. Lett. 2007,
9, 981.
10. Torisawa, Y.; Aki, S.; Minamikawa, J. Bioorg. Med. Chem. Lett. 2007, 17, 453.
11. Wang, B.; Gu, Y.; Luo, C.; Yang, T.; Yang, L.; Suo, J. Tetrahedron Lett. 2004, 45,
3369.
12. Chandrasekhar, S.; Gopalaiah, K. Tetrahedron Lett. 2003, 44, 755.
13. Torisawa, Y.; Nishi, T.; Minamikawa, J. Bioorg. Med. Chem. Lett. 2007, 17, 448.
14. Zhu, M.; Cha, C.; Deng, W.-P.; Shi, X.-X. Tetrahedron Lett. 2006, 47, 4861.
15. Anilkumar, A.; Chandrasekhar, S. Tetrahedron Lett. 2000, 41, 5427.
16. Sato, H.; Yoshioka, H.; Izumi, Y. J. Mol. Catal. A.: Chem. 1999, 149, 25.
17. Guo, S.; Deng, Y. Catal. Commun. 2005, 6, 225.
18. Thomas, B.; Sugunan, S. Microporous Mesoporous Mater. 2006, 96, 55.
19. Li, Z.; Ding, R.; Lu, Z.; Xiao, S.; Ma, X. J. Mol. Catal. A.: Chem. 2006, 250, 100.
20. Blotny, G. Tetrahedron 2006, 62, 9507.
21. De Luca, L.; Giacomelli, G.; Porcheddu, A. J. Org. Chem. 2002, 67, 6272.
22. (a) Pandey, G.; Dumbre, S. G.; Khan, M. I.; Shabab, M.; Puranik, V. G. Tetrahedron
Lett. 2006, 47, 7923; (b) Brandi, A.; Cicchi, S.; Cordero, F. M. Chem. Rev. 2008,
108, 3988; (c) Li, H. Q.; Liu, T.; Zhang, Y. M.; Favre, S.; Bello, C.; Vogel, P.;
Butters, T. D.; Oikonomakos, N. G.; Marrot, J.; Bleriot, Y. ChemBioChem 2008, 9,
253.
oxime carbonate
7
as
a
white sticky solid (0.4718 g, 54%).
½
a 2D0
ꢃ
¼ þ192:0 (c 1.0, CHCl3); IR (thin film):
m
(cmꢀ1): 2989 m (C–
H), 1784 s (C@O), 1458 w, 1373 m, 1236 s, 1158 m, 1066 m,
1027 m, 927 w, 854 m, 776 w, 740 w; 1H NMR (CDCl3): d 1.35
(3H, s, CH2CH3), 1.40 (3H, s, CH3), 1.44 (3H, s, CH3), 1.48 (3H, s,
CH3), 1.52 (3H, s, CH3), 3.95–4.04 (2H, m, 2 ꢁ H-6), 4.35 (2H, q, J
1.5, 7.0, CH2CH3), 4.39–4.47 (1H, m, H-5), 4.97 (1H, dd, J 1.5, 2.5,
H-4), 5.23 (1H, dd, J 1.0, 4.5, H-2), 6.04 (1H, dd, J 2.5, 4.5, H-1);
13C NMR (CDCl3): d 14.65 (CH2CH3), 25.67 (CH3), 26.33 (CH3),
27.78 (CH3), 28.08 (CH3), 64.74 (C-6), 65.72 (CH2CH3), 76.47 (C-
2), 77.94 (C-5), 78.29 (C-4), 105.26 (C-1), 110.52 (C(CH3)2),
114.88 (C(CH3)2), 153.61 (C-3), 165.67 (C@O); m/z (CI) 346
([M+H]+, 20%), 331 (13), 330 (82), 256 (14), 198 (100), 126 (40).
Found [M+H]+, 346.1492. C15H23NO8 requires [M+H]+, 346.1502.
23. Dongare, M. K.; Bhagwat, V. V.; Ramana, C. V.; Gurjar, M. K. Tetrahedron Lett.
2004, 45, 4759.
24. Tronchet, J. M. J.; Tronchet, J. F.; Rachidzadeh, F.; Barbalat-Rey, F. Carbohydr.
Res. 1988, 181, 97.
25. Drew, M. G. B.; Ennis, S. C.; Gridley, J. J.; Osborn, H. M. I.; Spackman, D. G.
Tetrahedron 2001, 57, 7919.
26. Garegg, P. J.; Samuelsson, B. Carbohydr. Res. 1978, 67, 267.
27. Alker, D.; Jones, N. D.; Taylor, M. G.; Wood, W. W. Tetrahedron Lett. 1991, 32, 1667.
28. Preuss, R.; Jung, K.-H.; Schmidt, R. R. Liebigs Ann. Chem. 1992, 4, 377.
29. Montchamp, J.-L.; Tian, F.; Hart, M. E.; Frost, J. W. J. Org. Chem. 1996, 61, 3897.
30. Hall, A.; Bailey, P. D.; Rees, D. C.; Rosair, G. M.; Wightman, R. H. J. Chem. Soc.,
Perkin Trans. 1 2000, 329.
Acknowledgements
We are grateful to the Department of Chemistry and the EPSRC
for a Ph.D. studentship to A.T., and to the University of Reading’s
RETF for a Ph.D. studentship to R.J.N.
References
1. Beckmann, E. Ber. 1886, 19, 988.
31. Lichtenthaler, F. W.; Jarglis, P. Tetrahedron Lett. 1980, 21, 1425.
32. Crugnola, A.; Lombardi, P.; Gandolfi, C.; Arcamone, F. Gazz. Chim. Ital. 1981, 111,
395.
2. Vasella, A. T.; Heightmann, T. D. Angew. Chem., Int. Ed. 1999, 38, 750.
3. Buser, S.; Vasella, A. Helv. Chim. Acta 2006, 89, 416.
4. Honda, T.; Hoshi, M.; Kanai, K.; Tsubuki, M. J. Chem. Soc., Perkin Trans. 1 1994,
2091.
33. Beynon, P. J.; Collins, P. M.; Overend, W. G. J. Chem. Soc. (C) 1969, 272.