Symmetric diarylsulfoxides as asymmetric sulfinylating reagents for dialkylmagnesium compounds

Article abstract of DOI:10.1021/jo502417j

At -78 °C, primary dialkylmagnesium compounds reacted with diarylsulfoxides when 1.5 equiv of the dilithium salt of (S)-BINOL was added as a promotor. Alkyl aryl sulfoxides resulted in up to quantitative yield and with up to 97% ee. This demonstrates the feasibility of asymmetric sulfinylations by achiral sulfinylating agents (from the perspective of Alkyl₂Mg) as well as the feasibility of asymmetric sulfoxide-magnesium exchanges (from the perspective of Ar₂SO).

Full text of DOI:10.1021/jo502417j

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Article
Symmetric Diarylsulfoxides as Asymmetric Sulfinylating
Reagents for Dialkylmagnesium Compounds
Simon Ruppenthal, and Reinhard Brückner
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo502417j • Publication Date (Web): 11 Dec 2014
Downloaded from http://pubs.acs.org on December 14, 2014
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The Journal of Organic Chemistry
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Symmetric Diarylsulfoxides as Asymmetric Sulfinylating Reagents
for Dialkylmagnesium Compounds
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Simon Ruppenthal and Reinhard Brückner*
Institut für Organische Chemie, AlbertꢀLudwigsꢀUniversität, Albertstraße 21, 79104 Freiburg im Breisgau, Germany
reinhard.brueckner@organik.chemie.uniꢀfreiburg.de
O
O
S
S
AlkylMg
O
Li
Alkyl
+
+ Alkyl2Mg +
O
Li
R
R
R
R
achiral
(S)-configured
up to 100% yield,
up to 97% ee
Li2-(S)-BINOLate
pro-(R)
pro-(S)
ABSTRACT: At −78°C primary dialkylmagnesium compounds reacted with diaryl sulfoxides when 1.5 equiv. of the dilithium salt
of (S)ꢀBINOL were added as a promotor. Alkyl aryl sulfoxides resulted in up to quantitative yield and with up to 97% ee. This
demonstrates the feasibility of asymmetric sulfinylations by achiral sulfinylating agents (from the perspective of Alkyl2Mg) as well
as the feasibility of asymmetric sulfoxideꢀmagnesium exchanges (from the perspective of Ar2SO).
ꢀ INTRODUCTION
Nonꢀracemic, i. e. enantioenriched or enantiomerically pure sulfoxides1 occur widely in asymmetric synthesis2 − either stoichioꢀ
metrically as carriers of chiral information3 or catalytically as ligands for transition metals4 − and natural product synthesis.5 Nonꢀ
racemic sulfoxides6 are prepared, inter alia, by the asymmetric oxidation of sulfides7 (the enantioselective oxidation leading to
esomperazole – one of the topꢀselling drugs for gastric diseases – is a prominent example8), by the functionalization of organomeꢀ
tallics with enantiomerically pure sulfinylating agents (e. g. ref.9,11ꢀ21), and by the asymmetric alkylation (or arylation) of sulfenate
anions by alkyl (or aryl) halides.10 Grignard reagents have provided nonꢀracemic sulfoxides upon functionalization by enantiomeriꢀ
cally pure sulfinic acid derivatives − e. g. by menthyl (S)ꢀparaꢀtoluenesulfinate,11 (4S)ꢀ4ꢀbenzylꢀNꢀ[(S)ꢀparaꢀtolueneꢀ
sulfinyl]oxazolidinone,12 and tertꢀbutyl [(R)ꢀtertꢀbutylsulfinyl] sulfide13 − or by enantiomerically pure sulfoxides (1,14 2,15 3,16 7,17
8,18 (S)ꢀ9,18 12,19,20 13,20 1421 or 15,21 Figure 1; ref. 22). When one of the mentioned sulfinic acid derivatives sulfinylates a Grignard
reagent, the leaving group is a magnesium alkoxide, a magnesium carbamate or a magnesium sulfide. When such sulfinylations are
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carried out with one of the sulfoxides 1ꢀ3, 7ꢀ(S)ꢀ9 or 12ꢀ15 the leaving group is a(nother) Grignard reagent. That feature makes the
1
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latter processes sulfoxideꢀmagnesium exchange reactions.23
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7
O
O
O
O
O
P(OEt)2
P(OEt)2
S
S
S
p-Tol
Me
p-Tol
Br
8
1
2
3
ref.14
:
PhMgI
9
ref.15
:
tBuMgI
ref.16
:
PhMgBr
Ph
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O
O
O
S
S
S
Me
t-Bu
p-Tol
p-Tol
Ph
(S)-4
(R)-5
(S)-6
O
S
O
O
S
S
Bn
Me
Pent
Br Br
Br
7
8
(S)-9
ref.17
:
ref.18
:
PentMgBr ref.18
:
DodecMgBr
HalMg
O
O
O
S
S
S
Pent
Pent
Dodec
Me
Br
(S)-10
(S)-9
(R)-11
O
S
Ph
O
O
S
Ph
N(i-Pr)2
S
Ar
p-Tol
p-Tol
Cl
O
BocN
12: Ar = p-Me-C6H4
O
14
13:
p-Cl-C6H4
15
ref.19,20
:
EtMgBr
ref.21
:
i-PrMgCl
ref.21
: i-PrMgCl
O
O
S
S
Ar
Et
i-Pr
p-Tol
(R)-16
(S)-17
Figure 1. Enantiomerically pure sulfinylating agent, which convert Grignard reagents into nonꢀracemic sulfoxides while expelling another
Grignard compound as a leaving group.
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In 2012 we reported that non-racemic isopropyl aryl sulfoxides are accessible by sulfinylating iꢀPr2Mg24 by symmetric (achiral!) diꢀ
arylsulfoxides.25 The bestꢀworking sulfinylating agent of the latter kind was the diaryl sulfoxide 18 (Scheme 1). One of its enanꢀ
tiotopic 2,4ꢀdimethylphenyl groups was replaced by the isopropyl group with a 95.5:4.5 preference over the other − i. e., with 91%
ee. The underlying enantiocontrol was exerted by 3.0 equiv. of the dilithium salt “Li2ꢀ(S)ꢀBINOLate” (20) of (S)ꢀBINOL. 20 forms
a 1:1 complex with Et2Mg in the solid state.26 An analogous interaction between 20 and iꢀPr2Mg was expected to arise upon mixing
“THF”27 solutions of the two components at −78°C.
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Scheme 1. Asymmetric Sulfinylation of a Secondary Dialkylmagnesium Compound by the Symmetric Diaryl Sulfoxide 18 in
the Presence of an Excess of the Dilithium Salt “Li2-(S)-BINOLate” (20) of (S)-BINOL (ref.25)
O
O
S
i-Pr2Mg (1.2 equiv.),
S
iPr
18
(S)-(−)-19
(91% yield,
91% ee)
O
Li
O
Li
20
["Li2-(S)-BINOLate" (3.0 equiv.)],
THF, −78°C, 1.5 h
ꢀ RESULTS AND DISCUSSION
The present study demonstrates that symmetric diaryl sulfoxides sulfinylate primary dialkylmagnesium compounds in good
yields,28 too, and even with up to 97% ee (Schemes 2ꢀ6). This required fulfilling three prerequisites: (1) In the preparatory phase of
the reaction the dialkylmagnesium reagent had to be separated from the Schlenk equilibrium of the initially prepared Grignard reaꢀ
gent by precipitating the accompanying MgBr2 with diglyme (0.39 equiv.) and 1,4ꢀdioxane (0.60 equiv.). (2) The resulting dialkylꢀ
magnesium reagent (1.2 equiv.) had to be complexed by “Li2ꢀ(S)ꢀBINOLate” (20; 1.5 equiv.) prior to adding the sulfoxide. (3) The
duration of the sulfinylation had to be monitored carefully. At −78°C29 the optima ranged from 10 s to 26 h. Even moderately longꢀ
er reaction times could decrease the yield and/or the enantioselectivity when we used Et2Mg or Bu2Mg. As previously,25 the inducꢀ
ing ligand was recoverable as (S)ꢀBINOL in almost quantitative yield by flash chromatography on silica gel;30 it elutes prior to no
matter which sulfoxide.
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Scheme 2. Li2-(S)-BINOLate (20)-Promoted Asymmetric Sulfinylations of Primary Dialkylmagnesium Compounds and of
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4
Dicyclohexylmagnesium by the Symmetric Diaryl Sulfoxide 18 (Configurational Assignments: Ref.32)a
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a
The sulfoxides 21 and 28 were obtained from differently composed reactant mixtures than the other sulfoxides, using the sulfoxide 18 and more of the exchangeꢀ
inducing reagents Me2Mg (2.4 equiv), Bn2Mg (2.4 equiv.), and 20 (3.0 equiv.). Under the “usual” conditions lower yields were obtained.
Scheme 2 shows Li2ꢀ(S)ꢀBINOLate (20)ꢀinduced sulfinylations of Me2Mg, Bn2Mg,31 five other examples of (Rprim)2Mg, and
(cꢀC6H11)2Mg with the symmetric diaryl sulfoxide 18. They proceeded with 15% ee, 2% ee,31 85ꢀ97% ee, and 92% ee, respectively.
In most cases the yield surpassed 90%. The preferentially formed sulfoxide enantiomer was levorotatory without an exception;32 the
products, whose absolute configurations we clarified [(−)ꢀ21, (−)ꢀ22] were (S)ꢀconfigured.32 According to the survey of Scheme 2
Et2Mg, Bu2Mg, and iꢀBu2Mg were sulfinylated by a mixture of sulfoxide 18 and Li2ꢀ(S)ꢀBINOLate (20) with the highest enantiꢀ
omeric excesses, namely with 96%, 96%, and 97%, respectively. This led us to explore how the same organometallics are sulfinylꢀ
ated by mixtures of Li2ꢀ(S)ꢀBINOLate (20; 1.25 equiv.) and symmetric diaryl sulfoxides (0.83 equiv.) other than 18 (Schemes 3ꢀ6).
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Scheme 3. Nonracemic Sulfoxides [(S)-Configurations: Ref.32] From Li2-(S)-BINOLate (20)-Promoted Asymmetric Sulfinyl-
3
4
ations of Et2Mg by Symmetric Diaryl Sulfoxidesa,33
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6
O
O
O
7
8
S
S
S
Et
Et
Et
9
(S)-(−)-29
(−78°C, 2 min;
77% yield,
71% ee)
(S)-(−)-30
(−78°C, 30 min;
39% yield,
(S)-(−)-22
(−78°C, 30 min;
97% yield,
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94% ee)
96% ee)
O
O
O
S
S
S
Et
Et
Et
Ph
MeO
(S)-(−)-31
(−78°C, 60 min;
60% yield,
(S)-(−)-32
(−78°C, 10 s;
82% yield,
70% ee)
(S)-(−)-33
(−78°C, 15 min;
77% yield,
77% ee)
81% ee)
O
O
S
S
Et
Et
(S)-(−)-34
(S)-(−)-35
(−78°C, 5 min;
67% yield,
93% ee)
(−78°C, 5 min;
62% yield,
66% ee)
a The aryl ethyl sulfoxide depicted here were prepared from a symmetric diarylsulfoxide and the exchangeꢀinducing reagents Et2Mg (1.2 equiv) and 20 (1.5 equiv.), i.
e., under the “usual” conditions of Scheme 2.
The Li2ꢀ(S)ꢀBINOLate (20)ꢀinduced asymmetric sulfinylations of Et2Mg (Scheme 3) reached completion at −78°C between as little
as 10 s [→ (S)ꢀ(−)ꢀ32] and 1 h at maximum [→ (S)ꢀ(−)ꢀ31].33 The ethyl aryl sulfoxides 22 and 29ꢀ35 resulted in an average yield of
70%. They were uniformly levorotatory and (S)ꢀconfigured.32 The highest enantiocontrol resulted from (2,4ꢀdimethylphenyl)sulfꢀ
inyl transfer [→ 97% (S)ꢀ(−)ꢀ22, 96% ee]. The runnersꢀup were paraꢀtolylsulfinyl transfer (94% ee) and αꢀnaphthylsulfinyl transfer
(93% ee).
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Scheme 4. Nonracemic Sulfoxides (Configurational Assignments: Ref.32) From Li2-(S)-BINOLate (20)-Promoted Asymmet-
3
4
ric Sulfinylations of Bu2Mg by Achiral Diaryl Sulfoxidesa
5
6
O
O
O
7
8
S
S
*
S
Bu
Bu
Bu
9
(S)-(−)-36
(−78°C, 2 min;
75% yield,
46% ee)
(S)-(−)-37
(−)-23
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19
20
21
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60
(−78°C, 10 s;
82% yield,
48% ee)
(−78°C, 1.5 h;
91% yield,
96% ee)
O
O
S
O
S
S
Bu
Bu
Bu
Ph
MeO
38
(S)-(−)-39
(−78°C, 10 s;
72% yield,
52% ee)
(S)-(−)-40
(−78°C, 15 min;
83% yield,
(−78°C, 10 s;
decomposition)
63% ee)
O
O
S
*
S
Bu
Bu
(−)-41
(S)-(−)-42
(−78°C, 2 min;
91% yield,
90% ee)
(−78°C, 2 min;
81% yield,
30% ee)
a The aryl butyl sulfoxide depicted here were prepared from a symmetric diarylsulfoxide and the exchangeꢀinducing reagents Bu2Mg (1.2 equiv) and 20 (1.5 equiv.), i.
e., under the “usual” conditions of Scheme 2.
The Li2ꢀ(S)ꢀBINOLate (20)ꢀinduced asymmetric sulfinylations of Bu2Mg (Scheme 4) were even faster than the analogous sulfinylaꢀ
tions of Et2Mg (cf. above). This rendered the nonꢀracemic sulfoxides 23, 36ꢀ37, and 39ꢀ42 in 62ꢀ91% yield. In contrast, butyl 2,4,6ꢀ
trimethylphenyl sulfoxide (38) did not form because of an almost instantaneous decomposition of a mixture of its precursors. The
sulfoxides of Scheme 4 were consistently levorotatory and the five sulfoxides, whose 3D structure we clarified, were (S)ꢀconꢀ
figured.32 The highest ee value in this series of (96%) was observed for the (2,4ꢀdimethylphenyl)sulfinylation [→ 91% (−)ꢀ23].
Scheme 5. Nonracemic Sulfoxides (Configurational Assignments: Ref.32) From Li2-(S)-BINOLate (20)-Promoted Asymmet-
ric Sulfinylations of i-Bu2Mg by Achiral Diarylsulfoxidesa
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a
The aryl isobutyl sulfoxides depicted here were prepared from a symmetric diarylsulfoxide and the exchangeꢀinducing reagents iꢀBu2Mg (1.2 equiv) and 20 (1.5
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equiv.), i. e., under the “usual” conditions of Scheme 2.
The third dialkyl magnesium reagent, which was sulfinylated asymmetrically in the presence of Li2ꢀ(S)ꢀBINOLate (20) by a variety
of symmetric diaryl sulfoxides was iꢀBu2Mg (Scheme 5). It was less reactive than Et2Mg and Bu2Mg so that full conversions reꢀ
quired 0.5ꢀ24 h and possibly a slightly elevated temperature (−68°C instead of −78°C). The newly formed sulfoxides were levorotaꢀ
tory, and those, whose absolute configurations we clarified (43, 44, 46, and 47), were (S)ꢀconfigured.32 Enantiocontrol was best
when the (2,4ꢀdimethylphenyl)sulfinyl group was transferred [→ 96% (S)ꢀ(−)ꢀ27, 97% ee] or the (4ꢀphenylphenyl)sulfinyl group
[→ 87% (S)ꢀ(−)ꢀ46, 94% ee].
