Copper-catalyzed asymmetric oxidation of sulfides

Article abstract of DOI:10.1021/jo2026178

Copper-catalyzed asymmetric sulfoxidation of aryl benzyl and aryl alkyl sulfides, using aqueous hydrogen peroxide as the oxidant, has been investigated. A relationship between the steric effects of the sulfide substituents and the enantioselectivity of th

Full text of DOI:10.1021/jo2026178

Article
pubs.acs.org/joc
Copper-Catalyzed Asymmetric Oxidation of Sulfides
Graham E. O’Mahony,† Alan Ford,† and Anita R. Maguire*,‡
‡
†Department of Chemistry, Department of Chemistry and School of Pharmacy, Analytical and Biological Chemistry Research
Facility, University College Cork, Cork, Ireland
S
* Supporting Information
ABSTRACT: Copper-catalyzed asymmetric sulfoxidation of
aryl benzyl and aryl alkyl sulfides, using aqueous hydrogen
peroxide as the oxidant, has been investigated. A relationship
between the steric effects of the sulfide substituents and the
enantioselectivity of the oxidation has been observed, with up
to 93% ee for 2-naphthylmethyl phenyl sulfoxide, in modest
yield in this instance (up to 30%). The influence of variation of
solvent and ligand structure was examined, and the optimized conditions were then used to oxidize a number of aryl alkyl and
aryl benzyl sulfides, producing sulfoxides in excellent yields in most cases (up to 92%), and good enantiopurities in certain cases
(up to 84% ee).
Scheme 1. Copper-Catalyzed Asymmetric Oxidation of
Sulfides
INTRODUCTION
■
Optically pure sulfoxides are widely used as building blocks and
chiral auxiliaries in asymmetric synthesis.1 The sulfinyl group
has been shown to be an effective chiral auxiliary in a broad
range of synthetic reactions from carbon−carbon bond-forming
reactions2 to cycloaddition reactions.3−5 Enantiopure sulfoxides
have also found use in the pharmaceutical industry due to their
important biological activity; for example, esomeprazole, the
(S)-enantiomer of omeprazole, has been one of the world’s
best-selling drugs since its launch in 2001. Modafinil is a
psychostimulant agent that has been used for the treatment of
narcolepsy; it is manufactured by Cephalon and is marketed in
the racemic form as Provigil.6
Since the 1980s, metal-catalyzed asymmetric sulfide
oxidation employing titanium, vanadium, and a number of
other metal-based systems has developed rapidly as a route to
enantiopure sulfoxides.7 The initial breakthrough came in 1984
when the research groups of Kagan8,9 and Modena10
independently reported an efficient titanium-mediated sulfide
oxidation based on the Sharpless asymmetric epoxidation
procedure.11 1n 1995, Bolm reported a robust vanadium
sulfoxidation procedure using a vanadium Schiff base
complex.12 The oxidation was carried out under mild
conditions using hydrogen peroxide as the oxidant. A number
of other metals, such as iron, manganese, aluminum, niobium,
zirconium, tungsten, molybdenum, and osmium, have also been
used to catalyze asymmetric oxidation of sulfides.7
However, there are disadvantages associated with the Kagan
and Bolm procedures for asymmetric oxidation. The Kagan
system is limited by its sensitivity to atmospheric moisture and
low turnover numbers, and it utilizes a complex and expensive
catalytic system.13 Although the Bolm procedure is robust and
operationally straightforward, the use of vanadium is not
advantageous since vanadium is known to exert toxic,
mutagenic, and genotoxic effects on a variety of biological
systems.14
Copper has received relatively little attention in metal-
catalyzed asymmetric sulfoxidation. The research groups of
Cross,15 Kraemer,16 Zhu,17 and Alcon18 have all used copper-
based systems to asymmetrically oxidize sulfides, but with
limited success (enantioselectivities of 0−30% ee). In an initial
study, we demonstrated good enantiocontrol in copper-
catalyzed asymmetric oxidation of aryl benzyl sulfides with up
to 81% ee, albeit with modest yields (typically 20−30%,
Scheme 1).19 Herein, we wish to describe the expansion of this
early investigation resulting in improved yields, while retaining
good enantioselectivity through variation of reaction con-
ditions. The influence of variation of solvent, ligand, and
substrate structure has been examined, rendering this oxidation
synthetically useful.
Received: January 11, 2012
Published: February 24, 2012
© 2012 American Chemical Society
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Table 1. Investigation of Solvent
d
toluene
% yield
CCl4
a
b
c
a
b
c
entry
1
Ar
Ar′
1:2
2
% ee (R)
1:2
% yield
% ee (R)
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
Ph
Ph
Ph
Ph
Ph
Ph
73:27
74:26
74:26
54:46
78:22
55:45
75:25
2a
2b
2c
2d
2e
2f
21
19
18
33
15
30
18
58
77
73
54
51
46
34
74:26
57:43
68:32
63:37
46:54
47:53
71:29
27
29
24
17
38
42
13
61
79
69
39
55
27
39
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
4-MeC6H4
4-MeC6H4
4-FC6H4
4′-MeOC6H4
1g
Ph
2g
a
b
Ratio of 1:2 determined by 1H NMR analysis of the crude product; no sulfone produced. Yield of 2 after purification by column chromatography.
c
Determined by HPLC analysis on chiral column (Daicel Chiracel OD-H). Absolute configuration determined by comparison of specific rotation
values for 2a and 2e to known literature values; for 2b, 2c, 2d, 2f, and 2g, proposed configuration based on HPLC elution order and the direction of
d
the specific rotations. Results obtained by Kelly et al.19
Table 2. Influence of Steric and Electronic Effects
d
no NMO
NMO
a
b
c
ad
,
b
cd
,
entry
sulfide 5
R
R′
sulfoxide 6
ligand
5:6
% yield
% ee (R)
5:6
% yield
% ee (R)
1
2
5a
5b
5c
5d
5e
5b
5c
5d
5e
5f
Ph
−CH2C6H4
Me
6a
6b
6c
6d
6e
6b
6c
6d
6e
6f
3
3
3
3
3
4
4
4
4
4
3
4
4
4
79:21
79:21
84:16
80:20
86:14
81:19
81:19
72:28
70:30
72:28
82:18
71:29
80:20
73:27
17
15
8
58
22
3
61:39
65:35
83:17
60:40
78:22
64:36
78:22
59:41
71:29
69:31
78:22
76:24
72:28
45:55
30
37
10
39
20
36
14
40
24
26
17
18
28
30
60
21
6
4-MeC6H4
3
4-MeC6H4
−CH2CCH
4
Ph
Et
12
23
11
4
40
54
19
5
49
60
16
4
5
Ph
−CH2-cyclohexyl
Me
6
4-MeC6H4
7
4-MeC6H4
−CH2CCH
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Et
22
19
19
13
15
15
46
57
50
51
61
71
93
53
63
64
56
61
71
93
9
−CH2-cyclohexyl
i-Pr
10
11
12
13
14
5g
5g
5h
5i
−CH2CH(CH3)2
−CH2CH(CH3)2
−CH2C(CH3)3
−CH2-2′-naphthyl
6g
6g
6h
6i
23
a
b
Ratio of 5:6 determined by 1H NMR analysis of the crude product; no sulfone produced. Yield of 6 after purification by column chromatography.
c
Determined by HPLC analysis on chiral column (Daicel Chiracel OD-H). Absolute configuration determined by comparison of specific rotation
values for 6a, 6b, 6d, 6e, 6f, and 6g to known literature values; for 6c, 6h, and 6i, proposed configuration based on HPLC elution order and direction
d
of specific rotations. Results obtained when oxidation was carried out in the presence of 2.5 mol % NMO.
stronger influence on the enantioselectivity of the oxidation
than the electronic effect (Table 2, entries 3 and 7). There is a
direct trend between the size of R′ and the enantioselectivity of
the oxidation; for example, substitution of a methyl group with
an ethyl group in the R′ position results in a large increase in
enantioselectivity (22% to 40% ee, Table 2, entries 2 and 4). A
similar increase in enantioselectivity is observed on replacing an
isobutyl with a neopentyl group in the R′ position (Table 2,
entries 12 and 13). The oxidation of 2-naphthylmethyl phenyl
sulfide produced the corresponding sulfoxide in 93% ee, the
highest to date in copper-catalyzed asymmetric sulfide
oxidation. We have previously shown that carrying out
copper-catalyzed oxidations in the presence of NMO results
in an improvement in the yield of sulfoxide.19 Thus, the above
experiments were repeated using NMO as an additive, and the
RESULTS AND DISCUSSION
■
The effects of varying sulfide substituents, Schiff base ligand,
and solvent were investigated in an attempt to optimize the
asymmetric oxidation and, in particular, to improve the
efficiency of the transformation. An initial solvent study
demonstrated that CCl4 could be replaced with toluene as
the solvent for copper-catalyzed asymmetric sulfoxidation with
no significant loss in yield or enantioselectivity, as shown in
Table 1.
We next examined the influence of steric and electronic
effects on the efficiency and enantioselectivity of the oxidation.
