Metal-Free Electrophilic Alkynylation of Sulfenate Anions with Ethynylbenziodoxolone Reagents

Article abstract of DOI:10.1021/acs.joc.9b00050

Alkynyl sulfoxides are important building blocks with a unique reactivity in organic chemistry, but only a few reliable methods have been reported to synthesize them. A novel route to access alkynyl sulfoxides is reported herein by using ethynyl benziodoxolone (EBX) reagents to trap sulfenate anions generated in situ, via a retro-Michael reaction. The reaction takes place under metal-free and mild conditions. It is compatible with aryl, heteroaryl, and alkyl sulfoxides with up to 90% yield. This practical access to alkynyl sulfoxides is expected to facilitate the application of these useful building blocks in organic synthesis.

Full text of DOI:10.1021/acs.joc.9b00050

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Note
Metal-Free Electrophilic Alkynylation of Sulfenate
Anions with Ethynylbenziodoxolone Reagents
Stephanie G. E. Amos, Stefano Nicolai, Alec Gagnebin, Franck Le Vaillant, and Jerome Waser
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00050 • Publication Date (Web): 07 Feb 2019
Downloaded from http://pubs.acs.org on February 8, 2019
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Metal-Free Electrophilic Alkynylation of Sulfenate Anions with Ethynylbenziodoxolone Reagents
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Stephanie G. E. Amos,† Stefano Nicolai,† Alec Gagnebin,†Franck Le Vaillant† and Jerome Waser†*
†Laboratory of Catalysis and Organic Synthesis, Institute of Chemical Sciences and Engineering, Ecole
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Polytechnique Fédérale de Lausanne, EPFL SB ISIC LCSO, BCH 4306, CH-1015, Lausanne, Switzer-
land.
jerome.waser@epfl.ch
ABSTRACT: Alkynyl sulfoxides are important building blocks with unique reactivity in organic chem-
istry, but only few reliable methods have been reported to synthesize them. Anovel route to access alkynyl
sulfoxides is reported herein by using Ethynyl BenziodoXolone (EBX) reagents to trap sulfenate anions
generated in-situ, via a retro-Michael reaction. The reaction takes place under metal-free and mild condi-
tions. It is compatible with aryl, heteroaryl and alkyl sulfoxides with up to 90% yield. This practical access
to alkynyl sulfoxides is expected to facilitate the application of these useful building blocks in organic
synthesis.
Sulfoxides are well represented in natural products.1 They constitute also important post-translational
modifications of proteins and are biological precursors of flavours and aromas.2 They have found appli-
cations in material science3 and are preponderant in pharmaceutical and bioactive compounds. Remarka-
ble examples include the top-selling proton pump inhibitor omeprazole (1),4 the insecticide ethiprole (2),
the anti-narcoleptic armodafinil (3) and the immunosuppressor oxisurane (4) (Figure 1).5 Furthermore,
chiral sulfoxides are often used as ligands or auxiliaries in asymmetric synthesis.6
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Figure 1 Examples of bioactive sulfoxide-containing compounds.
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Alkynes play an essential role in numerous chemical transformations.7 More specifically, alkynyl sul-
foxides have found applications as -sulfinyl carbene precursors (Scheme 1, A).8 They also provide easy
access to allenes (B)9 and they can undergo cycloadditions (C).10 They can also be converted to versatile
vinyl sulfoxides via simple Michael-addition11 or reduction to both cis and trans configuration (D).12 The
resulting ,-unsaturated sulfoxides are common in pharmacological compounds13 and can be used in
vinylogous Pummerer rearrangements and other pericyclic reactions.14
Scheme 1. Existing strategies to access alkynyl sulfoxides and their applications.
While the synthetic applications of these compounds look promising, further research and applications
are limited by the lack of robust methods to access them. In fact, only two routes have been routinely
used: oxidation of alkynyl sulfides and nucleophilic substitution on sulfoxide precursors (Scheme 1, E
and F).11,15 As alkynyl sulfides are strongly deactivated, the first approach relies on harsh oxidative con-
ditions, which are not compatible with sensitive functional groups. Concerning the second approach, the
use of acetylene nucleophiles like alkynyl Grignard reagents can lead to 1,4 addition after formation of
the desired compound and side-reactions with other acidic or electrophilic functional groups.11 In order
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to overcome these limitations, we envisaged the use of an inversed polarity strategy for the synthesis of
alkynyl sulfoxides. In this respect, Perrio and Metzner reported in 2005 the facile synthesis of alkylated
sulfoxides by trapping an in-situ generated sulfenate anion with an electrophile (Scheme 2, A and B).16
In this method the unstable sulfenate anion17 is generated via a chemoselective retro-Michael reaction
under mild conditions. This approach was later used for the synthesis of aryl and alkyl sulfoxides, in
particular using palladium-catalysed cross-couplings (C).18 During completion of our work, Bolm and
Chen and co-workers independently reported similar procedures for the arylation of sulfenates by using
diaryliodonium salts (D).19 Nevertheless, the alkynylation of sulfenate anions has never been reported so
far.
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Scheme 2. Retro-Michael approach for sulfenate anion generation and applications in sulfoxide
synthesis.
The exceptional reactivity of hypervalent iodine reagents20 has opened the door to the development of
electrophilic alkynylation reactions.21 In particular, our group has shown the efficacy of cyclic Ethynyl
BenziodoXolone (EBX) reagents as electrophilic alkynyl synthon transfer agents.22 Over the past decade,
they have been applied for the alkynylation of various carbon and heteroatom, more generally, soft nucle-
ophiles.22 In particular, our group has shown the convenient use of EBX reagents for the alkynylation of
thiols and sulfinates.23 These results demonstrated the high reactivity of EBX reagents towards sulfur
nucleophiles. Herein, we present the first method for the synthesis of alkynyl sulfoxides by the reaction
of in-situ generated sulfenates with EBX reagents (Scheme 2, E).
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We started our investigations by examining various retro-Michael sulfenate precursors under Perrio’s
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conditions16 with TIPS-EBX (9a, TIPS = triisopropylsilyl) in THF (Table 1).24
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Table 1: Initial reaction condition for sulfenate precursor screening.
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entry
EWG
solvent
THF
yield (%)
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5
CO2Me (5)
CO2Me (5)
CO2tBu (6a)
SO2Ph (7)
NO2 (8)
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64
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PhMe
PhMe
PhMe
PhMe
Reactions were performed with 5-8 (0.50 mmol, 1.0 equiv.), 9a (0.60 mmol, 1.2 equiv.) and KOtBu (0.59
a
mmol, 1.15 equiv.) in the indicated solvent (0.16 M) at -78 °C for 3 h. Reaction was left overnight to
achieve full conversion.
Methyl (p-tolylsulfinyl)propanoate (5)16 afforded the desired alkynyl sulfoxide 10a in 28% yield (Entry
1). Changing the solvent to toluene increased the yield to 48% (Entry 2). The other precursors were then
tested under the same conditions. Precursors 6a18b and 718c gave both better results (64%. Entries 3 and
4), whereas precursor 818c yielded the desired compound 10a in the same range of yield as 5 (Entry 5).
More easily accessible tert-butyl ester 625 was retained as the best candidate as its use led to a more
convenient protocol (shorter reaction time, easily removed volatile tert-butyl acrylate generated as a side
product).
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Henceforth, we proceeded with the optimisation of the reaction conditions (Table 2). First, diluting the
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reaction (0.056 M instead of 0.16 M) and raising the temperature to -40 °C allowed us to attain 77% NMR
yield (Entry 1) with a cleaner reaction profile. We then screened different bases, KOtBu proved to be the
best base, even though the results with KHMDS were comparable (Entries 2-4). We tested reverse stoi-
chiometry of 5 and 9a, which resulted in a similar isolated yield (Entry 5). Other solvents were not more
efficient than toluene (Entries 6-8). Meanwhile, tert-butyl p-tolylsulfinate was identified as an oxidation
side product by MS and NMR analysis. Accordingly, oxygen was more carefully excluded from the reac-
tion mixture by adding all of the dry reaction components under inert atmosphere (previously, KOtBu was
added after the solvent). This modification improved the isolated yield to 81% (Entry 9). Further increas-
ing the equivalents of KOtBu had a negative impact on the yield (Entry 10). Finally, when combining
reversed stoichiometry and oxygen free conditions the desired alkynyl sulfoxide 10a was isolated in 90%
yield (Entry 11). When the reaction was performed at room temperature under the optimized conditions,
a lower yield of 73% was obtained (Entry 12). Both tert-butyl p-tolylsulfinate and the alkynyl sulfone
corresponding to 10a were identified as side products in this case.
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Table 2: Optimisation of the reaction conditions.
entry
base
solvent
PhMe
PhMe
PhMe
PhMe
yield (%)a
70 (77)
(53)
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4
KOtBu
NaOtBu
KHDMS
LDAb
(70)
(52)
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5c
6
KOtBu
PhMe
DMF
75
28(<40)
(66)
(66)
81
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8
KOtBu
KOtBu
KOtBu
KOtBu
KOtBue
KOtBu
KOtBu
7
PhMe/DCM (9:1)
THF
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9d
PhMe
10d
11c,d
12c,d
PhMe
60
PhMef
90
PhMeg
73
Reactions were performed with 6a (0.10 mmol, 1.0 equiv.), (0.11 mmol, 1.1 equiv.) and the indicated
base (0.105 mmol l.05 equiv.) in the indicated solvent (0.056 M) at -40 °C for 3h. aIsolated yield. 1H-
NMR yields using 1.0 equiv. of CH2Br2 as internal standard is given in parenthesis. b1.1 equiv. c0.9
equiv. of 9a. dThe dry reaction components were added under inert atmosphere. e1.25 equiv. fDegassed
by bubbling Ar for 40 min at -40 °C prior to addition. gDegassing and reaction were performed at RT.
