An unusual observation in the rhodium carbenoids: [1,4]-migration in the sugar-derived α-diazo-β-ketoesters

Article abstract of DOI:10.1039/a908453c

In competition with [1,2]-migration, [2,3]-sigmatropic rearrangement and C-H insertion, product formation via an unusual [1,4]-migration is also found to be a prominent process in the rhodium carbenoids derived from sugar α-diazo-β-keto esters 2a-d. The R

Full text of DOI:10.1039/a908453c

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An unusual observation in the rhodium carbenoids: [1,4]-migration
in the sugar-derived ꢀ-diazo-ꢁ-ketoesters
Vijaya N. Desai, Nabendu N. Saha and Dilip D. Dhavale*
1
Department of Chemistry, Garware Research Centre, University of Pune, Pune - 411 007, India.
E-mail: ddd@chem.unipune.ernet.in
Received (in Cambridge, UK) 25th October 1999, Accepted 9th November 1999
In competition with [1,2]-migration, [2,3]-sigmatropic rearrangement and C–H insertion, product formation via
an unusual [1,4]-migration is also found to be a prominent process in the rhodium carbenoids derived from sugar
α-diazo-β-keto esters 2a–d.
Introduction
The rhodium()-catalysed reactions of α-diazocarbonyl com-
pounds and their applications in the selective formation of
polycyclic systems have received much attention over the years.1
In general, the rhodium carbenoids have been utilised in three
major reaction pathways which include (a) olefin cyclopropan-
ation, cyclopropenation and Buchner reaction, (b) X–H (X = C,
O, N, S, Si) insertion reactions, and (c) ylide formation. Thus,
for a given substrate several distinct possibilities are available
and the chemoselectivity of such processes is dependent on
steric, conformational, electronic factors and the nature of both
the substrate and the catalyst. Amongst rhodium()-catalysed
oxonium-ylide-formation reactions, the product derived from
either [2,3]-sigmatropic rearrangement2 or [1,2]-migration3 is
routinely observed; however, the product formation via [1,4]-
migration is unusual.4 Pirrung et al.5 first noticed an example of
the [1,4]-migration in rhodium()-mediated reaction pathway.
The second report, by F. G. West et al., described the isolation
of the [1,4]-migration product albeit in very low yield in the CuII
carbenoids-derived oxonium ylides. However, the same reaction
fails to give the [1,4]-migration product in the presence of
rhodium() acetate.6
Recently, we have reported the synthesis of sugar β-keto ester
1a and demonstrated its applicability in the synthesis of
6-deoxyheptulosurono-7,4-lactones,7a 1,6-dideoxynojirimycin7b
and coumarinyl C-glycosides.7c In order to explore the utility of
sugar β-keto esters 1a–d in the synthesis of polyether anti-
biotics, we have examined the rhodium()-catalysed reactions
Scheme 1
of α-diazo-β-keto esters 2a–d and the results thus obtained are
presented herein.
The assignment of the structures was based on IR and NMR
spectral data. The IR spectra of the compound with a high Rf-
value showed two carbonyl frequencies, at 1779 and 1744 cmϪ1
Results and discussion
,
The sugar β-keto esters 1a–d were prepared as reported earlier
by us.7a The reaction of 1a–d with mesyl azide in the presence of
triethylamine in acetonitrile afforded α-diazo-β-keto esters 2a–
d, respectively, in good yields (Scheme 1). The individual reac-
tions of 2a–d were performed using rhodium() acetate (1
mol%) under different conditions of solvent and temperature.
The reaction of 2a in dichloromethane at room temperature or
at reflux afforded a complex mixture of products, while in ben-
zene at 25 ЊC it was found to be very sluggish and even after
36 h nearly quantitative amounts of starting material were
recovered. However, the reaction of 2a and rhodium() acetate
(1 mol%) in benzene at reflux for 5 min afforded 3 and 4a in the
ratio 38:62 in 77% yield. The appreciable difference in the Rf-
values of these two compounds allowed us to separate the
products 3 and 4a in pure form by column chromatography.