Since Schiff base ligands 3 and 4 had produced the best results
in preliminary studies, these were used in this investigation, as
shown in Table 2. The results indicate that the steric effect
(Table 2, entries 5 and 9) of the R′ substituent has a much
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Table 3. Investigation of Solvent
a
b
c
entry
solvent
7:8:9
yield, 8 (%)
% ee (R)
1
2
ether
85:15:0
69:31:0
79:21:0
65:35:0
66:34:0
100:0:0
40:60:0
19:81:0
47:53:0
46:54:0
42:58:trace
48:52:0
3:96:1
8
25
17
27
26
0
10
1
dioxane
toluene
CCl4
3
58
61
69
4
5
benzene
hexane
MeOH
6
7
50
73
48
47
52
45
87
90
85
83
70
82
87
46
38
24
29
47
47
49
46
80
76
79
1
d
8
MeOH
9
50:50 toluene/MeOH
75:25 toluene/MeOH
90:10 toluene/MeOH
95:5 toluene/MeOH
90:10 hexane/MeOH
90:10 hexane/EtOH
90:10 cyclohexane/MeOH
90:10 hexane/IPA
10
11
12
13
14
15
16
17
18
19
20
21
1:98:1
8:91:1
7:92:1
90:10 CCl4/MeOH
21:76:3
9:89:2
62
63
7
d
90:10 CCl4/MeOH
90:10 hexane/benzyl alcohol
4:94:2
90:10 hexane/t-BuOH
45:55:trace
57:43:0
4
90:10 hexane/2-butanol
8
a
b
c
1
Ratio of 7:8:9 determined by H NMR analysis of the crude product. Yield of 8 after purification by column chromatography. Determined by
HPLC analysis on chiral column (Daicel Chiracel OD-H). Absolute configuration determined by comparison of rotation values to literature values.
d
Was carried out in the presence of 2.5 mol % NMO.
Table 4. Investigation of Effect of Ligand Structure
a
b
c
entry
ligand
7:8:9
yield, 8 (%)
% ee (R)
1
2
3
4
5
6
7
8
3
4
1:97:2
1:98:1
86
90
28
24
39
44
47
87
66
79
3
10
11
12
13
14
15
68:32:0
73:27:0
74:36:0
50:50:0
3
2
6
45:55:trace
3:96:1
37
58
a
b
c
1
Ratio of 7:8:9 determined by H NMR analysis of the crude product. Yield of 8 after purification by column chromatography. Determined by
HPLC analysis on chiral column (Daicel Chiracel OD-H). Absolute configuration determined by comparison of rotation values to literature values.
results are shown in Table 2. We found that the addition of
NMO (2.5 mol %) resulted in an improvement in yield in
nearly all cases. The poor yields obtained were attributed to
product inhibition of the oxidation, presumably through
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Table 5. Asymmetric Oxidation of Sulfides Using Optimized Conditions
a
b
c
entry
5
R
R′
ligand
5:6:16
6
% yield
% ee (R)
1
2
5a
5a
5b
5d
5f
Ph
Ph
−CH2C6H4
−CH2C6H4
Me
4
15
4
1:98:1
2:98:0
6a
6a
6b
6d
6f
90
91
90
92
74
82
79
79
58
23
44
60
48
71
3
4-MeC6H4
Ph
4:96:trace
2:98:trace
19:81:trace
10:90:trace
15:85:0
100:0:0
2:97:1
4
Et
4
5
Ph
i-Pr
4
6
5g
5h
5i
Ph
−CH2CH(CH3)2
−CH2C(CH3)3
−CH2-2′-naphthyl
−CH2C6H4
−CH2C6H4
4-MeOC6H4
−CH2C6H4
−CH2C6H4
−CH2C6H4
−CH2C6H4
−CH2C6H4
−CH2C6H4
−CH2-p-Tol
−CH2-m-Tol
−CH2-m-Tol
−CH2-o-Tol
4
6g
6h
6i
7
Ph
4
8
Ph
4
9
5j
4-MeC6H4
4-MeC6H4
4-MeC6H4
2-MeOC6H4
3-MeOC6H4
2-MeC6H4
2-MeC6H4
3-MeC6H4
3-MeC6H4
Ph
4
6j
91
90
90
85
47
91
88
84
83
89
83
90
80
81
84
47
29
21
64
71
54
69
55
50
10
11
12
13
14
15
16
17
18
19
20
21
5j
15
4
4:96:0
6j
5k
5l
2:97:1
6k
6l
4
8:92:trace
46:54:0
1:98:1
5m
5n
5n
5o
5o
5p
5q
5q
5r
4
6m
6n
6n
6o
6o
6p
6q
6q
6r
4
15
4
6:94:0
11:89:0
10:88:2
1:97:2
15
4
Ph
4
7:92:1
Ph
15
4:95:1
46
d
Ph
4
b
12:85:2
47
a
c
Ratio of 5:6:16 determined by 1H NMR analysis of the crude product. Yield of 6 after purification by column chromatography. Determined by
HPLC analysis on chiral column (Daicel Chiracel OD-H for 6a−6q, Chiracel As−H for 6r). Absolute configuration determined by comparison of
rotation values for 6a, 6b, 6d, 6f, and 6g to known literature values; for 6h, 6k, 6l, 6m, 6n, 6o, 6p, and 6q, proposed configuration based on HPLC
d
elution order and direction of specific rotations. Configuration of 6r not determined.
complexation of the sulfoxide to the copper catalyst. It is
believed that NMO coordinates to the copper catalyst,
removing sulfoxide, which results in an improvement in yield.
Entries 10 and 12 demonstrate that the presence of a CH2
group between the sulfur and the isopropyl group results in
improved enantioselection. However, the opposite trend was
observed when the oxidation was carried out in the presence of
NMO.
Similar results were achieved using solvent mixtures of hexane
and ethanol, and cyclohexane and methanol (Table 3, entries
14 and 15). Interestingly, the use of a mixture of hexane and the
bulky alcohol IPA afforded practically racemic sulfoxide (Table
3, entry 16). The use of hexane−methanol (partially miscible)
and hexane−ethanol (miscible) solvent mixtures afforded
sulfoxide in almost identical yield and enantioselectivity
(Table 3, entries 13 and 14). The dramatic improvements in
yields using solvent mixtures of methanol are further evidence
for sulfoxide inhibition. Presumably, methanol can coordinate
to the copper catalyst, thereby displacing the sulfoxide, which
results in improved yields.
An extensive ligand study was then undertaken in an attempt
to find the optimum ligand for this system (Table 4). The
results indicate that ligands 3, 4, and 15 perform much better
than the other Schiff bases in the oxidation of benzyl phenyl
sulfide. Ligand 4 performed the best, producing the sulfoxide in
90% yield and 79% ee. Replacement of the tert-butyl with an
isopropyl in the R3 position of the ligand results in a significant
reduction in yield and enantioselectivity (Table 4, entries 1 and
6). This indicates that the steric bulk at the R3 position is
crucial to maintaining the enantioselectivity of the oxidation.
Interestingly, the diiodo and difluoro ligands 10 and 14
perform poorly in terms of both yield and enantioselectivity
(Table 4, entries 3 and 7).
The results of the NMO study indicated that the use of more
polar solvents or solvent mixtures may overcome product
inhibition by coordinating to the copper catalyst. Katsuki
reported an enhancement in the enantioselectivity of the
vanadium Schiff base-catalyzed oxidation of thioanisole in the
presence of a small amount of methanol.20 An initial solvent
study indicated that low-polarity solvents, such as toluene,
benzene, and CCl4, produced the best results in terms of
enantioselectivity, as we had described previously (Table 3).19
Depending on the solvent(s) employed, the oxidation system
with aqueous hydrogen peroxide was either monophasic or
biphasic. When the oxidation was carried out in methanol, there
was a large increase in yield, but a decrease in enantioselectivity
(Table 3, entry 7) in comparison to the low-polarity solvents.
There was no sulfoxide produced when the oxidation was
carried out in hexane (Table 3, entry 6). Carrying out the
oxidation in a mixed solvent system of toluene−methanol
resulted in improved yield, but with a reduced enantioselectivity
(Table 3, entries 9−12). However, using a 90:10 hexane−
methanol solvent mixture produced benzyl phenyl sulfoxide in
excellent yield and good enantioselectivity (Table 3, entry 13).
Having established the optimum ligand (ligand 4) and
solvent system (90:10 hexane/methanol), these conditions
were then used in the asymmetric oxidation of a range of aryl
benzyl and aryl alkyl sulfides, as shown in Table 5. Excellent
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reported in racemic form only. Sulfoxides 6h, 6i, and 6o have not been
previously reported.
yields and modest to good enantiopurities were obtained; for
example, benzyl phenyl sulfoxide was obtained in 90% yield and
79% ee (Table 5, entry 1). Overoxidation to sulfone is either
entirely absent or very minimal (no more than 2%) despite the
dramatic improvements in oxidation efficiency using the
optimized conditions. The formation of significant amounts
of sulfone would have a detrimental effect on sulfoxide yield
and would lead to difficulties in isolation of the desired product.
A relationship between the steric bulk of the R′ substituent of
the sulfide and the enantioselectivity of the oxidation was
observed again. As R′ is changed from a methyl group to an
ethyl group and then to an isopropyl and neopentyl group,
there is an increase in enantioselectivity (Table 5, entries 3−7).
Interestingly, in Table 5, it is evident that, with the different
substrates, in some instances, the enantiopurity achieved was
higher with ligand 4, while in others, it was higher with ligand
15, although differences are relatively modest in most cases.
Thus, the optimum ligand appears to be substrate-specific.
Sulfide 5l did not fully dissolve in 1 mL of 90:10 hexane/
methanol, and as a result, an increased amount of solvent was
used. This may have resulted in reduced enantioselectivity, as
previous work in the group had demonstrated that increasing
dilution had a detrimental effect on the enantioselectivity of the
oxidation.21 Sulfide 5i was insoluble in 9:1 hexane/methanol,
and hence no oxidation was observed.
