Catalytic enantioselective tandem carbonyl ylide formation-intramolecular cycloaddition with unsaturated α-diazo-β,ε-diketo sulfones

Article abstract of DOI:10.1016/j.tetasy.2009.02.031

The synthesis and 1,3-dipolar cycloaddition reactions of unsaturated α-diazo-β,ε-diketo sulfones 7 using chiral rhodium catalysts (up to 71.5:28.5 er) are described.

Full text of DOI:10.1016/j.tetasy.2009.02.031

Tetrahedron: Asymmetry 20 (2009) 754–757
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Tetrahedron: Asymmetry
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Catalytic enantioselective tandem carbonyl ylide formation—intramolecular
cycloaddition with unsaturated a-diazo-b,e-diketo sulfones
a
b
David M. Hodgson a, , Rebecca Glen , Alison J. Redgrave
*
a Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
b GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis and 1,3-dipolar cycloaddition reactions of unsaturated
chiral rhodium catalysts (up to 71.5:28.5 er) are described.
a-diazo-b,e-diketo sulfones 7 using
Received 26 January 2009
Accepted 23 February 2009
Available online 1 April 2009
Ó 2009 Elsevier Ltd. All rights reserved.
This paper is dedicated to Professor George
Fleet, on the occasion of his 65th birthday
1. Introduction
similar carbonyl groups present in precursor 1 (R = ester). In con-
trast to
concerning the use of
transition-metal-catalysed transformations of diazo compounds
-bond (e.g., C–H, O–H) insertion and cyclopropanation]1a,g,6
a
-diazo-b-keto esters, there are significantly fewer studies
Transition-metal-catalysed tandem carbonyl ylide formation—
1,3-dipolar cycloadditions using diazo compounds (e.g., Scheme
1) were originally developed by Ibata and Padwa for the synthesis
of oxapolycycles;1 they are of interest due to the opportunities for
rapid generation of molecular complexity in a single operation.
Over the last decade, encouraging levels of asymmetric induction
have been obtained in such transformations using chiral catalysts
with certain classes of achiral diazo substrates and dipolarophiles.2
As the catalyst-free carbonyl ylide intermediate in these reactions
would be achiral, the chiral catalyst is likely associated with the
carbonyl ylide (e.g., 2, Scheme 1) to influence enantiofacial selec-
tivity in the cycloaddition; however, the origins of asymmetric
induction remain unclear.3 So as to assess the scope and determine
the factors influencing enantioselectivity in this asymmetric pro-
cess, part of our research programme in this area involves variation
of electronic (and steric) effects within the dipole (e.g., R = ester,
aryl).4
a-diazo sulfones in typical (asymmetric)
[r
and only one isolated report of an
a-diazo sulfone in (acyclic and
non asymmetric) carbonyl ylide formation—cycloaddition.7
2. Results and discussion
Cycloaddition substrate 7a was readily accessed (Scheme 2) by
a
-sulfonyl carbanion acylation5,8 with known ketal ester 5 (itself
prepared in 3 steps via lithiation–alkylation of 2,3-dihydrofuran
4),4 followed by diazo transfer using 4-acetamidobenzenesulfonyl
azide (ABSA).9
Although hexane is the preferred solvent for the (asymmetric)
cycloadditions with a-diazo-b,e
-diketo esters 1 (R = ester),4 phenyl
sulfone substrate 7a proved insoluble in hexane. However, another
hydrocarbon solvent toluene gave improved solubility. Initial stud-
ies examining the viability of the cycloaddition process in toluene
with achiral rhodium catalysts commenced with Rh2(OAc)4, which
gave cycloadduct 8a in 12% yield (Scheme 3 and Table 1, entry 1).