indicating the presence of a five-membered-ring ketone (furan-
3-one) and the ester carbonyl functionality, respectively. The 1H
NMR spectrum showed an AB quartet at δ 3.26 (J 14.0 Hz)
indicating the presence of a CCH2Ph group instead of OCH2Ph
functionality. The 13C NMR spectrum showed a ketone carb-
onyl at δC 202.3 and the ester carbonyl at δC 166.9. These
spectral data were found to be consistent with structure 3. The
formation of 3 could be explained via a five-membered oxo-
nium ylide followed by [1,2]-migration of the benzyl group as
shown in Scheme 2. The stereochemistry of the [1,2]-migration
was tentatively assigned as shown in structure 3 on the basis of
transition state A (Scheme 2) that resembles an oxabicyclo-
[3.1.0]hexane ring system with the key, stereochemically defin-
ing benzyl group coming from the same side (β-face) as that of
the 3-OBn functionality in the final product 3. In the compound
J. Chem. Soc., Perkin Trans. 1, 2000, 147–151
This journal is © The Royal Society of Chemistry 2000
147

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Scheme 3
was performed at lower temperatures. Thus, when the reaction
of 2c was carried out either in dichloromethane (for 1 h) or in
benzene (for 3 h) at 35 ЊC, compound 5 was obtained in 78 and
86% yield, respectively, indicating that the reaction pathway is
indeed a [2,3]-sigmatropic rearrangement.
Fig. 1 GHSQC (300 MHz; CDCl3) spectrum of 4a.
Strikingly different results were obtained on changing the
configuration of the OBn group at C-3. The reaction of
-allose-derived 3-O-benzyl-α-diazo-β-keto ester 2d in benzene
(reflux; 5 min) resulted in formation of the C–H insertion prod-
uct 6 in 80% yield. The presence of a six-membered ketone was
obvious from the IR spectrum at 1760 cmϪ1 and the 13C NMR
spectrum at δC 195.8. The structure was characterised by spectral
and analytical data and confirmed by 2D NMR COSY (Fig. 2)
and HETCORR (Fig. 3) experiments. The large coupling-
constant-value of 10.5 Hz between H-6 and H-7 indicated the
relative trans diaxial relationship of these protons. The absolute
stereochemistry of the C–H insertion, at C-6 and C-7, was
decided by DPFGNOE wherein irradiation of H-3 at δ 3.82
showed NOE enhancement for the H-7 signal at δ 5.15, indicat-
ing their spatial proximity. In structure 2d, the OBn substituent
at C-3 is α-orientated and the proton is β-oriented, therefore
the proton at C-7 was assigned the β-orientation based on
observed NOEs with H-3 and hence the C-6 proton was placed
α-oriented as shown in structure 6. The competition between
rearrangement or migration reaction versus C–H insertion
could be related to the steric strain involved in the formation of
the five-membered oxonium ylide. The relative trans geometry
of the substituents at C-3 and C-4 disfavours the trans ring
fusion of two five-membered rings in transition state C (Scheme
4). As a result the C–H insertion pathway, which proceeds via
a seven-membered transition state D as shown in Scheme 4,
results in the six-membered-ring product 6.
Scheme 2
with low Rf-value, the absence of a carbonyl frequency at ≈1770
cmϪ1 ruled out the presence of a five-membered ring carbonyl
(furan-3-one) and the lower ester carbonyl signal observed at
1714 cmϪ1 suggested an α,β-unsaturated ester. In the 1H NMR
spectrum, the appearance of an AB quartet at δ 5.16 (J 12.1 Hz)
suggested the OCH2Ph functionality. The 13C NMR spectrum
showed only one ester carbonyl, at δC 160.1, but additional sig-
nals at δC 146.4 and 127.9 indicated the presence of olefinic
carbons. Based on spectral and analytical data structure 4a was
assigned to the compound. The formation of compound 4a via
[1,4]-migration was unusual, therefore the structure was further
confirmed by 13C DEPT and HETCORR 2D NMR experi-
ments (Fig. 1).
It has been observed that the [1,4]-migration products 4a
and 4b are formed from the substrates 2a and 2b, respectively.
Although the different mechanisms involved in the formation
of products 3, 5 and 6 are well documented in the literature,1
an explanation for the [1,4]-migration product is lacking. We
assume that the metal-bound oxonium ylide 7 or 8 (Scheme 5),
generated from substrate 2a or 2b, plays an important role in
the reaction selectivity. The product formation via 8 can be
ruled out as the distance between the migration origin and ter-
minus is large, while in 7 we hypothesised a somewhat different
four-centred transition state 9, in which the C–Rh bond is
aligned with the O–CH2Ar bond. As the reaction proceeds, the
migration of CH2Ar from oxygen to Rh is completed giving
RhII species 10. Such a type of involvement of rhodium metal
in [1,2]-shifts of ylides has been proposed.2 Free rotation about
the Rh–C-6 bond brings CH2Ar close to the ketone carbonyl,
permitting [1,4]-migration at this juncture to give the product.8
The exclusive formation of 4b in case of 3-O-(4-methoxy-
benzyl)-substituted compound 2b could be due to the increase
in electron density at the benzyl carbon which renders better
coordination with the rhodium, or it may reflect the stabilis-
ation of the partial positive charge on the migrating group
during rearrangement.
