Synthesis of 4-nitrophenyl sulfones and application in the modified Julia olefination

Article abstract of DOI:10.1055/s-2006-939682

4-Nitrophenyl (NP) sulfones have been successfully employed in the modified Julia olefination reaction with carbonyl compounds. The olefination reaction proceeds through a sequence of aldol addition, Smiles rearrangement, and elimination. The sulfones are easily prepared in high yields in a two-step sequence starting from inexpensive commercially available para- fluoronitrobenzenes via nucleophilic aromatic substitution by a mercaptane and subsequent oxidation under standard conditions. The modified Julia reaction between NP sulfones and a wide variety of aromatic aldehydes affords the corresponding styrenes, stilbenes and cinnamate derivatives in yields up to 97% and good stereoselectivities. A mechanistic rationale is advanced to explain the observed results. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-939682

LETTER
1255
Synthesis of 4-Nitrophenyl Sulfones and Application in the Modified Julia
Olefination
NP
Sulfones in theaModified
Julia
Olefinai
Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France
Fax +33(1)69077247; E-mail: zhu@icsn.cnrs-gif.fr
Received 21 December 2005
variant has emerged as a powerful tool for the direct ole-
fination process.8 Furthermore, the modified Julia reac-
tion followed by hydrogenation of the newly formed
double bond has also been used in numerous total synthe-
Abstract: 4-Nitrophenyl (NP) sulfones have been successfully em-
ployed in the modified Julia olefination reaction with carbonyl com-
pounds. The olefination reaction proceeds through a sequence of
aldol addition, Smiles rearrangement, and elimination. The sulfones
are easily prepared in high yields in a two-step sequence starting ses for the creation of Csp3–Csp3 bonds.12 Recently, the
from inexpensive commercially available para-fluoronitrobenzenes
application of non-heteroaryl 3,5-bis(trifluoromethyl)
via nucleophilic aromatic substitution by a mercaptane and sub-
phenyl (BTFP) sulfones in the direct Julia–Kocienski ole-
sequent oxidation under standard conditions. The modified Julia
fination has been given account by Nájera et al.13
reaction between NP sulfones and a wide variety of aromatic alde-
In this article, we report in full the development of novel
alkenylation conditions using 4-nitrophenyl (NP) sulfones
in the modified Julia olefination for the direct and stereo-
selective synthesis of alkenes. The mechanistic rationale
is shown in Scheme 1. Thus, it was anticipated that nu-
cleophilic attack of sulfonyl carbanion 3 onto the alde-
hyde would proceed in analogous fashion to the first step
of the classical Julia olefination. Intramolecular nucleo-
philic addition of the resulting b-alkoxy sulfone 4 would
be followed by a Smiles14 rearrangement via spirocyclic
intermediate 5. A transfer of the arene from sulfur to oxy-
gen would result in sulfinate salt 6. Subsequent spontane-
ous elimination of sulfur dioxide and phenolate would
yield the alkene products 2 directly.
hydes affords the corresponding styrenes, stilbenes and cinnamate
derivatives in yields up to 97% and good stereoselectivities. A
mechanistic rationale is advanced to explain the observed results.
Key words: alkene, 4-nitrophenyl sulfone, nucleophilic aromatic
substitution, olefination, Smiles rearrangement
The stereoselective alkenylation reactions are highly
valued synthetic methods. Due to the great complexity of
natural products, the olefination procedures employed in
their total syntheses must be extremely regio- and stereo-
selective, as well as compatible with several other func-
tionalities exhibited by the target molecule. Many
different approaches to the synthesis of substituted alk-
enes have been developed over the past decades. The most
efficient and generally applicable methods involve the di-
rect olefination of carbonyl compounds. The well-known
Wittig,1 Wittig–Horner,2 Horner–Wadsworth–Emmons
(HWE),3 Peterson,4 and Johnson5 olefinations are exem-
plary methods for the introduction of E- or Z-alkene
moieties in complex natural occurring molecules. Another
outstanding example is the classical Julia olefination,6
also known as the Julia–Lythgoe olefination, which is
based on a reductive elimination of b-acyloxy sulfones in
the alkene-forming step. In the early 1990s, a significant
development was achieved by the replacement of the phe-
nyl sulfones traditionally used in the classical Julia olefi-
nation with certain heteroaryl sulfones like benzothiazol-
2-yl (BT) sulfone.7,8 Since then this methodology has been
extended to include other types of heterocyclic derivatives
such as pyrid-2-yl (PYR),7b,9 1-phenyl-1H-tetrazol-5-yl
(PT),10 and 1-tert-butyl-1H-tetrazol-5-yl (TBT)11 sul-
fones. The modified Julia olefination, also called the
Julia–Kocienski olefination, allows a one-pot synthesis of
alkenes, whereas the classical Julia olefination requires
four distinct synthetic operations. Undoubtedly, this new
We postulated that electron-deficient aryl sulfones in gen-
eral could undergo the Smiles1,4 rearrangement necessary
for the Julia–Kocienski olefination. Consequently, for
the investigation of a novel alkenylation protocol, four
O
O
O
O
O
S
R'
S
R'
R
base
M+
O2N
O2N
1
3
R'
O
S
O
O
O
M+
O
S
R'
R
R
O
O2N
O
N
O
M+
4
5
O
O
S
M+
O
R'
R'
R
R
O2N
SO2
+ MOAr
6
2
SYNLETT 2006, No. 8, pp 1255–1259
1
5.