EXPERIMENTAL PROCEDURE FOR ASYMMETRIC
SULFIDE OXIDATION
■
Copper(II) acetylacetonate (5.2 mg, 2.0 mol %) was added to a round-
bottom flask containing Schiff base ligand 4 (11.6 mg, 4.0 mol %), and
9:1 hexane/MeOH (1 mL). The resulting solution was stirred at room
temperature for 5 min, and then a solution of sulfide (1 mmol) in 9:1
hexane/MeOH (1 mL) was added. After 5 min of stirring at r.t., H2O2
(0.130 mL, 30%, 1.1 mmol) was added in one portion, dropwise, to
the solution. The reaction mixture was stirred at room temperature for
a further 16 h. H2O (1 mL) and CH2Cl2 (1 mL) were then added and
the phases separated; the organic layer was washed with water (2 × 5
mL) and brine (5 mL), dried, and concentrated under reduced
pressure to give the crude product. The ratio of sulfide−sulfoxide−
sulfone in the crude product was determined by 1H NMR. The
product was purified by column chromatography on silica gel (6:4
hexane/ethyl acetate). The Schiff base ligand can be recovered after
chromatography and can be reused.
In experiments in which NMO was used (Table 2), NMO (2.5 mol
%) was added 5 min after addition of the sulfide. The reaction mixture
was then stirred for 5 min, followed by addition of H2O2 (0.130 mL,
30%, 1.1 mmol).
(R)-(+)-Benzyl Phenyl Sulfoxide (6a, Table 5, Entry 1).22
Crude product contained a mixture of sulfide, sulfoxide, and sulfone
(1:98:1). Purification by chromatography afforded the product as a
white solid (194 mg, 90%, 79% ee).
CONCLUSION
1H NMR δH (300 MHz) 4.00 (1H, A of AB system, J = 12.5 Hz),
4.10 (1H, B of AB system, J = 12.5 Hz), 6.90−7.04 (2H, m), 7.19−
7.32 (3H, m), 7.33−7.52 (5H, m); mp 125−126 °C (lit. mp 127
°C);30 IR (KBr) ν = 2961, 1455, 1442, 1084, 1033, 746 cm−1; HPLC
tR (R) = 17.1 min, tR (S) = 21.3 min [Chiracel OD-H; flow rate = 1
mL min−1; hexane-2-PrOH (90:10); 40 °C]; [α]D20 = +146.5° (c 1.0,
acetone) {ref 22, [α]D20 = −169.8 (c 1.0, acetone) for (S) 79% ee}.
(R)-(+)-Methyl p-Tolyl Sulfoxide (6b, Table 5, Entry 3).23
Crude product contained a mixture of sulfide, sulfoxide, and sulfone
(4:96:trace). Purification by chromatography afforded the product as a
clear oil (138 mg, 90%, 23% ee).
■
Efficient enantioselective sulfide oxidation is effected using
copper−Schiff base catalysis. The procedure employed is clean,
inexpensive, and is not air-sensitive, utilizing aqueous hydrogen
peroxide as the oxidant. An important feature of this oxidation
system is that the Schiff base ligand can be recovered after
chromatography and can be reused without loss of activity. The
use of copper as the transition metal offers significant safety
benefits over other established methods, employing other toxic
metals. Another important feature of this system is the absence
or very limited amount of overoxidation to produce sulfones.
Use of a hexane−methanol solvent mixture overcomes catalyst
inhibition by the sulfoxide and thereby leads to excellent yields.
Steric effects are significant in determining the enantioselectiv-
ity of the oxidation.
1H NMR δH (400 MHz) 2.42 (3H, s), 2.71 (3H, s), 7.34 (2H, d, J =
8.4 Hz), 7.54 (2H, d, J = 8.4 Hz); HRMS (ESI) exact mass calculated
for C8H10OS [(M + H)+] 155.0531; found, 155.0526; HPLC tR (R) =
20.1 min, tR (S) = 23.8 min [Chiracel OD-H; flow rate = 1 mL min−1;
hexane-2-PrOH (95:5); 20 °C]; [α]D20 = +43.6° (c 1.0, acetone) {ref
23, [α]D20 = +150.4 (c 1.17, acetone) for (R) > 99% ee}.
(R)-(+)-Ethyl Phenyl Sulfoxide (6d, Table 5, Entry 4).25 Crude
product contained a mixture of sulfide, sulfoxide, and sulfone
(2:98:trace). Purification by chromatography afforded the product as
a clear oil (142 mg, 92%, 44% ee).
EXPERIMENTAL SECTION
■
General. Sulfides 5a, 5b, and 5d were commercially available. For
thin-layer chromatography (TLC), silica gel plates were used and
compounds were visualized using UV. Solvents were distilled prior to
1H NMR δH (400 MHz) 1.20 (3H, t, J = 3.5 Hz), 2.70−3.00 (2H,
m), 7.46−7.57 (3H, m), 7.58−7.66 (2H, m); IR (film) ν = 2935, 1479,
1444, 1087, 1021, 749 cm−1; HRMS (ESI) exact mass calculated for
C8H10OS [(M + H)+] 155.0531; found, 155.0532; HPLC tR (R) = 8.1
min, tR (S) = 9.8 min [Chiracel OD-H; flow rate = 1 mL min−1;
hexane-2-PrOH (90:10); 40 °C]; = +96.1° (c 1.0, acetone) {ref 25,
[α]D20 = +185.6 (c 0.71, acetone) for (R) > 99% ee}.
1
1
use. H (300 MHz), H (400 MHz), and 13C NMR (75 MHz) were
recorded with spectrometers at 20 °C using CDCl3 as the solvent.
Chemical shifts are given in parts per million relative to TMS as the
internal standard. Coupling constants (J) are reported in hertz. Chiral
HPLC was performed using Chiralpak OD-H, OJ-H, and AS-H
columns, eluting with n-hexane and 2-propanol. Specific rotations were
recorded at 20 °C in the solvents indicated. The Sodium D line (589
nm) was used unless otherwise indicated. Samples were analyzed in a 1
mL dual-walled thermostatted glass cell of path length 10 cm. Sample
temperature control was maintained using an immersion circulator.
Absolute configurations were assigned by comparison of the specific
rotations with the literature data for 6a, 6b, and 6d−6g. Notably, the
directions of the specific rotations were in complete agreement with
literature values; however, the magnitudes varied somewhat. Racemic
sulfoxides were prepared by treatment of the sulfide with 0.6 equiv of
oxone in acetone at 0 °C. All reactions are carried out at room
temperature unless otherwise indicated. Sulfoxides 6a,22 6b,23 6c,24
6d,25 6f,26 6g,27 6j,28 6k,29 6l,19 6m,19 and 6p30 have been reported in
enantioenriched form. Sulfoxides 6e,31 6n,32 6q,33 and 6r34 have been
(R)-(+)-Isopropyl Phenyl Sulfoxide (6f, Table 5, Entry 5).26
Crude product contained a mixture of sulfide, sulfoxide, and sulfone
(19:81:trace). Purification by chromatography afforded the product as
a clear oil (124 mg, 74%, 60% ee).
1H NMR δH (400 MHz) 1.15 (3H, d, J = 6.6 Hz), 1.23 (3H, d, J =
6.6 Hz), 2.75−2.91 (1H, m), 7.44−7.62 (5H, m); 13C NMR δC (75
MHz) 14.0, 15.9, 54.6, 125.0, 128.9, 131.0, 141.7; IR (KBr) ν = 2970,
1464, 1444, 1088, 1023 cm−1; HPLC tR (R) = 6.6 min, tR (S) = 7.5
min [Chiracel OD-H; flow rate = 1 mL min−1; hexane-2-PrOH
(90:10); 40 °C]; [α]D20 = +112.8 (c 1.0, CHCl3).
(R)-(+)-Isobutyl Phenyl Sulfoxide (6g, Table 5, Entry 6).27
Crude product contained a mixture of sulfide, sulfoxide, and sulfone
3292
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(10:90:trace). Purification by chromatography afforded the product as
a clear oil (149 mg, 82%, 48% ee).
116.5, 118.1, 128.3, 128.5, 129.1, 129.8, 130.4, 144.0, 160.1; IR (KBr)
ν = 2907, 1594, 1481, 1248, 1031, 697 cm−1; HRMS (ESI) exact mass
calculated for C14H14SO2 [(M + H)+] 247.0793; found, 247.0789;
HPLC tR (R) = 12.2 min, tR (S) = 14.0 min [Chiracel OD-H; flow rate
= 1 mL min−1; hexane-2-PrOH (90:10); 40 °C]; [α]D20 = +68.5 (c 1.0,
acetone), {ref 19, [α]D20 = +73.5 (c 0.17, acetone) for (R) = 69% ee}.
(R)-(+)-Benzyl o-Tolyl Sulfoxide (6n, Table 5, Entry 13).32
Crude product contained a mixture of sulfide, sulfoxide, and sulfone
(1:98:1). Purification by chromatography afforded the product as a
white solid (209 mg, 91%, 64% ee).
