One-pot synthesis of α-phenylsulfinyl ketones by reaction of phenyl benzenethiosulfinate with enolate anions, and synthesis of sulfoxides and sulfides by its reaction with Grignard reagents

Article abstract of DOI:10.1016/j.tet.2017.12.028

Phenyl benzenethiosulfinate reacts with enolate anions derived from ketones to give α-phenylsulfinyl ketones directly, together with minor amounts of α-phenylsulfanyl ketones. These are easily separated by forming the water-soluble sodium salts of the sulfinyl compounds. Grignard reagents also react with phenyl benzenethiosulfinate, to give mixtures of sulfoxides and sulfides.

Full text of DOI:10.1016/j.tet.2017.12.028

Accepted Manuscript
One-pot synthesis of α-phenylsulfinyl ketones by reaction of phenyl
benzenethiosulfinate with enolate anions, and synthesis of sulfoxides and sulfides by
its reaction with Grignard reagents
Jerome Fakhry, David H. Grayson
PII:
S0040-4020(17)31290-5
10.1016/j.tet.2017.12.028
TET 29184
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 5 April 2017
Revised Date: 9 December 2017
Accepted Date: 14 December 2017
Please cite this article as: Fakhry J, Grayson DH, One-pot synthesis of α-phenylsulfinyl ketones by
reaction of phenyl benzenethiosulfinate with enolate anions, and synthesis of sulfoxides and sulfides by
its reaction with Grignard reagents, Tetrahedron (2018), doi: 10.1016/j.tet.2017.12.028.
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ACCEPTED MANUSCRIPT
Graphical Abstract
One-pot synthesis of α-phenylsulfinyl ketones by reaction of phenyl
benzenethiosulfinate with enolate anions, and synthesis of sulfoxides and
sulfides by its reaction with Grignard reagents
Jerome Fakhry and David H. Grayson*
School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse Street,
Dublin 2, Ireland
O
O
O
(i) LDA
S(O)Ph
+
SPh
R
R
R
(ii) PhS-S(O)Ph
_
_
(4 15%)
(34 53%)
* Corresponding author: telephone +353-(0)1-896-2021; dgrayson@tcd.ie
1

ACCEPTED MANUSCRIPT
One-pot synthesis of α-phenylsulfinyl ketones by reaction of phenyl
benzenethiosulfinate with enolate anions, and synthesis of sulfoxides and
sulfides by its reaction with Grignard reagents
Jerome Fakhry and David H. Grayson†
School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse Street,
Dublin 2, Ireland
Abstract: Phenyl benzenethiosulfinate reacts with enolate anions derived from ketones
to give
α-phenylsulfinyl ketones directly,together with minor amounts of α-
phenylsulfanyl ketones. These are easily separated by forming the water-soluble sodium
salts of the sulfinyl compounds. Grignard reagents also react with phenyl
benzenethiosulfinate, to give mixtures of sulfoxides and sulfides.
Keywords: ketone enolate, sulfinylation, sulfoxide, thiosulfinate, Grignard
1. Introduction
In connection with other work we needed to access the α-sulfanylated ketone 1, in order to
engage its α-anion in an aldol condensation reaction with aldehyde 2 (Figure 1). We
prepared the ketone 1 from methylheptenone 3 by reaction of its enolate anion with phenyl
benzenethiosulfonate 4 according to a literature procedure.1
Figure 1
However, deprotonation of α-sulfanylketone 1 using LDA, followed by reaction of the
derived carbanion with aldehyde 2, failed to deliver the desired aldolisation product. Instead,
trienone 5, the dehydration product derived from the initially-formed ketol, was isolated in
good yield (Figure 2).
† Corresponding author: telephone +353-(0)1-896-2021; dgrayson@tcd.ie
2

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Figure 2
The (Z)-configuration of the 7,8-double bond of 5 was confirmed by the absence of any n.O.e
between H-8 and the ortho-protons of the neighbouring phenylsulfanyl group, and conforms
with literature precedent.2 A range of reaction conditions, including the addition3 of ZnCl2 to
the pre-formed enolate of 1, was investigated to try to drive the reaction with aldehyde 2
towards the desired aldolisation product, but without success.
We next turned to the α-sulfinylated ketone 6, since successful aldol reactions using the
carbanions of α-sulfinylated ketones have been described in the literature.4 The α-sulfinyl
ketone 6 could be produced by oxidation of the sulfanyl analogue 1 using m-CPBA, but it
occurred to us that 6 might also be accessible in one step by reaction of the enolate of
methylheptenone 3 with phenyl benzenethiosulfinate 7.
Scheme 1 (a) Cl2/AcOH; (b) PhSH/pyridine
Phenyl benzenethiosulfinate 7 is easily prepared (Scheme 1) by the chlorination5 of diphenyl
disulfide 8 to give phenylsulfinyl chloride 9, followed by reaction of 9 with thiophenol in the
presence of pyridine.6 The reagent is a crystalline solid that can be stored for long periods in a
refrigerator.
Kice and Liu7 have reported the reactions of phenyl benzenethiosulfinate 7 with a number of
nucleophiles. These authors found that hard nucleophiles such as oxy-anions attacked 7
preferentially at the sulfinyl (S=O) centre, whereas reactions with secondary amines and with
cyanide ion took place largely or exclusively at the alternative sulfanyl centre. Attack at the
sulfanyl sulfur atom was also observed when thiolate ions are used as nucleophiles. However,
3

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these authors did not describe any reactions of the thiosulfinate 7 with carbanionic
nucleophiles.
Results and Discussion
We now report that lithium enolates derived from ketones react with phenyl
benzenethiosulfinate 7 to yield α-phenylsulfinyl ketones 10 directly (Scheme 2). These are
generally easily separated from the α-phenylsulfanyl ketones 11 that are formed as minor co-
products by virtue of the fact that the carbon-acidic α-phenylsulfinyl ketones 10 give water-
soluble sodium salts on treatment with aqueous sodium hydroxide solution, from which they
can be regenerated by acidification.
Scheme 2 (a) LDA, −78 oC; (b) PhS-SOPh, 1 h
We initially studied the phenylsulfinylation of methylheptenone 3, and obtained optimum
yields of the α-sulfinyl ketone 6 by using LDA as base and allowing the reaction to proceed
o
during 1 h at –78 C. If the reaction was carried out at higher temperatures, varying amounts
of the N,N-diisopropylamino compounds 12 and 13 (minor) were also formed (Figure 3).
Figure 3
In an attempt to avoid the formation of 12 and 13, we utilised the more hindered base lithium
tetramethylpiperidide. However, much poorer yields of the α-sulfinyl ketone 6 were obtained
t
under these conditions, and when BuLi was employed as base none of the sulfinyl ketone 6
was formed.
A variety of ketones of different structural types were successfully converted into their α-
sulfinyl derivatives (6; 14a-21a) using this methodology (Table 1). The sulfoxides obtained
from methylheptenone 3 (entry 1) and from benzylacetone (entry 3) were those derived from
4