0
5.
2
0
0
6
Advanced online publication: 05.05.2006
DOI: 10.1055/s-2006-939682; Art ID: W33105ST
© Georg Thieme Verlag Stuttgart · New York
Scheme 1 Mechanistic rationale of the modified Julia olefination
with NP sulfones

1256
D. Mirk et al.
LETTER
Table 1 Modified Julia Olefination with NP Sulfones Using NaH as
Base
different NP sulfones 1a–d were easily prepared in high
yields in two steps (Scheme 2). Commercially available
1-fluoro-2,4-dinitrobenzene (Sanger’s reagent) or 1-fluo-
ro-4-nitrobenzene, respectively, were treated with the cor-
responding mercaptan at ambient temperature under basic
conditions to afford the corresponding sulfides via a
nucleophilic aromatic substitution.15 Without purifica-
tion, the crude sulfides were directly oxidized with
MCPBA16 to provide sulfones 117 in excellent overall
yields. Depending on the substituent R¢, unstabilized
(R¢ = n-pentyl; 1a,b), semi-stabilized (R¢ = phenyl; 1c),
and fully-stabilized (R¢ = CO2Et; 1d) NP sulfones were at
our disposal for further applications.
Entry Olefin R¢¢
E/Za
Yield (%)b
n-C5H11
R''
1
2
2ba
2bb
2bc
2bd
2be
2bf
2bg
2bh
2bi
H
94:6
43
68
81
64
53
64
78
82
89
54
84
4-Cl
80:20
82:18
75:25
77:23
72:28
81:19
84:16
88:12
>99:1
85:15
3
4-Br
4
4-NO2
5
3-NO2
X
X
O
O
6
2-NO2
1. R'CH2–SH, K2CO3,
DMF, r.t., 2–4.5 h
F
S
R'
7
4-OMe
3-OMe, 4-OMe
3-OMe, 5-OMe
2. MCPBA, CH2Cl2,
0 °C, 3–5 h
O2N
O2N
8
7
1
1a: X = NO2, R' = n-C5H11 (78%)
1b: X = H, R' = n-C5H11 (98%)
1c: X = H, R' = Ph (80%)
9
10
11
2bj
2bk
2-OMe, 4-OMe, 6-OMe
3-OMe, 4-OMe, 5-OMe
1d: X = H, R' = CO2Et (82%)
Scheme 2 Synthesis of NP sulfones 1a–d
Ph
R''
The modified Julia olefination was evaluated by treatment
of sulfones 1 with various bases in the presence of carbo-
nyl compounds under different reaction conditions. It
showed that 2,4-dinitrophenyl sulfone 1a was not suitable
for the desired transformation, presumably due to an inter-
nal oxidation of the anion by the ortho nitro group that
was also observed by Manchand et al.18
12
13
14
15
16
17
18
19
20
21
22
2ca
2cb
2cc
2cd
2ce
2cf
H
63:37
54:46
56:44
70:30
51:49
50:50
55:45
81:19
58:42
53:47
61:39
65:35
>99:1
74:26
73
78
47
97
94
85
97
87
88
78
92
92
97
92
4-Cl
4-Br
4-NO2
However, 4-nitrophenyl sulfones 1b–d were successfully
applied in the modified Julia olefination (Scheme 1). Ex-
tensive investigations of different reaction conditions in-
dicated that sodium hydride was the most efficient base
for the reaction of unstabilized NP sulfone 1b and semi-
stabilized NP sulfone 1c with aldehydes. The reactions
were carried out under Barbier-type conditions: a DMF
solution of aldehyde and sulfone was treated with an
excess of NaH at ambient temperature for just one hour.