The more electron-deficient catalyst Rh2(tfa)4 gave an improved
39% yield (Table 1, entry 2), whereas Rh2(cap)4 (cap = caprolacta-
mate) failed to decompose phenyl sulfone substrate 7a, even after
20 h (Table 1, entry 3). Rh2(oct)4, which is electronically very sim-
ilar to Rh2(OAc)4 but with higher solubility in non-polar solvents,
gave cycloadduct 8a in 72% yield (Table 1, entry 4). This last result
indicated the viability of tandem carbonyl ylide formation—intra-
Herein, we report on the enantioselective tandem carbonyl
ylide formation—intramolecular cycloaddition employing sulfonyl
functionality as a different type of electron-withdrawing group at
the ylidic carbon, specifically using unsaturated a-diazo-b,e-diketo
sulfones 1 (R = sulfonyl group). The sulfonyl functionality was
examined partly due to its subsequent potential utility in the cyc-
loadduct,5 but of principal interest was the effect of its presence on
the viability of the cycloaddition and especially on asymmetric
induction in the cycloadduct 3, since in substrate 1 (R = sulfonyl
group) there would be two rather different electron-withdrawing
groups spanning the diazo functionality, compared with the two
molecular cycloaddition with this class of a-diazo sulfone and set
the stage for an examination of chiral rhodium catalysts previously
shown to deliver good enantiomeric ratios10 in carbonyl ylide
cycloadditions.
* Corresponding author.
E-mail address: david.hodgson@chem.ox.ac.uk (D.M. Hodgson).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.02.031

D. M. Hodgson et al. / Tetrahedron: Asymmetry 20 (2009) 754–757
755
cat. Rh2L4
O
+
N2
O
O
O
O
O
R
R
3
2
R
Rh2L4
1
Scheme 1. Metal-catalysed carbonyl ylide formation—1,3-dipolar cycloaddition using diazocarbonyl compounds.
ABSA
3 steps4
MeSO2R / BuLi
Et3N or DBU
MeCN
THF
O
O
MeO OMe
O
N2
CO2Me
O
O
rt to reflux, 3 h
0 °C, 1.5 h
4
5
RO2S
RO2S
6a 61% (R = Ph)
6b 74% (R = Me)
7a 77% (R = Ph)
7b 15% (R = Me)
Scheme 2. Synthesis of cycloaddition substrates 7a,b.
with
a-diazo-b,e
-diketo esters.4a Reaction of phenyl sulfone sub-
strate 7a with proline-derived Rh2[(S)-DOSP]4 and binaphthyl-
based Rh2[(R)-DDBNP]4 was reasonably efficient (67% yield in both
cases, Table 1 entries 5 and 6), but only low levels of asymmetric
induction were observed.
Recently, Hashimoto et al. reported the efficient asymmetric
intermolecular cycloaddition of cyclic carbonyl ylides derived from
Rh2L4 (0.5 mol%)
25 °C
O
N2
O
O
O
RO2S
RO2S
7a (R = Ph)
7b (R = Me)
8a (R = Ph)
8b (R = Me)
a-diazo-b,e-diketo esters, using N-phthaloyl-amino acid-based
rhodium catalysts in PhCF3.2c In the present case with phenyl sul-
fone substrate 7a, improved levels of asymmetric induction were
observed using such catalysts compared with Rh2[(S)-DOSP]4 and
Rh2[(R)-DDBNP]4. Thus, a gradual rise in er for cycloadduct 8a
was found on moving from phenyl alanine-derived catalyst
Rh2[(S)-PTPA]4 (63.5:36.5, Table 1, entry 7) to the slightly more
hindered tert-leucine-based Rh2[(S)-PTTL]4 (67:33), to the ben-
zene-fused phthaloyl valine derivative Rh2[(S)-BPTV]4 (71.5:28.5).
Scheme 3. Cycloaddition of substrates 7a,b.
