Ethyl (benzothiazol-2-ylsulfonyl)acetate: A new reagent for the stereoselective synthesis of α,β-unsaturated esters from aldehydes

Article abstract of DOI:10.1039/b500713e

The title reagent engaged in the modified Julia olefination with aldehydes under mild reaction conditions (DBU, CH₂Cl₂, rt or -78°C) to yield α,β-unsaturated esters; aryl aldehydes and aliphatic aldehydes possessing significant chain branching elements gave trans alkene products with high stereoselectivity (E : Z up to >98 : 2), while straight chain aliphatic aldehydes gave cis products preferentially (Z : E up to 92 : 8). The Royal Society of Chemistry 2095.

Full text of DOI:10.1039/b500713e

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C O M M U N I C A T I O N
Ethyl (benzothiazol-2-ylsulfonyl)acetate: a new reagent for the
stereoselective synthesis of a,b-unsaturated esters from aldehydes†‡
Paul R. Blakemore,*§ Danny K. H. Ho and W. Mieke Nap
School of Chemistry, University of Leeds, Leeds, West Yorkshire, UK LS2 9JT.
E-mail: paul.blakemore@science.oregonstate.edu
Received 15th January 2005, Accepted 24th February 2005
First published as an Advance Article on the web 8th March 2005
The title reagent engaged in the modified Julia olefination
with aldehydes under mild reaction conditions (DBU,
Substrate substituent effects are a major determinant of
stereochemical outcome for the modified Julia olefination.3 For
example, BT-sulfonyl anions 2 which are semi-stabilized (R1 =
Ph, vinyl) generally react with straight-chain aliphatic aldehydes
to afford (Z)-alkene products preferentially.4a,b,5b This bias for the
cis olefin is heightened with analogous TBT-sulfones but may
be reversed with PT-sulfones.8 By contrast, branched aliphatic
and aromatic aldehydes often give (E)-alkenes preferentially
with all types of semi-stabilized heteroaryl sulfonyl anions 2.
Intrigued by whether similar behaviour would be exhibited by
fully stabilized heteroaryl sulfonyl anions 2 (R1 = carbonyl),
and cognizant of the fact that the modified Julia olefination had
not previously been applied to the synthesis of a,b-unsaturated
esters, we duly prepared sulfones 6–8 and set about exploring
their reactions with aldehydes.
◦
CH2Cl2, rt or −78 C) to yield a,b-unsaturated esters; aryl
aldehydes and aliphatic aldehydes possessing significant
chain branching elements gave trans alkene products with
high stereoselectivity (E : Z up to >98 : 2), while straight
chain aliphatic aldehydes gave cis products preferentially
(Z : E up to 92 : 8).
The a,b-unsaturated ester moiety boasts a rich chemistry and
this useful structural unit is a common target of synthesis.
Carbonyl olefination reactions, being inherently convergent
and often highly stereoselective, offer an attractive route to
conjugated enoates.1 Of these methods, the Horner–Wadsworth–
Emmons (HWE) reaction of phosphonoacetate derivatives
is arguably the most versatile.2 Herein, we report that the
modified Julia olefination (one-pot Julia olefination) employing
the title sulfonylacetate reagent offers a viable alternative to the
HWE reaction for the stereoselective synthesis of simple a,b-
unsaturated esters from aldehydes.
The modified Julia olefination, a direct synthesis of alkenes
via the condensation of certain heteroaryl/aryl sulfonyl anions
2 with carbonyl compounds, has emerged as a useful tool
for fragment linkage (Fig. 1).3,4 This process was originally
described with benzothiazol-2-yl (BT) sulfones5 but has since
been extended to include other types of heteroaryl sulfones
(e.g. pyrid-2-yl (PYR),5b,6 1-phenyl-1H-tetrazol-5-yl (PT),7 and
1-tert-butyl-1H-tetrazol-5-yl (TBT)8 sulfones) and more re-
cently non-heteroaryl 3,5-bis(trifluoromethyl)phenyl (BTFP)9
sulfones.10
BT-sulfone 6 was available in 71% overall yield (after recrys-
tallization) from inexpensive 2-mercaptobenzothiazole (3) by
base mediated S-alkylation with ethyl chloroacetate followed
by ammonium molybdate catalyzed oxidation with hydrogen
peroxide (Scheme 1).11 PT- and TBT-sulfones 7 and 8 were
similarly prepared, albeit in lower yield.12 With this selection
of sulfonyl acetates in hand, the synthesis of ethyl cinnamate (9)
from benzaldehyde via modified Julia olefination was pursued
in order to identify optimal reaction conditions (Table 1).