In order to ascertain the generality of the [1,4]-migration
product, the reaction sequence was carried out with different
sugar-derived α-diazo-β-keto esters by changing the C-3 sub-
stituent. Thus, when 3-O-(4-methoxybenzyl)-α-diazo-β-keto
ester 2b was allowed to react in benzene (reflux; 25 min) the
[1,4]-migration product 4b was the only isolable product, in
80% yield after purification. In its 1H NMR spectrum, the crude
reaction mixture showed no other stereoisomers or regio-
isomers. The spectral and analytical data were in accord with
the assigned structure 4b. However, when the reaction was per-
formed with 3-O-allyl-α-diazo-β-keto ester 2c, in benzene
(reflux, 5 min), the product 5 was obtained in 74% yield. As
shown in Scheme 3, this reaction pathway is presumably follow-
ing the [2,3]-sigmatropic rearrangement as the allylic oxonium
ylides have a preference for symmetry-allowed [2,3]-sigmatropic
rearrangement over [1,2]-migration.2a The assignment of the
configuration at C-6 in 5 was decided on the basis of transition
state B (Scheme 3) that resembles an oxabicyclo[3.3.0]octane
ring system in which the migrating group comes from the
β-face. In view of the fact that, in metal carbenoid reactions,
[2,3]-sigmatropic rearrangements have the lower activation
energy as compared with other possible pathways,4 the reaction
148
J. Chem. Soc., Perkin Trans. 1, 2000, 147–151

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Scheme 4
Fig. 2 2D COSY spectrum of compound 6.
Fig. 3 GHSQC (300 MHz; CDCl3) spectrum of 6.
Scheme 5
In conclusion, a novel rhodium carbenoid-mediated [1,4]-
migration pathway has been found to be a prominent process in
oxonium ylides. It has also been demonstrated that the path-
way is dependent on the nature of the diazocarbonyl precursor.
Further investigations into the substrate reactivity and the
scope of this reaction in the synthesis of polyether antibiotics
are in progress.
carried out using Kieselgel 60 (230–400 mesh) with petroleum
spirit (PS) (boiling range 60–80 ЊC)–ethyl acetate as eluent.
Rhodium acetate was purchased from Fluka and was dried
under high vacuum (0.01 mmHg) at 100 ЊC for 4 h before
use. Dichloromethane, acetonitrile and benzene were dried
according to standard procedures. Ethyl 3-O-benzyl-6-deoxy-
1,2-O-isopropylidene-α--xylo-hept-5-ulofuranuronate 1a and
ethyl 3-O-benzyl-6-deoxy-1,2-O-isopropylidene-α--ribo-hept-
5-ulofuranuronate 1d were prepared according to our previous
report.7a
Experimental
NMR spectra of CDCl3 solutions were recorded with a Bruker
AMX 500 MHz and a Varian VXR 300S MHz spectrometer.
Chemical shifts are reported in ppm (δ) downfield of TMS. IR
spectra were recorded with a Perkin-Elmer 1600 FTIR spectro-
photometer. Optical rotations were measured at 25 ЊC with a
Perkin-Elmer 241 polarimeter and [α]D-values are given in units
of 10Ϫ1 deg cm2 gϪ1. C, H analyses were performed on a Hosli
Carbon-Hydrogen analyser. Mps were taken on a Thomas-
Hoover capillary melting point apparatus and are uncorrected.