Table 1
½ ꢀ
a 2D5
—
—
—
—
b
Entry
Catalyst
Solvent
Yield 8a (%)
era
1
2
3
4
Rh2(OAc)4
Rh2(tfa)4
Rh2(cap)4
Rh2(oct)4
Toluene
Toluene
Toluene
Toluene
12
39
0c
—
—
—
—
As with the intramolecular cycloaddition of unsaturated
a-diazo-
72
b, -diketoesters
e
1
(R = ester),4a catalysts Rh2[(S)-DOSP]4 and
5
6
7
8
9
Rh2[(S)-DOSP]4
Rh2[(R)-DDBNP]4
Rh2[(S)-PTPA]4
Rh2[(S)-PTTL]4
Rh2[(S)-BPTV]4
Toluene
Toluene
PhCF3
PhCF3
PhCF3
67
67
37
80
75
52:48
ꢁ0.8
ꢁ2.9
+6.4
Rh2[(R)-DDBNP]4 gave the opposite sense of asymmetric induction
compared to catalysts Rh2[(S)-PTPA]4, Rh2[(S)-PTTL]4 and Rh2[(S)-
BPTV]4. An attempt to improve the er with Rh2[(S)-BPTV]4 by
reducing the reaction temperature to 0 °C simply led to the recov-
ery of phenyl sulfone substrate 7a. We also briefly examined
variation of the sulfone substituent with methyl sulfone 7b: com-
pared with phenyl sulfone substrate 7a, achiral catalysts Rh2(OAc)4
and Rh2(oct)4 in toluene were both less effective with methyl
sulfone 7b (20% and 43% yield of cycloadduct 8b, respectively),
whereas catalysis by Rh2(S-BPTV)4 in PhCF3 was of comparable
54.5:45.5
63.5:36.5
67:33
+9.6
71.5:28.5
+13.6
a
Determined by chiral HPLC.
All c 1, in CH2Cl2.
No reaction observed after 20 h at rt.
b
c
The asymmetric process was first studied with Rh2[(S)-DOSP]4
and Rh2[(R)-DDBNP]4 (Fig. 1): two hydrocarbon soluble catalysts
(due to the presence of the dodecyl chains) which have previously
provided useful levels of asymmetric induction in cycloadditions
efficiency (80% yield) but the er for cycloadduct 8b {½a D25
¼ þ3:1
ꢀ
(c 1.05, CH2Cl2)} was lowered (from 71.5:28.5 for 8a to 66.5:33.5
for 8b).
i-Pr
H
C12H25
O
O
Rh
Rh
O
O
Rh
Rh
R
N
O
O
Rh
Rh
O
O
N
N
O
O
O
O
Rh
Rh
SO2
P
O
O
C12H25
4
4
C12H25
4
4
Rh2[(S)-PTPA]4 (R = Bn)
Rh2[(S)-PTTL]4 (R = t-Bu)
Rh2[(S)-BPTV]4
Rh2[(S)-DOSP]4
Rh2[(R)-DBBNP]4
Figure 1.

756
D. M. Hodgson et al. / Tetrahedron: Asymmetry 20 (2009) 754–757
using a Perkin–Elmer 241 polarimeter with a cell of path length
3. Conclusion
either 1.0 dm or 0.1 dm, at T °C and are given in 10ꢁ1 deg cm2 gꢁ1
.
Concentrations (c) are given in grams per 100 cm3.
In conclusion, a route to unsaturated
a-diazo-b,e-diketo sulf-
ones 7 has been developed and such substrates have been shown
to undergo efficient tandem cyclic ylide formation—intramolecular
cycloaddition. Using these substrates, the first asymmetric induc-
tion in the cycloadditions of sulfone-substituted carbonyl ylides
has been observed, with the N-phthaloyl-amino acid-based rho-
dium catalysts giving the best enantioselectivities (up to
71.5:28.5 er for phenyl sulfone 8a) and extending their useful-
ness.2c Aside from further catalyst and intermolecular cycloaddi-
tion studies, as the level of asymmetric induction has been
shown to be sensitive to the sulfone group (phenyl, methyl) then
variation at this position11 could be a productive avenue to pursue.
