Thioboration of α,β-unsaturated ketones and aldehydes toward the synthesis of β-sulfido carbonyl compounds

Article abstract of DOI:10.1021/jo5026354

Herein a direct β-sulfido carbonyl compound synthesis by the easy activation of RS-Bpin reagents with α,β-unsaturated ketones and aldehydes is reported. This convenient methodology can be performed at room temperature with no other additives. The key poin

Full text of DOI:10.1021/jo5026354

Article
pubs.acs.org/joc
Thioboration of α,β-Unsaturated Ketones and Aldehydes toward the
Synthesis of β‑Sulfido Carbonyl Compounds
Marc G. Civit,† Xavier Sanz,†,‡ Christopher M. Vogels,§ Jonathan D. Webb,§ Stephen J. Geier,§
Andreas Decken,∥ Carles Bo,*,‡ Stephen A. Westcott,*,§ and Elena Fernandez*,†
́
†Dept. Química Física i Inorgan
̀
ica, Universitat Rovira i Virgili, C/Marcel·lí Domingo s/n, 43007 Tarragona, Spain
‡Institute of Chemical Research of Catalonia (ICIQ), Avda. Països Catalans, 16, 43007 Tarragona, Spain
§Department of Chemistry and Biochemistry, Mount Allison University, Sackville, New Brunswick E4L 1G8, Canada
∥Department of Chemistry, University of New Brunswick, Fredericton, New Brunswick E3B 5A3, Canada
S
* Supporting Information
ABSTRACT: Herein a direct β-sulfido carbonyl compound
synthesis by the easy activation of RS−Bpin reagents with α,β-
unsaturated ketones and aldehydes is reported. This
convenient methodology can be performed at room temper-
ature with no other additives. The key point of this reactivity is
based on the Lewis acidic properties of the boryl unit of the
RS−Bpin reagent interacting with the CO oxygen.
Consequently, the SR unit becomes more nucleophilic and
promotes the 1,4- versus the 1,2-addition, as a function of the involved substrate. The thioborated products can be further
transformed into β-sulfido carbonyl compounds by addition of MeOH.
alternative synthesis toward β-sulfido carbonyl compounds,
(Scheme 1).
INTRODUCTION
■
The synthesis of β-sulfido carbonyl compounds and related
compounds has been principally covered by the conjugate
addition of thiols to α,β-unsaturated carbonyl compounds.1
Metal catalysts and organocatalysts are required to activate both
the substrate and the reagent and promote the formation of the
Cβ−S bond in a precise way,2 particularly with asymmetric
induction.3 Despite the mild nucleophilicity of the sulfur moiety
in thiol reagents,4 the reaction conditions frequently lead to the
formation of byproducts from side reactions such as self-
condensation, polymerization, or rearrangements.5 Pointing at
the nature of the sulfur reagent, we focused our attention on
thiodioxaborolanes, since they are easy to prepare6 and the
push−pull effect of the boryl unit might enhance the
nucleophilic character of the interelement.7 In that context,
we have previously observed that alkoxides interact intermolec-
ularly with pinB−Bpin and pinB−NR2 bonds to deliver the
Bpin or NR2 moieties with enhanced nucleophilicity toward
activated and nonactivated alkenes.8,9 More recently, we have
been able to observe that PhSe−Bpin can also be activated by
Lewis bases, but the most remarkable circumstance is that the
electron rich CO of α,β-unsaturated ketones and aldehydes
can activate the phenylselenium borane reagent, without the
need for external Lewis bases or additives. This face to face
reactivity is unusual, and theoretical calculations have
demonstrated that this activation is more likely in B−E when
E = Se > S > O.10 With these data in mind, we became
determined to demonstrate the efficient thioboration on α,β-
unsaturated ketones and aldehydes that does not need catalysts
or drastic reaction conditions and eventually provide an
Scheme 1. Postulated Substrate-Reagent Interaction To
Promote 1,4- and 1,2-Thioboration and Protic Work-up Step
towards β-Sulfido Carbonyl Compounds
RESULTS AND DISCUSSION
■
With the aim of activating PhS−Bpin (1)11 and selectively
transfering the PhS moiety to activated olefins, we first
attempted the thioboration of 4-phenyl-3-buten-2-one (2).