All the reactions were conducted in oven-dried glassware
under dry nitrogen. TLC was carried out on Polygram Sil G/
UV 254 precoated plastic sheets, and flash chromatography was
Ethyl 6-deoxy-1,2-O-isopropylidene-3-O-(4-methoxybenzyl)-ꢀ-
D-xylo-hept-5-ulofuranuronate 1b
A solution of 1,2-O-isopropylidene-3-O-(4-methoxybenzyl)-α-
-xylo-pentodialdose (2 g, 6.49 mmol) and ethyl diazoacetate
(1.0 mL, 9.74 mmol) in dry CH2Cl2 (100 mL) was cooled to
Ϫ50 ЊC under N2. A solution of BF3–diethyl ether (0.25 mL,
1.95 mmol) in dry CH2Cl2 (10 mL) was added dropwise with
control of the evolution of N2 (30 min). The reaction mixture
was stirred at Ϫ50 ЊC for 3 h and quenched with a saturated
J. Chem. Soc., Perkin Trans. 1, 2000, 147–151
149

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solution of sodium bicarbonate. The organic layer was separ-
ated and the aqueous layer was extracted with dichloromethane
(20 mL × 3). The combined organic layer was dried (Na2SO4)
and evaporated on a rotary evaporator. The residue thus
obtained on column chromatography yielded β-keto ester 1b as
an oil (1.913 g, 75%), Rf 0.23 (PS–ethyl acetate 7:3); [α]D
Ϫ49.17 (c 0.4, CHCl3); νmax (neat)/cmϪ1 1724 (CO2Et), 1745
(N᎐N); δ (CDCl3; 90 MHz) 1.25 (3H, t, J 7.1 Hz, CH2CH3),
᎐
H
1.34 (3H, s, CH3), 1.50 (3H, s, CH3), 3.80 (3H, s, OCH3), 4.00–
4.20 (2H, m, OCH2CH3), 4.26 (1H, d, J 12.0 Hz, OCH2Ar), 4.43
(1H, d, J 3.8 Hz, 2-H), 4.61 (1H, d, J 4.2 Hz, 3-H), 4.62 (1H, d,
J 12.0 Hz, OCH2Ar), 5.40 (1H, d, J 4.0 Hz, 4-H), 6.12 (1H, d,
J 3.8 Hz, 1-H), 6.85 (2H, d, J 8.6 Hz, ArH), 7.16 (2H, d, J 8.6
Hz, ArH); δC (CDCl3; 22.5 MHz) 13.8, 26.5, 26.9, 54.9, 61.2,
71.5, 75.2, 81.7, 82.7, 83.5, 105.4, 112.2, 113.6, 129.0, 129.4,
159.4, 160.5, 184.9 (Calc. for C20H24N2O8: C, 57.13; H, 5.75.
Found: C, 56.91; H, 6.04%).
(C᎐O); δ (CDCl3; 200 MHz) 1.25 (3H, t, J 6.2 Hz, CH2CH3),
᎐
H
1.32 (3H, s, CH3), 1.45 (3H, s, CH3), 3.52 (1H, d, J 18.0 Hz,
COCH2CO), 3.72 (1H, d, J 18.0 Hz, COCH2CO), 3.80 (3H, s,
OCH3), 4.2 (2H, q, J 6.2 Hz, OCH2CH3), 4.26 (1H, d, J 3.6 Hz,
3-H), 4.40 (1H, d, J 2.0 Hz, OCH2Ph), 4.50 (1H, d, J 12.0 Hz,
OCH2Ph), 4.56 (1H, d, J 3.3 Hz, 2-H), 4.70 (1H, d, J 3.6 Hz,
4-H), 6.05 (1H, d, J 3.3 Hz, 1-H), 6.87 (2H, d, J 8.0 Hz, ArH),
7.20 (2H, d, J 8.0 Hz, ArH); δC (CDCl3; 22.5 MHz) 13.8, 25.9,
26.5, 47.1, 54.8, 60.7, 72.1, 81.8, 83.0, 84.6, 105.7, 112.2, 113.5,
128.5, 129.1, 159.2, 166.6, 200.7 (Calc. for C20H26O8: C, 60.90;
H, 6.64. Found: C, 61.08; H, 6.85%).
Ethyl
3-O-allyl-6-deoxy-6-diazo-1,2-O-isopropylidene-ꢀ-D-
xylo-hept-5-ulofuranuronate 2c. Thick oil; 77% yield; Rf 0.36
(PS–ethyl acetate 7:3); [α]D ϩ8.85 (c 0.76, CHCl3); νmax (neat)/
cmϪ1 1673 (C᎐O), 1713 (C᎐O), 2139 (N᎐N); δ (CDCl3; 90
᎐
᎐
᎐
H
MHz) 1.31 (6H, t, J 7.1 Hz, CH2CH3, CH3), 1.45 (3H, s, CH3),
3.50–4.03 (2H, m, OCH CH᎐CH ), 4.23 (2H, q, J 7.1 Hz,
᎐
2
2
OCH2CH3), 4.37 (1H, d, J 3.7 Hz, 3-H), 4.51 (1H, d, J 3.0 Hz,
2-H), 4.95–5.26 (2H, m, CH ᎐CH), 5.37 (1H, d, J 3.7 Hz,
᎐
2
Ethyl 3-O-allyl-6-deoxy-1,2-O-isopropylidene-ꢀ-D-xylo-hept-5-
ulofuranuronate 1c
4-H), 5.45–5.81 (1H, m, CH ᎐CH), 5.98 (1H, d, J 3.0 Hz,
᎐
2
1-H); δC (CDCl3; 22.5 MHz) 14.0, 26.3, 26.9, 42.5, 61.4,
71.0, 75.3, 82.6, 83.7, 105.3, 112.3, 117.4, 133.4, 160.9, 185.2
(Calc. for C15H20N2O7: C, 52.93; H, 5.92. Found: C, 52.80; H,
6.15%).