4.2. 1-(Phenylsulfonyl)dec-9-ene-2,5-dione 6a
n-BuLi (2.5 M in hexanes, 17.9 cm3, 44.8 mmol) was added to
a stirred solution of methylphenyl sulfone (7.00 g, 44.8 mmol) in
THF (100 cm3) at 0 °C. The reaction mixture was warmed to
room temperature for 30 min, then methyl 4,4-dimethoxynon-
8-enoate4 5 (3.43 g, 14.9 mmol) in THF (15 cm3) was added via
cannula. The mixture was stirred at room temperature for
20 min, then heated at reflux for 3 h. After being allowed to cool,
aq HCl (2 M, 100 cm3) was added and the mixture was extracted
with Et2O (3 ꢃ 250 cm3). The combined organic layers were
washed successively with H2O (300 cm3), saturated aq. NaHCO3
(150 cm3), brine (200 cm3), then dried over MgSO4 and evapo-
rated under reduced pressure. Purification of the residue by col-
umn chromatography (SiO2, 3:2 petrol/Et2O) gave a colourless
oil, which solidified upon standing, b-ketophenyl sulfone 6a
(2.82 g, 61%): mp 44–45 °C (petrol–EtOAc); Rf 0.15 (1:1 petrol/
Et2O); (C16H20O4S requires C, 62.3; H, 6.5. Found: C, 62.6; H,
6.7); mmax (KBr disc)/cmꢁ1 2929 m (CH), 1713s (C@O), 1448 m,
1388 m, 1309s (SO2) and 1149s (SO2); dH (400 MHz; CDCl3)
7.89-7.86 (2H, m, 2 ꢃ aromatic H), 7.67–7.62 (1H, m, aromatic
H), 7.56-–7.52 (2H, m, 2 ꢃ aromatic H), 5.70 (1H, ddt, J 17, 10
and 7, @CH), 4.99–4.91 (2H, m, CH2@), 4.22 (2H, s, CH2SO2),
2.93–2.90 (2H, m, COCH2CH2CO), 2.68–2.66 (2H, m, COCH2CH2-
CO), 2.40 (2H, t, J 7.5, @CH(CH2)2CH2), 1.99 (2H, q, J 7, @CHCH2)
and 1.61 (2H, quin, J 7.5, CH2CH2CH2); dC (100 MHz; CDCl3)
208.5 (C@O), 197.1 (C@O), 138.6 (aromatic C), 137.8 (@CH),
134.2 (aromatic CH), 129.3 (2 ꢃ aromatic CH), 128.2 (2 ꢃ aro-
matic CH), 115.3 (CH2@), 67.0 (CH2SO2), 41.5 (CH2), 37.8 (CH2),
36.3 (CH2), 32.9 (CH2) and 22.7 (CH2); m/z (APCI) 331 (M+Na+,
42%), 309 (M+H+, 76), 291 (35), 149 (100) and 122 (50).
4. Experimental
4.1. General
All reactions requiring anhydrous conditions were conducted in
flame- or oven-dried apparatus under an argon atmosphere. Syrin-
ges and needles for the transfer of reagents were oven-dried and
allowed to cool in a desiccator over self-indicating silica gel or
P2O5 prior to use. All solvents were distilled before use. Ethers were
distilled from sodium/benzophenone ketyl; (halogenated) hydro-
carbons and MeCN from CaH2. ‘Petrol’ refers to the fraction of light
petroleum ether boiling between 40 and 60 °C. Degassing in the
Rh(II)-catalysed reactions was performed by purging the reaction
mixture with argon. Reactions were monitored by TLC using com-
mercially available aluminium- or glass-backed plates pre-coated
with silica (0.25 mm, Merck 60 F254), which were developed using
standard visualising techniques: UV fluorescence (254 nm) and/or
potassium permanganate or vanillin solution, followed by heating.
Flash chromatography was performed on Kieselgel 60 (40–63 lm).