1H NMR δH (400 MHz) 1.07 (3H, d, J = 6.6 Hz), 1.17 (3H, d, J =
6.6 Hz), 2.14−2.33 (1H, m), 2.45 (1H, A of ABX system, J = 12.0 and
4.8 Hz), 2.82 (1H, B of ABX system, J = 12.0 and 4.8 Hz), 7.43−7.58
(3H, m), 7.59−7.69 (2H, m); 13C NMR δC (75 MHz) 21.7, 22.8, 24.2,
67.6, 123.9, 129.3, 130.9, 144.7; HRMS (ESI) exact mass calculated for
C10H14SO [(M + H)+] 183.0844; found, 183.0850; IR (KBr) ν =
2960, 1465, 1444, 1090, 1038, 750 cm−1; HPLC tR (R) = 5.9 min, tR
(S) = 6.7 min [Chiracel OD-H; flow rate = 1 mL min−1; hexane-2-
PrOH (90:10); 40 °C]; [α]D20 = +129.0 (c 1.0, CHCl3).
mp 69−71 °C; 1H NMR δH (300 MHz) 2.06 (3H, s), 4.00 (1H, A
of AB system, J = 12.3 Hz), 4.10 (1H, B of AB system, J = 12.6 Hz),
6.97 (2H, dd, J = 7.8 Hz and J = 1.3 Hz), 7.06−7.16 (1H, m), 7.19−
7.41 (5H, m), 7.67−7.78 (1H, m); 13C NMR δC (75.5 MHz) 18.0,
62.3, 124.2, 127.1, 128.3, 128.5, 129.3, 130.2, 130.4, 130.9, 135.6,
141.3; ESI-HRMS calcd for C14H14OS [(M + H)+] 231.0844; found,
231.0855 (found C, 73.06; H, 6.12; S, 14.20; C14H14OS requires C,
73.01; H, 6.13; S 13.92); HPLC tR (R) = 11.2 min, tR (S) = 13.2 min
[Chiracel OD-H; flow rate = 1 mL min−1; hexane-2-PrOH (90:10); 40
°C]; [α]D20 = +18.5 (c 1.0, CHCl3).
(R)-(+)-Neopentyl Phenyl Sulfoxide (6h, Table 5, Entry 7).
Crude product contained a mixture of sulfide and sulfoxide (15:85).
Purification by chromatography afforded the product as a clear oil
(155 mg, 79%, 71% ee).
1H NMR δH (300 MHz) 1.21 (9H, s), 2.54 (1H, A of AB system, J
= 13.5 Hz), 2.81 (1H, B of AB system, J = 13.8 Hz), 7.43−7.56 (3H,
m), 7.59−7.66 (2H, m); 13C NMR δC (75 MHz) 29.8, 32.0, 73.9,
123.8, 129.2, 130.7, 145.6; (found C, 67.10; H, 8.37; S, 16.29;
C11H16OS requires C, 67.30; H, 8.22; S 16.33); IR (film) ν = 2958,
1474, 1448, 1084, 1045, 709 cm−1; HPLC tR (R) = 6.6 min, tR (S) =
7.6 min [Chiracel OD-H; flow rate = 1 mL min−1; hexane-2-PrOH
(90:10); 40 °C]; [α]D20 = +87.9 (c 1.0, CHCl3).
(R)-(+)-Benzyl m-Tolyl Sulfoxide (6o, Table 5, Entry 15).
Crude product contained a mixture of sulfide, sulfoxide, and sulfone
(11:89:0). Purification by chromatography afforded the product as a
clear oil (193 mg, 84%, 62% ee).
(R)-(+)-Benzyl p-Tolyl Sulfoxide (6j, Table 5, Entry 8).28 Crude
product contained a mixture of sulfide, sulfoxide, and sulfone (2:97:1).
Purification by chromatography afforded the product as a white solid
(209 mg, 91%, 81% ee).
1H NMR δH (300 MHz) 2.34 (3H, s) 3.97 (1H, A of AB system, J =
12.6 Hz), 4.08 (1H, B of AB system, J = 12.3 Hz), 7.00 (2H, dd, J =
7.8 Hz and J = 2.1 Hz), 7.10−7.34 (7H, m); 13C NMR δC (75.5 MHz)
21.3, 63.7, 121.5, 124.7, 128.2, 128.4, 128.6, 129.3, 130.4, 131.9, 139.1,
142.7; IR (film) ν = 2919, 1454, 1038, 766 cm−1; ESI-HRMS calcd for
C14H14OS [(M + H)+] 231.0844; found, 231.0840 (found C, 72.96; H,
6.28; S, 14.0; C14H14OS requires C, 73.01; H, 6.13; S 13.92); HPLC tR
(R) = 15.1 min, tR (S) = 18.9 min [Chiracel OD-H; flow rate = 1 mL
min−1; hexane-2-PrOH (90:10); 40 °C]; [α]D20 = +48.6 (c 1.0, CHCl3).
(R)-(+)-4-Methylbenzyl Phenyl Sulfoxide (6p, Table 5, Entry
17).30 Crude product contained a mixture of sulfide, sulfoxide, and
sulfone (1:97:2). Purification by chromatography afforded the product
as a white solid (205 mg, 89%, 55% ee).
1H NMR δH (300 MHz) 2.40 (3H, s), 3.97 (1H, A of AB system, J
= 12.6 Hz), 4.09 (1H, B of AB system, J = 12.6 Hz), 7.00 (2H, dd, J =
7.5 Hz and J = 1.5 Hz), 7.17−7.37 (7H, m); HRMS (ESI) exact mass
calculated for C14H14SO [(M + H)+] 231.0844; found, 231.0839; IR
(KBr) ν = 2912, 1494, 1456, 1083, 1014, 768 cm−1; HPLC tR (R) =
16.3 min, tR (S) = 19.9 min [Chiracel OD-H; flow rate = 1 mL min−1;
hexane-2-PrOH (90:10); 40 °C]; [α]D20 = +106.0 (c 1.0, acetone), {ref
30, [α]D20 = −254.0 (c 0.7, acetone) for (S) > 99% ee}.
(R)-(+)-4-Methoxybenzyl 4′-Methylphenyl Sulfoxide (6k,
Table 5, Entry 10).29 Crude product contained a mixture of sulfide,
sulfoxide, and sulfone (2:97:1). Purification by chromatography
afforded the product as a white solid (234 mg, 90%, 47% ee).
mp 123−124 °C; 1H NMR δH (300 MHz) 2.40 (3H, s), 3.79 (3H,
s), 3.93 (1H, A of AB system, J = 12.6 Hz), 4.03 (1H, B of AB system,
J = 12.6 Hz), 6.75−6.81 (2H, m), 6.87−6.94 (2H, m), 7.19−7.32 (4H,
m); 13C NMR δC (75.5 MHz) 21.5, 55.3, 63.0, 113.9, 121.2, 124.5,
129.6, 131.6, 139.6, 141.5, 159.6; IR (KBr) ν = 2961, 1610, 1514,
1036, 809 cm−1; HRMS (ESI) exact mass calculated for C15H16SO2
[(M + H)+] 261.0949; found, 261.0947; HPLC tR (R) = 12.7 min, tR
(S) = 15.9 min [Chiracel OD-H; flow rate = 1 mL min−1; hexane-2-
1H NMR δH (300 MHz) 2.32 (3H, s), 3.96 (1H, A of AB system, J
= 12.6 Hz), 4.07 (1H, B of AB system, J = 12.6 Hz), 6.87 (2H, d, J =
7.8 Hz), 7.06 (2H, d, J = 7.8 Hz), 7.36−7.51 (5H, m); IR (KBr) ν =
2959, 1512, 1442, 1043, 687 cm−1 (found C, 73.12; H, 6.33; S, 13.94;
C14H14OS requires C, 73.01; H, 6.13; S 13.92); HPLC tR (R) = 12.7
min, tR (S) = 14.3 min [Chiracel OD-H; flow rate = 1 mL min−1;
hexane-2-PrOH (90:10); 40 °C]; [α]D20 = +42.2 (c 1.0, CHCl3).
(R)-(+)-3-Methylbenzyl Phenyl Sulfoxide (6q, Table 5, Entry
18).33 Crude product contained a mixture of sulfide, sulfoxide, and
sulfone (7:92:1). Purification by chromatography afforded the product
as a clear oil (191 mg, 83%, 50% ee).
PrOH (90:10); 40 °C]; [α]D20 = +37.9 (c 1.0, CHCl3), {ref 29, [α]D20
−87 (c 0.2, CHCl3) for (S) > 99% ee}.
=
1H NMR δH (300 MHz) 2.27 (3H, s), 3.94 (1H, A of AB system, J
= 12.3 Hz), 4.08 (1H, B of AB system, J = 12.6 Hz), 6.80 (2H, d, J =
5.7 Hz), 7.06−7.19 (2H, m), 7.36−7.51 (5H, m); 13C NMR δC (75
MHz) 21.3, 63.9, 124.5, 127.4, 128.4, 128.8, 129.0, 129.1, 131.1, 131.2,
138.2, 143.0; IR (KBr) ν = 2967, 1604, 1444, 1040, 736 cm−1; ESI-
HRMS calcd for C14H14OS [(M + H)+] 231.0844; found, 231.0846
(found C, 73.42; H, 6.13; S, 13.97; C14H14OS requires C, 73.01; H,
6.13; S, 13.92); HPLC tR (R) = 16.2 min, tR (S) = 18.7 min [Chiracel
OD-H; flow rate = 1 mL min−1; hexane-2-PrOH (90:10); 40 °C];
[α]D20 = +36.8 (c 1.0, CHCl3).