The reaction of 3-O-allyl-1,2-O-isopropylidene-α--xylo-pento-
dialdose (1.5 g, 6.58 mmol) and ethyl diazoacetate (1.05 mL,
9.87 mmol) in dry CH2Cl2 (100 mL) at Ϫ10 ЊC for 3 h as per the
procedure for 1b gave β-keto ester 1c as an oil (1.811 g, 88%). Rf
0.39 (PS–ethyl acetate 7:3); [α]D Ϫ61.0 (c 0.4, CHCl3); νmax
Ethyl 3-O-benzyl-6-deoxy-6-diazo-1,2-O-isopropylidene-ꢀ-D-
ribo-hept-5-ulofuranuronate 2d. Thick oil; 88% yield; Rf 0.5 (PS–
ethyl acetate 7:3); [α]D ϩ64.7 (c 0.25, CHCl3); νmax (neat)/cmϪ1
(Nujol)/cmϪ1 1723 (CO Et), 1747 (C᎐O); δ (CDCl3; 300
᎐
2
H
MHz) 1.27 (3H, t, J 7.1 Hz, CH2CH3), 1.33 (3H, s, CH3),
1.47 (3H, s, CH3), 3.55 (1H, d, J 16.8 Hz, COCH2CO), 3.74
(1H, d, J 16.8 Hz, COCH2CO), 3.94 (1H, ddt, J 1.5, 5.7, 12.6
1660 (C᎐O), 1720 (CO Et), 2140 (N᎐N); δH (CDCl3; 300 MHz)
᎐
᎐
2
1.32 (3H, t, J 7.1 Hz, CH2CH3), 1.38 (3H, s, CH3), 1.67 (3H,
s, CH3), 4.22 (1H, dd, J 8.4, 4.4 Hz, 3-H), 4.25–4.33 (2H, m,
OCH2CH3), 4.56 (1H, d, J 12.0 Hz, CH2Ph), 4.60 (1H, d, J 3.4
Hz, 2-H), 4.74 (1H, d, J 12.0 Hz, OCH2Ph), 5.41 (1H, d, J 8.6
Hz, 4-H), 5.81 (1H, d, J 3.4 Hz, 1-H), 7.28–7.39 (5H, m, Ph);
δC (CDCl3; 22.5 MHz) 14.3, 26.8, 27.1, 61.8, 72.7, 78.3, 78.4,
79.6, 104.9, 113.8, 128.0, 128.0, 128.4, 128.6, 137.5, 160.1, 187.7
(Calc. for C19H22N2O7: C, 58.45; H, 5.68. Found: C, 58.18; H,
5.63%).
Hz, OCH CH᎐CH ), 4.05 (1H, ddt, J 1.1, 5.5, 12.6 Hz,
᎐
2
2
CH CH᎐CH ), 4.12–4.30 (3H, m, OCH CH , 3-H), 4.56 (1H,
᎐
2
2
2
3
d, J 3.5 Hz, 2-H), 4.69 (1H, d, J 3.6 Hz, 4-H), 5.18–5.28 (2H,
m, CH ᎐CH), 5.70–5.85 (1H, m, CH ᎐CH), 6.06 (1H, d, J 3.5
᎐
᎐
2
2
Hz, 1-H); δC (CDCl3; 22.5 MHz) 13.8, 26.1, 26.7, 47.1, 60.6,
71.3, 79.2, 83.5, 84.9, 105.9, 112.2, 117.4, 133.4, 166.5, 200.8
(Calc. for C13H22O7: C, 53.78; H, 7.64. Found: C, 53.90; H,
7.86%).
General procedure for the synthesis of ꢀ-diazo-ꢁ-keto esters 2a–d
Ethyl 3,6-anhydro-6-benzyl-1,2-O-isopropylidene-ꢀ-D-gluco-
hept-5-ulofuranuronate 3 and ethyl 3,6-anhydro-5-O-benzyl-1,2-
O-isopropylidene-ꢀ-D-xylo-hept-5-enofuranuronate 4a
To a solution of α-diazo-β-keto ester (1 mmol) in dry aceto-
nitrile (30 mL) were added triethylamine (2 mmol) and meth-
anesulfonyl azide (1.1 mmol). The reaction mixture was stirred
at room temperature for 3 h and quenched with aq. sodium
hydroxide (2 M; 1 mL). The organic layer was separated and the
aqueous layer was extracted with ethyl acetate (20 mL × 3). The
combined organic layer was dried (Na2SO4), and evaporated on
a rotary evaporator to give a thick oil, which on column
chromatography (PS–ethyl acetate 19:1) yielded the α-diazo-β-
keto ester.