Solvents were removed using a Büchi rotary evaporator under re-
duced pressure and residual solvent was removed with a static
oil pump (ꢂ1 mmHg). Melting points were determined using a
Griffin melting point apparatus and are uncorrected. IR spectra
were recorded as thin films on NaCl discs or as KBr discs on a Per-
kin–Elmer Paragon 1000 Fourier transform spectrometer. Selected
4.3. 1-Diazo-1-(phenylsulfonyl)dec-9-ene-2,5-dione 7a
Et3N (1.0 cm3, 7.2 mmol) was added dropwise to a stirred
solution of b-ketophenyl sulfone 6a (2.00 g, 6.49 mmol) and
4-acetamidobenzenesulfonyl azide (1.72 g, 7.16 mmol) in MeCN
(50 cm3) at 0 °C. After 1.5 h, the mixture was filtered through
Celite, saturated aq NH4Cl (100 cm3) was added and the mix-
ture was extracted with Et2O (3 ꢃ 100 cm3). The combined or-
ganic layers were washed with brine (250 cm3), dried over
MgSO4 and evaporated under reduced pressure. Purification of
the residue by column chromatography (SiO2, 2:1 petrol/Et2O)
absorbances (mmax) are reported. Peak intensities are specified as
strong (s), medium (m) or weak (w). 1H and 13C NMR spectra were
recorded using Bruker DPX400 (400 MHz), AM500 (500 MHz) or
AMX500 (500 MHz) spectrometers. Chemical shifts (dH) are quoted
in parts per million (ppm), referenced to the appropriate solvent
peak (CHCl3, 7.27). Coupling constants (J) are reported to the near-
est 0.5 Hz; multiplicities are given as multiplet (m), singlet (s),
doublet (d), triplet (t), quartet (q) and quin (quintet). Chemical
shifts (dC) are quoted in ppm, referenced to the appropriate resid-
ual solvent peak (CDCl3, central line of triplet, 77.0). Mass Spectra
were obtained from the EPSRC Mass Spectrometry Service Centre,
Swansea using a Micromass Quattro II low resolution triple quad-
rupole mass spectrometer for EI or CI. Alternatively they were re-
corded on an Open Linx Micromass Platform 1 using APCI.
Accurate masses were obtained by the EPSCR Mass Spectrometry
Service Centre, Swansea using a Finnigan MAT 900 XLT high reso-
lution double focusing mass spectrometer with tandem ion trap.
Microanalyses were performed by Elemental Microanalysis Lim-
ited, Okehampton, Devon. Chiral stationary phase HPLC was per-
formed using a Daicel Chiralpak OD column (4.6 mm ꢃ 250 mm)
on a Gilson System with 712 Controller Software and a 118 UV–
vis detector set at 254 nm. Chiral GC was performed using a Ther-
moQuest CE Instruments TRACE GC, running Chrom-Card for
TRACE software, fitted with a CYDEX-b column at 180 °C. Retention
gave a pale yellow oil, which solidified on standing,
a-diazo-
b-ketophenyl sulfone 7a (1.66 g, 77%): mp 28–29 °C (Et2O); Rf
0.45 (1:1 petrol/Et2O); (C16H18N2O4S requires C, 57.5; H, 5.4;
N, 8.4. Found: C, 57.35; H, 5.5; N, 8.2); mmax (thin film)/cmꢁ1
2934w (CH), 2117s (CN2), 1714s (C@O), 1667s (C@O), 1448m,
1336s (SO2) and 1155s (SO2); dH (400 MHz; CDCl3) 8.06–7.98
(2H, m, 2 ꢃ aromatic H), 7.69–7.65 (1H, m, aromatic H),
7.61–7.57 (2H, m, 2 ꢃ aromatic H), 5.73 (1H, ddt,
J 17, 10
and 7, @CH), 5.01–4.95 (2H, m, CH2@), 2.84–2.81 (2H, m,
COCH2CH2CO), 2.73–2.70 (2H, m, COCH2CH2CO), 2.41 (2H, t, J
7.5, @CH(CH2)2CH2), 2.01 (2H, q, J 7, @CHCH2) and 1.63 (2H,
quin,
J 7.5, CH2CH2CH2); dC (100 MHz; CDCl3) 208.4 (C@O),
187.2 (C@O), 141.8 (aromatic C), 137.8 (@CH), 134.1 (aromatic
CH), 129.5 (2 ꢃ aromatic CH), 127.3 (2 ꢃ aromatic CH), 115.3
(CH2@), 41.6 (CH2), 35.9 (CH2), 32.9 (CH2), 32.9 (CH2) and
þ
22.6 (CH2) (CN2 not observed); m/z (CI, NH3) 352 M+(NH4
,
100%), 335 (M+H+, 25) and 326 (59) (C16H19N2O4S requires
times (tR) are given in min. Optical rotations ½a DT
ꢀ
were measured
M, 335.1066. Found: M+H+, 335.1064).