(R)-(+)-Benzyl 2-Methoxyphenyl Sulfoxide (6l, Table 5, Entry
11).19 Crude product contained a mixture of sulfide, sulfoxide, and
sulfone (8:92:trace). Purification by chromatography afforded the
product as a white solid (209 mg, 85%, 29% ee).
mp 31−33 °C; 1H NMR δH (300 MHz) 3.87 (3H, s), 3.98 (1H, A
of AB system, J = 12.0 Hz), 4.24 (1H, B of AB system, J = 12.0 Hz),
6.90 (1H, d, J = 7.8 Hz), 6.99−7.11 (3H, m), 7.17−7.30 (3H, m),
7.36−7.49 (2H, m); 13C NMR δC (75.5 MHz) 55.8, 59.7, 110.3, 121.5,
125.8, 127.9, 128.2, 130.2, 130.3, 130.4, 132.0, 155.1; IR (KBr) ν =
2959, 1596, 1496, 1086, 1032, 697 cm−1; HRMS (ESI) exact mass
calculated for C14H14SO2 [(M + H)+] 247.0793; found, 247.0783;
HPLC tR (R) = 16.2 min, tR (S) = 18.6 min [Chiracel OD-H; flow rate
= 1 mL min−1; hexane-2-PrOH (90:10); 40 °C]; [α]D20 = +60.3 (c 1.0,
acetone), {ref 19, [α]D20 = +351 (c 0.32, CHCl3) for (R) = 81% ee}.
(R)-(+)-Benzyl 3-Methoxyphenyl Sulfoxide (6m, Table 5,
Entry 12).19 Crude product contained a mixture of sulfide and
sulfoxide (46:54). Purification by chromatography afforded the
product as a clear oil (115 mg, 47%, 21% ee).
(-)-2-Methylbenzyl Phenyl Sulfoxide (6r, Table 5, Entry
20).34 Crude product contained a mixture of sulfide, sulfoxide, and
sulfone (12:85:2). Purification by chromatography afforded the
product as a clear oil (184 mg, 80%, 47% ee).
1H NMR δH (300 MHz) 2.18 (3H, s), 3.99 (1H, A of AB system, J
= 12.3 Hz), 4.27 (1H, B of AB system, J = 12.3 Hz), 6.85 (1H, d, J =
6.6 Hz), 7.02−7.25 (3H, m), 7.35−7.52 (5H, m); IR (KBr) ν = 2926,
1443, 1094, 1030, 750 cm−1 (found C, 73.19; H, 6.02; S, 13.85;
C14H14OS requires C, 73.01; H, 6.13; S, 13.92); HPLC tR = 67.1 min,
tR = 85.3 min [Chiracel AS-H; flow rate = 1 mL min−1; hexane-2-
PrOH (90:10); 20 °C]; [α]D20 = −16.5 (c 1.0, CHCl3).
1H NMR δH (300 MHz) 3.72 (3H, s), 4.00 (1H, A of AB system, J
= 12.5 Hz), 4.07 (1H, B of AB system, J = 12.5 Hz) 6.87−7.03 (5H,
m), 7.20−7.37 (4H, m); 13C NMR δC (75 MHz) 55.5, 63.5, 108.4,
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(R)-(+)-4-Methylphenyl prop-2′-ynyl Sulfoxide (6c, Table 2,
Entry 7).24 Crude product contained a mixture of sulfide and
sulfoxide (78:22). Purification by chromatography afforded the
product as a white solid (23 mg, 14%, 4% ee).
(1H, dd, J = 11.2 and 9.8 Hz), 3.82−4.10 (1H, brs), 3.96−4.06 (1H,
brm), 7.04 (1H, d, J = 2.5 Hz), 7.27 (1H, d, J = 2.4 Hz), 8.12 (1H, s);
13C NMR δC (75.5 MHz) 26.9, 32.9, 61.7, 78.5, 116.9, 120.2, 124.5,
129.6, 133.4, 162.3, 164.8; m/z (ESI) [(M + H)+] 290; HRMS (ESI)
exact mass calculated for C13H17Cl2NO2 [(M + H)+] 290.0715; found,
290.0723; IR νmax/cm−1 (KBr) 3322, 2971, 1645, 1502 1209, 1058
(found C, 54.07; H, 5.91; N, 4.64; C13H17Cl2NO2 requires C, 53.81;
H, 5.90; N, 4.64); [α]D20 = −23.6 (c 1.0, acetone).
(S)-2-(N-3,5-Diiodosalicylidene)-amino-3,3-dimethyl-1-buta-
nol (10, Table 4):.22,36 Yellow solid, 79%, mp 164−165 °C (lit. mp
163−164);22 1H NMR δH (300 MHz) 1.00 (9H, s), 2.53 (1H, brs),
3.08 (1H, dd, J = 9.5 and 2.5 Hz), 3.68 (1H, dd, J = 11.1 and 9.8 Hz),
3.93−4.07 (1H, brm), 7.51 (1H, d, J = 2.1 Hz), 8.01 (1H, d, J = 2.1
Hz), 8.10 (1H, s); IR νmax/cm−1 (KBr) 3320, 2965, 1638, 1479, 1217,
1060; [α]D20 = −18.5 (c 0.1, acetone), lit.22 [α]D20 = −16.6 (c 1.0 for S in
acetone).
(S)-2-(N-3′-tert-Butylsalicylidene)-amino-3,3-dimethyl-1-bu-
tanol (11, Table 4):.37 Yellow oil, 88%; 1H NMR δH (300 MHz) 0.99
(9H, s), 1.44 (9H, s), 2.93 (1H, dd, J = 9.4 and 2.7 Hz), 3.73 (1H, dd,
J = 11.0 and 9.7 Hz), 3.90 (1H, dd, J = 11.1 and 2.8 Hz), 6.84 (1H, t, J
= 7.5 Hz), 7.15 (1H, dd, J = 7.6 and 1.6 Hz), 7.35 (1H, dd, J = 7.6 and
1.6 Hz), 8.42 (1H, s); IR νmax/cm−1 (film) 3367, 2959, 1633, 1458,
1436; [α]D20 = −54.3 (c 0.3, acetone).
1H NMR δH (300 MHz) 2.33 (1H, t, J = 2.7 Hz), 2.44 (3H, s), 3.59
(1H, A of ABX system, JAB = 14.2 Hz, JAX = 2.6 Hz), 3.67 (1H, B of
ABX system, JAB = 14.4 Hz, JBX = 2.6 Hz) 7.35 (2H, d, J = 8.3 Hz),
7.61 (2H, d, J = 8.2 Hz); HPLC tR (R) = 14.6 min, tR (S) = 17.5 min
[Chiracel OD-H; flow rate = 1 mL min−1; hexane-2-PrOH (90:10); 20
°C]; [α]D20 = +5.2 (c 1.0, CHCl3).
(R)-(+)-2-Naphthylmethyl Phenyl Sulfoxide (6i, Table 2,
Entry 14). Crude product contained a mixture of sulfide and sulfoxide
(45:55). Purification by chromatography afforded the product as a
white solid (80 mg, 30%, 93% ee).
mp 85−87 °C; 1H NMR δH (400 MHz) 4.15 (1H, A of AB system,
J = 12.4 Hz), 4.26 (1H, B of AB system, J = 12.4 Hz), 7.08 (1H, dd, J =
8.6 Hz and J = 1.6 Hz), 7.31−7.53 (8H, m), 7.66−7.85 (3H, m); 13C
NMR δC (75 MHz) 64.0, 124.5, 126.3, 126.4, 126.7, 127.7, 127.75,
127.9, 128.1, 128.9, 129.8, 131.2, 132.9, 133.1, 142.9 (found C, 76.43;
H, 5.58; S, 12.10; C17H14OS requires C, 76.66; H, 5.30; S, 12.04);
HPLC tR (R) = 32.1 min, tR (S) = 40.6 min [Chiracel OD-H; flow rate
= 1 mL min−1; hexane-2-PrOH (90:10); 20 °C]; [α]D20 = +75.4 (c 1.0,
CHCl3).
(R)-(+)-Benzyl 4-Methoxyphenyl Sulfoxide (2d, Table 1,
Entry 4).19,35 Crude product contained a mixture of sulfide and
sulfoxide (54:46). Purification by chromatography afforded the
product as a white solid (81 mg, 33%, 54% ee).
(S)-2-(N-5′-tert-Butylsalicylidene)-amino-3,3-dimethyl-1-bu-
tanol (12, Table 4).38 Yellow solid, 82%, mp 119−120 °C; 1H NMR
δH (300 MHz) 0.96 (9H, s), 1.31 (9H, s), 1.62 (1H, brs), 2.93 (1H,
dd, J = 9.5 and 2.8 Hz), 3.75 (1H, dd, J = 11.0 and 9.6 Hz), 3.92 (1H,
dd, J = 11.1 and 2.8 Hz), 6.91 (1H, d, J = 8.6 Hz), 7.26−7.28 (1H, m),
7.36 (1H, dd, J = 8.6 and 2.5 Hz), 8.36 (1H, s); 13C NMR δC (75.5
MHz) 27.0, 31.4, 33.2, 34.0, 62.5, 81.3, 116.5, 117.8, 128.0, 129.8,
141.5, 158.9, 166.4 (HCN); IR νmax/cm−1 (KBr) 3422, 2958, 1633,
1493 (found C, 73.31; H, 9.89; N, 5.12; C17H27NO2 requires C, 73.61;
H, 9.81; N, 5.05); [α]D20 = −46.8 (c 0.3, acetone).
1H NMR δH (300 MHz) 3.84 (3H, s), 3.95 (1H, A of AB system, J
= 12.0 Hz), 4.11 (1H, B of AB system, J = 12.0 Hz), 6.89−7.02 (4H,
m), 7.20−7.33 (5H, m), δC (75.5 MHz) 55.5, 63.8, 114.4, 126.4, 128.2,
128.5, 129.3, 130.4, 133.6, 162.0; HPLC tR (R) = 15.5 min, tR (S) =
18.4 min [Chiracel OD-H; flow rate = 1 mL min−1; hexane-2-PrOH
(90:10); 40 °C]; [α]D20 = +48.2 (c 1.0, acetone), {ref 19, [α]D20 = +31.9
(c 0.28, acetone) for (R) = 44% ee}.
