Stereoselective one-pot 1, 4-elimination and the [1, 2]-wittig rearrangement of (E)-δ-(arylmethoxy or 3-silyl-2-propynyloxy)-substituted allylicsulfones

Article abstract of DOI:10.1246/cl.2011.521

The successive treatment of (E)-δ-(arylmethoxy)-substiruted allylicsulfones with t-BuOK and LDA afforded the corresponding (Z)-2,4-dienyl alcoholswith high stereoselectivities via 1, 4- elimination and the [1, 2]-Wittig rearrangement. The predominant form

Full text of DOI:10.1246/cl.2011.521

doi:10.1246/cl.2011.521
Published on the web April 23, 2011
521
Stereoselective One-pot 1,4-Elimination and the [1,2]-Wittig Rearrangement
of (E)-¤-(Arylmethoxy or 3-Silyl-2-propynyloxy)-substituted Allylic Sulfones
Susumu Horii, Isao Ishimaru, Yutaka Ukaji,* and Katsuhiko Inomata*
Division of Material Sciences, Graduate School of Natural Science and Technology,
Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192
(Received February 16, 2011; CL-110132; E-mail: inomata@se.kanazawa-u.ac.jp)
The successive treatment of (E)-¤-(arylmethoxy)-substituted
allylic sulfones with t-BuOK and LDA afforded the correspond-
ing (Z)-2,4-dienyl alcohols with high stereoselectivities via 1,4-
elimination and the [1,2]-Wittig rearrangement. The predom-
inant formation of (Z)-isomers, due to “syn-effect” in the
elimination step, was further successfully applied to (E)-¤-(3-
silyl-2-propynyloxy)-substituted allylic sulfones.
Ts
LDA
–Ts
O
Ph
O
Ph
O
O
Ph
4a
5a
6a
[1,2]-Wittig
rearrangement
H O
3
LDA
2a
3a
1a
Ph 7a
Ts
Ts
[2,3]-Wittig
rearrangement
H O
3
Stereoselective preparation of olefins is one of the most
important problems in organic chemistry. In the course of studies
on the preparation of allylic sulfones,1 we investigated the
stereochemistry of isomerization of ¡-unsubstituted (E)-vinylic
sulfones to the corresponding allylic sulfones in the presence of a
base and found that the sterically unfavorable (Z)-allylic sulfones
were predominantly formed.2 This experimental fact was ration-
alized by a “syn-effect,”3 which is primarily caused by · ¼ ³*
interaction and/or 6³-electron homoaromaticity.2,4 In related
studies on the “syn-effect,” we revealed that it works also in
various kinds of isomerization reactions and elimination reactions
utilizing a base.4,5 In particular, oxygen-substituted substrates
always realized high Z-selectivities. During the course of the
investigation of the 1,4-eliminative ring opening reaction of a
benzyloxy-substituted (E)-vinyloxirane with LDA, the [1,2]-
Wittig rearrangement6 was found to proceed following the initial
1,4-eliminative ring opening reaction to give an (E,Z)-2,4-dienyl
1,6-diol in a highly stereoselective manner.5g This shows that the
highest Z-selectivity based on the “syn-effect” observed for the
oxygen-substituted substrates could be utilized for the successive
stereoselective C-C bond formation. Herein we describe a one-pot
1,4-elimination of allylic sulfones and the subsequent [1,2]-Wittig
rearrangement of (E)-¤-(arylmethoxy)-substituted allylic sulfones
to give the corresponding (Z)-dienyl alcohols stereoselectively.
As described above, the “syn-effect” of 1,4-elimination of
allylic sulfones by the treatment with a base was investigated
and a ¤-(benzyloxy)allylic sulfone was found to afford the
corresponding (Z)-vinyl ether stereoselectively.5a If the ¤-
(benzyloxy)allylic sulfone was treated with excess amounts of
a base, the successive 1,4-elimination and the [1,2]-Wittig
rearrangement was also anticipated to proceed. When (E)-¤-
(benzyloxy)allylic sulfone 1a was treated with 3.0 equiv of
LDA, the desired successive reaction product 2a was obtained in
60% yield. Stereoselectivity of the double bond in 2a was high
as expected (E/Z = 11/89). However, a by-product 3a was also
produced (eq 1). As shown in Scheme 1, the 1,4-elimination via
O
Ph
O
Ph
8a
Scheme 1.