With the optimised reaction conditions in hand, we explored the scope of aryl sulfoxides (Scheme 3,
A). The reaction tolerated both electron rich and electron poor para substitution affording compounds
10a-g in good to excellent yields (55-90%). Ortho and meta substitution also provided the desired alkynyl
sulfoxides 10h-j in up to 81% yield. The method also allowed the synthesis of heteroaryl sulfoxides.
Alkynyl pyridine sulfoxide 10k and alkynyl thiophene sulfoxide 10l were obtained in 85 and 83% yield
respectively, and furanyl sulfoxide 10m in 91% yield after warming the reaction to room temperature
overnight. We then moved our attention onto the synthesis of alkyl alkynyl sulfoxides (Scheme 3, B). We
discovered that the reaction needed to be warmed to room temperature and left overnight to ensure optimal
yields. Primary and secondary alkyl groups were both well tolerated affording 10n and 10o in 77 and 79%
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yield respectively. We then proceeded to test other EBX reagents (Scheme 3, C). TBDPS-EBX (9b)
(TBDPS = tert-butyldiphenylsilyl) and tBu-EBX (9c) (tBu = tert-butyl) both served as efficient alkynyl
transfer agents affording 10p and 10q in 81 and 48% yield respectively. However, attempts with C14H29-
EBX and Ph-EBX reagents were unsuccessful.
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Scheme 3. Scope of the alkynylation reaction.
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aThe reaction was maintained at -40 °C for 2 h, then left to warm to rt over 18 h.
A speculative reaction mechanism can be proposed based on literature precedence (Scheme 4).16,23b,d
A
base-initiated retro-Michael reaction first generates the unstable sulfenate anion I.16 Based on our previous
studies on the addition of sulfur nucleophiles onto EBX reagents,23b,d two mechanism pathways can then
be envisaged: 1) Direct concerted addition to give sulfoxide 10 via 3-atom transition state TS1 (path a)
or 2) Conjugate addition via 4-atom transition state TS2 leading to vinyl benziodoxolone II. At this stage,
a 1,2-shift of either the sulfoxide (path b1) or the R substituent (path b2) together with -elimination of
the iodine leads to sulfoxide 10. This latter step can be either concerted, or via a carbene intermediate if
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-elimination precedes 1,2-shift. The exact reaction pathway is expected to be dependent on the nature of
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the R group on the alkyne.
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Scheme 4. Speculative reaction mechanism.
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We then wondered if the functionalisation of sulfenate anions could be extended to vinylation using
recently introduced Vinyl BenziodoXolone (VBX) reagents.26 To our delight, we were able to access (E)-
alkenyl sulfoxides 12a and 12b in yields of 52% and 25% respectively without changing the experimental
procedure using the corresponding VBX reagents (eq. 1).
To confirm the synthetic utility of this procedure, we performed the reaction on gram-scale affording
the desired alkynyl sulfoxide 10a in 86% yield (eq. 2). Finally, the free alkyne 13 was obtained in 58%
after deprotection of 10a with potassium fluoride under mild conditions (eq. 3).
In conclusion, we have designed a new efficient route to access alkynyl sulfoxides. The use of an EBX
reagent as a soft electrophilic acetylene transfer agent has allowed us to develop the first general synthetic
method for alkynyl sulfoxides based on an inversed-polarity alkynylation under metal-free conditions. We
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have been able to generate in-situ alkyl, heteroaryl and aryl sulfenate anions by using potassium tert-
butoxide at low temperature to initiate a retro-Michael elimination. The trapping of the resulting sulfenate
anions with EBX reagents afforded alkyl and aryl alkynyl sulfoxides in high yields. Additionally, two aryl
vinyl sulfoxides were also isolated when using VBX reagents. When considering the availability of the
starting materials and the straightforward reaction conditions, the developed method has the potential to
facilitate the use of alkynyl sulfoxides in synthetic chemistry, chemical biology and material science.
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Experimental Section
General methods
HPLC grade or distilled solvents purchased from Sigma-Aldrich were used for flash chromatography. For
non-air-sensitive reactions, analytical or reagent grade solvents purchased from Merck or Sigma-Aldrich
were used unless specified. For all alkynylation reactions, toluene and THF dried by passage over acti-
vated alumina under nitrogen atmosphere (H2O content < 7 ppm, Karl-Fisher titration) or anhydrous sol-
vents purchased from Sigma-Aldrich were used. Toluene was degassed by bubbling with a balloon of
argon when mentioned. Reagents were purchased from Sigma-Aldrich, Acros, TCI, Fluorochem, Fluka,
VWR or Merck, unless specified. Chromatographic purification was performed as flash chromatography
using Macherey-Nagel silica 40-63, 60 Å, using the solvents indicated as eluent with 0.1-0.5 bar pressure
or using Biotage Isolera Spektra One with pre-packaged silica cartridges purchased from Buchi, models:
Sepacore or GraceResolve (4 g, 12 g, 25 g). TLC was performed on Merck silica gel 60 F254 TLC glass
plates or aluminium plates and visualized with UV light, permanganate stain, CAN stain. Melting points
were measured using a calibrated Buchi B-540 apparatus using open glass capillaries. 1H-NMR spectra
were recorded on a Brucker DPX-400, 400 MHz, in CDCl3, (CD3)2SO or CD3OD. All signals are reported
in ppm using the residual solvent signal as internal reference (CDCl3: 7.26 ppm, (CD3)2SO: 2.50 ppm or
CD3OD: 3.31 ppm). The data is reported as (multiplicity, coupling constants in Hz, integration, interpre-
tation) using these abbreviations: s = singulet, d = doublet, t = triplet, m = multiplet, bs = broad signal.
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13C{1H}-NMR spectra were carried out with 1H decoupling on a Brucker DPX-400, 101 MHz. All sig-
nals are reported in ppm using the residual solvent signal as internal reference (CDCl3: 77.0 ppm,
(CD3)2SO: 39.5 ppm or CD3OD: 49.0). Infrared spectra were obtained on a JASCO FT-IR B4100 spec-
trophotometer with an ATR PRO410-S and a ZnSe prisma and are reported in cm-1 as (w = weak, m =
medium, s = strong). High resolution mass spectrometric measurements were performed by the mass
spectrometry service of ISIC at the EPFL on a MICROMASS (ESI) Q-TOF Ultima API. Cooling baths
were assured by using Huber TC100E and TC50E cryostats with an ethyl acetate bath.
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Synthesis of 1-Hydroxy-1 λ3,2-benziodoxol-3(1H)-one (14)
Following a reported procedure,27 NaIO4 (7.24 g, 33.8 mmol, 1.05 equiv.) and 2-iodobenzoic
acid (8.00 g, 32.2 mmol, 1.00 equiv.) were suspended in 30% (v:v) aq. AcOH (48 mL). The
mixture was stirred vigorously and refluxed for 4 hours. The reaction mixture was then diluted with cold
water (180 mL) and allowed to cool to rt, protecting it from light. After 1 hour, the crude product was
collected by filtration, washed on the filter with ice water (3 x 20 mL) and acetone (3 x 20 mL), then air-
dried in the dark to give the pure product 14 (8.3 g, 31 mmol, 98%) as a colorless solid. 1H-NMR (400
MHz, (CD3)2SO)  = 8.02 (dd, J = 7.7, 1.4 Hz, 1H), 7.97 (m, 1H), 7.85 (dd, J = 8.2, 0.7 Hz, 1H), 7.71 (td,
J = 7.6, 1.2 Hz, 1H) ppm. 13C{1H}-NMR (101 MHz, (CD3)2SO)  = 167.7, 134.5, 131.5, 131.1, 130.4,
126.3, 120.4 ppm. The values of the NMR spectra are in accordance with reported literature data.27
Synthesis of triisopropylsilyl(trimethylsilyl)acetylene (15)
Following a reported procedure,28 n-butyl lithium (2.5 M in hexanes, 12.0 mL, 29.9 mmol,
0.98 equiv.) was added dropwise to a solution of ethynyltrimethylsilane (3.0 g, 30 mmol, 1.0 equiv.) in
THF (48 mL) at -78 °C in a two-neck 100 mL oven-dried flask under nitrogen. The mixture was warmed
to 0 °C and stirred for 5 minutes. The mixture was cooled back to -78 °C and chlorotriisopropylsilane (6.4
mL, 30 mmol, 1 equiv.) was added dropwise. The mixture was then warmed to room temperature and
stirred overnight. The reaction was then quenched with aq. sat. ammonium chloride (40 mL). The reaction
mixture was extracted with diethyl ether (3 x 60 mL). The organic phases were combined, washed with
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water and brine, dried with MgSO4, filtered and concentrated under reduced pressure to obtain a colourless
liquid which was further purified by Kugelrohr distillation (56-57 °C, 0.25 mmHg) affording 15 as a clear
oil (4.57 g, 18 mmol, 85% yield). 1H-NMR (400 MHz, CDCl3)  = 1.08 (m, 21H), 0.18 (s, 9H) ppm. The
values of the 1H-NMR spectra are in accordance with reported literature data.28
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Synthesis of 1-[(Triisopropylsilyl)ethynyl]-1λ3,2-benziodoxol-3(1H)-one (TIPS-EBX, 9a)
Following a reported procedure,29 2-iodosylbenzoic acid (14) (21.7 g, 82.0 mmol, 1.0
equiv.) was introduced into an oven-dried three-neck 1 L flask equipped with a magnetic
stirrer. After 3 vacuum/nitrogen cycles, anhydrous acetonitrile (500 mL) was added via cannula and
cooled to 0 °C. Trimethylsilyltriflate (16.4 mL, 90.0 mmol, 1.1 equiv.) was added dropwise via a dropping
funnel over 30 minutes (no temperature increase was observed). After 15 minutes, triisopropylsilyl(tri-
methylsilyl)acetylene (15) (23.0 g, 90.0 mmol, 1.1 equiv.) was added via cannula over 15 min (no tem-
perature increase was observed). After 30 min, the suspension became an orange solution. After 10
minutes, pyridine (7.0 mL, 90 mmol, 1.1 equiv.) was added via syringe. After 15 min, the reaction mixture
was transferred to a one-neck 1 L flask and concentrated under vacuum to provide an yellowish solid. The
latter was dissolved in DCM (200 mL) and transferred to a 1 L separatory funnel. The organic layer was
added and washed with aq. HCl (1.0 M; 200 mL) and the aqueous layer was extracted with dichloro-
methane (200 mL). The organic layers were combined, washed with a saturated aqueous solution of Na-
HCO3 (2 x 200 mL), dried over MgSO4, filtered and concentrated under reduced pressure. Recrystalliza-
tion from acetonitrile (ca. 120 mL) afforded 9a (30.1 g, 70.2 mmol, 86%) as a colorless crystalline solid.
