Julia-Kocienski reaction-based 1,3-diene synthesis: Aldehyde-dependent (E, E/E, Z)-selectivity

Article abstract of DOI:10.1021/jo300929a

A new modification of Julia-Kocienski olefination reaction based on the use of cation-specific chelating agents that yields 1,3-dienes with predictable (E/Z)-selectivity on newly created double bond was developed. The influence of the aldehyde structure on reaction (E/Z) selectivity is discussed and rationalized.

Full text of DOI:10.1021/jo300929a

Note
pubs.acs.org/joc
Julia−Kocienski Reaction-Based 1,3-Diene Synthesis: Aldehyde-
Dependent (E,E/E,Z)-Selectivity
Franco̧ is Billard, Raphael Robiette, and Jirí Pospísil*
̌ ̌
̈
́
Institute of Condensed Matter and Nanosciences−Molecules, Solids and Reactivity (IMCN/MOST), Universite Catholique de
Louvain, Place Louis Pasteur 1, bte L4.01.02, 1348 Louvain-la-Neuve, Belgium
S
* Supporting Information
ABSTRACT: A new modification of Julia−Kocienski olefina-
tion reaction based on the use of cation-specific chelating
agents that yields 1,3-dienes with predictable (E/Z)-selectivity
on newly created double bond was developed. The influence
of the aldehyde structure on reaction (E/Z) selectivity is
discussed and rationalized.
ver the past few decades, our synthetic tools were
enriched by various novel and fundamentally different
Scheme 2. Proposed Equilibrium-Based Approach to (Z)-
Olefins
O
approaches to alkene synthesis. Unfortunately, none of the
developed methods yet provided a universal solution in terms
of yield, selectivity, and functional group tolerance. Since the
mid-1990s, the second-generation Julia olefination reaction has
become a privileged synthetic method when two complex
molecular fragments should be connected (Scheme 1).1 The
Scheme 1. Second-Generation Julia Olefination Reaction
we assumed that if allylic or benzylic anions 4 (R1 = alkyl or
benzyl) would be reacted with aldehyde 2, the addition reaction
might be reversible.5 To investigate this hypothesis, the
reactivity and reaction selectivity of α-sulfonyl anions generated
from allylic and benzylic sulfones6 were studied in the context
of 1,3-diene synthesis.7
Our study started with the investigation of the key step of
our hypothesis, the reversibility of the addition of allylic and
benzylic sulfonyl anions to aldehydes. Thus, hydroxy sulfones
8a and 8b were prepared8 and reacted with LiN(TMS)2 or
KN(TMS)2 in the presence of p-nitrobenzaldehyde 12b (Table
1).9 The goal of these experiments was to find suitable reaction
conditions under which alcoholate 9 would not undergo Smiles
rearrangement (transformation of alcoholate 9 to olefin 13a)
but rather retroaddition reaction (transformation of alcoholate
9 to benzylic anion 11 and aldehyde 12a) (Scheme 3). The
formation of the benzylic anion 11 would then be proved by its
trapping with reactive aldehyde 12b and the consecutive olefin
13b formation.
popularity of this synthetic method is based not only on its
versatility, wide functional group tolerance and mild reaction
conditions under which the reaction proceeds, but also on its
generally high (E)-selectivity.
In our group, we are focused on the development of new
more selective modifications of Julia−Kocienski olefination
reaction.2 After our recent success where we were able to
increase the (E)-selectivity of this reaction,2 we decided to
focus our attention on the development of (Z)-selective
modification of this reaction (Scheme 2). Taking into account
the mechanism of the Julia−Kocienski reaction,1 we reasoned
that if the addition of sulfonyl anion 4 to aldehyde 2 was
reversible,3 reaction selectivity would be determined by the
relative rate of Smiles rearrangement of syn and anti alkoxides 5.
It is known that for steric reasons the Smiles rearrangement of
syn-5 adduct that yields (Z)-olefins proceeds faster as compared
to the rearrangement of anti-5 adduct that yields (E)-olefins.4
In the literature, the addition of sulfonyl anion 4 to aldehyde
2 (R1, R2 = alkyl) is reported to be nonreversible.1b,4 However,
Received: May 22, 2012
Published: July 5, 2012
© 2012 American Chemical Society
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Note
Table 1. Hydroxy Sulfone 8 Retroaddition Reaction Evaluation
a
entry
sulfone
conditions
13a:13b ratio
1
2
3
4
5
6
8a
8a
8a
8a
8b
LiN(TMS)2 (2.2 equiv),−60 °C, DMF/HMPA = 3:1
KN(TMS)2 (1.2 equiv), DMF, −55 °C
KN(TMS}2 (1.2 equiv), 18-crown-6 (2.5 equiv), DMF, −55 °C
KN(TMS)2 (1.2 equiv), DMF/TDA-1 = 3:1,−60 °C
KN(TMS)2 (1.2 equiv), −55 °C, 18-crown-6 (2.5 equiv), DMF
KN(TMS)2 (1.2 equiv), DMF/TDA-1 = 3:1, −60 °C
>98:<2
>98:<2
34:66
b
22:78 (72)
b
15:85 (65)
b
8b
<2:>98 (93)
a
b
Based on HPLC analysis. Isolated yield of 13b (in %).
explained by the difference in reactivity of the imine-like
electrophilic centers present in BT- and PT-sulfones.1,9,10
Having established the conditions under which the addition
of benzylic sulfones to aldehydes is reversible, we focused our
attention on the (E/Z)-selectivity of the newly created olefin
bond evaluation (Table 2).9 Our goal was to find reaction
conditions under which the transformation of syn-5 adduct to
spiro 6 (k1, yields olefin (Z)-3) proceeds faster than the adduct
anti-5 to spiro 7 (k2, yields olefin (E)-3) (Scheme 2).
Scheme 3. Competitive Experiment Designed To Determine
if Hydroxy Sulfone 8 Can Undergo Retroaddition Reaction
First, the reaction of allyl PT-sulfone 16 and aldehyde 12c
was carried out using the standard Barbier-type11Julia
olefination protocol (Table 1, entries 1 and 2). As expected,
if THF was used as solvent, (E)-13c olefin was formed
predominantly (entry 1). The use of “equilibrating” reaction
conditions, DMF as a solvent and 18-crown-6 as cation
scavenger, flipped the selectivity and yielded (Z)-13c olefin as
the major product (entry 2). To increase further the (Z)-
selectivity, we decided to premetalate sulfone 16 with
KN(TMS)2 and add aldehyde 12c 30 min later (entry 3).