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the kinetic enolates of these ketones. Where mixtures of diastereoisomers were produced it
was often possible to effect their separation, either by fractional crystallisation or by
chromatography. The moderate yields of α-sulfinyl ketones that were obtained is likely due
to the fact that the nucleophilic thiophenolate anion formed as a by-product tends to react
with the reagent 7 to give some diphenyl disulfide.7 Yields were not enhanced if two
equivalents of 7 were employed.
X
X
O
O
X
N
SPh
SPh
SPh
Ph
Ph
14a X = O
O
15a X = O
15b X = n/a
16a X = O
16b X = n/a
14b X = n/a
O
X
O
X
O
X
SPh
SPh
SPh
19a X = O
19b X = n/a
18a X = O
18b X = n/a
17a X = O
17b X = n/a
X
O
SPh
X
SPh
O
(CH2)7
20a X = O
20b X = n/a
21a X = O
21b X = n/a
Table 1
Reactions of ketone enolates with phenyl benzenethiosulfinatea
Ketone Phenylsulfinyl ketone Phenylsulfanyl ketone
Entry
_________________________________________________________________________________________________________
1.
2.
3.
4.
5.
6.
methylheptenone
acetophenone
6 (46%)
2 (6%)
14a (45%)
15a (47%)
16a (53%)
17a (44%)
18a (34%)
14b (6%)
15b (4%)
16b (5%)
17b (-)
4-phenylbutan-2-one
2-acetylpyridine
2,5-dimethylheptan-4-one
cyclohexanone
18b (-)
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19a (41%)
7.
8.
9.
cyclopentanone
19b (-)
cyclododecanone
20a (51%)
20b (15%)
21b (-)
4-tert-butylcyclohexanone
21a (42%)
______________________________________________________________________
aYields are of pure materials after recrystallisation or chromatography
We have also investigated the reactions of some organomagnesium halides with phenyl
benzenethiosulfinate 7 (cf. the work of Cogan et al. on the reaction of Grignard reagents with
tert-butyl-tert-butylthiosulfinate8). With the exception of vinylmagnesium chloride (entry 5),
which reacted to give only the derived sulfoxide, significant amounts of sulfides were also
formed in each of these reactions (Table 2), together with some diphenyl disulfide, the
reduction product of phenylbenzenethiosulfinate 7. The highest yields of sulfoxides 22a-29a
were obtained when 2.5 equivalents of Grignard reagent were used, at a temperature of −78
oC and with a reaction time of 2 h.
Table 2
Reactions of Grignard reagents with phenyl benzenethiosulfinate
Entry
Grignard reagent
Sulfoxide
Sulfide
_________________________________________________________________________________________________________
1.
2.
3
EtMgBr
22a (56%)
23a (57%)
24a (51%)
22b (15%)
23b (14%)
24b (9%)
BuMgBr
2-BuMgBr
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4.
5.
6.
7.
8.
cyclohexylmagnesium bromide
25a (51%)
26a (42%)
27a (33%)
28a (46%)
29a (50%)
25b (42%)
26b (-)
vinylmagnesium chloride
allylmagnesium chloride
phenylmagnesium chloride
benzylmagnesium chloride
27b (43%)
28b 34%)
29b (41%)
_______________________________________________________________________
In pursuit of our original synthetic goal, the α-sulfinylated ketone 6 was reduced using
o
DIBAL at −100 C to give the corresponding alcohol 30 as a single diastereoisomer (Figure
4), or with DIBAL in the presence of ZnCl2 to give alcohol 31, also as a single
diastereoisomer (Figure 4). The relative stereochemistries of these alcohols are tentatively
assigned on the basis of literature precedent.4
Figure 4
When the sulfinyl alcohol 31 was deprotonated using two equivalents of n-BuLi and then
reacted with iodomethane, the methylated product 32 was obtained as a single
diastereoisomer in 54% yield (Figure 5). The relative stereochemistry of the new asymmetric
centre is again tentatively assigned on the basis of literature precedent.4
Figure 5
Surprisingly, when the sulfinyl alcohol 31 was deprotonated and then reacted with the
aldehyde 2, none of the expected alkylation product was obtained. However, when the same
sequence was carried out using alcohol 30, all four possible diastereoisomers of the diol 33
7