D. M. Hodgson et al. / Tetrahedron: Asymmetry 20 (2009) 754–757
757
4.4. General procedure for cycloadditions
A Rh(II) catalyst (0.5 mol%) was added to
1712m (C@O), 1663s (C@O), 1330s (SO2) and 1147s (SO2); dH
(400 MHz; CDCl3) 5.74 (1H, ddt, J 17, 10 and 7, @CH), 5.03–4.95
(2H, m, CH2@), 3.35 (3H, s, Me), 2.87–2.80 (4H, m, COCH2CH2CO),
2.46 (2H, t, J 7.5, @CH(CH2)2CH2), 2.04 (2H, q, J 7, @CHCH2) and
1.67 (2H, quin, J 7.5, CH2CH2CH2); dC (100 MHz; CDCl3) 209.1
(C@O), 187.9 (C@O), 137.7 (@CH), 115.4 (CH2@), 84.2 (CN2), 45.6
(Me), 41.5 (CH2), 36.6 (CH2), 32.9 (CH2), 32.6 (CH2) and 22.7
(CH2); m/z (CI, NH3) 290 M+(NH4þ, 100%), 273 (M+H+, 14), 264
(40) and 246 (46) (C11H17N2O4S requires M, 273.0909. Found:
M+H+, 273.0902).
a-diazo-b-keto sulfone
7a or 7b (ꢂ0.2 mmol) in the desired solvent (3 cm3) and the mix-
ture was stirred until the substrate was consumed (typically with-
in 2 h, by TLC monitoring). The reaction mixture was then
evaporated under reduced pressure and the residue was purified
by column chromatography (SiO2, 1:1 petrol/Et2O).
4.5. 7-(Phenylsulfonyl)-11-oxatricyclo[5.3.1.01,5]undecan-8-
one 8a
4.8. 7-(Methylsulfonyl)-11-oxatricyclo[5.3.1.01,5]undecan-8-
one 8b
Following the General Procedure for the cycloadditions using a-
diazo-b-ketophenyl sulfone 7a gave white crystals, cycloadduct 8a:
mp (racemate) 196–198 °C (petrol–CH2Cl2); Rf 0.10 (1:2 petrol/
Et2O); (C16H18O4S requires C, 62.7; H, 5.9. Found: C, 62.4; H,
5.95); mmax (KBr disc)/cmꢁ1 2931w (CH), 1732s (C@O), 1448m,
1323s (SO2), 1310s, 1168s and 1145s (SO2); dH (400 MHz; CDCl3)
7.99–7.97 (2H, m, 2 ꢃ aromatic H), 7.67–7.62 (1H, m, aromatic
H), 7.55–7.51 (2H, m, 2 ꢃ aromatic H), 2.60 (1H, dd, J 13.5 and 9,
CHH), 2.49–2.43 (3H, m, CH and CH2), 2.35–2.30 (1H, m, CHH),
2.22 (1H, dd, J 13.5 and 5.5, CHH), 2.05-2.00 (1H, m, CHH), 1.88–
1.77 (2H, m, 2 ꢃ CHH), 1.66–1.58 (2H, m, 2 ꢃ CHH), 1.53–1.45
(1H, m, CHH) and 1.41–1.36 (1H, m, CHH); dC (100 MHz; CDCl3)
201.7 (C@O), 136.0 (aromatic C), 134.1 (aromatic CH), 130.6
(2 ꢃ aromatic CH), 128.5 (2 ꢃ aromatic CH), 99.8 (C–O), 96.5 (C–
O), 45.4 (CH), 39.8 (CH2), 36.9 (CH2), 35.2 (CH2), 33.8 (CH2), 32.5
(CH2) and 24.7 (CH2); m/z (APCI) 329 (M+Na+, 50%), 307 (M+H+,
75), 143 (82), 135 (100) and 122 (78) (C16H22NO4S requires M,
324.1270. Found: M+NH4þ, 324.1271). ees were determined by
HPLC (Daicel Chiralpak OD, 60:40 heptane/EtOH, 1 cm3 minꢁ1) tR
11.8 and 13.8 (major enantiomer elutes first when specific rotation
is positive).