(R)-(+)-Cyclohexylmethyl Phenyl Sulfoxide (6e, Table 2,
Entry 5).31 Crude product contained a mixture of sulfide and
sulfoxide (71:29). Purification by chromatography afforded the
product as a clear oil that solidified to form a white solid (44 mg,
20%, 60% ee).
(S)-2-(N-3′,5′-Dibromosalicylidene)-amino-3-methyl-1-buta-
1
nol (13, Table 4). Yellow solid, 76%, mp 136−138 °C; H NMR δH
(300 MHz) 0.99 (3H, d, J = 6.7 Hz), 1.01 (3H, d, J = 6.7 Hz), 1.88−
2.07 (1H, m), 3.17−3.30 (1H, m), 3.65−3.80 (1H, m), 3.99 (1H, dd, J
= 11.4 and 2.6 Hz), 7.25 (1H, d, J = 2.5 Hz), 7.60 (1H, d, J = 2.5 Hz)
8.14 (1H, s); 13C NMR δC (75.5 MHz) 18.4, 19.8, 29.6, 64.0, 74.8,
1H NMR δH (300 MHz) 1.01−1.41 (5H, m), 1.60−1.83 (4H, m),
1.89−2.08 (1H, m), 2.09−2.17 (1H, m), 2.45−2.52 (1H, A of ABX
system, J = 12.9 and 9.0 Hz), 2.76−2.82 (1H, B of ABX system, J =
12.9 and 4.8 Hz), 7.42−7.72 (5H, m); IR (KBr) ν = 2920, 1443, 1034,
752 cm−1; HPLC tR (R) = 17.3 min, tR (S) = 20.3 min [Chiracel OD-
H; flow rate = 1 mL min−1; hexane-2-PrOH (90:10); 20 °C]; [α]D20=
+47.8 (c 1.0, CHCl3).
107.2, 114.8, 117.6, 133.5, 138.8, 163.0, 164.6; m/z IR (KBr) νmax
/
cm−1 3259, 2965, 1645, 1497, 1212, 1043, 857, 690 (found C, 39.73;
H, 4.14; N, 3.57; C12H15Br2NO2 requires C, 39.48; H, 4.14; N, 3.84);
[α]D20 = −9.1 (c 1.0, acetone).
(S)-2-(N-3′,5′-Difluorosalicylidene)-amino-3,3-dimethyl-1-
butanol (14, Table 4). Yellow solid, 57%, mp 161−163 °C; 1H NMR
δH (300 MHz) 0.99 (9H, s), 2.08 (1H, brs), 3.01 (1H, dd, J = 9.6 and
2.7 Hz), 3.70 (1H, dd, seen as t, J = 9.9 and 9.9 Hz), 3.99 (1H, brd, J =
9.8 Hz), 6.75−6.82 (1H, m), 6.86−6.96 (1H, m), 8.26 (1H, s); 13C
NMR δC (75.5 MHz) 26.9, 33.1, 62.0, 80.4, 107.4−108.0 (m), 111.2−
111.5 (m), 164.6; m/z (ESI) [(M + H)+] 258; HRMS (ESI) exact
mass calculated for C13H17F2NO2 [(M + H)+] 258.1328; found,
258.1317; IR (KBr) νmax/cm−1 3308, 2966, 1638, 1479, 1215, 1059,
857; [α]D20 = −35.6 (c 0.5, acetone).
(S)-2-(N-3′-Chloro-5′-fluorosalicylidene)-amino-3,3-dimeth-
yl-1-butanol (15, Table 4). Yellow solid, 75%, mp 103−105 °C; 1H
NMR δH (300 MHz) 1.00 (9H, s), 2.81 (1H, bs), 3.06 (1H, dd, J = 9.6
and 2.4 Hz), 3.70 (1H, overlapping dd, J = 11.1 and 9.6 Hz), 3.99 (1H,
dd, J = 11.4 and 2.7 Hz), 6.87 (1H, dd, J = 8.1 and 3.0 Hz), 7.14 (1H,
dd, J = 8.1 and 3.0 Hz), 8.22 (1H, s); 13C NMR δC (75.5 MHz) 26.9,
33.0, 61.9, 79.8, 115.2, 117.0 (d, 3JCF = 8 Hz), 121.0 (d, 2JCF = 26 Hz),
122.8 (d, 3JCF = 10 Hz), 153.4 (d, 1JCF = 239 Hz), 157.0, 164.6 (d, 4JCF
= 3 Hz, HCN); m/z (ESI) [(M + H)+] 274; HRMS (ESI) exact
mass calculated for C13H17FClNO2 [(M + H)+] 274.1010; found,
274.1006; IR (KBr) νmax/cm−1 3288, 2973, 1643, 1471, 1366, 1209,
1063, 803 (found C, 57.41; H, 6.30; N, 5.24; C13H17ClFNO2 requires
C, 57.04; H, 6.26; N, 5.12); [α]D20 = −27.4 (c 1.0, acetone).
EXPERIMENTAL PROCEDURE FOR SCHIFF BASE
LIGAND SYNTHESIS
■
Commercially available salicylaldehyde (1 mmol) and sodium sulfate
(0.5 g) were added to a solution of (S)-tert-leucinol (1 mmol) or L-
valinol (1 mmol) in ethanol (20 mL). The reaction mixture was stirred
under reflux for 16 h, filtered, and concentrated under reduced
pressure. The reaction mixture was then dissolved in dichloromethane
(10 mL) and washed with water (3 × 10 mL) and brine (15 mL). The
organic layer was dried and concentrated under reduced pressure to
leave the crude product, which was purified by column chromatog-
raphy on silica gel (8:2 hexane/ethyl acetate) to yield the pure ligand.
(S)-2-(N-3′,5′-Dibromosalicylidene)-amino-3,3-dimethyl-1-
butanol (3, Table 4):.36,37 Yellow solid, 73%, mp 160−162 °C; H
1
NMR δH (300 MHz) 1.01 (9H, s), 3.10 (1H, dd, J = 9.5 and 2.4 Hz),
3.11 (1H, brs), 3.70 (1H, dd, J = 11.2 and 9.8 Hz), 3.98−4.08 (1H,
brm), 7.35 (1H, d, J = 2.5 Hz), 7.58 (1H, d, J = 2.4 Hz), 8.12 (1H, s);
13C NMR δC (75.5 MHz) 27.3, 33.4, 62.2, 79.2, 107.9, 114.8, 118.2,
133.8, 139.1, 162.9, 164.9; m/z (ESI) [(M + H)+] 378; HRMS (ESI)
exact mass calculated for C13H1779Br2NO2 [(M + H)+] 377.9704;
found, 377.9710; [α]D20 = −16.1 (c 1.0, acetone).
(S)-2-(N-3′,5′-Dichlorosalicylidene)-amino-3,3-dimethyl-1-
butanol (4, Table 4): Yellow solid, 72%, mp 153−156 °C; 1H NMR
δH (300 MHz) 1.02 (9H, s), 3.11 (1H, dd, J = 9.5 and 2.4 Hz), 3.69
3294
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2-Naphthylmethyl Phenyl Sulfide45 (5i): White solid, 82%; H
1
EXPERIMENTAL PROCEDURE FOR SYNTHESIS OF
SULFIDES
Method A.39 This method was used for the synthesis of sulfides
5e−5g, 5i−5r, and 1d.
■
NMR δH (300 MHz) 4.26 (2H, s), 7.11−7.27 (3H, m), 7.28−7.36
(2H, m), 7.38−7.51 (3H, m), 7.63−7.85 (4H, m); 13C NMR δC (75
MHz) 39.5, 125.8, 126.1, 126.5, 127.0, 127.4, 127.7, 127.7, 128.3,
128.9, 130.1, 132.6, 133.3, 134.9, 136.3 (CAr(q)); IR (KBr) νmax/cm−1
3048, 2917, 1438, 832, 738.
The thiolate anion was first prepared by treatment of the thiol with
an excess of sodium ethoxide. The thiolate anion was then treated with
an equimolar amount of aryl or alkyl halide and stirred for 16 h at
room temperature. Water (20 mL) and dichloromethane (20 mL)
were added to the flask. The layers were separated, and the aqueous
layer was extracted with dichloromethane (10 mL). The combined
organic layers were washed with aqueous sodium hydroxide (2 M, 3 ×
20 mL) and brine (20 mL), dried, filtered, and concentrated under
reduced pressure to give the sulfides, which were purified by column
chromatography.
Benzyl-(4-methylphenyl)-sulfide39 (5j): White solid, 76%, mp
42−43 °C (lit. 45 °C);8 1H NMR δH (300 MHz) 2.30 (3H, s), 4.06
(2H, s), 7.05 (2H, d, J = 8.2 Hz), 7.15−7.32 (7H, m); 13C NMR δC
(75.5 MHz) 21.0, 39.7, 127.1, 128.4, 128.8, 129.6, 130.7, 132.4, 136.5,
137.8; νmax/cm−1 (KBr) 2921, 1494, 1454, 1265, 740, 697;
4-Methoxybenzyl-(4′-methylphenyl)-sulfide39 (5k): White
solid, 75%, mp 65−67 °C, (lit. 67 °C);46 1H NMR δH (300 MHz)
2.30 (3H, s,), 3.78 (3H, s), 4.03 (2H, s), 6.76−6.84 (2H, m), 7.03−
7.11 (2H, m), 7.13−7.28 (4H, m); 13C NMR δC (75.5 MHz) 21.0,
39.2, 55.3, 113.9, 129.6, 129.8, 129.9, 130.7, 132.7, 136.5, 158.7; IR
νmax/cm−1 (KBr) 2958, 2833, 1609, 1510, 1492, 1241, 1174, 1030,
799; m/z (ESI) [(M + OH)+] 261; HRMS (ESI) exact mass calculated
for C15H16OS [(M + OH)+] 261.0949; found, 261.0937.