Gratifyingly, olefin 13c was formed in an increased 25:75 (E/Z)
ratio. Addition of K+-specific chelating agent, 18-crown-6,
increased further the (Z)-selectivity of the olefin 3c formation
((E/Z) = 16:84) but substantially diminished the reaction yield
(entry 4).
Our competitive experiments showed that the hydroxy
sulfones 8 undergo retroaddition only when polar solvents and
efficient cation-chelating agents (18-crown-6, TDA-1 for K+)
are used. Moreover, it was shown that BT-containing sulfone 8a
underwent retroaddition less readily as compared to sulfone 8b
(Table 1, entries 3 vs 5 and 4 vs 6). This observation could be
It was found that prolonged premetalation reaction time
carried out in the presence of cation scavenger led to rapid
sulfone 16 degradation. Gratifyingly, the stirring of sulfone 16
with KN(TMS)2 and 18-crown-6 for only 2 min prior to
aldehyde 12c addition yielded the targeted olefin 13c with a
15:85 (E/Z) ratio and 74% yield (entry 6). If a shorter
Table 2. Reaction between Allyl Sulfones 16 and 17 and Dihydrocinnamaldehyde 12c
b
yield
a
c
entry
conditions
(%)
E/Z
1
2
3
4
5
6
7
KN(TMS)2 added to a solution of 16 and 12c in THF at −78 °C
KN(TMS)2 added to a solution of 16, 12c and 18-crown-6 in DMF at −55 °C
nd
73
64
17
79
78
52
68:32
35:65
25:75
16:84
23:77
14:86
16:84
KN(TMS)2 added to a solution of 16 in DMF at −55 °C, stirred for 30 min, aldehyde 12c added at −55 °C
KN(TMS)2 added to a solution of 16 and 18-crown-6 in DMF at −55 °C, stirred for 30 min, aldehyde 12c added at −55 °C
KN(TMS)2 added to a solution of 16 and 18-crown-6 in DMF at −55 °C, stirred for 1 min, aldehyde 12c added at −55 °C
KN(TMS)2 added to a solution of 16 in DMF/TDA-1 = 3:1 (v/v) at −60 °C, stirred for 2 min, aldehyde 12c added at −60 °C
KN(TMS)2 added to a solution of 17 in DMF/TDA-1 = 3:1 (v/v) at −60 °C, stirred for 2 min, aldehyde 12c added at −60 °C
a
The following quantities of given reagents were used: sulfone 16 or 17 (1.0 equiv), KN(TMS)2 (1.1 equiv), aldehyde 12c (1.1 equiv), and 18-
b
c
crown-6 (2.3 equiv). Average of two runs. Isolated yield. Average of two runs. Based on GC analysis.
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Table 3. Synthesis of Dienes 13 via Julia−Kocienski and Julia−Silvestre Reactions
premetalation period (1 min) was employed, erosion of the
(Z)-selectivity was observed (entry 5). To further increase the
(Z)-13c formation, TDA-112 was used as cosolvent (entries 6
and 7). The use of DMF/TDA-1 = 3:1 (V/V) solvent mixture
afforded olefin 13c in the same (E/Z) ratio but slightly better
yield (entry 6).
The selectivity of BT-containing sulfone 17 under the
developed reaction conditions was also evaluated. Because of
the results of our preliminary addition/retroaddition study
(Table 1), we expected that the reaction of BT-sulfone 17 with
aldehyde 12c might proceed with lower (Z)-selectivity.
However, under all tested reaction conditions, olefins 13c
were obtained with similar (E/Z)-selectivity, although in lower
yield (see Table 2, entry 6 vs entry 7).9
Having established the optimal reaction conditions, the scope
and limitations of this method (Table 3) were examined and
the results were compared with reactions performed without
the presence of chelating agents.13
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Scheme 4. Proposed Mechanism of “Cation-Free” Julia−Kocienski Reaction of Allyl PT-sulfones
In general, reactions of PT-sulfones 16, 18, and 19 (Table 3,
entries 1−60) were more stereoselective than those performed
with BT-sulfones 17 and 20−22 (Table 3, entries 61−96). In
both cases, the (E/Z)-selectivity of newly formed olefins 13
proved to be aldehyde dependent. When primary α-non-
branched aldehydes 12c,d were used, the newly created olefins
formed under “cation-free” conditions (methods C and D)
were obtained with higher (Z)-selectivity as compared to
standard conditions (methods A and B). The only exception
was found when nonbranched α-alkoxy aldehyde 12e was used
(entries 9−12, 17−20, 49−52, 69−72, and 93−96). In these
cases, the reactions yielded the corresponding olefins 13h−
l,n,p,q with moderate to good (E)-selectivity. The same trend
was observed when α di- and trisubstituted or aromatic
aldehydes 12g−j and n were used (entries 21−40, 45−48, 53−
60, and 77−80). In these cases, the (E)-olefins 13h−l,n,p,q
were formed as main products of the reaction. Interestingly, in
these cases the obtained (E/Z) ratio was also superior to that
obtained under the standard reaction conditions.
We believe that the stereochemical outcome of the 1,3-dienes
13 prepared by Julia−Kocienski and Julia−Silvestre reactions
and presented in Table 3 can be easily rationalized (Scheme 4).
If the olefination reactions were carried out under standard
reaction conditions (methods A or B, addition step is not
reversible (k′1,k′2 ≪ k3,k4)), the (E/Z) ratio of 13 corresponds
to the syn/anti-24 adduct ratio.1,2a Thus, the Smiles rearrange-
ment becomes the rate-determining step, but the addition step
is the selectivity-determining step.
determining selectivity; anti addition is predicted to be
preferred (k2 > k1).
In summary, we have developed a new modification of the
Julia reaction that allows us to prepare 1,3-dienes, starting from
PT- and BT-allyl sulfones, with high (Z) or (E) selectivity. It
was shown that the olefin stereoselectivity is substrate
(aldehyde) dependent. A rational explanation for observed
(E,Z) selectivity is also proposed.
EXPERIMENTAL SECTION
■
General Procedures for Olefination Reactions. Method A. A
solution of aldehyde 12c (131 μL, 1.1 mmol) and allyl sulfone 16 (250
mg, 1.0 mmol) in THF (10 mL, 0.1 M) was cooled to −78 °C, and
KN(TMS)2 (0.6 M solution in toluene) (1.83 mL, 1.1 mmol) was
added over 2 min. The resulting mixture was stirred at −78 °C for 1 h
before it was allowed to warm to rt. After being stirred at rt for 6 h, a
saturated aqueous solution of NH4Cl (10 mL) was added. The whole
mixture was extracted with EtOAc (3 × 10 mL); the combined organic
layers were washed with brine (10 mL), dried over MgSO4, and
filtered; the solvents were removed under reduced pressure. The
residue was purified by flash column chromatography on SiO2
(petroleum ether/EtOAc = 50:1), and the reaction yielded 114 mg
(72%, E/Z = 63:37) of 13c as a yellowish oil.