Following the General Procedure for cycloadditions using a-dia-
zo-b-ketomethyl sulfone 7b gave a white solid, cycloadduct 8b: mp
(racemate) 120–121 °C (EtOAc); Rf 0.30 (1:3 petrol/Et2O);
(C11H16O4S requires C, 54.1; H, 6.6. Found: C, 54.0; H, 6.95); mmax
(KBr disc)/cmꢁ1 2936w (CH), 1728s (C@O), 1444w, 1312s (SO2),
1165m and 1142m (SO2); dH (500 MHz; CDCl3) 3.02 (3H, s, Me),
2.67–2.62 (3H, m, CH and CH2), 2.57 (1H, dd, J 13.5 and 9, CHH),
2.50–2.41 (2H, m, 2 ꢃ CHH), 2.16–2.12 (1H, m, CHH), 2.04–1.96
(3H, m, 3 ꢃ CHH) and 1.78–1.59 (3H, m, 3 ꢃ CHH); dC (125 MHz;
CDCl3) 201.7 (C@O), 99.2 (C–O), 98.3 (C–O), 45.8 (CH), 38.6 (Me),
38.2 (CH2), 36.9 (CH2), 35.7 (CH2), 34.5 (CH2), 34.4 (CH2) and
25.7 (CH2); m/z (CI, NH3) 262 M+(NH4þ, 100%) and 184 (8)
(C11H20NO4S requires M, 262.1113. Found: M+NH4þ, 262.1117).
ee was determined by GC (CYDEX-b, 180 °C) tR 31.6 and 33.0.
Acknowledgements
We thank the EPSRC and GlaxoSmithKline for a CASE award (to
R.G.), Dr. B. Odell for NMR experiments and the EPSRC National
Mass Spectrometry Service Centre for mass spectra.
4.6. 1-(Methylsulfonyl)dec-9-ene-2,5-dione 6b
References
Following the procedure for ketophenyl sulfone 6a, but using n-
BuLi (2.5 M in hexanes, 13.0 cm3, 32.5 mmol), dimethylsulfone
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Synthesis with Diazo Compounds; John Wiley & Sons: New York, 1998;; (b)
Hodgson, D. M.; Stupple, P. A.; Forbes, D. C. In Rodd’s Chemistry of Carbon
Compounds; Sainsbury, M., Ed.; Topical Volume, Asymmetric Catalysis;
Elsevier: Oxford, 2001; pp 65–99; (c) McMills, M. C.; Wright, D. In Synthetic
Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and
Natural Products; Padwa, A., Pearson, W. H., Eds.; John Wiley & Sons: New York,
2002; pp 253–314; (d) Clark, J. S. Nitrogen, Oxygen and Sulfur Ylide Chemistry;
Oxford University Press: Oxford, 2002;; (e) Mehta, G.; Muthusamy, S.
Tetrahedron 2002, 58, 9477–9504; (f) Selden, D. A.; Hodgson, D. M.. In
Comprehensive Organic Functional Group Transformations II; Jones, K., Ed.;
Elsevier: Oxford, 2004; Vol. 3, pp 309–353; (g) Zhang, Z.; Wang, J. Tetrahedron
2008, 64, 6577–6605.
2. For the first report: (a) Hodgson, D. M.; Stupple, P. A.; Johnstone, C. Tetrahedron
Lett. 1997, 38, 6471–6472; For more recent examples, see: (b) Hodgson, D. M.;
Brückl, T.; Glen, R.; Labande, A. H.; Selden, D. A.; Dossetter, A. G.; Redgrave, A. J.
Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5450–5454; (c) Shimada, N.; Anada, M.;
Nakamura, S.; Nambu, H.; Tsutsui, H.; Hashimoto, S. Org. Lett. 2008, 10, 3603–
3606.