After a normal work-up, the desired products 219 could be
isolated in high yields up to 97% and also in good selec-
tivities for most cases (Table 1). It is well known, that the 23
in situ metallation of the sulfone and its subsequent addi-
tion to an aldehyde compete against a self-condensation
mechanism resulting in an ipso-substitution of the sul-
fones,20 whereas Barbier conditions diminish this side re-
action. In fact, premetallation of NP sulfones 1b and 1c
followed by the addition of an aldehyde under otherwise
identical reaction conditions gave the corresponding
olefins in much lower yields.
3-NO2
2-NO2
2cl
2-Me
2cm
2cn
2cg
2ch
2ci
2-Cl, 5-NO2
4-NMe2
4-OMe
3-OMe, 4-OMe
3-OMe, 5-OMe
2-OMe, 4-OMe, 6-OMe
3-OMe, 4-OMe, 5-OMe
Ph
24
2cj
25
2ck
26
2co
n.d.
77
a Determined by 1H NMR.
b Isolated yield of E/Z mixture after flash chromatography.
Benzaldehydes worked smoothly as reaction partners.
Different substitution patterns on the arene core were ap-
plicable and a large variety of substituents, including elec-
tron-withdrawing groups as well as electron donors, were
tolerated. Generally, the yields of stilbenes 2c (Table 1,
entries 12–25) were higher compared to the correspond-
Synlett 2006, No. 8, 1255–1259 © Thieme Stuttgart · New York

LETTER
NP Sulfones in the Modified Julia Olefination
1257
Table 2 Modified Julia Olefination with NP Sulfones Using Cs2CO3
as Base
ing alkyl substituted alkenes 2b (entries 1–11), whereas a
better selectivity was obtained for styrenes 2b.
In all examples, the trans isomer was favored. It is note-
worthy, that in the case of 2,4,6-trimethoxybenzaldehyde
only the E isomer was detected (entries 10 and 24). Sur-
prisingly, aliphatic aldehydes were not suitable in this
transformation under the examined reaction conditions,
probably due to the competitive self-condensation of the
aldehyde. Indeed, aldol adduct was isolated in some cases.
Ketones such as benzophenone, acetophenone and cyclo-
hexanone, which are less electrophilic compared to alde-
hydes, were also tested, but gave no olefin product.
However, cinnamaldehyde participated well in this reac-
tion and led to the formation of 1,4-diphenylbutadiene
(2co) in 77% yield (Table 1, entry 26).
Entry Olefin R¢¢
Temp
Time
E/Za
Yield (%)b
CO2Et
R''
1
2db
2dc
2dd
2dg
4-Cl
60 °C
r.t.
2 d
4 d
>99:1
>99:1
>99:1
>99:1
50
49
41
40
2
3
4
4-Br
4-NO2
4-OMe
r.t.
18 h
6 d
60 °C
a Determined by 1H NMR.
b Isolated yield of E/Z mixture after flash chromatography.
Further studies of different reaction conditions were con-
ducted. No reaction was observed when the phosphazene
base P4-t-Bu was used which was applied by Nájera et al.
in the Julia–Kocienski olefination with BTFP sulfones.13
Employing KOH resulted in the desired alkenes, but pro-
longed reaction times were required and the yields were
Due to the fact that the choice of counterion seemed to
have a substantial influence for the metal-HMDS bases,
KH was also tested under the reaction conditions that had
already been elaborated for NaH, but in those examples,
no significant amelioration was observed.
much lower compared to the NaH protocol. Likewise, the For sulfone 1d, particular features arose due to the in-
transformation with LiHMDS at –78 °C in THF as solvent creased acidity of the a-proton and the higher stability of
was unsuccessful, whereas upon deprotonation with KH- the anion compared to the other sulfones. Herein, a weak-
MDS under the same conditions the alkene products could er base, Cs2CO3, had to be used together with prolonged
be obtained. A significant amelioration of the reaction reaction times and higher reaction temperatures (60 °C).
outcome was obtained by adding one equivalent of high Furthermore, a premetallation of fully stabilized NP sul-
cation chelating crown ether (18-crown-6) to the reaction fone 1d by Cs2CO3 was necessary in contrast to sulfones
mixture. Now, the desired alkenes could be obtained in 1b and 1c, that were treated under Barbier conditions. The
reasonable yields, while at the same time the selectivity expected cinnamates 2d19 were obtained in moderate
was improved compared to the transformation with NaH, yields as E isomers selectively (Table 2). During the prep-
especially when unstabilized NP sulfone 1b was ap- aration of this manuscript, a synthesis of a,b-unsaturated
plied.21 The use of crown ethers in combination with NaH esters via the modified Julia olefination was developed by
as base had no effect.