4a stereoselectively gave (Z)-vinyl ether 5a originating from the
“syn-effect,” which was further deprotonated at the benzylic
position followed by the [1,2]-Wittig rearrangement to give 2a.
On the other hand, when deprotonation at the benzylic position
initially occurred, the benzylic anion 8a might afford 3a by the
[2,3]-Wittig rearrangement.
In order to suppress the generation of 8a, a weaker base t-
BuOK was first used for generation of 4a selectively to complete
the 1,4-elimination, followed by addition of LDA for further the
[1,2]-Wittig transformation via 6a. In this way, only the desired
reaction proceeded to give 2a with high Z-selectivity (Table 1).7
When 3.5 equiv of LDA was used, a by-product 9a was also
obtained (Entry 1), which might be produced via deprotonation
of the rearranged intermediate 7a and subsequent isomerization
(Scheme 2).8 By decreasing the amount of LDA and shortening
the reaction time for the [1,2]-Wittig rearrangement, the
production of the by-product 9a was rather inhibited and the
stereoselectivity was further improved (Entries 2-4). By treating
with 2.5 equiv of LDA for 5 min, 2a was obtained with excellent
stereoselectivity in high yield (Entry 3). Several other ¤-
(arylmethoxy)allylic sulfones 1b-1d were subjected to the
present one-pot 1,4-elimination reaction and the [1,2]-Wittig
rearrangement, and the corresponding (Z)-dienyl alcohols 2b-2d
were stereoselectively obtained (Entries 5-7).
Next, propargylic ethers instead of benzylic ethers 1, were
investigated in the one-pot transformation. When (E)-3-phenyl-
2-propynyl ether 10 was treated with t-BuOK, 1,4-elimination to
12 was monitored by TLC. After the addition of LDA, the
reaction became messy and desired rearranged product 11 was
not obtained (eq 2).9
Ts
LDA
(3.0 equiv)
Ts
Ts
α
1) t-BuOK (2.0 equiv)
γ
β
rt, 30 min
ð1Þ
3a
δ
ð2Þ
2) LDA (2.5 equiv)
O
–78 °C → 0 °C
Ph
O
Ph
O
Ph
0 °C, 5 min
THF
THF, 4.5 h
HO
HO
Ph
24%
HO
Ph
Ph
2a
1a
11 not obtained
12
60% (E/Z = 11/89)
10
Chem. Lett. 2011, 40, 521-523
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

522
Table 1. One-pot 1,4-elimination and the [1,2]-Wittig rear-
rangement of 1
could not be prepared by the conventional Lindlar reduction of
diynols.
Ts
1) t-BuOK (2.0 equiv)
n-Bu NF (1.0 equiv)
4
rt, 30 min
ð3Þ
0 °C, 30 min
Sii-Pr
3
2) LDA (n equiv)
then rt, 10 min
THF
O
Ar
HO
HO
2
9
HO
Ar
O
Ar
1
0 °C, t min
THF
14c (E/Z =1/99)
15 88% (E/Z = 1/99)
As described above, the one-pot transformation of (E)-¤-
Yield E/Za Yield
of 2/% of 2 of 9/%
(arylmethoxy)- or (3-silyl-2-propynyloxy)-substituted allylic
sulfones into (Z)-2,4-dienyl alcohols via 1,4-elimination and
the [1,2]-Wittig rearrangement were developed,11 which dem-
onstrates a smart application of the “syn-effect” to stereo-
selective C-C bond formation.
Entry Ar
1 n/equiv t/min
1
2
3
4
5
6
7
Ph
a
3.5
3.0
2.5
2.0
2.5
2.5
2.5
80
15
5
1
5
69
65
5/95
2/98
4
4
1
®
®
2
89b 1/99
80b 2/98
The present work was financially supported in part by Grant-
in-Aid for Scientific Research from Japan Society for the
Promotion of Science (JSPS).
