Organocatalytic sulfoxidation

Article abstract of DOI:10.1016/j.tet.2020.131784

Treatment of a sulfide with a catalytic amount of a 1,3-diketone in the presence of silica sulfuric acid as a co-catalyst and hydrogen peroxide (50% aq) as the stoichiometric oxidant leads to the corresponding sulfoxide product. The reaction is effective for diaryl, aryl-alkyl and dialkyl sulfides and is tolerant of oxidisable and acid sensitive functional groups. Investigations have shown that the tris-peroxide 2, formed on reaction of pentane-2,4-dione with hydrogen peroxide under acidic reaction conditions, can oxidise two equivalents of sulfide using the exocyclic peroxide groups whereas the endocyclic peroxide remains intact. Calculations provide a mechanism consistent with experimental observations and suggest the reaction proceeds via an initial acid catalysed ring opening of a protonated tris-peroxide prior to oxygen transfer to a sulfur nucleophile.

Full text of DOI:10.1016/j.tet.2020.131784

Journal Pre-proof
Organocatalytic sulfoxidation
Stuart C. Davidson, Gabriel dos Passos Gomes, Leah R. Kuhn, Igor V. Alabugin, Alan
R. Kennedy, Nicholas C.O. Tomkinson
PII:
S0040-4020(20)31027-9
https://doi.org/10.1016/j.tet.2020.131784
TET 131784
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 19 October 2020
Accepted Date: 15 November 2020
Please cite this article as: Davidson SC, Gomes GdP, Kuhn LR, Alabugin IV, Kennedy AR, Tomkinson
NCO, Organocatalytic sulfoxidation, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131784.
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Organocatalytic sulfoxidation
Stuart C. Davidson,a Gabriel dos Passos Gomes,b,c,d Leah R. Kuhn,b Igor V. Alabugin,b Alan
R. Kennedya and Nicholas C. O. Tomkinsona,*
aDepartment of Pure and Applied Chemistry, WestCHEM, Thomas Graham Building,
University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, U.K.
bDepartment of Chemistry and Biochemistry, Florida State University, Tallahassee, FL,
32306, USA.
cDepartment of Chemistry, University of Toronto, 80 St George St, Toronto, Ontario M5S
3H6, Canada.
d Department of Computer Science, University of Toronto, 214 College St., Toronto, Ontario
M5T 3A1, Canada.
Nicholas.Tomkinson@strath.ac.uk
Abstract
Treatment of a sulfide with a catalytic amount of a 1,3-diketone in the presence of silica
sulfuric acid as a co-catalyst and hydrogen peroxide (50% aq) as the stoichiometric oxidant
leads to the corresponding sulfoxide product. The reaction is effective for diaryl, aryl-alkyl
and dialkyl sulfides and is tolerant of oxidisable and acid sensitive functional groups.
Investigations have shown that the tris-peroxide 2, formed on reaction of pentane-2,4-dione
with hydrogen peroxide under acidic reaction conditions, can oxidise two equivalents of
sulfide using the exocyclic peroxide groups whereas the endocyclic peroxide remains intact.
Calculations provide a mechanism consistent with experimental observations and suggest the
reaction proceeds via an initial acid catalysed ring opening of a protonated tris-peroxide prior
to oxygen transfer to a sulfur nucleophile.
Introduction
Peroxides possess a rich and fascinating chemistry.1 Of particular interest is their high
reactivity and ability to act as effective reagents in a number of important oxidative
transformations. One challenging aspect of peroxide chemistry is the high energy nature of
these compounds.2 Whilst this renders peroxides synthetically versatile, safety considerations
have often limited the uptake and development of their chemistry.
1

The design and development of new catalytic procedures is a fundamental challenge for the
synthetic community. Of specific relevance is the invention of benign procedures to perform
functional group transformations in a clean and efficient manner.3 The in-situ catalytic
generation of active peroxide reagents represents a particularly useful way in which to
harness the synthetic power of this important functional group whilst avoiding the challenges
associated with handling and manipulating these compounds.
Perhydrates represent a readily accessible and versatile peroxide derivative of both ketones
and aldehydes.4 This functionality reversibly forms under a range of reaction conditions,
allowing formation of an activated peroxide functionality in situ. For example, it has been
shown that perhydrates of hexafluoroacetone, and its derivatives, can be used in a series of
catalytic oxidation procedures including the epoxidation of alkenes,5 the Bayer-Villager
oxidation of ketones6 and the oxidation of heteroatoms such as nitrogen7 and sulfur.8 More
recently, Kokotos reported the use of trifluoroacetophenone in the presence of acetonitrile
and hydrogen peroxide in a series of reactions including the oxidation of alkenes9 as well as
heteroatoms such as silicon,10 nitrogen11 and sulfur.12 Mechanistic studies showed that the
Payne reaction conditions13 were key to the success of these transformations, through the
generation of a highly reactive acetonitrile hydrogen peroxide adduct within the catalytic
cycle.14
The high oxygen content perhydrate derivative 2, formed by the condensation of three
molecules of hydrogen peroxide with acetylacetone, was first reported by Reich in 196115 and
was later characterised spectroscopically by Milas and co-workers.16 30 years later, Azarifar
reported 2 to be an effective reagent for the oxidation of sulfides to sulfoxides.17 In this
report, the peroxide 2 was generated in one-step from acetyl acetone 1 by treatment with
aqueous hydrogen peroxide in the presence of tin(II) chloride dihydrate and was assigned the
trans-configuration based on 1H NMR spectroscopy. Subsequent work showed this peroxide
could also be prepared using silica-sulfuric acid (SSA)18 (90% yield) providing a more
benign and recyclable catalyst for peroxide generation.19 Of particular note with this work
were the rapid reaction times, mild conditions and selectivity for the sulfoxide product with
no over oxidation to the corresponding sulfone being noted. Repeating this work, we were
able to prepare the peroxide 2 (85%) and found this peroxide to be an effective reagent for
the oxidation of 4-tolyl methyl sulfide 3 to the corresponding sulfoxide 4 (96%) (Scheme 1).
2