mp: 170-176 °C (decomposition); 1H-NMR (400 MHz, CDCl3)  = 8.44 (m, 1H), 8.29 (m, 1H), 7.77 (m,
2H), 1.16 (m, 21H) ppm. 13C{1H}-NMR (101 MHz, CDCl3)  = 166.4, 134.6, 132.3, 131.4, 131.4, 126.1,
115.6, 114.1, 64.6, 18.4, 11.1 ppm. The values of the NMR spectra are in accordance with reported liter-
ature data.29
Synthesis of tert-butyldiphenylsilyl(trimethylsilyl)acetylene (16)
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Following a reported procedure,30 n-butyllithium (2.5 M in hexanes, 8.0 mL, 20 mmol, 0.98
equiv) was added dropwise to a stirred solution of ethynyltrimethylsilane (2.90 mL, 20.4 mmol, 1.0 equiv)
in THF (30 mL) at –78 °C. The mixture was then warmed to 0 °C and stirred for 5 minutes. The mixture
was then cooled back to –78 °C and tertbutylchlorodiphenylsilane (6.4 mL, 30 mmol, 1.0 equiv.) was
added dropwise. The mixture was then allowed to warm to room temperature and stirred overnight. A
saturated aqueous solution of ammonium chloride (30 mL) was added, and the reaction mixture was ex-
tracted with diethyl ether (2 x 50 mL). The organic layer was washed with water and brine, then dried
over MgSO4, filtered and concentrated under reduced pressure to obtain a colorless liquid which was
further purified by Kugelrohr distillation (150 °C, 0.25 mmHg) to yield 16 (2.95 g, 8.76 mmol, 44% yield)
as a colorless liquid. 1H-NMR (400 MHz, CDCl3)  = 7.80 (m, 4H), 7.38 (m, 6H), 1.08 (s, 9H), 0.27 (s,
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9H) ppm. 13C{1H}-NMR (101 MHz, CDCl3)  = 135.6, 133.2, 129.5, 127.7, 119.0, 108.7, 27.0, 18.5, -
0.0 ppm. The values of the NMR spectra are in accordance with reported literature data.30
Synthesis of 1-[(tert-Butyldiphenylsilyl)ethynyl]-1λ3,2-benziodoxol-3(1H)-one (TBDPS-EBX, 9b)
Following a reported procedure,31 trimethylsilyltriflate (freshly distilled; 1.6 mL, 8.7
mmol, 1.1 equiv.) was added dropwise to a stirred solution of 2-iodosylbenzoic acid (14)
(2.07 g, 7.90 mmol, 1.0 equiv.) in acetonitrile (30 mL). tert-Butyldiphenyl((trimethylsilyl)ethynyl)silane
(16) (2.95 g, 3.70 mmol, 1.1 equiv.) was then added dropwise, followed, after 15 min, by the addition of
pyridine (710 μL, 3.70 mmol, 1.1 equiv.). The mixture was stirred 10 minutes. The solvent was then
removed under reduced pressure and the resulting yellow crude oil was dissolved in dichloromethane.
The organic layer was washed with aq. HCl (1.0 M, 15 mL), and the aqueous layer was extracted with
dichloromethane. The organic layers were combined, washed with a sat. aq. NaHCO3, dried over MgSO4,
filtered and concentrated under reduced pressure. The resulting oil was stirred in hexane and ether and
then concentrated under vacuum to afford a colorless solid. Recrystallization from acetonitrile (ca 20 mL)
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afforded 9b (2.77 g, 5.42 mmol, 69% yield) as a colorless solid. H-NMR (400 MHz, CDCl3)  = 8.43
(d, J = 6.5 Hz, 1H), 8.29 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 6.6 Hz, 4H), 7.75 (t, J = 7.2 Hz, 1H), 7.66 (m,
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1H), 7.53-7.41 (m, 6H), 1.21 (s, 9H) ppm. C{1H}-NMR (101 MHz, CDCl3)  = 166.6, 135.5, 134.8,
132.4, 131.5, 131.3, 130.2, 128.1, 126.3, 116.0, 112.2, 68.5, 27.0, 18.7 ppm. The signal corresponding to
one aromatic carbon was not resolved. The values of the NMR spectra are in accordance with reported
literature data.31
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Synthesis of 1-[(tert-Butylsilyl)ethynyl]-1λ3,2-benziodoxol-3(1H)-one (tBu-EBX, 9c)
Following a reported procedure,31 trimethylsilyltriflate (freshly distilled; 1.5 mL, 8.4
mmol, 1.0 equiv) was added dropwise to a stirred solution of 2-iodosylbenzoic acid (14)
(2.69 g, 10.1 mmol, 1.2 equiv) in acetonitrile (30 mL). Commercially available 3,3-dimethylbut-1-yn-1-
yl)trimethylsilane (1.30 g, 8.42 mmol, 1.0 equiv) was then added dropwise, followed, after 15 min, by the
addition of pyridine (680 μL, 8.42 mmol, 1.0 equiv). The mixture was stirred 10 min. The solvent was
then removed under reduced pressure. Dichloromethane and aq. NaOH (1.0 M) were added. The resulting
suspension was filtered. The layers were separated and the aqueous layer was extracted with dichloro-
methane. The organic layers were combined, dried over MgSO4, filtered and the solvent was evaporated
under reduced pressure. Two recrystallisations (with hot filtration) from acetonitrile were necessary to
afford 1-[3,3- dimethylbutynyl]-1,2-benziodoxol-3(1H)-one (9c) (1.43g, 4.36 mmol, 57% yield) as a col-
orless solid. 1H-NMR (400 MHz, CDCl3)  = 8.39 (m, 1H), 8.12 (m, 1H), 7.75 (m, 2H), 1.37 (s, 9H) ppm.
The values of the NMR spectra are in accordance with reported literature data.31
General procedure A: Synthesis of VBX reagents (11a and 11b):
Following a slightly modified reported proceedure,32 to a suspension of 2-iodosylbenzoic acid (14) (0.343
g, 1.30 mmol, 1.00 equiv.) in dry dichloromethane (13 mL) was added TMSOTf (0.27 mL, 1.5 mmol,
1.15 equiv.) dropwise over 10 minutes and stirred for 30 minutes at room temperature. Afterwards, the
corresponding vinyl boronic acid (20a or 20b) (1.50 mmol, 1.15 equiv.) was added and the reaction mix-
ture was stirred for 2 hours at room temperature. Pyridine (0.12 mL, 1.5 mmol, 1.15 equiv.) was added,
after which the mixture was stirred for additional 10 minutes at room temperature. The solvent was then
removed under reduced pressure. The resulting solid was dissolved in dihloromethane (20 mL) and
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washed with aqueous HCl (1.0 M; 10 mL). The aqueous layer was extracted with dichloromethane (3 x
20 mL). The organic layers were combined, washed successively with a saturated aqueous solution of
NaHCO3 (40 mL) and water (3 x 20 mL), dried over MgSO4, filtered, and concentrated under reduced
pressure. The resulting solid was dissolved again in dichloromethane (minimum amount until dissolution)
and precipitated in diethyl ether (ca. 100 mL). After precipitation at 4 °C for 2 hours, the solid was col-
lected by filtration and washed with Et2O to afford the corresponding VBX reagent.
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(E)-1-Styryl-1λ3-benzo[d][1,2]iodaoxol-3(1H)-one (11a)
Following the general procedure A, 11a was obtained as a colourless solid from trans-
2-phenylvinylboronic acid (0.221 g, 1.50 mmol) and 2-iodosylbenzoic acid (14) (0.343 g,
1.30 mmol). Yield: 77% (0.351 g, 1.00 mmol). 1H-NMR (400 MHz, CD3OD)  = 8.32 - 8.25 (m, 1H),
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7.97 (d, J = 15.5 Hz, 1H), 7.77 – 7.63 (m, 6H), 7.54 – 7.45 (m, 3H) ppm. C{1H}-NMR (101 MHz,
CD3OD)  = 170.1, 155.8, 136.7, 135.3, 134.5, 133.3, 132.1, 131.8, 130.2, 129.0, 129.0, 115.5, 100.0
ppm. The values of the NMR spectra are in accordance with reported literature data.32
(E)-1-(4-Methylstyryl)-1λ3-benzo[d][1,2]iodaoxol-3(1H)-one (11b)
Following the general procedure A, 11b was obtained as a colourless solid from trans-
2-(4-methylphenyl)vinylboronic acid (0.242 g, 1.50 mmol) and 2-iodosylbenzoic acid
(14) (0.343 g, 1.30 mmol). Yield: 71% (0.335 g, 0.920 mmol). 1H-NMR (400 MHz, CD3OD)  = 8.32 –
8.25 (m, 1H), 7.92 (d, J = 15.4 Hz, 1H), 7.76 – 7.64 (m, 3H), 7.62 – 7.54 (m, 3H), 7.31 (d, J = 7.9 Hz,
2H), 2.42 (s, 3H) ppm. 13C{1H}-NMR (101 MHz, CD3OD)  = 169.9, 155.7, 142.8, 135.0, 134.3, 133.8,
133.1, 131.6, 130.6, 128.8, 115.3, 98.1, 21.3 ppm. The values of the NMR spectra are in accordance with
reported literature data.32
1-Chloro-1,3-dihydro-3,3-bis(trifluoromethyl)-1,2-benziodoxole (17)
Following a reported procedure,33 TMEDA (distilled over KOH) (0.63 mL, 4.1 mmol, 0.2
equiv) was added to a solution of nBuLi (2.5 M in hexanes, 18.3 mL, 45.8 mmol, 2.2 equiv).