4-CH3C6H4
4-CH3OC6H4
2-Nap
b
c
d
89
2/98
5
5
85c 3/97
89c 2/98
1
aThe ratios were determined by 400 MHz 1H NMR spectra.
bVinyl ether 5a was obtained in 7% (Entry 3) and 10%
(Entry 4) yields, respectively. Vinyl ethers 5c and 5d were
References and Notes
1
2
3
N. S. Simpkins, Sulphones in Organic Synthesis, Pergamon
Press, Oxford, 1993, pp. 40-50.
c
obtained in 7% (Entry 6) and 6% (Entry 7) yields, respectively.
T. Hirata, Y. Sasada, T. Ohtani, T. Asada, H. Kinoshita, H.
Senda, K. Inomata, Bull. Chem. Soc. Jpn. 1992, 65, 75.
The “syn-effect” is herein defined as an effect which
stabilizes the syn-conformation against the steric hindrance
at the transition state.
H3O
LDA
7a
O
Ph
O
Ph
O
Ph
9a
4
5
K. Inomata, J. Synth. Org. Chem., Jpn. 1992, 50, 326; K.
Inomata, J. Synth. Org. Chem., Jpn. 2009, 67, 1172.
Related studies on the “syn-effect:” a) A. Shibayama, T.
Nakamura, T. Asada, T. Shintani, Y. Ukaji, H. Kinoshita,
K. Inomata, Bull. Chem. Soc. Jpn. 1997, 70, 381. b) T.
Nakamura, S. K. Guha, Y. Ohta, D. Abe, Y. Ukaji, K.
Inomata, Bull. Chem. Soc. Jpn. 2002, 75, 2031. c) S. K.
Guha, A. Shibayama, D. Abe, Y. Ukaji, K. Inomata, Chem.
Lett. 2003, 32, 778. d) S. K. Guha, Y. Ukaji, K. Inomata,
Chem. Lett. 2003, 32, 1158. e) S. K. Guha, A. Shibayama, D.
Abe, M. Sakaguchi, Y. Ukaji, K. Inomata, Bull. Chem. Soc.
Jpn. 2004, 77, 2147. f) H. Takenaka, Y. Ukaji, K. Inomata,
Chem. Lett. 2005, 34, 256. g) N. Takeda, T. Chayama, H.
Takenaka, Y. Ukaji, K. Inomata, Chem. Lett. 2005, 34, 1140.
h) M. Yamazaki, S. K. Guha, Y. Ukaji, K. Inomata, Chem.
Lett. 2006, 35, 514. i) M. Yamazaki, S. K. Guha, Y. Ukaji, K.
Inomata, Bull. Chem. Soc. Jpn. 2008, 81, 740.
H3O
2a
Scheme 2.
Table 2. One-pot 1,4-elimination and the [1,2]-Wittig rear-
rangement of ¤-(3-silyl-2-propynyloxy)allylic sulfones 13
Ts
1) t-BuOK (2.0 equiv)
rt, 30 min
2) LDA (n equiv)
Si
O
HO
HO
0 °C, 5 min
THF
Si
15
13
14
Entry Si
13 n/equiv Products Yield/% E/Za
1
2
Me3Si
a
b
c
2.5
2.5
2.5
2.2
15
45
12/88
3/97
1/99
1/99
t-BuPh2Si
14b
14c
14c
29
70c
74c
3b i-Pr3Si
4b
6
U. Schöllkopf, Angew. Chem., Int. Ed. Engl. 1970, 9, 763;
J. A. Marshall, in Comprehensive Organic Synthesis:
Selectivity, Strategy and Efficiency in Modern Organic
Synthesis, ed. by B. M. Trost, I. Fleming, Pergamon Press,
Oxford, 1991, Vol. 3, pp. 979-981; K. Tomooka, J. Synth.
Org. Chem., Jpn. 2001, 59, 322; N. C. Giampietro, J. W.
Kampf, J. P. Wolfe, J. Am. Chem. Soc. 2009, 131, 12556;
N. C. Giampietro, J. P. Wolfe, Angew. Chem., Int. Ed. 2010,
49, 2922.
aThe ratios were determined by 400 MHz 1H NMR spectra.
bOn step 1, 13c was treated with t-BuOK at 0 °C for 20 min. cA
by-product, 7-methyl-1-(triisopropylsilyl)-6-octen-1-yn-3-one,
produced via deprotonation of the rearranged intermediate
followed by isomerization, was obtained in 14% (Entry 3) and
15% (Entry 4) yields, respectively.