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were obtained as a mixture in 53% aggregate yield, together with unreacted starting material
30. Two of these diastereoisomers could be obtained in pure form by column
chromatography, but in low isolated yields (16% and 13%, respectively), and we have not
pursued their full stereochemical characterization or further applications for that reason.
3.
Conclusions
The utility of the reagent phenyl benzenethiosulfinate 7 for the direct, one-step formation of
sulfoxides from carbon nucleophiles is clearly of limited synthetic value when Grignard
reagents are employed, because of the non-selective nature of the reactions. However, when
ketone enolates are used as nucleophiles the method delivers α-sulfinyl ketones directly in
yields that are comparable to those obtained overall from the sequence ketone → α-sulfanyl
ketone → α-sulfinyl ketone, via sulfanylation of the ketone followed by mono-oxidation at
sulfur. Furthermore, functional groups that do not tolerate even mildly oxidative conditions
can potentially be present in the ketone moiety. These include, for example, thioether,
selenide and tertiary amino groups, all of which are susceptible to oxidation by reagents such
as cold hydrogen peroxide, and 1,2-diols, which are cleaved by periodate. Additionally, the
method is complementary to existing procedures that rely on reactions of acylating agents,
such as esters or acyl halides, with α-lithiated sulfoxides,9,10 or of ketone enolates with alkyl
arenesulfinates.11
4.
Experimental
General
4.1
1H and 13C NMR spectra were recorded in CDCl3 using a Bruker Avance DPX 400 MHz
spectrometer. Coupling constants are recorded in Hz. Assignments were verified by
appropriate H-H COSY, C-H COSY and DEPT experiments. IR spectra were recorded for
Nujol mulls (N) or liquid films (L) between NaCl plates using Perkin Elmer 883 or Paragon
1000 spectrometers. High-resolution mass spectra were obtained under positive ion
conditions using a Micromass LCT electrospray TOF instrument with a Waters 2690
autosampler. Melting points (uncorrected) were measured in unsealed capillaries using a
Stuart Scientific SMP2 digital apparatus or an Electrothermal IA9100 apparatus. Thin layer
chromatography was carried out using Merck Kieselgel 60 F254 0.2 mm silica gel plates.
Column chromatography was carried out using Merck Kieselgel 60 (70-230 mesh) silica gel.
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All solvents were dried and distilled before use. Grignard reagents were prepared from aryl or
alkyl bromides using magnesium turnings. Vinylmagnesium chloride, allylmagnesium
chloride and benzylmagnesium chloride were purchased from Sigma-Aldrich Chemical Co.
All solutions of organomagnesium compounds were titrated before use. All previously
reported compounds were identified by comparing their spectroscopic data with literature
values. New compounds and compounds for which incomplete literature data is listed were
subjected to IR, NMR and HRMS (accurate mass) analyses.
4.2
Phenyl benzenethiosulfonate 4: This was prepared in 85% yield by the oxidation of
diphenyl disulfide using hydrogen peroxide in acetic acid according to a literature
procedure,12 m. p. 44 oC from methanol (lit.12 m. p. 44-45 oC).
4.3
6-Methyl-1-phenylsulfanylhept-5-ene-2-one 1: 6-Methyl-5-heptene-2-one 3 (5.04
g; 42.8 mol) in dry THF (5 mL) was added dropwise to a solution of LDA, prepared from
diisopropylamine (7.2 mL; 5.16 g; 51 mmol) and n-BuLi (2.5 M in hexanes, 19.2 mL; 48
mmol) in dry THF (100 mL) at −78 oC under an atmosphere of nitrogen. After 20 min at this
temperature the solution of enolate was added by syringe to phenyl benzenethiosulfonate 4
(11 g; 44 mmol ) in THF (10 mL). After 10 min the mixture was quenched using 1 M HCl
solution and extracted with ether. The combined extract was washed with sodium hydrogen
carbonate solution, dried and evaporated. The crude product was purified by column
chromatography (hexane/EtOAc, 10/1) to give 6-methyl-1-phenylsulfanylhept-5-ene-2-one 1
as a colourless oil (6.64 g; 71%) with spectroscopic features consistent with literature data13,
νmax(L) 1710 cm-1; δH 1.61 (3H, s, CH3), 1.68 (3H, s CH3), 2.25 (2H, m, 4-CH2), 2.63 (2H, t,
J 7.5, 3-CH2), 5.08 (1H, t, J 6.5, 5-CH), 7.23-7.41 (5H, m, Ar) ppm.
4.4
2,9-Dimethyl-7-phenylsulfanyldodeca-2,7,11-triene-6-one 5: Sulfanyl ketone 1
(0.65 g; 2.8 mmol), in dry THF (3 mL) was added dropwise to a solution of LDA, prepared
from diisopropylamine (0.85 mL; 0.61 g; 6 mmol) and n-BuLi (2.5 M in hexanes, 2.25 mL;
o
5.6 mmol) in dry THF (10 mL) at −78 C under an atmosphere of nitrogen. After 20 min at
this temperature, 2-methylpent-4-enal 2 (0.3 g; 3 mmol) in dry THF (3 mL) was added and
the cold bath was removed. After 30 min the reaction was quenched using ammonium
chloride solution, extracted with ether, dried and evaporated. The resulting oil was purified
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by column chromatography (hexane : EtOAc, 10 : 1) to give 2,9-dimethyl-7-
phenylsulfanyldodeca-2,7,11-triene-6-one 5 as an oil (0.61 g; 70%). νmax(L) 2966, 2925,
1689, 1640, 1585, 1478, 1439, 1375, 1343, 1119, 1024, 993, 915, 741 cm-1; δH 1.11 (3H, d, J
6.5, CH3), 1.55 (3H, s, CH3), 1.64 (3H, s, CH3), 2.18 (4H, m, 4-CH2 and 10-CH2), 2.67 (2H,
t, J 7.5, 5-CH2), 3.12 (1H, m, 9-H), 4.97 (1H, t, J 6.5, 3-H), 5.01-5.12 (2H, m, 12-CH2), 5.74
(1H, m, 11-CH), 7.00 (1H, d, J 10, 8-H), 7.17 (3H, m, 2’-H and 4’-H), 7.26 (2H, t, J 7, 3-
H)ppm; δC 17.1 (CH3), 19.0 (CH3), 22.6 (CH2), 25.1 (CH3), 34.6 (CH), 39.1 (CH2), 40.2
(CH2), 116.4 (CH2), 122.4 (CH), 125.5 (CH), 127.1 (CH), 128.7 (CH), 129.1 (CH), 132.0
(C), 132.6 (C), 135.5 (C), 154.8 (CH), 199.4 (C=O)ppm; HRMS (ESI): MH+ found:
315.1775. C20H26OS requires 315.1783.
4.5
1-Phenylsulfinyl-6-methylhept-5-en-2-one 6: m-Chloroperoxybenzoic acid (75%;
0.9 g; 4 mmol) was added slowly to a solution of 6-methyl-1-phenylsulfanylhept-5-ene-2-one
o
1 (1 g; 4.3 mmol) in dichloromethane (20 mL) at 0 C. After 1 h at this temperature the
mixture was diluted with dichloromethane and washed with sodium hydrogen carbonate
solution, dried and evaporated. The resulting oil was purified by column chromatography
(hexane : EtOAc 10 : 1 → 1 : 1) to give 1-phenylsulfinyl-6-methylhept-5-en-2-one 6 as an oil
(0.82 g; 76%) (lit.13 an oil), νmax(L) 3080, 2870, 1712, 1444, 1400, 1376, 1088, 1045, 1023,
748 cm-1; δH 1.59 (3H, s, CH3), 1.66 (3H, s, CH3), 2.22 (2H, m, 4-CH2), 2.49 (2H, m, 3-CH2),
3.77 (1H, d, JAB 13.5, 1-CHa), 3.88 (1H, d, JBA 13.5, 1-CHb), 5.00 (1H, t, J 7, 5-CH), 7.53
(3H, m, ArH), 7.66 (2H, m, ArH) ppm; δC 17.7 (CH3), 21.9 (4-CH2), 25.6 (CH3), 45.0 (3-
CH2), 68.2 (1-CH2), 122.0 (5-CH), 124.1 (CH), 129.4 (CH),131.6 (6-C), 133.2 (CH), 143.2
(1’-C), 201.4 (C=O) ppm.
4.6
Phenyl benzenethiosulfinate 7: Diphenyl disulfide (15 g; 68.8 mmol), in acetic acid
(8 mL), was treated at 0 ºC with chlorine gas (CAUTION) until the initial red colouration
had been discharged. After removal of excess chlorine and acetyl chloride under reduced
pressure the product was distilled to give phenylsulfinyl chloride 9 (16.1 g; 0.1 mol; 73 %),
b.p. 73 ºC @ 1 mm Hg (lit.14 bp 71−72 ºC @ 1.5 mm Hg); νmax(L) 3063, 1580, 1447, 1378,
1186, 1151, 1077, 998, 749, 683 cm-1; δH 7.65 (3H, m), 7.90 (2H, m); dC 123.3 (CH), 129.1
(CH), 134.8 (CH), 148.3 (C) ppm. To a solution of phenylsulfinyl chloride 9 (3.21 g; 20
mmol) in dry ether (50 mL) at –10 ºC under N2 was added dry pyridine (1.8 g; 22.8 mmol).
10