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After 15 min, the cloudy solution was cooled to 0 °C and ,-bis(trifluoromethyl)benzyl alcohol (3.5 mL,
21 mmol, 1 equiv) in THF (3 mL) was added dropwise. The reaction was stirred 30 min at 0 °C and then
18 h at rt. I2 (5.6 g, 22 mmol, 1.06 equiv.) was then added portion-wise at 0 °C and the mixture stirred at
0 °C for 30 min and 4 h at rt. The reaction was quenched with a saturated aqueous solution of NH4Cl.
Diethyl ether (50 mL) was added and the layers were separated. The aqueous layer was then extracted
twice with diethyl ether (2 x 50 mL). The organic layers were combined, washed twice with a saturated
aqueous solution of NaS2O3 (2 x 50 mL), dried over MgSO4, filtered and reduced to afford 7.83 g of 2-
iodo-,-bis(trifluoromethyl)-benzenemethanol as an orange oil which was used without further purifi-
cation. The crude oil was dissolved in dichloromethane (20 mL) in the dark under air. tBuOCl (2.6 mL,
22 mmol, 1.05 equiv.) was then added dropwise at 0 °C. After 30 min, the resulting suspension was
filtered to afford 17 (3.52 g, 8.70 mmol, 42%) as a yellow oil. The mother liquors were carefully reduced
to one third and filtered to afford 17 (2.33 g, 5.76 mmol, 28%) as a yellow solid. Combined yield: 70%.
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1H-NMR (400 MHz, CDCl3)  = 8.09 (d, 1H, J = 8.4 Hz), 7.85 (m, 1H), 7.73 (m, 2H) ppm. C{1H}-
NMR (101 MHz, CDCl3)  = 133.8, 132.1, 131.6, 129.7, 128.5,122.8 (q, 289 Hz), 113.4, 84.8 ppm. The
values of the NMR spectra are in accordance with reported literature data.34
1-Hydroxy-3,3-bis(trifluoromethyl)-3-(1H)-1,2-benziodoxole (18)
Following a reported procedure,35 Et3BnNCl (0.083 g, 0.36 mmol, 0.05 equiv) was added to
a stirring solution of 17 (3.00 g, 7.41 mmol, 1 equiv) in dichloromethane (50 mL) and KOH (0.415 g,
7.41 mmol, 1 equiv) in water (8 mL). The reaction was stirred for 3.5 hours under air. The organic layer
was separated and dried over MgSO4. The resulting solid was purified over a silica plug with ethyl acetate,
then recrystallised in ethyl acetate and washed with pentane to afford 18 (1.24 g, 3.21 mmol, 43%) as a
colourless solid. The mother liquors were reduced and recrystallised in ethyl acetate to afford a second
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batch of 18 (0.279 g, 0.723 mmol, 10 %) as a colourless solid. Combined yield: 53%. H-NMR (400
MHz, (CD3)2SO)  = 7.96 (m, 2H), 7.73 (m, 2H) ppm. 13C{1H}-NMR (101 MHz, (CD3)2SO)  = 133.3,
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131.0, 130.8, 128.9, 127.9, 123.4 (q, J = 290 Hz), 117.2, 83.7 (m) ppm. The values of the NMR spectra
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1-[(Triisopropylsilyl)ethynyl]-3,3-bis(trifluoromethyl)-3(1H)-1,2-benziodoxole (19)
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TMSOTf (310 μL, 1.71 mmol, 1.1 equiv) was added to 18 (0.600 g, 1.55 mmol, 1.0
equiv) in dichloromethane (20 mL) at rt. After 20 min, the solution was reduced and the
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resulting oil was dissolved in acetonitrile (30 mL). (trimethylsilyl)(triisopropylsilyl)acetylene (16) (0.514
g, 1.71 mmol, 1.1 equiv) was added and after 20 min pyridine (76 μL, 0.94 mmol, 0.6 equiv) was added.
The reaction was then reduced under vacuum, dissolved in diethyl ether and filtered over a silica plug
(eluant: diethyl ether). The resulting solid was purified by column chromatography (Petroleum ether:di-
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ethyl ether 95:5) to afford 19 (0.816 g, 1.48 mmol, 95%) as a colourless solid. H-NMR (400 MHz,
Choroform-d)  = 8.36 (dd, 1H, J = 7.9, 1.7 Hz), 7.84 (d, 1H, J = 6.7 Hz), 7.68 (m, 2H), 1.15 (m, 21H)
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ppm. C{1H}-NMR (101 MHz, CDCl3)  = 132.7, 131.1, 129.9, 129.9 (m), 128.2, 123.6 (q, 288 Hz),
112.1, 110.8, 81.4 (m), 69.7, 18.5, 11.2 ppm.
Phenyl(triisopropylsilyl)iodonium triflate (20)
Following a reported procedure,36 phenyliodonium diacetate (2.53 g, 7.85 mmol, 1.00
equiv) was diluted with dichloromethane (7 mL) and the mixture was stirred for 5 minutes.
Triflic anhydride (0.60 mL, 3.9 mmol, 0.50 equiv.) was added dropwise at 0 °C and the resulting yellow
mixture was stirred 30 min. (Trimethylsilyl)(triisopropylsilyl)acetylene (15) (2.00 g, 7.86 mmol, 1.00
equiv) was added and the mixture was then stirred 2 h. Water was then added (30 mL) followed by ex-
traction of the aqueous layer with dichloromethane (2 x 30 mL). The combined organic layers were dried
over MgSO4, filtered and the solvent was evaporated under reduced pressure. The resulting solid was
triturated in hexane (10 mL). Filtration and removal of solvent in vacuo afforded phenyl(triisopropylsi-
lyl)iodonium triflate (20) (2.90 g, 11.2 mmol, 70% yield) as a colorless solid. 1H-NMR (400 MHz, CDCl3)
 = 8.09 (m, 2H), 7.65 (m, 1H), 7.52 (m, 2H), 1.15-1.01 (m, 21H) ppm. 13C{1H}-NMR (100 MHz, CDCl3)
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 = 133.7, 132.5, 132.4, 119.7, 117.6, 117.6, 44.9, 18.3, 11.1 ppm. The values of the NMR spectra are in
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accordance with reported literature data.36
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Preparation of Starting Materials
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All thiols were commercially avaiable and purhased from Sigma-Aldrich, Alfa-Aesar, Fluorochem or TCI
and used as purchased without any purification.
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General procedure B: synthesis of tert-butyl β-sulfanyl esters (21a-21k)
Following a slightly modified version of a reported procedure,37 the thiol (1 equiv.), tert-butyl acrylate
(1.05 equiv.) and triethylamine (0.1 equiv.) were introduced into a microwave vial equipped with a mag-
netic stirrer. The vial was sealed and the reaction mixture was stirred at rt for 10 minutes then heated to
60 °C for 1-3 hours (until full conversion based on TLC analysis). The volatiles were then removed
through evaporation under reduced pressure to afford β-sulfanyl esters (21a-21k) in sufficient purity to
be used in next step without further purification.
In order to characterise the new compounds, preparative TLC (SiO2, Heptane/EtOAc) was used to afford
pure compounds.
General procedure C: synthesis of tert-butyl β-sulfanyl esters (21l, 21m)
Following a reported procedure,18e the thiol (1.0 equiv.) and tert-butyl acrylate (1.0 equiv.) were dissolved
in THF (5 M based on the thiol) in a round-bottomed flask equipped with a magnetic stirrer. Triethylamine
(0.1 equiv.) was added and the reaction mixture was stirred at rt. overnight. It was then concentrated under
reduced pressure to remove the volatiles. The crude was then submitted to column chromatography (SiO2,
pentane:Et2O) affording β-sulfanyl esters (21l, 21m).
General alkylation procedure D: synthesis of tert-butyl β-sulfanyl esters (21n, 21o)
Following a slightly modified reported procedure,38 the thiol (1.0 equiv.) was added to a suspension of
KF/alumina 45wt% (4.2 equiv – 4.6 equiv) in acetonitrile (0.05 M based on the thiol). The reaction mix-
ture was stirred for 5 minutes at rt. tert-Butyl acrylate (1.0 equiv.) was added and the reaction was heated
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to 50-60 °C for 15 minutes. The reaction mixture was filtered on a Celite pad then concentrated under
reduced pressure and filtered a second time on Celite and sand, washed with DCM. Solvents were evap-
orated under reduced pressure affording in sufficient purity the desired tert-butyl alkylthiopropanoate
(21n, 21o).
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Synthesis of alumina supported potassium fluoride 45wt%
Following a reported procedure,38 basic alumina (5.5 g) and potassium fluoride (4.5 g, 77 mmol) were
charged in a 25 mL flask equipped with a magnetic stirrer. Water (10 mL) was added and the mixture was
stirred at room temperature for 15 min. The water was evaporated under reduced pressure and the catalyst
was left to dry in a vacuum oven at 110 °C overnight, yielding 10 g 45wt% KF/basic alumina support.