The reaction conditions entail substrate 2 (0.1 mmol scale)
with an excess of 1 (for complete conversion) in 2 mL of THF,
Received: November 21, 2014
© XXXX American Chemical Society
A
DOI: 10.1021/jo5026354
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
at room temperature. Within 16 h, the 1,4-thioborated
intermediate (2a) was observed in 83% conversion, as a single
regioisomer (Table 1, entry 1). When we extended the
two carbons at 130 ppm in the 13C NMR spectra, in agreement
with the formation of the 1,2-thioborated intermediate (6b)
(Figure 2). The minor signals appeared at 5.4 and 3.9 ppm in
the 1H NMR spectra, which were correlated with an allylic and
vinylic carbon, respectively, in the HSQC 2D NMR experiment
(Figure 2). These data agreed with the minor formation of the
1,4-thioborated intermediate (6a). Interestingly, when the
thioboration of the α,β-unsaturated aldehyde crotonaldehyde
(7) was performed under the same reaction conditions, the
unique thioborated intermediate observed was the 1,2-
thioborated isomer (7b) (Figure 3). The signals appeared at
5.8 and 5.6 ppm correlated with two carbons at about 128 ppm,
and the doublet at 5.9 ppm correlates with the carbon at 83
ppm, supporting that the aldehyde functional group has been
transformed into −CH(OBpin)(SPh).
Table 1. 1,4-Thioboration versus 1,2-Thioboration of
a
Electron Deficient Ketones
Figure 2. Enlargement of HSQC 2D of the thioboration of 6.
a
Thioboration carried out with α,β-unsaturated carbonyl substrate (0.1
mmol), PhS−Bpin (4.5 equiv), THF (2 mL), 25 °C, 16 h.
b
Regioselectivity determined by NMR spectroscopy.
thioboration reaction to other substrates such as 4-(4-
methoxyphenyl)-3-buten-2-one (3), trans-1-phenyl-2-buten-1-
one (4), and 4-(4-chlorophenyl)-3-buten-2-one (5), it was
possible to observe a similar trend toward the quantitative 1,4-
thioborated intermediate formation, (Table 1, entries 2−4,
Figure 1).
Figure 3. Enlargement of HSQC 2D of 7b in the reaction crude.
However, the thioboration of the cyclic α,β-unsaturated
ketone 2-cyclohexenone (6) gave a mixture of 1,4- and 1,2-
thioborated products. The 1H NMR spectra of the 2-
cyclohexenone’s crude thioboration reaction shows two differ-
ent groups of signals in 7:3 ratio. The major signals are two
doublets of triplets at 5.9 and 5.7 ppm that were correlated with
After quantitative conversion of substrates 2−8 into
thioborated products, the protic work up carried out with
addition of MeOH (2 mL) provided the corresponding β-
sulfido carbonyl compounds 2-SPh to 8-SPh (Table 2, entries
1−7). A plausible rearrangement of 1,2-thioborated intermedi-
ates 6b and 7b toward the β-sulfido carbonyl compounds seems
to occur under the in situ protic work up. In order to discard
the possible in situ formation of PhSH and direct interaction
with the α,β-unsaturated carbonyl substrates, we ran the same
reaction as in Table 2, entry 5, using PhSH instead of
PhS−Bpin. As was expected, there is no β-sulfido cyclo-
hexenone formation due to the lack of catalytic activation of the
thiol. The thioboration of the less sterically hindered α,β-
unsaturated substrates 1-penten-3-one (9), 3-hepten-2-one
(10), and 3-nonene-2-one (11) required less of the PhS−Bpin
reagent (1.1−3 equiv) to obtain quantitative conversion into
the β-sulfido carbonyl compounds 9-SPh, 10-SPh, and 11-SPh
(Table 2, entries 8−10). When the thioboration of 10 was
carried out in MeOH as the unique solvent, quantitative
formation of the desired β-sulfido ketone was observed within 6
Figure 1. Enlargement of HSQC 2D in the reaction crude of chalcone.
B
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The Journal of Organic Chemistry
Article
Table 2. Thioboration/Protonation of Electron Deficient
a
Ketones
Figure 4. Molecular structure of 12b with ellipsoids drawn at the 50%
probability level and hydrogen atoms omitted for clarity.
from this study ultimately suggests that the B−S bond in 12b is
predominantly single and that negligible dative bonding from
the sulfur lone pair to the boron empty orbital is occurring.
We became interested to evaluate the potential application of
the thiodioxaborolanes BnS−Bpin (12a) and TolS−Bpin (12b,
Tol = 4-MeC6H4), in comparison with PhS−Bpin (1).