Scheme 6. Nonracemic (2-Bromophenyl) Sulfoxides [(S)-Configurations: Ref.32] From Li2-(S)-BINOLate (20)-Promoted
Asymmetric Sulfinylations by the Symmetric Bis(2-bromophenyl) Sulfoxide 50
O
Br
Br
O
S
Br
R2Mg (1.2 equiv.),
S
R
20 (1.5 equiv.),
THF, −78°C
50
51 and (S)-(−)-52-55
R = i-Bu:
(S)-(−)-54
R = i-Pr:23
(S)-(−)-55
R = Me:
51
R = Et:
(S)-(−)-52
R = Bu:
(S)-(−)-53
(decomp.) (−78°C, 10 s; (−78°C, 10 s;
(−78°C, 1.5 h; (−78°C, 1.5 h;
83% yield,
53% ee)
69% yield,
79% yield,
70% yield,
36% ee)
89% ee)
86% ee)
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In the presence of Li2ꢀ(S)ꢀBINOLate (20) bis(2ꢀbromophenyl) sulfoxide (50) had been a capricious sulfinylating agent for iꢀ
Pr2Mg:25 3.9 equiv. of this additive were required for accelerating the sulfinylation proper [→ 70% (S)ꢀ55] at the expense of an enꢀ
suing Br→Mg exchange; the latter interfered unavoidably under standard conditions.25 No Br→Mg exchanges occurred when mixꢀ
tures of bis(2ꢀbromophenyl) sulfoxide (50) and Li2ꢀ(S)ꢀBINOLate (20) sulfinylated Et2Mg, Bu2Mg, and iꢀBu2Mg − yet not Me2Mg
− asymmetrically (Scheme 6). The corresponding brominated sulfoxides (S)ꢀ52 - (S)ꢀ5432 resulted in 69ꢀ83% yield and with 53ꢀ
89% ee.
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ꢀ CONCLUSION
In summary, we have shown that symmetric diaryl sulfoxides transfer arylsulfinyl groups on di(primꢀalkyl) magnesium compounds
asymmetrically when 1.5 equiv. of Li2ꢀ(S)ꢀBINOLate (20) are present. This transformation is a novel entry into the synthesis of
nonꢀracemic alkyl aryl sulfoxides.
Ethyl, butyl, and isobutyl aryl sulfoxides arose with up to 97% ee. Hexyl and phenylethyl 2,4ꢀdimethylphenyl sulfoxide resulted
with 93 and 87% ee, respectively. In stark contrast, methyl 2,4ꢀdimethylphenyl sulfoxide resulted with little enantiocontrol (15%
ee) and benzyl 2,4ꢀdimethylphenyl sulfoxide virtually without (2% ee). We are at a loss interpreting these substituent dependencies.
Hence it remains unclear to which extent − and in the affirmative case: where − steric effects and/or electronic effects and/or other
effects are operative the eeꢀdetermining or the yieldꢀdetermining step. This is not least because the sulfoxide/magnesium exchange
− let alone our asymmetric variant thereof − is only poorly understood mechanistically.
The strategy, which underlies our present synthesis of alkyl aryl sulfoxides would become more generally useful if enantiomerically
pure additives like Li2ꢀ(S)ꢀBINOLate (20) allowed to sulfinylate organometallics asymmetrically also by other symmetric sulfoxꢀ
ides than diaryl sulfoxides. At least there are many kinds of (admittedly: unsymmetric) sulfoxides, which sulfinylate Grignard reꢀ
agents while expelling a magnesiumꢀcontaining leaving group (examples: Figure 1). The latter may be stable,34 βꢀeliminate,35 αꢀ
eliminate/rearrange36 or undergo a semipinacol rearrangement.37 If a pair of progenitors of any such leaving group binds to a
−S(=O)− linchpin a symmetric sulfoxide candidate for effecting another asymmetric sulfinylation like contemplated above would
be defined. Such a sulfoxide might act not just on R2Mg but also on RMgHal, RMgOX(=O)nR’, R3MgLi or other organometalꢀ
lics.38,39
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ꢀ EXPERIMENTAL SECTION
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5
6
7
8
General
9
Working technique: All reactions were carried out under an atmosphere of N2. Prior to use reaction flasks were dried in vacuo with a heat
gun. Liquids were added with a syringe through a septum. Prior to use THF, Et2O, and diglyme were distilled over sodium or potassium
under an atmosphere of N2. iꢀPr2NH was distilled over CaH2 similarly. Other solvents and reagents were employed as obtained commerꢀ
cially, i. e. without further purification. Flash chromatography on silica gel: Purification by flash chromatography was conducted on siliꢀ
ca gel 60 (230ꢀ400 mesh). All eluents were distilled prior to use. Chromatography conditions are documented in a shorthand form like, e.
g. “(cꢀC6H12:EtOAc a:b, F. 10ꢀ20)”, which means we eluted with an a:b mixture (v:v) of cꢀC6H12 and EtOAc and that the product was isoꢀ
lated from fractions 10ꢀ20. Fraction and column size were chosen in accordance to the parameters described by Still et al.40 Nuclear mag-
netic resonance spectra: NMR spectra were registered with 300 MHz and 400 MHz spectrometers (1H NMR) and with a 100 MHz specꢀ
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1
trometer (13C NMR); referenced internally to the Hꢀ and 13CꢀNMR signals of the solvent [CDCl3: 7.26 ppm (1H) and 77.10 ppm (13C)].
1HꢀNMR data are reported as follows: chemical shift (δ in ppm), multiplicity (s for singlet; d for doublet; t for triplet; q for quartet; m for
multiplet; mc for symmetric multiplet; br for broad signal), coupling constant(s) (Hz), integral, assignment. 13CꢀNMR data are reported in
terms of chemical shift and assignment. Assignments of 1HꢀNMR and 13CꢀNMR resonances refer to the IUPAC nomenclature except withꢀ
in substituents (where primed numbers are used) or where explicitly indicated otherwise. NMR assignments were supported by a combinaꢀ
tion of 1D and 2D techniques (DQFꢀCOSY and edꢀHSQC). High-resolution mass spectra were obtained employing a CI/NH3 (110 eV)
mode and using an orbitrap analyzer. Elemental analyses were obtained with a CHNS analyzer. Melting points are uncorrected and were
determined using open glass capillaries. IR spectra were measured with an FTꢀIR spectrometer irradiating sample films spread on a NaCl
plate. The ee values were determined by chiral HPLC. Optical rotations were measured at 365, 436, 546, 578, and 589 nm at 20°C and
were calculated by the Drude equation {[α] = (αexp × 100)/(c × d)}; rotational values are the average of five measurements of αexp in a givꢀ
en solution of the respective sample.
Preparation of Reactants
Preparation of Alkyl2Mg solutions in Et2O (Alkyl = Et, Bu, n-Hex, (CH2)2Ph, Bn, i-Bu and c-C6H11)41
At room temperature the appropriate alkyl bromide (128 mmol) was added dropwise to a suspension of Mg turnings (3.14 g, 129 mmol,
1.0 equiv.) in Et2O (60 mL) within 1.5 h. The dark grey suspension was heated under reflux for 4 h. After cooling to 0°C, diglyme
(7.20 mL, 6.75 g, 50.3 mmol, 0.39 equiv.) in Et2O (9 mL) and thereafter dioxane (6.60 mL, 6.80 g, 77.2 mmol, 0.60 equiv.) in Et2O (6 mL)
were added dropwise with a syringe pump within 75 and 50 min, respectively. The white suspension was stirred at −10°C for 16 h and then
filtered with suction an atmosphere of nitrogen. The clear and colorless filtrate was concentrated to about half its volume by a stream of niꢀ
trogen. Usually a small amount of a white precipitate formed concomitantly; it remained in the solution without decreasing its activity. The
resulting solution of Alkyl2Mg could be stored at 4°C for several weeks. Its concentration was determined by titration with salicylic aldeꢀ
hyde phenylhydrazone.42
Preparation of Me2Mg and Hex2Mg solutions in Et2O43
At room temperature MeLi or HexLi (solutions in THF, 12.0 mmol, 1.0 equiv.) was added dropwise to a solution of the corresponding Alꢀ
kylMgCl (solution in THF, 12.0 mmol, 1.0 equiv.). After 5 min the solvent was removed by applying high vacuo (~ 0.4 mbar). The residue
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was extracted with Et2O (3 × 10 mL) from precipitated LiCl. The concentration of the resulting clear and colorless solution was determined
by titration with salicylic aldehyde phenylhydrazone.42 At 4°C such solutions could be stored for several weeks.
1
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3
4
Preparation of the Symmetric Diaryl Sulfoxides
5
6
7
8
The symmetric diaryl sulfoxides used in this work were materials from our previous study.25
Preparation of Alkyl Aryl Sulfoxides:
9
General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides44
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Alkyl2Mg (0.38ꢀ0.80
M solutions in Et2O, 0.55ꢀ1.2 equiv.) was added to a solution of the appropriate diaryl sulfoxide (0.148ꢀ0.494 mmol,
1.0 equiv.) in THF (1 mL) at room temperature (for further details and deviations from this procedure: cf. individual descriptions). After
complete conversion, the reaction was quenched by the addition of MeOH (1 mL) and a saturated aqueous solution of NH4Cl (1 mL). The
layers were separated. The aqueous layer was extracted with tꢀBuOMe (3 × 2 mL). The combined organic layers were dried over MgSO4
and evaporated. The crude product was purified by flash chromatography on silica gel40 (further details: cf. individual descriptions).
Asymmetric Sulfinylations of Dialkylmagnesium Compounds by Symmetric Diaryl Sulfoxides
At 0°C nꢀBuLi [2.05ꢀ2.27
M solution in hexane, 3.0 equiv.] was added to a precooled solution of (S)ꢀBINOL (1.5 equiv.) in THF (2 mL).
After 10 min stirring was continued at room temperature for another 10 min. Subsequently, a solution of Alkyl2Mg (0.38ꢀ0.80 m solution
in Et2O, 1.2 equiv.) was added dropwise. After 10 min the reaction mixture was cooled to −78°C and a solution of the appropriate diaryl
sulfoxide (0.174ꢀ0.786 mmol, 1.0 equiv.) in THF (1.5 mL) was added during 10 min. If Alkyl2Mg was Et2Mg or Bu2Mg, the solution of
the appropriate diaryl sulfoxide had to be (1) precooled to −78°C and (2) added to the Li2ꢀ(S)ꢀBINOLate/Alkyl2Mg mixture very fast. After
full conversion was achieved (10 s to 24 h) the reaction was quenched by the addition of MeOH (2 mL). The resulting mixture was
warmed to room temperature and diluted with tꢀBuOMe (5 mL). A saturated, aqueous solution of NH4Cl (3 mL) was added. The layers
were separated. The aqueous layer was extracted with tꢀBuOMe (3 × 2 mL). The combined organic layers were dried over mgSO4 and
evaporated. The crude product was purified by flash chromatography on silica gel40 (details: cf. individual descriptions) to yield the title
compound.
(2,4-Dimethylphenyl) Methyl Sulfoxide (21): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 did not follow the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides): At
0°C nꢀBuLi (2.1
M
in hexane, 0.56 mL, 1.2 mmol, 6.1 equiv.) was added to a solution of racꢀBINOL (169 mg,
in Et2O, 1.18 mL, 0.472 mmol, 2.4 equiv.) was
0.591 mmol, 3.0 equiv.) in THF (1 mL). After 10 min Me2Mg (0.40
M
added. After another 10 min a solution of bis(2,4ꢀdimethylphenyl) sulfoxide (50.9 mg, 0.197 mmol) in THF (0.75 mL) was added. After
stirring at room temperature for 9 h the reaction was quenched and the resulting mixture was worked up. Flash chromatography on silica
gel40 (cꢀC6H12:EtOAc 55:45, F. 30ꢀ42) delivered racꢀ21 (26.2 mg, 79%) as a colorless oil. The asymmetric synthesis followed the Proce-
dure for the Asymmetric Sulfinylations of Dialkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using bis(2,4ꢀdimethylphenyl)
sulfoxide (101 mg, 0.391 mmol), (S)ꢀBINOL (3.0 equiv.) and Me2Mg (2.4 equiv.). After 72 h this delivered (S)ꢀ(−)ꢀ21 (61.4 mg, 93%;
15% ee) as a colorless oil. 1H NMR (300.1 MHz, CDCl3): δ = 2.34 (s, 3 H, ArꢀCH3), 2.37 (s, 3 H, ArꢀCH3), 2.66 (s, 3 H, 1‘ꢀH3), 7.01 (br. s,
1 H, 3ꢀH), 7.25 (d, lowꢀfield branch superimposed by the singlet of CHCl3, J5,6 = 7.9 Hz, 1 H, 5ꢀH), 7.83 ppm (d, J6,5 = 8.1, 1 H, 6ꢀH). The
preceding data are consistent with those reported in the literature.46 The ee was determined by chiral HPLC (Chiralcel ODꢀH, nꢀheptane/iꢀ
20
365
20
436
20
546
20
578
[α
]
[α
]
[α
]
[ ]
α
PrOH 90:10, 1 mL/min, λdetector = 250 nm): tr(R) = 16.83 min, tr(S) = 22.21 min.
= −163.1,
= −81.2,
= −40.2,
=
20
589
20
589
= −32.1 (c = 2.00 in EtOH; the respective sample had 15% ee); Lit.47:
[
= −87.8 [c = 1.3 in acetone, a sample of the (S)ꢀ
[α
]
α
]
−34.6,
enantiomer with 73% ee]. The absolute configuration was determined by comparing the sense of the optical rotation with literature data.47
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The Journal of Organic Chemistry
(2,4-Dimethylphenyl) Ethyl Sulfoxide (22): (S)-(−)-Enantiomer and Racemic45
1
2
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5
6
7
8
9
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides using
bis(2,4ꢀdimethylphenyl) sulfoxide (100 mg, 0.387 mmol) with Et2Mg (0.52
M in Et2O, 0.91 mL, 0.47 mmol, 1.2 equiv.)
within 30 min. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 60:40, F. 24ꢀ38) delivered racꢀ22 (34.3 mg, 49%)
as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagnesium Compounds
by Symmetric Diaryl Sulfoxides (cf. Section 3.2) using bis(2,4ꢀdimethylphenyl) sulfoxide (200 mg, 0.774 mmol). After 30 min this delivꢀ
1
ered (S)ꢀ(−)ꢀ22 (137 mg, 97%; 96% ee) as a colorless oil. H NMR (400.1 MHz, CDCl3): δ = 1.23 (dd, J2‘,1‘ꢀA = J2‘,1‘ꢀB = 7.3 Hz, 3 H, 2‘ꢀ
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H3), 2.34 (s, 3 H, ArꢀCH3), 2.36 (s, 3 H, ArꢀCH3), AB signal (δA = 2.71, δB = 2.86, JA,B = 13.6 Hz, A part additionally split by q, J1‘ꢀA,2‘
=
8.0 Hz, 1‘ꢀHA; B part additionally split by q, J1‘ꢀB,2‘ = 6.9 Hz, 1‘ꢀHB), 7.01 (mc, 1 H, 3ꢀH), 7.22 (mc49, J5,6 = 7.9 Hz, 1 H, 5ꢀH), 7.75 ppm (d,
J6‘,5‘ = 8.1 Hz, 1 H, 6ꢀH). 13C NMR (100.6 MHz, CDCl3): δ = 6.4 (Cꢀ2‘), 18.3 (ArꢀCH3), 21.3 (ArꢀCH3), 48.5 (Cꢀ1‘), 124.4 (Cꢀ6), 127.9
(Cꢀ5), 131.5 (Cꢀ3), 134.5, 138.6, 141.2 ppm (Cꢀ1, Cꢀ2, and Cꢀ4). The preceding data are consistent with those reported in the literature.46
The ee was determined by chiral HPLC (Chiralcel ODꢀ3, nꢀheptane/iꢀPrOH 96:4, 22°C, 1 mL/min, λdetector = 204 nm): tr(R) = 9.06 min,
20
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20
546
20
578
20
589
[ ]
α
[α
]
[α
]
[α
]
[α]
tr(S) = 13.49 min.
= −1247.6,
= −614.3,
= −305.5,
= −261.8,
= −248.7 (c = 1.64 in EtOH; the respective samꢀ
ple had 96% ee). The absolute configuration was assigned by chemical correlation (cf. Supporting Information).