Tert-butyl 3-(4-methylphenylthio)propanoate (21a)
Following general procedure B, 21a was obtained as a yellow oil from 4-methylben-
zenethiol (1.24 g, 10.0 mmol) and tert-butyl acrylate (1.5 mL, 10 mmol). Yield: 99% (2.51 g, 9.95 mmol,
88% purity). 1H-NMR (400 MHz, CDCl3)  7.28 (m, 2H), 7.11 (m, 2H), 3.07 (t, J = 7.5 Hz, 2H), 2.51 (t,
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J = 7.5 Hz, 2H ), 2.32 (s, 3H), 1.45 (s, 9H ppm C{1H}-NMR (101 MHz, CDCl3)  = 171.2, 136.8,
131.8, 131.0, 129.9, 80.9, 35.8, 30.1, 28.2, 21.2 ppm. The values of the NMR spectra are in accordance
with reported literature data.39
Tert-butyl 3-(phenylthio)propanoate (21b)
Following general procedure B, 21b was obtained as a colourless oil from benzenethiol
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(0.73 mL, 7.1 mmol) and tert-butyl acrylate (1.1 mL, 7.5 mmol). Yield: 99% (1.68 g, 7.10 mmol). H-
NMR (400 MHz, CDCl3)  = 7.39 – 7.33 (m, 2H), 7.33 – 7.26 (m, 2H), 7.24 – 7.17 (m, 1H), 3.13 (dd, J
= 7.9, 7.1 Hz, 2H ), 2.54 (dd, J = 7.8, 7.1 Hz, 2H ), 1.45 (s, 9H) ppm. 13C{1H}-NMR (101 MHz, CDCl3)
 = 171.1, 135.6, 130.0, 129.0, 126.4, 81.0, 35.6, 29.2, 28.1 ppm. HRMS (APCI) calcd. For C13H18O2S+°
[M]+° 238.1028; found 238.1022. IR (film): 푣̃= 2977 (m), 2935 (w), 1729 (s), 1480 (m), 1368 (m), 1249
(m), 1152 (s) cm-1.
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Tert-butyl 3-(4-methoxyphenylthio)propanoate (21c)
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Following general procedure B, 21c was obtained as a yellow oil from 4-methox-
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3.55 mmol). H-NMR (400 MHz, CDCl3)  = 7.37 (dt, J = 8.8, 2.1 Hz, 2H), 6.84 (dt, J = 8.8, 2.1 Hz,
2H), 3.80 (s, 3H), 3.00 (t, J = 7.5 Hz, 2H ), 2.47 (t, J = 7.5 Hz, 2H ), 1.44 (s, 9H) ppm. 13C{1H}-NMR
(101 MHz, CDCl3)  = 171.3, 159.4, 134.2, 125.5, 114.7, 81.0, 55.5, 35.8, 31.4, 28.2 ppm. HRMS (ESI)
calcd. for C14H20NaO3S+ [M+Na]+ 291.1025; found 291.1034. IR (film): 푣̃= 2979 (w), 2934 (w), 2840
(w), 1727 (s), 1596 (m), 1579 (w), 1497 (m), 1368 (m), 1304 (w), 1250 (s), 1155 (s), 1089 (s), 1043 (s),
834 (m) cm-1.
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Tert-butyl 3-(4-bromophenylthio)propanoate (21d)
Following general procedure B, 21d was obtained as an off-white solid from 4-bro-
mobenzenethiol (0.510 g, 2.70 mmol) and tert-butyl acrylate (0.4 mL, 3 mmol). Yield 96% (0.827 g, 2.61
mmol). mp: 46.8-47.9 °C; 1H-NMR (400 MHz, CDCl3)  = 7.41 (dt, J = 8.5, 2.0 Hz, 2H), 7.22 (dt, J =
8.5, 2.0 Hz, 2H), 3.10 (t, J = 7.4 Hz, 2H ), 2.52 (t, J = 7.4 Hz, 2H ), 1.45 (s, 9H) ppm. 13C{1H}-NMR (101
MHz, CDCl3)  = 171.0, 134.9, 132.2, 131.6, 120.4, 81.3, 35.5, 29.4, 28.2 ppm. HRMS (ESI) calcd. for
C13H1779BrNaO2S+ [M+Na]+ 339.0030; found 339.0029. IR (film): 푣̃= 2979 (w), 2938 (w), 1729 (s),
1476 (m), 1391 (w), 1367 (m), 1252 (m), 1156 (s), 1094 (w), 1009 (w), 814 (w) cm-1.
Tert-butyl 3-(4-fluorophenylthio)propanoate (21e)
Following general procedure B, 21e was obtained as a yellow oil from 4-fluoroben-
zenethiol (0.42 mL, 3.9 mmol) and tert-butyl acrylate (0.64 mL, 4.4 mmol). Yield: 92% (95% pure ac-
cording to NMR analysis; 0.97 g, 3.6 mmol). 1H-NMR (400 MHz, CDCl3)  = 7.38 (m, 2H), 7.12 – 6.72
(m, 2H), 3.06 (t, J = 7.4 Hz, 2H), 2.49 (t, J = 7.4 Hz, 2H), 1.44 (s, 9H) ppm. 13C{1H}-NMR (101 MHz,
CDCl3)  = 171.0, 162.1 (d, J = 246.8 Hz), 133.2 (d, J = 8.1 Hz), 130.3 (d, J = 3.4 Hz), 116.1 (d, J = 21.8
Hz), 81.0, 35.5, 30.6, 28.1 ppm. 19F NMR (376 MHz, CDCl3)  = -115.0 ppm. HRMS (ESI) calcd. for
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C13H17FNaO2S+ [M+Na]+ 279.0825; found 279.0817. IR (film): 푣̃= 2983 (m), 2923 (w), 1728 (s), 1591
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Tert-butyl 3-(4-trifluoromethylphenylthio)propanoate (21f)
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Following general procedure B, 21f was obtained as a pale yellow oul from 4-trifluo-
romethylbenzenethiol (0.30 mL, 2.2 mmol) and tert-butyl acrylate (0.36 mL, 2.5 mmol). Yield: 99%
(0.665 g, 2.17 mmol). 1H-NMR (400 MHz, CDCl3)  = 7.52 (m, 2H), 7.38 (m, 2H), 3.20 (t, J = 7.4 Hz,
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2H ), 2.58 (dd, J = 7.7, 7.1 Hz, 2H ), 1.45 (s, 9H) ppm. C{1H}-NMR (101 MHz, CDCl3)  = 170.7,
141.4, 128.0, 127.8 (q, J = 32.8 Hz), 125.8 (q, J = 3.7 Hz), 124.2 (q, J = 271.7 Hz), 81.3, 35.1, 28.1, 27.9
ppm. 19F NMR (376 MHz, CDCl3)  = -62.9 ppm. HRMS (ESI) calcd. for C14H17F3O2S+ [M]+ 306.0896;
found 306.0902. IR (film): 푣̃= 2977 (w), 2935 (w), 1728 (m), 1608 (m), 1370 (m), 1327 (s), 1166 (s),
1127 (s), 1097 (s), 1065 (m), 1014 (m) cm-1.
Tert-butyl 3-(4-nitrophenylthio)propanoate (21g)
Following general procedure B, 21g was obtained as a yellow crystalline solid from
4-nitrobenzenethiol (0.50 g, 3.2 mmol) and tert-butyl acrylate (0.56 mL, 3.9 mmol). Yield: 55% (0.50 g,
1.8 mmol). mp: 70.1 - 71.8 °C. 1H-NMR (400 MHz, CDCl3)  = 8.14 (m, 2H), 7.35 (m, 2H), 3.26 (t, J =
7.4 Hz, 2H ), 2.62 (t, J = 7.3 Hz, 2H ), 1.46 (s, 9H) ppm. 13C{1H}-NMR (101 MHz, CDCl3)  = 170.4,
146.7, 145.2, 126.5, 124.1, 81.6, 34.7, 28.1, 27.2 ppm. HRMS (ESI) calcd. for C13H17NNaO4S+
[M+Na]+ 306.0770; found 306.0761. IR (film): 푣̃= 3094 (w), 3072 (w), 3002 (w), 2970 (w), 2932 (w),
1731 (s), 1591 (m), 1581 (m), 1503 (s), 1336 (s), 1225 (m), 1153 (s), 1089 (s), 855 (m), 836 (s), 744 (m)
cm-1.
Tert-butyl 3-(2-bromophenylthio)propanoate (21h)
Following general procedure B, 21h was obtained as a yellow oil from 2-bromoben-
zenethiol (0.31 mL, 2.6 mmol) and tert-butyl acrylate (0.46 mL, 3.2 mmol). Yield: 99% (0.89 g, 2.6
mmol). 1H-NMR (400 MHz, CDCl3)  = 7.51 (dd, J = 7.9, 1.2 Hz, 1H), 7.30 – 7.19 (m, 2H), 7.01 (ddd,
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J = 7.9, 6.6, 2.3 Hz, 1H), 3.13 (t, J = 7.5 Hz, 2H), 2.55 (t, J = 7.5 Hz, 2H), 1.43 (s, 9H) ppm. 13C{1H}-
NMR (101 MHz, CDCl3)  = 170.8, 137.2, 133.1, 128.7, 127.8, 127.0, 124.2, 81.2, 34.9, 28.2, 28.1 ppm.
HRMS (ESI) calcd. for C13H1779BrNaO2S+ [M+Na]+ 339.0025; found 339.0017. IR (film): 푣̃= 3002 (w),
2976 (w), 2932 (w), 1725 (s), 1582 (w), 1449 (m), 1427 (m), 1367 (m), 1251 (m), 1147 (s), 1021 (m),
838 (m), 744 (s) cm-1.
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Tert-butyl 3-(3-methylphenylthio)propanoate (21i)
Following general procedure B, 21i was obtained as a pale yellow oil from 3-
methylbenzenethiol (1.00 mL, 8.4 mmol) and tert-butyl acrylate (1.3 mL, 9.0 mmol). Yield: 99% (2.1 g,
8.3 mmol). 1H-NMR (400 MHz, CDCl3)  = 7.19 – 7.13 (m, 3H), 6.96 (m, 1H), 3.10 (t, J = 7.5 Hz, 2H),
13
2.52 (t, J = 7.5 Hz, 2H), 2.30 (s, 3H), 1.44 (s, 9H) ppm. C{1H}-NMR (101 MHz, CDCl3)  = 171.0,
138.6, 135.3, 130.5, 128.8, 127.2, 126.9, 80.8, 35.5, 29.1, 28.0, 21.3 ppm. HRMS (APPI) calcd. for
C14H20O2S+° [M]+° 252.1179; found 252.1174. IR (film): 푣̃= 3008 (w), 2976 (w), 2932 (w), 1726 (s),
1595 (w), 1472 (w), 1364 (m), 1248 (m), 1149 (s), 844 (m), 771 (s) cm-1.