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Thiophenol (2.08 mL; 2.24 g; 20.4 mmol ) in dry ether (20 mL) was added dropwise and
stirring was continued for 30 min until the temperature reached 0 ºC. The mixture was
quenched with aqueous HCl (0.25 M), washed 4 times with cold water, dried over CaCl2 and
carefully concentrated under reduced pressure. The resulting solid was quickly recrystallised
from chloroform : hexane to afford pure phenyl benzenethiosulfinate 7 (3.79 g; 81%), m. p.
69 ºC (lit.5 m. p. 69-70 ºC), νmax(N) 3055, 1576, 1464, 1442, 1378, 1148, 1097, 1061, 1025,
742, 687 cm-1; δH 7.36-7.72 (10H, m) ppm; δC 123.9 (CH), 128.5 (CH), 128.8 (CH), 129.8
(CH), 131.1 (CH), 130.7 (C), 134.9 (CH), 145.0 (C) ppm.
4.7 General procedure for the synthesis of α-phenylsulfinylketones
To a solution of LDA, prepared from diisopropylamine (3.56 mmol) and n-BuLi (2.5 M in
hexanes; 3.48 mmol) in dry THF (10 mL) at –78 ºC under N2, was added a ketone (3.15
o
mmol) in dry THF (2 cm3). After stirring during 1hr at −78 C the solution of enolate was
added via syringe to phenyl benzenethiosulfinate 7 (0.5 g; 2 mmol) in dry THF (15 mL) at –
78 ºC. After 1h the mixture was quenched with aqueous NH4Cl and extracted with ether. The
combined ethereal extract was then extracted using aqueous sodium hydroxide (1 M).15 The
alkaline aqueous phase was separated, acidified using concentrated HCl and extracted with
ether. This ethereal extract was washed with sodium hydrogen carbonate solution, dried
(MgSO4) and evaporated. The product was then further purified by chromatography over
silica gel using hexane : ethyl acetate as eluant. The ethereal extract remaining after treatment
with aqueous sodium hydroxide solution was dried and evaporated to give any α-sulfanyl
ketone that had been formed.
4.8
spectroscopic data as given above.
1-Phenylsulfinyl-6-methylhept-5-en-2-one13 6: obtained as an oil (0.24 g; 46%),
4.9
spectroscopic data as given above.
1-Phenylsulfanyl-6-methylhept-5-en-2-one13 1: obtained as an oil (45 mg; 6%),
4.10
1-Phenyl-2-phenylsulfinylethanone 14a16: obtained as a solid (0.23 g; 45%), m.p.
70 ºC (ether - hexane) (lit.9 mp 69-72 oC); νmax(N) 3450, 3058, 2906, 1673, 1597, 1579, 1444,
1279, 1196, 1086, 1045, 993, 748, 688 cm-1; δH 4.31 (1H, d, JAB 14.5, 2-CHa), 4.58 (1H, d,
JBA 14.5, 2-CHb), 7.46 (2H, m, ArH’), 7.50 (3H, m, ArH’’), 7.60 (1H, m, ArH’), 7.70 (2H, m,
11

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ArH’’), 7.88 (2H, m, ArH’) ppm; δC 65.6 (CH2), 124.2, 128.7, 128.8, 129.3, 131.6 and 134.2
(all CH), 135.5 (C, 1’-C), 143.8 (C, 1’’-C), 191.0 (C=O) ppm.
4.11 1-Phenyl-2-phenylsulfanylethanone 14b: obtained as an oil (lit.17 an oil) (45 mg;
6%); δH 4.27 (2H, s), 7.21-7.46 (7H, m), 7.55 (1H, t, J 6.5), 7.93 (2H, d, J 6.5) ppm.
4.12 4-Phenyl-1-phenylsulfinylbutan-2-one 15a: obtained as a solid (0.27 g; 47%), m.p.
43 ºC (ether - hexane) (lit.9 an oil), νmax(N) 3413, 3026, 2925, 1711, 1603, 1496, 1444, 1367,
1184, 1088, 1045, 748, 700 cm-1; δH 2.84 (4H, m, 3- and 4-CH2), 3.76 (1H, d, JAB 13.5, 1-
CHa) 3.86 (1H, d, JBA 13.5, 1-CHb), 7.19 (2H, m, ArH’), 7.28 (3H, m, ArH’), 7.53 (3H, m,
ArH’’), 7.61 (2H, m, ArH’’) ppm; δC 28.7 (4-CH2), 46.0 (3-CH2), 67.6 (1-CH2), 124.0, 126.2,
128.3, 128.5, 129.4 and 131.5 (CH), 139.8 (1’-C), 142.6 (1’’-C), 200.1 (C=O) ppm.
4.13 4-Phenyl-1-phenylsulfanylbutan-2-one 15b: obtained as an oil (30 mg; 4%), (lit.17
an oil); δH 2.84-2.91 (4H, m), 3.61 (2H, s), 7.11-7.30 (10H, m) ppm.
4.14 1-(2’-Pyridyl)-2-phenylsulfinylethanone 16a: obtained as a viscous oil (0.27 g;
0
53%), (lit.18 a solid, m. p. 70 C); νmax(L) 3461, 3056, 2916, 1693, 1583, 1475, 1441, 1307,
1286, 1248, 1145, 1085, 1047, 995, 748, 690 cm-1; δH 4.62 (1H, d, JAB 14, 2-CHa), 4.82 (1H,
d, JBA 14, 2-CHb), 7.47 (4H, m, ArH and 5’-CH), 7.71 (2H, m, ArH), 7.83 (1H, dt, J 2 and
7.5, 4’-CH), 8.03 (1H, d, J 8, 3’-CH), 8.64 (1H, d, J 5, 6’-CH) ppm; δC 64.4 (2-CH2), 122.2,
124.2, 127.7, 129.1, 131.3 and 137 (CH), 143.0 (1’’-C), 149.0 (6’-CH), 151.7 (2’-C), 192.1
(C=O) ppm. HRMS (ESI): MNa+, found 268.0388. C13H11O2NS requires 268.0408.
4.15 1-(2’-Pyridyl)-2-phenylsulfanylethanone19 16b: obtained as an oil (45 mg; 5%);
νmax(L) 3055, 1693, 1582, 1437, 1393, 1356, 1303, 1284, 1246, 1202, 1148, 1088, 1068,
1046, 1024, 993, 905, 819, 738, 689, 680 cm-1; δH 4.58 (s, 2-CH2), 7.21 (1H, t, J 8, 4’’-H),
7.3 (2H, t, J 8, 3’’-H and 5’’-H), 7.44 (2H, d, J 8, 2’’-H and 6’’-H), 7.51 (1H, apparent t, J 6,
5’-H), 7.87, (1H, apparent t, J 6, 4’-H), 8.12 (1H, d, J 6, 3’-H) 8.65 (1H, d, J 6, 6’-H) ppm; δC
39.63 (2-CH2), 123.34 (C-3’), 126.67 (C-4’’), 128.92 (C-3’’ and C-5’’), 129.96 (C-2’’ and C-
6’’), 133.54 (C-5’), 136.3 (C, 2’’-C), 137.18 (C-4’), 151.52 (C-6’), 152.4 (C, 2’-C), 195.2
(C=O) ppm. HRMS (ESI): MNa+, found 252.0458. C13H11NOS requires 252.0459.
12