Scheme 1 Synthesis of heteroaryl sulfonyl acetates 6–8.
Under conditions previously employed for the modified Julia
olefination (NaHMDS, THF, −78 ◦C → rt), BT-sulfone 6
failed to react with benzaldehyde to any significant extent.
This negative result was not surprising given that the stabilized
enolate derived from 6 was expected to be a poor nucleophile.
Nucleophilic competancy was conferred on the anion of 6 by
briefly heating the reaction mixture to reflux. In this manner,
trans-ethyl cinnamate (E : Z > 98 : 2) was produced in 63%
yield based on benzaldehyde as the limiting reagent (entry 1).
Disappointingly, little (if any) reaction was observed for tetra-
zolyl sulfones 7 and 8 under the same conditions (entries 2, 3)13
and subsequent experiments were conducted with BT-sulfone 6.
Weaker ionic bases were next examined and both potassium tert-
butoxide and cesium carbonate gave a modest yield of alkene
product, although heating was again necessary (entries 4, 5).
In an effort to identify milder conditions that might permit
olefination at ambient temperature, the reaction was attempted
with a series of neutral amine bases in tetrahydrofuran (en-
tries 7 to 10). Triethylamine and 1,4-diazabicyclo[2.2.2]octane
(DABCO) failed to promote olefination, but a combination
of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and anhydrous
Fig. 1 The modified Julia olefination and common aromatic activators
(Act): BT = benzothiazol-2-yl, PYR = pyrid-2-yl, PT = 1-phenyl-
1H-tetrazol-5-yl, TBT = 1-tert-butyl-1H-tetrazol-5-yl, BTFP = 3,5-
bis(trifluoromethyl)phenyl.
† Dedicated to the memory of Prof. Sylvestre A. Julia.
‡ Electronic supplementary information (ESI) available: experimen-
tal procedures and characterisation data for compounds 7 and 8,
spectral data (IR, 1H NMR, 13C NMR) for alkene products. See
http://www.rsc.org/suppdata/ob/b5/b500713e/
§ Present address: Department of Chemistry, Oregon State University,
153 Gilbert Hall, Corvallis, Oregon 97331-4003, USA.
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 3 6 5 – 1 3 6 8
1 3 6 5
©

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Table 1 Synthesis of ethyl (E)-cinnamate (9) by modified Julia olefination with heteroaryl sulfonyl acetates 6–8
Entry
Sulfone (1.5 eq.)
Base (1.5 eq.)
Solvent
Temperature/◦C
Time/h
Yield (%)a
1b
2b
3b
4
5
6
7
8
9
10
11c
12
13
14
15
16d
17e
6
7
8
6
6
6
6
6
6
6
6
6
6
6
6
6
6
NaHMDS
NaHMDS
NaHMDS
t-BuOK
Cs2CO3
None
THF
THF
THF
THF
THF
THF
THF
THF
65
65
65
65
65
65
23
23
23
23
23
23
23
23
23
23
23
2
2
2
63
5
0
30
31
0
16
24
16
70
16
20
24
16
16
16
16
16
16
16
Et3N
0
0
DABCO
DBU–LiCl
DBU
DBU
DBU
DBU
DBU
DBU
DBU
THF
THF
21
45
57
66
68
54
61
78
88
MeOH
EtOH
MeCN
Et2O
CH2Cl2
CH2Cl2
CH2Cl2
DBU
1H NMR analysis indicated E : Z ≥ 95 : 5 for all entries where 9 was produced. b NaHMDS (1.1 eq.) added to sulfone (1.2 eq.) at 0 ◦C, stirred
a
for 30 min, then benzaldehyde added and heated to reflux for 2 h. c Reaction yielded methyl cinnamate. d Sulfone 6 (2 eq.)–DBU (2 eq.). e Sulfone 6
(3 eq.)–DBU (3 eq.).