Method B.40 This method was used for the synthesis of neopentyl
phenyl sulfide, 5h.
1-Bromo-2,2-dimethyl propane (3.02 g, 20 mmol), aqueous
benzenethiolate (20 mmol), and Aliquat 336 (0.033 mol equiv)
were added to a 2-neck round-bottom flask under nitrogen. The
mixture was heated at 70 °C with vigorous stirring for 16 h. After the
mixture had cooled to room temperature, the organic layer was
separated and the aqueous phase was extracted with two 20 mL
portions of diethyl ether. The combined organic phases were washed
with 20 mL of 10% aqueous sodium chloride and dried over
magnesium sulfate. After removal of the solvent, the resulting residual
oil was distilled using a Kugelrohr apparatus to give neopentyl phenyl
sulfide, bp 145−147° (0.1 mm. Hg).
Benzyl-(2-methoxyphenyl)-sulfide47,48 (5l): White solid, 55%,
mp 68−70 °C; 1H NMR δH (300 MHz) 3.88, 4.09 (2H, s), 6.79−6.91
(2H, m), 7.12−7.35 (7H, m); 13C NMR δC (75.5 MHz) 37.3, 55.8,
110.5, 121.0, 124.5, 127.0, 127.6, 128.4, 128.9, 130.5, 137.5, 157.6; IR
νmax/cm−1 (KBr) 2934, 1577, 1476, 1245, 1071, 1025, 747; m/z (ESI)
[(M + OH)+] 247; HRMS (ESI) exact mass calculated for C14H14OS
[(M + OH)+] 247.0793; found, 247.0799.
Benzyl-(3-methoxyphenyl)-sulfide47 (5m): Clear oil, 83%; H
1
NMR δH (300 MHz) 3.73 (3H, s,), 4.12 (2H, s), 6.67−6.75 (1H, m),
6.80−6.85 (1H, m), 6.87−6.94 (1H, m), 7.12−7.35 (6H, m); 13C
NMR δC (75.5 MHz) 38.9, 55.2, 112.2, 114.8, 121.8, 127.2, 128.5,
128.8, 129.7, 137.4, 137.8, 159.7; IR νmax/cm−1 (film) 3062, 3029,
2936, 1590, 1479, 1249, 1043, 769; m/z (ESI) [(M + OH)+] 247;
HRMS (ESI) exact mass calculated for C14H14OS [(M + OH)+]
247.0793; found, 247.0796.
Method C.41 This method was used for the synthesis of 4-
methylphenyl prop-2′-ynyl sulfide, 5c.
NaH (0.72 g of 67% dispersion in mineral oil, 20 mmol) was added
to a two-neck flask under nitrogen. After washing with hexane (3 × 5
mL), dry dimethylformamide (DMF) (15 mL) was added to the flask
and the mixture was stirred for 5 min. The reaction mixture was cooled
to 0 °C, and 4-methylbenzene thiol (20 mmol, 2.48 g) was added
slowly. After stirring for 5 min, a solution of propargyl bromide (20
mmol, 1.72 mL) in DMF (10 mL) was added. The mixture was
removed from the ice bath, allowed to return to room temperature,
and stirred for 16 h under nitrogen. HCl (2 M, 20 mL) and
dichloromethane (20 mL) were added to the flask. The layers were
separated, and the organic layers were washed with aqueous HCl (2 M,
3 × 20 mL) and brine (15 mL), dried, and concentrated under
reduced pressure, to yield the crude product as a yellow oil. This was
purified by column chromatography on silica gel (100% hexane) to
yield the product.
Benzyl o-Tolyl Sulfide49 (5n): Clear oil, 90%; H NMR δH (300
1
MHz) 2.32 (3H, s), 4.08 (2H, s), 7.04−7.18 (3H, m), 7.19−7.33 (6H,
m); 13C NMR δC (75.5 MHz) 20.3, 38.3, 126.1, 126.4, 127.2, 128.5,
128.8, 128.9, 130.1, 135.8, 137.2, 137.9; IR (film) νmax/cm−1 3061,
3029, 1469, 1454, 1066, 744, 697 (found C, 78.50; H, 6.62; C14H14S
requires C, 78.46; H, 6.58); m/z (ESI) [(M + OH)+] 231; HRMS
(ESI) exact mass calculated for C14H14S [(M + OH)+] 231.0844;
found, 231.0848.
1
Benzyl m-Tolyl Sulfide (5o): Clear oil, 91%; H NMR δH (300
MHz) 2.29 (3H, s), 4.11 (2H, s), 6.95−7.02 (1H, m), 7.07−7.34 (8H,
m); 13C NMR δC (75.5 MHz) 21.4, 39.0, 126.7, 127.2, 128.5, 128.8,
128.9, 130.4, 136.2, 137.6, 138.6; IR (film) νmax/cm−1 3029, 2921,
1592, 1495, 1453, 770, 693 (found C, 78.55; H, 6.62; S, 14.93;
C14H14S requires C, 78.46; H, 6.58; S 14.96); m/z (ESI) [(M + OH)+]
231; HRMS (ESI) exact mass calculated for C14H14S [(M + OH)+]
231.0844; found, 231.0843.
4-Methylphenyl prop-2′-ynyl Sulfide41 (5c). Clear oil, 47%; 1H
NMR δH (400 MHz) 2.23 (1H, t, J = 2.6 Hz), 2.34 (3H, s), 3.56 (2H,
d, J = 2.6 Hz), 7.14 (2H, d, J = 8.5 Hz), 7.38 (2H, d, J = 8.5 Hz); IR
(film) νmax/cm−1 2117, 1231, 643.
Cyclohexylmethyl Phenyl Sulfide42 (5e): Clear oil, 95%; 1H
NMR δH (400 MHz) 0.89−1.08 (2H, m), 1.10−1.32 (3H, m), 1.45−
1.80 (4H, m), 1.82−1.94 (2H, m), 2.80 (2H, d, J = 6.8 Hz) 7.09−7.18
(1H, m), 7.21−7.38 (4H, m); IR (film) νmax/cm−1 2924, 1584, 1480,
1448, 736.
4-Methylbenzyl Phenyl Sulfide50 (5p): White solid, 87%, mp
69−71 °C (lit. 63.5−64.4 °C);50 1H NMR δH (300 MHz) 2.32 (3H,
s), 4.09 (2H, s), 7.03−7.36 (9H, m); 13C NMR δC (75.5 MHz) 21.1,
38.7, 126.2, 128.7, 128.8, 129.2, 129.6, 134.3, 136.7, 136.8; IR (film)
νmax/cm−1 3058, 2918, 1582, 1479, 1435, 1090, 738, 690 (found C,
78.13; H, 6.59; S, 15.30; C14H14S requires C, 78.46; H, 6.58; S 14.96);
m/z (ESI) [(M + OH)+] 231; HRMS (ESI) exact mass calculated for
C14H14S [(M + OH)+] 231.0844; found, 231.0849.
Isopropyl Phenyl Sulfide43 (5f): Clear oil, 70%; H NMR δH
1
(300 MHz) 1.29 (6H, d, J = 6.9 Hz), 3.30−3.45 (1H, m), 7.18−7.33
(3H, m), 7.38−7.42 (2H, m); 13C NMR δC (75 MHz) 23.1, 38.2,
126.7, 128.8, 131.9, 135.5; IR (film) νmax/cm−1 2962, 2925, 1584,
1480, 1439, 1026, 741, 692.
1
3-Methylbenzyl Phenyl Sulfide (5q): Clear oil, 77%; H NMR
δH (300 MHz) 2.31 (3H, s), 4.09 (2H, s), 7.00−7.37 (9H, m); 13C
NMR δC (75.5 MHz) 21.3, 39.0, 125.9, 126.3, 128.0, 128.4, 128.8,
129.6, 129.7, 136.6, 137.3, 138.2; IR (film) νmax/cm−1 3057, 2920,
1584, 1480, 1438, 1089, 738, 690 (found C, 78.20; H, 6.51; S, 15.3;
C14H14S requires C, 78.46; H, 6.58; S 14.96); m/z (ESI) [(M + OH)+]
231; HRMS (ESI) exact mass calculated for C14H14S [(M + OH)+]
231.0844; found, 231.0843.
Isobutyl Phenyl Sulfide44 (5g): Clear oil, 97%; 1H NMR δH (300
MHz) 1.03 (6H, d, J = 6.6 Hz), 1.79−1.94 (1H, m), 2.81 (2H, d, J =
6.6 Hz), 7.11−7.19 (1H, m), 7.22−7.35 (4H, m); 13C NMR δC (75
MHz) 22.1, 28.3, 42.6, 125.6, 128.8, 128.8, 137.4; IR (film) νmax/cm−1
2958, 2927, 1586, 1481, 1438, 1026, 737, 690.
Neopentyl Phenyl Sulfide40 (5h): Clear oil, 37%; H NMR δH
1
1
(300 MHz) 1.04 (9H, s), 2.90 (2H, s), 7.10−7.18 (1H, m), 7.21−7.30
(2H, m), 7.32−7.38 (2H, m); 13C NMR δC (75 MHz) 29.1, 32.5, 48.6,
125.5, 128.8, 128.9, 138.5; IR (film) νmax/cm−1 2958, 2907, 1584,
1480, 1438, 1026, 736, 690.