Method B. A solution of aldehyde 12c (131 μL, 1.1 mmol) and allyl
sulfone 16 (250 mg, 1.0 mmol) in DMF (10 mL, 0.1 M) was cooled to
−55 °C, and KN(TMS)2 (0.6 M solution in toluene) (1.83 mL, 1.1
mmol) was added over 2 min. The resulting mixture was stirred at −55
°C for 1 h before it was allowed to warm to rt. After 6 h at rt, the
reaction was terminated and purified using the same protocol as
mentioned in method A. The reaction yielded 103 mg (65%, E:Z =
58:42) of 13c as a yellowish oil.
Method C. A solution of allyl sulfone 16 (250 mg, 1.0 mmol) and
18-crown-6 (661 mg, 2.5 mmol) in DMF (10 mL, 0.1 M) was cooled
to −55 °C, and KN(TMS)2 (0.6 M solution in toluene) (1.83 mL, 1.1
mmol) was added dropwise within 10 s. The resulting mixture was
stirred at −55 °C for 2 min, and aldehyde 12c (131 μL, 1.1 mmol) in
DMF (0.2 mL) was added dropwise. The resulting mixture was stirred
at −55 °C for 1 h before it was allowed to warm to rt. After 6 h at rt,
the reaction was terminated and purified using the same protocol as
mentioned in method A. The reaction yielded 117 mg (74%, E/Z =
15:85) of 13c as a yellowish oil.
However, if chelating agents are employed (methods C and
D), the addition step is reversible (k′1,k′2 ≪ k3,k4) and the
Smiles rearrangement becomes the rate and selectivity
determination step. However, the final stereochemical outcome
of the reaction ((E/Z) ratio) strongly depends on the aldehyde
structure. If α-nonbranched aldehydes are employed, we expect
that, for steric reasons, the Smiles rearrangement of adduct syn-
24 to intermediate 27 proceeds faster than the rearrangement
of adduct anti-24 to intermediate 28 (k3 > k4). (Z)-Olefins are
thus preferentially formed.
Method D. A solution of allyl sulfone 16 (250 mg, 1.0 mmol) in
DMF/TDA-1 = 3:1 (v/v) (10 mL, 0.1 M) was cooled to −60 °C, and
KN(TMS)2 (0.6 M solution in toluene) (1.83 mL, 1.1 mmol) was
added dropwise within 10 s. The resulting mixture was stirred at −60
°C for 2 min, and aldehyde 12c (131 μL, 1.1 mmol) in DMF (0.2 mL)
However, the reaction becomes (E)-selective if the steric
repulsion between R2 and the vinyl group in TS-1 becomes
important (α-branched and aromatic aldehydes). In this case,
the relative rate of syn and anti addition starts to play a role in
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Note
was added dropwise. The resulting mixture was stirred at −60 °C for 1
h before it was allowed to warm to rt. After 6 h at rt, the reaction was
terminated and purified using the same protocol as mentioned in
method A. The reaction yielded 123 mg (78%, E/Z = 14:86) of 13c14
as a yellowish oil: 1H NMR15 (300 MHz, CDCl3) δ 2.45 (dd, J = 15.1,
7.2 Hz, 2H*), 2.55 (dd, J = 15.3, 7.6 Hz, 2H), 2.67−2.80 (m, 2H),
5.01 (d, J = 9.7 Hz, 1H*), 5.12 (d, J = 10.0 Hz, 1H), 5.22 (dd, J = 16.9,
1.7 Hz, 1H), 5.53 (dt, J = 10.5, 7.7 Hz, 1H), 5.79 (dt, J = 15.1, 7.1 Hz,
1H*), 6.06 (t, J = 10.9 Hz, 1H), 6.15 (dd, J = 15.1, 10.4 Hz, 1H*),
6.35 (dt, J = 16.9, 10.2 Hz, 1H*), 6.65 (dtd, J = 16.9, 10.6, 1.0 Hz,
1H), 7.15−7.26 (m, 3H), 7.28−7.37 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ 29.8, 34.6*, 35.8*, 36.0, 115.4*, 117.5, 126.1, 128.5, 128.6,
129.9, 131.6 (E), 131.8, 132.3, 134.5, 137.4, 141.9, 142.0*; IR (film)
1H*), 5.46 (dd, J = 15.2, 7.6 Hz, 1H), 5.54 (dd, J = 15.4, 7.4 Hz,
1H*), 5.71 (dt, J = 15.0, 7.2 Hz, 1H), 6.05 (dd, J = 14.9, 10.5 Hz, 1H),
6.21 (dd, J = 15.3, 10.4 Hz, 1H), 6.52 (dd, J = 11.1, 9.3 Hz, 1H*),
7.28−7.48 (m, 11H), 7.61−7.74 (m, 4H); 13C NMR (75 MHz,
CDCl3) δ 13.7, 15.0*, 19.3, 22.4, 22.8*, 24.4*, 26.8, 34.7, 34.9, 66.7*,
67.0, 70.4, 70.5*, 80.6*, 80.7, 127.3, 127.58, 127.64, 127.9*, 128.3,
128.4*, 129.6, 129.7*, 133,4*, 133.9, 135.5*, 135.7, 137.2, 138.8*,
138.9; IR (film) ν−1 3069, 3031, 2986, 2928, 2852, 1470, 1431, 1103,
1089, 989, 702; MS (FAB) m/z 507 (65) [M + Na]+, 271 (56), 249
(42), 198 (100); HRMS (FAB) m/z calcd for C32H40O2SiNa
507.2695, found 507.2698.
Olefin 13i:.15,17 yellowish oil; H NMR (300 MHz, CDCl3) δ 0.91
1
(t, J = 5.9 Hz, 3H), 0.99−1.50 (m, 10H), 1.50−1.88 (m, 3H), 1.90−
2.11 (m, 2H), 2.15 (dd, J = 13.9, 6.4 Hz, 2H*), 5.16 (t, J = 10.1 Hz,
1H*), 5.32 (dt, J = 15.5, 6.2 Hz, 1H*), 5.49−5.73 (m, 2H), 5.91−6.09
(m, 2H), 6.23−6.37 (m, 2H*); 13C NMR (75 MHz, CDCl3) δ 14.0,
22.8, 23.1*, 26.1*, 26.3, 26.4, 30.0*, 33.2, 33.5*, 35.0, 35.2*, 37.0*,
40.9, 41.2*, 127.0*, 128.0, 131.0, 132.6, 134.7*, 136.3*, 138.5, 140.7*;
IR (film) ν−1 3016, 2957, 2921, 2851, 1448, 1377, 986; MS (EI) m/z
178 (56) [M]+, 170 (11), 135 (28), 121 (28), 112 (33), 96 (54), 93
(42), 86 (100); HRMS (EI) m/z calcd for C13H22 178.1716, found
178.1715.