Table 2 Olefination of aromatic and alkyl aldehydes with ethyl
(benzothiazol-2-ylsulfonyl)acetate (6)
lithium chloride, a reagent system introduced by Roush and
Masamune for deprotonation of ketophosphonates in the HWE
reaction,14 gave 21% of 9 after 20 h at rt (entry 9). Pleasingly,
the same experiment conducted without lithium chloride gave
an improved yield of 9 in a comparable time period (entry
10).15 With a mild and effective base identified, attention was
directed at finding an optimum solvent for the Julia olefination
between 6 and benzaldehyde (entries 11 to 15).16 The reaction
performed moderately well in all of the new media examined,
including polar protic solvents, and in all cases, ethyl cinnamate
was produced with E : Z ≥ 95:5. Dichloromethane has favorable
attributes for laboratory scale preparative chemistry (e.g. water
immiscibility, low boiling point, low cost) and was chosen as the
preferred solvent for further study. Acceptable yields of ethyl
cinnamate (with E : Z = 96 : 4) were obtained within a convenient
time frame by employing sulfone and base in two- or three-fold
excess (entries 16, 17). Adopting the less extravagant of these
two protocols, the wider scope of the olefination reaction with a
range of different aldehydes was examined (Table 2).
Sulfone 6 olefinated aryl aldehydes in generally good yields
using the standard reaction conditions (Table 2, entries 1 to
10). As expected from earlier results with benzaldehyde, (E)-
configurated a,b-unsaturated esters were formed preferentially.
Stereoselectivity was dependent on the steric demand of the
aldehyde and its electronic character. Electron rich aryl alde-
hydes gave lower trans stereoselectivity than electron deficient
examples (e.g. decreasing E : Z from entry 1 to entry 4), while
sterically congested aldehydes gave higher trans selectivity than
comparable less encumbered examples (cf. entry 6 vs. entry 5;
entry 9 vs. entry 8).
Entry
Aldehyde
Yield (%)
E : Za,b
1
2c
3
4
5
6
7
8
9
10
11
12
13
14
15
16d
17e
4-(NO2)C6H4CHO
4-(HO2C)C6H4CHO
4-ClC6H4CHO
4-(MeO)C6H4CHO
2-ClC6H4CHO
2,6-Cl2C6H3CHO
2,4,6-Me3C6H2CHO
2-Naphthaldehyde
1-Naphthaldehyde
Ferrocenecarboxaldehyde
n-C5H11CHO
89
57
77
93
72
83
70
65
86
82
41
64
80
88
21
80
—
>98 : 2
96 : 4
95 : 5
92 : 8
95 : 5
>98 : 2
>98 : 2
93 : 7
96 : 4
96 : 4
19 : 81
30 : 70
80 : 20
>98 : 2
>98 : 2
>98 : 2
N/a
Citronellal
c-C6H11CHO
Et2CHCHO
t-BuCHO
PhCH2CHO
=
(E)-PhCH CHCHO
a Determined by 1H NMR analysis before chromatographic purification.
b E : Z > 98 : 2 indicates only trans-isomer observable by 1H NMR. c DBU
(3 eq.). d Product was a mixture of a,b- and b,c -unsaturated esters (1 : 9
respectively, both regioisomers E : Z > 98 : 2). e Reaction gave a complex
mixture of intractable products.
The reactions of sulfone 6 with a series of aliphatic aldehydes
revealed interesting, though not entirely unexpected behaviour
(entries 11 to 15). The stabilized anion of sulfone 6 reacted
with n-hexanal to give a (Z)-enoate as the major product (entry
11).17 Any preference for the cis isomer was, however, eroded
upon incremental introduction of chain-branching elements
onto the aldehyde substrate. Thus, citronellal, a representative
b-branched aldehyde (RC(Me)HCH2CHO), gave a significantly
reduced Z : E ratio as compared to n-hexanal (entry 12). With
cyclohexanecarboxaldehyde, an a-branched aldehyde, the stere-
ochemical bias was reversed in favor of the trans enoate (entry
13). Aliphatic aldehydes possessing greater steric encumbrance
gave trans alkenes as the only detectable products (entries 14,
15). Olefination yield within the aliphatic series increased to a
maximum for 2-ethylbutanal (entry 14), presumably a conse-
quence of the greater stability of this hindered aldehyde (and
the derived enoate product) to base mediated decomposition
pathways. Pivalaldehyde, while also stable to decomposition,
proved too hindered to react effectively with sulfone 7 and gave
only 21% of alkene product (entry 15).
1 3 6 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 3 6 5 – 1 3 6 8

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The reactions of two miscellaneous carbonyl compounds
with sulfone 6 revealed limitations to our method. Alkene
formation from phenylacetaldehyde was non-regiospecific and
the b,c -unsaturated ester product predominated (entry 16).