Tert-butyl 3-(3-bromophenylthio)propanoate (21j)
Following general procedure B, 21j was obtained as a pale yellow oil from 3-bromo-
benzenethiol (0.30 mL, 2.6 mmol) and tert-butyl acrylate (0.4 mL, 3 mmol). Yield: 99% (0.82 g, 2.6
mmol). 1H-NMR (400 MHz, CDCl3)  = 7.48 (t, J = 1.8 Hz, 1H), 7.32 (ddd, J = 7.9, 1.9, 1.0 Hz, 1H),
7.26 (ddd, J = 7.9, 1.8, 1.0 Hz, 1H), 7.15 (t, J = 7.9 Hz, 1H), 3.13 (t, J = 7.4 Hz, 2H), 2.54 (t, J = 7.4 Hz,
2H), 1.45 (s, 9H) ppm. 13C{1H}-NMR (101 MHz, CDCl3)  = 170.8, 138.2, 131.8, 130.3, 129.3, 127.9,
122.9, 81.2, 35.3, 28.9, 28.1 ppm. HRMS (APPI) calcd. for C13H1779BrO2S+° [M]+° 316.0127; found
316.0132. IR (film): 푣̃= 2977 (m), 2923 (w), 1728 (s), 1576 (m), 1557 (m), 1459 (m), 1391 (m), 1370
(m), 1247 (m), 1152 (s), 844 (m).
Tert-butyl 3-(pyridin-2-ylthio)propanoate (21k)
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Following slightly modified general procedure B, 21k was obtained as a dark brown oil
from pyridine-2-thiol (0.82 g, 7.4 mmol) and tert-butyl acrylate (1.2 mL, 7.8 mmol) after
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heating to 80 °C over 16 hours. Yield: 90% (90% pure according to NMR analysis;1.75 g, 6.64 mmol).
1H-NMR (400 MHz, CDCl3)  = 8.42 (ddd, J = 5.0, 1.9, 1.0 Hz, 1H), 7.46 (ddd, J = 8.0, 7.4, 1.9 Hz, 1H),
7.16 (dt, J = 8.1, 1.1 Hz, 1H), 6.96 (ddd, J = 7.4, 4.9, 1.1 Hz, 1H), 3.39 (t, J = 7.1 Hz, 2H), 2.68 (t, J = 7.1
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Hz, 2H), 1.46 (s, 9H) ppm. C{1H}-NMR (101 MHz, CDCl3)  = 171.4, 158.5, 149.5, 135.9, 122.3,
119.4, 80.8, 35.8, 28.1, 25.1 ppm. HRMS (ESI) calcd. for C12H18NO2S+ [M+H]+ 240.1053; found
240.1047. IR (film): 푣̃= 3049 (w), 2977 (w), 2935 (w), 1728 (s), 1580 (m), 1560 (w), 1534 (w), 1457
(m), 1418 (s), 1367 (s), 1285 (m), 1254 (s), 1151 (s), 1130 (s) cm-1.
Tert-butyl 3-((thiophen-2-yl)thio)propanoate (21l)
Following general procedure C, 21l was obtained as a yellow oil from thiophenethiol
(1.0 mL, 11 mmol, 1.0 equiv.) and tert-butyl acrylate (1.6 mL, 11 mmol, 1.0 equiv.). Yield: 70% (1.83 g,
7.48 mmol). 1H-NMR (400 MHz, CDCl3)  = 7.36 (dd, J = 5.4, 1.2 Hz, 1H), 7.14 (dd, J = 3.6, 1.2 Hz,
1H), 6.98 (dd, J = 5.4, 3.6 Hz, 1H), 2.97 (t, J = 7.3 Hz, 2H), 2.53 (t, J = 7.4 Hz, 2H), 1.45 (s, 9H) ppm.
13C{1H}-NMR (101 MHz, CDCl3)  = 170.1, 145.3, 131.2, 129.7, 127.5, 81.7, 53.0, 28.2, 28.0 ppm.
HRMS (ESI) calcd. for C11H16NaO2S2 [M+Na]+ 267.0484; found 267.0474. IR (film): 푣̃= 2974 (m),
+
2928 (w), 1725 (s), 1407 (w), 1366 (m), 1247 (m), 1143 (s), 991 (w), 846 (s) cm-1.
Tert-butyl 3-((2-methylfuran-3-yl)thio)propanoate (21m)
Following general procedure C, 21m was obtained as a colorless oil from 2-methylfu-
ran-3-thiol (0.50 mL, 4.5 mmol) and tert-butyl acrylate (0.66 mL, 4.5 mmol). Yield: 76% (0.828 g, 3.42
mmol). 1H-NMR (400 MHz, CDCl3)  = 7.28 (d, J = 2.0 Hz, 1H), 6.34 (d, J = 2.0 Hz, 1H), 2.81 (t, J =
7.3 Hz, 2H), 2.43 (t, J = 7.3 Hz, 2H), 2.34 (s, 3H), 1.44 (s, 9H) ppm. 13C{1H}-NMR (101 MHz, CDCl3)
 = 171.2, 155.4, 140.7, 115.1, 109.5, 80.8, 35.9, 31.1, 28.1, 11.8 ppm. HRMS (ESI) calcd. for
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C12H18NaO3S+ [M+Na]+ 265.0869; found 265.0858. IR (film): 푣̃= 2979 (m), 2934 (w), 1730 (s), 1514
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(w), 1370 (m), 1253 (m), 1142 (s), 1091 (m), 935 (m), 850 (m), 739 (m) cm-1.
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Tert-butyl 3-(pentylthio)propanoate (21n)
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Following general procedure D, 21n was obtained as a yellow oil from 1-pentanethiol
(1.24 g, 10.0 mmol, 1.0 equiv.), KF/alumina 45wt% (6.0 g, 42 mmol, 4.2 equiv.) and tert-butyl acrylate
(1.5 mL, 10 mmol, 1 equiv.).Yield: 99% (2.51 g, 10.0 mmol). 1H-NMR (400 MHz, CDCl3)  = 2.73 (t, J
= 7.4 Hz, 2H), 2.59-2.43 (m, 4H), 1.65-1.49 (m, 2H), 1.45 (s, 9H), 1.40-1.26 (m, 4H), 0.95-0.82 (m, 3H,)
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ppm. C{1H}-NMR (101 MHz, CDCl3)  = 171.5, 80.9, 36.3, 32.2, 31.2, 29.4, 28.2, 27.3, 22.5, 14.1
ppm. HRMS (ESI) calcd. for C12H24NaO2S+ [M+Na]+ 255.1389; found 255.1394. IR (film): 푣̃= 2960
(m), 2929 (m), 2861 (w), 1731 (s), 1462 (w), 1392 (w), 1371 (w), 1251 (m), 1145 (s), 971 (w), 934 (w),
849 (w) cm-1.
Tert-butyl 3-(cyclohexylthio)propanoate (21o)
Following general procedure D, 21o was obtained as a colorless oil from cyclohexylthiol
(0.73 mL, 6.0 mmol, 1.0 equiv.), KF/alumina 45wt% (3.6 g, 25 mmol, 4.2 equiv.) and tert-butyl acrylate
(0.90 mL, 6.2 mmol, 1.05 equiv.). 1H-NMR (400 MHz, CDCl3)  = 2.75 (dd, J = 8.0, 7.1 Hz, 2H), 2.64
(tt, J = 10.4, 3.6 Hz, 1H), 2.49 (dd, J = 8.1, 7.1 Hz, 2H), 2.01 – 1.89 (m, 2H), 1.91 – 1.72 (m, 2H), 1.65 –
1.55 (m, 1H), 1.45 (s, 9H), 1.38 – 1.17 (m, 5H) ppm. 13C{1H}-NMR (101 MHz, CDCl3)  = 171.4, 80.7,
43.6, 36.5, 33.7, 28.1, 26.1, 25.8, 25.3 ppm. HRMS (ESI) calcd. for C13H24NaO2S+[M+Na]+ 267.1389;
found 267.1390. IR (film): 푣̃= 2981 (m), 2929 (s), 2857 (m), 1732 (s), 1447 (m), 1370 (s), 1250 (s), 1155
(s) cm-1.
General oxidation procedure E (compounds 5, 6a-6j, 6n and 8)
Following a slightly modified version of a reported procedure,16 in a two-necked flask equipped with a
magnetic stirrer, the sulfide 21 (1 equiv.) was dissolved in methanol (40 mL) and cooled to 0 °C. Sodium
periodate (1.0 equiv. or 1.2 equiv.) dissolved in water (20 mL) was then added dropwise using a syringe
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over a period of 30 minutes. The reaction mixture was then left to warm to room temperature under stirring
overnight. The precipitated solids were then filtered off through a Celite pad and washed with methanol
(20 mL). Methanol was evaporated under reduced pressure. The obtained aqueous layer was extracted
three times with DCM (3 x 20 mL). The organic layers were combined, washed with brine (10 mL), dried
over Na2SO4 and filtered. Solvents were then evaporated under reduced pressure before submitting the
crude to column chromatography (silica gel, DCM/EtOAc) affording the pure tert-butyl sulfinyl propano-
ates 5, 6a-j, 6n and 8.
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General oxidation procedure F (compounds 6k-6l and 6o)
Following a slightly modified reported procedure,18e in a 25 mL round-bottomed flask, tert-butyl 3-thio-
propanoate 21 (1.0 equiv.) was dissolved in TFE (2 M based on thiopropanoate) and the resulting solution
was cooled to 0 °C (ice-water bath). H2O2 (30% v/v in water; 1.8 equiv.) was added drop-wise at the same
temperature. The mixture was then allowed to warm to room temperature and stirred for 5 hours. After
this time, soldium sulfite (1.8 equiv.) was added and the the mixture was vigorously stirred for 30 minutes.