Scheme 1. a) Synthesis of acetylacetone derived peroxide 2. b) Application of peroxide 2 in
sulfoxidation. c) Potential catalytic cycle for sulfoxidation.
Based upon the findings of Azarifar, we saw potential to develop a novel catalytic oxidation
procedure (Scheme 1c). This involved the in-situ generation of active peroxide 2 through the
acid catalysed reaction of acetylacetone 1 with a source of hydrogen peroxide. To achieve
success, we required the reaction of a substrate sulfide 5 with the peroxide reagent 2 to be
compatible with the acidic conditions necessary to form the perhydrate. Within this
manuscript we describe the development of this novel catalytic process, exploration of the
scope of the transformation and the development of an understanding of the nature of the
catalytically active species.
Results and discussion
Our investigation began with the oxidation of 4-tolyl methyl sulfide 3, in the presence of
H2O2 (30% aq, 5.0 equiv), acetylacetone 1 (100 mol%) and SnCl2·2H2O (20 mol%) (Table 1,
entry 1). After stirring in chloroform at 25 °C for 24 h, the sulfoxide 4 was prepared in 98%
yield as determined by a calibrated HPLC analysis. This result showed the sulfoxidation
could occur under acidic conditions. We therefore performed the reaction in the presence of
substoichiometric amounts of 1 (20 mol%) and SnCl2·2H2O (20 mol%), which led to the
sulfoxide product 4 in 77% yield providing a novel catalytic procedure (entry 2). SSA also
proved to be an effective co-catalyst for the transformation (entry 3; 54%) providing a more
benign, easily removable and recyclable additive. Increasing the amount of SSA added to the
3

reaction mixture led to a more efficient transformation (entries 4 and 5). A brief examination
of the reaction concentration suggested that whilst lower concentrations were less effective
(entry 6; 54%) conducting the process at 0.4 M provided the product in 88% yield (entry 7).
Whilst some background reaction was apparent within the transformation in the absence of 1
(entry 8; 20%), overall, this provided a simple and effective process for the oxidation of
4-tolyl methyl sulfide 3 to the sulfoxide 4 catalysed by the commercial diketone 1 under mild
reaction conditions.
Table 1. Initial optimisation of reaction conditions.
In order to optimise the ketone used within the transformation a number of dicarbonyl
compounds were examined, a selection of which are shown in Table 2, that revealed some
key features of the conversion of 3 to 4. Electron withdrawing groups were introduced α- to
the reactive ketone functionality to increase the electrophilicity of the carbonyl groups.
Whilst trifluoromethyl groups had little effect on the reaction outcome (entry 3; 32%), phenyl
groups proved detrimental to the process (entry 2; 4%). Believing the origin of this
observation to reside in the steric hindrance around the ketone, we examined a bis-acetal
(entry 4; 31%) which showed no improvement in reactivity. Postulating that the presence of
a readily enolisable proton in the diketone would reduce the electrophilicity of the carbonyl
groups we sought to prevent this from happening (entries 5–7). Whilst benzylidene
substitution was ineffective (entry 7; 23%), cyclopropylidene (entry 5; 51%) and dimethyl
substitution (entry 6; 70%)20 proved significantly more effective. A 1,4 diketone (entry 8;
45%) was more effective than a 1,3-diketone (entry 1; 35%), however, further optimisation of
4

this structure did not reach the efficiency of entry 6. Changing to 50% H2O2 (aq) resulted in
complete conversion of the substrate sulfide 3 to the corresponding sulfoxide 4 in 2.5 h.
Table 2. Effect of ketone structure.
Having developed effective conditions for the oxidation of 4-tolyl methyl sulfide 3 we went
on to examine the scope of the procedure (Scheme 2). The reaction was effective for aryl-
alkyl (entries 1–11, 14–18 and 20), diaryl (entry 12) and dialkyl (entries 13 and 19) sulfides.
Reactions with electron rich sulfides (e.g. entries 5 and 13) proceeded considerably faster
than reactions with electron deficient sulfides (e.g. entry 9). The reaction rate was also
affected by steric interactions with larger substituents around the sulfide (e.g. entry 12; 48 h)
reacting considerably slower than sulfides with smaller substituents (e.g. entry 1; 4 h).
Substitution of the aryl group was tolerated in all positions (entries 2–4) and functional
groups including ether, nitro, chloride, bromide, iodide, ketone, alcohol, alkene, carbamate
and ester did not significantly alter the reaction outcome (entries 5–10 and 15–20). Acid
sensitive groups such as methyl and tert-butyl esters (entries 18 and 19) and N-Boc carbamate
(entry 19) remained unaffected during the oxidation and oxidisable groups including alkene
(entries 15 and 20), alcohol (entry 16) and ketone (entry 22) were compatible with the
process. Conducting the reaction of 4-tolyl methyl sulfide on a 10 mmol scale lead to the
expected sulfoxide 4 in a 96% isolated yield after the same reaction time of 2.5 h (cf. entry 2)
suggesting this catalytic process should be scalable. Overall, this simple and effective
catalytic oxidation occurs under mild reaction conditions, on a variety of substrates in
excellent yield and selectivity with no apparent over oxidation to the corresponding sulfone, a
challenge associated with many sulfur oxidation procedures. Oxidation to the sulfone did
prove possible through the use of extended reaction times. For example, reaction of 4-tolyl
methyl sulfide with H2O2 (50% aq, 5 equiv), SSA (100 mg mmol-1) at 25 °C for 7 days gave
5

the corresponding sulfone in 85% isolated yield (see experimental section for full details),
confirming that the second oxidation step was significantly slower using the catalytic
procedure described.
Scheme 2. Substrate scope.
To gain an understanding of the transformation we prepared and characterised a series of
peroxides we considered could be the reactive species within the catalytic cycle (Scheme 3).
Tris-peroxide 2 was made in 76% isolated yield by the reaction of an acetonitrile solution of
acetylacetone with H2O2 (30% aq) in the presence of SSA (100 mg/mmol). Conducting the
reaction in chloroform with H2O2 (50% aq) allowed isolation of the tetraoxane 27 in 20%
yield. The endocyclic mono-peroxide 28 was prepared in 95% yield by the reaction of 1 with
50% aq H2O2 in the absence of an organic solvent (95%).16 The structures of each of these
peroxides (2, 27 and 28) were confirmed by single crystal X-ray analysis which showed 2 and
28 unequivocally had the trans-relationship of their exocyclic oxygen substituents. Exposure
6

of each of these peroxides to the catalytic reaction conditions (SSA 100 mg/mmol, H2O2 50
mol% (aq) 5 equiv, CDCl3, 25 °C) and monitoring by 1H NMR spectroscopy showed each of
these species to be in equilibrium.
Scheme 3. Preparation and single crystal X-ray structure of potential reactive species.
Reaction of either the endocyclic mono-peroxide 28 or the tetraoxane 27 with 4-tolyl methyl
sulfide 3 in chloroform under anhydrous reaction conditions resulted in recovery of both
unreacted sulfide and peroxide in each case (Table 3, entries 1 and 2). This suggests that
these peroxides were not the active species within our catalytic cycle. In stark contrast,
reaction of the tris-peroxide 2 (1.0 equiv) with 4-tolyl methyl sulfide 3 in anhydrous
chloroform gave the sulfoxide 4 in 92% after 6 h (entry 3). More interestingly, conducting
the reaction in the presence of 0.5 equiv peroxide 2 gave the sulfoxide product in 79% (entry
4), in the presence of 0.33 equiv peroxide 2 the product 4 was isolated in 60% yield (entry 5)
and in the presence of 0.2 equiv peroxide the product 4 was formed in 39% (entry 6). These
results suggest that the tris-peroxide 2 transfers two equivalents of oxygen to the sulfide
substrate 3. We believe that it is the exocyclic peroxide groups contained within 2 which
oxidise the substrate. This is consistent with the results using peroxides 27 and 28 which
contain endocyclic peroxide groups and which were unreactive to the sulfide nucleophile 3.
Table 3. Oxidation of sulfide 3 with peroxides 2, 27 and 28.
7