Attempted reaction with (E)-cinnamaldehyde, a representative
a,b-unsaturated aldehyde, gave a complex mixture of intractable
products (entry 17). Finally, it is worth noting that, acetophe-
none did not react with BT-sulfone 6 at all under two sets of
reaction conditions tested (DBU, CH2Cl2, rt, or NaHMDS,
THF, D).
The stereochemical outcomes of the reactions discussed above
for sulfone 6 (Tables 1 and 2) are in accord with trends previously
observed for semi-stabilized BT-sulfonyl anions (vide supra).
At the outset of this study, we had hoped to develop a new
synthesis of a,b-unsaturated esters which would allow for control
of stereochemical preference by a simple choice of reaction
conditions and/or activating group. Such programmability is
possible in most cases with the HWE reaction.18 The failure
of tetrazolyl sulfones 7 and 8 to effectively olefinate aldehydes
prevented us from achieving this goal by the exploitation of
activator effects alone; however, in one case at least, we were able
to demonstrate stereodivergent enoate formation by variation
of reaction conditions (Scheme 2). Thus, treatment of n-hexanal
(10) with BT-sulfone 6 and DBU in dichloromethane at −78 ◦C
gave (Z)-oct-2-enoate 11-Z with Z : E = 92 : 8, while (E)-oct-
2-enoate 11-E was formed preferentially from the same starting
materials using NaHMDS as base in refluxing tetrahydrofuran.19
It is anticipated that future advances along these lines will lead
to a variant of the modified Julia olefination which will truly
rival the HWE reaction for the programmable synthesis of (E)-
or (Z)-configurated enoates.
72 mmol). The mixture was heated at reflux for 20 h, allowed to
cool and filtered. Concentration of the filtrate in vacuo yielded
15.3 g of crude ethyl (benzothiazol-2-ylsulfanyl)acetate as a
brown oil. A stirred solution of this material in EtOH (50 mL)
at 0 ◦C was treated with (NH4)6Mo7O24·4H2O (3.7 g, 3.0 mmol)
followed by aq. H2O2 (23.1 mL, d = 1.18, 27.2 g, 30 wt%,
240 mmol). The resulting solution was allowed to warm slowly
to rt and stirred for 42 h. After this time, the bulk of the
EtOH solvent was removed in vacuo and the residue partitioned
between EtOAc (50 mL) and H2O (50 mL). The layers were
separated and the aqueous phase extracted with EtOAc (2 ×
25 mL). The combined organic extracts were washed with brine
(20 mL), dried (Na2SO4) and concentrated in vacuo to yield 16.1 g
of sulfone 6 as an off-white solid (>90% purity as adjudged
by 1H NMR analysis). Recrystallisation from tert-butyl methyl
ether (TBME) afforded analytically pure ethyl (benzothiazol-
2-ylsulfonyl)acetate (6, 12.1 g, 42.4 mmol, 71%) as colourless
◦
prisms: mp 58–59 C (TBME) [lit.11 mp 61–62 ◦C); IR (neat)
3461, 2983, 1736, 1470, 1273, 1152, 1026, 910, 853, 770, 614 cm−1;
1H NMR (300 MHz, CDCl3) d 8.23 (1H, dd, J = 7.1, 1.8 Hz),
8.04 (1H, dd, J = 7.0, 1.9 Hz), 7.67 (1H, td, J = 7.2, 1.6 Hz),
7.62 (1H, td, J = 7.3, 1.6 Hz), 4.58 (2H, s), 4.18 (2H, q, J =
7.2 Hz), 1.17 (3H, t, J = 7.1 Hz) ppm; 13C NMR (75 MHz,
CDCl3) d 165.0 (0), 161.7 (0), 152.5 (0), 137.1 (0), 128.4 (1),
127.9 (1), 125.7 (1), 122.5 (1), 62.9 (2), 58.9 (2), 13.9 (3) ppm;
MS (ES+) m/z 286 (M + H)+; Anal. Calcd. for C11H11NO4S2: C,
46.30; H, 3.89; N, 4.91. Found: C, 46.40; H, 4.00; N, 4.95.