ν
−1 3031, 2956, 2887, 1524, 1487, 1334, 1001, 906, 800, 746, 702; MS
(EI) m/z 158 (14) [M+], 143 (6), 117 (32), 91 (100), 65 (12);
HRMS (EI) m/z calcd for C12H14 158.1090, found 158.1094.
Olefin 13d:.15,16 yellow oil; 1H NMR (500 MHz, CDCl3) δ 2.43 (q,
J = 6.7 Hz, 2H*), 2.54 (dd, J = 14.2, 7.2 Hz, 2H), 3.54 (td, J = 6.8, 4.6
Hz, 2H), 4.53 (s, 2H*), 4.55 (s, 2H), 5.01 (d, J = 9.8 Hz, 1H*), 5.12
(d, J = 9.8 Hz, 1H), 5.15 (s, 1H*), 5.23 (d, J = 15.6 Hz, 1H), 5.51 (dt,
J = 10.4, 7.7 Hz, 1H), 5.74 (dt, J = 15.3, 7.0 Hz), 6.06−6.19 (m, 1H),
6.33 (dt, J = 16.9, 10.3 Hz, 1H), 6.66 (dt, J = 17.2, 10.9 Hz, 1H),
7.47−7.16 (m, 5H); 13C NMR (125 MHz, CDCl3) δ 28.7*, 33.2,
69.85, 69.88*, 73.1, 115.7, 117.8, 127.8, 127.86, 127.89*, 128.6, 131.1,
131.4*, 132.3, 132.9*, 137.3, 138.6*; IR (film) ν−1 3031, 3024, 2986,
1604, 1582, 1463, 1132, 1041, 952, 863, 704; MS (CI) m/z 188 (100)
[M]+, 189 (35) [M + H]+; HRMS (EI) m/z calcd for C13H16O
188.1201, found 188.1203.
Olefin 13j:.15,18 colorless oil; 1H NMR (300 MHz, CDCl3) δ 0.062
(s, 3H), 0.067 (s, 3H), 0.88−0.95 (s, 12H), 1.22 (d, J = 6.3 Hz, 3H),
1.31−1.58 (m, 2H), 2.06 (dd, J = 14.4, 7.1 Hz, 2H), 4.33 (p, J = 6.2
Hz, 1H), 5.57 (dd, J = 14.6, 5.7 Hz, 1H), 5.66 (dd, J = 14.5, 7.0 Hz,
1H), 5.94−6.17 (m, 2H); 13C NMR (75 MHz, CDCl3) δ −4.61,
−4.42, 14.0, 18.51, 22.7, 25.9*, 26.1, 35.0, 65.5*, 69.3, 128.7, 130.1,
134.4, 135.6; IR (film) ν−1 2957, 2927, 2891, 2858, 1550, 1504, 1462,
1252, 1089, 987, 832; MS (CI) m/z 254 (100) [M]+, 255 (35) [M +
H]+, 139 (43), 115 (65); HRMS (CI) m/z calcd for C15H30OSi
254.2066, found 254.2068.
Olefin 13e:.15,16 yellow oil; 1H NMR (300 MHz, CDCl3) δ 4.09 (d,
J = 6.3 Hz, 2H), 4.22 (dd, J = 6.7, 1.3 Hz, 2H*), 4.54 (s, 2H and 2H*),
5.08−5.44 (m, 2H and 2H*), 5.66 (dt, J = 11.8, 6.8 Hz, 1H*), 5.84
(dt, J = 14.4, 6.0 Hz, 1H), 6.19 (t, J = 11.1 Hz, 1H*), 6.26−6.45 (m,
2H), 6.60 (dt, J = 16.8, 10.6 Hz, 1H*), 7.27−7.42 (m, 5H); 13C NMR
(75 MHz, CDCl3) δ 66.0, 70.4, 72.3, 117.8, 119.4, 121.4, 122.5, 124.8,
125.1, 126.6, 128.0, 128.6, 130.3, 131.9, 132.3, 133.5, 136.5, 138.4; IR
(film) ν−1 3086, 3028, 2930, 2851, 1456, 1427, 1238, 1095, 1074,
1003, 910, 756, 727; MS (CI) m/z 174 (84) [M+], 175 (20) [M++1],
149 (100), 145 (54), 133 (49), 118 (56), 117 (81), 115 (62), 105
(94); HRMS (EI) m/z calcd for C12H14O 174.1039, found 174.1038.
Olefin 13f:15 yellow oil; 1H NMR (500 MHz, CDCl3) δ 0.93 (t, J =
7.3 Hz, 3H), 0.94 (t, J = 7.3 Hz, 3H*), 1.39−1.47 (m, 2H), 2.02−2.19
(m, 2H), 2.37−2.57 (m, 2H), 2.72 (dd, J = 8.9, 6.7 Hz, 2H,), 5.37 (dt,
J = 10.8, 7.5 Hz, 1H), 5.50 (td, J = 15.8, 7.6 Hz, 1H), 5.59−5.78 (m,
2H), 5.98−6.14 (m, 2H), 6.30 (dd, J = 15.2, 10.9, 1H), 6.39 (dd, J =
15.1, 11.1 Hz, 1H), 7.19−7.34 (m, 5H); 13C NMR (125 MHz, CDCl3)
δ 13.95, 13.99*, 22.72, 22.76*, 29.8, 34.7*, 34.9*, 35.2, 36.11*, 36.16;
123.8, 124.4, 125.8, 126.0, 126.5, 128.5, 129.4, 130.5, 131.1, 132.6,
133.5, 135.2, 142.2; IR (film) ν−1 3086, 3028, 2930, 2851, 1456, 1427,
1238, 1095, 1074, 1003, 910, 756, 727; MS (EI) m/z 200 (13) [M+],
201 (2) [M++1], 143 (12), 129 (13), 117 (15), 109 (68), 91 (100);
HRMS (EI) m/z calcd for C15H20 200.1560, found 200.1560.