Along with the tris-peroxide 2, both the mono-endocyclic peroxide 28 and the tetraoxane 27
were shown to be catalytically competent within the sulfoxidation process (Scheme 4). Using
2 or 27 or 28 (20 mol%) in chloroform in the presence of SSA (100 mg/mmol) and H2O2
(30% aq, 5 equiv) converted the sulfide 3 into the corresponding sulfoxide 4. The oxidation
with tris-peroxide 2 was faster than the reaction with acetyl acetone 1, the endocyclic mono-
peroxide 28 or the tetroxane 27. We believe this is because the active peroxide is added
directly to the reaction mixture rather than being prepared in situ. The initial rate of reaction
with tetroxane 27 was substantially slower than the reaction using 2 or 28, however, over
time this rate improved. We believe this is due to the equilibration of tetroxane 27 and the
active tris-peroxide 2 under the reaction conditions. The oxidation of 4-tolyl methyl sulfide 3
using tris-peroxide 2 was found to obey second order kinetics with a first order dependence
in both 2 and 3 (k = 3.17 M-1 s-1, 25 °C, CHCl3) (see the supporting information for full
details).
Scheme 4. Relative activity of peroxides 2, 27 and 28 within the catalytic sulfoxidation
process.
8

100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
0
1
2
3
4
5
6
Time (h)
Within the optimised catalytic procedure (7 0.2 equiv, SSA 100 mg/mmol, 50% H2O2 5
equiv, CH2Cl2, 25 °C), on completion of the reaction, we were unable to gain evidence for
the starting diketone 7 through 1H NMR spectroscopy on the crude reaction mixture,
presumably due to the presence of excess hydrogen peroxide within the reaction mixture,
which led to the formation of further peroxide derivatives. In order to recover the diketone 7,
we treated the crude reaction mixture from a sulfoxidation procedure with sodium sulfate and
then triphenylphosphine, continuing stirring for 18 h. This resulted in a 49% recovery of the
diketone 7 after aqueous workup and purification by column chromatography (see supporting
information for full details). Repeating this protocol with polymer supported triphenyl
phosphine21 returned the diketone in a similar 51% yield (see supporting information for full
details). We believe this reduced recovery of the diketone 7 is primarily due to a pinacol
rearrangement of the active peroxide leading to pivalic acid and acetic acid as described by
Payne.22
To support and rationalise the synthetic work we examined the tris-peroxide 2 using DFT
calculations at the (SMD=CHCl3)/M06-2X(D3)/6-311++G(d,p)/int=ultrafine, level of theory.
The tris-peroxide can exist in two diastereomeric forms, the cis-isomer 29 and the trans-
isomer 2. The trans-isomer 2 was found to be 1.6 kcal mol-1 lower in energy than the
9

corresponding cis-isomer 29 (Scheme 5). Given this difference, and the observed reactivity
of 2 with a sulfide, all subsequent calculations were performed with this isomer.
Scheme 5. Stability of tris-peroxide isomers.
To investigate the importance of acid catalysis in peroxide reactions, we compared the SN2
reactions of dimethyl sulfide 30 with MeOOMe 31 and with MeOOH 32, i.e., the parent
organic peroxide and the parent hydroperoxide (Scheme 6). For the neutral peroxides, the
reactions are >40 kcal/mol endergonic and, as a consequence, have an even higher activation
barrier. This thermodynamic penalty results from the unfavorable charge separation
associated with the formation of the two charged products. However, the charge-separated
products of the MeOOH/Me2S reaction can “neutralise” each other via a highly exergonic
proton transfer. These simple calculations illustrate the intrinsic preference of
hydroperoxides over peroxides as the O-transfer agents and suggest that a path that avoids
charge separation should be intrinsically much more favorable. Indeed, the reactions of
dimethyl sulfide 30 with the two protonated peroxides 33 or 34 proceed through the much
lower (6–14 kcal/mol) barriers and are highly exergonic.
Scheme 6. Reactions of dimethyl sulfide 30 with neutral and protonated parent organic
peroxide and hydroperoxide.
10

Guided by these results, we investigated sulfoxidation pathways starting from a protonated
peroxide species. Interestingly, protonation of an endocyclic oxygen atom of the peroxide 2
leads to a ring-opened peroxycarbenium ion 35 (Scheme 7). Although peroxycarbenium ions
are generally relatively high energy reactive intermediates,23 this particular cation is more
stable than the isomeric cyclic peroxonium ion, perhaps due to the strain relief associated
with the ring opening. The subsequent reaction of the peroxycarbenium cation with the
sulfide nucleophile is > 50 kcal/mol exergonic and forms the protonated sulfoxide product
through a low activation barrier (~15 kcal/mol). The bis-peroxide 36 can quickly close into a
cyclic bis-peroxide24 prior to undergoing a second similar O-transfer reaction.
Scheme 7. Protonation of endocyclic oxygen in peroxide 2 leads to a favourable reaction
with the sulfide nucleophile.
Based upon these mechanistic insights we propose the reaction is proceeding through the
catalytic cycle outlined in Scheme 8. Reaction of hydrogen peroxide with a diketone 37 leads
to the endocyclic mono-peroxide 38. This can react with either one or two equivalents of
hydrogen peroxide to give the reactive species 39 or 40. Loss of water from 39 or hydrogen
peroxide from 40, under the acidic reaction conditions, followed by intramolecular
cyclisation leads to the tetroxane 41, which is not active in the sulfoxidation process. Each of
11

the peroxides 38, 39, 40 and 41 are in a dynamic equilibrium under the reaction conditions.
Reaction of an exocyclic peroxide from 39 or 40 with a sulfide nucleophile leads to the
oxidised product 6.
Scheme 8. Proposed catalytic cycle.
Conclusions
In summary, we have developed a novel catalytic procedure for the oxidation of sulfides to
sulfoxides. Treatment of a sulfide with a catalytic amount of a diketone in the presence of a
silica sulfuric acid co-catalyst and hydrogen peroxide (50% aq) leads to the corresponding
sulfoxide. Investigations have shown that the tris-peroxide 2 can oxidise two equivalents of
sulfide using the exocyclic peroxide groups whereas endocyclic peroxides are not reactive
within this transformation. Electronic structure calculations suggest that oxidation of the
substrate proceeds via an initial acid catalysed ring opening of the protonated tris-peroxide 2
prior to oxygen transfer to the sulfur nucleophile. Peroxide 2 has also been used as a
stoichiometric reagent in a number of alternative transformations including the oxidation of
alcohols to ketones,25 oxidative cleavage of alkenes,26 halogenation of aromatic rings,27
epoxidation of α,β-unsaturated carbonyl compounds,28 oxidation of heterocycles29 and the
synthesis of nitriles.30 Ongoing work within the laboratory to apply our knowledge to these
transformations will be reported in due course.
12