General olefination procedure using DBU in CH2Cl2
A solution of BT-sulfone 6 (228 mg, 0.80 mmol) in CH2Cl2
(5 mL) was treated with DBU (0.12 mL, d = 1.02, 122 mg,
0.80 mmol) followed by the neat aldehyde (0.40 mmol) and
stirred at rt for 16 h. After this time, saturated aqueous NH4Cl
(5 mL) was added and the layers shaken and separated. The
aqueous phase was extracted (2 × 10 mL, CH2Cl2) and the
combined organic phases were washed with brine (10 mL), dried
(Na2SO4) and concentrated in vacuo. The residue was purified
by column chromatography (SiO2, eluting with 5–20% EtOAc
in hexanes) to yield the a,b-unsaturated ester product.
General olefination procedure using NaHMDS in THF
A stirred solution of BT-sulfone 6 (342 mg, 1.20 mmol) in
anhydrous THF (10 mL) at 0 ◦C under N2 was treated dropwise
with NaHMDS (1.10 mL, 1.0 M in THF, 1.10 mmol). After
stirring at 0 ◦C for 30 min, neat aldehyde (1.0 mmol) was added
and the reaction mixture heated at reflux for 2 h. The mixture
was then allowed to cool and partitioned between sat. aq. NH4Cl
(15 mL) and EtOAc (15 mL). The layers were separated and the
aqueous phase was extracted with EtOAc (2 × 15 mL). The
combined organic extracts were washed with brine (15 mL),
dried (Na2SO4), and concentrated in vacuo. The residue was
purified by column chromatography (SiO2, eluting with 5–20%
EtOAc in hexanes) to yield the a,b-unsaturated ester product.
Scheme 2 Stereodivergent synthesis of ethyl oct-2-enoate (11) from
n-hexanal (10) by modified Julia olefination.
In summary, ethyl (benzothiazol-2-ylsulfonyl)acetate (6), a
shelf-stable and easily handled crystalline solid,20 has been
demonstrated as a new reagent for the synthesis of a,b-
unsaturated esters. Modified Julia olefination employing sulfone
6 occurred under mild reaction conditions (DBU, CH2Cl2, rt),
required no special precautions (rigorous exclusion of air and
moisture unnecessary), and gave excellent yields of trans enoate
products for aromatic and moderately hindered aliphatic alde-
hydes. Non-hindered aliphatic aldehydes gave low to moderate
yields of either (E)- or (Z)-enoate products depending on the
reaction conditions.
Acknowledgements
The Royal Society are thanked for a University Research Fel-
lowship (to P.R.B.) and generous financial support. D.K.H.H.
and W.M.N. thank Pfizer Central Research (Sandwich, U.K.)
for summer research studentships.
Experimental
For a description of general techniques, details for the synthesis
of sulfones 7 and 8, and characterization data for all other
compounds, refer to the electronic supplementary information.
References
1 Preparation of Alkenes, ed. J. M. J. Williams, Oxford University Press,
Oxford, 1996.
Ethyl (benzothiazol-2-ylsulfonyl)acetate (6)
2 B. E. Maryanoff and A. B. Reitz, Chem. Rev., 1989, 89, 863.
3 For a comprehensive review, which includes discussion of mechanism
and a comparison of BT-, PYR-, PT-, and TBT-sulfones, see: P. R.
Blakemore, J. Chem. Soc., Perkin Trans. 1, 2002, 2563.
A stirred suspension of 2-mercaptobenzothiazole (3, 10.0 g, 59.8
mmol) and K2CO3 (9.9 g, 72 mmol) in acetone (100 mL) was
treated with neat ethyl chloroacetate (7.6 mL, d = 1.16, 8.8 g,
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 3 6 5 – 1 3 6 8
1 3 6 7

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4 Recent applications of the modified Julia olefination. With BT-
sulfones: (a) A. Sorg and R. Bru¨ckner, SYNLETT, 2005, 289; (b) B.
Vaz, R. Alvarez, J. A. Souto and A. R. de Lera, SYNLETT, 2005,
294; (c) Y. Jiang, J. Hong and S. D. Burke, Org. Lett., 2004, 6, 1445;
(d) D. R. Li, C. Y. Sun, G.-Q. Lin and W.-S. Zhou, Org. Lett., 2004,
6, 4261; (e) With PT-sulfones: J. M. Joo, H. S. Kwak, J. H. Park,
H. Y. Song and E. Lee, Bioorg. Med. Chem. Lett., 2004, 14, 1905;
(f) B. M. Trost and M. L. Crawley, Chem. Eur. J., 2004, 10, 2237;
(g) K. Ishigami and T. Kitahara, Heterocycles, 2004, 63, 785; (h) With
PYR-sulfones: P. Mauleo´n and J. C. Carretero, Org. Lett., 2004, 6,
3195.
5 (a) J. B. Baudin, G. Hareau, S. A. Julia and O. Ruel, Tetrahedron
Lett., 1991, 32, 1175; (b) J. B. Baudin, S. A. Hareau, S. A. Julia, R.
Lorne and O. Ruel, Bull. Soc. Chim. Fr., 1993, 130, 856.
6 A. B. Charette, C. Berthelette and D. St-Martin, Tetrahedron Lett.,
2001, 42, 5149; Correction: Tetrahedron Lett., 2001, 42, 6619.
7 P. R. Blakemore, W. J. Cole, P. J. Kocienski and A. Morley,
SYNLETT, 1998, 26.
W. Choy, J. T. Davis, A. P. Essenfeld, S. Masamune, W. R. Roush
and T. Sakai, Tetrahedron Lett., 1984, 25, 2183.
15 HWE reactions of diphenylphosphonate esters with DBU alone in
THF solvent have recently been reported, see: N. Ji, B. M. Rosen and
A. G. Myers, Org. Lett., 2004, 6, 4551.
16 From this stage forward, all experiments were conducted with GPR
grade solvents used as received, and no attempt was made to exclude
air or adventitious moisture from reaction vessels.
17 In an attempt to increase cis selectivity in this case, the analogous
reaction with TBT-sulfone 8 was conducted; however, the tetrazolyl
sulfone again proved unreactive and was recovered in quantitative
yield. Subsequently, the desired increase in stereoselectivity was
achieved by conducting the coupling reaction of BT-sulfone 6 with
n-hexanal at −78 ◦C (see Scheme 2).
18 The traditional HWE reaction employing diethylphosphonoacetates
is generally (E)-selective (see ref. 2); however, bis(trifluoroethyl)-
and diarylphosphonoacetates give (Z)-configurated enoates prefer-
entially under appropriate reaction conditions, see: (a) W. C. Still
and C. Gennari, Tetrahedron Lett., 1983, 24, 4405; (b) K. Ando,
Tetrahedron Lett., 1995, 36, 4105; (c) K. Ando, T. Oishi, M. Hirama,
H. Ohno and T. Ibuka, J. Org. Chem., 2000, 65, 4745.
8 P. J. Kocienski, A. Bell and P. R. Blakemore, SYNLETT, 2000, 365.
9 D. A. Alonso, C. Na´jera and M. Varea, Tetrahedron Lett., 2004, 45,
573.
10 Any aromatic moiety which can support ipso substitution of a
sulfinate nucleofuge can potentially be used as an activating group in
the modified Julia olefination.
11 Ethyl (benzothiazol-2-ylsulfonyl)acetate (6) has been previously
prepared in an analogous manner using AcOH–H2O2 in the oxidation
step, see: V. M. Svetlaeva, E. A. Kuznetsova and S. V. Zhuravlev, Zh.
Obshch. Khim., 1964, 34, 983.
12 1-Phenyl-1H-tetrazole-5-thiol (4) is commercially available. 1-tert-
Butyl-1H-tetrazole-5-thiol (5) was prepared by Quast’s method: H.
Quast and L. Bieber, Chem. Ber., 1981, 114, 3253.
13 In each of these two experiments, >85% of tetrazolyl sulfone starting
materials were recovered, indicating that failure of the reactions was
not due to decomposition of the metalated sulfones.
19 That (E)-stereoselectivity in this case was not simply the result of
base induced alkene isomerization was established as follows: Julia
olefination of benzaldehyde by BT-sulfone 6 was carried out as
previously described (Table 1, entry 1) in the presence methyl oct-
2-enoate with E : Z = 1 : 4. Following work-up, and purification by
column chromatography, the expected ethyl cinnamate product was
obtained in 58% yield (with E : Z > 98 : 2) together with 78% of
recovered methyl oct-2-enoate with E : Z = 1 : 4.
20 A colorless sample of crystalline sulfone 6 (mp 58–59 ◦C, TBME)
darkened significantly during 12 months of storage in a screw-
capped clear glass jar. Despite this discoloration, the aged sul-
fone exhibited no obvious signs of decomposition by 1H NMR
analysis and gave identical results in its olefination reactions with
aldehydes as compared to those conducted with freshly prepared
material.
14 This reagent system was originally employed by Masamune et al.
in MeCN, a weakly Lewis basic solvent, see: M. A. Blanchette,
1 3 6 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 3 6 5 – 1 3 6 8