A solution of α-diazo β-keto ester 2a (0.150 g, 0.385 mmol) and
Rh2(OAc)4 (0.002 g, 0.002 mmol) in benzene (5 mL) under N2
atmosphere was refluxed for 5 min. On cooling, the reaction
mixture was directly loaded onto a silica gel column and puri-
fied by eluting with PS–ethyl acetate (9.5:0.5) to afford, first,
bicycle 3 as a thick oil (0.066 g, 48%), Rf 0.69 (PS–ethyl acetate
7:3); [α]D ϩ54.0 (c 1.0, CHCl3); νmax (neat)/cmϪ1 1779 (C᎐O),
᎐
1744 (C᎐O); δ (CDCl3; 500 MHz) 1.27 (3H, t, J 6.5 Hz,
᎐
H
CH2CH3), 1.30 (3H, s, CH3), 1.39 (3H, s, CH3), 3.26 (2H, AB
quartet, J 14.0 Hz, CCH2Ph), 4.17–4.24 (4H, m, 3-H, 4-H,
OCH2CH3), 4.87 (1H, d, J 3.5 Hz, 2-H), 5.94 (1H, d, J 3.5 Hz,
1-H), 7.17–7.25 (5H, m, Ph); δC (CDCl3; 125 MHz) 13.9, 26.6,
27.3, 40.6, 62.4, 79.1, 82.7, 85.3, 86.9, 107.7, 113.4, 127.1, 128.4,
130.4, 133.8, 166.9, 202.3 (Calc. for C19H22O7: C, 62.97; H, 6.12.
Found: C, 62.76; H, 6.39%).
Ethyl 3-O-benzyl-6-deoxy-6-diazo-1,2-O-isopropylidene-ꢀ-D-
xylo-hept-5-ulofuranuronate 2a. Thick oil; 77% yield; Rf 0.42
(PS–ethyl acetate 7:3); [α]D ϩ1.6 (c 0.44, CHCl3); νmax (neat)/
cmϪ1 1680 (C᎐O), 1712 (C᎐O), 2141 (N᎐N); δ (CDCl3; 500
MHz) 1.24 (3H, t, J 7.1 Hz, CH2CH3), 1.34 (3H, s, CH3), 1.49
(3H, s, CH3), 4.04–4.20 (2H, m, OCH2CH3), 4.34 (1H, d, J 12.3
Hz, CH2Ph), 4.46 (1H, d, J 3.9 Hz, 3-H), 4.63 (1H, d, J 3.6 Hz,
2-H), 4.68 (1H, d, J 12.3 Hz, OCH2Ph), 5.42 (1H, d, J 3.8 Hz,
4-H), 6.12 (1H, d, J 3.6 Hz, 1-H), 7.22–7.34 (5H, m, Ph);
δC (CDCl3; 22.5 MHz) 14.2, 26.6, 27.2, 61.6, 71.9, 75.8, 81.8,
82.6, 83.6, 105.6, 112.6, 128.1, 128.2, 128.3, 137.0, 160.7, 185.2
(Calc. for C19H22N2O7: C, 58.45; H, 5.68. Found: C, 58.55; H,
5.81%).
᎐
᎐
᎐
H
Further elution gave the isomeric bicycle 4a as a white solid
(0.041 g, 29%), mp 75–77 ЊC; Rf 0.57 (PS–ethyl acetate 7:3);
[α]D ϩ26.81 (c 0.45, CHCl3); νmax (Nujol)/cmϪ1 1714 (C᎐O);
᎐
δH (CDCl3; 300 MHz) 1.33 (3H, t, J 7.1 Hz, CH2CH3), 1.36 (3H,
s, CH3), 1.51 (3H, s, CH3), 4.3 (2H, q, J 7.1 Hz, OCH2CH3),
4.84 (1H, d, J 7.0 Hz, 4-H), 4.85 (1H, d, J 3.0 Hz, 2-H), 5.16
(2H, AB quartet, J 12.1 Hz, OCH2Ph), 5.48 (1H, d, J 7.0 Hz,
3-H), 5.93 (1H, d, J 3.0 Hz, 1-H), 7.31–7.43 (5H, m, Ph);
δC (CDCl3; 75 MHz) 14.3, 26.9, 27.8, 61.2, 73.0, 82.8, 83.9, 85.1,
106.1, 113.7, 127.3, 127.9, 128.2, 128.6, 136.5, 146.4, 160.1
(Calc. for C19H22O7: C, 62.97; H, 6.12. Found: C, 62.59; H,
6.72%).