ACCEPTED MANUSCRIPT
4.16
2,6-Dimethyl-3-benzenesulfinylheptan-4-one 17a: obtained as a 1:1 mixture of
diastereoisomers (0.23 g; 44%) that were separated by chromatography over silica gel using
hexane/ethyl acetate 4/1 as eluant. Diastereoisomer A: was obtained as a solid (0.1 g), m.p.
94 ºC (ether/hexane); νmax(N) 1702, 1462, 1402, 1377, 1296, 1262, 1113, 1085, 1045, 747,
688 cm-1; δH 0.75 (3H, d, J 6.5, 7-CH3), 0.77 (3H, d, J 6.5, 7-CH3), 1.04 (3H, d, J 6.5, 1-
CH3), 1.35 (3H, d, J 6.5, 1-CH3), 1.95 (1H, m, J 6.5, 6-CH), 1.98 (1H, dd, J 6.5, 18.5, 5-
CHa), 2.22 (1H, dd, J 6.5, 18.5, 5-CHb), 2.49 (1H, m, J 6.5, 10.5, 2-CH), 3.09 (1H, d, J 10.5,
3-CH), 7.52 (5H, m, ArH) ppm; δC 20.1 (7-CH3), 20.5 (7-CH3), 22.0 (1-CH3), 22.1 (1-CH3),
22.5 (6-CH), 26.8 (2-CH), 53.4 (5-CH2), 80.3 (3-CH), 123.9, 128.8, 130.7 (CH), 140.5 (1’-
C), 204.6 (C=O) ppm. HRMS (ESI): [MNa]+, found 289.1222. C15H22O2S requires 289.1238.
Diastereoisomer B: was obtained as an oil (0.1 g); νmax(L) 3469, 3059, 2959, 2872, 1701,
1468, 1444, 1392, 1367, 1291, 1172, 1085, 1053, 1032, 747, 691 cm-1; δH 0.60 (3H, d, J 6.5,
7-CH3), 0.75 (3H, d, J 6.5, 7-CH3), 1.14 (3H, d, J 6.5, 1-CH3), 1.24 (3H, d, J 6.5, 1-CH3),
1.63 (1H, dd, J 6.5, 18.6, 5-CHa), 1.82 (1H, m, J 6.5, 6-CH), 2.11 (1H, dd, J 6.5, 18.5, 5-
CHb), 2.55 (1H, m, J 6.5, 2-CH), 3.65 (1H, d, J 6, 3-CH), 7.49 (3H, m, ArH), 7.61 (2H, m,
ArH) ppm; δC 18.6 (7-CH3), 20.8 (7-CH3), 21.8 (1-CH3), 21.9 (1-CH3), 22.6 (6-CH), 27.7
(7-CH), 55.5 (5-CH2), 83.3 (3-CH), 125.0, 128.7 and 131.2 (CH), 141.9 (1’-C), 204.6 (C=O)
ppm. HRMS (ESI): MNa+, found 289.1245. C15H22O2S requires 289.1238.
4.17 2-Phenylsulfinylcyclohexanone16 18a: obtained as a solid (0.16 g; 34%), m.p. 108 ºC
o
(ether/hexane) (lit.20 mp 108-109 C), comprising a ca. 2 : 1 inseparable mixture of
diastereoisomers; νmax(N) 3462, 2945, 2864, 1709, 1444, 1292, 1126, 1086, 1040, 750, 690
cm-1; δΗ 1.55−2.60 (8H, m, CH2 groups), 3.40 (0.7H, dd, J 5, 10, 2-CH), 3.58 (0.3H, dd, J
6.5, 6.5, 2-CH), 7.51 (3H, m, ArH), 7.60 (2H, m, ArH) ppm; δC 22.3 (CH2), 22.8 (CH2), 24.4
(CH2), 25.9 (CH2), 26.0 (CH2), 27.3 (CH2), 41.9 (CH2), 42.6 (CH2), 72.56 (CH), 74.0 (CH),
124.3 (CH), 124.8 (CH), 128.6 (CH), 127.7 (CH), 130.7 (CH), 131.0 (CH), 142.1 (C), 204.8
(C=O) ppm.
4.18 2-Phenylsulfinylcyclopentanone 19a: obtained as an oil (0.18 g; 41%) (lit.21 an oil),
comprising a ca. 4 : 1 inseparable mixture of diastereoisomers; νmax (L) 3461, 2966, 2887,
1736, 1444, 1313, 1144, 1084, 1049, 1036, 750, 690 cm-1; δH 1.70−2.60 (6H, m, CH2
groups), 3.30 (0.8H, apparent t, J 9, 9, 2-CH), 3.77 (0.2 H, dd, J 6, 9, 2-CH), 7.52 (3H, m,
ArH), 7.60 (2H, m, ArH) ppm; δC 18.7 (CH2), 19.9 (CH2), 20.00 (CH2), 22.3 (CH2), 38.7
13

ACCEPTED MANUSCRIPT
(CH2), 38.8 (CH2), 68.4 (CH2), 70.6 (CH), 123.5 (CH), 124.4 (CH), 128.6 (CH), 128.8 (CH),
130.6 (CH), 131.1 (CH), 141.9 (C), 211.3 (C=O) ppm.
4.19 2-Phenylsulfinylcyclododecanone22 20a: obtained via column chromatography
(hexane/EtOAc 10/1 → 1/1) as a solid (0.33 g; 51%), consisting of a ca. 3 : 2 mixture of
diastereoisomers; δH 1.20−2.20 (m, 18H, CH2 groups), 2.55 (m, 2H, 12-CH2), 3.83 (dd,
0.43H, J 3; 11, 2-CH), 3.98 (dd, 0.57H, J 3.5; 11, 2-CH), 7.50-7.55 (m, 3H, ArH), 7.62 (m,
2H, ArH) ppm.
The minor diastereoisomer of 20a could be obtained in pure form by fractional crystallisation
of the mixture, m.p. 115 ºC (diethyl ether); νmax(N) 1693, 1465, 1442, 1398, 1375, 1136,
1084, 1039, 750, 698 cm-1; δH 1.20−2.20 (18H, m, CH2 groups), 2.55 (2H, m, 12-CH2), 3.83
(1H, dd, J 3; 11, 2-CH), 7.50-7.55 (3H, m, ArH) and 7.62 (2H, m, ArH) ppm; δC 21.8 (CH2),
22.0 (CH2), 23.2 (CH2), 24.00 (CH2), 24.3 (CH2), 24.55 (CH2), 24.6 (CH2), 24.7 (CH2), 25.1
(CH2), 41.8 (CH2), 74.0 (CH), 123.4 (CH), 128.8 (CH), 131.3 (CH), 141.8 (C), 205.0 (C=O)
ppm. HRMS (ESI): MNa+, found 329.1563. C18H26O2S requires 329.1551.
4.20 2-Phenylsulfanylcyclododecanone 20b: isolated via column chromatography as a
o
solid (91 mg; 15%), m.p. 95 ºC (ether/hexane) (lit.23 mp 94−98 C); δH 1.10−2.20 (18H, m,
CH2 groups), 2.62 (2H, m, 12-CH2), 3.90 (1H, dd, J = 3.5 and 12, 2-CH), 7.31 (5H, m, ArH)
ppm.
4.21 2-Phenylsulfinyl-4-tert-butylcyclohexanone24 21a: obtained as an oil (0.25 g; 42%),
consisting of a ca. 1 : 1 mixture of diastereoisomers; δH 0.91 (9H, s, tert-CH3), 1.53 (2H, m,
5-CH2), 1.88 (1H, m, 4-CH), 2.05−2.55 (4H, m, 3- and 6-CH2), 3.41 (0.46H, m, 2-CH), 3.43
(0.54H, dd, J 6; 13.5, 2-CH), 7.51 (3H, m, ArH), 7.70 (2H, m, ArH) ppm. One of these
diastereoisomers could be obtained in pure form by fractional crystallisation of the mixture
from diethyl ether, m.p. 101 ºC; νmax(N) 1712, 1678 1581, 1475, 1440, 1367, 1329, 1145,
1088, 1047, 746, 690 cm-1; δH 0.91 (9H, s, tert-CH3), 1.53 (2H, m, 5-CH2), 1.88 (1H, m, 4-
CH), 2.05−2.55 (4H, m, 3- and 6-CH2), 3.43 (1H, dd, J 6; 13.5, 2-CH), 7.51 (3H, m, ArH),
7.70 (2H, m, ArH) ppm; δC 25.3 (CH2), 26.8 (CH2), 27.1 (CH3), 32.5 (1’-C), 41.2 (CH2), 45.7
(CH), 72.7 (CH), 124.4 (CH), 128.6 (CH), 130.5 (CH), 142.7 (C), 205.7 (C=O) ppm. HRMS
(ESI): MNa+, found 301.1258. C16H22O2S requires 301.1238.
14