When (E)-¤-(3-silyl-2-propynyloxy)allylic sulfones 13 were
used as substrates, the desired [1,2]-Wittig rearrangement was
found to proceed (Table 2). In the case of trimethylsilyl-
substituted substrate 13a, the rearranged desilylated product 15
was obtained (Entry 1). In order to prevent the desilylation,
bulky silyl groups were introduced (Entries 2-4). £-(Triisopro-
pylsilyl)propargylic ether was a substrate of choice to give the
desired product 14c with excellent Z-selectivity (Entries 3 and
4). The desilylation of 14c was readily carried out by treating
with tetrabutylammonium fluoride to afford 15 (eq 3),10 which
7
Vinyl migration in the [1,2]-Wittig rearrangement is known
to proceed with retention of geometry: V. Rautenstrauch, G.
Büchi, H. Wüest, J. Am. Chem. Soc. 1974, 96, 2576; K.
Tomooka, T. Inoue, T. Nakai, Chem. Lett. 2000, 418. It was
also confirmed 2a was generated via 5a while retaining
stereochemistry: The treatment of 5a (E/Z = 3/97) with
LDA (1.5 equiv) in THF at 0 °C for 5 min afforded 2a
(E/Z = 2/98) in 46% yield and 34% of 5a (E/Z = 3/97)
was recovered.
Chem. Lett. 2011, 40, 521-523
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

523
8
9
The formation of 9a was not observed by the treatment of 2a
with LDA (2.5 equiv) in THF at 0 °C for 80 min. However,
after 1 d at rt, 9a was confirmed to be produced in ca. 4%
yield based on the analysis of a H NMR spectrum of the
crude products. Furthermore, isomerization was also ob-
served (E/Z of 2a; from 5/95 to 14/86).
Delocalization of the generated propargylic anion into the
benzene ring through the triple bond might retard the [1,2]-
Wittig rearrangement.
0 °C, LDA¢THF (0.934 mL, 1.40 mmol, 1.5 M in cyclohex-
ane) was added and the reaction mixture was stirred for
5 min at 0 °C. The reaction was quenched by the addition of
saturated aqueous solution of NH4Cl, and the organic
substances were extracted with AcOEt. The combined
organic extracts were washed with water and brine, dried
over Na2SO4, and condensed in vacuo. The residue was
separated by flash column chromatography (SiO2, hexane/
AcOEt = 30/1-15/1, v/v) to give 2a (94 mg, 89%, E/Z =
1/99) and a mixture of 5a (7%) and 9a (1%) (total 8 mg).
1H NMR (400 MHz, CDCl3): (Z)-2a; ¤ 1.78 (3H, s), 1.85
(3H, s), 1.87 (1H, br s), 5.50 (1H, dd, J = 10.7, 8.8 Hz), 5.71
(1H, d, J = 8.8 Hz), 6.26 (1H, d, J = 11.7 Hz), 6.34 (1H, dd,
J = 11.7, 10.7 Hz), 7.24-7.42 (5H, m). (E)-2a; ¤ 1.78 (6H,
s), 1.91 (1H, br s), 5.26 (1H, d, J = 7.0 Hz), 5.73 (1H, dd,
J = 15.0, 7.0 Hz), 5.83 (1H, d, J = 11.0 Hz), 6.53 (1H, dd,
J = 15.0, 11.0 Hz), 7.24-7.42 (5H, m).
1
10 J. A. Marshall, S. L. Crooks, B. S. DeHoff, J. Org. Chem.
1988, 53, 1616.
11 A representative procedure for the one-pot 1,4-elimination
and the [1,2]-Wittig rearrangement of 1a (Table 1, Entry 3):
To a suspension of t-BuOK (125 mg, 1.12 mmol) in THF
(1.1 mL), a THF (4.5 mL) solution of 1a (193 mg, 0.56
mmol) was added under a N2 atmosphere and the mixture
was stirred for 30 min at rt. After the mixture was cooled to
Chem. Lett. 2011, 40, 521-523
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/