Olefin 13k:15 yellowish oil; 1H NMR (300 MHz, CDCl3) δ 0.94 (t,
J = 7.3 Hz, 3H*), 0.96 (t, J = 7.4 Hz, 3H), 1.32−1.61 (m, 2H), 2.14 (p,
J = 6.9 Hz, 2H), 2.28 (dt, J = 14.9, 7.4 Hz, 2H*), 5.47−5.73 (m. 1H*),
5.76−60.2 (m, 2H), 6.40 (d, J = 15.7 Hz, 1H), 6.51 (d, J = 10.1 Hz,
1H*), 6.75 (dd, J = 15.6, 10.4 Hz, 1H), 7.06 (dt, J = 11.1, 9.2 Hz,
1H*), 7.22−7.45 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 13.94,
14.01*, 22.6, 23.1*, 30.3*, 35.2, 124.6*, 125.3*, 126.4, 127.5, 127.7*,
128.6, 128.8*, 128.9, 130.6, 130.8*, 131.4, 132.7*, 136.4*, 136.5*,
136.7, 138.9; IR (film) ν−1 3012, 2959, 2928, 2872, 1641, 1489, 1456,
1091, 1012, 986, 845, 820, 798, 735; MS (EI) m/z 206 (68) [M]+, 207
(18) [M + 1]+, 208 (33) [M + 2]+, 209 (6) [M + 3]+, 205 (11), 179
(37), 177 (100), 167 (37), 165 (87), 163 (46), 141 (49); HRMS (EI)
m/z calcd for C13H15Cl 206.0857, found 206.0857.
Olefin 13l:15 yellowish solid; mp = 32−33 °C; 1H NMR (300 MHz,
CDCl3) δ 0.95 (t, J = 7.8 Hz, 3H), 1.42−1.53 (m, 2H), 2.16 (dt, J =
14.2, 6.8 Hz, 2H), 2.31 (dt, J = 13.1, 6.6 Hz, 2H*), 5.68 (dt, J = 15.6,
8.6 Hz, 1H*), 5.76−6.02 (m, 2H), 6.19 (dt, J = 15.4, 9.4 Hz, 1H*),
6.47 (d, J = 15.5 Hz, 1H), 6.53 (d, J = 10.6 Hz, 1H*), 6.88 (dd, J =
15.7, 10.4 Hz, 1H), 7.19 (dt, J = 11.2, 9.3 Hz, 1H*), 7.46 (t, J = 8.1
Hz, 2H), 7.51 (t, J = 7.8 Hz, 2H*), 8.03 (d, J = 8.7 Hz, 2H), 8.09 (d, J
= 8.2 Hz, 2H*); 13C NMR (75 MHz, CDCl3) δ 13.9, 22.5, 35.2, 124.9,
125.6, 127.4, 129.3, 129.6, 130.1, 132.0, 132.7, 133.3, 135.0, 138.7,
139.8, 140.7, 141.6, 148.9; IR (film) ν−1 3062, 2983, 2945, 2875, 1523,
1346, 995, 825, 864, 723; MS (EI) m/z 217 (75) [M]+, 218 (11) [M +
1]+, 188 (67), 158 (34), 142 (81), 141 (100), 128 (58), 115 (46);
HRMS (EI) m/z calcd for C13H15O2N 217.1097, found 217.1093.
Olefin 13m:15 yellow oil; 1H NMR (300 MHz, CDCl3) δ 2.49 (dd,
J = 14.9, 7.1 Hz, 2H*), 2.64 (dd, J = 14.6, 7.3 Hz, 2H), 2.75−2.86 (m,
2H), 5.59 (dt, J = 10.7, 7.6 Hz, 1H), 5.88 (dt, J = 15.2, 7.1 Hz, 1H*),
6.20 (t, J = 10.9 Hz, 1H), 6.27 (dd, J = 15.0, 10.0 Hz, 1H*), 6.47 (d, J
= 15.8 Hz, 1H*), 6.54 (d, J = 15.5 Hz, 1H), 6.77 (dd, J = 15.6, 10.4
Hz, 1H*), 7.03 (ddd, J = 15.4, 11.3 Hz, 1H), 7.19−7.42 (m, 10H); 13C
NMR (125 MHz, CDCl3) δ 30.1, 34.9*, 36.0*, 36.1, 124.5, 126.2,
126.4*, 126.6, 127.4*, 127.6, 128.6, 128.7, 128.8, 129.5, 130.7*,
131.3*, 132.0, 132.6, 134.8*, 137.8, 141.9; IR (film) ν−1 3071, 3024,
2924, 2870, 1495, 1452, 1074, 986, 945, 748, 729; MS (EI) m/z 234
(18) [M], 235 (3) [M + H]+, 143 (100), 128 (47), 91 (54), 84 (41);
HRMS (EI) m/z calcd for C18H18 234.1403, found 234.1400.
Olefin 13g:15 yellowish oil; 1H NMR (300 MHz, CDCl3) δ 0.93 (t,
J = 6.1 Hz, 3H), 0.96 (t, J = 5.2 Hz, 3H*), 1.39−1.51 (m, 2H), 2.10 (q,
J = 7.1 Hz, 2H), 2.20 (q, J = 7.5 Hz, 2H*), 4.08 (d, J = 6.3 Hz, 2H),
4.12 (d, J = 6.2 Hz, 1H*), 4.21 (d, J = 6.8 Hz, 1H*), 4.54 (s, 2H), 4.56
(s, 2H*), 5.50 (dt, J = 15.1, 7.6 Hz, 1H), 5.64−5.78 (m, 2H and 1H*),
6.09 (dd, J = 14.7, 10.5 Hz, 1H), 6.27 (dd, J = 15.2, 10.3 Hz, 1H), 6.59
(ddd, J = 15.2, 11.0, 1.1 Hz, 1H*), 7.27−7.47 (m, 5H); 13C NMR (75
MHz, CDCl3) δ 13.88, 22.6, 23.0*, 30.0*, 34.9, 35.0*, 66.0*, 70.8,
72.1, 72.3*, 125.0, 125.5, 127.5, 127.7, 127.8, 128.3, 130.2, 130.4,
132.3, 133.1, 135.4, 138.4; IR (film) ν−1 3063, 3026, 2957, 2927, 2858,
1659, 1497, 1454, 1362, 1099, 1070, 989, 734, 696; MS (CI) m/z 216
(64) [M]+, 217 (12) [M + H]+, 159 (100), 134 (78), 125 (52), 91
(82); HRMS (CI) m/z calcd for C15H20O 216.1514, found 216.1521.