Butyl (2,4-Dimethylphenyl) Sulfoxide (23): (−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides usꢀ
ing bis(2,4ꢀdimethylphenyl) sulfoxide (95.7 mg, 0.370 mmol) with Bu2Mg (0.69
M in Et2O, 0.65 mL, 0.45 mmol,
1.2 equiv.) within 1.5 h at 0°C. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 24ꢀ40) delivered
racꢀ23 (60.0 mg, 77%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric
Sulfinylations of Dialkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using bis(2,4ꢀdimethylphenyl) sulfoxide (102 mg,
0.393 mmol). After 1.5 h this delivered (−)ꢀ23 (75.3 mg, 91%; 96% ee) as a colorless oil. 1H NMR (400.1 MHz, CDCl3): δ = 0.93 (t, J4‘,3‘
=
7.6 Hz, 3 H, 4‘ꢀH3), 1.35ꢀ1.56 (m, 2 H, 3‘ꢀH2), 1.59ꢀ1.83 (m, 2 H, 2‘ꢀH2), 2.33 (s, 3 H, ArꢀCH3), 2.36 (s, 3 H, ArꢀCH3), AB signal (δA =
2.70, δB = 2.75, JA,B = 13.3 Hz, A part additionally split by dd, J1‘ꢀA,2‘ꢀA = 9.4, J1‘ꢀA,2‘ꢀB = 5.2 Hz, 1ꢀHA; B part additionally split by dd, J1‘ꢀ
B,2‘ꢀB = 9.4 Hz, J1‘ꢀB,2‘ꢀA = 5.7 Hz, 1ꢀHB), 7.01 (d, J3,5 = 0.7 Hz, 1 H, 3ꢀH), 7.22 (dd, J5,6 = 8.1 Hz, J5,3 = 0.8 Hz, 1 H, 5ꢀH), 7.77 ppm (d, J6,5
= 8.4 Hz, 1 H, 6ꢀH). 13C NMR (100.6 MHz, CDCl3): δ = 13.9 (Cꢀ4‘), 18.3 (ArꢀCH3), 21.3 (ArꢀCH3), 22.0 (Cꢀ3‘), 24.5 (Cꢀ2‘), 55.5 (Cꢀ1‘),
124.2 and 128.2 (Cꢀ5, and Cꢀ6‘), 131.7 (Cꢀ3), 134.3, 139.4, and 141.3 ppm (Cꢀ1, Cꢀ2, and Cꢀ4). IR (CDCl3): ν̃ = 3900, 3450, 3530, 3225,
3030, 2960, 2930, 2870, 2735, 2615, 2295, 2280, 2260, 2055, 1920, 1635, 1605, 1575, 1455, 1400, 1380, 1345, 1280, 1230, 1185, 1155,
1070, 1035, 970, 915, 880, 820, 730 cm−1. HRMS (CI, NH4Cl): C12H19SO (M + H+), calculated: 211.11566, found: 211.11560 (∆ = −0.3
ppm). Elemental analysis: calculated (%) for C12H18SO (210.3 g/mol): C 68.52, H 8.63, S 15.24; found: C 68.53, H 8.74, S 15.26. The ee
was determined by chiral HPLC (Chiralpak ADꢀH, nꢀheptane/iꢀPrOH 90:10, 1 mL/min, λdetector = 250 nm): tr(1) = 8.02 min, tr(2) = 9.05
20
365
20
436
20
546
20
578
20
589
[α
]
[α
]
[α
]
[α
]
[α]
min.
= −1273.5,
= −634.2,
= −391.3,
= −273.6,
= −253.9 (c = 1.74 in EtOH; the respective sample had 96%
ee).
Hexyl (2,4-Dimethylphenyl) Sulfoxide (24): (−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfox-
ides using bis(2,4ꢀdimethylphenyl) sulfoxide (38.0 mg, 0.147 mmol) with Hexyl2Mg (1.4 in Et2O, 0.13 mL,
M
0.18 mmol, 1.2 equiv.) within 15 min. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 85:15, F. 27ꢀ36)
delivered racꢀ24 (17.0 mg, 48%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of
Dialkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using bis(2,4ꢀdimethylphenyl) sulfoxide (50.0 mg, 0.193 mmol). After 30
1
min this delivered (−)ꢀ24 (39.1 mg, 85%; 93% ee) as a colorless oil. H NMR (400.1 MHz, CDCl3, sample contained 10% of the starting
material): δ = 0.86ꢀ0.89 (m, 3 H, 6’ꢀH3), 1.26ꢀ1.51 (m, 6 H, 3’ꢀ, 4’ꢀ, and 5’ꢀH2), 1.61ꢀ1.84 (m, 2 H, 2’ꢀH2), 2.34 (s, ArꢀCH3), 2.36 (s, Arꢀ
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CH3), AB signal (δA =2.70, δB = 2.75, JA,B = 13.1 Hz, A part additionally split by dd, J1‘ꢀA,2‘ꢀA = 7.2 Hz, J1‘ꢀA,2‘ꢀB = 5.5 Hz, 1‘ꢀHA; B part
additionally split by dd, J1‘ꢀB,2ꢀA = 9.3 Hz, J1‘ꢀB,2‘ꢀB = 6.7 Hz, 1‘ꢀHB), 7.01 (mc, 1 H, 3ꢀH), 7.22 (mc, 1 H, 5ꢀH), 7.77 ppm (d, J6,5 = 7.9 Hz, 1
H, 6ꢀH). 13C NMR (100.6 MHz, CDCl3): δ = 14.0 (Cꢀ1’), 18.2 (ArꢀCH3), 21.3 (ArꢀCH3), 22.49, 22.55, 28.5, 31.5, 55.9 (Cꢀ1’), 124.1 (Cꢀ6),
1
2
3
4
128.0 (Cꢀ5), 131.5 (Cꢀ3), 134.4, 139.5, 140.7 ppm (Cꢀ1, Cꢀ2, and Cꢀ4). IR (CDCl3): ν
̃ = 3470, 2955, 2930, 2860, 1605, 1570, 1480, 1465,
5
6
1455, 1400, 1380, 1275, 1230, 1160, 1060, 1035, 920, 820, 725 cm−1. HRMS (CI, NH4Cl): C14H23SO (M + H+), calculated: 239.14696,
found: 239.14660 (∆ = −1.5 ppm). The ee was determined by chiral HPLC (Chiralcel ODꢀH, nꢀheptane/iꢀPrOH 90:10, 1 mL/min, λdetector
=
7
8
9
20
365
20
436
20
546
20
578
20
589
[α
]
[α
]
[α
]
[α
]
[α]
209 nm): tr(1) = 7.35 min, tr(2) = 9.76 min.
= −1098.5,
= −550.5,
= −282.0,
= −224.0,
= −225.5 (c = 0.20 in
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EtOH; the respective sample had 93% ee).
(2,4-Dimethylphenyl) (2-Phenylethyl) Sulfoxide (25): (−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides usꢀ
ing bis(2,4ꢀdimethylphenyl) sulfoxide (91.8 mg, 0.355 mmol) with 2ꢀPhenylethyl2Mg (0.98 in Et2O, 0.40 mL,
M
0.39 mmol, 1.1 equiv.) within 30 min. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 21ꢀ36) delivꢀ
ered racꢀ25 (31.6 mg, 34%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Di-
alkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using bis(2,4ꢀdimethylphenyl) sulfoxide (600 mg, 2.32 mmol).48 After 3 h
this delivered (−)ꢀ25 (581 mg, 97%; 85% ee) as a colorless oil. 1H NMR (400.1 MHz, CDCl3): δ = 2.28 (s, 3 H, ArꢀCH3), 2.36 (s, 3 H, Arꢀ
CH3), 2.90ꢀ3.15 (m, 4 H, 1’ꢀ and 2’ꢀH2), 7.01 (mc, 1 H, 1 × ArꢀH), 7.17ꢀ7.25 (m, 4 H, 4 × ArꢀH), 7.26ꢀ7.30 (m, 2 H, 2 × ArꢀH), 7.80 ppm
3
(d, J6,5 = 8.0 Hz, 1 H, 6ꢀH). 13C NMR (100.6 MHz, CDCl3): δ = 18.1 (ArꢀCH3), 21.3 (ArꢀCH3), 28.6 (Cꢀ2’), 56.6 (Cꢀ1’), 124.2 (Cꢀ6),
126.7, 128.0, 128.6, 128.8, 131.6, 134.3, 138.9, 139.1, 141.2 ppm. IR (CDCl3): ν̃ = 3455, 3060, 3030, 2965, 2920, 2865, 2095, 1640, 1605,
1495, 1480, 1455, 1400, 1380, 1325, 1275, 1232, 1155, 1060, 1030, 965, 920, 875, 820, 750, 700 cm−1. HRMS (CI, NH4Cl): C16H19SO (M
+ H+), calculated: 259.11566, found: 259.11580 (∆ = +0.5 ppm). Elemental analysis: calculated (%) for C16H18SO (258.4 g/mol): C 74.38,
H 7.02, S 12.41; found: C 74.05, H 6.94, S 12.02. The ee was determined by chiral HPLC (Chiralpak ADꢀ3, nꢀheptane/iꢀPrOH 95:5, 1
20
365
20
436
20
546
20
20
589
[α
]
[α
]
[α
]
[α
]
[α]
578
mL/min, λdetector = 206 nm): tr(1) = 8.17 min, tr(2) = 15.73 min.
= −885.7,
= −432.8,
= −216.2,
= −185.6,
=
−175.0 (c = 0.90 in EtOH; the respective sample had 85% ee).
Benzyl (2,4-Dimethylphenyl) Sulfoxide (26): (−)-Enantiomer and Racemic45
The racemic synthesis44 did not follow the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfox-
ides: At 0°C nꢀBuLi (2.1 in hexane, 0.56 mL, 1.2 mmol, 6.1 equiv.) was added to a solution of racꢀBINOL
(167 mg, 0.583 mmol, 3.0 equiv.) in THF (1 mL). After 10 min Bn2Mg (0.40 in Et2O, 1.18 mL, 0.473 mmol, 2.4
M
M
equiv.) was added. After another 10 min a solution of bis(2,4ꢀdimethylphenyl) sulfoxide (50.9 mg, 0.197 mmol) in
THF (0.75 mL) was added. After stirring for 9 h at room temperature the reaction was quenched and the resulting mixture was worked up.
Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 30ꢀ42) delivered racꢀ26 (38.0 mg, 79%) as a colorless solid (mp. = 65ꢀ
66°C). The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagnesium Compounds by Sym-
metric Diaryl Sulfoxides using bis (2,4ꢀdimethylphenyl) Sulfoxide (101 mg, 0.391 mmol), (S)ꢀBINOL (3.0 equiv.), and Bn2Mg (2.4
equiv.). After 72 h this delivered 72 h (−)ꢀ26 (58.3 mg, 61%; 2% ee) as a colorless solid (mp. = 65ꢀ66°C). 1H NMR (400.1 MHz, CDCl3): δ
= 2.01 (s, 3 H, ArꢀCH3), 2.35 (s, 3 H, ArꢀCH3), AB signal (δA = 3.98, δB = 4.09, JA,B = 12.4 Hz, 2 H, 1’ꢀH), 6.91 (d, J3,5 = 0.6 Hz, 1 H, 3ꢀ
H), 6.98ꢀ7.01 (m, 2 H, 2 × ArꢀH), 7.15 (dd, J5,6 = 6.3 Hz, J5,3 = 0.6 Hz, 1 H, 5ꢀH), 7.21ꢀ7.30 (m, 3 H, 3 × ArꢀH superimposed by the singlet
of CHCl3), 7.61 ppm (d, J6,5 = 7.0 Hz, 1 H, 6ꢀH). 13C NMR (100.6 MHz, CDCl3): δ = 18.0 (ArꢀCH3), 21.4 (ArꢀCH3), 62.7 (Cꢀ1’), 124.4
(Cꢀ6), 128.0 (Cꢀ5), 128.3, 128.5, 129.6, 130.5, 131.0 (Cꢀ3), 135.6, 138.4, 141.3 ppm. IR (CDCl3): ν̃ = 3895, 3545, 3255, 3030,2920, 2860,
2610, 2260, 1650, 1795, 1775, 1675, 1625, 1600, 1600, 1565, 1550, 1515, 1490, 1450, 1400, 1380, 1340, 1235, 1155, 1060, 1035, 925,
820, 765, 700 cm−1. HRMS (CI, NH4Cl): C15H17SO (M + H+), calculated: 245.10000, found: 245.10001 (∆ = ±0.0 ppm). Elemental analyꢀ
sis: calculated (%) for C15H16SO (244.4 g/mol): C 73.73, H 6.60, S 13.12; found: C 73.52, H 6.64, S 12.82. The ee was determined by chiꢀ
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365
[α]
ral HPLC (Chiralcel ODꢀH, nꢀheptane/iꢀPrOH 90:10, 1 mL/min, λdetector = 250 nm): tr(1) = 14.85 min, tr(2) = 20.81 min.
= −18.8,
1
2
3
20
436
20
546
20
578
20
589
[α
]
[α
]
[α
]
[α]
= −9.0,
= −5.6,
= −6.5,
= −6.3 (c = 0.53 in EtOH; the respective sample had 2% ee).
4
5
(2,4-Dimethylphenyl) Isobutyl Sulfoxide (27): (−)-Enantiomer and Racemic45
6
7
8
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides using
bis(2,4ꢀdimethylphenyl) sulfoxide (100 mg, 0.387 mmol) with iꢀBu2Mg (0.80 in Et2O, 0.59 mL, 0.47 mmol, 1.2
M
equiv.) within 5 h at 0°C. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 75:25, F. 12ꢀ20) delivered racꢀ27
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(54.2 mg, 67%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagne-
sium Compounds by Symmetric Diaryl Sulfoxides using bis(2,4ꢀdimethylphenyl) sulfoxide (601 mg, 2.33 mmol) and delivered after 3.5 h
1
(−)ꢀ27 (470 mg, 96%; 97% ee) as a colorless oil. H NMR (400.1 MHz, CDCl3): δ = 1.05 (d, J3‘,2’ = 6.8 Hz, 3 H, 3‘ꢀH3), 1.17 (d, J3‘‘,2’
=
6.5 Hz, 3 H, 3‘‘ꢀH3), 2.25ꢀ2.35 (m, 1 H, 2‘ꢀH superimposed by the singlet of ArꢀCH3 at 2.33 ppm), 2.33 (s, 3 H, ArꢀCH3), 2.36 (s, 3 H, Arꢀ
CH3), AB signal (δA = 2.67, δB = 2.46, JA,B = 13.1 Hz, A part additionally split by d, J1‘ꢀA,2‘ = 9.7 Hz, 1‘ꢀHA; B part additionally split by dd,
J
1‘ꢀB,2‘ꢀA = 4.3 Hz, J1‘ꢀB,2‘ꢀB = 0.4 Hz, 1‘ꢀHB), 7.01 (mc, 1 H, 3ꢀH), 7.23 (mc49, J5,6 = 7.9 Hz, 1 H, 5ꢀH), 7.79 ppm (d, J6‘,5‘ = 8.0 Hz, 1 H, 6ꢀH).
13C NMR (100.6 MHz, CDCl3): δ = 18.1 (ArꢀCH3), 21.3 (ArꢀCH3) 23.0 (Cꢀ3’), 24.4 (Cꢀ3’’), 66.3(Cꢀ1’), 123.8 (Cꢀ6), 128.2 (Cꢀ5), 131.5
(Cꢀ3), 134.1, 140.0, 140.9 ppm (Cꢀ1, Cꢀ2, and Cꢀ4). IR (CDCl3): ν = 2910, 2510, 2960, 2925, 2870, 2735, 2195, 1775, 1605, 1460, 1380,
̃
1330, 1230, 1170, 1075, 1030, 820, 695 cm−1. HRMS (CI, NH4Cl): C12H19SO (M + H+), calculated: 211.11566, found: 211.11570 (∆ =
+0.2 ppm). The ee was determined by chiral HPLC (Chiralpak ADꢀH, nꢀheptane/iꢀPrOH 90:10, 1 mL/min, λdetector = 209 nm): tr(1) = 6.95
20
546
20
578
20
589
20
365
20
436
[α
]
[α
]
α
[ ]
[α
]
[ ]
α
min, tr(2) = 8.96 min.
= −1425.9,
= −720.6,
= −366.2,
= −314.5,
= −299.1 (c = 1.90 in EtOH; the respective
sample had 97% ee).
Cyclohexyl (2,4-Dimethylphenyl) Sulfoxide (28): (−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides using
bis(2,4ꢀdimethylphenyl) sulfoxide (100 mg, 0.387 mmol) with (cꢀC6H11)2Mg (0.38 in Et2O, 1.24 mL, 0.472 mmol,
M
1.2 equiv.) within 6 h at 0°C. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 70:30, F. 12ꢀ21) delivered racꢀ28
(86.3 mg, 94%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinyla-
tions of Dialkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using bis(2,4ꢀdimethylphenyl) sulfoxide (100 mg, 0.387 mmol).