Experimental section
General information: Commercially available solvents and reagents were used without
further purification. Flash chromatography was carried out using Merck Kieselgel 60 H silica
or Matrex silica 60. Analytical thin layer chromatography was carried out using aluminium-
backed plates coated with Merck Kieselgel 60 GF254 that were visualised under UV light (at
254 and/or 360 nm). Reactions were heated using an oil bath. Nuclear magnetic resonance
(NMR) spectra were recorded in CDCl3 at 18 °C unless otherwise stated and were reported in
ppm; J values were recorded in Hz and multiplicities were expressed by the usual
conventions. Low-resolution mass spectra (MS) were determined using atmospheric pressure
chemical ionisation (APCI) unless otherwise stated. ES refers to electrospray ionisation, CI
refers to chemical ionisation (methane) and EI refers to electron ionisation. High-resolution
mass spectra were obtained courtesy of the EPSRC Mass Spectrometry Service at University
of Wales, Swansea, U.K. using the ionisation methods specified. In vacuo refers to
evaporation at reduced pressure using a rotary evaporator and diaphragm pump, followed by
the removal of trace volatiles using a vacuum (oil) pump. Melting points were determined
with a Gallenkamp SG92 melting point apparatus and are uncorrected.
Synthesis of SSA
Chlorosulfonic acid (13.5 mL, 203 mmol) was added via dropping funnel, under a constant
flow of N2, over 1.5 hours to stirred silica (60 g). The exhaust from the reaction vessel was
run through 4 M NaOH to quench the HCl gas generated. The silica was allowed to stir for a
further hour to give silica sulfuric acid (SSA) (77 g). Titration with NaOH gave a H+
concentration of 5.6 mmol/g.
General procedure for catalytic sulfoxidation
H2O2(aq) (50%, 285 µL, 5.00 mmol, 5 equiv) was added to a solution of sulfide (1.00 mmol, 1
equiv), 3,3-dimethylpentane-2,4-dione 7 (26 µL, 0.20 mmol, 0.2 equiv) and SSA (100 mg) in
CHCl3 (2.5 mL). The resulting biphasic solution was stirred at 25 °C for the time indicated
and monitored by TLC or HPLC. The reaction was filtered into saturated Na2S2O5(aq) (2 mL)
and H2O (10 mL) and the solid washed with EtOAc (3 × 5 mL). The aqueous layer was
further extracted with EtOAc (2 × 15 mL). The combined organics were washed with brine
(10 mL), dried with MgSO4 and filtered. The solvent was removed in vacuo and the crude
material was then purified by silica gel chromatography (petrol:EtOAc) to obtain the target
products. All oxidations were run in duplicate and presented results are an average of 2 runs.
13

1-Methyl-4-(methylsulfinyl)benzene 431
Reaction of methyl(p-tolyl)sulfane (135 µL, 1.00 mmol), 3,3-dimethylpentane-2,4-dione 7
(26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in CHCl3 (2.5
mL) at 25 °C for 2.5 hours according to the General Procedure. The crude material was
purified by silica gel chromatography (petrol:EtOAc, 1:1) to give the title compound 7 (Run
1: 152 mg, 0.99 mmol, 99%, Run 2: 153 mg, 0.99 mmol, 99%, Average Yield: 99%) as an
orange oil which crystallised to a yellow solid upon cooling; mp 40–42 °C [Lit = 52–54 °C]31
IR (ATR)/cm-1 2991, 2922, 1496, 1040; 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.2 Hz,
2H), 7.33 (d, J = 8.0 Hz, 2H), 2.70 (s, 3H), 2.41 (s, 3H).; 13C NMR (101 MHz, CDCl3) δ
142.7, 141.6, 130.2, 123.7, 44.1, 21.5; LRMS (GCMS-CI) m/z 154.9 [M+H]+.
(Methylsulfinyl)benzene 832
Reaction of thioanisole (117 µL, 1.00 mmol), 3,3-dimethylpentane-2,4-dione 7 (26 µL, 0.20
mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in CHCl3 (2.5 mL) at 25 °C
for 4 hours according to the General Procedure. The crude material was purified by silica gel
chromatography (petrol:EtOAc, 1:1) to give the title compound 8 (Run 1: 139 mg, 0.99
mmol, 99%, Run 2: 136 mg, 0.97 mmol, 97%, Average Yield: 98%) as a yellow oil; IR
(ATR)/cm-1 3055, 2997, 1444, 1035; 1H NMR (400 MHz, CDCl3) δ 7.67–7.62 (m, 2H), 7.56–
7.47 (m, 3H), 2.72 (s, 3H).; 13C NMR (101 MHz, CDCl3) δ 145.8, 131.2, 129.5, 123.6, 44.0;
LRMS (GCMS-CI) m/z 140.9 [M+H]+.
1-Methyl-3-(methylsulfinyl)benzene 9
Reaction of methyl(m-tolyl)sulfane (138 mg, 1.00 mmol), 3,3-dimethylpentane-2,4-dione 7
(26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in CHCl3 (2.5
mL) at 25 °C for 4 hours according to the General Procedure. The crude material was
purified by silica gel chromatography (petrol:EtOAc, 1:1) to give the title compound 9 (Run
1: 152 mg, 0.99 mmol, 99%, Run 2: 144 mg, 0.94 mmol, 94%, Average Yield: 97%) as a
colourless oil; IR (ATR)/cm-1 2993, 2921, 1415, 1042; 1H NMR (400 MHz, CDCl3) δ 7.49 (s,
1H), 7.40 (app d, J = 5.1 Hz, 2H), 7.32–7.28 (m, 1H), 2.71 (s, 3H), 2.43 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 145.6, 139.8, 132.0, 129.3, 123.9, 120.7, 44.1, 21.6; LRMS (GCMS-CI)
m/z 154.9 [M+H]+; HRMS (ASAP) calculated for C8H11OS [M+H]+ 155.0531, found
155.0532.
1-Methyl-2-(methylsulfinyl)benzene 10
14