Olefin 13h:15 yellowish oil; 1H NMR (300 MHz, CDCl3) δ 0.93 (t,
J = 7.4 Hz, 3H, H-1), 1.06 (s, J = 9.8 Hz, 9H), 1.44 (dq, J = 14.6, 7.3
Hz, 2H), 2.02−2.17 (m, 2H), 2.13−2.24 (m, 2H*), 3.65 (dd, J = 10.5,
4.8 Hz, 1H), 3.81 (dd, J = 10.5, 6.6 Hz, 1H), 4.01 (dt, J = 12.1, 6.9 Hz,
2H*), 4.45 (d, J = 10.0 Hz, 1H*), 4.46 (d, J = 12.1 Hz, 1H), 4.49 (d, J
= 9.9 Hz, 1H*), 4.65 (d, J = 12.1 Hz, 1H), 5.18 (dd, J = 10.0, 9.6 Hz,
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Note
Olefin 13n:15 slightly yellow oil; H NMR (300 MHz, CDCl3) δ
128.7, 129.0, 129.1*, 132.0*, 132.7, 136.7*, 136.9, 138.3*, 138.4; IR
(film) ν−1 3061, 3026, 2922, 2848, 1494, 1452, 1360, 1112, 1072, 966,
732, 692; MS (FAB) m/z 295 (15) [M + Na]+, 281 (61), 263 (20),
247 (100), 237 (35), 221 (56), 199 (42), 180 (65); HRMS (FAB) m/
z calcd for C16H16ONa 247.1099, found 247.1097.
1
0.96 (d, J = 6.6 Hz, 3H), 1.11−1.34 (m, 1H), 1.34−1.52 (m, 1H),
1.52−1.62 (m, 1H), 1.64 (s, 3H), 1.72 (s, 3H), 2.04 (dq, J = 14.3, 7.3
Hz, 2H), 2.11−2.26 (m, 1H), 2.32 (dt, J = 13.5, 6.7 Hz, 1H), 5.14 (t, J
= 7.0 Hz, 1H), 5.57 (dt, J = 10.5, 8.0 Hz, 1H), 5.84 (dt, J = 15.0, 7.4
Hz, 1H*), 6.24 (t, J = 10.9, 1H), 6.47 (d, J = 15.7 Hz, 1H*), 6.55 (d, J
= 15.6 Hz, 1H), 6.80 (dd, J = 15.6, 10.3 Hz, 1H*), 7.09 (dd, J = 15.5,
11.1 Hz, 1H), 7.18−7.48 (m, 5H); 13C NMR (125 MHz, CDCl3) δ
17.9, 19.8, 25.9, 26.0, 29.9, 33.1*, 33.4, 35.4, 37.0, 40.6*, 124.8, 125.0,
126.3*, 126.5, 127.3*, 127.5, 128.8, 129.7, 130.1*, 131.4, 131.9*,
132.2, 132.2, 134.7*, 137.9; IR (film) ν−1 3078, 3058, 2926, 2908,
2870, 1595, 1493, 1448, 1377, 984, 945, 908; MS (CI) m/z 254 (100)
[M]+, 255 (31) [M + 1]+, 211 (23), 163 (11), 143 (16); HRMS (CI)
m/z calcd for C19H26 254.2035, found 254.2027.
Hydroxysulfone 8 Synthesis. Epoxide Opening.8 A solution of
styrene oxide (690 μL, 6.07 mmol) and BT-SH (1.12 g, 6.68 mmol) in
CH2Cl2 (66.8 mL, 0.1 M) was cooled to 0 °C, and Sm(OTf)3 (36 mg,
0.06 mmol) was added in one portion. The resulting mixture was
allowed to warm to rt and stirred for 8 h. After the mixture was stirred
at rt for 8 h, a saturated aqueous solution of NaHCO3 (50 mL) was
added. The resulting layers were separated, and the aqueous layer was
extracted with CH2Cl2 (3 × 70 mL); the combined organic layers were
washed with brine (50 mL), dried over MgSO4, and filtered; and the
solvents were removed under reduced pressure. The residue was
purified by flash column chromatography on SiO2 (petroleum ether/
EtOAc = 4:1 → 2:1), and the reaction yielded 1.70 g (98%) of
Olefin 13o:15 yellow viscous oil; H NMR (300 MHz, CDCl3) δ
1
4.19 (d, J = 6.1 Hz, 2H), 4.36 (d, J = 6.8 Hz, 2H*), 4.63 (d, J = 6.0 Hz,
2H), 5.77 (dt, J = 11.1, 6.8 Hz, 1H*), 6.00 (dt, J = 15.1, 6.1 Hz, 1H),
6.41 (t, J = 11.0 Hz, 1H*), 6.51 (dd, J = 15.2, 10.5 Hz, 1H), 6.62 (d, J
= 15.7 Hz, 1H), 6.65 (d, J = 15.5 Hz, 1H*), 6.87 (dd, J = 15.6, 10.5
Hz, 1H), 7.07 (dd, J = 15.5, 11.2 Hz, 1H*), 7.24−7.54 (m, 10H); 13C
NMR (75 MHz, CDCl3) δ 65.9*, 70.5, 72.1*, 72.2, 123.8, 126.5,
126.6*, 127.66, 127.70, 127.74, 127.8, 128.0, 128.3*, 128.48, 128.50,
128.7, 130.2, 132.0, 132.8, 133.0, 134.3, 137.1*, 137.2, 138.3*, 138.4;
IR (film) ν−1 3080, 3059, 3026, 2920, 2850, 1597, 1494, 1450, 1360,
1097, 1070, 989, 732, 692; MS (EI) m/z 250 (8) [M]+, 159 (22), 131
(53), 117 (56), 115 (75); HRMS (CI) m/z calcd for C18H18O
250.1352, found 250.1346.
1
hydroxy BT-sulfide as a colorless viscous oil: H NMR (300 MHz,
CDCl3) δ 3.97 (broad s, 1H), 4.17−4.35 (m, 2H), 5.16 (dd, J = 7.2,
5.6 Hz, 1H), 7.29−7.48 (m, 7H), 7.75 (d, J = 8.0 Hz, 1H), 7.90 (d, J =
8.1 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 55.4, 67.5, 121.3, 121.8,
124.9, 126.5, 128.1, 128.6, 129.3, 135.7, 137.7, 152.8, 166.7; MS (CI)
m/z 288 (100) [M + 1]+, 289 (19) [M + 2]+, 290 (11) [M + 2]+, 151
(8), 149 (25); HRMS (CI) m/z calcd for C15H14ONS2 288.0517,
1
found 288.0515. Hydroxy PT-sulfide: colorless viscous oil; H NMR
(300 MHz, CDCl3) δ 3.06 (broad s, 1H), 4.24 (d, J = 6.1 Hz, 2H),
5.19 (t, J = 6.3 Hz, 1H), 7.28−7.44 (m, 5H), 7.53 (broad s, 5H); 13C
NMR (75 MHz, CDCl3) δ 55.5, 67.5, 121.3, 121.8, 124.9, 126.5, 128.1,
128.6, 129.3, 135.7, 137.7, 152.8, 166.7; MS (ESI) m/z 299 (100) [M
+ 1]+, 300 (21) [M + 2]+, 301 (8) [M + 3]+, 239 (30), 151 (20);
HRMS (ESI) m/z calcd for C15H15ON4S 299.0961, found 299.0964.