It was then filtered through a plug of celite, which was then washed with several portions of DCM. The
filtrate was dried over MgSO4, filtered and concentrated under vacuum. The resulting crude oil was sub-
mitted to column chromatography (SiO2; DCM:MeOH) to afford desired tert-butyl 3-sulfinylpropanoates
6.
Synthesis of Methyl 3-((4-methylphenyl)sulfinyl)propanoate (5)
Following a slightly modified version of a reported procedure,37 4-methylbenzenethiol
(2.8 g, 22 mmol, 1.0 equiv.), methyl acrylate (2.0 mL, 22 mmol, 1.0 equiv.) and triethylamine (0.30 mL,
2.2 mmol, 0.1 equiv.) were introduced into a microwave vial equipped with a magnetic stirrer. The vial
was sealed and the reaction mixture was stirred at rt for 10 minutes then heated to 60 °C for 3 hours (until
full conversion based on TLC analysis). The volatiles were then removed through evaporation under re-
duced pressure to afford methyl 3-((4-methylphenyl)thio)propanoate in 99% yield (4.6 g, 22 mmol) with
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sufficient purity to be used in next step without further purification. Following general oxidation proce-
dure E, 5 was obtained as a colorless oil from methyl 3-((4-methylphenyl)thio)propanoate (2.50 g, 21.4
mmol) and NaIO4 (4.58 g, 21.4 mmol). Yield: 70% (3.41 g, 5.07 mmol). 1H-NMR (400 MHz, CDCl3) 
= 7.52-7.50 (m, 2H), 7.34 (d, 2H, J = 8.1 Hz), 3.67 (s, 3H), 3.25-3.18 (m, 1H), 3.00-2.92 (m, 1H), 2.87-
2.79 (m, 1H), 2.59-2.51 (m, 1H), 2.43 (s, 3H) ppm. 13C{1H}-NMR (101 MHz, CDCl3)  = 171.7, 141.7,
139.7, 130.0, 124.1, 52.1, 51.2, 26.0, 21.4 ppm. The values of the NMR spectra are in accordance with
reported literature data.40
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Tert-butyl 3-[(4-methylphenyl)sulfinyl]propanoate (6a)
Following general procedure E, 6a was obtained as a yellow solid from 21a (1.49 g,
5.90 mmol, 1.0 equiv.) and sodium periodate (1.26 g, 5.90 mmol , 1.0 equiv.). Yield:
69% (1.09 g, 4.06 mmol). mp: 56.1 -57.7 °C. 1H-NMR (400 MHz, CDCl3)  = 7.50 (d, J = 8.0 Hz, 2H),
7.33 (d, J = 8.0 Hz, 2H), 3.14 (ddd, J = 13.5, 8.5, 6.7 Hz, 1H), 2.92 (ddd, J = 13.5, 8.4, 5.8 Hz, 1H) 2.73
(ddd, J = 17.2, 8.5, 6.8 Hz, 1H), 2.51-2.38 (m, 5H), 1.42 (s, 9H) ppm. 13C{1H}-NMR (101 MHz, CDCl3)
 = 170.5, 141.6, 139.9, 130.1, 124.1, 81.5, 51.6, 28.1, 27.4, 21.5 ppm. The values of the NMR spectra
are in accordance with reported literature data.8
Tert-butyl 3-[(phenyl)sulfinyl]propanoate (6b)
Following general procedure E, 6b was obtained as a colorless oil from 21b (1.0 g, 4.2
mmol, 1.0 equiv.) and sodium periodate (1.1 g, 5.0 mmol, 1.2 equiv.). Yield: 56% (0.59
g, 2.3 mmol). 1H-NMR (400 MHz, CDCl3)  = 7.61 (dt, J = 7.6, 1.6 Hz, 2H), 7.58 – 7.47 (m, 3H), 3.16
(m, 1H), 2.92 (ddd, J = 13.8, 8.4, 5.7 Hz, 1H), 2.75 (ddd, J = 17.1, 8.5, 6.7 Hz, 1H), 2.43 (ddd, J = 17.1,
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8.6, 5.8 Hz, 1H), 1.41 (s, 9H) ppm. C{1H}-NMR (101 MHz, CDCl3)  = 170.4, 143.1, 131.1, 129.3,
124.0, 81.6, 51.5, 28.0, 27.3 ppm. The values of the NMR spectra are in accordance with reported litera-
ture data.40
Tert-butyl 3-[(4-methoxyphenyl)sulfinyl]propanoate (6c)
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Following general procedure E, 6c was obtained as a yellow solid from 21c (0.950
g, 3.54 mmol, 1.0 equiv.) and sodium periodate (0.909 g, 4.25 mmol, 1.2 equiv.).
Yield: 89% (0.900 g, 3.16 mmol). mp: 41.4-44.6 °C; 1H-NMR (400 MHz, CDCl3)  = 7.53 (dd, J = 8.9,
2.2 Hz, 2H), 7.00 (dd, J = 8.9, 2.2 Hz, 2H), 3.82 (s, 3H), 3.08 (ddd, J = 13.3, 8.5, 6.7 Hz, 1H), 2.98 - 2.84
(m, 1H), 2.77 - 2.61 (m, 1H), 2.48 - 2.35 (m, 1H), 1.39 (s, 9H) ppm. 13C{1H}-NMR (101 MHz, CDCl3) 
= 170.5, 162.1, 133.9, 126.0, 114.9, 81.5, 55.6, 51.7, 28.1, 27.6 ppm. HRMS (ESI) calcd. for
C14H20NaO4S+ [M+Na]+ 307.0974; found 307.0971. IR (film): 푣̃= 3068 (w), 2979 (w), 2934 (w), 2840
(w), 1727 (s), 1596 (m), 1579 (w), 1498 (m), 1461 (w), 1368 (m), 1304 (m), 1250 (s), 1155 (s), 1089 (s),
1043 (s), 834 (m) cm-1.
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Tert-butyl 3-[(4-bromophenyl)sulfinyl]propanoate (6d)
Following general procedure E, 6d was obtained as an off white solid from 21d
(0.428 g, 1.35 mmol, 1.0 equiv.) and sodium periodate (0.289 g, 1.35 mmol, 1.0 equiv.).
Yield: 42% (0.190 g, 0.570 mmol). mp: 69.4-71.7 °C. 1H-NMR (400 MHz, CDCl3)  = 7.67 (dd, J = 8.5,
2.0 Hz, 2H), 7.49 (dd, J = 8.5, 2.0 Hz, 2H), 3.17 (ddd, J = 13.5, 8.2, 6.9 Hz, 1H), 2.90 (ddd, J = 13.5, 8.1,
5.8 Hz, 1H), 2.75 (ddd, J = 17.3, 8.1, 6.9 Hz, 1H), 2.44 (ddd, J = 17.3, 8.2, 5.8 Hz, 1H), 1.42 (s, 9H) ppm.
13C{1H}-NMR (101 MHz, CDCl3)  = 170.4, 142.4, 132.6, 125.8, 125.7, 81.8, 51.6, 28.1, 27.3 ppm.
HRMS (ESI) calcd. for C13H1779BrNaO3S+ [M+Na]+ 354.9974; found 354.9985. IR (film): 푣̃= 2978 (w),
2933 (w), 1730 (s), 1573 (w), 1474 (w), 1369 (m), 1250 (m), 1159 (s), 1086 (m), 1051 (s), 1009 (m), 844
(w), 822 (w) cm-1.
Tert-butyl 3-[(4-fluorophenyl)sulfinyl]propanoate (6e)
Following general procedure E, 6e was obtained as a colorless solid from 21e (0.920
g, 3.59 mmol, 1.0 equiv.) and sodium periodate (0.921 g, 4.31 mmol, 1.2 equiv.). Yield:
83% (0.811 g, 2.98 mmol). mp: 82.4 - 83.5 °C. 1H-NMR (400 MHz, CDCl3)  = 7.61 (ddd, J = 9.8, 5.0,
2.5 Hz, 2H), 7.22 (m, 2H), 3.14 (ddd, J = 13.4, 8.3, 6.9 Hz, 1H), 2.91 (ddd, J = 13.5, 8.1, 5.8 Hz, 1H),
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2.74 (ddd, J = 17.3, 8.1, 7.0 Hz, 1H), 2.45 (ddd, J = 17.3, 8.3, 5.8 Hz, 1H), 1.41 (s, 9H) ppm. 13C{1H}-
NMR (101 MHz, CDCl3)  = 170.3, 164.4 (d, J = 251.5 Hz), 138.6 (d, J = 3.1 Hz), 126.3 (d, J = 9.0 Hz),
116.7 (d, J = 22.7 Hz), 81.7, 51.7, 28.0, 27.3 ppm. 19F NMR (376 MHz, CDCl3)  = -108.5 ppm. HRMS
calcd. for C13H17FNaO3S+[M+Na]+ 295.0775; found 295.0777. IR (film): 푣̃= 3062 (w), 2977 (w), 2931
(w), 1728 (s), 1591 (m), 1493 (s), 1369 (m), 1295 (w), 1233 (s), 1153 (s), 1086 (m), 838 (s), 815 (m) cm-
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Tert-butyl 3-[(4-trifluoromethylphenyl)sulfinyl]propanoate (6f)
Following general procedure E, 6f was obtained as an off-white solid from 21f (0.645
g, 2.10 mmol, 1.0 equiv.) and sodium periodate (0.540 g, 2.53 mmol, 1.2 equiv.).