Blakemore et al.22
O
N
O
O
SO2
R'
fast
H
R
H
R
R
anti
trans
R'
SO2
R'
O2S
H
4a
Ar
2
O
H
O
R
6a
SO2
+
5a
Ar
R'
OAr
O
Ar
R'
+
SO2
R
3
O
N
O
SO2
O
O
R
H
H
R'
R'
cis
R
R'
syn
O2S
R
R
O
SO2
H
SO2
+
6b
2
4b
5b
Ar
Ar
R'
H
OAr
Scheme 3 Proposed mechanism for the modified Julia reaction with NP sulfones
Synlett 2006, No. 8, 1255–1259 © Thieme Stuttgart · New York

1258
D. Mirk et al.
LETTER
The one-pot olefination of aldehydes with NP sulfones
1b–d is readily explained on the basis of the reaction se-
quence depicted in Scheme 1. The Smiles rearrangement
might occur easily since the intermediate b-hydroxy sul-
fone 4 was not isolable under the present reaction condi-
tions. The favorable entropic factor together with the good
leaving group ability of 4-nitrophenolate might coopera-
tively facilitate the rearrangement process.
SO2
R
R'
H
H
5a
8
OAr
R
R'
2
SO2
SO2
The preferential formation of the trans isomer could be
tentatively explained by discussing the details of the pro-
posed reaction mechanism (Scheme 3).7b,8,20 The nucleo-
philic attack of sulfonyl carbanion 3 onto an aldehyde led
to the anti and syn adducts. The equilibrium between both
resulting b-alkoxy sulfones 4 was known to take place by
an addition–retroaddition process. Besides, the formation
of spirocyclic intermediate 5 was also reversible. That
means that 5 either breaks up following the same way as
it was formed via 4 or a transfer of the aryl moiety pro-
ceeds from the sulfur to the oxygen leading to 6.
5b
H
R'
R
H
8
OAr
Scheme 4 Loss of selectivity for NP sulfone 1c (R¢ = Ph)
lation resulted in the trans olefins selectively, due to the
stabilizing influence of its ester moiety. The predominant
formation of the E isomer was also observed when hexyl
sulfone 1b was applied. On the other hand, the trans-
formation of benzyl sulfone 1c seems to follow a different
reaction pathway via a zwitterionic species, which is
stabilized by the aromatic substituents, and resulted in
decreased selectivities.
The subsequent elimination process from 6 should be ste-
reospecific, since an antiperiplanar arrangement of sulfur
and oxygen has to be assumed. Because of the disadvan-
tageous eclipsed/gauche arrangement between substitu-
ents R and R¢ in 5a, the elimination process leading to the
trans olefin would occur much faster than via the more
stable transition state 5b. These statements could explain
the higher E selectivities for sulfone 1d (R¢ = CO2Et)
compared to hexyl sulfone 1b. The ester moiety has a
strong stabilizing effect on the sulfonyl carbanion 3,
therefore the equilibrium adjusts easily and the thermody-
namically favored trans olefins were obtained selectively.
The prolonged reaction times and higher temperatures
emphasize this conclusion. Accordingly, the E selectivi-
ties for less-stabilized hexyl sulfones 1b were lower. But
when the reactions with 1b were performed at lower tem-
peratures using KHMDS as base instead of NaH, higher E
selectivities were obtained. This fact can be explained by
a kinetically controlled addition of the sulfone carbanion
3 to an aldehyde, wherein the anti-adduct 4a is favored,
resulting in the trans olefin.
In summary, a new one-pot version of the modified Julia
reaction based on 4-nitrophenyl sulfones has been devel-
oped. The advantage of the present method is the easy
accessibility of the NP sulfones and the user-friendly con-
ditions for performing the Julia olefination reaction (r.t.,
NaH as base). Nevertheless, at the present stage of devel-
opment, the NP-sulfone method is only applicable to
aromatic aldehydes, whereas Julia’s BT-sulfone and
Kocienski’s TBT-sulfone methodologies have been ap-
plied to aliphatic aldehydes. Work is in progress to en-
large the applicability of the present methodology by
varying reaction conditions, the structure of the NP-sul-
fone and will be presented in due course.