Ethyl
6-deoxy-6-diazo-1,2-O-isopropylidene-3-O-(4-meth-
oxybenzyl)-ꢀ-D-xylo-hept-5-ulofuranuronate 2b. Thick oil; 86%
yield; Rf 0.19 (PS–ethyl acetate 7:3); [α]D ϩ14.81 (c 0.42,
CHCl3); νmax (neat)/cmϪ1 1713 (CO Et), 1777 (C᎐O), 2142
᎐
2
150
J. Chem. Soc., Perkin Trans. 1, 2000, 147–151

View Article Online
Ethyl 3,6-anhydro-1,2-O-isopropylidene-5-O-(4-methoxy-
benzyl)-ꢀ-D-xylo-hept-5-enofuranuronate 4b
and Rh2(OAc)4 (0.004 g, 0.001 mmol) in benzene (5 mL) was
performed as per the procedure for 2a to give 6 as a white solid
(0.29 g, 80%), mp 131–132 ЊC; Rf 0.36 (PS–ethyl acetate 7:3);
A solution of α-diazo-β-keto ester 2b (0.150 g, 0.357 mmol) and
Rh2(OAc)4 (0.003 g, 0.007 mmol) in benzene (5 mL) under
N2 atmosphere was refluxed for 25 min. On cooling, the reac-
tion mixture was directly loaded onto a silica gel column
and purified by eluting with PS–ethyl acetate (9:1) to afford 4b
as a thick oil (0.113 g, 80%), Rf 0.31 (PS–ethyl acetate 7:3);
[α]D ϩ48.53 (c 0.5, CHCl3); νmax (Nujol)/cmϪ1 1760 (C᎐O), 1720
᎐
(C᎐O); δ (CDCl3; 300 MHz) 1.12 (3H, t, J 7.1 Hz, CH2CH3),
᎐
H
1.39 (3H, s, CH3), 1.65 (3H, s, CH3), 3.75 (1H, dd, J 1.5, 10.5
Hz, 6-H), 3.82 (1H, dd, J 3.3, 10.2 Hz, 3-H), 4.05–4.17 (2H, m,
OCH2CH3), 4.70 (1H, dd, J 1.5, 10.2 Hz, 4-H), 4.83 (1H, t, J 3.3
Hz, 2-H), 5.15 (1H, d, J 10.5 Hz, 7-H), 5.91 (1H, d, J 3.3 Hz,
1-H), 7.32–7.45 (5H, m, Ph); δC (CDCl3; 75 MHz) 13.9, 26.0,
26.5, 61.5, 62.8, 77.0, 79.0, 82.3, 84.8, 105.1, 114.7, 127.2, 128.7,
129.2, 137.1, 166.0, 195.8 (Calc. for C19H22O7: C, 62.97; H, 6.12.
Found: C, 62.66; H, 5.96%).
[α]D ϩ15.47 (c 0.42, CHCl3); νmax (neat)/cmϪ1 1716 (C᎐O);
᎐
δH (CDCl3; 300 MHz) 1.33 (3H, t, J 7.1 Hz, CH2CH3), 1.37 (3H,
s, CH3), 1.51 (3H, s, CH3), 3.81 (3H, s, OCH3), 4.29 (2H, q, J 7.1
Hz, OCH2CH3), 4.83 (1H, d, J 3.9 Hz, 2-H), 4.84 (1H, d, J 4.8
Hz, 3-H), 5.09 (2H, AB quartet, J 11.7 Hz, OCH2Ar), 5.48 (1H,
d, J 6.4 Hz, 4-H), 5.94 (1H, d, J 3.5 Hz, 1-H), 6.89 (2H, d, J 8.7
Hz, ArH), 7.34 (2H, d, J 8.7 Hz, ArH); δC (CDCl3; 75 MHz)
14.3, 26.8, 27.8, 55.3, 61.1, 72.9, 82.8, 83.9, 85.1, 106.1, 113.6,
113.9 (s), 128.7, 129.2 (s), 130.6, 146.4, 159.9, 160.0 (Calc. for
C20H24O8: C, 61.21; H, 6.17. Found: C, 61.10; H, 6.45%).
Acknowledgements
We are thankful to BRNS for financial assistance, to UGC for
the JRF to one of us (V. N. D.) and to Dr Hari, Varian, India,
for 2D NMR experiments. We are grateful to Professor M. S.
Wadia and Professor M. C. Pirrung, Duke University, North
Carolina for helpful discussions.
Ethyl 6-allyl-3,6-anhydro-1,2-O-isopropylidene-ꢀ-D-gluco-hept-
5-ulofuranuronate 5
The reaction of α-diazo-β-keto ester 2c (0.100 g, 0.294 mmol)
and Rh2(OAc)4 (0.001 g, 0.003 mmol) in benzene (5 mL) was
performed as per the procedure for the reaction of 2a, to give 5
(0.68 g, 74%) as a thick oil.