ACCEPTED MANUSCRIPT
4.22
General procedure for reaction of Grignard reagents with phenyl
benzenethiosulfinate 7: A Grignard reagent (in THF; 1 mmol; 2.5 equivalents)25 was added
to phenyl benzenethiosulfinate 7 (0.1 g; 0.4 mmol) dissolved in dry THF (3 mL) at –78 ºC.
The resulting mixture was stirred at –78 ºC during 2 h and then quenched with aqueous
ammonium chloride solution. The aqueous layer was extracted several times with ether and
the combined organic layers were washed with sodium hydrogen carbonate solution, dried,
and concentrated at reduced pressure. Products were then purified by chromatography over
silica gel using hexane/EtOAc as eluant
.
4.23 1-Phenylsulfinylethane26 22a: an oil (36 mg; 56%); νmax(L) 2975, 2933, 1479, 1444,
1088, 1045, 1022, 748, 694 cm-1; δH 1.19 (3H, t, J 7.5 , 2-CH3), 2.76 (1H, apparent sextet, J
7; 14.6, 1-CHa), 2.90 (1H, apparent sextet, J 7; 14.5, 1-CHb), 7.49 (3H, m, ArH), 7.60 (2H, m,
ArH) ppm; δC 5.9 (CH3), 49.8 (CH2), 123.7 (CH), 128.7 (CH), 130.4 (CH), 142.9 (C) ppm.
4.24 1-Phenylsulfanylethane27 22b: an oil (9 mg; 15%); δH 1.36 (3H, t, J 7.5, 2-CH3), 2.76
(2H, q, J 7.5, 1-CH2), 7.23 (5H, m, ArH) ppm; δC 14.4 (CH3), 27.8 (CH2), 125.7 (CH), 128.3
(CH), 129.3 (CH), 135.8 (C) ppm.
4.25 1-Phenylsulfinylbutane28 23a: an oil (44 mg; 57%); νmax(L) 2958, 2931, 2871, 1458,
1444, 1088, 1038, 997, 750, 692 cm-1; δH 1.69 (2H, m, 2-CH2), 2.81 (2H, t, J 7, 1-CH2), 7.50
(3H, m, ArH), 7.62 (2H, m, 2H, ArH) ppm; δC 13.5 (CH3), 21.8 (CH2), 24.1 (CH2), 57.0
(CH2), 124.0 (CH), 129.1 (CH), 130.8 (CH),141.4 (C) ppm.
4.26 1-Phenylsulfanylbutane29 23b: an oil (10 mg; 14%); δH 0.98 (3H, t, J 7.5, 4-CH3),
1.49 (2H, m, 3-CH2), 1.69 (2H, m, 2-CH2), 2.97 (2H, t, J 7.5, 1-CH2), 7.24 (5H, m, ArH)
ppm; δC 13.6 (CH3), 21.9 (CH2), 31.2 (CH2), 33.2 (CH2), 125.1 (CH), 126.2 (CH), 128.4
(CH), 135.3 (C) ppm.
4.27 2-Phenylsulfinylbutane30, 31 24a: was obtained as a 4 : 5 mixture of diastereoisomers
(39 mg; 51%) that were separated by chromatography over silica gel using hexane/EtOAc 4/1
as eluant. Diastereoisomer A: an oil; νmax(L) 2967, 2931, 2875, 1460, 1444, 1087, 1037,
750, 694 cm-1; δH 1.05 (3H, d, J 7, 1-CH3), 1.09 (3H, t, J 7.5, 4-CH3), 1.48 (1H, m, part of an
AB system, 3-CHa), 1.94 (1H, m, part of an AB system, 3-CHb), 2.53 (1H, m, 2-CH), 7.49
15

ACCEPTED MANUSCRIPT
(3H, m, ArH), 7.55 (2H, m, ArH) ppm; δC 9.7 (CH3), 11.1 (CH3), 23.4 (CH2), 60.7 (CH),
124.2 (CH), 128.4 (CH) 130.1 (CH), 141.7 (C) ppm. Diastereoisomer B: an oil; νmax(L)
2966, 2933, 2875, 1477, 1458, 1444, 1086, 1037, 998, 750, 692 cm-1; δH 0.97 (3H, t, J 7.5,
4-CH3), 1.06 (3H, d, J 6.5, 1-CH3), 1.44 (1H, m, part of an AB system, 3-CHa), 1.78 (1H, m,
part of an AB system, 3-CHb), 2.68 (1H, m, 2-CH), 7.47 (3H, m, ArH), 7.66 (2H, m, ArH)
ppm; δC 10.5 (CH3), 11.5 (CH3), 21.6 (CH2), 60.5 (CH), 124.9 (CH), 128.4 (CH), 130.6
(CH), 141.1 (C) ppm.
4.28 2-Phenylsulfanylbutane32 24b: an oil (6 mg, 9%); δH 1.04 (3H, t, J 7, 4-CH3), 1.30
(3H, d, J 7, 1-CH3), 1.64 (2H, m, 3-CH2), 3.19 (1H, sextet, J 6.5, 2-CH), 7.28 (5H, m, ArH)
ppm; δC 10.9 (CH3), 21.4 (CH3), 31.1 (CH2), 42.7 (CH), 125.9 (CH), 128.4 (CH), 130.1
(CH), 135.2 (C) ppm.
4.29 1-Phenylsulfinylcyclohexane 25a: a solid (45 mg, 51%), m.p. 62 ºC (ether - hexane)
(lit.33, 34 mp 62−64 oC); νmax(N) 3462, 3057, 2931, 2854, 1477, 1458, 1444, 1084, 1041, 997,
750, 692 cm-1; δH 1.21 (4H, m, 2- and 6-CH2), 1.37 (2H, m, 4-CH2), 1.81 (4H, m, 3- and 5-
CH2), 2.54 (1H, m, 1-CH), 7.47 (3H, m, ArH), 7.58 (2H, m, ArH) ppm; δC 23.9 (CH2), 25.2
(CH2), 25.4 (CH2), 25.5 (CH2), 26.2 (CH2), 63.0 (CH), 124.5 (CH), 128.4 (CH), 130.4 (CH),
141.4 (C) ppm.
4.30 1-Phenylsulfanylcyclohexane34 25b: an oil (34 mg, 42%); νmax(L) 2928, 2852, 1581,
1477, 1439, 1263, 1091, 1024, 998 cm-1; δH 1.18 (4H, m, 2- and 6-CH2), 1.37 (2H, m, 4-
CH2), 1.74 (4H, m, 3- and 5-CH2), 3.16 (1H, m, 1-CH), 7.28 (5H, m, ArH) ppm; δC 25.7
(CH2), 26.0 (CH2), 33.3 (CH2), 46.5 (CH), 126.1 (CH, 128.3 (CH), 131.4 (CH), 134.7 (C)
ppm.
4.31 1-Phenylsulfinylethene16 26a: an oil (37 mg, 58%); νmax(L) 3469, 3059, 2926, 1475,
1444, 1086, 1049, 1022, 956, 752, 690 cm-1; δH 5.90 (1H, d, J 9.6, 2-CHZ), 6.21 (1H, d, J
16.5, 2-CHE), 6.61(1H, dd, J 9.5, 16.5, 1-CH), 7.51 (3H, m, ArH), 7.64 (2H, m, ArH) ppm;
δC 120.8 (CH2), 124.2 (CH), 129.0 (CH), 130.7 (CH), 142.7 (CH), 143.0 (C) ppm.
16