Reaction of methyl(o-tolyl)sulfane (138 mg, 1.00 mmol), 3,3-dimethylpentane-2,4-dione 7
(26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in CHCl3 (2.5
mL) at 25 °C for 6 hours according to the General Procedure. The crude material was
purified by silica gel chromatography (petrol:EtOAc, 1:1) to give the title compound 10 (Run
1: 139 mg, 0.90 mmol, 90%, Run 2: 137 mg, 0.89 mmol, 89%, Average Yield: 90%) as a
colourless oil; IR (ATR)/cm-1 3051, 2978, 1474, 1035; 1H NMR (400 MHz, CDCl3) δ 7.95
(dd, J = 7.7, 1.5 Hz, 1H), 7.45 (app td, J = 7.6, 0.8 Hz, 1H), 7.39 (td, J = 7.4, 1.5 Hz, 1H),
7.20 (app d, J = 7.4 Hz, 1H), 2.68 (s, 3H), 2.37 (s, 3H).; 13C NMR (101 MHz, CDCl3) δ
144.0, 134.1, 130.9, 130.8, 127.6, 123.1, 42.2, 18.2; LRMS (GCMS-CI) m/z 154.9 [M+H]+;
HRMS (ASAP) calculated for C8H11OS [M+H]+ 155.0531, found 155.0532.
1-Methyl-4-(methylsulfinyl)benzene 1133
Reaction of (4-methoxyphenyl)(methyl)sulfane (154 mg, 1.00 mmol), 3,3-dimethylpentane-
2,4-dione 7 (26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in
CHCl3 (2.5 mL) at 25 °C for 2 hours according to the General Procedure. The crude material
was purified by silica gel chromatography (EtOAc) to give the title compound 11 (Run 1: 165
mg, 0.97 mmol, 97%, Run 2: 161 mg, 0.95 mmol, 95%, Average Yield: 96%) as a colourless
solid; mp 47–49 °C [Lit = 43–47 °C]33; IR (ATR)/cm-1 2989, 2958, 1249, 1022; 1H NMR
(400 MHz, CDCl3) δ 7.60 (dt, J = 8.9, 2.9 Hz, 2H), 7.03 (dt, J = 8.9, 2.9 Hz, 2H), 3.86 (s,
3H), 2.70 (s, 3H). ; 13C NMR (101 MHz, CDCl3) δ 162.1, 136.8, 125.6, 115.0, 55.7, 44.2;
LRMS (GCMS-CI) m/z 171.0 [M+H]+.
1-Chloro-4-(methylsulfinyl)benzene 1233
Reaction of (4-chlorophenyl)(methyl)sulfane (130 µL, 1.00 mmol), 3,3-dimethylpentane-2,4-
dione 7 (26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in
CHCl3 (2.5 mL) at 25 °C for 7 hours according to the General Procedure. The crude material
was purified by silica gel chromatography (petrol:EtOAc, 1:1) to give the title compound 12
(Run 1: 164 mg, 0.94 mmol, 94%, Run 2: 165 mg, 0.95 mmol, 95%, Average Yield: 95%) as
a colourless oil; IR (ATR)/cm-1 3081, 2913, 1478, 1040, 742; 1H NMR (400 MHz, CDCl3) δ
7.60 (dt, J = 8.9, 2.3 Hz, 2H), 7.51 (dt, J = 8.9, 2.2 Hz, 2H), 2.72 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 144.4, 137.4, 129.8, 125.1, 44.2; LRMS (GCMS-CI) m/z 174.9 [M+H]+.
1-Bromo-4-(methylsulfinyl)benzene 13
15

Reaction of (4-bromophenyl)(methyl)sulfane (203 mg, 1.00 mmol), 3,3-dimethylpentane-2,4-
dione 7 (26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in
CHCl3 (2.5 mL) at 25 °C for 7 hours according to the General Procedure. The crude material
was purified by silica gel chromatography (petrol:EtOAc, 1:1) to give the title compound 13
(Run 1: 188 mg, 0.86 mmol, 86%, Run 2: 180 mg, 0.83 mmol, 83%, Average Yield: 85%) as
a colourless solid; mp 89–91 °C; IR (ATR)/cm-1 2989, 2911, 1422, 1038, 817; 1H NMR (400
MHz, CDCl3) δ 7.67 (dt, J = 8.9, 2.3 Hz, 2H), 7.52 (dt, J = 9.0, 2.2 Hz, 2H), 2.72 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 145.1, 132.7, 125.6, 125.3, 44.1.; LRMS (GCMS-CI) m/z
218.9 [M(Br79)+H]; HRMS (ASAP) calculated for C7H8OS(Br79) [M+H]+ 218.9475, found
218.9479.
1-Iodo-4-(methylsulfinyl)benzene 14Reaction of (4-iodophenyl)(methyl)sulfane (250 mg,
1.00 mmol), 3,3-dimethylpentane-2,4-dione 7 (26 µL, 0.20 mmol), SSA (100 mg) and
H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in CHCl3 (2.5 mL) at 25 °C for 7 hours according to
the General Procedure. The crude material was purified by silica gel chromatography
(petrol:EtOAc, 1:1) to give the title compound 14 (Run 1: 230 mg, 0.86 mmol, 86%, Run 2:
231 mg, 0.87 mmol, 87%, Average Yield: 87%) as a colourless solid; mp 117–119 °C; IR
(ATR)/cm-1 2989, 2911, 1422, 1033, 811; 1H NMR (400 MHz, CDCl3) δ 7.88 (dt, J = 8.8, 2.1
Hz, 2H), 7.39 (dt, J = 8.8, 2.2 Hz, 2H), 2.71 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 145.9,
138.6, 125.3, 97.5, 44.1; LRMS (GCMS-CI) m/z 266.9 [M+H]+; HRMS (ASAP) calculated
for C7H8OSI [M+H]+ 266.9341, found 266.9344.
1-(Methylsulfinyl)-4-nitrobenzene 1532
Reaction of methyl(4-nitrophenyl)sulfane (169 mg, 1.00 mmol), 3,3-dimethylpentane-2,4-
dione 7 (26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in
CHCl3 (2.5 mL) at 25 °C for 48 hours according to the General Procedure. The crude
material was purified by silica gel chromatography (EtOAc) to give the title compound 15
(Run 1: 147 mg, 0.79 mmol, 79%, Run 2: 142 mg, 0.76 mmol, 76%, Average Yield: 78%) as
an off-white solid; mp 156–158 °C [Lit = 153–155°C]32; IR (ATR)/cm-1 3101, 2922, 1517,
1342, 1048; 1H NMR (400 MHz, CDCl3) δ 8.40 (dt, J = 9.1, 2.2 Hz, 2H), 7.84 (dt, J = 9.1,
2.3 Hz, 2H), 2.79 (s, 3H).; 13C NMR (101 MHz, CDCl3) δ 153.4, 149.7, 124.8, 124.6, 44.0.;
LRMS (GCMS-CI) m/z 185.9 [M+H]+.
1-(Methylsulfinyl)-3-nitrobenzene 16
16