2-Methylbenzyl Phenyl Sulfide (5r): Clear oil, 86%; H NMR
δH (300 MHz) 2.39 (3H, s), 4.10 (2H, s), 7.02−7.37 (9H, m); 13C
NMR δC (75.5 MHz) 19.2, 37.4, 126.0, 126.5, 127.5, 128.9, 129.8,
130.3, 130.5, 135.1, 136.7, 136.8; IR (film) νmax/cm−1 3060, 2929,
3295
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The Journal of Organic Chemistry
Article
1583, 1479, 1438, 737, 690 (found C, 78.61; H, 6.32; S, 15.02;
C14H14S requires C, 78.46; H, 6.58; S 14.96); m/z (ESI) [(M + OH)+]
231; HRMS (ESI) exact mass calculated for C14H14S [(M + OH)+]
231.0844; found, 231.0844.
(20) Ohta, C.; Shimizu, H.; Kondo, A.; Katsuki, T. Synlett 2002, 161.
(21) Kelly, P. Ph.D. Thesis, National University of Ireland, Cork,
Cork, Ireland, 2008.
(22) Legros, J.; Bolm, C. Chem.Eur. J. 2005, 11, 1086.
(23) Mancheno, O. G.; Dallimore, J.; Plant, A.; Bolm, C. Org. Lett.
2009, 11, 2429.
(24) Shimizu, M.; Shibuya, K.; Hayakawa, R. Synlett 2000, 1437.
(25) Umemura, K.; Matsuyama, H.; Watanabe, N.; Kobayashi, M.;
Kamigata, N. J. Org. Chem. 1989, 54, 2374.
(26) Benson, S. C.; Snyder, J. K. Tetrahedron Lett. 1991, 32, 5885.
(27) Duddeck, H.; Korek, U.; Rosenbaum, D.; Drabowicz, J. Magn.
Reson. Chem. 1986, 24, 792.
(28) Davis, F. A.; Reddy, R. T.; Han, W.; Carroll, P. J. J. Am. Chem.
Soc. 1992, 114, 1428.
(29) Kelly, P.; Lawrence, S. E.; Maguire, A. R. Eur. J. Org. Chem.
2006, 4500.
(30) Guo, Y.; Jenks, W. S. J. Org. Chem. 1995, 60, 5480.
(31) King, J. F.; Coppen, M. J. Can. J. Chem. 1971, 49, 3714.
(32) Kwart, O. J. Am. Chem. Soc. 1971, 93, 7250.
(33) Samanta, R.; Antonchick, A. P. Angew. Chem., Int. Ed. 2011, 50,
5217.
Benzyl-(4-methoxyphenyl)-sulfide47,48 (1d): White solid, 95%,
mp 47−49 °C (lit. 48−49 °C);9 1H NMR δH (300 MHz) 3.77 (3H, s),
3.98 (2H, s), 6.73−6.83 (2H, m), 7.13−7.31 (7H, m); 13C NMR δC
(75.5 MHz) 41.2, 55.3, 114.4, 126.1, 127.0, 128.4, 128.9, 134.1, 138.1,
159.2; IR νmax/cm−1 (KBr) 2920, 2834, 1595, 1493, 1288, 1246, 1179,
1026, 810.
ASSOCIATED CONTENT
* Supporting Information
■
S
1H NMR spectra are available for compounds 5o, 5r, 5q, 6a,
6b, 6c, 6d, 6e, 6f, 6g, 6h, 6i, 6j, 6k, 6l, 6m, 6n, 6o, 6p, 6q, 6r,
2d, 4, 13, 14, and 15. 13C NMR spectra are available for
compounds 5o, 5r, 5q, 6h, 6i, 4, 13, 14, and 15. HPLC data are
available for sulfoxides 6i and 6h. This material is available free
of charge via the Internet at http://pubs.acs.org.
(34) Rodríguez, N.; Cuenca, A.; Ramírez de Arellano, C.; Medio-
AUTHOR INFORMATION
Corresponding Author
*E-mail: a.maguire@ucc.ie.
■
́
Simon, M.; Asensio, G. Org. Lett. 2003, 5, 1705.
(35) Baciocchi, E.; Rol, C.; Scamosci, E.; Sebastiani, G. V. J. Org.
Chem. 1991, 56, 5498.
(36) Pelotier, B.; Anson, M. S.; Campbell, I. B.; MacDonald, S. J. F.;
Priem, G.; Jackson, R. F. W. Synlett 2002, 1055.
(37) Cogan, D. A.; Liu, G.; Kim, K.; Backes, B. J.; Ellman, J. A. J. Am.
Chem. Soc. 1998, 120, 8011.
(38) Balcells, D.; Maseras, F.; Ujaque, G. J. Am. Chem. Soc. 2005, 127,
3624.
(39) Ding, Q.; Cao, B.; Yuan, J.; Liu, X.; Peng, Y. Org. Biomol. Chem.
2011, 9, 748.
(40) Landini, D.; Rolla, F. Org. Synth. 1978, 58, 143.
(41) Glaspy, P. E.; Hancock, R. A.; Thyagarajan, B. S. Org. Mass
Spectrom. 1985, 20, 281.
(42) King, J. F.; Coppen, M. J. Can. J. Chem. 1971, 49, 3714.
(43) Jean, M.; Renault, J.; van der Weghe, P.; Asao, N. Tetrahedron
Lett. 2010, 51, 378.
(44) Russell, G. A.; Ngoviwatchai, P.; Tashtoush, H. I.; Pla-Dalmau,
A.; Khanna, R. K. J. Am. Chem. Soc. 1988, 110, 3530.
(45) Chai, C. L. L.; Christen, D.; Halton, B.; Neidlein, R.; Starr, M. A.
E. Aust. J. Chem. 1995, 48, 577.
(46) Lapkin, I. I.; Bogoslovskii, N. V.; Mozhova, N. F Chem. Abstr.
1966, 64, 11115.
(47) Ham, J.; Yang, I.; Kang, H. J. Org. Chem. 2004, 69, 3236.
(48) Barry, N.; Brondel, N.; Lawrence, S. E.; Maguire, A. R.
Tetrahedron 2009, 65, 10660.
(49) Vowinkel, E. Synthesis 1974, 430.
(50) Sakai, N.; Moritaka, K.; Konakahara, T. Eur. J. Org. Chem. 2009,
24, 4123.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to IRCSET Embark initiative for funding. We
would also like to thank the following for their assistance:
Cormac Tobin, Aoife Ring, and Stephen Stokes.
REFERENCES
■
(1) Carreno, M. C.; Hernandez-Torres, G.; Ribagorda, M.; Urbano,
A. Chem. Commun. 2009, 6129.
(2) Sklute, G.; Amsallem, D.; Shabli, A.; Varghese, J. P.; Marek, I. J.
Am. Chem. Soc. 2003, 125, 11776.
(3) García Ruano, J. L.; Cid de la Plata, B. Top. Curr. Chem. 1999,
204, 1.
(4) Lee, A. W. M.; Chan, W. H. Top. Curr. Chem. 1997, 190, 103.
(5) Arai, Y.; Koizumi, T. Sulfur Rep. 1993, 15, 41.
(6) Myrick, H.; Malcolm, R.; Taylor, B.; LaRowe, S. Ann. Clin.
Psychiatry 2004, 16, 101.
(7) O’Mahony, G. E.; Kelly, P.; Lawrence, S. E.; Maguire, A. R.
ARKIVOC (Gainesville, FL, U.S.) 2011, 1, 1.
(8) Pitchen, P.; Kagan, H. B. Tetrahedron Lett. 1984, 25, 1049.
(9) Pitchen, P.; Dunach, E.; Deshmukh, M. N.; Kagan, H. B. J. Am.
Chem. Soc. 1984, 106, 8188.
(10) Di, F. F.; Modena, G.; Seraglia, R. Synthesis 1984, 325.
(11) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974.
(12) Bolm, C.; Bienewald, F. Angew. Chem., Int. Ed. Engl. 1996, 34,
2640.
(13) Bryliakov, K. P.; Talsi, E. P. Curr. Org. Chem. 2008, 12, 386.
(14) Willsky, G. R. Vanadium in the Biosphere. In Vanadium in
Biological Systems: Physiology and Biochemstry; Chasteen, N. D., Ed.;
Kluwer Academic Publishers: Dordrecht, The Netherlands, 1990; pp
1−24.
(15) Bunce, S.; Cross, R. J.; Farrugia, L. J.; Kunchandy, S.; Meason, L.
L.; Muir, K. W.; O’Donnell, M.; Peacock, R. D.; Stirling, D.; Teat, S. J.
Polyhedron 1998, 17, 4179.
(16) Plitt, P.; Pritzkow, H.; Oeser, T.; Kraemer, R. J. Inorg. Biochem.
2005, 99, 1230.
(17) Zhu, H.-B.; Dai, Z.-Y.; Huang, W.; Cui, K.; Gou, S.-H.; Zhu, C.-
J. Polyhedron 2004, 23, 1131.
(18) Alcon, M. J.; Corma, A.; Iglesias, M.; Sanchez, F. J. Mol. Catal.
A: Chem. 2002, 178, 253.
(19) Kelly, P.; Lawrence, S. E.; Maguire, A. R. Synlett 2007, 1501.
3296
dx.doi.org/10.1021/jo2026178 | J. Org. Chem. 2012, 77, 3288−3296