Selecting 3-nonene-2-one (11) and 4-hexen-3-one (13) as
the Michael acceptors, we conducted the thioboration/
protonation within 16 h at room temperature. The formation
of the corresponding β-sulfido carbonyl compounds containing
PhS and TolS were isolated up to 71% and 75%, respectively
(Figure 5). Kinetic studies based on reaction progress
a
Reaction conditions: α,β-unsaturated carbonyl substrate (0.1 mmol),
PhS−Bpin (4.5 equiv), THF (2 mL), 25 °C, 16 h; addition MeOH (2
b
mL), 2 h. Conversion calculated from an average of two assays.
c
d
PhS−Bpin (1.1 equiv). PhS−Bpin (3 equiv).
h. We have noticed, in that case, that the use of MeOH as
solvent reduces the reaction time.
In order to have a general picture of this boryl-assisted
synthesis of β-sulfido carbonyl compounds, we considered the
activation and reactivity of the analogue thiodioxaborolanes
BnS−Bpin (12a) and TolS−Bpin (12b, Tol = 4-MeC6H4),
which were also synthesized following the literature proto-
col.6,11 Both sulfur boron compounds were characterized using
multinuclear NMR spectroscopy and elemental analysis. To
confirm the formation of these S−B bonded species, a single
crystal X-ray diffraction study was carried out on 12b,
whereupon the molecular structure is shown in Figure 4. The
B(1)−S(2) distance of 1.828(3) Å is similar to those found in
an unusual hypervalent pentacoordinate boron compound
bearing an anthracene backbone with B−S single bonds of
1.816(5) and 1.809(4) Å.12 Likewise the S−B−O angles in 12b
are 126(2)° and 118.6(2)°, just slightly larger than those found
in the related borothiolate osmium(II) complex [OsH(SBpin)-
(η2-H2)(CO)(PiPr3)2] at 113.86(11)°.13 The C(3)−S(2)−
B(1) angle of 104.09(14)° is only slightly compressed
compared with a pure tetrahedral environment. Data derived
Figure 5. Comparative study of thioboration/protonation with
thiodioxaborolanes PhS−Bpin (1), BnS−Bpin (12a), and TolS−Bpin
(12b).
concentration profile analyzed by NMR spectroscopy provided
a first order reaction for the substrate in the thioboration of 11
with 12a.
Since we have recently unraveled the mechanism for the
reaction of α,β-unsaturated carbonyl compounds with PhSe−
Bpin species by means of DFT studies,10 we envisaged a similar
mechanistic behavior in the thioboration approach. Therefore,
we postulate that the reaction occurs in three main steps, the
first being the interaction of the carbonylic oxygen with the
empty p orbital of the boron atom through a first transition
state TS1 and forming the corresponding intermediate I1
(Figure 6). Two electrophilic positions can further receive the
sulfido group: the carbonylic carbon, passing through the
C
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The Journal of Organic Chemistry
Article
1,4-addition with TolS−Bpin and BnS−Bpin. It can be
observed that for the 1,2-addition of the PhS−Bpin reagent
the activation free energies of both the TS2-1_2 (ΔGT⧧S2‑1_2
=
20.1 kcal·mol−1) and TS3-1_2 (ΔGT⧧S3‑1_4 = 18.6 kcal·mol−1)
are higher than the corresponding ones for the 1,4-addition
pathway (ΔG⧧TS2‑1_4 = 13.5 kcal·mol−1 and ΔGT⧧S3‑1_4 = 10.3
kcal·mol−1, respectively). Also, the intermediate I2-1_2
(ΔGI2‑1_2 = −7.8 kcal·mol−1) is less stable than the
corresponding I2-1_4 (ΔGI2‑1_4 = −11.3 kcal·mol−1) and the
formation of the product P-1_2 (ΔGP‑1_2 = −10.3 kcal·mol−1)
is less favored than the formation of the P-1_4 (ΔGP‑1_4
=
−25.3 kcal·mol−1). Thus, we only display herein the 1,4-
addition pathway for the TolS−Bpin and BnS−Bpin, which
show the same behavior. The thiodioxaborolane BnS−Bpin is
less reactive than the other two reagents by the fact that all the
activation energies ΔG⧧TS1, ΔG⧧TS2‑1_4, and ΔGT⧧S3‑1_4 are higher
Figure 6. Optimized geometries of TS1, I1, TS2-1_2, I2-1_2, TS2-
1_4 and I2-1_4 for the substrate 4-phenyl-3-buten-2-one (2) with the
selected bond distances in Å.
as well as the corresponding intermediates ΔGI1 and ΔGI2‑1_4
.
transition state TS2-1_2 or the Cβ position through the TS2-
1_4 (Figure 6). These transition states give rise to the
intermediates I2-1_2 and I2-1_4 (Figure 6), respectively,
which finally undergo the protonation to give the correspond-
ing β-sulfido carbonyl compounds and the byproduct HOBpin.
In order to clarify the different nucleophilic character of the
thiodioxaborolanes used, we calculated the nucleophilicity
index (N) based on relating the nucleophilicity to the
computed highest occupied molecular orbital (HOMO) energy
by the Kohn−Sham scheme14 through the next formula
introduced by Perez et al.15
Note also that the computed values for the TolS−Bpin and
PhS−Bpin reactions are very similar, the TolS−Bpin being
slightly more reactive.
We also computed the reaction pathway for the thioboration
reaction of substrate 2-cyclohexenone (6) with PhS−Bpin. In
this case, the initial step based on the interaction of the
carbonylic oxygen with the empty p orbital of the boron atom is
the same as described above, but after the first transition state
TS1 (ΔG⧧TS1 = 9.7 kcal·mol−1) and the formation of the
intermediate I1 (ΔGI1 = 8.4 kcal·mol−1), the 1,2-addition takes
place trough a TS2-1_2 (ΔG⧧TS2 = 18.1 kcal·mol−1) giving the
1,2-addition intermediate I2-1_2 (6b) (ΔGI2 = −9.5 kcal·
mol−1). However, despite many efforts, the transition states
corresponding to a direct 1,4-addition or an interconversion
from 1,2- to 1,4-addition intermediates were not located. The
trans disposition of the double bond in the 2-cyclohexenone
substrate prevents the direct 1,4-addition because of geometric
restraints. It is worth mentioning that during the course of
these investigations aimed at characterizing the evolution of the
1,2-addition intermediate, when we introduced water (or
methanol) as protonation agents, the models evolved directly
to the formation of the final 1,4-product and BpinOH (or
BpinOMe). Thus, we think that the interconversion from 1,2-
to 1,4-addition intermediates does not take place directly but is
coupled with the final protonation step. In any case, our results
justify the observation of the 1,2-addition intermediate in the
reaction crude. A very recent report on phosphinoboration of
aldehydes and α,β-unsaturated aldehydes has also proved the
preferred 1,2 addition intermediates.12
We conclude that the synthesis of β-sulfido carbonyl
compounds can be achieved through a direct thioboration/
protonation, where the PhS, TolS, and BnS moieties can be
delivered from the thiodioxaborolanes PhS−Bpin, 4-
MeC6H4S−Bpin, and BnS−Bpin by the simple activation of
the Bpin moiety with a carbonyl group. This strategy is
performed at room temperature in the absence of any catalyst.
The thioboration generates 1,4-addition as well as 1,2-addition
intermediates, depending on the structural nature of the
substrate. Protic workup delivers the corresponding β-sulfido
carbonyl compounds in good isolated yields. From the
thiodioxaborolanes studied, the BnS−Bpin is less activated
presumably because of the lack of electron delocalization from
sulfur, making the boron atom less Lewis acidic. DFT-based
studies provide a suitable mechanism for the reaction and a
useful tool to analyze the change in the nucleophilicity of the
N = EHOMO(Nu)(eV) − EHOMO(TCE)(eV)
where tetracyanoethylene (TCE) is taken as reference. In this
scale, the nucleophilicity index for TCE is N = 0.0 eV,
presenting the lowest HOMO energy in a long series of organic
molecules already considered. According to a same author’s
latter study16 the nucleophiles can be classified as strong, N >
3.00 eV, moderate, 2.00 < N < 3.00 eV, and marginal, N < 2.00
eV. Table 3 collects the N values for the PhSe−Bpin, TolS−
Table 3. Nucleophilicity Indexes (N) for Some X−Bpin
Reagents and for the Intermediates I1 Formed on the
Reaction of 4-Phenyl-3-buten-2-one (2) with TolS−Bpin,
a
PhS−Bpin, and BnS−Bpin
I1
I1
I1
PhSe− TolS− PhS− PhO− BnS−
TolS−
PhS−
BnS−
Bpin
3.48
Bpin
3.35
Bpin
3.24
Bpin
3.09
Bpin
2.89
Bpin
Bpin
Bpin
3.86
3.79
3.99
a
All energies are in eV.
Bpin (TolS = 4-MeC6H4S), PhS−Bpin, PhO−Bpin, and BnS−
Bpin species. Hence, the first four species have a strong
nucleophilic character, whereas BnS−Bpin is considered as a
moderate nucleophile. This is in agreement with the observed
lower reactivity of the BnS−Bpin species compared with TolS−
Bpin and PhS−Bpin. Also, they show the expected trend in
nucleophilicity: Se > S > O. The N values for the intermediates
I1 formed in the reaction of the substrate 4-phenyl-3-buten-2-
one (2) with TolS−Bpin, PhS−Bpin, and BnS−Bpin species
are also collected in Table 3, confirming that its nucleophilicity
is enhanced in relation to the reagents.
Scheme 2 collects the relative Gibbs free energies of the
species involved in the thioboration of 4-phenyl-3-buten-2-one
(2) through 1,2- and 1,4-addition with PhS−Bpin, as well as the
D
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The Journal of Organic Chemistry
Article
Scheme 2. Relative Gibbs Free Energies for the Reaction Pathway of the 1,2- and 1,4-Addition of the RS−Bpin Reagents to the
a
Substrate 4-Phenyl-3-buten-2-one (2)
a
All energies are in kcal·mol−1.
[M + H]+ calcd for C16H16SO 257.3753; found 257.0993; [M + Na]+
calcd for C16H16SO 279.3512; found 279.0812.
reagents by the modification of the substituent on the RS
moieties.
4-(4-Methoxyphenyl)-4-phenylthio-2-butanone (3-SPh). Yield for
1
3-SPh: 20.0 mg (70%) as an oil. H NMR (400 MHz, CDCl3) δ
EXPERIMENTAL SECTION
(ppm):7.31−7.16 (m, 7H), 6.81−6.76 (m, 2H), 4.68 (dd, J = 8.3, 6.4
■
Hz, 1H), 3.77 (s, 3H), 3.05 (dd, J = 17.0, 8.5 Hz, 1H), 2.99 (dd, J =
16.9, 6.5 Hz, 1H), 2.05 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
(ppm): 205.9, 158.9, 134.3, 133.0, 132.9, 129.0, 128.9, 127.6, 114.0,
55.4, 49.9, 47.6, 30.9. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C17H18SO2 309.0974; found 309.0927.
Synthesis of PhS−Bpin (1), BnS−Bpin (12a), and TolS−Bpin
(12b) and X-ray data for 12b. To a toluene (10 mL) solution of the
corresponding RSH (2.50 g, 20.13 mmol) and pinacolborane (2.60 g,
20.33 mmol) was added RhCl(PPh3)3 (4 mg, 0.0040 mmol, 0.02 mol
%) as a solid. The reaction was allowed to proceed for 18 h, at which
point solvent was removed under vacuum to give an off-white solid.6,11
The solid was dissolved in Et2O (4 mL) and stored at −30 °C. The
resulting precipitate was collected by suction filtration to afford 1, 12a,
and 12b as a white solid. Compounds 1 and 12a were previously
reported.11 Yield for 12b: 4.68 g (93%). Spectroscopic NMR data for
12b (in CDCl3): 1H δ 7.36 (d, J = 8.2 Hz, 2H, Ar), 7.07 (d, J = 8.2 Hz,
2H, Ar), 2.31 (s, 3H, CH3), 1.29 (s, 12H, pin); 11B δ 32 (br); 13C{1H}
δ 136.7, 133.1, 129.6, 126.0, 85.2, 24.6, 21.2. Anal. Calcd for
C13H19BO2S (250.16): C, 62.41; H, 7.66. Found: C, 62.22; H, 7.31.
General Method for β-Sulfonylation of α,β-Unsaturated
Ketones and Aldehydes with PhS−Bpin (1), BnS−Bpin (12a),
and TolS−Bpin (12b). The sulfur reagent, PhS−Bpin (1), BnS−Bpin
(12a), or TolS−Bpin (12b) (1.1−4.5 equiv), was weighed and
transferred into an oven-dried Schlenk tube inside the glovebox. The
corresponding substrate (0.10 mmol) was introduced in the Schlenk
tube under argon, and dry THF (2 mL) was added. The mixture was
stirred for 16 h at room temperature. The solvent was removed under
1-Phenyl-4-phenylthio-1-butanone (4-SPh). Yield for 4-SPh: 18.5
mg (72%) as an oil. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.87−7.84
(m, 2H), 7.54−7.48 (m, 1H), 7.43−7.37 (m, 4H), 7.28−7.17 (m, 3H),
3.87 (dqd, J = 9.0, 6.7, 4.6 Hz, 1H), 3.25 (dd, J = 16.9, 4.5 Hz, 1H),
3.06 (dd, J = 16.9, 9.0 Hz, 1H), 1.32 (d, J = 6.7 Hz, 3H). 13C NMR
(100 MHz, CDCl3) δ (ppm): 198.2, 136.9, 134.5, 133.4, 132.4, 129.1,
128.8, 128.2, 127.4, 45.6, 38.8, 21.1. HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C16H16SO 257.3753; found 257.1065; [M + Na]+ calcd
for C16H16SO 279.0892; found 279.0812.
4-(4-Chlorophenyl)-4-phenylthio-2-butanone (5-SPh). Yield for
1
5-SPh: 21.8 mg (75%) as an oil. H NMR (400 MHz, CDCl3) δ
(ppm): 7.31−7.18 (m, 9H), 4.69 (t, J = 7.3 Hz, 1H), 3.05 (d, J = 7.3
Hz, 2H), 2.10 (s, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 205.3,
139.8, 133.6, 133.2, 133.2, 129.2, 129.1, 128.7, 128.0, 49.4, 47.5, 30.8.
HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C16H15SOCl 313.0426;
found 313.0429.
3-Phenylthio-1-cyclohexanone (6-SPh). Yield for 6-SPh: 14.4 mg
1
1
vacuum, and the resulting residue was analyzed by H NMR. When
(70%) as an oil. H NMR (400 MHz, CDCl3) δ (ppm): 7.45−7.40
the 1,2 or the 1,4 intermediates were detected by 1H NMR, a
methanolysis was carried out. The content of the NMR tube was
added into a Schlenk with 2 mL of DCM and excess of MeOH (0.05
mL). The reaction was stirred for 2 h at room temperature. The
solvent was removed under vacuum, and the resulting residue was
(m, 2H), 7.34−7.27 (m, 3H), 3.43 (tdd, J = 10.4, 4.5, 3.4 Hz, 1H),
2.69 (ddt, J = 14.2, 4.4, 1.6 Hz, 1H), 2.41−2.26 (m, 3H), 2.21−2.09
(m, 2H), 1.80−1.64 (m, 2H). 13C NMR (100 MHz, CDCl3) δ (ppm):
208.9, 133.4, 133.1, 129.2, 127.9, 47.9, 46.3, 41.0, 31.4, 24.2. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C12H14SO 207.0816; found
207.0845; [M + Na]+ calcd for C12H14SO 229.0745; found 229.0663.
3-Phenylthiobutanal (7-SPh). Yield for 7-SPh: 14.4 mg (80%) as
an oil. 1H NMR (400 MHz, CDCl3) δ (ppm): 9.76 (t, J = 1.7 Hz, 1H),
7.45−7.41 (m, 2H), 7.35−7.27 (m, 3H), 3.75−3.65 (m, 1H), 2.71
(ddd, J = 17.3, 6.0, 1.8 Hz, 1H), 2.59 (ddd, J = 17.3, 7.6, 1.7 Hz, 1H),
1.37−1.34 (m, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 200.7,
137.8, 133.1, 129.2, 127.8, 50.2, 37.7, 21.3. HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C10H12SO 181.0784; found 181.0534.
1
analyzed by H NMR. Conversion was determined by correlation of
the integrals of the protons of the product and the substrate. The
products, β-(phenylthio), β-(benzylthio), or β-(p-tolylthio) substituted
ketone or aldehyde were purified by flash chromatography using a
silica gel column and the mixture of petroleum ether and ethyl acetate
adequate for each case.