Sulfide Oxidation. A solution of hydroxy BT-sulfide (500 mg, 1.74
mmol) in EtOH (17.4 mL, 0.2 M) was cooled to 0 °C, and a cold (0
°C) yellow solution of molybdate (108 mg, 87 μmol) in 35% aqueous
H2O2 (2 mL, 17.5 mmol) was added dropwise. The resulting mixture
was allowed to warm to rt and stirred for an additional 18 h. The
resulting slightly yellow milky solution was cooled to 0 °C, and
aqueous saturated Na2S2O3 (10 mL) was added dropwise. Water (10
mL) was added, and the whole mixture was extracted with EtOAc (3 ×
25 mL). The combined organic layers were washed with brine (10
mL), dried over MgSO4, and filtered, and the solvents were removed
under reduced pressure. The residue was purified by flash column
chromatography on SiO2 (petroleum ether/EtOAc = 2:1 → 1:1 →
0:100), and the reaction yielded 410 mg (74%) of 8a as a colorless
solid: mp = 161−162 °C; 1H NMR (500 MHz, CDCl3) δ 2.60 (broad
s, 2H), 4.30 (dd, J = 12.4, 4.9 Hz, 1H), 4.78 (dd, J = 12.4, 7.5 Hz, 1H),
4.93 (dd, J = 7.4, 4.9 Hz, 1H), 7.21−7.35 (m, 5H), 7.58 (dd, J = 11.2,
4.1 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 4.64 (dt, J = 7.7, 1.0 Hz, 1H),
8.24 (d, J = 8.3 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 61.5, 72.6,
111.6, 122.4, 125.7, 127.9, 128.3, 129.2, 129.8, 130.1, 137.3, 152.7,
165.3; MS (ESI) m/z 342 (100) [M + Na]+, 301 (64), 214 (17), 121
(8); HRMS (ESI) m/z calcd for C15H14O3NS2 320.0410, found
320.0412.
Olefin 13p:15 yellowish syrup; 1H NMR (300 MHz, CDCl3) δ 1.06
(s, 9H*), 1.07 (s, 9H), 3.70 (dd, J = 10.6, 5.0 Hz, 1H and 1H*), 3.86
(dd, J = 10.7, 6.4 Hz, 1H and 1H*), 3.89 (dd, J = 11.4, 6.8 Hz, 1H*),
4.06 (dd, J = 11.9, 6.7 Hz, 1H), 4.49 (dd, J = 12.1, 6.3 Hz, 1H and
1H*), 4.68 (dd, J = 12.2, 3.8 Hz, 1H and 1H*), 5.41 (dd, J = 10.1, 9.8
Hz, 1H*), 5.71 (dd, J = 15.4, 7.5 Hz, 1H), 6.39 (dd, J = 15.5, 10.5 Hz,
1H, H-1), 6.45 (dd, J = 10.8, 6.2 Hz, 1H*), 6.56 (d, J = 15.7 Hz, 1H,
H-1), 6.57 (d, J = 15.4 Hz, 1H*), 6.78 (dd, J = 15.5, 10.2 Hz, 1H),
6.87 (dd, J = 14.9, 10.5 Hz, 1H*), 7.28−7.52 (m, 15), 7.58−7.80 (m,
5H); 13C NMR (75 MHz, CDCl3) δ 19.5, 26.9*, 27.1, 66.9*, 67.1,
70.4*, 70.9, 75.4, 80.6, 124.3, 126.6, 126.8, 127.7, 128.1, 128.5, 128.76,
128.85, 129.5, 129.8, 132.0, 132.8, 135.1, 135.9, 137.4, 138.8, 138.9; IR
(film) ν−1 3068, 3028, 2957, 2929, 2856, 1471, 1427, 1110, 1083, 991,
700; MS (FAB) m/z 541 (85) [M + Na]+, 411 (24), 271 (68), 249
(32), 197 (100); HRMS (FAB) m/z calcd for C35H38O2SiNa
541.2539, found 541.2543.
Olefin 13q:.15,18 yellowish oil; 1H NMR (300 MHz, CDCl3) δ 1.25
(s, 9H*), 1.27 (s, 9H), 5.51 (d, J = 11.9 Hz, 1H*), 5.88 (d, J = 15.5
Hz, 1H), 6.02 (t, J = 11.8 Hz, 1H*), 6.17 (dd, J = 15.5, 10.2 Hz, 1H),
6.46 (d, J = 15.4 Hz, 1H*), 6.49 (d, J = 15.7 Hz, 1H), 6.77 (dd, J =
15.6, 10.2 Hz, 1H), 7.18−7.40 (m, 5H); 13C NMR (75 MHz, CDCl3)
δ 22.9, 29.6*, 29.8, 124.1*, 125.6, 126.3, 126.6*, 127.2, 127.6*, 128.8,
130.1, 130.4, 131.9*, 137.9, 147.0; IR (film) ν−1 3024, 2958, 2916,
2849, 1595, 1488, 1462, 1361, 1232, 987, 910, 744; MS (EI) m/z 186
(27) [M]+, 187 (2) [M + H]+, 171 (26), 86 (66), 84 (100), 57 (14);
HRMS (EI) m/z calcd for C14H18 186.1403, found 186.1399.
Olefin 13r:.15,19 yellowish oil; 1H NMR (500 MHz, CDCl3) δ 2.62
(dd, J = 15.0, 7.0 Hz, 2H*), 2.69−2.80 (m, 2H), 2.80−3.01 (m, 2H
and 2H*), 5.79 (dt, J = 11.6, 6.9 Hz, 1H), 6.35 (dt, J = 15.8, 6.7 Hz,
1H*), 6.51 (d, J = 15.9 Hz, 1H*), 6.54 (d, J = 11.6 Hz, 1H), 7.21−
7.49 (m, 10H); 13C NMR (125 MHz, CDCl3) δ 30.6, 35.1*, 36.1*,
36.3, 126.1*, 126.2, 126.8, 127.1*, 128.3, 128.5, 128.7, 128.9, 129.6,
130.1*, 130.5*, 132.0, 137.7, 137.9*, 141.8, 141.9*; IR (film) ν−1
3061, 3024, 2922, 2854, 1601, 1495, 1452, 1074, 1030, 964, 908, 735,
696; MS (EI) m/z 208 (7) [M]+, 209 (2) [M + 1]+, 129 (12), 117
(100), 115 (66), 91 (86); HRMS (EI) m/z calcd for C16H16 208.1247,
found 208.1248.