General Olefination Procedure with NaH
To a stirred solution of NP sulfone (1.08 mmol, 1.0 equiv) and cor-
responding aldehyde (2.16 mmol, 2.0 equiv) in DMF (5.0 mL) un-
der an argon atmosphere was added NaH (technical grade, free-
flowing powder, moistened with oil, 55–65%; 3.24 mmol, 3.0
equiv) at ambient temperature and the colored reaction mixture was
stirred for 1 h. After quenching with H2O (20 mL), the mixture was
extracted with EtOAc (2 × 15 mL). The combined organic phases
were washed with brine (15 mL), dried over anhyd Na2SO4 and con-
centrated in vacuo. Purification was performed via flash chromatog-
raphy on silica using mixtures of heptane or light PE and EtOAc as
eluents to afford pure olefins as mixture of their E/Z isomers. The
E/Z ratio was determined by 1H NMR.
However, for the transformation of semi-stabilized benzyl
sulfone 1c into stilbenes 2c another reaction pathway has
to be anticipated, involving a non-stereospecific elimina-
tion process which is responsible for the lower E selectiv-
ities. In this case, the loss of phenolate and sulfur dioxide
may proceed in two consecutive steps via zwitterionic
conformers 8, whereas the intermediate carbenium ion
present in 8 is stabilized by the two aryl moieties R and R¢
(Scheme 4).
In conclusion, 4-nitrophenyl (NP) sulfones are useful sub-
strates for the modified Julia olefination. NP sulfones
were easily synthesized from inexpensive commercially
available material in high yields applying standard proce-
dures. Alkenylations of a large variety of aromatic alde-
hydes took place to provide the corresponding olefins in
yields up to 97% with moderate to good selectivities.
Addition of NP sulfone 1d to an aldehyde after premetal-
General Olefination Procedure with KHMDS
NP sulfone (0.55 mmol, 1.0 equiv), corresponding aldehyde (1.10
mmol, 2.0 equiv), and 18-crown-6 (0.55 mmol, 1.0 equiv) were dis-
solved in anhyd THF (2.0 mL) under an argon atmosphere and
cooled to –78 °C. KHMDS (0.5 M in toluene; 0.83 mmol, 1.5 equiv)
was added dropwise. The colored reaction mixture was stirred at
low temperature for 45 min, subsequently warmed to ambient
temperature over a period of 2 h, and quenched with brine (15 mL).
The aqueous phase was extracted with EtOAc (2 × 15 mL) and the
Synlett 2006, No. 8, 1255–1259 © Thieme Stuttgart · New York

LETTER
NP Sulfones in the Modified Julia Olefination
1259
combined organic phases were dried over anhyd Na2SO4 and
concentrated in vacuo. Purification was performed via flash
chromatography on silica using mixtures of heptane or light PE and
EtOAc as eluents to afford pure olefins as mixture of their E/Z iso-
mers. The E/Z ratio was determined by proton NMR.
(14) Truce, W. E.; Kreider, W. M.; Brand, W. W. Org. React.
1970, 18, 99.
(15) (a) Levy, A. L.; Chung, D. J. Am. Chem. Soc. 1955, 77,
2899. (b) Wieland, T.; Mohr, H. Justus Liebigs Ann. Chem.
1956, 599, 222. (c) Khanna, I. K.; Weier, R. M.; Yu, Y.;
Collins, P. W.; Miyashira, J. M.; Koboldt, C. M.;
Veenhuizen, A. W.; Currie, J. L.; Seibert, K.; Isakson, P. C.
J. Med. Chem. 1997, 40, 1619.
General Olefination Procedure with Cs2CO3
Under an argon atmosphere, NP sulfone 1d (0.73 mmol, 1.0 equiv)
was dissolved in DMF (3 mL). To this homogeneous solution,
Cs2CO3 (1.1–1.7 equiv) was added in one portion and the heteroge-
neous dark orange mixture was stirred for 30 min at the specified
temperature (Table 2). Aldehyde (1.0–1.5 equiv) was added and the
reaction mixture was stirred at the same temperature for the indicat-
ed time (Table 2). The reaction mixture was diluted with sat.
NaHCO3 solution (10 mL) and the aqueous phase was extracted
with EtOAc (3 × 15 mL). The combined organic layers were washed
with brine, dried over Na2SO4 and concentrated in vacuo. Purifi-
cation was performed via flash chromatography on silica using
mixtures of heptane and EtOAc as eluents.
(16) Pasto, D. J.; Cottard, F.; Jumelle, L. J. Am. Chem. Soc. 1994,
116, 8978.