Reaction of methyl(3-nitrophenyl)sulfane (169 mg, 1.00 mmol), 3,3-dimethylpentane-2,4-
dione 7 (26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in
CHCl3 (2.5 mL) at 25 °C for 30 hours according to the General Procedure. The crude
material was purified by silica gel chromatography (EtOAc) to give the title compound 16
(Run 1: 154 mg, 0.83 mmol, 83%, Run 2: 153 mg, 0.83 mmol, 83%, Average Yield: 83%) as
a pale yellow solid; mp 122–124 °C; IR (ATR)/cm-1 3094, 2922, 1521, 1348, 1072; 1H NMR
(400 MHz, CDCl3) δ 8.49 (app t, J = 1.9 Hz, 1H), 8.36 (ddd, J = 8.2, 2.2, 1.0 Hz, 1H), 8.01
(ddd, J = 7.8, 1.5, 1.1 Hz, 1H), 7.76 (t, J = 7.9 Hz, 1H), 2.80 (s, 3H).; 13C NMR (101 MHz,
CDCl3) δ 148.9, 148.8, 130., 129.41, 125.9, 119.1, 44.2.; LRMS (GCMS-CI) m/z 185.9
[M+H]+; HRMS (ASAP) calculated for C787NO3S [M+H]+ 186.0225, found 186.0222.
1-Methyl-4-(methylsulfinyl)benzene 1733
Reaction of methyl(naphthalen-2-yl)sulfide (174 mg, 1.00 mmol), 3,3-dimethylpentane-2,4-
dione 7 (26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in
CHCl3 (2.5 mL) at 25 °C for 6 hours according to the General Procedure. The crude material
was purified by silica gel chromatography (petrol:EtOAc, 1:1) to give the title compound 17
(Run 1: 170 mg, 0.89 mmol, 89%, Run 2: 182 mg, 0.96 mmol, 96%, Average Yield: 93%) as
a colourless solid; mp 113–115 °C [Lit = 92–99 °C]33; IR (ATR)/cm-1 3058, 2991, 1420,
1035; 1H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 1.4 Hz, 1H), 7.99 (d, J = 8.6 Hz, 1H), 7.97–
7.89 (m, 2H), 7.63–7.58 (m, 3H), 2.80 (s, 3H).; 13C NMR (101 MHz, CDCl3) δ 142.9, 134.6,
133.1, 129.8, 128.7, 128.2, 128.0, 127.5, 124.2, 119.6, 44.0; LRMS (LCMS-ESI) m/z 191.0
[M+H]+.
Sulfinyldibenzene 1831
Reaction of diphenylsulfide (165 µL, 1.00 mmol), 3,3-dimethylpentane-2,4-dione 7 (26 µL,
0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in CHCl3 (2.5 mL) at
25 °C for 48 hours according to the General Procedure. The crude material was purified by
silica gel chromatography (petrol:EtOAc, 3:1) to give the title compound 18 (Run 1: 182 mg,
0.90 mmol, 90%, Run 2: 192 mg, 0.95 mmol, 95%, Average Yield: 93%) as a colourless
solid; mp 71–73 °C [Lit = 67–68 °C]31; IR (ATR)/cm-1 3051, 1442, 1024; 1H NMR (400
MHz, CDCl3) δ 7.68–7.62 (m, 4H), 7.50–7.42 (m, 6H).; 13C NMR (101 MHz, CDCl3) δ
145.73, 131.21, 129.48, 124.94, 77.16.; LRMS (GCMS-CI) m/z 203.0 [M+H]+.
1-(Butylsulfinyl)butane 1931
17

Reaction of di-n-butylsulfide (175 µL, 1.00 mmol), 3,3-dimethylpentane-2,4-dione 7 (26 µL,
0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in CHCl3 (2.5 mL) at
25 °C for 1 hour according to the General Procedure. The crude material was purified by
silica gel chromatography (petrol:EtOAc, 1:1) to give the title compound 19 (Run 1: 155 mg,
0.96 mmol, 96%, Run 2: 154 mg, 0.95 mmol, 95%, Average Yield: 96%) as a colourless oil;
IR (ATR)/cm-1 2960, 2932, 1022; 1H NMR (400 MHz, CDCl3) δ 2.72–2.57 (m, 4H), 1.80–
1.68 (m, 4H), 1.56–1.39 (m, 4H), 0.95 (t, J = 7.4 Hz, 6H).; 13C NMR (101 MHz, CDCl3) δ
52.3, 24.7, 22.2, 13.8.; LRMS (GCMS-CI) m/z 163.0 [M+H]+.
((Methylsulfinyl)methyl)benzene 2033
Reaction of benzyl(methyl)sulfane (135 µL, 1.00 mmol), 3,3-dimethylpentane-2,4-dione 7
(26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in CHCl3 (2.5
mL) at 25 °C for 2 hours according to the General Procedure. The crude material was
purified by silica gel chromatography (EtOAc) to give the title compound 20 (Run 1: 120 mg,
0.78 mmol, 78%, Run 2: 126 mg, 0.82 mmol, 82%, Average Yield: 80%) as a colourless
solid; mp 61–63 °C [Lit = 53–59 °C]33; IR (ATR)/cm-1 3034, 2967, 1498, 1037; 1H NMR
(400 MHz, CDCl3) δ 7.41–7.27 (m, 5H), 4.06 (d, J = 12.8 Hz, 1H), 3.92 (d, J = 12.8 Hz, 1H),
2.45 (s, 3H).; 13C NMR (101 MHz, CDCl3) δ 147.3, 130.2, 129.2, 128.6, 60.5, 37.5.; LRMS
(LCMS-ESI) m/z 155.1 [M+H]+.
(Allylsulfinyl)benzene 2133
Reaction of allyl(phenyl)sulfane (150 µL, 1.00 mmol), 3,3-dimethylpentane-2,4-dione 7 (26
µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in CHCl3 (2.5
mL) at 25 °C for 4.5 hours according to the General Procedure. The crude material was
purified by silica gel chromatography (petrol:EtOAc, 3:1) to give the title compound 21 (Run
1: 141 mg, 0.85 mmol, 85%, Run 2: 139 mg, 0.84 mmol, 84%, Average Yield: 85%) as a
colourless oil; IR (ATR)/cm-1 3055, 2980, 1636, 1446, 1040; 1H NMR (400 MHz, CDCl3) δ
7.62–7.58 (m, 2H), 7.55–7.47 (m, 3H), 5.65 (ddt, J = 17.6, 10.2, 7.5 Hz, 1H), 5.33 (app d, J =
10.1, 1H), 5.19 (dq, J = 17.0, 1.2 Hz, 1H), 3.57 (ddq, J = 12.8, 7.5, 0.5 Hz, 1H), 3.51 (ddq, J
= 12.8, 7.5, 0.8 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 143.1, 131.2, 129.2, 125.4, 124.5,
124.0, 61.0; LRMS (LCMS-ESI) m/z 167.0 [M+H]+.
2-(Phenylsulfinyl)ethan-1-ol 22
18