Sulfone 8b: colorless viscous syrup; 1H NMR (300 MHz, CDCl3) δ
1H NMR (300 MHz, CDCl3) δ 3.09 (broad s, 1H), 4.20 (dd, J = 12.3,
4.8 Hz, 1H), 4.64 (dd, J = 12.3, 8.5 Hz, 1H), 5.02 (dd, J = 8.4, 4.8 Hz,
1H), 7.21−7.43 (m, 7H), 7.45−7.63 (m, 3H); 13C NMR (75 MHz,
CDCl3) δ 61.4, 73.8, 126.2, 127.6, 129.4, 130.3, 130.5, 131.6, 132.9,
153.7; MS (ESI) m/z 353 (100) [M + Na]+, 331 (15) [M + 1]+, 267
(8), 119 (10); HRMS (ESI) m/z calcd for C15H15O3N4S 331.0859,
found 331.0863.
Olefin 13s:.15,20 yellowish oil; 1H NMR (300 MHz, CDCl3) δ 4.25
(d, J = 6.0 Hz, 2H), 4.36 (dd, J = 6.4, 1.1 Hz, 2H*), 4.58 (s, 2H*),
4.63 (s, 2H), 5.97 (dt, J = 12.4, 6.3 Hz, 1H*), 6.39 (dt, J = 15.9, 6.0
Hz, 1H), 6.67 (d, J = 11.2 Hz, 1H*), 6.69 (d, J = 16.0 Hz, 1H), 7.21−
7.53 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 67.1*, 70.9, 72.3,
72.6*, 126.2, 126.7, 127.3*, 127.8, 127.98, 128.04*, 128.4*, 128.6,
ASSOCIATED CONTENT
■
S
* Supporting Information
Optimization tables, additional information, and H and 13C
1
NMR spectra for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
6363
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The Journal of Organic Chemistry
Note
(15) Characterization data corresponds to (E/Z)-mixtures of olefins.
Characteristic peaks for minor isomer obtained using method D
reaction protocol are marked with an asterisk.
(16) Borg, T; Tuzina, P; Somfai, P. J. Org. Chem. 2011, 76, 8070−
8075.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: jiri.pospisil@uclouvain.be.
Notes
(17) Ikeda, Y.; Ukai, J.; Ikeda, N.; Yamamoto, H. Tetrahedron 1987,
The authors declare no competing financial interest.
43, 731−742.
(18) Gallagher, W. P.; Terstiege, I.; Maleczka, R. E. J. Am. Chem. Soc.
2001, 3194−3204.
ACKNOWLEDGMENTS
■
(19) Irfan, M.; Fuchs, M.; Glasnov, T. N.; Kappe, C. O. Chem.Eur.
Fabio Lucaccioni (U.C.L) is gratefully acknowledged for his
help with GC and HPLC separation method development. J.P.
J. 2009, 11608−11618.
(20) Parrish, J. P.; Jung, Y. C.; Shin, S. I.; Jung, K. W. J. Org. Chem.
2002, 7127−7130.
is grateful to Prof. Istvan
support. The Universite
de la Recherche Scientific (Charge
to J.P., Chercheur Qualifie F.R.S.-FNRS to R.R.) are gratefully
́
E. Marko
Catholique de Louvain and the Fond
de Recherche F.R.S.-FNRS
́
(U.C.L.) for his continuous
́
́
́
acknowledged for financial support.
REFERENCES
■
(1) (a) Blakemore, P. R. J. Chem. Soc., Perkin Trans. 1 2002, 2563−
2585. (b) Aïssa, C. Eur. J. Org. Chem. 2009, 1831−1844. (c) Marko,
́
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(2) (a) Pospísi
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I. E. Org. Lett. 2006, 8, 5983−5986.
(b) Pospísil, J.; Marko,
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(3) The addition/retroaddition process was already proposed
previously as a possible explanation of unusual high (Z)-selectivity
of newly created olefin; see: Kikuchi, R.; Fujii, M.; Akita, H.
Tetrahedron: Asymmetry 2009, 20, 1975−1983.
(4) Baudin, B. D.; Hareau, G.; Julia, S. A.; Ruel, O. Bull. Soc. Chim. Fr.
1993, 130, 336−357.
(5) This assumption was based on analogy with the olefination
reaction of 2-pyridyl sulfones with various aldehydes; see refs 1b, 4,
and: Charette, A. B.; Berthelette, C.; St-Martin, D. Tetrahedron Lett.
2001, 42, 5149−5153.
(6) Allyl and benzyl BT- and PT-sulfones were prepared in two steps
from the corresponding allylic or benzylic alcohols; see: Pospísi
̌
l, J.;
Sato, H. J. Org. Chem. 2011, 76, 2269−2272.
(7) The stereoselective synthesis of 1,3-dienes is very important since
they are highly versatile synthetic building blocks; see, e.g.
(a) Oppolzer, W. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, pp 315−377.
(b) Roush, W. R. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, pp 513−546.
(c) Weinreb, S. M. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, pp 401−444.
(d) Clennan, E. L. Tetrahedron 1991, 47, 1343−01382.
(8) Sulfones 14 were prepared in two steps starting from styryl oxide;
see: Vougioukas, A. E.; Kagan, H. B. Tetrahedron Lett. 1987, 28, 6065−
6068.
(9) For more details, see the Supporting Information.
(10) (a) Kocienski, P. J.; Bell, A. G.; Blakemore, P. R. Synlett 2000,
̌
365−367. (b) Pospísil, J.; Robiette, R.; Sato, H.; Debrus, K. Org.
Biomol. Chem. 2012, 10, 1225−1234.
(11) Barbier-like reaction conditions: the base is added to the
reaction mixture containing sulfone 16 and aldehyde 12c in
appropriate solvent.
(12) TDA-1 = tris[2-(2-methoxy)ethyl]amine; selective K+-specific
chelating agent, see, e.g., ref 2 or Tamao, K.; Nakagawa, Y.; Ito, Y. Org.
Synth. 1996, 73, 1035−1042.
(13) The same substrates (sulfone and aldehyde) were reacted with
KHMDS using THF (method A) and DMF (method B) as solvents.
Selectivity of the reaction was then compared with the reactions
carried out under our optimized reaction conditions using 18-crown-
6/DMF (method C) or DMF/TDA-1 = 3:1 (v/v) (method D)
systems.
(14) Habrant, D.; Stengel, B.; Meunier, S.; Mioskowski, C. Chem.
Eur. J. 2007, 13, 5433−5440.
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