1
After 3.5 h this delivered (−)ꢀ28 (84.9 mg, 93%; 92% ee) as a colorless oil. H NMR (400.1 MHz, CDCl3): δ = 1.16ꢀ1.31 (m, 3 H), 1.43ꢀ
1.57 (m, 2 H), 1.61ꢀ1.67 (m, 1 H), 1.76ꢀ1.88 (m, 4 H), 2.35 (s, 3 H, ArꢀCH3), 2.36 (s, 3 H, ArꢀCH3), 2.57 (dddd, J1‘,2‘ꢀax = J1‘,6‘ꢀax = 11.7 Hz,
J1‘,2‘ꢀeq = J1‘,6‘ꢀeq = 3.4 Hz, 1 H, 1‘ꢀH), 7.01 (mc, 1 H, 3ꢀH), 7.20 (mc49, J5,6 = 8.1 Hz, 1 H, 5ꢀH), 7.70 ppm (d, J6,5 = 8.1 Hz, 1 H, 6ꢀH). 13C
NMR (100.6 MHz, CDCl3): δ = 18.7 (ArꢀCH3), 21.4 (ArꢀCH3), 24.0, 25.47, 25.57, 25.9, 26.8, 62.1 (Cꢀ1), 125.3 (Cꢀ6), 127.8 (Cꢀ5), 131.4
(Cꢀ3), 135.7, 137.7, 141.0 ppm (Cꢀ1, Cꢀ2, and Cꢀ4). IR (CDCl3): ν̃ = 3935, 3760, 3525, 3280, 3030, 3005, 2930, 2855, 2735, 2655, 2615,
2360, 2295, 2240, 2055, 1920, 1720, 1635, 1605, 1475, 1450, 1380, 1340, 1270, 1230, 1180, 1155, 1120, 1060, 1035, 920, 890, 820, 745,
710 cm−1. HRMS (CI, NH4Cl): C14H21SO (M + H+), calculated: 237.13131, found: 237.13150 (∆ = +0.8 ppm). The ee was determined by
20
365
[α]
chiral HPLC (Chiralcel ODꢀH, nꢀheptane/iꢀPrOH 96:4, 1 mL/min, λdetector = 254 nm): tr(1) = 6.84 min, tr(2) = 9.98 min.
= −1168.7,
20
436
20
546
20
578
20
589
[α
]
[α
]
[α
]
[α]
= −564.0,
= −275.7,
= −237.9,
= −226.2 (c = 1.10 in EtOH; the respective sample had 92% ee).
Ethyl Phenyl Sulfoxide (29): (S)-(−)-Enantiomer33 and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides using diꢀ
phenyl sulfoxide (39.8 mg, 0.197 mmol) with Et2Mg (0.33 in Et2O, 0.33 mL, 0.11 mmol, 0.55 equiv.) within 30 min.
M
Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 55:45, F. 32ꢀ46) delivered racꢀ29 (25.1 mg, 83%) as a colorless
oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagnesium Compounds by Symmetric
Diaryl Sulfoxides using diphenyl sulfoxide (39.8 mg, 0.197 mmol). After 2 min this delivered (S)ꢀ(−)ꢀ29 (23.3 mg, 77%; 71% ee) as a colꢀ
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orless oil. After 30 min (S)ꢀ(−)ꢀ29 was obtained in a lower yield with a lower ee (34%; 31% ee). 1H NMR (300.1 MHz, CDCl3): δ = 1.20
(dd, J2‘,1‘ꢀA = J2‘,1‘ꢀB = 7.5 Hz, 3 H, 2‘ꢀH3), AB signal (δA = 2.76, δB = 2.90, JA,B = 13.4 Hz, A part additionally split by q, J1‘ꢀA,2‘ = 7.5 Hz,
1‘ꢀHA; B part additionally split by q, J1‘ꢀB,2‘ = 7.4 Hz, 1‘ꢀHB), 7.46ꢀ7.55 (m, 3 H, 3 × ArꢀH), 7.59ꢀ7.64 ppm (m, 2 H, 2 × ArꢀH). The precedꢀ
ing data are consistent with those reported in the literature.50 The ee was determined by chiral HPLC (Chiralcel OJꢀH, nꢀheptane/EtOH
1
2
3
4
5
6
20
436
20
365
20
546
20
578
[ ]
α
[α
]
[α
]
[ ]
α
95:5, 1 mL/min, λdetector = 250 nm): tr(R) = 11.86 min, tr(S) = 12.76 min.
= −354.0,
= −179.5,
= −92.5,
= −78.0,
7
8
9
20
589
20
589
= −73.5 (c = 0.20 in EtOH; the respective sample had 31% ee); Lit.51:
= −219.6 [c = 1.4 in EtOH, a sample of the (S)ꢀ
[α
]
[α]
enantiomer with 99% ee]. The absolute configuration was determined by comparing the sense of the optical rotation with literature data.51
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ethyl (p-Tolyl) Sulfoxide (30): (S)-(−)-Enantiomer33 and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides using
bis(pꢀtolyl) sulfoxide (45.4 mg, 0.197 mmol) with Et2Mg (0.16
M in Et2O, 1.35 ml, 0.216 mmol, 1.1 equiv.) within
1.25 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 50:50, F. 27ꢀ40) delivered racꢀ30 (7.0 mg, 21%) as a colorꢀ
less oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagnesium Compounds by Sym-
metric Diaryl Sulfoxides using bis(pꢀtolyl) sulfoxide (45.3 mg, 0.197 mmol). After 10 s this delivered (S)ꢀ(−)ꢀ30 (29.8 mg, 90%; 69% ee)
as a colorless oil. After 30 min (S)ꢀ(−)ꢀ30 was obtained in a lower yield with a higher ee (39%; 94% ee). 1H NMR (300.1 MHz, CDCl3): δ
= 1.19 (dd, J2‘,1‘ꢀA = J2‘,1‘ꢀB = 7.4 Hz, 3 H, 2‘ꢀH3), AB signal (δA = 2.75, δB = 2.87, JA,B = 14.8 Hz, A part additionally split by q, J1‘ꢀA,2‘
=
7.3 Hz, 1‘ꢀHA; B part additionally split by q, J1‘ꢀB,2‘ = 7.4 Hz, 1‘ꢀHB), AA’BB’ signal with signal centers at δA = 7.32 and δB = 7.50 ppm (4
H, 2 × 2ꢀH and 2 × 3ꢀH). The preceding data are consistent with those reported in the literature.50 The ee was determined by chiral HPLC
20
365
20
436
[α
]
[ ]
α
(Chiralcel OJꢀH, nꢀheptane/EtOH 98:2, 1 mL/min, λdetector = 250 nm): tr(R) = 17.63 min, tr(S) = 20.92 min.
= −723.5,
= −361.6,
20
546
20
578
20
589
20
589
= −148.5 (c = 0.55 in EtOH; the respective sample had 69% ee was used); Lit.50:
= −247 [c =
[α
]
[α
]
[α
]
[α]
= −183.6,
= −157.3,
2.60 in CHCl3; the respective sample had 94% ee]. The absolute configuration was determined by comparing the sense of the optical rotaꢀ
tion with literature data.50
Ethyl (2,4,5-Trimethylphenyl) Sulfoxide (31): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides using
bis(2,4,6ꢀtrimethylphenyl) sulfoxide (56.5 mg, 0.197 mmol) with Et2Mg (0.42
equiv.) within 2 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 60:40, F. 24ꢀ30) delivered racꢀ31 (16.2 mg,
M in Et2O, 0.52 mL, 0.22 mmol, 1.1
42%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dial-
kylmagnesium Compounds by Symmetric Diaryl Sulfoxides using bis(2,4,6ꢀtrimethylphenyl) sulfoxide (56.4 mg, 0.197 mmol). After 1 h
this delivered (S)ꢀ(−)ꢀ31 (23.2 mg, 60%; 77% ee) as a colorless oil. 1H NMR (400.1 MHz, CDCl3, the sample contained a small amount of
inseparateable impurity with signals at 1.23, 2.26, 2.68ꢀ2.75, 2.80ꢀ2.87, 6.97 and 7.60 ppm): δ = 1.28 (dd, J2‘,1‘ꢀA = J2‘,1ꢀB = 7.5 Hz, 3 H, 2‘ꢀ
H3), 2.28 (s, 3 H, ArꢀCH3), 2.54 (s, 6 H, 2 × ArꢀCH3), AB signal (δA = 2.95, δB = 3.21, JA,B = 12.9 Hz, A part additionally split by q, J1‘ꢀA,2‘
= 7.6 Hz, 1‘ꢀHA; B part additionally split by q, J1‘ꢀB,2‘ = 7.5 Hz, 1‘ꢀHB), 6.86 ppm (s, 2 H, 2 × ArꢀH). 13C NMR (100.6 MHz, CDCl3): δ =
8.6 (Cꢀ1‘), 19.5 (2 × ArꢀCH3), 21.2 (ArꢀCH3), 46.2 (Cꢀ2‘), 131.0 (Cꢀ3 and Cꢀ5), 134.5, 138.6, 141.1 ppm (Cꢀ1, Cꢀ2, Cꢀ4, and Cꢀ6). IR
(CDCl3): ν
HRMS (CI, NH4Cl): C11H17SO (M + H+), calculated: 197.10001, found: 197.10020 (∆ = +1.0 ppm). The ee was determined by chiral
̃
= 3290, 2970, 2925, 2855, 2450, 2045, 1600, 1570, 1455, 1380, 1295, 1250, 1070, 1045, 1015, 965, 850, 775, 715, 665 cmꢀ1.
20
365
20
436
[α
]
[ ]
α
HPLC (Chiralcel ODꢀ3, nꢀheptane/iꢀPrOH 98:2, 1.0 mL/min, λdetector = 205 nm): tr(R) = 11.91 min, tr(S) = 20.69 min.
= −1256.8,
20
546
20
578
20
589
[α
]
[α
]
[α]
= −552.7,
= −255.5
= −219.5,
= −210.0 (c = 0.22 in EtOH; the respective sample had 77% ee). The absolute configuration
was assigned by chemical correlation (cf. Supporting Information).
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The Journal of Organic Chemistry
Ethyl (4-Phenylphenyl) Sulfoxide (32): (S)-(−)-Enantiomer33 and Racemic45
1
2
3
4
5
6
7
8
9
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides
using bis(4ꢀphenylphenyl) sulfoxide (74.1 mg, 0.209 mmol) with Et2Mg (0.33
M in Et2O, 0.35 mL, 0.116 mmol,
0.55 equiv.) within 30 min. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 52:48, F. 26ꢀ42) delivered
racꢀ32 (37.3 mg, 77%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmet-
ric Sulfinylations of Dialkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using bis(4ꢀphenylphenyl)
1
sulfoxide (69.8 mg, 0.197 mmol). After 10 s this delivered (S)ꢀ(−)ꢀ32 (37.4 mg, 82%; 70% ee) as a colorless oil. H NMR (400.1 MHz,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
CDCl3): δ = 1.24 (dd, J2‘‘,1‘‘ꢀA = J2‘‘,1‘‘ꢀB = 7.5 Hz, 3 H, 2‘‘ꢀH3), AB signal (δA = 2.82, δB = 2.94, JA,B = 13.3 Hz, A part additionally split by
q, J1‘‘ꢀA,2‘‘ = 7.3 Hz, 1‘‘ꢀHA; B part additionally split by q, J1‘‘ꢀB,2‘‘ = 7.5 Hz, 1‘‘ꢀHB), 7.37ꢀ7.42 (m, 1 H, 4‘ꢀH), 7.45ꢀ7.49 (m, 2 H, 2 × 2‘ꢀ
H*), 7.59ꢀ7.62 (m, 2 H, 2 × 3‘ꢀH*), AA’BB‘ signal with signal centers at δA = 7.67 and δB = 7.74 ppm (4 H, 2 × 2ꢀH and 2 × 3ꢀH);
*assignments interchangeable. 13C NMR (100.6 MHz, CDCl3): δ = 6.2 (Cꢀ2‘‘), 50.5 (Cꢀ1‘‘), 124.8 (Cꢀ2), 127.3 (Cꢀ2‘*), 127.9 (Cꢀ3), 128.2
(Cꢀ4‘), 129.1 (Cꢀ3‘*), 139.9, 142.2, 144.1 ppm (Cꢀ1, Cꢀ4, and Cꢀ1’); *assignments interchangeable. IR (CDCl3): ν̃ = 3520, 3055, 3030,
3000, 2920, 2850, 2455, 2065, 1660, 1595, 1560, 1480, 1390, 1265, 1110, 1090, 1045, 1025, 965, 915, 935, 835, 760, 720, 695, 655 cmꢀ1.
HRMS (CI, NH4Cl): C14H15SO (M + H+), calculated: 231.08436, found: 231.08460 (∆ = +1.0 ppm). Elemental analysis: calculated (%) for
C14H14SO (230.3 g/mol): C 73.01, H 6.13, S 13.92; found: C 72.74, H 6.08, S 13.73. The ee was determined by chiral HPLC (Chiralcel OJꢀ
20
365
20
436
20
546
[α
]
[α
]
[ ]
α
H, nꢀheptane/EtOH 95:5, 1.0 mL/min, λdetector = 250 nm): tr(R) = 27.54 min, tr(S) = 29.81 min.
= −834.0,
= −374.6,
=
20
578
20
589
[α
]
[α]
−178.7,
= −153.0,
= −145.4 (c = 1.4 in EtOH; the respective sample had 70% ee). The absolute configuration was assigned by
chemical correlation (cf. Supporting Information).
Ethyl (4-Methoxyphenyl) Sulfoxide (33): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides usꢀ
ing bis(4ꢀmethoxyphenyl) sulfoxide (51.8 mg, 0.197 mmol) with Et2Mg (0.16 in Et2O, 1.35 mL, 0.216 mmol,
M
1.1 equiv.) within 1.25 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 40:60, F. 21ꢀ36) delivered racꢀ33
(11.5 mg, 32%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagne-
sium Compounds by Symmetric Diaryl Sulfoxides using bis(4ꢀmethoxyphenyl) sulfoxide (51.7 mg, 0.196 mmol). After 15 min this delivꢀ
ered (S)ꢀ(−)ꢀ33 (28.0 mg, 77%; 81% ee) as a colorless oil. 1H NMR (300.1 MHz, CDCl3): δ = 1.18 (dd, J2‘,1‘ꢀA = J2‘,1‘ꢀB = 7.5 Hz, 3 H, 2‘ꢀ
H3), AB signal (δA = 2.84, δB = 2.77, JA,B = 13.1 Hz, A part additionally split q, J1‘ꢀA,2‘ = 7.4 Hz, 1‘ꢀHA; B part additionally split by q, J1‘ꢀ
B,2‘ = 7.5 Hz, 1‘ꢀHB), 3.86 (s, 3 H, OꢀCH3), AA’BB‘ signal with signal centers at δA = 7.03 and δB = 7.55 ppm (4 H, 2 × 2ꢀH and 2 × 3ꢀH).
The preceding data are consistent with those reported in the literature.52 The ee was determined by chiral HPLC (Chiralcel ODꢀ3, nꢀ
20
365
20
436
20
546
[
α
]
[α
]
[ ]
α
heptane/iꢀPrOH 98:2, 1.0 mL/min, λdetector = 230 nm): tr(R) = 20.03 min, tr(S) = 22.32 min.
= −819.1,
= −396.6,
= −196.0,
20
589
20
578
20
589
52
α
[ ]
[α
]
[α]
= −167.6,
= −161.8 (c = 0.82 in EtOH; the respective sample had 81% ee); Lit. :
= +130.0 [c = 1.4 in MeOH for a samꢀ
ple of the (R)ꢀenantiomer. The ee of this sample is not stated in ref. 52]. The absolute configuration was determined by comparing the
sense of the optical rotation with literature data.52
Ethyl (1-Naphthyl) Sulfoxide (34): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides using
di(1ꢀnaphthyl) sulfoxide (59.8 mg, 0.198 mmol) with Et2Mg (0.33
M in Et2O, 0.33 mL, 0.109 mmol, 0.55 equiv.)
within 1.5 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 55:45, F. 14ꢀ24) delivered racꢀ34 (17.0 mg, 42%)
as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagnesium Compounds
by Symmetric Diaryl Sulfoxides using di(1ꢀnaphthyl) sulfoxide (59.6 mg, 0.197 mmol). After 5 min this delivered (S)ꢀ(−)ꢀ34 (27.0 mg,
67%; 93% ee) as a colorless oil. 1H NMR (400.1 MHz, CDCl3): δ = 1.22 (dd, J2‘,1‘ꢀA = J2‘,1‘ꢀB = 7.3 Hz, 3 H, 2‘ꢀH3), AB signal (δA = 2.85,
δB = 3.12, JA,B = 13.6 Hz, A part additionally split q, J1‘ꢀA,2‘ = 7.5 Hz, 1‘ꢀHA; B part additionally split by q, J1‘ꢀB,2‘ = 7.6 Hz, 1‘ꢀHB), 7.55ꢀ
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7.61 (m, 2 H, 2 × ArꢀH), 7.67 (dd, 3J = 8.2 Hz, 3J = 7.0 Hz, 1 H, 1 × ArꢀH), 7.93ꢀ7.99 (m, 3 H, 3 × ArꢀH), 8.11 ppm (dd, 3J = 7.2 Hz, 4J =
1
2
3
4
1.2 Hz, 1 H, 1 × ArꢀH). 13C NMR (100.6 MHz, CDCl3): δ = 6.2 (Cꢀ2‘), 48.8 (Cꢀ1‘), 121.7, 123.6, 125.6, 126.7, 127.3, 129.1, 129.2, 131.2,
133.6, 139.1 ppm. IR (CDCl3): ν̃ = 3470, 3055, 2955, 2925, 2870, 2850, 2425, 2045, 1645, 1590, 1505, 1455, 1405, 1370, 1345, 1260,
1190, 1140, 1065, 1055, 1045, 1020, 965, 920, 865, 805, 775, 740, 665 cmꢀ1. HRMS (CI, NH4Cl): C12H13SO (M + H+), calculated:
5
6
7
8
205.06871, found: 205.06860 (∆ = −0.5 ppm). The ee was determined by chiral HPLC (Chiralcel OJꢀH, nꢀheptane/iꢀPrOH 80:20, 0.8
20
436
20
546
20
578
20
589
20
365
[α
]
[α
]
[α
]
α
[ ]
[α]
mL/min, λdetector = 250 nm): tr(R) = 9.17 min, tr(S) = 10.45 min.
= −1098.4,
= −512.3,
= −277.6,
= −221.8,
=
−248.7 (c = 1.40 in EtOH; the respective sample had 93% ee). The absolute configuration was assigned by chemical correlation (cf. Supꢀ
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
porting Information).
Ethyl (2-Naphthyl) Sulfoxide (35): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides usꢀ
ing di(2ꢀnaphthyl) sulfoxide (59.6 mg, 0.197 mmol) with Et2Mg (0.33
M in Et2O, 0.33 mL, 0.109 mmol, 0.55
equiv.) within 1.5 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 55:45, F. 42ꢀ50) delivered racꢀ35
(30.0 mg, 75%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinyl-
ations of Dialkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using di(2ꢀnaphthyl) sulfoxide (59.6 mg, 0.197 mmol). After 5
min this delivered (S)ꢀ(−)ꢀ35 (25.1 mg, 62%; 66% ee) as a colorless oil. 1H NMR (300.1 MHz, CDCl3): δ = 1.22 (dd, J2‘,1‘ꢀA = J2‘,1‘ꢀB = 7.4
Hz, 3 H, 2‘ꢀH3), AB signal (δA = 2.99, δB = 2.84, JA,B = 13.4 Hz, A part additionally split by q, J1‘ꢀA,2‘ = 7.3 Hz, 1‘ꢀHA; B part additionally
split by q, J1‘ꢀB,2‘ = 7.4 Hz, 1‘ꢀHB), 7.55ꢀ7.62 (m, 3 H, 3 × ArꢀH), 7.90ꢀ7.99 (m, 3 H, 3 × ArꢀH), 8.18x ppm (br. s, 1 H, 1ꢀH). The preceding
data are consistent with those reported in the literature.53 The ee was determined by chiral HPLC (Chiralcel OJꢀH, nꢀheptane/EtOH 95:5, 1
20
365
20
436
20
546
20
578
20
589
[
α
]
[α
]
[α
]
[α
]
α
[ ]
mL/min, λdetector = 250 nm): tr(R) = 17.24 min, tr(S) = 18.35 min.
= −501.0,
= −244.7,
= −123.9,
= −106.3,
=
20
589
−99.8 (c = 0.49 in EtOH; the respective sample had 66% ee); Lit.51:
enantiomer had >99% ee]; The absolute configuration was determined by comparing the sense of the optical rotation with literature data.51
= −180.5 [c = 1.3 in acetone; the respective sample of the (S)ꢀ
[α
]
Butyl Phenyl Sulfoxide (36): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides using
diphenyl sulfoxide (39.8 mg, 0.197 mmol) with Bu2Mg (0.75
M in Et2O, 0.14 mL, 0.105 mmol, 0.53 equiv.) within
30 min. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, 28ꢀ40) delivered racꢀ36 (24.1 mg, 67%) as a
colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagne-
sium Compounds by Symmetric Diaryl Sulfoxides using diphenyl sulfoxide (39.7 mg, 0.196 mmol). After 2 min this delivered (S)ꢀ(−)ꢀ36
(27.0 mg, 75%; 46% ee) as a colorless oil. 1H NMR (300.1 MHz, CDCl3): δ = 0.92 (t, J4‘,3‘ = 7.2 Hz, 3 H, 4‘ꢀH3), 1.35ꢀ1.82 (m, 4 H, 2‘ꢀ
and 3‘ꢀH2), AB signal (δA = 2.79, δB = 2.80, JA,B = 7.1 Hz, 2 H, 1’ꢀHA and 1‘ꢀHB), 7.48ꢀ7.55 (m, 3 H, 3 × ArꢀH), 7.60ꢀ7.64 ppm (m, 2 H, 2
× ArꢀH). The preceding data are consistent with those reported in the literature.53 The ee was determined by chiral HPLC (Chiralcel OJꢀH,
20
365
20
436
20
546
[
α
]
[α
]
[ ]
α
nꢀheptane/EtOH 98:2, 1 mL/min, λdetector = 250 nm): tr(R) = 11.72 min, tr(S) = 12.45 min.
= −498.7,
= −254.5,
= −131.6,
20
589
20
578
20
589
53
α
[ ]
[α
]
[α]
= −113.9,
= −107.2 (c = 0.86 in EtOH; the respective sample had 46% ee); Lit. :
= +150 [c = 0.1 in CH2Cl2, a sample of
the (R)ꢀenantiomer with 75% ee]. The absolute configuration was determined by comparing the sense of the optical rotation with literature
data.53
Butyl (p-Tolyl) Sulfoxide (37): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides
using bis(pꢀtolyl) sulfoxide (45.6 mg, 0.198 mmol) with Bu2Mg (0.75
M in Et2O, 0.14 mL, 0.105 mmol, 0.53
equiv.) within 30 min. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 60:40, F. 12ꢀ18) delivered racꢀ37
(23.8 mg, 62%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagne-
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sium Compounds by Symmetric Diaryl Sulfoxides using bis(pꢀtolyl) sulfoxide (45.5 mg, 0.198 mmol). After 10 s this delivered (S)ꢀ(−)ꢀ37
1
2
3
4
5
6
1
(31.8 mg, 82%; 48% ee) as a colorless oil. H NMR (300.1 MHz, CDCl3): δ = 0.92 (t, J4‘,3‘ = 7.2 Hz, 3 H, 4‘ꢀH3), 1.34ꢀ1.51 (m, 2 H,
3‘ꢀH2), 1.52ꢀ1.74 (m, 2 H, 2‘ꢀH2), 2.42 (s, 3 H, ArꢀCH3), 2.70ꢀ2.86 (m , 2 H, 1‘ꢀH2), AA’BB‘ signal with signal centers at δA = 7.32 and δB
= 7.51 ppm (2 × 2ꢀH and 2 × 3ꢀH). The preceding data are consistent with those reported in the literature.54 The ee was determined by chiꢀ
20
365
α
[ ]
ral HPLC (Chiralcel ODꢀ3, nꢀheptane/iꢀPrOH 98:2, 1 mL/min, λdetector = 205 nm): tr(R) = 12.21 min, tr(S) = 15.35 min.
= −507.6,
7
8
9
20
578
20
436
20
546
20
589
= −108.1 (c = 0.37 in EtOH; the respective sample had 48% ee); Lit.55:
=
[α]
[α
]
[α
]
[α]
20
= −257.8,
= −131.6,
= −113.5,
[ ]
α 589
−162.3 (c = 3.2 in acetone, a sample of the (S)ꢀenantiomer with 91% ee); The absolute configuration was determined by comparing the
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
sense of the optical rotation with literature data.55
Butyl (4-Phenylphenyl) Sulfoxide (39): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfox-
ides using bis(4ꢀphenylphenyl) sulfoxide (69.9 mg, 0.197 mmol) with Bu2Mg (0.75
M in Et2O, 0.14 mL,
0.11 mmol, 0.55 equiv.) within 30 min. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 27ꢀ
44) delivered racꢀ39 (27.3 mg, 54%) as a colorless oil. The asymmetric synthesis followed the Procedure
for the Asymmetric Sulfinylations of Dialkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using
1
bis(4ꢀphenylphenyl) sulfoxide (83.1 mg, 0.234 mmol). After 10 s this delivered (S)ꢀ(−)ꢀ39 (43.5 mg, 72%; 52% ee) as a colorless oil. H
NMR (400.1 MHz, CDCl3): δ = 0.94 (t, J4‘‘,3‘‘ = 7.3 Hz, 3 H, 4‘‘ꢀH3), 1.37ꢀ1.56 (m, 2 H, 3‘‘ꢀH2), 1.58ꢀ1.72 (m, 1 H, 2‘‘ꢀHA), 1.73ꢀ1.80 (m,
1 H, 2‘‘ꢀHB), 2.78ꢀ2.89 (m, 2 H, 1‘‘ꢀH2), 7.37ꢀ7.42 (m, 1 H, 4‘ꢀH), 7.45ꢀ7.49 (m, 2 H, 2 × 2‘ꢀH*), 7.59ꢀ7.62 (m, 2 H, 2 × 3‘ꢀH*), AA’BB‘
signal with signal centers at δA = 7.68 and δB = 7.74 ppm (4 H, 2 × 2ꢀH and 2 × 3ꢀH); *assignments interchangeable. 13C NMR (100.6
MHz, CDCl3): δ = 13.8 (Cꢀ4‘‘), 22.0 (Cꢀ3‘‘), 24.3 (Cꢀ2‘‘), 57.2 (Cꢀ1‘‘), 124.7 (Cꢀ2), 127.3 (Cꢀ2‘*), 128.0 (Cꢀ3), 128.2 (Cꢀ4‘), 129.1 (Cꢀ
3‘*), 139.9, 142.9, 144.1 ppm (Cꢀ1, Cꢀ4, and Cꢀ1’); *assignments interchangeable. IR (CDCl3): ν̃ = 3650, 3240, 3055, 2955, 2930, 2870,
2395, 1950, 1560, 1480, 1465, 1450, 1395, 1165, 1095, 1075, 1030, 1015, 105, 915, 835, 750, 715, 690, 655 cmꢀ1. HRMS (CI, NH4Cl):
C16H19SO (M + H+), calculated: 259.11566, found: 259.11590 (∆ = +0.9 ppm). Elemental analysis: calculated (%) for C16H18SO (258.4
g/mol): C 73.38, H 7.02, S 12.41; found: C 74.23, H 6.93, S 12.49. The ee was determined by chiral HPLC (Chiralcel ODꢀ3, nꢀheptane/iꢀ
20
436
20
546
20
365
20
578
[α
]
[
α
]
[
α
]
[ ]
α
PrOH 96:4, 1.0 mL/min, λdetector = 206 nm): tr(R) = 12.47 min, tr(S) = 13.65 min.
= −561.3,
= −255.5,
= −124.7,
=
20
589
α
[ ]
−106.6,
= −100.9 (c = 0.47 in EtOH; the respective sample had 52% ee). The absolute configuration was assigned by chemical correꢀ
lation (cf. Supporting Information).
Butyl (4-Methoxyphenyl) Sulfoxide (40): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides
using bis(4ꢀmethoxyphenyl) sulfoxide (51.6 mg, 0.196 mmol) with Bu2Mg (0.75 in Et2O, 0.29 mL,
M
0.22 mmol, 1.1 equiv.) within 1 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 55:45, F. 24ꢀ34) deꢀ
livered racꢀ40 (15.6 mg, 37%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of
Dialkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using bis(4ꢀmethoxyphenyl) sulfoxide (51.8 mg, 0.197 mmol). After 15
min this delivered (S)ꢀ(−)ꢀ40 (34.6 mg, 83%; 63% ee) as a colorless oil. 1H NMR (300.1 MHz, CDCl3): δ = 0.92 (t, J4‘,3‘ = 7.2 Hz, 3 H, 4‘ꢀ
H3), 1.34ꢀ1.50 (m, 2 H, 3‘ꢀH2), 1.51ꢀ1.75 (m, 2 H, 2‘ꢀH2), 2.69ꢀ2.86 (m, 1 H, 1‘ꢀH2), 3.86 (s, 3 H, OꢀCH3), AA’BB‘ signal with signal cenꢀ
ters at δA = 7.02 and δB = 7.56 ppm (4 H, 2 × 2ꢀH and 2 × 3ꢀH). The preceding data are consistent with those reported in the literature.56
The ee was determined by chiral HPLC (Chiralcel OJꢀH, nꢀheptane/EtOH 98:2, 1 mL/min, λdetector = 250 nm): tr(S) = 19.94 min, tr(R) =
20
365
20
436
20
546
20
578
20
589
[
α
]
[
α
]
[
α
]
[
α
]
α
[ ]
21.38 min.
= −468.4,
= −238.9,
= −126.6,
= −117.7,
= −114.7 (c = 0.64 in EtOH; the respective sample had
63% ee). The absolute configuration was assigned by chemical correlation (cf. Supporting Information).
Butyl (1-Naphthyl) Sulfoxide (41): (−)-Enantiomer and Racemic45
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The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides
using di(1ꢀnaphthyl) sulfoxide (57.9 mg, 0.192 mmol) with Bu2Mg (0.75 in Et2O, 0.14 mL, 0.11 mmol, 0.57
equiv.) within 35 min. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 20ꢀ30) delivered racꢀ41
(25.5 mg, 56%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagne-
sium Compounds by Symmetric Diaryl Sulfoxides using di(1ꢀnaphthyl) sulfoxide (59.4 mg, 0.197 mmol). After 2 min this delivered (−)ꢀ41
1
2
3
4
5
6
7
M
1
(41.5 mg, 91%; 90% ee) as a colorless oil. H NMR (400.1 MHz, CDCl3): δ = 0.91 (t, J4‘,3‘ = 7.3 Hz, 3 H, 4‘ꢀH3), 1.34ꢀ1.56 (m, 2 H,
8
9
3‘ꢀH2), 1.59ꢀ1.69 (m, 1 H, 2‘ꢀHA), 1.81ꢀ1.91 (m, 1 H, 2‘ꢀHB), AB signal (δA = 2.83, δB = 3.03, JA,B = 13.2 Hz, A part additionally split by
dd, J1‘ꢀA,2‘ꢀB = 9.5 Hz, J1‘ꢀA,2‘ꢀA = 4.9 Hz, 1‘ꢀHA; B part additionally split by dd, J1‘ꢀB,2‘ꢀB = 10.2 Hz, J1‘ꢀB,2‘ꢀA = 6.8 Hz, 1‘ꢀHB), 7.55ꢀ7.61 (m,
2 H, 2 × ArꢀH), 7.67 (dd, 3J = 6.9 Hz, 3J = 5.9 Hz, 1 H, 1 × ArꢀH), 7.94ꢀ7.98 (m, 3 H, 3 × ArꢀH), 8.13 ppm (dd, 3J = 7.2 Hz, 4J = 1.2 Hz, 1
H, 1 × ArꢀH). 13C NMR (100.6 MHz, CDCl3): δ = 13.8 (Cꢀ4‘), 22.0 (Cꢀ3‘), 24.6 (Cꢀ2‘), 55.9 (Cꢀ1‘), 121.6, 123.2, 125.7, 126.7, 127.2,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
129.0, 129.2, 131.1, 133.6, 139.9 ppm. IR (CDCl3): ν̃ = 3535, 3055, 2930, 2925, 2870, 2405, 2045, 1645, 1590, 1505, 1465, 1400, 1380,
1345, 1260, 1215, 1190, 1140, 1100, 1070, 1040, 965, 800, 770, 740, 665 cmꢀ1. HRMS (CI, NH4Cl): C14H17SO (M + H+), calculated:
233.10001, found: 233.10000 (∆ = −0.1 ppm). Elemental analysis: calculated (%) for C14H16SO (232.3 g/mol): C 72.37, H 6.94, S 13.80;
found: C 72.00, H 6.90, S 13.83. The ee was determined by chiral HPLC (Chiralpak ADꢀH, nꢀheptane/iꢀPrOH 95:5, 1 mL/min, λdetector
=
20
365
20
436
20
546
20
578
20
589
[
α
]
[
α
]
[
α
]
[
α
]
α
[ ]
209 nm): tr(1) = 17.39 min, tr(2) = 24.68 min.
= −2378.2,
= −1147.8,
= −573.0,
= −491.5,
= −466.8 (c = 1.28
in EtOH; the respective sample had 90% ee).
Butyl (2-Naphthyl) Sulfoxide (42): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides
using di(2ꢀnaphthyl) sulfoxide (61.0 mg, 0.202 mmol) with Bu2Mg (0.75 in Et2O, 0.15 mL, 0.11 mmol, 0.55
M
equiv.) within 35 min. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 24ꢀ37) delivered racꢀ42
(20.1 mg, 47%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagne-
sium Compounds by Symmetric Diaryl Sulfoxides using di(2ꢀnaphthyl) sulfoxide (59.6 mg, 0.197 mmol). After 2 min this delivered (S)ꢀ
(−)ꢀ42 (37.2 mg, 81%; 30% ee) as a colorless oil. 1H NMR (300.1 MHz, CDCl3): δ = 0.92 (t, J4‘,3‘ = 7.1 Hz, 3 H, 4‘ꢀH3), 1.36ꢀ1.55 (m, 2 H,
3‘ꢀH2), 1.57ꢀ1.67 (m, 1 H, 2‘ꢀHA), 1.71ꢀ1.86 (m, 1 H, 2‘ꢀHB), 2.85ꢀ2.91 (m, 2 H, 1‘ꢀH2), 7.56ꢀ7.62 (m, 3 H, 3 × ArꢀH), 7.89ꢀ7.99 (m, 3 H, 3
× ArꢀH), 8.19 ppm (br. s, 1 H, 1ꢀH). The preceding data are consistent with those reported in the literature.53 The ee was determined by
20
365
α
[ ]
chiral HPLC (Chiralcel ODꢀ3, nꢀheptane/iꢀPrOH 98:2, 1 mL/min, λdetector = 224 nm): tr(R) = 13.40 min, tr(S) = 15.81 min.
= −288.0,
= +188 [c
20
20
20
20
20
589
53
[
α
]
[
α
]
[
α
]
[
α
]
α
[ ]
436
546
578
589
= −139.8,
= −71.5,
= −61.3,
= −58.0 (c = 0.61 in EtOH; the respective sample had 30% ee); Lit. :
= 0.12 in CH2Cl2, a sample of the (R)ꢀenantiomer with 67% ee]. The absolute configuration was determined by comparing the sense of the
optical rotation with literature data.53
Isobutyl Phenyl Sulfoxide (43): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides using
diphenyl sulfoxide (70.0 mg, 0.346 mmol) with iꢀBu2Mg (0.80
M in Et2O, 0.24 mL, 0.19 mmol, 0.55 equiv.) within
1.5 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 27ꢀ39) delivered racꢀ43 (46.6 mg, 74%) as a
colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagnesium Compounds by
Symmetric Diaryl Sulfoxides using diphenyl sulfoxide (80.5 mg, 0.393 mmol). After 1 h this delivered (S)ꢀ(−)ꢀ43 (54.7 mg, 76%; 61% ee)
as a colorless oil. 1H NMR (400.1 MHz, CDCl3): δ = 1.06 (d, J3‘,2‘ = 6.8 Hz, 3 H, 3‘ꢀH3), 1.16 (d, J3‘‘,2‘ = 6.5 Hz, 3 H, 3‘‘ꢀCH3), 2.24 (mc, 1
H, 2‘ꢀH), 2.47 (dd, J1‘ꢀA,1‘ꢀB = 13.0 Hz, J1‘ꢀA,2‘ = 9.2 Hz, 1 H, 1‘ꢀHA), 2.81 (dd, J1‘ꢀB,1‘ꢀA = 13.0 Hz, J1‘ꢀB,2‘ = 5.0 Hz, 1 H, 1‘ꢀHB), 7.45ꢀ7.54
(m, 3 H, 3 × ArꢀH), 7.61ꢀ7.65 ppm (m, 2 H, 2 × ArꢀH). The preceding data are consistent with those reported in the literature.57 The ee was
determined by chiral HPLC (Chiralcel ODꢀ3, nꢀheptane/iꢀPrOH 95:5, 1 mL/min, λdetector = 209 nm): tr(R) = 6.57 min, tr(S) = 8.23 min.
20
365
20
436
20
546
20
578
20
589
[
α
]
[
α
]
[
α
]
[
α
]
α
[ ]
= −721.2,
= −374.3,
= −194.2,
= −167.2,
= −159.8 (c = 1.45 in EtOH; the respective sample had 61% ee);
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20
589
57
α
[ ]
Lit. :
= +129.0 [c = 1.0 in CHCl3, a sample of the (R)ꢀenantiomer with 48% ee]. The absolute configuration was determined by comꢀ
paring the sense of the optical rotation with literature data.57
1
2
3
4
Isobutyl (p-Tolyl) Sulfoxide (44): (S)-(−)-Enantiomer and Racemic45
5
6
7
8
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides using
bis(pꢀtolyl) sulfoxide (101 mg, 0.439 mmol) with iꢀBu2Mg (0.80 in Et2O, 0.61 mL, 0.49 mmol, 1.1 equiv.) within
1.5 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 37ꢀ49) delivered racꢀ44 (74.3 mg, 86%) as a
colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagnesium Compounds by
Symmetric Diaryl Sulfoxides using bis(pꢀtolyl) sulfoxide (45.3 mg, 0.197 mmol). After 1 h this delivered (S)ꢀ(−)ꢀ44 (32.9 mg, 85%; 58%
M
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
ee) as a colorless oil. HꢀNMR (300.1 MHz, CDCl3): δ = 1.05 (d, J3‘,2‘ = 5.9 Hz, 3 H, 3‘ꢀH3), 1.14 (d, J3‘‘,2‘ = 6.3 Hz, 3 H, 3‘‘ꢀH3), 2.13ꢀ
2.27 (m, 1 H, 2‘ꢀH), 2.41 (s, 3 H, ArꢀCH3 superimposed by AB signal), AB signal (δA = 2.44, δB = 2.45, JA,B = 8.4 Hz, 2 H, 1‘ꢀCH2),
AA’BB‘ signal with signal centers at δA = 7.31 and δB = 7.52 ppm (2 × 2ꢀH and 2 × 3ꢀH). The preceding data are consistent with those reꢀ
ported in the literature.50 The ee was determined by chiral HPLC (Chiralcel ODꢀ3, nꢀheptane/iꢀPrOH 150:1, 1 mL/min, λdetector = 249 nm):
20
365
20
436
20
546
20
578
20
589
[
α
]
[
α
]
[
α
]
[
α
]
α
[ ]
tr(R) = 17.66 min, tr(S) = 20.84 min.
= −657.2,
= −334.5,
= −172.0,
= −148.3,
= −139.9 (c = 1.27 in EtOH;
20
589
the respective sample had 58% ee); Lit.57:
= −150 [c = 0.75 in CHCl3, a sample of the (S)ꢀenantiomer with 71% ee]. The absolute
α
[ ]
configuration was determined by comparing the sense of the optical rotation with literature data.50
Isobutyl (2,4,6-Trimethylphenyl) Sulfoxide (45): (−)-Enantiomer and Racemic45
The racemic synthesis44 did not follow the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides
: At 0°C nꢀBuLi (2.1
M
in hexane, 0.56 mL, 1.2 mmol, 3.0 equiv.) was added to a solution of racꢀBINOL (167 mg,
in Et2O, 0.59 mL, 0.47 mmol, 1.2 equiv.) was
0.584 mmol, 1.5 equiv.) in THF (1 mL). After 10 min iꢀBu2Mg (0.80
M
added. After another 10 min a solution of bis(2,4,6ꢀtrimethylphenyl) sulfoxide (113 mg, 0.395 mmol) in THF (1.5
mL) was added. After stirring for 24 h at room temperature the reaction was quenched and the resulting mixture was worked up. Flash
chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 18ꢀ24) delivered racꢀ45 (45.9 mg, 52%) as a colourless oil. The asymmetric
synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagnesium Compounds by Symmetric Diaryl Sulfoxides usꢀ
ing bis(2,4,6ꢀtrimethylphenyl) sulfoxide (56.4 mg, 0.197 mmol). After 24 h at −68°C this delivered (−)ꢀ45 (11.0 mg, 25%; 23% ee) as a
colorless oil. 1H NMR (300.1 MHz, CDCl3): δ = 1.11 (d, J3‘,2’ = 5.4 Hz, 3 H, 3‘ꢀH3), 1.13 (d, J3‘‘,2’ = 5.7 Hz, 3 H, 3‘‘ꢀH3), 2.17ꢀ2.27 (m, 1
H, 2‘ꢀH superimposed by singlet of 4ꢀCH3), 2.27 (s, 3 H, 4ꢀCH3), 2.50 (dd, J1‘ꢀA,1‘ꢀB = 13.0 Hz, J1‘ꢀA,2‘ = 8.8 Hz, 1 H, 1‘ꢀHA superimposed
by singlet of 2ꢀ and 6ꢀCH3), 2.54 (s, 6 H, 2ꢀ and 6ꢀCH3), 3.27 (dd, J1‘ꢀB,1‘ꢀA = 13.4 Hz, J1‘ꢀB,2‘ = 5.0 Hz, 1 H, 1‘ꢀHB), 6.85 ppm (s, 2 H, 3ꢀ
and 5ꢀH). The preceding data are consistent with those reported in the literature.58 The ee was determined by chiral HPLC (Chiralpak ADꢀ
20
365
20
436
20
546
[
α
]
[
α
]
[ ]
α
H, nꢀheptane/iꢀPrOH 97:3, 1 mL/min, λdetector = 265 nm): tr(1) = 11.33 min, tr(2) = 12.61 min.
= −107.3,
= −73.5,
= −32.9,
20
578
20
589
[
α
]
α
[ ]
= −26.7,
= −22.2 (c = 0.80 in EtOH; the respective sample had 23% ee).
Isobutyl (4-Phenylphenyl) Sulfoxide (46): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfox-
ides using bis(4ꢀphenylphenyl) sulfoxide (101 mg, 0.286 mmol) with iꢀBu2Mg (0.80 in Et2O, 0.20 mL,
M
0.16 mmol, 0.55 equiv.) within 1 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 27ꢀ48)
delivered racꢀ46 (64.3 mg, 87%) as a colorless solid (mp. = 56ꢀ57°C). The asymmetric synthesis followed
the Procedure for the Asymmetric Sulfinylations of Dialkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using bis(4ꢀ
phenylphenyl) sulfoxide (139.3 mg, 0.393 mmol). After 1 h this delivered (S)ꢀ(−)ꢀ46 (87.8 mg, 87%; 94% ee) as a colorless solid (mp. =
56ꢀ57°C). 1H NMR (400.1 MHz, CDCl3): δ = 1.09 (d, J3‘‘,2‘‘ = 6.9, 3 H, 3‘‘ꢀH3), 1.18 (d, J3‘‘‘,2‘‘ = 6.5 Hz, 3 H, 3‘‘‘ꢀH3), 2.27 (mc, 1 H, 2‘‘ꢀ
H), 2.52 (dd, J1‘‘ꢀA,1‘‘ꢀB = 12.9 Hz, J1‘‘ꢀA,2‘‘ = 9.2 Hz, 1 H, 1‘‘ꢀHA), 2.87 (dd, J1‘‘ꢀB,1‘‘ꢀA = 13.0 Hz, J1‘‘ꢀB,2‘‘ = 5.0 Hz, 1 H, 1‘‘ꢀHB), 7.37ꢀ7.42
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(m, 1 H, 4‘ꢀH), 7.44ꢀ7.49 (m, 2 H, 2 × 2‘ꢀH), 7.59ꢀ7.62 (m, 2 H, 2 × 3‘ꢀH), AA’BB‘ signal with signal centers at δA = 7.70 and δB = 7.74
ppm (4 H, 2 × 2ꢀH und 2 × 3ꢀH). 13C NMR (100.6 MHz, CDCl3): δ = 21.8 (Cꢀ3‘‘‘), 22.9 (Cꢀ3‘‘), 24.3 (Cꢀ2‘‘), 67.7 (Cꢀ1‘‘), 124.5 (Cꢀ2),
127.3 (Cꢀ2‘*), 128.1 (Cꢀ3), 128.2 (Cꢀ4‘), 129.1 (Cꢀ3‘*), 140.0, 143.6, 144.1 ppm (Cꢀ1, Cꢀ4, and Cꢀ1’); *assignments interchangeable. IR
1
2
3
4
(CDCl3): ν̃ = 3280, 3055, 3030, 2955, 2925, 2855, 2410, 2045, 1665, 1595, 1480, 1465, 1385, 1370, 1240, 1090, 1040, 1005, 840, 810,
5
6
7
8
760, 720 700, 655 cmꢀ1. HRMS (CI, NH4Cl): C16H19SO (M + H+), calculated: 259.11566, found: 259.11550 (∆ = −0.6 ppm). Elemental
analysis: calculated (%) for C16H18SO (258.4 g/mol): C 74.38, H 7.02, S 12.41; found: C 74.23, H 6.77, S 12.06. The ee was determined by
20
365
α
[ ]
chiral HPLC (Chiralpak ADꢀH, nꢀheptane/iꢀPrOH 90:10, 1 mL/min, 22°C, λdetector = 204 nm): tr(S) = 12.90 min, tr(R) = 16.83 min.
=
9
20
436
20
546
20
578
20
589
[
α
]
[
α
]
[
α
]
α
[ ]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
−1512.3,
= −819.5,
= −410.7,
= −352.5,
= −334.7 (c = 1.16 in EtOH; the respective sample had 94% ee). The absoꢀ
lute configuration of the title compound was elucidated by Xꢀray crystal structure analysis (Figure 1). Detailed information are given in
Section 2 of the “Supporting Information − Spectra and HPLC Traces. XꢀRay Details”.
Figure 2: ORTEP plot of the crystal structure of sulfoxide (−)ꢀ46 (at 100 K).59 The unit cell contains two crystallographically independent
molecules.
Isobutyl (4-Methoxyphenyl) Sulfoxide (47): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides
using bis(4ꢀmethoxyphenyl) sulfoxide (130 mg, 0.496 mmol) with iꢀBu2Mg (0.80
M in Et2O, 0.68 mL,
0.54 mmol, 1.1 equiv.) within 2 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 55:45, F. 17ꢀ35) delivꢀ
ered racꢀ47 (70.8 mg, 67%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Di-
alkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using bis(4ꢀmethoxyphenyl) sulfoxide (51.7 mg, 0.198 mmol). After 24 h at
−68°C this delivered (S)ꢀ(−)ꢀ47 (41.8 mg, 100%; 62% ee) as a colorless oil. 1H NMR (400.1 MHz, CDCl3): δ = 1.06 (d, J3‘,2‘ = 6.7 Hz, 3 H,
3‘ꢀH3), 1.13 (d, J3‘‘,2‘ = 6.5 Hz, 3 H, 3‘‘ꢀH3), 2.17 (mc, 1 H, 2‘ꢀH), 2.44 (dd, J1‘ꢀA,1‘ꢀB = 13.3 Hz, J1‘ꢀA,2‘ = 9.0 Hz, 1 H, 1‘ꢀHA), 2.82 (dd, J1‘ꢀ
B,1‘ꢀA = 12.8 Hz, J1‘ꢀB,2‘ = 5.5 Hz, 1 H, 1‘ꢀHB), 3.85 (s, 3 H, OꢀCH3), AA’BB‘ signal with signal centers at δA = 7.02 and δA = 7.57 ppm (2 ×
2ꢀH and 2 × 3ꢀH). 13C NMR (100.6 MHz, CDCl3): δ = 21.9 (Cꢀ3‘‘), 22.9 (Cꢀ3‘), 24.4 (Cꢀ2‘), 55.8 (OꢀCH3), 67.8 (Cꢀ1‘), 114.9 (Cꢀ2), 126.1
(Cꢀ3), 135.8, 162.1 ppm (Cꢀ1 and Cꢀ4). IR (CDCl3): ν̃ = 3460, 3070, 2960, 2870, 2840, 2425, 2045, 1645, 1595, 1580, 1495, 1465, 1445,
1405, 1385, 1370, 1305, 1251, 1170, 1110, 1090, 1070, 1030, 1005, 830, 810, 795 cmꢀ1. HRMS (CI, NH4Cl): C11H17SO2 (M + H+), calcuꢀ
lated: 213.09493, found: 213.09510 (∆ = +0.8 ppm). Elemental analysis: calculated (%) for C11H16SO2 (212.3 g/mol): C 62.23, H 7.60, S
15.10; found: C 62.11, H 7.55, S 14.94. The ee was determined by chiral HPLC (Chiralpak ADꢀH, nꢀheptane/iꢀPrOH 95:5, 1 mL/min,
20
365
20
436
20
546
20
578
20
589
[
α
]
[
α
]
[
α
]
[
α
]
α
[ ]
22°C, λdetector = 204 nm): tr(R) = 21.00 min, tr(S) = 24.79 min.
= −576.0,
= −284.0,
= −142.5,
= −122.8,
=
−117.0 (c = 1.0 in EtOH; the respective sample had 62% ee). The absolute configuration was assigned by chemical correlation (cf. Supꢀ
porting Information).
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The Journal of Organic Chemistry
Isobutyl (1-Naphthyl) Sulfoxide (48): (−)-Enantiomer and Racemic45
1
2
3
4
5
6
7
8
9
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides using
di(1ꢀnaphthyl) sulfoxide (50.1 mg, 0.166 mmol) with iꢀBu2Mg (0.80
M in Et2O, 0.11 mL, 0.088 mmol, 0.53 equiv.)
within 2 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 18ꢀ25) delivered racꢀ48 (27.8 mg, 72%)
as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkylmagnesium Compounds
by Symmetric Diaryl Sulfoxides using di(1ꢀnaphthyl) sulfoxide (57.5 mg, 0.190 mmol). After 30 Min this delivered (−)ꢀ48 (37.0 mg, 84%;
1
91% ee) as a colorless oil. H NMR (400.1 MHz, CDCl3): δ = 1.06 (d, J3‘,2‘ = 6.8 Hz, 3 H, 3‘ꢀH3), 1.27 (d, J3‘‘,2‘ = 6.6 Hz, 3 H, 3‘‘ꢀH3),
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2.36ꢀ2.46 (m, 1 H, 2‘ꢀH), 2.72ꢀ2.80 (m, 2 H, 1‘ꢀH2), 7.55ꢀ7.61 (m, 2 H, 2 × ArꢀH), 7.65ꢀ7.68 (dd, 3J = 8.2 Hz, 3J = 7.3 Hz, 1 H, 1 × ArꢀH),
7.91ꢀ7.97 (m, 3 H, 3 × ArꢀH), 8.15 ppm (dd, 3J = 7.3 Hz, 4J = 1.2 Hz, 1 H, 1 × ArꢀH). 13C NMR (100.6 MHz, CDCl3): δ = 21.6 (Cꢀ3‘), 22.9
(Cꢀ3‘‘), 24.6 (Cꢀ2‘), 66.7 (Cꢀ1‘), 121.5, 122.8, 125.9, 126.7, 127.3, 128.9, 129.2, 131.1, 133.6, 140.8 ppm. IR (CDCl3): ν̃ = 3055, 2960,
2870, 1590, 1505, 1465, 1400, 1380, 1345, 1260, 1170, 1140, 1040, 965, 860, 800, 770, 740, 665, 560 cmꢀ1. HRMS (CI, NH4Cl):
+
C14H17SO (M + H+), calculated: 233.10001, found: 233.10000 (∆ = −0.1 ppm) and C14H20SNO (M + NH4 ), calculated: 250.12656, found:
250.12660 (∆ = +0.2 ppm). The ee was determined by chiral HPLC (Chiralcel ODꢀH, nꢀheptane/iꢀPrOH 90:10, 1 mL/min, λdetector = 209
20
365
20
436
20
546
20
578
20
589
[
α
]
[
α
]
[
α
]
[
α
]
α
[ ]
nm): tr(1) = 5.29 min, tr(2) = 24.19 min.
EtOH; the respective sample had 91% ee).
= −1512.3,
= −819.5,
= −410.8,
= −352.5,
= −334.7 (c = 1.10 in
Isobutyl (2-Naphthyl) Sulfoxide (49): (−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides
using di(2ꢀnaphthyl) sulfoxide (101 mg, 0.333 mmol) with iꢀBu2Mg (0.8 in Et2O, 0.23 mL, 0.18 mmol, 0.55
M
equiv.) within 3 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 21ꢀ34) delivered racꢀ49
(52.1 mg, 67%) as a colorless solid (mp. = 59ꢀ60°C). The asymmetric synthesis followed the Procedure for the
Asymmetric Sulfinylations of Dialkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using di(2ꢀnaphthyl) sulfoxide (58.1 mg,
1
0.192 mmol). After 5.5 h this delivered (−)ꢀ49 (32.8 mg, 74%; 42% ee) as a colorless solid (mp. = 59ꢀ60°C). H NMR (400.1 MHz,
CDCl3): δ = 1.09 (d, J3‘,2‘ = 6.9 Hz, 3 H, 3‘ꢀH3), 1.19 (d, J3‘‘,2‘ = 6.9 Hz, 3 H, 3‘‘ꢀH3), 2.23ꢀ2.33 (m, 1 H, 2‘ꢀH), 2.57 (dd, J1‘ꢀA.,1‘ꢀB = 13.1
Hz, J1‘ꢀA,2‘ = 8.4 Hz, 1 H, 1‘ꢀHA), 2.88 (dd, J1‘ꢀB,1‘ꢀA = 13.1 Hz, J1‘ꢀB,2‘ = 4.7 Hz, 1 H, 1‘ꢀHB), 7.58ꢀ7.61 (m, 3 H, 3 × ArꢀH), 7.89ꢀ7.99 (m, 3
H, 3 × ArꢀH), 8.20 ppm (br. s, 1 H, 1ꢀH). 13C NMR (100.6 MHz, CDCl3): δ = 21.9 (Cꢀ3‘), 23.0 (Cꢀ3‘‘), 24.4 (Cꢀ2‘), 67.5 (Cꢀ1‘), 120.0,
124.6 (Cꢀ1), 127.4, 127.8, 128.2, 128.6, 129.6, 133.0, 134.6, 142.0 ppm (Cꢀ2). IR (CDCl3): ν̃ = 3470, 3055, 2960, 2930, 2900, 2870, 1430,
2035, 1625, 1590, 1505, 1465, 1390, 1385, 1370, 1345, 1265, 1235, 1195, 1170, 1135, 1110, 1080, 1035, 945, 905, 860, 810, 765, 750 cmꢀ
1. HRMS (CI, NH4Cl): C14H17SO (M + H+), calculated: 233.10001, found: 233.10000 (∆ = −0.1 ppm). Elemental analysis: calculated (%)
for C14H16SO (232.3 g/mol): C 72.37, H 6.94, S 13.80; found: C 72.24, H 6.79, S 13.63. The ee was determined by chiral HPLC (Chiralcel
20
365
20
436
20
546
[
α
]
[
α
]
[ ]
α
ODꢀ3, nꢀheptane/EtOH 97:3, 1 mL/min, λdetector = 209 nm): tr(1) = 7.97 min, tr(2) = 8.64 min.
= −344.3,
= −204.1,
=
20
578
20
589
[
α
]
α
[ ]
−103.5,
= −89.3,
= −73.7 (c = 1.78 in EtOH; the respective sample had 42% ee).
(2-Bromophenyl) Ethyl Sulfoxide (52): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides using
bis(2ꢀbromophenyl) sulfoxide (53.2 mg, 0.148 mmol) with Et2Mg (0.16 in Et2O, 0.51 mL, 0.081 mmol, 0.55 equiv.)
M
within 1.25 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 18ꢀ27) delivered racꢀ52 (17.0 mg, 49%)
as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Dialkyl-
magnesium Compounds by Symmetric Diaryl Sulfoxides using bis(2ꢀbromophenyl) sulfoxide (70.9 mg, 0.197 mmol). After 10 s this delivꢀ
ered (S)ꢀ(−)ꢀ52 (31.9 mg, 69%; 89% ee) as a colorless oil. 1H NMR (300.1 MHz, CDCl3): δ = 1.25 (dd, J2‘,1‘ꢀA = J2‘,1‘ꢀB = 7.3 Hz, 3 H, 3‘ꢀ
H3), AB signal (δA = 2.85, δB = 3.13, JA,B = 13.6 Hz, A part additionally split by q, J1‘ꢀA,2‘ = 7.4 Hz, 1‘ꢀHA; B part additionally split by q,
J1‘ꢀB,2‘ = 7.4 Hz, 1‘ꢀHB), 7.36 (ddd, 3J = 8.8 Hz, 3J = 7.7 Hz, 4J = 1.7 Hz, 4ꢀ or 5ꢀH), 7.53ꢀ7.58 (m, 2 H, 2 × ArꢀH), 7.86 ppm (dd, 3J = 8.1
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4
Hz, J = 1.8 Hz, 3ꢀ or 6ꢀH). The preceding data are consistent with those reported in the literature.60 The ee was determined by chiral
1
2
3
4
20
365
α
[ ]
HPLC (Chiralcel OJꢀH, nꢀheptane/EtOH 300:1, 1.0 mL/min, λdetector = 250 nm): tr(S) = 29.23 min, tr(R) = 33.41 min.
= −1090.0,
20
436
20
546
20
578
20
589
[
α
]
[
α
]
[
α
]
α
[ ]
= −562.9,
= −290.6,
= −250.8,
= −239.5 (c = 0.62 in EtOH; the respective sample had 89% ee). The absolute conꢀ
figuration was determined by chemical correlation (cf. Supporting Information).
5
6
7
8
(2-Bromophenyl) Butyl Sulfoxide (53): (S)-(−)-Enantiomer and Racemic45
9
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides usꢀ
ing bis(2ꢀbromophenyl) sulfoxide (70.9 mg, 0.197 mmol) with Bu2Mg (0.69 in Et2O, 0.14 mL, 0.10 mmol, 0.51
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
M
equiv.) within 30 min. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 13ꢀ20) delivered racꢀ53
(25.5 mg, 50%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinyla-
tions of Dialkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using bis(2ꢀbromophenyl) sulfoxide (70.8 mg, 0.197 mmol). After
10 s this delivered 10 s (S)ꢀ(−)ꢀ53 (40.4 mg, 79%; 86% ee) as a colorless oil. 1H NMR (400.1 MHz, CDCl3): δ = 0.95 (t, J4‘,3‘ = 7.3 Hz, 3
H, 4‘ꢀH3), 1.39ꢀ1.50 (m, 2 H, 3‘ꢀH2), 1.51ꢀ1.67 (m, 1 H, 2‘ꢀHA), 1.85ꢀ1.91 (m, 1 H, 2‘ꢀHB), AB signal (δA = 2.76, δB = 3.09, JA,B = 14.5 Hz,
A part additionally split by dd, J1‘ꢀA,2‘ꢀA = 9.5 Hz, J1‘ꢀA,2‘ꢀB = 5.0 Hz, 1‘ꢀHA; B part additionally split by dd, J1‘ꢀB,2‘ꢀA = 9.6 Hz, J1‘ꢀB,2‘ꢀB = 6.7
Hz, 1‘ꢀHB), 7.36 (ddd, 3J = 7.8 Hz, 3J = 7.5 Hz, 4J = 1.8 Hz, 1 H, 4ꢀor 5ꢀH), 7.54ꢀ7.58 (m, 2 H, 2 × ArꢀH), 7.88 ppm (dd, 3J = 8.1 Hz, 4J =
1.8 Hz, 1 H, 3ꢀ or 6ꢀH). 13C NMR (100.6 MHz, CDCl3): δ = 13.8 (Cꢀ4‘), 21.9 (Cꢀ3‘), 24.3 (Cꢀ2‘), 54.7 (Cꢀ1‘), 118.7 (Cꢀ2*), 126.7 (Cꢀ3 or
Cꢀ6), 128.5, 132.2 (Cꢀ4 or Cꢀ5), 133.0, 143.9 ppm (Cꢀ1*); *assignments interchangeable. IR (CDCl3): ν̃ = 3555, 3060, 2960, 2930, 2870,
2385, 1965, 1565, 1445, 1430, 1380, 1245, 1160, 1095, 1045, 1015, 755, 715 cmꢀ1. HRMS (CI, NH4Cl): C10H14SOBr (M + H+), calculated:
260.99487, found: 260.99480 (∆ = −0.3 ppm). The ee was determined by chiral HPLC (Chiralcel OJꢀH, nꢀheptane/EtOH 98:2, 1 mL/min,
20
365
20
436
20
546
20
578
20
589
[
α
]
[
α
]
[
α
]
[
α
]
[α]
λdetector = 250 nm): tr(S) = 7.96 min, tr(R) = 9.00 min.
= −1207.1,
= −632.3,
= −330.6,
= −284.5,
= −270.0 (c =
0.31 in EtOH; the respective sample had 86% ee). The absolute configuration was assigned by chemical correlation (cf. Supporting Inforꢀ
mation).
(2-Bromophenyl) Isobutyl Sulfoxide (54): (S)-(−)-Enantiomer and Racemic45
The racemic synthesis44 followed the General Procedure for the Preparation of Racemic Alkyl Aryl Sulfoxides usꢀ
ing bis(2ꢀbromophenyl) sulfoxide (100 mg, 0.278 mmol) with iꢀBu2Mg (0.80
M in Et2O, 0.19 mL, 0.15 mmol, 0.55
equiv.) within 2 h. Flash chromatography on silica gel40 (cꢀC6H12:EtOAc 80:20, F. 10ꢀ15) delivered racꢀ54 (58.9 mg,
81%) as a colorless oil. The asymmetric synthesis followed the Procedure for the Asymmetric Sulfinylations of Di-
alkylmagnesium Compounds by Symmetric Diaryl Sulfoxides using bis(2ꢀbromophenyl) sulfoxide (70.9 mg, 0.197 mmol). After 1 h this
delivered (S)ꢀ(−)ꢀ54 (42.9 mg, 83%; 53% ee) as a colorless oil. 1H NMR (400.1 MHz, CDCl3): δ = 1.07 (d, J3‘,2‘ = 7.3 Hz, 3 H, 3‘ꢀH3), 1.23
(d, J3‘‘,2‘ = 8.0 Hz, 3 H, 3‘‘ꢀH3), 2.39 (mc, 1 H, 2‘ꢀH), 2.60 (dd, J1‘ꢀA,1‘ꢀB = 12.8 Hz, J1‘ꢀA,2‘ = 4.2 Hz, 1 H, 1‘ꢀHA), 2.91 (dd, J1‘ꢀB,1‘ꢀA = 12.9
Hz, J1‘ꢀB,2‘ = 10.4 Hz, 1 H, 1‘ꢀHB), 7.35 (ddd, 3J = 9.6 Hz, 3J = 7.4 Hz, 4J = 1.6 Hz, 1 H, 4ꢀ or 5ꢀH), 7.54ꢀ7.58 (m, 2 H, 2 × ArꢀH), 7.91 ppm
(dd, 3J = 7.6 Hz, 4J = 1.8 Hz, 1 H, 3ꢀ or 6ꢀH). 13C NMR (100.6 MHz, CDCl3): δ = 21.4 (Cꢀ3‘‘), 23.0 (Cꢀ3‘), 24.5 (Cꢀ2‘), 65.6 (Cꢀ1‘), 118.6
(Cꢀ2*), 126.3 (Cꢀ3 or Cꢀ6), 128.7, 132.2 (Cꢀ4 or Cꢀ6), 133.0, 144.7 ppm (Cꢀ1*); *assignments interchangeable. IR (CDCl3): ν̃ = 3665,
3260, 2960, 2925, 2870, 2405, 195, 1565, 1465, 1445, 1400, 1385, 1370, 1145, 1095, 1070, 1050, 1015, 755, 715 cmꢀ1. HRMS (CI,
NH4Cl): C10H14SOBr (M + H+), calculated: 260.99487, found: 260.99490 (∆ = +0.1 ppm). The ee was determined by chiral HPLC (Chiralꢀ
20
365
20
436
20
546
[
α
]
[
α
]
[ ]
α
cel ODꢀH, nꢀheptane/EtOH 97:3, 1 mL/min, λdetector = 210 nm): tr(R) = 8.32 min, tr(S) = 9.49 min.