Reaction of of 2-(phenylthio)ethan-1-ol (135 µL, 1.00 mmol), 3,3-dimethylpentane-2,4-dione
7 (26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in CHCl3
(2.5 mL) at 25 °C for 2 hours according to the General Procedure. The crude material was
purified by silica gel chromatography (EtOAc) to give the title compound 22 (Run 1: 74 mg,
0.44 mmol, 44%, Run 2: 84 mg, 0.49 mmol, 49%, Average Yield: 47%) as a colourless oil;
IR (ATR)/cm-1 3341, 2924, 1446, 1020; 1H NMR (400 MHz, CDCl3) δ 7.67–7.63 (m, 2H),
7.58–7.50 (m, 3H), 4.17 (ddd, J = 11.8, 8.7, 2.9 Hz, 1H), 4.04 (ddd, J = 12.3, 5.4, 3.9 Hz,
1H), 3.27 (bs, 1H), 3.19 (ddd, J = 13.6, 8.7, 3.8 Hz, 1H), 2.87 (ddd, J = 13.6, 5.7, 3.0 Hz,
1H).; 13C NMR (101 MHz, CDCl3) δ 143.1, 131.4, 129.6, 124.1, 57.9, 57.5; LRMS (LCMS-
ESI) m/z 171.0 [M+H]+.
1-(4-(Methylsulfinyl)phenyl)ethan-1-one 23Reaction of 1-(4-(methylthio)phenyl)ethan-1-
one (166 mg, 1.00 mmol), 3,3-dimethylpentane-2,4-dione 7 (26 µL, 0.20 mmol), SSA (100
mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in CHCl3 (2.5 mL) at 25 °C for 7 hours
according to the General Procedure. The crude material was purified by silica gel
chromatography (EtOAc) to give the title compound 23 (Run 1: 148 mg, 0.81 mmol, 81%,
Run 2: 150 mg, 0.82 mmol, 82%, Average Yield: 82%) as a white solid; mp 114–116 °C; IR
(ATR)/cm-1 2986, 2919, 2850, 1671, 1266, 1046; 1H NMR (400 MHz, CDCl3) δ 8.13–8.09
(dt, J = 8.6, 1.8 Hz, 2H), 7.76–7.72 (dt, J = 8.6, 1.7 Hz, 2H), 2.76 (s, 3H), 2.65 (s, 3H).; 13C
NMR (101 MHz, CDCl3) δ 197.1, 151.1, 139.2, 129.3, 123.9, 44.0, 26.9; LRMS (GCMS-EI)
m/z 182.1 [M+H]+; HRMS (ASAP) calculated for C9H11O2S [M+H]+ 183.0480, found
183.0476.
Methyl 2-(phenylsulfinyl)acetate 24
Reaction of methyl 2-(phenylthio)acetate (155 µL, 1.00 mmol), 3,3-dimethylpentane-2,4-
dione 7 (26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in
CHCl3 (2.5 mL) at 25 °C for 32 hours according to the General Procedure. The crude
material was purified by silica gel chromatography (petrol:EtOAc, 1:1) to give the title
compound 24 (Run 1: 190 mg, 0.96 mmol, 96%, Run 2: 183 mg, 0.92 mmol, 92%, Average
Yield: 94%) as a colourless oil; IR (ATR)/cm-1 3058, 2954, 1733, 1437, 1264, 1046; 1H
NMR (400 MHz, CDCl3) δ 7.71–7.66 (m, 2H), 7.57–7.52 (m, 2H), 3.85 (d, J = 13.7 Hz, 1H),
3.71 (s, 3H), 3.67 (d, J = 13.7 Hz, 1H).; 13C NMR (101 MHz, CDCl3) δ 165.3, 143.2, 132.0,
129.6, 124.3, 61.8, 52.9; LRMS (GCMS-CI) m/z 198.9 [M+H]+.
t-Butyl(2S)-2-((t-butoxycarbonyl)amino)-4-(methylsulfinyl)butanoate 25
19

Reaction of t-butyl(t-butoxycarbonyl)-L-methioninate (305 mg, 1.00 mmol), 3,3-
dimethylpentane-2,4-dione 7 (26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285
µL, 5.00 mmol) in CHCl3 (2.5 mL) at 25 °C for 2 hours according to the General Procedure.
The crude material was purified by silica gel chromatography (EtOAc) to give the title
compound 25 (Run 1: 285 mg, 0.89 mmol, 89%, Run 2: 294 mg, 0.92 mmol, 92%, Average
Yield: 91%) as a viscous yellow oil as a 1:1 mixture of diastereomers; IR (ATR)/cm-1 3253,
2973, 2926, 1708, 1366, 1151, 1020; 1H NMR (400 MHz, CDCl3) δ 5.31–5.15 (m, 1H),
4.36–4.20 (m, 1H), 2.85–2.64 (m, 2H), 2.57 (app d, J = 2.0 Hz, 3H), 2.38–2.25 (m, 1H),
2.10–1.98 (m, 1H), 1.47 (app d, J = 1.2 Hz, 9H), 1.44 (s, 9H).; 13C NMR (101 MHz, CDCl3)
some signals doubled due to diastereomeric mixture δ 170.8, 155.6, 83.0, 82.9, 80.2, 53.4,
53.0, 51.0, 50.7, 38.9, 38.8, 28.4, 28.1, 26.4; LRMS (LCMS-ESI) m/z 344.0 [M+Na]+.
1-(Dec-1-en-1-yl)-4-(methylsulfinyl)benzene 26
Reaction of (4-(dec-1-en-1-yl)phenyl)(methyl)sulfane (262 mg, 1 mmol, 1:1 mixture of E:Z),
3,3-dimethylpentane-2,4-dione 7 (26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq,
285 µL, 5.00 mmol) in CHCl3 (2.5 mL) at 25 °C for 4 hours according to General Procedure.
The crude material was purified by silica gel chromatography (petrol:EtOAc, 2:1) to give the
title compound 26 (Run 1 226 mg, 0.81 mmol, 81%, Run 2: 243 mg, 0.87 mmol, 87%,
Average Yield: 84%) as a viscous yellow oil which was a 1:1 mixture of diastereomers; 1H
NMR (600 MHz, CDCl3, mixture of diastereomers) δ 7.60 (d, J = 8.3 Hz, 2H), 7.57 (d, J =
8.4 Hz, 2H), 7.48 (d, J = 8.3 Hz, 2H), 7.42 (d, J = 8.2 Hz, 2H), 6.43–6.39 (m, 2H), 6.34 (dt, J
= 15.8, 6.6 Hz, 1H), 5.77 (dt, J = 11.7, 7.3 Hz, 1H), 2.73 (s, 3H), 2.71 (s, 3H), 2.31 (qd, J =
7.5, 1.7 Hz, 2H), 2.23 (q, J = 6.8 Hz, 2H), 1.50–1.43 (m, 4H), 1.37–1.21 (m, 20H), 0.89–0.86
(m, 4H); 13C NMR (151 MHz, CDCl3) δ 143.7, 143.5, 141.2, 141.0, 135.6, 134.1, 129.7,
128.7, 127.7, 126.9, 124.0, 123.6, 44.1, 44.1, 33.2, 32.0, 32.0, 30.0, 29.6, 29.6, 29.5, 29.4,
29.4, 29.3, 28.9, 22.8, 14.2; LRMS (LCMS-ESI) m/z 295.0 [M+NH4]+; HRMS (NSI)
calculated for C17H27OS [M+H]+ 279.1777, found 279.1775.
1-Methyl-4-(methylsulfonyl)benzene 4234
Reaction of methyl(p-tolyl)sulfide (135 µL, 1.00 mmol), 3,3-dimethylpentane-2,4-dione 7
(26 µL, 0.20 mmol), SSA (100 mg) and H2O2(aq) (50% aq, 285 µL, 5.00 mmol) in CHCl3 (2.5
mL) at 25 °C for 7 days according to the General Procedure. The crude material was purified
by silica gel chromatography (petrol:EtOAc, 1:1) to give the title compound 43 (145 mg, 0.85
mmol, 85%) as an amorphous solid; IR (ATR)/cm-1: 2926, 1286, 1143; 1H NMR (400 MHz,
20