References
1 J. Adams and D. M. Spero, Tetrahedron, 1991, 47, 1765; A. Padwa
and K. E. Krumpe, Tetrahedron, 1992, 48, 5385; T. Ye and M. A.
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Tetrahedron, 1995, 51, 10811; A. Padwa and M. D. Weingarten,
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Sulikowski, Tetrahedron: Asymmetry, 1998, 9, 3145; M. P. Doyle and
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3 J. B. Brogan, C. B. Bauer, R. D. Rogers and C. K. Zercher, Tetra-
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and J. S. Tedrow, Tetrahedron Lett., 1997, 38, 4367.
4 For prior reports of minor amounts of [1,4]-shift products in
rearrangements of sulfonium and ammonium ylides see: J. E.
Baldwin, W. F. Erickson, R. E. Hackler and R. M. Scott, J. Chem.
Soc., Chem. Commun., 1970, 576; K. Chantrapromma, W. D. Ollis
and I. O. Sutherland, J. Chem. Soc., Perkin Trans. 1, 1983, 1049.
5 M. C. Pirrung, W. L. Brown, S. Rege and P. Laughton, J. Am. Chem.
Soc., 1991, 113, 8561.
Reaction in benzene at 35 ЊC. To a solution of α-diazo-β-keto
ester 2c (0.100 g, 0.294 mmol) and Rh2(OAc)4 (0.001 g, 0.003
mmol) in benzene (5 mL) was stirred for 3 h at 35 ЊC. Solvent
was evaporated off and the residue was chromatographed (PS–
ethyl acetate 9.5:0.5) to afford 5 (0.079 g, 86%) as a thick oil.
Reaction in dichloromethane at 35 ЊC. To a solution of
α-diazo-β-keto ester 2c (0.100 g, 0.294 mmol) and Rh2(OAc)4
(0.001 g, 0.003 mmol) in dichloromethane (5 mL) was stirred
for 1 h at 35 ЊC. Solvent was evaporated off and the residue was
chromatographed (PS–ethyl acetate 9.5:0.5) to afford 5 as a
thick oil (0.72 g, 78%), Rf 0.48 (PS–ethyl acetate 7:3); [α]D
ϩ31.64 (c 0.3, CHCl3); νmax (neat)/cmϪ1 1779 (C᎐O), 1744
᎐
(C᎐O); δ (CDCl3; 300 MHz) 1.27 (3H, t, J 7.1 Hz, CH2CH3),
᎐
H
1.36 (3H, s, CH3), 1.48 (3H, s, CH3), 2.60 (1H, ddt, J 1.1, 7.1,
14.3 Hz, CH CH᎐CH ), 2.75 (1H, br dd, J 7.1, 14.3 Hz,
᎐
2
2
CH CH᎐CH ), 4.21 (2H, dq, J 1.8, 7.1 Hz, OCH CH ), 4.50
᎐
2
2
2
3
6 F. G. West, B. N. Naidu and R. W. Tester, J. Org. Chem., 1994, 59,
6892.
7 (a) D. D. Dhavale, N. N. Bhujbal, P. Joshi and S. G. Desai,
Carbohydr. Res., 1994, 263, 303; (b) D. D. Dhavale, N. N. Saha and
V. N. Desai, J. Org. Chem., 1997, 62, 7482; (c) N. N. Saha, V. N. Desai
and D. D. Dhavale, J. Org. Chem., 1999, 64, 1715.
8 Analogous experimental evidence for rotational degree of freedom in
rhodium carbeniods is known. See: D. F. Taber and S. C. Malcolm,
J. Org. Chem., 1998, 63, 3717.
(1H, d, J 3.6 Hz, 3-H), 4.78 (1H, d, J 3.6 Hz, 4-H), 4.98 (1H, d,
J 3.3 Hz, 2-H), 5.13–5.21 (2H, m, CH ᎐CH), 5.60–5.74 (1H, m,
᎐
2
CH ᎐CH), 5.99 (1H, d, J 3.3 Hz, 1-H); δ (CDCl3; 75 MHz)
᎐
2
C
14.1, 26.8, 27.5, 39.2, 62.5, 79.2, 82.9, 85.7, 86.0, 108.1, 113.6,
120.8, 130.3, 167.1, 201.3 (Calc. for C15H20O7: C, 57.68; H, 6.46.
Found: C, 57.88; H, 6.74%).
3,7-Anhydro-6-deoxy-6-ethoxycarbonyl-1,2-O-isopropylidene-7-
(S)-phenyl-ꢀ-D-allo-heptofuran-5-ulose 6
The reaction of α-diazo-β-keto ester 2a (0.390 g, 1.00 mmol)
Paper a908453c
J. Chem. Soc., Perkin Trans. 1, 2000, 147–151
151