ACCEPTED MANUSCRIPT
4.32 1-Phenylsulfinylprop-2-ene16 27a: an oil (23 mg, 33%); νmax(L) 3473, 3057, 2920,
1477, 1444, 1090, 1043, 997, 931, 750 and 690 cm-1; δH 3.53 (1H, dd, J 7.5; 13, 1-CHa), 3.58
(1H, dd, J 7.5; 13, 1-CHb), 5.21 (1H, d, J 17, 3-CHE), 5.35 (1H, d, J 10, 3-CHZ), 5.67 (1H, m,
2-CH), 7.53 (3H, m, ArH), 7.63 (2H, m, ArH) ppm; δH 60.5 (CH2), 123.7 (CH2), 123.9 (CH),
124.8 (CH) 128.6 (CH), 130.6 (CH), 142.6 (C) ppm.
4.33 1-Phenylsulfanylprop-2-ene35 27b: an oil (27 mg, 43%); νmax(L) 2916, 1637, 1584,
1480, 1438, 1229, 1089, 1025, 987, 919 cm-1; δH 3.58 (2H, d, J 7, 1-CH2), 5.10 (1H, d, J 10,
3-CHZ), 5.16 (1H, d, J 17, 3-CHE), 5.91 (1H, m, 2-CH), 7.22 (5H, m, ArH) ppm; δC 36.7
(CH2), 117.6 (CH2), 125.8 (CH), 128.4 (CH), 129.4 (CH), 133.1 (CH, 135.5 (C) ppm.
4.34 1-Phenylsulfinylbenzene 28a: a solid (39 mg, 46%); m.p. 71 ºC (ethyl acetate/hexane)
o
(lit.36 mp 71 C); νmax(N) 1463, 1444, 1377, 1088, 1036, 1022, 995, 755, 737, 694 cm-1; δH
7.47 (6H, m, ArH) and 7.67 (4H, m, ArH) ppm; δC 124.3 (CH), 128.9 (CH), 130.6 (CH),
145.2 (C) ppm.
4.35 1-Phenylsulfanylbenzene 28b: an oil (27 mg, 34%); δH 7.27 (2H, m, ArH), 7.33 (4H,
m, ArH), 7.38 (4H, ArH) ppm.
4.36 1-Phenylsulfinylphenylmethane 29a: a solid (45 mg, 50%), m.p. 122 ºC (ethyl
o
acetate) (lit.37 mp 120−122 C); νmax 1495, 1443, 1377, 1086, 1034, 1020, 997, 914, 765,
744, 690 cm-1; δH 4.01 (1H, d, JAB 12.5, 1-CHa), 4.11 (1H, d, JAB 12.5, 1-CHb), 6.99 (2H, m,
ArH’), 7.27 (3H, m, ArH’), 7.42 (5H, m, ArH’’) ppm; δC 63.1 (CH2), 124.4 (CH), 128.2
(CH), 128.4 (CH), 128.6 (CH), 128.8 (C), 130.3 (CH), 131.1 (CH), 142.6 (C) ppm.
4.37
1-Phenylsulfanylphenylmethane38 29b: a solid, (35 mg, 41%), m.p. 42 ºC
(ether/hexane) (lit.39 mp 41−42 oC); δH 4.16 (2H, s, 1-CH2), 7.19-7.36 (10H, m, ArH) ppm.
4.38 Diastereoselective reduction of 1-phenylsulfinyl-6-methylhept-5-en-2-one 6:
(a) With DIBAL: A solution of DIBAL (1.5 M in toluene; 0.6 mL; 1 mmol) was added to a
solution of the ketone 6 (0.1 g; 0.4 mmol) in dry THF (10 mL) at −100 oC under N2. After 30
min at this temperature the reaction was quenched using aqueous ammonium chloride
17