(3.08 g, 32.7 mmol) and methyl 4,4-dimethoxynon-8-enoate4
5
(2.51 g, 10.9 mmol) gave, after purification of the residue by column
chromatography (SiO2, CH2Cl2), a colourless oil which solidified
upon standing, b-ketomethyl sulfone 6b (1.99 g, 74%): mp 43–
44 °C (petrol-Et2O); Rf 0.20 (1:2 petrol/Et2O); (C11H18O4S requires
C, 53.6; H, 7.4. Found: C, 53.7; H, 7.7); m
max (KBr disc)/cmꢁ1 3004w,
2940m (CH), 1718s (C@O), 1644w, 1388m, 1310s (SO2) and 1144s
(SO2); dH (400 MHz; CDCl3) 5.75 (1H, ddt, J 17, 10 and 7, @CH),
5.04–4.96 (2H, m, CH2@), 4.13 (2H, s, CH2SO2), 3.04 (3H, s, Me),
2.93–2.90 (2H, m, COCH2CH2CO), 2.77–2.74 (2H, m, COCH2CH2CO),
2.46 (2H, t, J 7.5, @CH(CH2)2CH2), 2.04 (2H, q, J 7, @CHCH2) and
1.67 (2H, quin, J 7.5, CH2CH2CH2); dC (100 MHz; CDCl3) 208.6
(C@O), 198.5 (C@O), 137.8 (@CH), 115.3 (CH2@), 65.0 (CH2SO2),
41.5 (CH2), 41.4 (Me), 37.8 (CH2), 36.3 (CH2), 32.9 (CH2) and 22.7
(CH2); m/z (CI, NH3) 264 M+(NH4þ, 100%) and 246 (M+, 47)
(C11H22NO4S requires M, 264.1270. Found: M+NH4þ, 264.1268).
3. Hodgson, D. M.; Pierard, F. Y. T. M.; Stupple, P. A. Chem. Soc. Rev. 2001, 30, 50–
61.
4. (a) Hodgson, D. M.; Stupple, P. A.; Pierard, F. Y. T. M.; Labande, A. H.; Johnstone,
C. Chem. Eur. J. 2001, 7, 4465–4476; (b) Hodgson, D. M.; Glen, R.; Grant, G. H.;
Redgrave, A. J. J. Org. Chem. 2003, 68, 581–586.
4.7. 1-Diazo-1-(methylsulfonyl)dec-9-ene-2,5-dione 7b
5. Simpkins, N. S. Sulphones in Organic Synthesis; Pergamon Press: Oxford, 1993.
6. For recent examples, see: (a) Watanabe, H.; Nakada, M. Tetrahedron Lett. 2008,
49, 1518–1522; (b) Gomes, L. F. R.; Trindade, A. F.; Candeias, N. R.; Gois, P. M. P.;
Afonso, C. A. M. Tetrahedron Lett. 2008, 49, 7372–7375.
Following the procedure for
a-diazo-b-ketophenyl sulfone 7a,
but using DBU (1.1 cm3, 7.36 mmol), b-ketomethyl sulfone 6b
(1.50 g, 6.10 mmol) and 4-acetamidobenzenesulfonyl azide
(1.76 g, 7.33 mmol) gave, after purification of the residue by col-
umn chromatography (SiO2, 1:2 petrol/Et2O), a pale yellow oil
7. Johnson, T.; Cheshire, D. R.; Stocks, M. J.; Thurston, V. T. Synlett 2001, 647–648;
For
isomünchnone
formation—intermolecular
cycloaddition
from
diazosulfones, see: Padwa, A.; Sheehan, S. M.; Straub, C. S. J. Org. Chem. 1999,
64, 8648–8659.
8. House, H. O.; Larson, J. R. J. Org. Chem. 1968, 33, 61–65.
9. Baum, J. S.; Shook, D. A.; Davies, H. M. L.; Smith, H. D. Synth. Commun. 1987, 17,
1709–1716.
10. Gawley, R. E. J. Org. Chem. 2005, 71, 2411–2416.
11. Takeda, H.; Nakada, M. Tetrahedron: Asymmetry 2006, 17, 2896–2906.
which solidified on standing,
a-diazo-b-ketomethyl sulfone 7b
(249 mg, 15%): mp 32–33 °C (Et2O); Rf 0.60 (1:3 petrol/Et2O);
(C11H16N2O4S requires C, 48.5; H, 5.9; N, 10.3. Found: C, 48.6; H,
6.0; N, 10.2); mmax (thin film)/cmꢁ1 2928w (CH), 2122 (CN2),