4-Phenyl-4-phenylthio-2-butanone (2-SPh). Yield for 2-SPh: 16.4
mg (64%) as an oil. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.31−7.25
(m, 6H), 7.25−7.18 (m, 4H), 4.71 (dd, J = 8.0, 6.6 Hz, 1H), 3.09 (dd,
J = 16.2, 7.3 Hz, 1H), 3.03 (dd, J = 16.3, 6.0 Hz, 1H), 2.08 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ (ppm): 205.7, 141.1, 134.1, 133.0, 129.0,
128.6, 127.8, 127.8, 127.6, 49.6, 48.1, 30.9. HRMS (ESI-TOF) m/z:
3-Phenylthio-1-cyclopentanone (8-SPh). Yield for 8-SPh: 15.0 mg
1
(78%) as an oil. H NMR (400 MHz, CDCl3) δ (ppm): 7.44−7.37
(m, 2H), 7.35−7.26 (m, 3H), 3.94−3.86 (m, 1H), 2.65−2.44 (m, 4H),
2.40−2.13 (m, 4H).13C NMR (100 MHz, CDCl3) δ (ppm): 216.7,
E
DOI: 10.1021/jo5026354
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The Journal of Organic Chemistry
Article
134.4, 132.2, 129.3, 127.7, 45.4, 43.6, 37.0, 29.9. HRMS (ESI-TOF)
m/z: [M + H]+ calcd for C11H12SO 193.0726; found 193.0668.
1-Phenylthio-3-butanone (9-SPh). Yield for 9-SPh: 15.7 mg (81%)
as an oil. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.35−7.26 (m, 4H),
7.22−7.17 (m, 1H), 3.15 (t, J = 7.3 Hz, 2H), 2.73 (t, J = 7.3 Hz, 2H),
2.42 (q, J = 7.3 Hz, 2H), 1.05 (t, J = 7.3 Hz, 3H). 13C NMR (100
MHz, CDCl3) δ (ppm): 209.6, 135.9, 129.6, 129.2, 126.4, 41.9, 36.4,
27.7, 7.9. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C11H14SO
195.0876; found 195.0835.
free energies (T = 298 K, p = 1 bar). Single points with the functional
B3LYP16 were computed with the same basis set. Hydrogens have
been omitted for clarity in the graphic representation of the
geometries.
ASSOCIATED CONTENT
■
S
* Supporting Information
X-ray diffraction study for 12b, general method for β-
sulfonylation of α,β-unsaturated ketones and aldehyde, 1H
and 13C NMR of products, computational details, functional
comparison, computed nucleophilicity indexes (N), structures
and electronic energies of the involved species, and kinetic
studies. This material is available free of charge via the Internet
at http://pubs.acs.org.
4-Phenylthio-2-heptanone (10-SPh). Yield for 10-SPh: 17.8 mg
1
(80%) as an oil. H NMR (400 MHz, CDCl3) δ (ppm): 7.42−7.38
(m, 2H), 7.33−7.21 (m, 3H), 3.64−3.56 (m, 1H), 2.72 (dd, J = 17.2,
6.1 Hz, 1H), 2.63 (dd, J = 17.2, 7.4 Hz, 1H), 2.13 (s, 3H), 1.57−1.42
(m, 4H), 0.90 (t, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ
(ppm): 207.1, 134.6, 132.5, 129.1, 127.3, 49.3, 43.6, 37.1, 30.9, 20.3,
14.0. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C13H18SO
223.1216; found 223.1142; [M + Na]+ calcd for C13H18SO 245.1089;
found 245.0964.
AUTHOR INFORMATION
■
4-Phenylthio-2-nonanone (11-SPh). Yield for 11-SPh: 17.7 mg
Corresponding Authors
1
(71%) as an oil. H NMR (400 MHz, CDCl3) δ (ppm): 7.39−7.34
*E-mail: mariaelena.fernandez@urv.cat.
*E-mail: cbo@iciq.cat.
*E-mail: swestcott@mta.ca.