Yield: 87% (0.592 g, 1.84 mmol). mp: 64.0-64.8 °C. 1H-NMR (400 MHz, CDCl3)  = 7.94 – 7.49 (m,
4H), 3.23 (ddd, J = 13.6, 8.0, 7.1 Hz, 1H), 2.93 (ddd, J = 13.6, 7.8, 5.8 Hz, 1H), 2.78 (ddd, J = 17.4, 7.8,
7.1 Hz, 1H), 2.46 (ddd, J = 17.4, 8.0, 5.8 Hz, 1H), 1.41 (s, 9H) ppm. 13C{1H}-NMR (101 MHz, CDCl3)
 = 170.1, 147.7, 133.1 (q, J = 32.8 Hz), 126.3 (q, J = 3.8 Hz), 124.6, 123.5 (q, J = 272.6 Hz), 81.8, 51.4,
28.0, 27.0 ppm. 19F NMR (376 MHz, CDCl3)  = -62.9 ppm. HRMS calcd. for C14H17F3NaO3S+
[M+Na]+ 345.0743; found 345.0737. IR (film): 푣̃= 3053 (w), 2988 (w), 1728 (m), 1422 (w), 1403 (w),
1368 (w), 1325 (m), 1265 (s), 1169 (m), 1133 (m), 1060 (m), 1016 (w), 845 (w) cm-1.
Tert-butyl 3-[(4-nitrophenyl)sulfinyl]propanoate (6g)
Following general procedure E, 6g was obtained as a yellow crystalline solid from
21g (0.400 g, 1.41 mmol, 1.0 equiv.) and sodium periodate (0.362 g, 1.69 mmol, 1.2
equiv.). Yield: 29% (0.124 g, 0.414 mmol). mp: 90.4-91.2 °C. 1H-NMR (400 MHz, CDCl3)  = 8.38 (m,
2H), 7.82 (m, 2H), 3.26 (dt, J = 13.5, 7.6 Hz, 1H), 2.95 (ddd, J = 13.4, 7.6, 5.7 Hz, 1H), 2.81 (dt, J = 17.5,
7.5 Hz, 1H), 2.48 (ddd, J = 17.5, 7.8, 5.7 Hz, 1H), 1.41 (s, 9H) ppm. 13C{1H}-NMR (101 MHz, CDCl3)
 = 170.0, 150.9, 149.6, 125.2, 124.4, 82.0, 51.6, 28.0, 27.0 ppm. HRMS (ESI) calcd. for C13H17NNaO5S+
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[M+Na]+ 322.0720; found 322.0715. IR (film): 푣̃= 3121 (w), 2966 (m), 2922 (m), 2854 (m), 1727 (s),
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Tert-butyl 3-[(2-bromophenyl)sulfinyl]propanoate (6h)
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Following general procedure E, 6h was obtained as a colorless crystalline solid from
21h (0.734 g, 2.32 mmol, 1.0 equiv.) and sodium periodate (0.500 g, 2.33 mmol, 1.0
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equiv.). Yield: 79% (0.609 g, 1.83 mmol). mp: 72.6-73.5 °C. 1H-NMR (400 MHz, CDCl3)  = 7,83 (m,
1H), 7.66 – 7.49 (m, 2H), 7.37 (td, J = 7.6, 1.7 Hz, 1H), 3.39 (ddd, J = 13.7, 8.9, 6.5 Hz, 1H), 3.08 (ddd,
J = 13.7, 8.9, 5.8 Hz, 1H), 2.79 (ddd, J = 17.1, 8.9, 6.5 Hz, 1H), 2.44 (ddd, J = 17.1, 8.9, 5.8 Hz, 1H),
1.40 (s, 9H) ppm. 13C{1H}-NMR (101 MHz, CDCl3)  = 170.3, 142.5, 133.1, 132.4, 128.4, 126.8, 118.9,
81.5, 47.8, 28.0, 26.8 ppm. HRMS calcd. for C13H1779BrNaO3S+ [M+Na]+ 354.9974; found 354.9976. IR
(film): 푣̃= 3062 (w), 2979 (w), 2930 (w), 2854 (w), 1730 (s), 1568 (w), 1449 (m), 1423 (w), 1393 (w),
1368 (m), 1245 (m), 1155 (s), 1095 (m), 1062 (s), 1016 (s), 954 (w), 843 (m) cm-1.
Tert-butyl 3-[(3-methylphenyl)sulfinyl]propanoate (6i)
Following general procedure E, 6i was obtained as a pale yellow oil from 21i (1.50
g, 5.94 mmol, 1.0 equiv.) and sodium periodate (1.27 g, 5.94 mmol, 1.0 equiv.). Yield:
66% (1.05 g, 3.91 mmol). 1H-NMR (400 MHz, CDCl3)  = 7.42 (m, J = 1.8, 0.9 Hz, 1H), 7.39 – 7.34 (m,
2H), 7.27 (m, 1H), 3.13 (ddd, J = 13.4, 8.6, 6.7 Hz, 1H), 2.90 (ddd, J = 13.4, 8.6, 5.7 Hz, 1H), 2.73 (ddd,
J = 17.1, 8.6, 6.7 Hz, 1H), 2.57 – 2.35 (m, 4H), 1.40 (s, 9H) ppm. 13C{1H}-NMR (101 MHz, CDCl3)  =
170.4, 143.0, 139.5, 131.9, 129.1, 124.3, 121.1, 81.5, 51.5, 28.0, 27.4, 21.4 ppm. HRMS (APPI) calcd.
for C14H20O2S+° [M]+° 252.1179; found 252.1174. IR (film): 푣̃= 2984 (w), 2928 (w), 1728 (s), 1362 (m),
1238 (m), 1153 (s), 1081 (m), 1045 (s), 974 (w), 948 (w), 842 (m), 785 (m), 693 (m) cm-1.
Tert-butyl 3-[(3-bromophenyl)sulfinyl]propanoate (6j)
Following general procedure E, 6j was obtained as a colorless oil from 21j (0.815 g,
2.57 mmol, 1.0 equiv.) and sodium periodate (0.659 g, 3.08 mmol, 1.2 equiv.). Yield:
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88% (0.754 g, 2.26 mmol). 1H-NMR (400 MHz, CDCl3)  = 7.77 (t, J = 1.8 Hz, 1H), 7.61 (ddd, J = 7.9,
1.9, 1.0 Hz, 1H), 7.51 (ddd, J = 7.9, 1.8, 1.0 Hz, 1H), 7.39 (t, J = 7.9 Hz, 1H), 3.18 (ddd, J = 13.5, 8.2,
7.0 Hz, 1H), 2.92 (ddd, J = 13.5, 8.2, 5.8 Hz, 1H), 2.76 (ddd, J = 17.3, 8.2, 7.0 Hz, 1H), 2.45 (ddd, J =
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130.8, 126.9, 123.6, 122.6, 81.7, 51.6, 28.0 27.2 ppm. HRMS (ESI) calcd. for C13H1779BrNaO3S+
[M+Na]+ 354.9974; found 354.9968. IR (film): 푣̃= 3056 (w), 2980 (m), 1728 (s), 1569 (w), 1491 (w),
1459 (w), 1416 (w), 1395 (w), 1368 (m), 1248 (m), 1158 (s), 1079 (w), 1050 (m), 844 (w) cm-1.
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Tert-butyl 3-[(pyridin-2-yl)sulfinyl]propanoate (6k)
Following general procedure F, 6k was obtained as a yellow oil from 21k (0.500 g, 2.09
mmol, 1.0 equiv.), H2O2 (30% v/v in water; 0.39 mL, 3.8 mmol, 1.8 equiv.) and sodium sulfite (0.474 g,
3.76 mmol, 1.8 equiv.). Yield: 35% (0.474 g, 1.29 mmol). 1H-NMR (400 MHz, CDCl3)  = 8.63 (ddd, J
= 4.7, 1.7, 1.0 Hz, 1H), 7.96 (m, 1H), 7.92 (m, 1), 7.37 (ddd, J = 7.1, 4.7, 1.6 Hz, 1H), 3.44 (ddd, J = 13.6,
9.6, 6.0 Hz, 1H), 3.13 (ddd, J = 13.6, 9.5, 5.8 Hz, 1H), 2.79 (ddd, J = 17.0, 9.4, 6.0 Hz, 1H), 2.34 (ddd, J
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= 17.0, 9.5, 5.7 Hz, 1H), 1.41 (s, 9H) ppm. C{1H}-NMR (101 MHz, CDCl3)  = 170.3, 163.9, 149.8,
137.9, 124.6, 120.1, 81.4, 48.3, 28.0, 26.8 ppm. HRMS (ESI) calcd. for C12H17NNaO3S+ [M+Na]+
278.0821; found 278.0825. IR (film): 푣̃= 2977 (m), 2941 (w), 3054 (w), 1730 (s), 1576 (m), 1458 (m),
1423 (m), 1368 (m), 1248 (s), 1154 (s), 1053 (s), 849 (w) cm-1.
Tert-butyl 3-((thiophen-2-yl)sulfinyl)propanoate (6l)
Following general procedure F, 6l was obtained as a yellow oil from 21l (0.900 g, 3.68
mmol, 1.0 equiv.), H2O2 (30% v/v in water; 0.68 mL, 6.6 mmol, 1.8 equiv.) and sodium
sulfite (0.836 g, 6.63 mmol, 1.8 equiv.). Yield: 35% (0.335 g, 1.29 mmol). mp: 38.2-39.0 °C. 1H-NMR
(400 MHz, CDCl3)  = 7.66 (dd, J = 5.0, 1.3 Hz, 1H), 7.47 (dd, J = 3.7, 1.3 Hz, 1H), 7.14 (dd, J = 5.0,
3.7 Hz, 1H), 3.25 (dd, J = 7.6, 7.0 Hz, 2H), 2.74 (m, 1H), 2.58 (dt, J = 17.2, 7.2 Hz, 1H), 1.44 (s, 9H)
ppm. 13C{1H}-NMR (101 MHz, CDCl3)  = 170.1, 145.3, 131.2, 129.7, 127.5, 81.7, 53.0, 28.2, 28.1 ppm.
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