ACCEPTED MANUSCRIPT
solution and extracted with ether. The combined extract was washed with 1 M HCl followed
by brine, dried and evaporated. The resulting oil was purified by column chromatography
(hexane : EtOAc 1 : 1) to give, as a single diastereoisomer, the phenylsulfinyl alcohol 30a as
an oil (0.81 g; 80%); νmax(L) 3368, 3057, 2965, 2360, 2342, 1476, 1443, 1377, 1085, 1046,
1019, 997, 749 cm-1 δH 1.46 (2H, m, 4-CH2), 1.59 (3H, s, CH3), 1.65 (3H, s, CH3), 2.07 (2H,
;
m, CH2), 2.74 (1H, dd, J 2; 13.5, 1-CHa), 3.04 (1H, dd, J 10; 13.5, 1-CHb), 4.22, (1H, m, 2-
CH), 5.04 (1H, t, J 7, 5-CH), 7.53 (3H, m, ArH), 7.64 (2H, m, ArH) ppm; δC 17.2 (CH3),
23.4 (4-CH2), 25.2 (CH3), 36.6 (3-CH2), 61.9 (1-CH2), 65.7 (2-CH), 123.3 (5-CH), 123.9
(CH), 129.4 (CH), 131.3 (CH), 132.1 (C, 6-C), 143.6 (C 1’-C) ppm. HRMS (ESI): MNa+,
found 275.1087. C14H20O2S requires 275.1082.
(b) With DIBAL/ZnCl2: This reduction was carried out exactly as described above, except
that the THF solution of the ketone 6 was stirred with freshly-fused zinc chloride (7 mg)
o
during 30 min at r.t. prior to cooling to −100 C before the addition of DIBAL. Work-up
afforded the phenylsulfinyl alcohol 30b as an oil (71%), which was again a single
diastereoisomer, but different to 30a; δH 1.59 (2H, m, 4-CH2), 1.61 (3H, s, CH3), 1.69 (3H, s,
CH3), 2.13 (2H, m, CH2), 2.82 (1H, dd, J 2; 13, 1-CHa), 2.99 (1H, dd, J 10.5; 13.0, 1-CHb),
4.29, (1H, m, 2-CH), 5.10 (1H, t, J 7, 5-CH), 7.54 (3H, m, ArH), 7.67 (2H, m, ArH) ppm; δC
17.2 (CH3), 23.2 (4-CH2), 25.2 (CH3), 36.8 (3-CH2), 62.3 (1-CH2), 67.8 (2-CH), 122.9 (5-
CH), 123.4 (CH), 129.0 (CH), 130.9 (CH), 132.1 (C, 6-C), 143.6 (C 1’-C) ppm. HRMS
(ESI): MNa+, found 275.1083. C14H20O2S requires 275.1082.
4.39 C-Methylation of sulfinyl alcohol 30b: 2-phenylsulfinyl-7-methyloct-6-ene-3-ol 31:
n-BuLi (2.5 M in hexane, 0.2 mL; 0.5 mmol) was added to a solution of sulfinyl alcohol 30b
o
(55 mg; 0.2 mmol) in dry THF (5 mL) at −78 C under N2. After 30 min at this temperature,
iodomethane (37 mg; 0.3 mmol) in dry THF (1 mL) was added and the mixture was allowed
to warm up to rt during 1 h. After quenching with aqueous ammonium chloride solution the
mixture was extracted with ether and the combined extract was washed and dried.
Evaporation of solvent afforded an oil that was purified by column chromatography to give a
single40 diastereoisomer of 2-phenylsulfinyl-7-methyloct-6-ene-3-ol 31 as a colourless oil (32
mg, 54%); νmax(L) 3369, 3058, 2967, 2927, 2856, 1475, 1444, 1376, 1308, 1263, 1161, 1085,
1059, 1018, 996, 750 cm-1; δH 0.98 (3H, d, J 7, 1-CH3), 1.53 (2H, m, 5-CH2), 1.65 (3H, s,
18

ACCEPTED MANUSCRIPT
CH3), 1.71 (3H, s, CH3), 2.20 (2H, m, 4-CH2), 2.96 (1H, apparent quintet, J 7.5, 2-CH), 4.05
(1H, m, 3-CH), 5.14 (1H, t, J 7, 6-CH), 7.56 (3H, m, ArH), 7.75 (2H, m, Ar H) ppm; δC 9.2
(1-CH3), 17.2 (CH3), 22.9 (5-CH2), 25.2 (CH3), 37.8 (4-CH2), 64.3 (2-CH), 72.2 (3-CH),
123.2 (6-CH), 125.3 (CH), 128.7 (CH), 131.3 (CH), 132.1 (C; 7-C), 141.9 (C) ppm. HRMS
(ESI): MH+, found 267.1424. C15H22O2S requires 267.1419.
4.40 Alkylation of sulfinyl alcohol 30a with 2-methylpent-4-enal 3:- 6-benzenesulfinyl-
4,11-dimethyldodeca-1,10-diene-5,7-diol 32: n-BuLi (2.5 M in hexane, 0.4 mL; 1 mmol)
was added to a solution of sulfinyl alcohol 30a (110 mg; 0.4 mmol) in dry THF (5 mL) at −78
oC under N2. After 30 min at this temperature, 2-methylpent-4-enal 3 (52 mg; 0.5 mmol) in
dry THF (1 mL) was added and the mixture was allowed to warm up to rt during 1 h. After
quenching with aqueous ammonium chloride solution the mixture was extracted with ether
and the combined extract was washed and dried. Evaporation of solvent afforded an oil which
was purified by column chromatography using hexane/EtOAc 3/1 to give 6-benzenesulfinyl-
4,11-dimethyldodeca-1,10-diene-5,7-diol as, sequentially, diastereoisomer 32a, a colourless
solid (24 mg, 16%), diastereoisomer 32b, a colourless oil (19 mg, 13%) and an inseparable
mixture of diastereoisomers 32c and 32d as an oil (36 mg, 24%).
o
Diastereoisomer 32a had m.p. 75 C (ether/hexane); νmax(N) 3408, 1639, 1443, 1277, 1260,
1084, 1059, 1020, 996, 913, 800, 746, 701 cm-1; δH 1.04 (3H, d, J 7, CH3), 1.28 (2H, m, 8-
CH2), 1.49 (3H, s, CH3), 1.58 (3H, s, CH3), 2.22 (2H, m, 9-CH2), 2.36 (1H, m, 4-CH), 2.59
(1H, dd, J 1.5; 9, 6-CH), 4.26 (1H, apparent t, J 7, 7-CH), 4.53 (1H, dd, J 2; 9, 5-CH), 4.74
(1H, t, J 7, 10-CH), 5.11 (2H, m, 1-CH2), 5.87 (1H, m, 2-CH), 7.56 (5H, m, ArH) ppm; δC
12.1 (CH3), 17.1 (12-CH3), 23.6 (9-CH2), 25.2 (12-CH3), 35.5 (3-CH2), 36.4 (4-CH), 38.2 (8-
CH2), 67.7 (7-CH), 68.1 (5-CH), 71 (6-CH), 116.3 (1-CH2), 122.5 (10-CH), 123.8 (CH),
128.9 (CH), 130.6 (CH), 132.0 (11-C), 136.4 (2-CH), 140.8 (C) ppm. HRMS (ESI): MNa+,
found 373.1796. C20H30O3S requires 373.1813.
Diastereoisomer 32b was obtained as an oil; δH 0.91 (3H, d, J 6.5, CH3), 1.28 (2H, m, 8-
CH2), 1.48 (3H, s, CH3), 1.57 (3H, s, CH3), 1.90 (2H, m, 3-CH2), 2.12−2.38 (3H, m, 9-CH2
and 4-CH), 2.70 (1H, m, 6-CH), 4.15 (1H, dd, J 1; 9.5, 5-CH), 4.49 (1H, apparent t, J 6.5, 7-
CH), 4.81 (1H, t, J 7, 10-CH), 5.12 (2H, m, 1-CH2), 5.89 (1H, m, 2-CH), 7.59 (5H, m, ArH)
ppm; δC 15.1 (CH3), 17.1 (12-CH3), 23.4 (9-CH2), 25.1 (12-CH3), 33.8 (3-CH2), 35.9 (4-CH),
36.2 (8-CH2), 67.4 (7-CH), 68.8 (5-CH), 71.5 (6-CH), 116.4 (1-CH2), 122.2 (10-CH), 123.6
(CH), 129.0 (CH), 130.4 (CH), 132.3 (11-C), 136.0 (2-CH), 142.4 (C) ppm. HRMS (ESI):
MNa+, found 373.1804. C20H30O3S requires 373.1813.
19

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Acknowledgements
We gratefully acknowledge the assistance of Dr Martin Feeney (mass spectra) and Dr John
O’Brien (NMR spectra).
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21