(m, 2H), 7.29−7.17 (m, 3H), 3.55 (m, 1H), 2.68 (dd, J = 17.2, 6.2 Hz,
1H), 2.60 (dd, J = 17.2, 7.4 Hz, 1H), 2.09 (s, 3H), 1.54−1.38 (m, 4H),
1.26−1.20 (m, 4H), 0.84 (t, J = 7.0 Hz, 3H). 13C NMR (100 MHz,
CDCl3) δ (ppm): 207.0, 134.7, 132.5, 129.1, 127.3, 49.3, 43.9, 34.9,
31.7, 30.8, 26.7, 22.7, 14.2. HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C15H22SO 251.1547; found 251.1462; [M + Na]+ calcd for
C15H22SO 273.1335; found 273.1279.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
4-Benzylthio-2-nonanone (11-SBn). Yield for 11-SBn: 8.0 mg
■
1
(30%) as an oil. H NMR (400 MHz, CDCl3) δ (ppm): 7.29−7.21
Research supported by the Spanish Ministerio de Economia y
Competitividad (MINECO) through projects CTQ2013-
43395-P and CTQ2011-29054-C02-02, the Generalitat de
Catalunya 2009SGR-00259, and the ICIQ Foundation, the
Natural Sciences and Engineering Research Council of Canada
(m, 4H), 7.21−7.15 (m, 1H), 3.67 (d, J = 1.4 Hz, 2H), 2.98 (p, J = 6.8
Hz, 1H), 2.61 (dd, J = 16.8, 7.1 Hz, 1H), 2.53 (dd, J = 16.8, 6.7 Hz,
1H), 2.03 (s, 3H), 1.42 (dd, J = 7.6, 6.5 Hz, 2H), 1.31−1.17 (m, 6H),
0.80 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm):
207.1, 138.6, 129.0, 128.6, 127.1, 49.8, 40.5, 35.9, 35.2, 31.7, 30.7, 26.4,
22.7, 14.2. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H24SO
265.1657; found 265.1723.
́
and Mount Allison University. Mr. M. Garcia-Civit thanks
URV-La Caixa for the grant, and Mr. X. Sanz thanks URV-ICIQ
for the grant.
4-(p-Tolylthio)nonan-2-one (11-STol). Yield for 11-STol: 19.8 mg
1
(75%) as an oil. H NMR (400 MHz, CDCl3) δ (ppm): 7.31 (d, J =
8.1 Hz, 2H), 7.10 (d, J = 7.8 Hz, 2H), 3.53−3.45 (m, 1H), 2.69 (dd, J
= 17.0, 6.3 Hz, 1H), 2.59 (dd, J = 17.0, 7.4 Hz, 1H), 2.33 (s, 3H), 2.12
(s, 3H), 1.57−1.44 (m, 4H), 1.32−1.26 (m, 4H), 0.87 (t, J = 7.0 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 207.1, 137.6, 133.3,
130.6, 129.8, 49.3, 44.3, 34.8, 31.7, 30.8, 26.7, 22.7, 21.3, 14.2. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C16H24SO 265.1626; found
265.1624.
REFERENCES
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1
(55%) as an oil. H NMR (400 MHz, CDCl3) δ (ppm): 7.34−7.28
(m, 4H), 7.26−7.20 (m, 1H), 3.76 (s, 2H), 3.23−3.13 (m, 1H), 2.66
(dd, J = 16.6, 6.0 Hz, 1H), 2.50 (dd, J = 16.6, 8.0 Hz, 1H), 2.36 (qd, J
= 7.3, 2.2 Hz, 2H), 1.26 (d, J = 6.7 Hz, 3H), 1.02 (t, J = 7.3 Hz, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm): 209.4, 138.5, 128.9, 128.7,
127.2, 49.7, 36.7, 35.7, 35.2, 21.7, 7.8. HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C13H18SO 223.1215; found 223.1153; [M + Na]+ calcd
for C13H18SO 245.1062; found 245.0971.
5-(p-Tolylthio)hexan-3-one (13-STol). Yield for 13-STol: 13.5 mg
1
(61%) as an oil. H NMR (400 MHz, CDCl3) δ (ppm): 7.32 (d, J =
8.1 Hz, 2H), 7.11 (d, J = 7.9 Hz, 2H), 3.69−3.59 (m, 1H), 2.71 (dd, J
= 16.8, 5.4 Hz, 1H), 2.51 (dd, J = 16.8, 8.5 Hz, 1H), 2.40 (qd, J = 7.3,
2.4 Hz, 2H), 2.33 (s, 3H), 1.26 (d, J = 6.6 Hz, 3H), 1.03 (t, J = 7.3 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ (ppm): 209.5, 137.7, 133.2,
130.5, 129.8, 49.3, 38.9, 36.8, 21.3, 21.2, 7.8. HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C13H18SO 223.1215; found 223.1161.
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constraints. The nature of the stationary points encountered was
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harmonic vibrational frequencies analysis. The zero-point, thermal, and
entropy corrections were evaluated to compute enthalpies and Gibbs
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