(17) All synthesized sulfones were employed in analytically pure
manner, their data correspond to the literature. (a)
Compound 1a: Bost, R. W.; Turner, J. O.; Norton, R. D. J.
Am. Chem. Soc. 1932, 54, 1985. (b) Compounds 1b, 1c:
Pasto, D. J.; Cottard, F.; Jumelle, L. J. Am. Chem. Soc. 1994,
116, 8978. (c) Compound 1d: Cao, S.; Zhang, Z.; Fan, A.-
L.; Huang, Z.-M. Monatsh. Chemie 2003, 134, 529.
(18) Manchand, P. S.; Rosenberger, M.; Sauci, G.; Wehrli, P. A.;
Wong, H.; Chambers, L.; Ferro, M. P.; Jackson, W. Helv.
Chim. Acta 1976, 59, 387.
(19) Analytical data for known olefins correspond to the
literature: (a) Compound 2ba: Wenkert, E.; Michelotti, E.
L.; Swindell, C. S.; Tingoli, M. J. Org. Chem. 1984, 49,
4894. (b) Compound 2bb: Kudo, T.; Nose, A. Yakugaku
Zashhi 1975, 95, 1411. (c) Compound 2bc: Bernstein, P.
R.; Snyder, D. W.; Adams, E. J.; Krell, R. D.; Vacek, E. P.;
Willar, A. K. J. Med. Chem. 1986, 29, 2477. (d)
Acknowledgment
We thank CNRS and this institute for financial support. A post-doc-
toral fellowship from the ‘Alexander von Humboldt Foundation’
for D.M. is gratefully acknowledged.
Compound 2bd: Denmark, S. E.; Sweis, R. F. J. Am. Chem.
Soc. 2001, 123, 6439. (e) Compound 2be: Denmark, S. E.;
Wang, Z. Org. Lett. 2001, 3, 1073. (f) Compound 2bf:
Bodalia, R.; Stern, R.; Batich, C.; Duran, R. J. Polym. Sci.,
Part A: Polym. Chem. 1993, 31, 2123. (g) Compound 2bg:
Denmark, S. E.; Choi, J. Y. J. Am. Chem. Soc. 1999, 121,
5821. (h) Compound 2bi: Lytollis, W.; Scannel, R. T.; An,
H.; Murty, V. S.; Reddy, K. S.; Barr, J. R.; Hecht, S. M. J.
Am. Chem. Soc. 1995, 117, 12683. (i) For compound 2ca:
analytical data correspond to a commercial sample. (j)
Compounds 2cb, 2cg, 2co, 2db: Aggarwal, V. K.; Fulton, J.
R.; Sheldon, C. G.; de Vicente, J. J. Am. Chem. Soc. 2003,
125, 6034. (k) Compound 2cc: Selvakumar, K.; Zapf, A.;
Spannenberg, A.; Beller, M. Chem. Eur. J. 2002, 8, 3901.
(l) Compounds 2cd, 2ce, 2cf: Dai, M.; Liang, B.; Wang, C.;
Chen, J.; Yang, Z. Org. Lett. 2004, 6, 221. (m) Compounds
2cl, 2dd, 2dg: Masllorens, J.; Moreno-Manas, M.; Pia-
Quintana, A.; Roglans, A. Org. Lett. 2003, 5, 1559. (n)
Compound 2cn: Colberg, J. C.; Rane, A.; Vaquer, J.;
Soderquist, J. A. J. Am. Chem. Soc. 2003, 115, 6065. (o)
Compounds 2ch, 2ci: Roberts, J. C.; Pincock, J. A. J. Org.
Chem. 2004, 69, 4279. (p) Compound 2cj: Ali, M. A.;
Kondo, K.; Tsuda, Y. Chem. Pharm. Bull. 1992, 40, 1130.
(q) Compound 2ck: Yasuda, M.; Isami, T.; Kubo, J.;
Mizutani, M.; Yamashita, T. J. Org. Chem. 1992, 57, 1351.
(r) Compound 2dc: Costa, A.; Nájera, C.; Sansano, J. M. J.
Org. Chem. 2002, 67, 5216.
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chromatography for 2ba: 14% (97:3), 2bb: 55% (>99:1),
2bd: 33% (96:4), 2bg: 58% (95:5), 2ca: 23% (88:12), 2cb:
48% (52:48), 2cd: 32% (94:6), 2cg: 73% (59:41).
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Synlett 2006, No. 8, 1255–1259 © Thieme Stuttgart · New York