= −888.8,
= −466.2,
=
20
578
20
589
[
α
]
α
[ ]
−243.8,
= −210.5,
= −200.1 (c = 1.06 in EtOH; the respective sample had 53% ee). The absolute configuration was assigned by
chemical correlation (cf. Supporting Information).
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ꢀ ASSOCIATED CONTENT
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Supporting Information
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Detailed procedures for the configurational assignments, copies of NMR spectra, copies of HPLC traces, and Xꢀray data. This material is
available free of charge via the Internet at http://pubs.acs.org
8
9
ꢀ AUTHOR INFORMATION
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Corresponding Author
* reinhard.brueckner@organik.chemie.uniꢀfreiburg.de
ꢀ ACKNOWLEDGMENT
Financial support by the Deutsche Forschungsgemeinschaft is gratefully acknowledged.
ꢀ REFERENCES
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lines if the O atom is above the drawing plane; for reinforcing the 3D impression, we attach a hatched bond to the sulfur atom of such a sulfoxide
for indicating that there is a lone pair below the drawing plane. When the S=O bond of an asymmetric disulfoxide is oppositely configured, we deꢀ
pict the S=O bond by one a bond and a parallel hatched bond for making clear that the O atom lies below the drawing plane; for reinforcing the 3D
impression, we attach a wedged bond to such a sulfur atom for emphasizing that there is a lone pair above the drawing plane..
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(14) Cardellicchio, C.; Fiandese, V.; Naso, F.; Scilimati, A. Tetrahedron Lett. 1992, 33, 5121ꢀ5124.
(15) Capozzi, M. A. M.; Cardellicchio, C.; Fracchiola, G.; Naso, F.; Tortorella, P. J. Am. Chem. Soc. 1999, 121, 4708ꢀ4709.
(16) Cardellicchio, C.; Iacuone, A.; Naso, F.; Tortorella, P. Tetrahedron Lett. 1996, 37, 6017ꢀ6020.
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(17) Capozzi, M. A. M.; Cardellicchio, C.; Naso, F.; Tortorella, P. J. Org. Chem. 2000, 65, 2843ꢀ2846.
(18) Capozzi, M. A. M.; Cardellicchio, C.; Naso, F.; Rosito, V. J. Org. Chem. 2002, 67, 7289ꢀ7294.
(19) Hoffmann, R. W.; Nell, P. G. Angew. Chem. 1999, 111, 354ꢀ355; Angew. Chem. Int. Ed. 1999, 38, 338ꢀ340.
(20) (a) Hoffmann, R. W.; Hölzer, B.; Knopff, O.; Harms, K. Angew. Chem. 2000, 112, 3206ꢀ3207; Angew. Chem. Int. Ed. 2000, 39, 3072ꢀ3074.
(b) Hoffmann, R. W.; Nell, P. G.; Leo, R.; Harms, K. Chem. Eur. J. 2000, 6, 3359ꢀ3365.
(21) Rayner, P. J.; O’Brien, P.; Horan, R. A. J. J. Am. Chem. Soc. 2013, 135, 8071ꢀ8077.
Complete chirality transfer was deꢀ
scribed for the sulfinylation of methylꢀ
and propylmagnesium halide by sulꢀ
foxide 56: ref.14.
(22)
O
Br
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11
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19
20
21
22
23
24
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28
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33
34
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45
46
47
48
49
50
51
52
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55
56
57
58
59
60
S
*
56 (80% ee)
(23) (a) First sulfoxide/Mg exchange: Nokami, J.; Kunieda, N.; Kinoshita, M. Chem. Lett. 1977, 249ꢀ252. (b) First sulfoxide/Mg exchange in a
racemic alkyl aryl sulfoxide: Hojo, M.; Masuda, R.; Saeki, T.; Fujimoi, K.; Tsutsumi, S. Synthesis 1977, 789ꢀ791. (c) First sulfoxide/Mg exchange
in aryl heteroaryl sulfoxides: Furukawa, N.; Shibutani, T.; Matsumura, K.; Fujihara, H.; Oae, S. Tetrahedron Lett. 1986, 27, 3899ꢀ3902. (d) First
sulfoxide/Mg exchange in diaryl sulfoxides with RMgHal: Furukawa, N.; Shibutani, T.; Fujihara, H. Tetrahedron Lett. 1987, 28, 2727ꢀ2730. (e)
First sulfoxide/Mg exchanges in diaryl sulfoxides with iꢀPrMgCl ꢁ LiCl for making functionalized arylmagnesium reagents: Rauhut, C. B.; Melzig,
L.; Knochel, P.; Org. Lett. 2008, 10, 3891ꢀ3894.
(24) Boymond, L.; Rottländer, M.; Cahiez, G.; Knochel, P. Angew. Chem. 1998, 110, 1801ꢀ1803; Angew. Chem. Int. Ed. 1998, 37, 1701ꢀ1703.
(25) T. Hampel, S. Ruppenthal, D. Sälinger R. Brückner, Chem. Eur. J. 2012, 18, 3136ꢀ3140.
N
OYORI et al. elucidated the
(26)
structure of the Li2ꢀ(S)ꢀBINOLate
complex 57 of Et2Mg in THF or in
DME: Noyori, R., Suga, S., Kawai,
K., Okada, S., Kitamura, M. Pure
Appl. Chem. 1988, 60, 1597ꢀ1606.
Since our reagents consisted of
Li2ꢀ(S)ꢀBINOLate and R2Mg (inꢀ
cluding Et2Mg) we consider “Li2ꢀ(S)ꢀBINOLate ꢁ R2Mg” as plausible active reagents in our sulfinylation reactions.
(27) The quotation marks shall indicate that we used a solvent mixture, in which THF was the major but not the only ingredient. This is because
nꢀBuLi was used as a solution in hexane and the dialkylmagnesiums were used as solutions in Et2O.
(28) To the best of our knowledge, these are the first sulfoxide/magnesium exchange reactions in diaryl sulfoxides, which work with organoꢀ
magensium reagents containing primary alkyl groups. All previous sulfoxide/magnesium exchange reactions in diaryl sulfoxides, of which we are
aware, were effected with PhMgBr [(a) N. Furukawa, T. Shibutani, K. Matsumura, H. Fujihara, S. Oae, Tetrahedron Lett. 1986, 27, 3899ꢀ3902;
(b) T. Satoh, Y. Kitoh, K. Onda, K. Yamakawa, Tetrahedron Lett. 1993, 34, 2331ꢀ2334], with iPr−MgCl • LiCl [(c) C. B. Rauhut, L. Melzig, P.
Knochel, Org. Lett. 2008, 10, 3891ꢀ3894; (d) L. Melzig, C. B. Rauhut, P. Knochel, Synthesis 2009, 1041ꢀ1048; (e) L. Melzig, C. B. Rauhut, P.
Knochel, Chem. Comm. 2009, 24, 3536ꢀ3538; (f) L. Melzig, C. B. Rauhut, N. NarediꢀRainer, P. Knochel, Chemistry 2011, 17, 5362ꢀ5372] or with
iPr2Mg (ref.25).
(29) The sulfinylations of iꢀBu2Mg giving 45 or 47 and the sulfinylation of Bn2Mg were effected at −68°C and +22°C, respectively.
(30) The yield and ee of the 2,4ꢀdimethylphenyl isopropyl sulfoxide (S)ꢀ(−)ꢀ19 shown in Scheme 1 did not change when that compound was
kept under the reaction conditions unnecessarily long.25 This means that (S)ꢀ(−)ꢀ19 sulfinylated neither residual iꢀPr2Mg nor the stoichiometric byꢀ
product 2,4ꢀdimethylphenyl isopropyl magnesium.
(31) The sulfinylation of Bn2Mg had to be carried out at +22°C in order to achieve any conversion at all.
(32) The 32 nonꢀracemic sulfoxides, which emerged from the asymmetric sulfinylations of the present study are levorotatory. This consistency
is paralleled by the consistency of attributing an (S)ꢀconfiguration to 21 of these sulfoxides by independent evidence. Details: Supporting Inforꢀ
mation.
(33) When we sulfinylated iꢀPr2Mg asymmetrically under almost exactly the conditions specified in Scheme 1 the ee of the sulfoxide (S)ꢀ(−)ꢀ19
did not change and the yield did not change more than marginally when we varied the reaction time between 10 min and 3 h.25 In contrast some
sulfinylations of our present study revealed ee and yield variations with time, e. g.: • The sulfinylation of Et2Mg delivering the sulfoxide (S)ꢀ(−)ꢀ29
rendered 71% ee and 77% yield after 2 min (= experiment reported in Scheme 3) but 31% ee and 34% yield after 30 min (not mentioned elsewhere
in this manuscript); the followꢀup reaction, which occurred in between, thus consumed (S)ꢀ(−)ꢀ29 faster than its (R)ꢀenantiomer. • The sulfinylation
of Et2Mg delivering the sulfoxide (S)ꢀ(−)ꢀ30 rendered 90% yield and 69% ee after 10 s (not mentioned elsewhere in this manuscript) and 39% yield
and 94% ee after 30 min (= experiment reported in Scheme 3); the followꢀup reaction, which occurred in between, thus consumed (S)ꢀ(−)ꢀ30 more
slowly than its (R)ꢀenantiomer. • The sulfinylation of Et2Mg delivering the sulfoxide (S)ꢀ(−)ꢀ32 rendered 82% yield and 70% ee after 10 s (= exꢀ
periment reported in Scheme 3) and 11% yield and 89% ee after 30 min (not mentioned elsewhere in this manuscript); the followꢀup reaction,
which occurred in between, thus consumed (S)ꢀ(−)ꢀ32 more slowly than its (R)ꢀenantiomer.
(34) (a) H2C=C(−Oꢁ)Ph: ref.23a. (b) CHRCl + CH2Br: ref.23b. R1HalC=C(−Oꢁ)R2: (c) Satoh, T.; Onda, K.ꢀi.; Itoh, N.; Yamakawa, K. Tetrahe-
dron Lett. 1991, 32, 5599ꢀ5600. (d) Kopp, F.; Sklute, G.; Marek, I.; Knochel, P. Org. Lett. 2005, 7, 3789ꢀ3791. R1R2C=C=Nꢁ: (e) Nath, D.;
Fleming, F. Angew. Chem. 2011, 123, 11994ꢀ11997; Angew. Chem. Int. Ed. 2011, 50, 11790ꢀ11793. (f) Nath, D.; Fleming, F. Chem. Eur. J. 2013,
19, 2023ꢀ2029.
(35) Freeman, F.; Kim, D. S. H. L. J. Org. Chem. 1992, 57, 1722ꢀ1727.
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(36) (a) Satoh, T.; Takano, K. Tetrahedron 1996, 52, 2349ꢀ2358. (b) Satoh, T.; Kurihara, T.; Fujita, K. Tetrahedron 2001, 57, 5369ꢀ5375. (c)
Satoh, T.; Kondo, A.; Musashi, J. Tetrahedron 2004, 60, 5453ꢀ5460.
(37) Satoh, T.; Mizu, Y.; Kawashima, T.; Yamakawa, K. Tetrahedron 1995, 51, 703ꢀ710.
(38) Sulfoxideꢀlithium exchanges: (a) Lockard, J. P.; Schroeck, C. W.; Johnson, C. R. Synthesis 1973, 485ꢀ486. (b) Durst, T.; LeBelle, M. J.;
Van den Elzen, R.; Tin, K.ꢀC. Can. J. Chem. 1974, 52, 761ꢀ766. (c) Satoh, T.; Kaneko, Y.; Yamakawa, K. Tetrahedron Lett. 1986, 27, 2379ꢀ2382.
(d) Zhao, S. H.; Kagan, H. B. Tetrahedron 1987, 43, 5135ꢀ5144. (e) Satoh, T.; Itoh, N.; Onda, K.ꢀi.; Kitoh, Y.; Yamakawa, K. Tetrahedron Lett.
1992, 33, 1483ꢀ1484.
(39) Sulfoxideꢀzinc exchanges: (a) Ref.34e. (b) Ref.34f
.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
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57
58
59
60
(40) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923ꢀ2925.
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(44) The racemic sulfoxides of this study were required for optimizing enantiomer separation by chiral HPLC. They were prepared by sulfinylatꢀ
ing a given dialkylmagnesium compound with the appropriate diarylsulfoxide in the absence of enantiomerically pure Li2ꢀBINOLATE. There was
no emphasis on yield optimization because we considered any such synthesis as “accomplished” after having isolated a sufficient amount of the reꢀ
spective sulfoxide. We attempted each sulfinylation first under “conditions A” of the ensuing scheme. If more forcing conditions seemed to be
called for, we tried “conditions B” and finally “conditions C”.
conditions A:
saving Alkyl2Mg and 20:
Alkyl2Mg (0.50−0.55 equiv.),
THF
or conditions B:
assuring the exchange
with more Alkyl2Mg:
O
S
O
S
Ar
Ar
Ar
Alkyl
Alkyl2Mg (1.1−1.2 equiv.),
(racemic)
THF
or conditions C:
assuring the exchange
with more Alkyl2Mg and with 20:
Alkyl2Mg (1.2 equiv.), or more,
rac-20 (1.5 equiv. or more), THF
(45) The yield of this sulfoxide was calculated such as to account for the expected sulfinylation Ar−S(=O)−Ar + Alkyl−Mg−Alkyl →
Ar−S(=O)−Alkyl + Ar−Mg−Alkyl plus − when employing only 0.50−0.55 equiv. of Alkyl−Mg−Alkyl − the unexpected overꢀreaction
Ar−S(=O)−Ar + Ar−Mg−Alkyl → Ar−S(=O)−Alkyl + Ar−Mg−Ar. The latter materialized repeatedly, as indicated, e. g., by a 82% yield of sulfoxꢀ
ide applying “conditions A”.
(46) Malik, P.; Chakraborty, D. Tetrahedron Lett. 2012, 53, 5652ꢀ5655.
(47) Akazome, M.; Ueno, Y.; Ooiso, H.; Ogura, K. J. Org. Chem. 2000, 65, 68ꢀ76.
(48) This reaction was carried out in 20 mL THF.
(49) This signal can be interpreted as a “d of mc”: the doublet would be caused by the coupling of 5ꢀH to 6ꢀH and the mc by the coupling of 5ꢀH
to 3ꢀH.
(50) Blakemore, P. R.; Burge, M. S. J. Am. Chem. Soc. 2007, 129, 3068ꢀ3069.
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(58) Han, Z.; Krishnamurthy, D.; Grover, P.; Fang, Q. K.; Su, X.; Wilkinson, H. S.; Lu, Z.ꢀH.; Magiera, D.; Senanayake, C. H. Tetrahedron
2005, 61, 6386ꢀ6408.
(59) The crystallographic data of sulfoxide (−)ꢀ46 are contained in CCDC 1016608. They can be obtained free of charge from the Cambridge
Crystallographic Data Centre via the link www.ccdc.cam.ac.uk/data_request/cif.
(60) Chakraborty, D.; Malik, P.; Goda, V. K. Appl. Organomet. Chem. 2012, 26, 21ꢀ26.
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