CDCl3) δ 7.83 (d, J = 8.3 Hz, 2H), 7.37 (d, J = 8.2 Hz, 2H), 3.03 (s, 3H), 2.46 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 139.1, 137.6, 130.1, 127.6, 44.8; LRMS (GCMS-CI) m/z 171
[M+H]+.
3,5-Dihydroperoxy-3,5-dimethyl-1,2-dioxolane 217
H2O2(aq) (30%, 10.0 mL, 100 mmol) was added to a solution of acetylacetone 1 (2.00 mL, 20
mmol) and SSA (2 g) in MeCN (80 mL) at room temperature. The resulting solution was
stirred at room temperature for 18 hours. The reaction was diluted with H2O (50 mL) and the
aqueous was extracted with EtOAc (3 × 50 mL). The combined organic extracts were dried
over MgSO4 and filtered. The solvent was removed in vacuo to give the title compound 2 as
a white solid (2.52 g, 15.2 mmol, 76%); mp 100–102 °C [Lit: 98–100 °C]17; IR (ATR)/cm-1
3338, 3004, 2952, 1433, 1381, 1165; 1H NMR (400 MHz, CD3CN) δ 9.64 (bs, 2H), 2.59 (s,
2H), 1.50 (s, 6H); 13C NMR (101 MHz, CD3CN) δ 113.1, 52.2, 18.1.
1,4-Dimethyl-2,3,5,6-tetraoxabicyclo[2.2.1]heptane 2735
H2O2(aq) (50%, 2.85 mL, 50 mmol) was added to a solution of acetylacetone 1 (200 μL, 2
mmol) and SSA (1.00 g) in CHCl3 (25 mL). The resulting biphasic solution was stirred at
room temperature for 18 hours. Saturated Na2S2O5(aq) (25 mL) was added dropwise at 0 °C.
The resulting layers were separated and the aqueous was further extracted with CH2Cl2 (3 ×
25 mL). The combined organic extracts were dried over MgSO4 and filtered. The solvent
was removed in vacuo and the crude material was purified by silica gel chromatography
(petrol:EtOAc, 5:1) to afford the title compound as a white solid (50 mg, 0.38 mmol, 19%);
mp 121–123 °C [Lit: 123–125 °C]35; IR (ATR)/cm-1 2956, 2919, 2852, 1467, 1368; 1H NMR
(400 MHz, CDCl3) δ 2.74 (s, 2H), 1.67 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 110.0, 50.7,
10.8.
3,5-Dihydroxy-3,5-dimethyl-1,2-dioxolane 2816
H2O2(aq) (50%, 0.57 mL, 10.0 mmol) was added every 5 minutes in 0.1 mL portions to
acetylacetone 1 (1.00 mL, 10.0 mmol) which was cooled to 0 °C with regular shaking. The
vessel was maintained at 0 °C for 4 hours with regular shaking. After warming to rt, the now
crystalline material was vacuum dried over P2O5 overnight giving the title compound 27 (1.27
g, 9.62 mmol, 96%) as a white solid; mp 89–91 °C [Lit: 90–91 °C]16; IR (ATR)/cm-1 3350,
2931, 2864; 1H NMR (400 MHz, CD3CN) δ 2.57 (s, 2H), 2.38 (bs, 2H), 1.46 (s, 6H);
13C NMR (101 MHz, CD3CN) δ 106.4, 59.4, 23.3; LRMS.
21

Calculations
All DFT calculations were performed at the (SMD=CHCl3)M06-2X(D3)/6-
311++G(d,p)/int=ultrafine, level of theory. All energies are in kcal/mol.
In order to compare the contributions of different basic sites in these multifunctional
molecules, we employed the (“Geometry, Frequency, Noncovalent, eXtended Tight
Binding”) GFN-xTB method by Grimme and coworkers36 for an automated search and
energy-ranking of protomers.37 GFN-xTB is semiempirical (TB) method for the calculation
of structures, vibrational frequencies, and noncovalent interactions of large molecular system
stakes. After placing a proton on each heteroatom, each geometry was optimised by GFN-
xTB, and ranked by energies within a threshold of 50 kcal/mol. These calculations took
implicit solvation into account using GBSA (Generative Born Surface Area)38 for
chloroform. The lowest energy protomers were then fully optimised at our standard level of
theory.
Acknowledgements
We thank the EPSRC Mass Spectrometry Service, Swansea, for high-resolution spectra. G.
P. G. gratefully acknowledges the Natural Sciences and Engineering Research Council of
Canada (NSERC) for the Banting Postdoctoral Fellowship. Computational analysis at FSU
was supported by the U.S. National Science Foundation (CHE-1800329, I. V. A.).
References
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22

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Declaration of interests
☒ The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.
☐The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests: