S-allyl thiocarbamates from allylic alcohols by in situ [3,3]-sigmatropic rearrangement of a thiocarbonyldiimidazole adduct

Article abstract of DOI:10.1055/s-0032-1316746

Treatment of allylic alcohols with thiocarbonyldiimidazole generates an unstable O-allyl imidazolyl thione ester, which rearranges spontaneously and in high yield to the corresponding S-allyl imidazolyl thiol ester. Displacement of the imidazole by N-alky

Full text of DOI:10.1055/s-0032-1316746

PAPER
▌2723
paper
S-Allyl Thiocarbamates from Allylic Alcohols by in situ [3,3]-Sigmatropic
Rearrangement of a Thiocarbonyldiimidazole Adduct
S-Allyl Thiocarbamates from Allylic Alcohols
Gaëlle Mingat, Jonathan Clayden*
School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, UK
Fax +44(161)2754939; E-mail: clayden@man.ac.uk
Received: 18.04.2012; Accepted after revision: 22.06.2012
catalysed processes17c,19 have also been reported. The
Abstract: Treatment of allylic alcohols with thiocarbonyldiimid-
thermal reaction seems to be a standard [3,3]-sigmatropic
azole generates an unstable O-allyl imidazolyl thione ester, which
rearrangement, with a broad range of substituents
rearranges spontaneously and in high yield to the corresponding S-
allyl imidazolyl thiol ester. Displacement of the imidazole by N-al-
tolerated16,17 although the rate of the reaction strongly de-
kylanilines in the presence of a nucleophilic catalyst (HOBt or pends on the allylic substitution pattern.16,17,20
ECHIA) gives S-allyl N-aryl thiocarbamates in excellent yields (up
to 97%) over two steps.
[3,3]-sigmatropic
rearrangement
R2
O
NR3
S
NR3
2
R1
2
Key words: sigmatropic rearrangement, thiocarbamates, alcohols,
stereospecificity, sulfur
R1
S
R2
O
2
1
Scheme 1 [3,3]-Sigmatropic rearrangement of O-allyl thiocarba-
mates
Thiocarbamates are valuable as precursors of important
sulfur-containing compounds1 and strategic intermediates
in the synthesis of natural products.2 They also display bi-
ological activities as analgesics3 and anaesthetics,1,4
fungicides1,3–5 and bactericides3,4,6 or antiviral1,4 and der-
matological agents.5,7 They have been reported to have
hypnotic3 and tuberculostatic activity3 and can be em-
ployed in flavour and fragrance chemistry.8 S-Alkyl thio-
carbamates are most known for their use as commercial
herbicides.1,4,9 Allylic thiocarbamates have been used as
terminators in radical-based cyclisation reactions.10
Hoppe made extensive use of S-alkyl-, S-benzyl-, and S-
allylthiocarbamates in his seminal work on lithiation and
his studies of the configurational stability of the resulting
sulfur-stabilised organolithium compounds.11
Starting from enantioenriched O-allyl thiocarbamates 1,
the [3,3]-sigmatropic rearrangement proceeds with excel-
lent transfer of chirality (up to 97% ee conservation).11c,e
Enantioselectivity can furthermore be achieved in the re-
arrangement of achiral or racemic O-allyl thiocarba-
mates.19 Using a chiral bisphosphine ligand, Gais
prepared cyclic and acyclic symmetrical S-allylic thiocar-
bamates with ee values ranging from 85% to ≥99% via a
palladium-catalysed reaction.19a,b Overman obtained good
to excellent ee values (76–88%) in the palladium-cata-
lysed [3,3]-sigmatropic rearrangement of unsymmetrical
acyclic substrates using (R)-(–)-COP-Cl as the chiral cat-
alyst,19c providing the first catalytic asymmetric method
for the preparation of secondary allylic thiocarbamates.
The most straightforward methods for the preparation of
thiocarbamates are nucleophilic substitutions of carbamo-
yl chlorides with thiols or thiolates,12,13 alkyl chlorothio-
formates with amines,13 or sequential attack on
trichloroacetyl chloride by a thiol and an amine.4 Less
practical methods employ carbon monoxide and elemen-
tal sulfur,4,14 reactions of unstable N,N-dialkylcarbamoyl
lithiums with sulfur compounds,9a or the condensation of
gaseous carbonyl sulfide and an amine followed by treat-
ment with a base and alkyl halide.12 Condensation of a thi-
ol with an isocyanate6 or hydration of an organic
thiocyanate1,15 also affords a thiocarbamate.
We have recently reported that benzyllithiums stabilised
by urea,21 carbamate,22 or thiocarbamate23 functions may
undergo arylation by intramolecluar migration of an aro-
matic ring to the carbanionic centre. As part of a pro-
gramme of research extending this anion arylation
methodology to the related allyllithiums,24 we required a
straightforward and efficient general synthesis of a range
of allyl thiocarbamate substrates.
Initially, we chose the route to thiocarbamates 7 shown in
Scheme 2. Successive substitutions of chloride from thio-
phosgene gave the O-allyl-substituted thiocarbamate 6a
via thiocarbamoyl chloride 4a. The [3,3]-sigmatropic re-
arrangement of 6a to give 7a took place on refluxing in
toluene for 2 to 3 days, or more conveniently on heating
for 45 minutes in a microwave at 135 °C.
S-Allyl thiocarbamates 2 are readily prepared by rear-
rangement of their O-allyl counterparts 1 (Scheme 1),4
driven by the thermodynamically favoured formation of a
C=O bond from a C=S bond.16 The rearrangement can be
promoted thermally17 or photochemically,18 and metal-
Replacing thiophosgene with thiocarbonyldiimidazole
(TCDI; 8)25 resulted in a complex mixture of several un-
identified products. Changing the order of the substitu-
tions, with the aim of first converting 5a to the imidazole
SYNTHESIS 2012, 44, 2723–2734
Advanced online publication: 30.07.2012
DOI: 10.1055/s-0032-1316746; Art ID: SS-2012-N0371-OP
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

2724
G. Mingat, J. Clayden
PAPER
Nonetheless, the rearranged thiocarbonyl imidazoles 10
are themselves valuable intermediates for the synthesis of
thiocarbamates. Such acylimidazole intermediates are
rather unreactive towards nucleophiles, and displacement
of the imidazole is typically achieved25 by activation us-
ing N-methylation. In the case of 10, however, a range of
different methylating conditions led only to decomposi-
tion. Substitution of an acylimidazole has alternatively
been achieved in the presence of various nucleophilic cat-
alysts,27 and Table 2 shows the results of treating 10a with
a series of N-methylanilines 328 in the presence of DBU,
HOBt, or ethyl 2-cyano-2-(hydroxyimino)acetate
(ECHIA) (Scheme 4).
NH
N
Cl
b
a
S
OH
3a
4a
5a
N
S
N
O
c or d
O
S
7a 80–95%
6a 68% (2 steps)
Scheme 2 Synthesis of S-allyl thiocarbamates from chlorothiofor-
mates. Reagents and conditions: a) CSCl2, Et3N, THF, 0 °C to r.t.; b)
NaH, NaI, THF, 0 °C, then 5a; c) K2CO3, toluene, 72 h; d) 0.4 M, μW,
135 °C, 45 min.
N
derivative 9, revealed that under the conditions required to
displace imidazole from TCDI the O-allyl thiocarbamate
product 9 rearranged spontaneously to the S-allyl imidaz-
olthiocarboxylate 10, as previously reported by other
groups26 (Scheme 3). The reaction proved to be reproduc-
ible with various alcohols (Table 1).
S
N
O
10a
see Table 2
THF
S
N
+
O
R3
NH
7a–c
S
R1
R3
a
3a–c
N
N
R2
OH
+
N
N
5
Scheme 4 Catalysed formation of the thiocarbamates 7
8
R1
S
N
HOBt generally gave better yields than ECHIA (Table 2,
entries 3, 5, 7, 10, 14, and 16). Although 0.5 equivalent of
additive gave satisfying yields in most cases, a higher
amount led to improved yields for some substrates (entries
10–12). Reactions run in the microwave always gave
poorer yields than under thermal conditions (entries 4, 6,
8, 13, and 15).
R1
S
N
R2
O
N
N
R2
10
O
9
Scheme 3 [3,3]-Sigmatropic rearrangement of the thiocarbonyl im-
idazole adduct. Reagents and conditions: a) DMAP, CH2Cl2, r.t., 18 h.
The optimised conditions were then applied to various
substrates 10 and N-methylanilines 3 (Scheme 5), and
turned out to be general for a range of substitution patterns
in both the acylimidazole and aniline reactants. Remark-
ably, even the very hindered N,2,4,6-tetramethylaniline
gave a very high yield (96%). Electron-deficient anilines
performed less well: while 4-fluoro- and the 4-chloro-N-
methylaniline gave good yields (65% and 86%), the 4-tri-
fluoromethyl-N-methylaniline afforded thiocarbamate 5g
in only moderate yield (33%) while no product at all was
obtained from 4-(methylamino)benzonitrile.
The unstable O-allyl intermediate 9a (R1 = Me, R2 = H)
could be isolated by using THF as the solvent and lower-
ing the temperature to –20 °C for six hours. Replacing
DMAP with HOBt led to a marked increase in the rate of
substitution of imidazole from 8, affording the imidazole
adduct 9a after one hour in CH2Cl2 without rearrangement
(as indicated by 1H NMR analysis). However 9a is too un-
stable to isolate as a pure compound, undergoing rapid
[3,3]-sigmatropic rearrangement during workup and puri-
fication via filtration through silica gel. It decomposes
over a matter of days in a freezer.
Table 1 Scope of the Nucleophilic Substitution of Thiocarbonyldiimidazole by Allylic Alcohol
Entry
5
R1
R2
Conditions
Product, yield (%)
1
3
5
6
7
8
5a
5b
5c
5d
5e
5f
H
Me
CH2Cl2, r.t., 3 days
10a, 98
10b, 100
10c, 65
10d, 88
10e, 98
10f, 90
H
n-Pr
DCE, reflux, 24 h
H
CH=CHMe
i-Pr
CH2Cl2, r.t., 2.5 d
H
DCE, r.t. 6 h, then 40 °C, 20 h
DCE, r.t. 2 h, then 40 °C, 24 h
DCE, 40 °C, 26 h
Me
Me
c-C6H11
Me
Synthesis 2012, 44, 2723–2734
© Georg Thieme Verlag Stuttgart · New York

PAPER
S-Allyl Thiocarbamates from Allylic Alcohols
2725
Because of the reported stereospecificity26a–d,g,h of related ly enriched thiocarbamates. Thus, treatment of (R)-5f,
sigmatropic rearrangements,11c,e we expected the method produced in 94:6 er using Sharpless’ kinetic resolution,29
to be equally effective for the synthesis of enantiomerical- with TCDI under the conditions of Table 1, entry 8, gen-
N
NH
R1
S
N
a
R1
S
N
+
R2
O
R2
10a–f
O
R3
3a–l
R3
7
S
N
S
N
S
N
S
N
O
O
O
O
OMe
Cl
7a: 68%
7b: 87%
7c: 65%
7d: 88%
S
N
S
N
S
N
Cl
S
N
O
O
O
O
CF3
F
Me
7e: 96%
7f: 86%
7g: 33%
7h: 45%
OMe
S
N
O
S
N
O
OMe
S
N
S
N
O
OMe
Cl
O
7i: 87%
7j: 71%a
7k: 51%b
7l: 89%a
S
N
O
S
N
O
S
N
S
N
O
O
Cl
F
7m: 77%a
7n: 97%a
7o: 93%a
7p: 46%a
OMe
S
N
S
N
O
S
N
O
S
N
O
O
OMe
Cl
7q: 67%a
7r: 59%
7s: 78%
7t: 79%
S
N
S
N
O
S
N
O
S
N
O
O
F
Cl
Cl
7u: 78%
7v: 81%
7w: 84%
7x: 49%
S
N
O
S
N
O
Cl
7y: 73%
7z: 86%
OMe
S
N
Cl
S
N
S
N
OMe
O
O
O
7aa: 77%
7bb: 77%
7cc: 78%
S
N
S
N
F
O
O
7dd: 41%
7ee: 59%
Scheme 5 Imidazoles derivatives 10 as precursors to S-allyl thiocarbamates 7. Reagents and conditions: a) HOBt (0.5 or 1.0 equiv), THF, heat,
24 h. a Using ECHIA (0.5 or 1.0 equiv); b Using HOBt (1.2 equiv).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2723–2734

2726
G. Mingat, J. Clayden
PAPER
Table 2 Optimisation of the Nucleophilic Displacement of Imidazole from 10a by N-Methylanilines 3
Entry
3
R3
Additive
Equiv
Conditions
Product, yield (%)
1
2
3b
3c
3c
3c
3c
3c
3b
3b
3b
3b
3b
3b
3b
3a
3a
3a
OMe
Cl
DBU
0.5
0.5
0.5
0.5
1.0
1.0
0.5
0.5
0.5
0.5
1.0
1.5
0.5
0.5
0.5
0.5
reflux, 24 h
0
DBU
reflux, 24 h
0
3
Cl
HOBt
reflux, 24 h
7c, 65
0
4
Cl
HOBt
μw, 100 °C, 2 h
reflux, 24 h
5
Cl
ECHIA
ECHIA
HOBt
7c, 56
7c, 21
7b, 87
7b, 72
7b, 68
7b, 64
7b, 76
7b, 81
7b, 51
7a, 68
7a, 38
7a, 60
6
Cl
μw, 100 °C, 2 h
reflux, 24 h
7
OMe
OMe
OMe
OMe
OMe
OMe
OMe
H
8
HOBt
μw, 100 °C, 2 h
reflux, 24 h
9
ECHIAa
ECHIA
ECHIA
ECHIA
ECHIA
HOBt
10
11
12
13
14
15
16
reflux, 24 h
reflux, 24 h
reflux, 24 h
μw, 100 °C, 1 h
reflux, 24 h
H
HOBt
μw, 100 °C, 2 h
reflux, 24 h
H
ECHIA
a Solvent: CH2Cl2.
determined on a Bibby Stuart Scientific Melting Point SMP10 ap-
paratus and are uncorrected. Optical rotation measurements were
taken on a AA-100 polarimeter or a PerkinElmer 241 polarimeter
using a cell with a path length of 0.25 dm, with the solvent, concen-
tration (in g/mL) and sample temperature as stated.
erated (S)-10f in 94:6 er. This enantioenriched material
gave, on reaction with 3-methoxy-N-methylaniline, a
thiocarbamate 7cc of undiminished enantiomeric enrich-
ment.
In summary, we have shown that simple acylation of al-
lylic alcohols with thiocarbonyldiimidazole (TCDI, 8)
initiates a rapid stereospecific [3,3]-sigmatropic rear-
rangement to give an S-allyl thiocarbonylimidazole deriv-
ative. HOBt-promoted substitution of imidazle from this
product provides a general two-step synthesis of S-allyl N-
arylthiocarbamates. The method tolerates a wide range of
substituents, either in the alcohol or the aniline compo-
nent, and gives the thiocarbamate products in generally
good to excellent yields.
TLC was performed using commercially available precoated plates
(Macherey-Nagel Polygram® Sil G/UV254 for TLC, 0.20 mm) and
visualised with UV light at 254 nm, phosphomolybdic acid dip,
Seebach’s dip (2.5 g of phosphomolybdic acid hydrate, 1.0 g of ce-
rium(IV) sulfate tetrahydrate, 3.2 mL of concd H2SO4 and 90.5 mL
of H2O) or KMnO4 dip. Flash chromatography was carried out us-
ing Fluorochem Davisil 40–63 μm 60 Å silica gel, under a positive
pressure by means of compressed air.
All reactions were conducted under an N2 atmosphere unless other-
wise stated. Glassware was oven or flame dried. THF was distilled
under N2 from Na, using benzophenone indicator. CH2Cl2, cumene,
i-Pr2NH, and DMPU were purified by distillation from CaH2 under
N2. Anhyd Et2O and toluene were provided by the SPS (Solvent Pu-
rification System) Pure Solv model PS-MD-5, serial PS-08-150 ap-
paratus from Innovative Technology Inc. PE refers to the fraction of
light petroleum ether (PE) boiling between 40 and 65 °C. All other
solvents and commercially available reagents were used as re-
ceived.
NMR spectra were recorded on a Bruker Ultrashield 300 or 400
spectrometer. The chemical shifts (δ) are reported in ppm downfield
of TMS and coupling constants (J) are reported in hertz and rounded
to 0.5 Hz. Standard abbreviations were used for denoting the split-
ting patterns. Solvents were used as internal standards when assign-
ing NMR spectra (δH: CDCl3 7.26; δC CDCl3 77.0; δH: DMSO 2.50;
δC DMSO 39.43). Coupling constants were calculated manually us-
ing the chemical shifts given by ChemDraw Ultra 11.0 software.
Chiral HPLC measurements were carried out using a Hewlett Pack-
ard Series 1050 instrument fitted with a Daicel Chiralcel OD-H, a
Daicel Chiralcel AD-H, or a (R,R)-Whelk-01 stationary phase with
a mixture of hexane and i-PrOH as eluent. Absorption was mea-
sured at 214 or 254 nm.
Low- and high-resolution mass spectra were recorded by staff at the
University of Manchester. Electrospray spectra were recorded on a
Micromass Platform II and high-resolution mass spectra were re-
corded either on a Waters QTOF or a Thermo Finnigan MAT95XP
mass spectrometer, and are accurate to ± 0.001 Da. IR spectra were
recorded on a PerkinElmer FT-IR Spectrum BX spectrometer. Ab-
sorptions reported are the most intense. Melting points (mp) were
1H-Imidazole-1-carbothioates 10a–f;25 General Procedure A
To a stirred solution of alcohol 5 (1.0 equiv) in CH2Cl2 or DCE at
r.t. were added TCDI (8; 2.0 equiv) and DMAP (0.1 equiv). The re-
action mixture was stirred at r.t. or heated until completion. Once at
Synthesis 2012, 44, 2723–2734
© Georg Thieme Verlag Stuttgart · New York

PAPER
S-Allyl Thiocarbamates from Allylic Alcohols
2727
r.t., EtOAc was added and the crude mixture was washed with brine
(2 ×). The organic layer was separated, dried (MgSO4), filtered, and
concentrated down. Further purification by column chromatogra-
phy afforded the pure 1H-Imidazole-1-carbothioates 10.
13C NMR (100 MHz, CDCl3): δ = 168.3, 142.2, 139.7, 129.6, 128.5,
114.7, 42.9, 38.3, 20.1.
MS (ES+): m/z (%) = 222 ([M + H]+, 50), 244 ([M + Na]+, 100), 276
([M + Na + MeOH]+, 40).
Phenyl(methyl)carbamothioates 7a–z,aa–ee;26 General Proce-
dure B
HRMS: m/z [M + H]+ calcd for C12H15NOS: 222.0948; found:
222.0945.
To a solution of 1H-imidazole-1-carbamathioate 10 (1.0 equiv) in
THF at r.t. were added either HOBt or ECHIA (either 0.5 or 1.0
equiv) and N-methylaniline 3 (1.2 equiv). The reaction mixture was
heated to reflux for 24 h, and cooled to r.t. EtOAc was added and
the organic mixture was washed with aq HCl for the indicated time.
The organic layer was separated, dried (MgSO4), filtered, and con-
centrated. Further purification by column chromatography afforded
the pure phenyl(methyl)carbamothioates 7.
S-But-3-en-2-yl 4-Methoxyphenyl(methyl)carbamothioate
(7b)26
General procedure B was followed using 10a (50 mg, 0.27 mmol)
in THF (1 mL), HOBt (18 mg, 0.133 mmol, 0.5 equiv), and 4-
methoxy-N-methylaniline (45 mg, 0.33 mmol). The crude mixture
was washed with aq 1 M HCl (2 mL) for 15 min and concentrated
down. The crude product was purified by column chromatography
(PE–EtOAc, 95:5) to afford the title compound as a yellow oil (59
mg, 87%); Rf = 0.41 (PE–EtOAc, 8:2).
(E)-O-But-2-enyl Methyl(phenyl)carbamothioate (6a)
To a solution of crotyl alcohol (5a; 1.11 g, 15.6 mmol, 1.0 equiv) in
THF (12 mL) at 0 °C was added a suspension of NaH (60% in min-
eral oil, 1.87 g, 46.8 mmol, 3.0 equiv) in THF (60 mL). The reaction
mixture was stirred at 0 °C for 30 min and NaI (280 mg, 1.87 mmol,
0.1 equiv) followed by methyl(phenyl)carbamic chloride (4a; 3.47
g, 18.7 mmol, 1.2 equiv) were added. The reaction mixture was
warmed to r.t., stirred at r.t. for 45 min, warmed to 30 °C, and stirred
at 30 °C for 45 min. Sat. aq NH4Cl (60 mL) was added and the aque-
ous layer was extracted with Et2O (3 × 20 mL). The combined or-
ganic fractions were washed with H2O (20 mL) and brine (20 mL),
dried (MgSO4), filtered, and concentrated down. Further purifica-
tion by column chromatography (PE–Et2O, 95:5 to 7:3) afforded the
title compound as a pale yellow fluffy powder (2.80 g, 81%); mp
60–62 °C; Rf = 0.70 (PE–EtOAc, 8:2).
IR (film): 1652, 1511, 1246 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.17 (d, J = 9.0 Hz, 2 H), 6.91 (d,
J = 9.0 Hz, 2 H), 5.87 (ddd, J = 17.0, 10.0, 7.0 Hz, 1 H), 5.17 (ddd,
J = 17.0, 1.0, 1.0 Hz, 1 H), 5.01 (ddd, J = 10.0, 1.0, 1.0 Hz, 1 H),
4.09 (quint, J = 7.0 Hz, 1 H), 3.82 (s, 3 H), 3.28 (s, 3 H), 1.36 (d, J =
7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.5, 159.4, 139.6, 134.5, 129.7,
114.6, 114.5, 55.4, 42.7, 38.3, 19.9.
MS (ES+): m/z (%) = 274 ([M + Na]+, 100), 306 ([M + Na +
MeOH]+, 50).
HRMS: m/z [M + Na]+ calcd for C13H17NO2S: 274.0873; found:
274.0876.
IR (neat): 1490, 1445, 1382, 1273, 1199 cm–1.
S-But-3-en-2-yl 4-Chlorophenyl(methyl)carbamothioate (7c)26
General procedure B was followed using 10a (50 mg, 0.27 mmol)
in THF (1 mL), HOBt (18 mg, 0.133 mmol, 0.5 equiv) and 4-chloro-
N-methylaniline (0.04 mL, 0.32 mmol). The crude mixture was
washed with aq 1 M HCl (2 mL) for 15 min and concentrated down.
The crude product was purified by column chromatography (PE–
EtOAc, 98:2 to 85:15) to afford the title compound as a yellow oil
(45 mg, 65%); Rf = 0.48 (PE–EtOAc, 8:2).
1H NMR (400 MHz, DMSO-d6, 90 °C): δ = 7.42 (t, J = 7.5 Hz, 2 H),
7.31 (t, J = 7.5 Hz, 1 H), 7.24 (d, J = 7.5 Hz, 2 H), 5.67 (m, 1 H),
5.55 (m, 1 H), 4.85 (d, J = 6.0 Hz, 2 H), 3.52 (s, 3 H), 1.64 (d, J =
6.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 153.7, 143.5, 130.4, 129.1, 127.3,
125.9, 125.8, 124.9, 72.1, 44.2, 17.8.
MS (ES+): m/z = 244 ([M + Na]+, 100%).
IR (film): 1653, 1488, 1277 cm–1.
HRMS: m/z [M + Na] calcd for C12H15NOS: 244.0767; found:
244.0765.
1H NMR (400 MHz, CDCl3): δ = 7.37 (d, J = 9.0 Hz, 2 H), 7.21 (d,
J = 9.0 Hz, 2 H), 5.86 (ddd, J = 17.0, 10.5, 7.0 Hz, 1 H), 5.18 (ddd,
J = 17.0, 1.0, 1.0 Hz, 1 H), 5.03 (ddd, J = 10.5, 1.0, 1.0 Hz, 1 H),
4.11 (quint, J = 7.0 Hz, 1 H), 3.29 (s, 3 H), 1.37 (d, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.0, 140.5, 139.3, 134.1, 129.7,
129.6, 114.7, 42.8, 38.1, 19.9.
S-But-3-en-2-yl Methyl(phenyl)carbamothioate (7a)26
Method A: To a solution of 6a (100 mg, 0.46 mmol, 1.0 equiv) in
toluene (1 mL) was added K2CO3 (6 mg, 0.046 mmol, 0.1 equiv).
The reaction mixture was heated to 135 °C for 45 min in a micro-
wave oven. K2CO3 was filtered through a cotton plug and the organ-
ic layer was concentrated down. 1H NMR of the crude showed 95%
conversion. Further purification by column chromatography (PE–
Et2O, 95:5 to 85:15) afforded the title compound as a colourless oil.
MS (ES+): m/z (%) = 278 ([M + Na]+, 100), 310 ([M + Na +
MeOH]+, 80).
HRMS: m/z [M + H]+ calcd for C12H14ClNOS: 274.0558; found:
256.0561.
Method B: General procedure B was followed using S-but-3-en-2-
yl 1H-imidazole-1-carbothioate (10a; 300 mg, 1.65 mmol) in THF
(3 mL), HOBt (111 mg, 0.82 mmol, 0.5 equiv), and N-methylaniline
(0.21 mL, 1.94 mmol). The crude mixture was washed with aq 1 M
HCl (3 mL) for 15 min and concentrated down. The crude product
was purified by filtration over silica gel (PE–Et2O, 9:1) to afford the
title compound as a yellow-orange oil (250 mg, 68%); Rf = 0.32
(PE–Et2O, 9:1); [α]D20 +16.1 (c 2.0, CHCl3).
S-But-3-en-2-yl Methyl(p-tolyl)carbamothioate (7d)26
General procedure B was followed using 10a (250 mg, 1.37 mmol)
in THF (5 mL), HOBt (93 mg, 0.685 mmol, 0.5 equiv), and 4-meth-
yl-N-methylaniline (0.21 mL, 1.64 mmol). The crude mixture was
washed with aq 1 M HCl (2 mL) for 30 min and concentrated down.
The crude product was purified by filtration over silica gel (PE–
EtOAc, 9:1) to afford the title compound as a yellow oil (280 mg,
88%); Rf = 0.71 (PE–EtOAc, 8:2).
HPLC: OD-H, hexane–i-PrOH (99:1), 1 mL/min, tR: minor 30.02
min, tR: major 32.76 min.
IR (film): 1651, 1594, 1494, 1341, 1268 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.39 (m, 3 H), 7.27 (m, 2 H), 5.87
(ddd, J = 17.0, 10.0, 7.0 Hz, 1 H), 5.18 (ddd, J = 17.0, 1.0, 1.0 Hz,
1 H), 5.02 (ddd, J = 10.0, 1.0, 1.0 Hz, 1 H, H-4), 4.12 (quint, J = 7.0,
1.0 Hz, 1 H), 3.32 (s, 3 H), 1.37 (d, J = 7.0 Hz, 3 H).
IR (film): 1652, 1513, 1342, 1258 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.21 (d, J = 8.5 Hz, 2 H), 7.14 (d,
J = 8.5 Hz, 2 H), 5.87 (ddd, J = 17.0, 10.0, 7.0 Hz, 1 H), 5.17 (ddd,
J = 17.0, 1.0, 1.0 Hz, 1 H), 5.01 (ddd, J = 10.0, 1.0, 1.0 Hz, 1 H),
4.10 (quint, J = 7.0, 1.0 Hz, 1 H), 3.29 (s, 3 H), 2.24 (s, 3 H), 1.36
(d, J = 7.0 Hz, 3 H).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2723–2734

2728
G. Mingat, J. Clayden
PAPER
13C NMR (100 MHz, CDCl3): δ = 168.2, 139.6, 139.3, 138.5, 130.1,
128.1, 114.5, 42.7, 38.2, 21.2, 19.9.
13C NMR (100 MHz, CDCl3): δ = 168.0, 145.3, 139.2, 128.2, 126.6,
126.5, 125.1, 122.4, 115.0, 43.0, 37.9, 19.9.
MS (ES+): m/z (%) = 258 ([M + Na]+, 100), 290 ([M + Na +
MS (ES+): m/z (%) = 290 ([M + H]+, 20), 312 ([M + Na]+, 60).
HRMS: m/z [M + H]+ calcd for C13H14F3NOS: 290.0821; found:
MeOH]+, 50).
HRMS: m/z [M + Na]+ calcd for C13H17NOS: 258.0924; found:
290.0816.
258.0918.
S-But-3-en-2-yl 3-Chlorophenyl(methyl)carbamothioate (7h)26
General procedure B was followed using 10a (50 mg, 0.27 mmol)
in THF (1 mL), HOBt (37 mg, 0.27 mmol, 1.0 equiv) or ECHIA (38
mg, 0.27 mmol, 1.0 equiv), and 3-chloro-N-methylaniline (0.04 mL,
0.32 mmol). The crude mixture was washed with aq 1 M HCl (2
mL) for 15 min and concentrated down. The crude product was pu-
rified by filtration over silica gel (PE–EtOAc, 9:1) to afford the title
compound as a yellow oil (31 mg, 45%); Rf = 0.41 (PE–Et2O, 8:2).
S-But-3-en-2-yl Mesityl(methyl)carbamothioate (7e)26
General procedure B was followed using 10a (51 mg, 0.28 mmol)
in THF (1 mL), HOBt (18 mg, 0.133 mmol, 0.5 equiv), and 2,4,6-
trimethyl-N-methylaniline (0.05 mL, 0.34 mmol). The crude mix-
ture was washed with aq 1 M HCl (2 mL) for 15 min and concen-
trated down. The crude product was purified by filtration over silica
gel (PE–EtOAc, 8:2) to afford the title compound as a yellow oil (71
mg, 96%); Rf = 0.80 (PE–EtOAc, 8:2).
IR (film): 1656, 1589, 1337, 1278 cm–1.
IR (film): 1655, 1300, 1270 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.33 (m, 2 H), 7.28 (m, 1 H), 7.18
(m, 1 H), 5.88 (ddd, J = 17.0, 10.0, 7.0 Hz, 1 H), 5.19 (ddd, J = 17.0,
1.5, 1.5 Hz, 1 H), 5.04 (ddd, J = 10.0, 1.5, 1.5 Hz, 1 H), 4.12 (quint,
J = 7.0, 1.5 Hz, 1 H), 3.30 (s, 3 H), 1.38 (d, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.0, 143.2, 139.3, 134.7, 130.3,
128.4, 126.4, 114.8, 42.9, 38.0, 19.9.
1H NMR (400 MHz, CDCl3): δ = 6.92 (br s, 2 H), 5.85 (ddd, J =
17.0, 10.0, 7.0 Hz, 1 H), 5.17 (ddd, J = 17.0, 1.0, 1.0 Hz, 1 H), 4.99
(ddd, J = 10.0, 1.0, 1.0 Hz, 1 H), 4.08 (quint, J = 7.0, 1.0 Hz, 1 H),
3.16 (s, 3 H), 2.30 (s, 3 H), 2.18 (d, J = 4.5 Hz, 6 H), 1.34 (d, J = 7.0
Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.3, 139.7, 138.8, 136.9, 136.2,
129.5, 114.3, 42.1, 35.2, 21.1, 19.9, 17.6.
MS (ES+): m/z (%) = 256 ([M + H]+, 50), 278 ([M + Na]+, 100), 310
([M + Na + MeOH]+, 50).
MS (ES+): m/z (%) = 286 ([M + Na]+, 100%), 318 ([M + Na +
HRMS: m/z [M + H]+ calcd for C12H14ClNOS: 256.0557; found:
256.0561.
MeOH]+, 40).
HRMS: m/z [M + Na]+ calcd for C15H21NOS: 286.1237; found:
286.1228.
S-But-3-en-2-yl 2-Methoxyphenyl(methyl)carbamothioate
(7i)26
S-But-3-en-2-yl 4-Fluorophenyl(methyl)carbamothioate (7f)26
General procedure B was followed using 10a (250 mg, 1.37 mmol)
in THF (5 mL), HOBt (93 mg, 0.685 mmol, 0.5 equiv) and 4-fluoro-
N-methylaniline (0.20 mL, 1.64 mmol). The crude mixture was
washed with aq 1 M HCl (5 mL) for 25 min and concentrated down.
The crude product was purified by filtration over silica gel (PE–
EtOAc, 9:1) to afford the title compound as a yellow oil (281 mg,
86%); Rf = 0.73 (PE–EtOAc, 8:2).
General procedure B was followed using 10a (280 mg, 1.54 mmol)
in THF (6 mL), HOBt (208 mg, 1.54 mmol, 1.0 equiv), and 2-me-
thoxy-N-methylaniline (254 mg, 1.85 mmol). The crude mixture
was washed with aq 1 M HCl (5 mL) for 20 min and concentrated
down. The crude product was purified by filtration over silica gel
(PE–EtOAc, 95:5) to afford the title compound as a yellow oil (336
mg, 87%); Rf = 0.38 (PE–Et2O 8:2).
IR (film): 1652, 1499, 1271 cm–1.
IR (film): 1652, 1508, 1220 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.36 (td, J = 8.0, 1.5 Hz, 1 H), 7.21
(dd, J = 8.0, 1.5 Hz, 1 H), 6.96 (d, J = 8.0 Hz, 2 H), 5.86 (2 ddd,
rotamers, J = 17.0, 10.0, 7.0 Hz, 1 H), 5.16 (2 d, rotamers, J = 17.0
Hz, 1 H), 5.00 (2 d, rotamers, J = 10.0 Hz, 1 H), 4.09 (quint, J = 7.0
Hz, 1 H), 3.85 (2 s, rotamers, 3 H), 3.22 (s, 3 H), 1.35 (2 d, rotamers,
J = 7.0 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.28 (dd, J = 9.5, 5.5 Hz, 2 H),
7.12 (t, J = 9.5 Hz, 2 H), 5.90 (ddd, J = 17.0, 10.0, 7.0 Hz, 1 H), 5.22
(ddd, J = 17.0, 1.0, 1.0 Hz, 1 H), 5.06 (ddd, J = 10.0, 1.0, 1.0 Hz, 1
H), 4.14 (quint, J = 7.0, 1.0 Hz, 1 H), 3.33 (s, 3 H), 1.40 (d, J = 7.0
Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.8, 156.1, 139.8/139.7 (rota-
mers), 130.8/130.7 (rotamers), 130.3, 129.9, 120.8/120.7 (rotam-
ers), 114.3/114.2 (rotamers), 112.2, 55.6, 42.5/42.4 (rotamers),
36.7, 20.0/19.9 (rotamers).
MS (ES+): m/z = 274 ([M + Na]+, 100%).
HRMS: m/z [M + Na]+ calcd for C13H17NO2S: 274.0873; found:
13C NMR (100 MHz, CDCl3): δ = 168.3, 163.4, 139.4, 138.0, 130.3,
130.2, 116.6, 116.3, 114.7, 42.9, 38.2, 20.0.
MS (ES+): m/z (%) = 262 ([M + Na]+, 100), 294 ([M + Na +
MeOH]+, 40).
HRMS: m/z [M + Na]+ calcd for C12H14FNOS: 262.0673; found:
262.0668.
274.0875.
S-But-3-en-2-yl Methyl[4-(trifluoromethyl)phenyl]carbamo-
thioate (7g)26
S-But-3-en-2-yl 3-Methoxyphenyl(methyl)carbamothioate
(7j)26
General procedure B was followed using 10a (50 mg, 0.27 mmol)
in THF (1 mL), HOBt (18 mg, 0.133 mmol, 0.5 equiv), and 4-tri-
fluoromethyl-N-methylaniline (0.05 mL, 0.32 mmol). The crude
mixture was washed with aq 1 M HCl (2 mL) for 30 min and con-
centrated down. The crude product was purified by column chroma-
tography (PE–EtOAc, 95:5 to 9:1) to afford the title compound as a
yellow oil (26 mg, 33%); Rf = 0.48 (PE–EtOAc, 8:2).
General procedure B was followed using 10a (50 mg, 0.27 mmol)
in THF (1 mL), HOBt (37 mg, 0.27 mmol, 1.0 equiv), and 3-meth-
oxy-N-methylaniline (0.04 mL, 0.32 mmol). The crude mixture was
washed with aq 1 M HCl (2 mL) for 15 min and concentrated down.
The crude product was purified by filtration over silica gel (PE–
EtOAc, 7:3) to afford the title compound as a yellow oil (48 mg,
71%); Rf = 0.42 (PE–Et2O, 8:2).
IR (film): 1650, 1608, 1321, 1107 cm–1.
IR (film): 1651, 1599, 1587, 1486, 1282, 1216 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.66 (d, J = 8.0 Hz, 2 H), 7.41 (d,
J = 8.0 Hz, 2 H), 5.88 (ddd, J = 17.0, 10.0, 7.0 Hz, 1 H), 5.20 (ddd,
J = 17.0, 1.0, 1.0 Hz, 1 H), 5.05 (ddd, J = 10.0, 1.0, 1.0 Hz, 1 H),
4.14 (quint, J = 7.0, 1.0 Hz, 1 H), 3.34 (s, 3 H), 1.39 (d, J = 7.0 Hz,
3 H).
1H NMR (400 MHz, CDCl3): δ = 7.31 (t, J = 8.0 Hz, 1 H), 6.90 (ddd,
J = 8.0, 2.5, 1.5 Hz, 1 H), 6.86 (ddd, J = 8.0, 2.5, 1.5 Hz, 1 H), 6.80
(t, J = 1.6 Hz, 1 H), 5.88 (ddd, J = 17.0, 10.0, 7.0 Hz, 1 H), 5.18
(ddd, J = 17.0, 1.0, 1.0 Hz, 1 H), 5.02 (ddd, J = 10.0, 1.0, 1.0 Hz, 1
Synthesis 2012, 44, 2723–2734
© Georg Thieme Verlag Stuttgart · New York

PAPER
S-Allyl Thiocarbamates from Allylic Alcohols
2729
H), 4.11 (quint, J = 7.0, 1.0 Hz, 1 H), 3.82 (s, 3 H), 3.31 (s, 3 H),
1.37 (d, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.1, 160.2, 143.1, 139.6, 130.1,
1H NMR (400 MHz, CDCl3): δ = 7.37 (d, J = 8.5 Hz, 2 H), 7.21 (d,
J = 8.5 Hz, 2 H), 5.73 (ddd, J = 17.0, 10.0, 7.5 Hz, 1 H), 5.21 (ddd,
J = 17.0, 1.0, 1.0 Hz, 1 H), 5.05 (ddd, J = 10.0, 1.0, 1.0 Hz, 1 H),
3.99 (q, J = 7.5 Hz, 1 H), 3.29 (s, 3 H), 1.60 (m, 2 H), 1.36 (2 sext,
J = 7.5 Hz, 2 H), 0.89 (t, J = 7.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.1, 140.6, 138.6, 134.1, 129.7,
129.6, 115.6, 48.3, 38.1, 36.4, 20.3, 13.7.
120.4, 114.5, 114.0, 113.9, 55.4, 42.7, 38.1, 19.9.
MS (ES+): m/z (%) = 274 ([M + Na]+, 100), 306 ([M + Na +
MeOH]+, 15).
HRMS: m/z [M + Na]+ calcd for C13H17NO2S: 274.0873; found:
274.0869.
MS (ES+): m/z (%) = 284 ([M + H]+, 100), 306 ([M + Na]+, 55).
HRMS: m/z [M + H]+ calcd for C14H18ClNOS: 284.0871; found:
S-But-3-en-2-yl Methyl(naphthalen-1-yl)carbamothioate (7k)26
General procedure B was followed using 10a (50 mg, 0.27 mmol)
in THF (1 mL), HOBt (44 mg, 0.32 mmol, 1.2 equiv), and N-meth-
ylnaphthalen-1-amine (50 mg, 0.32 mmol). The crude mixture was
washed with aq 1 M HCl (2 mL) for 30 min and concentrated down.
The crude product was purified by column chromatography (100%
PE, then PE–EtOAc, 95:5 to 9:1) to afford the title compound as a
yellow oil (37 mg, 51%); Rf = 0.61 (PE–EtOAc, 8:2).
284.0872.
S-Hex-1-en-3-yl Methyl(p-tolyl)carbamothioate (7n)26
General procedure B was followed using 10b (50 mg, 0.24 mmol)
in THF (1 mL), ECHIA (17 mg, 0.12 mmol, 0.5 equiv), and 4-meth-
yl-N-methylaniline (0.04 mL, 0.29 mmol). The crude mixture was
washed with aq 1 M HCl (2 mL) for 15 min and concentrated down.
The crude product was purified by filtration over silica gel (PE–
EtOAc, 9:1) to afford the title compound as a yellow oil (61 mg,
97%); Rf = 0.48 (PE–EtOAc, 9:1).
IR (film): 1651, 1276, 774 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.91 (dd, J = 7.0, 2.5 Hz, 2 H),
7.81 (d, J = 8.0 Hz, 1 H), 7.56 (m, 2 H), 7.50 (td, J = 8.5, 1.0 Hz, 1
H), 7.45 (d, J = 7.0 Hz, 1 H), 5.81 (2 ddd, rotamers, J = 17.0, 10.5,
7.0 Hz, 1 H), 5.14 (dd, J = 16.0, 16.0 Hz, 1 H), 4.98 (dd, J = 19.5,
10.0 Hz, 1 H), 4.12 (m, 1 H), 3.42 (2 s, rotamers, 3 H), 1.30 (2 d,
rotamers, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 169.1/169.0 (rotamers), 139.5,
137.9, 134.6, 130.5, 129.4, 128.6, 127.6/127.5 (rotamers), 127.3,
126.7, 125.7/125.6 (rotamers), 122.5/122.4 (rotamers), 114.5/114.3
(rotamers), 42.6, 38.0, 19.8.
IR (film): 1654, 1513, 1270 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.21 (d, J = 8.0 Hz, 2 H), 7.14 (d,
J = 8.0 Hz, 2 H), 5.73 (ddd, J = 17.0, 10.0, 7.5 Hz, 1 H), 5.20 (ddd,
J = 17.0, 1.0, 1.0 Hz, 1 H), 5.03 (dd, J = 10.0, 1.0 Hz, 1 H), 3.98 (q,
J = 7.5 Hz, 1 H), 3.28 (s, 3 H), 2.38 (s, 3 H), 1.58 (2 sept, J = 7.5
Hz, 2 H), 1.36 (2 sext, J = 7.5 Hz, 2 H), 0.88 (t, J = 7.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.2, 139.4, 138.8, 138.4, 130.1,
128.1, 115.4, 48.2, 38.3, 36.4, 21.2, 20.3, 13.7.
MS (ES+): m/z = 286 ([M +Na]+, 60%).
HRMS: m/z [M + Na]+ calcd for C15H21NOS: 286.1237; found:
MS (ES+): m/z (%) = 272 ([M + H]+, 100), 294 ([M + Na]+, 100).
HRMS: m/z [M + H]+ calcd for C16H17NOS: 272.1104; found:
286.1237.
272.1109.
S-Hex-1-en-3-yl 4-Fluorophenyl(methyl)carbamothioate (7o)26
General procedure B was followed using 10b (50 mg, 0.24 mmol)
in THF (1 mL), ECHIA (17 mg, 0.12 mmol, 0.5 equiv), and 4-fluo-
ro-N-methylaniline (0.04 mL, 0.29 mmol). The crude mixture was
washed with aq 1 M HCl (2 mL) for 25 min and concentrated down
to afford the title compound as a yellow oil (60 mg, 93%); Rf = 0.71
(PE–EtOAc, 8:2).
S-Hex-1-en-3-yl 4-Methoxyphenyl(methyl)carbamothioate
(7l)26
General procedure B was followed using S-hex-1-en-3-yl 1H-imid-
azole-1-carbothioate (10b; 50 mg, 0.24 mmol) in THF (1 mL),
ECHIA (17 mg, 0.12 mmol, 0.5 equiv), and 4-methoxy-N-methyl-
aniline (40 mg, 0.29 mmol). The crude mixture was washed with aq
1 M HCl (2 mL) for 15 min and concentrated down. The crude prod-
uct was purified by filtration over silica gel (PE–EtOAc, 9:1) to af-
ford the title compound as a yellow oil (60 mg, 89%); Rf = 0.53 (PE–
EtOAc, 8:2).
IR (film): 1655, 1508, 1220 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.26 (dd, J = 9.0, 5.0 Hz, 2 H),
7.10 (dd, J = 9.0 Hz, 2 H), 5.74 (ddd, J = 17.0, 10.0, 7.0 Hz, 1 H),
5.22 (ddd, J = 17.0, 1.0, 1.0 Hz, 1 H), 5.05 (dd, J = 10.0, 1.0 Hz, 1
H), 3.99 (q, J = 7.0 Hz, 1 H), 3.30 (s, 3 H), 1.61 (m, 2 H), 1.38 (sext,
J = 7.5 Hz, 2 H), 0.90 (t, J = 7.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.3, 163.4, 138.7, 138.1, 130.2,
116.5, 116.3, 115.6, 48.3, 38.3, 36.4, 20.3, 13.7.
IR (film): 1652, 1510, 1244 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.17 (d, J = 9.5 Hz, 2 H), 6.90 (d,
J = 9.5 Hz, 2 H), 5.72 (ddd, J = 17.0, 10.0, 8.0 Hz, 1 H), 5.20 (ddd,
J = 17.0, 1.0, 1.0 Hz, 1 H), 5.03 (d, J = 10.0 Hz, 1 H), 3.97 (q, J =
8.0 Hz, 1 H), 3.82 (s, 3 H), 3.27 (s, 3 H), 1.58 (m, 2 H), 1.37 (sext,
J = 8.0 Hz, 2 H), 0.88 (t, J = 8.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.5, 159.4, 138.8, 134.6, 129.7,
115.3, 114.6, 55.4, 48.2, 38.4, 36.4, 20.3, 13.7.
MS (ES+): m/z (%) = 268 ([M + H]+, 70), 290 ([M + Na]+, 100), 322
([M + Na + MeOH]+, 25).
HRMS: m/z [M + H]+ calcd for C14H18FNOS: 268.1166; found:
268.1164.
MS (ES+): m/z (%) = 302 ([M + Na]+, 100), 334 ([M + Na +
MeOH]+, 60).
S-Hex-1-en-3-yl 3-Chlorophenyl(methyl)carbamothioate (7p)26
General procedure B was followed using 10b (250 mg, 1.19 mmol)
in THF (5 mL), HOBt (161 mg, 1.18 mmol, 1.0 equiv), and 3-chlo-
ro-N-methylaniline (0.18 mL, 1.43 mmol). The crude mixture was
washed with aq 2 M HCl (5 mL) for 15 min and concentrated down.
The crude product was purified by column chromatography (100%
PE, then PE–EtOAc, 98:2, then 95:5) to afford the title compound
as a yellow oil (157 mg, 46%); Rf = 0.67 (PE–EtOAc 8:2).
HRMS: m/z [M + Na]+ calcd for C17H21NO2S: 302.1186; found:
302.1190.
S-Hex-1-en-3-yl 4-Chlorophenyl(methyl)carbamothioate (7m)26
General procedure B was followed using 10b (50 mg, 0.24 mmol)
in THF (1 mL), ECHIA (34 mg, 0.24 mmol, 1.0 equiv), and 4-chlo-
ro-N-methylaniline (0.04 mL, 0.29 mmol). The crude mixture was
washed with aq 2 M HCl (2 mL) for 30 min and concentrated down.
The crude product was purified by filtration over silica gel (PE–
EtOAc, 9:1) to afford the title compound as a yellow oil (52 mg,
77%); Rf = 0.70 (PE–EtOAc, 8:2).
IR (film): 1656, 1589, 1336, 1277 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.34–7.32 (m, 2 H), 7.28 (m, 1 H),
7.18 (ddd, J = 5.5, 3.5, 2.0 Hz, 1 H), 5.74 (ddd, J = 17.0, 10.0, 8.0
Hz, 1 H), 5.22 (ddd, J = 17.0, 1.0, 1.0 Hz, 1 H), 5.05 (ddd, J = 10.0,
IR (film): 1648, 1485, 1261 cm–1.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2723–2734

2730
G. Mingat, J. Clayden
PAPER
1.5, 1.0 Hz, 1 H), 4.00 (q, J = 8.0 Hz, 1 H), 3.30 (s, 3 H), 1.60 (m, 2
H), 1.38 (sext, J = 7.5 Hz, 2 H), 0.90 (t, J = 7.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.1, 143.3, 138.5, 134.7, 130.3,
128.4, 126.4, 115.6, 48.3, 38.1, 36.4, 20.3, 13.7.
MS (ES+): m/z = 306 ([M + Na]+, 100%).
IR (film): 1654, 1488, 1277 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.37 (d, J = 8.0 Hz, 2 H), 7.21 (d,
J = 8.0 Hz, 2 H), 5.87 (ddd, J = 17.0, 10.0, 7.5 Hz, 1 H), 5.66 (dqd,
J = 15.0, 6.5, 1.0 Hz, 1 H), 5.48 (ddq, J = 15.0, 7.5, 1.5 Hz, 1 H),
5.21 (ddd, J = 17.0, 1.0, 1.0 Hz, 1 H), 5.08 (ddd, J = 10.0, 1.0, 1.0
Hz, 1 H), 4.62 (br t, J = 7.5 Hz, 1 H), 3.29 (s, 3 H), 1.67 (d, J = 6.5
Hz, 3 H).
HRMS: m/z [M + H]+ calcd for C14H18ClNOS: 284.0871; found:
284.0868.
13C NMR (100 MHz, CDCl3): δ = 167.6, 137.1, 129.7, 129.6, 128.7,
128.2, 116.0, 50.0, 38.1, 17.9;
S-Hex-1-en-3-yl 2-Methoxyphenyl(methyl)carbamothioate
(7q)26
MS (ES+): m/z (%) = 282 ([M + H]+, 100), 304 ([M + Na]+, 60), 336
General procedure B was followed using 10b (250 mg, 1.19 mmol)
in THF (5 mL), HOBt (161 mg, 1.18 mmol, 1.0 equiv), and 2-me-
thoxy-N-methylaniline (0.18 mL, 1.43 mmol). The crude mixture
was washed with aq 1 M HCl (5 mL) for 15 min and concentrated
down. The crude product was purified by column chromatography
(100% PE, then PE–EtOAc, 98:2, then 95:5) to afford the title com-
pound as a yellow oil (223 mg, 67%); Rf = 0.57 (PE–EtOAc, 8:2).
([M + Na + MeOH]+, 30).
HRMS: m/z [M + Na]+ calcd for C14H16ClNOS: 304.0533; found:
304.0528.
(E)-S-Hexa-1,4-dien-3-yl Methyl(p-tolyl)carbamothioate (7t)26
General procedure B was followed using 10c (50 mg, 0.24 mmol)
in THF (1 mL), HOBt (16 mg, 0.118 mmol, 0.5 equiv), and 4-meth-
yl-N-methylaniline (0.04 mL, 0.29 mL). The crude mixture was
washed with aq 1 M HCl (2 mL) for 15 min and concentrated down.
The crude product was purified by filtration over silica gel (PE–
EtOAc, 9:1) to afford the title compound as a yellow oil (50 mg,
79%); Rf = 0.37 (PE–EtOAc, 9:1).
IR (film): 1655, 1499, 1271, 747 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.37 (t, J = 7.5 Hz, 1 H), 7.21 (d,
J = 7.5 Hz, 1 H), 6.97 (d, J = 7.5 Hz, 2 H), 5.72 (m, rotamers, 1 H),
5.19 (2 d, rotamers, J = 17.0 Hz, 1 H), 5.01 (2 d, rotamers, J = 10.0
Hz, 1 H), 3.97 (q, J = 7.5 Hz, 1 H), 3.84 (2 s, rotamers, 3 H), 3.21
(s, 3 H), 1.61–1.52 (m, 2 H), 1.36 (sept, J = 7.5 Hz, 2 H), 0.88 (2 t,
rotamers, J = 7.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.9, 156.2, 139.0/138.9 (rota-
mers), 130.9/130.7 (rotamers), 130.2, 130.2/130.1 (rotamers),
120.8/120.7 (rotamers), 115.2/115.1 (rotamers), 112.2/112.1 (rota-
mers), 55.6, 47.9/47.8 (rotamers), 36.8, 36.4, 20.4/20.2 (rotamers),
13.7.
IR (film): 1653, 1513, 1268 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.20 (d, J = 8.5 Hz, 2 H), 7.15 (d,
J = 9.0 Hz, 2 H), 5.87 (ddd, J = 17.0, 10.0, 7.5 Hz, 1 H), 5.65 (dqd,
J = 15.5, 6.5, 1.0 Hz, 1 H), 5.48 (ddq, J = 15.5, 7.5, 1.5 Hz, 1 H),
5.20 (ddd, J = 17.0, 1.0, 1.0 Hz, 1 H), 5.06 (ddd, J = 10.0, 1.0, 1.0
Hz, 1 H), 4.62 (br t, J = 7.5 Hz, 1 H), 3.29 (s, 3 H), 2.37 (s, 3 H),
1.66 (d, J = 6.5 Hz, 3 H).
MS (ES+): m/z = 302 ([M + Na]+, 100%).
13C NMR (100 MHz, CDCl3): δ = 167.8, 139.2, 138.5, 137.4, 130.1,
HRMS: m/z [M + H]+ calcd for C17H21NO2S: 280.1366; found:
280.1353.
129.0, 128.2, 127.9, 115.7, 49.9, 38.3, 21.2, 17.9.
MS (ES+) m/z (%) = 262 ([M + H]+, 100), 284 ([M + Na]+, 60).
HRMS: m/z [M + Na]+ calcd for C15H19NOS: 284.1080; found:
284.1071.
(E)-S-Hexa-1,4-dien-3-yl 4-Methoxyphenyl(methyl)carbamo-
thioate (7r)26
General procedure B was followed using (E)-S-hexa-1,4-dien-3-yl
1H-imidazole-1-carbothioate (10c; 50 mg, 0.24 mmol) in THF (1
mL), ECHIA (16 mg, 0.12 mmol, 0.5 equiv), and 4-methoxy-N-
methylaniline (40 mg, 0.29 mmol). The crude mixture was washed
with aq 1 M HCl (2 mL) for 15 min and concentrated down. The
crude product was purified by filtration over silica gel (PE–EtOAc,
9:1) to afford the title compound as a yellow oil (40 mg, 59%); Rf =
0.65 (PE–EtOAc, 8:2).
(E)-S-Hexa-1,4-dien-3-yl 4-Fluorophenyl(methyl)carbamothio-
ate (7u)26
General procedure B was followed using 10c (50 mg, 0.24 mmol)
in THF (1 mL), HOBt (32 mg, 0.236 mmol, 1.0 equiv), and 4-fluo-
ro-N-methylaniline (0.04 mL, 0.29 mmol). The crude mixture was
washed with aq 1 M HCl (2 mL) for 25 min and concentrated down
to afford the title compound as a yellow oil (50 mg, 78%); Rf = 0.63
(PE–EtOAc, 8:2).
IR (film): 1652, 1510, 1245 cm–1.
IR (film): 1650, 1503, 1219 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.17 (d, J = 9.0 Hz, 2 H), 6.90 (d,
J = 9.0 Hz, 2 H), 5.87 (ddd, J = 17.0, 10.0, 7.0 Hz, 1 H), 5.65 (m, 1
H), 5.47 (dqd, J = 15.0, 7.0, 1.0 Hz, 1 H), 5.20 (ddd, J = 17.0, 1.0,
1.0 Hz, 1 H), 5.06 (d, J = 10.0 Hz, 1 H), 4.60 (t, J = 7.0 Hz, 1 H),
3.82 (s, 3 H), 3.27 (s, 3 H), 1.67 (d, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.1, 159.5, 137.4, 134.4, 129.7,
129.0, 127.8, 115.7, 114.6, 55.4, 49.9, 38.4, 17.9.
1H NMR (400 MHz, CDCl3): δ = 7.25 (dd, J = 9.0, 5.0 Hz, 2 H),
7.08 (dd, J = 9.0 Hz, 2 H), 5.87 (ddd, J = 17.0, 10.0, 7.5 Hz, 1 H),
5.67 (dqd, J = 15.0, 6.5, 1.0 Hz, 1 H), 5.48 (ddq, J = 15.0, 7.5, 1.5
Hz, 1 H), 5.22 (ddd, J = 17.0, 1.5, 1.5 Hz, 1 H), 5.08 (ddd, J = 10.0,
1.5, 1.5 Hz, 1 H), 4.62 (br t, J = 7.5 Hz, 1 H), 3.29 (s, 3 H), 1.67 (d,
J = 6.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 167.8, 161.5, 137.9, 137.2, 130.3,
128.8, 128.1, 116.5, 116.3, 115.9, 50.0, 38.3, 17.9.
MS (ES+): m/z (%) = 266 ([M + H]+, 30), 388 ([M + Na]+, 70).
HRMS: m/z [M + Na]+ calcd for C14H16FNOS: 288.0829; found:
MS (ES+): m/z (%) = 300 ([M + Na]+, 100), 332 ([M + Na +
MeOH]+, 55).
HRMS: m/z [M + Na]+ calcd for C15H19NO2S: 300.1029; found:
300.1023.
288.0835.
(E)-S-Hexa-1,4-dien-3-yl 4-Chlorophenyl(methyl)carbamothio-
ate (7s)26
(S)-4-Methylpent-1-en-3-yl 4-Chlorophenyl(methyl)carbamo-
thioate (7v)26
General procedure B was followed using 10c (50 mg, 0.24 mmol)
in THF (1 mL), HOBt (32 mg, 0.236 mmol, 1.0 equiv), and 4-chlo-
ro-N-methylaniline (0.04 mL, 0.29 mL). The crude mixture was
washed with aq 2 M HCl (2 mL) for 30 min and concentrated down.
The crude product was purified by filtration over silica gel (PE–
EtOAc, 9:1) to afford the title compound as a pale orange oil (53
mg, 78%); Rf = 0.70 (PE–EtOAc, 8:2).
General procedure B was followed using (S)-4-methylpent-1-en-3-
yl 1H-imidazole-1-carbothioate (10d; 200 mg, 0.95 mmol) in THF
(4.5 mL), HOBt (128 mg, 0.95 mmol, 1.0 equiv), and 4-chloro-N-
methylaniline (0.14 mL, 1.14 mmol). The crude mixture was
washed with aq 1 M HCl (3 mL) for 15 min and concentrated down.
The crude product was purified by column chromatography (100%
Synthesis 2012, 44, 2723–2734
© Georg Thieme Verlag Stuttgart · New York

PAPER
S-Allyl Thiocarbamates from Allylic Alcohols
2731
PE, then PE–EtOAc, 95:5) to afford the title compound as a pale
yellow oil (219 mg, 81%); Rf = 0.53 (PE–EtOAc, 8:2).
IR (film): 1657, 1488, 1277 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.37 (d, J = 9.0 Hz, 2 H), 7.21 (d,
J = 9.0 Hz, 2 H), 5.73 (ddd, J = 17.0, 10.0, 9.0 Hz, 1 H), 5.22 (ddd,
J = 17.0, 1.5, 1.0 Hz, 1 H), 5.07 (dd, J = 10.0, 1.0 Hz, 1 H), 3.93 (dd,
J = 9.0, 6.0 Hz, 1 H), 3.28 (s, 3 H), 1.91 (oct, J = 6.0 Hz, 1 H), 0.93
(d, J = 6.0 Hz, 3 H), 0.91 (d, J = 6.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.1, 140.7, 136.7, 136.3, 129.6,
129.5, 116.4, 55.8, 38.2, 32.2, 20.2, 19.6;
The crude product was purified by filtration over silica gel (PE–
EtOAc, 9:1) to afford the title compound as a yellow oil (169 mg,
73%); Rf = 0.77 (PE–EtOAc, 8:2).
IR (film): 2921, 1651, 1486, 1280, 964 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.36 (d, J = 9.0 Hz, 2 H), 7.20 (d,
J = 9.0 Hz, 2 H), 5.54 (dd, J = 15.5, 6.5 Hz, 1 H), 5.41 (ddd, J = 15.5,
7.0, 1.0 Hz, 1 H), 4.08 (quint, J = 7.0 Hz, 1 H), 3.28 (s, 3 H), 1.93–
1.84 (m, 1 H), 1.71–1.58 (m, 4 H), 1.37 (d, J = 7.0 Hz, 3 H), 1.28–
0.96 (m, 6 H).
13C NMR (100 MHz, CDCl3): δ = 168.4, 140.7, 137.2, 133.9, 129.6,
129.5, 128.1, 42.7, 40.3, 38.1, 32.8/32.7, 26.1/26.0, 21.1.
MS (ES+): m/z (%) = 338 [M + H]+, 70), 360 ([M + Na]+, 100).
MS (ES+): m/z (%) = 284 ([M + H]+, 70), 306 ([M + Na]+, 100), 338
([M + Na + MeOH]+, 54).
HRMS: m/z [M + H]+ calcd for C14H18ClNOS: 284.0871; found:
HRMS: m/z [M + H]+ calcd for C18H24ClNOS: 338.1340; found:
284.0871.
338.1346.
S-4-Methylpent-1-en-3-yl Methyl(p-tolyl)carbamothioate
(7w)26
(E)-S-4-Cyclohexylbut-3-en-2-yl Methyl(p-tolyl)carbamothio-
ate (7z)26
General procedure B was followed using 10d (50 mg, 0.24 mmol)
in THF (1 mL), HOBt (16 mg, 0.12 mmol, 0.5 equiv), and 4-methyl-
N-methylaniline (0.04 mL, 0.29 mmol). The crude mixture was
washed with aq 1 M HCl (2 mL) for 40 min and concentrated down.
The crude product was purified by filtration over silica gel (PE–
EtOAc, 9:1) to afford the title compound as a yellow oil (353 mg,
84%); Rf = 0.75 (PE–EtOAc, 8:2).
General procedure B was followed using 10f (180 mg, 0.68 mmol)
in THF (2.5 mL), HOBt (46 mg, 0.34 mmol, 0.5 equiv), and 4-meth-
yl-N-methylaniline (0.11 mL, 0.82 mmol). The crude mixture was
washed with aq 1 M HCl (3 mL) for 20 min and concentrated down.
The crude product was purified by filtration over silica gel (PE–
EtOAc, 9:1) to afford the title compound as a yellow oil (185 mg,
86%); Rf = 0.76 (PE–EtOAc, 8:2).
IR (film): 1654, 1513, 1266 cm–1.
IR (film): 2921, 1651, 1513, 1268, 1107 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.21 (d, J = 8.0 Hz, 2 H), 7.15 (d,
J = 8.0 Hz, 2 H), 5.73 (ddd, J = 17.5, 10.5 Hz, 9.0, 1 H), 5.22 (dd,
J = 17.5, 1.5 Hz, 1 H), 5.06 (dd, J = 10.5, 1.5 Hz, 1 H), 3.93 (dd, J =
9.0, 6.0 Hz, 1 H), 3.28 (s, 3 H), 2.38 (s, 3 H), 1.89 (oct, J = 6.0 Hz,
1 H), 0.92 (d, J = 6.0 Hz, 3 H), 0.91 (d, J = 6.0 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.20 (d, J = 8.0 Hz, 2 H), 7.14 (d,
J = 8.0 Hz, 2 H), 5.52 (dd, J = 15.5, 6.0 Hz, 1 H), 5.40 (ddd, J = 15.5,
7.0, 1.0 Hz, 1 H), 4.07 (quint, J = 7.0 Hz, 1 H), 3.28 (s, 3 H), 2.37
(s, 3 H), 1.91–1.83 (m, 1 H), 1.69–1.60 (m, 4 H), 1.36 (d, J = 7.0 Hz,
3 H), 1.27–0.95 (m, 6 H).
13C NMR (100 MHz, CDCl3): δ = 168.2, 139.6, 138.3, 137.0, 130.1,
13C NMR (100 MHz, CDCl3): δ = 168.6, 139.5, 138.3, 136.9, 130.1,
128.1, 116.2, 55.6, 38.4, 32.2, 21.2, 20.3, 19.6.
128.3, 128.0, 42.6, 40.3, 38.2, 32.8/32.7, 26.1/26.0, 21.2, 21.1.
MS (ES+): m/z (%) = 264 ([M + H]+, 30), 286 ([M + Na]+, 50).
MS (ES+): m/z (%) = 318 ([M + H]+, 100), 340 ([M + Na]+, 60).
HRMS: m/z [M + H]+ calcd for C15H21NOS: 264.1417; found:
264.1413.
HRMS: m/z [M + H]+ calcd for C19H27NOS: 338.1887; found:
318.1892.
(E)-S-Pent-3-en-2-yl 4-Chlorophenyl(methyl)carbamothioate
(7x)26
(E)-S-4-Cyclohexylbut-3-en-2-yl 3-Chlorophenyl(methyl)car-
bamothioate (7aa)26
General procedure B was followed using (E)-S-pent-3-en-2-yl 1H-
imidazole-1-carbothioate (10e; 50 mg, 0.25 mmol) in THF (2.5
mL), HOBt (18 mg, 0.13 mmol, 0.5 equiv), and 4-chloro-N-methyl-
aniline (0.04 mL, 0.30 mmol). The crude mixture was washed with
aq 3 M HCl (3 mL) for 50 min and concentrated down. The crude
product was purified by column chromatography (100% PE, then
PE–EtOAc, 95:5, then 9:1) to afford the title compound as a colour-
less oil (33 mg, 49%), Rf = 0.36 (PE–EtOAc, 8:2).
General procedure B was followed using 10f (180 mg, 0.68 mmol)
in THF (2.5 mL), HOBt (92 mg, 0.68 mmol, 1.0 equiv), and 3-chlo-
ro-N-methylaniline (0.10 mL, 0.82 mmol). The crude mixture was
washed with aq 2 M HCl (3 mL) for 30 min and concentrated down.
The crude product was purified by filtration over silica gel (PE–
EtOAc, 9:1) to afford the title compound as a yellow oil (178 mg,
77%); Rf = 0.79 (PE–EtOAc, 8:2).
IR (film): 2922, 1656, 1589, 1277, 965, 694 cm–1.
IR (film): 1651, 1487, 1013 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.33–7.32 (m, 2 H), 7.28–7.27 (m,
1 H), 7.18 (ddd, J = 5.5, 3.5, 2.0, 1 H), 5.55 (ddd, J = 15.5, 6.5, 1.0
Hz, 1 H), 5.41 (ddd, J = 15.5, 7.0, 1.0 Hz, 1 H), 4.09 (quint, J = 7.0
Hz, 1 H), 3.29 (s, 3 H), 1.93–1.85 (m, 1 H), 1.71–1.60 (m, 4 H), 1.38
(d, J = 7.0 Hz, 3 H), 1.27–0.97 (m, 6 H).
1H NMR (400 MHz, CDCl3): δ = 7.36 (d, J = 9.0 Hz, 2 H), 7.20 (d,
J = 9.0 Hz, 2 H), 5.62 (dqd, J = 15.0, 6.5, 1.0 Hz, 1 H), 5.47 (ddq,
J = 15.0, 7.0, 1.5 Hz, 1 H), 4.07 (quint, J = 7.0 Hz, 1 H), 3.29 (s, 3
H), 1.64 (d, J = 6.5 Hz, 3 H), 1.36 (d, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.4, 140.7, 134.0, 132.1, 129.6,
13C NMR (100 MHz, CDCl3): δ = 168.4, 143.4, 137.2, 134.7, 130.3,
129.5, 126.1, 42.7, 38.0, 21.0, 17.8.
128.3, 128.0, 126.4, 42.7, 40.3, 38.0, 32.8/32.7, 26.1/26.0, 21.1.
MS (ES+): m/z (%) = 270 ([M + H]+, 40), 292 ([M + Na]+, 100).
MS (ES+): m/z (%) = 338 ([M + H]+, 50), 360 ([M + Na]+, 100).
HRMS: m/z [M + Na]+ calcd for C13H16ClNOS: 292.0534; found:
292.0525.
HRMS: m/z [M + H]+ calcd for C18H24ClNOS: 338.1340; found:
338.1349.
(E)-S-4-Cyclohexylbut-3-en-2-yl 4-Chlorophenyl(methyl)car-
bamothioate (7y)26
(E)-S-4-Cyclohexylbut-3-en-2-yl 2-Methoxyphenyl(methyl)car-
bamothioate (7bb)26
General procedure B was followed using (E)-S-4-cyclohexylbut-3-
en-2-yl 1H-imidazole-1-carbothioate (10f; 180 mg, 0.68 mmol) in
THF (2.5 mL), HOBt (46 mg, 0.34 mmol, 0.5 equiv), and 4-chloro-
N-methylaniline (0.10 mL, 0.82 mmol). The crude mixture was
washed with aq 2 M HCl (3 mL) for 30 min and concentrated down.
General procedure B was followed using (200 mg, 0.76 mmol) in
THF (4.0 mL), HOBt (154 mg, 1.14 mmol, 1.5 equiv), and 2-meth-
oxy-N-methylaniline (125 mg, 0.91 mmol). The crude mixture was
washed with aq 1 M HCl (5 mL) for 25 min and concentrated down.
The crude product was purified by column chromatography (100%
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2723–2734

2732
G. Mingat, J. Clayden
PAPER
PE, then PE–EtOAc, 98:2, then 96:4, then 95:5) to afford the title
compound as a colourless sticky oil (196 mg, 77%); Rf = 0.48 (PE–
EtOAc, 8:2).
IR (film): 2921, 1651, 1499, 1271, 747 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.36 (ddd, J = 8.0, 8.0, 1.5 Hz, 1
H), 7.21 (br d, J = 8.0 Hz, 1 H), 6.96 (m, 2 H), 5.50 (m, 1 H), 5.40
(m, 1 H), 4.07 (m, 1 H), 3.85 (s, 3 H), 3.21 (s, 3 H), 1.91–1.84 (m,
1 H), 1.69–1.60 (m, 4 H), 1.34 (2 d, rotamers, J = 7.0 Hz, 3 H), 1.25–
0.95 (m, 6 H).
13C NMR (100 MHz, CDCl3): δ = 156.2/156.1 (rotamers),
136.7/136.6 (rotamers), 130.8, 130.2, 128.6/128.5, 120.8,
112.2/112.1 (rotamers), 55.6, 42.3/42.2 (rotamers), 40.4, 36.7,
32.8/32.7, 26.1/26.0, 21.1.
(rotamers), 122.6 /122.4 (rotamers), 42.4, 40.3/40.2 (rotamers),
40.0, 32.8/32.6, 26.0/25.9, 20.9/20.7 (rotamers).
MS (ES+): m/z (%) = 354 ([M + H]+, 100), 376 ([M + Na]+, 80).
HRMS: m/z [M + H]+ calcd for C22H27NOS: 354.1887; found:
354.1889.
(E)-S-4-Cyclohexylbut-3-en-2-yl 3-Fluorophenyl(methyl)car-
bamothioate (7ee)26
General procedure B was followed using 10f (200 mg, 0.76 mmol)
in THF (4.0 mL), HOBt (154 mg, 1.14 mmol, 1.5 equiv), and 3-
fluoro-N-methylaniline (0.10 mL, 0.91 mmol). The crude mixture
was washed with aq 1 M HCl (5 mL) for 25 min and concentrated
down. The crude product was purified by column chromatography
(100% PE, then PE–EtOAc, 98:2, then 96:4) to afford the title com-
pound as a yellow oil (145 mg, 59%); Rf = 0.68 (PE–EtOAc, 8:2).
MS (ES+): m/z = 334 ([M + H]+, 100%).
HRMS: m/z [M + Na]+ calcd for C19H27NO2S: 356.1655; found:
IR (film): 2922, 1656, 1485, 1282, 1194, 966, 696 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.36 (ddd, J = 8.0, 8.0, 6.5 Hz, 1
H), 7.08–7.05 (m, 2 H), 7.03–6.99 (m, 1 H), 5.55 (ddd, J = 15.5, 6.5
Hz, 1 H), 5.41 (ddd, J = 15.5, 7.0, 1.0 Hz, 1 H), 4.09 (quint, J = 7.0
Hz, 1 H), 3.30 (s, 3 H), 1.94–1.85 (m, 1 H), 1.71–1.60 (m, 4 H), 1.37
(d, J = 7.0 Hz, 3 H), 1.28–0.97 (m, 6 H).
356.1659.
(E)-S-4-Cyclohexylbut-3-en-2-yl 3-Methoxyphenyl(methyl)car-
bamothioate (7cc)26
General procedure B was followed using 10f (200 mg, 0.76 mmol)
in THF (4.0 mL), HOBt (154 mg, 1.14 mmol, 1.5 equiv), and 3-
methoxy-N-methylaniline (0.12 mL, 0.91 mmol). The crude mix-
ture was washed with aq 1 M HCl (5 mL) for 25 min and concen-
trated down. The crude product was purified by column
chromatography (100% PE, then PE–EtOAc, 98:2, then 96:4, then
95:5) to afford the title compound as a yellow oil (197 mg, 78%);
Rf = 0.48 (PE–EtOAc, 8:2); [α]D20 –10.75 (c 0.16, CHCl3).
13C NMR (100 MHz, CDCl3): δ = 168.4, 164.0, 143.7/143.6 (rota-
mers),
137.2,
130.4/130.4
(rotamers),
128.1,
123.8,
115.6/115.4/115.3/115.2, 42.7, 40.3, 38.0, 32.8/32.7, 26.1/26.0,
21.0.
MS (ES+): m/z = 344 [M + Na]+; 100%).
HRMS: m/z [M + Na]+ calcd for C18H24FNOS: 344.1455; found:
344.1445.
HPLC: er 94:6; (R,R)-Whelk-01, hexane–i-PrOH (95:5), 1 mL/min,
254.4 nm; S-enantiomer (major), tR = 8.9 min, R-enantiomer (mi-
nor), tR = 11.2 min.
IR (film): 2921, 1651, 1599, 1283, 1217, 1042 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.30 (dd, J = 8.0, 8.0 Hz, 1 H),
6.89 (ddd, J = 8.5, 2.5, 1.0 Hz, 1 H), 6.86 (ddd, J = 8.0, 2.5, 1.0 Hz,
1 H), 6.80 (dd, J = 2.5, 2.5 Hz, 1 H), 5.53 (ddd, J = 15.5, 6.5, 1.0 Hz,
1 H), 5.41 (ddd, J = 15.5, 7.0, 1.0 Hz, 1 H), 4.08 (quint, J = 7.0 Hz,
1 H), 3.82 (s, 3 H), 3.30 (s, 3 H), 1.93–1.84 (m, 1 H), 1.71–1.58 (m,
4 H), 1.37 (d, J = 7.0 Hz, 3 H), 1.28–0.96 (m, 6 H).
13C NMR (100 MHz, CDCl3): δ = 168.4, 160.2, 143.3, 137.0, 130.0,
128.3, 120.3, 113.9, 113.7, 55.4, 42.6, 40.4, 38.1, 32.8/32.7,
26.1/26.0, 21.1.
S-But-3-en-2-yl 1H-Imidazole-1-carbothioate (10a)25
General procedure A was followed using crotyl alcohol (5a; 500
mg, 6.9 mmol), TCDI (2.5 g, 13.8 mmol), DMAP (86 mg, 0.70
mmol), and CH2Cl2 (70 mL). The crude product was purified by
column chromatography (PE–EtOAc, 8:2) to afford the title com-
pound as a yellow oil (1.24 g, 98%); Rf = 0.44 (PE–EtOAc, 1:1).
IR (film): 1687, 1468, 1210 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.17 (br s, 1 H), 7.44 (t, J = 1.0
Hz, 1 H), 7.08 (m, 1 H), 5.94 (ddd, J = 17.0, 10.5, 7.0 Hz, 1 H), 5.36
(ddd, J = 17.0, 1.0, 1.0 Hz, 1 H), 5.20 (ddd, J = 10.5, 1.0, 1.0 Hz, 1
H), 4.38 (quint, J = 7.0, 1.0 Hz, 1 H), 1.55 (d, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 165.1, 136.9, 135.2, 130.7, 116.8,
115.6, 43.2, 19.4.
MS (ES+): m/z (%) = 334 ([M + H]+ ,100), 356 ([M + Na]+, 40).
HRMS: m/z [M + Na]+ calcd for C19H27NO2S: 356.1655; found:
MS (ES+): m/z (%) = 183 ([M + H]+, 30), 205 ([M + Na]+, 70), 237
356.1649.
([M + Na + MeOH]+, 100).
HRMS: m/z [M + H]+ calcd for C8H10N2OS: 183.0587; found:
183.0586.
(E)-S-4-Cyclohexylbut-3-en-2-yl Methyl(naphthalen-1-yl)car-
bamothioate (7dd)26
General procedure B was followed using 10f (200 mg, 0.76 mmol)
in THF (4.0 mL), HOBt (153 mg, 1.14 mmol, 1.5 equiv), and N-
methylnaphthalen-1-amine (143 mg, 0.91 mmol). The crude mix-
ture was washed with aq 1 M HCl (5 mL) for 25 min and concen-
trated down. The crude product was purified by column
chromatography (PE–EtOAc, 95:5, then 9:1) to afford the title com-
pound as a brown solid (110 mg, 41%); mp 83–85 °C; Rf = 0.36
(PE–EtOAc 8:2).
S-Hex-1-en-3-yl 1H-Imidazole-1-carbothioate (10b)25
General procedure A was followed using hex-2-en-1-ol (500 mg,
5.0 mmol), TCDI (1.8 g, 10.1 mmol), DMAP (60 mg, 0.49 mmol),
and CH2Cl2 (50 mL). The crude product was purified by filtration
over silica gel (PE–EtOAc, 1:1) to afford the title compound as a
yellow oil (1.05 g, 100%); Rf = 0.16 (PE–EtOAc, 8:2).
IR (film): 1689, 1467, 1211 cm–1.
IR (neat): 2927, 1643, 1338, 1279, 777 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.16 (br s, 1 H), 7.43 (br s, 1 H),
7.06 (br s, 1 H), 5.81 (ddd, J = 17.0, 10.0, 7.5 Hz, 1 H), 5.34 (d, J =
17.0 Hz, 1 H), 5.17 (d, J = 10.0 Hz, 1 H), 4.24 (q, J = 7.5 Hz, 1 H),
1.76 (q, J = 7.5 Hz, 2 H), 1.50–1.40 (m, 2 H), 0.94 (t, J = 7.5 Hz, 3
H).
13C NMR (100 MHz, CDCl3): δ = 165.2, 136.4, 135.4, 130.8, 117.6,
115.8, 48.7, 35.8, 20.2, 13.5.
1H NMR (400 MHz, CDCl3): δ = 7.80–7.76 (m, 2 H), 7.70–7.67 (m,
1 H), 7.47–7.31 (m, 4 H), 5.41–5.34 (m, 1 H), 5.21 (2 dd, rotamers,
J = 15.5, 7.0 Hz, 1 H), 4.01–3.96 (m, 1 H), 3.30/3.29 (2 s, rotamers,
3 H), 1.75–1.68 (m, 1 H), 1.57–1.48 (m, 4 H), 1.19 (2 d, J = 7.0 Hz,
3 H), 1.12–0.81 (m, 6 H).
13C NMR (100 MHz, CDCl3): δ = 169.4/169.3 (rotamers),
138.1/138.0, 136.9/136.6, 134.6, 130.5, 129.3, 128.5, 128.4, 128.2,
127.5/127.4 (rotamers), 127.2/127.2 (rotamers), 126.5, 125.6/125.6
MS (ES+) m/z (%) = 233 ([M + Na]+, 50), 265 ([M + Na + MeOH]+,
100).
Synthesis 2012, 44, 2723–2734
© Georg Thieme Verlag Stuttgart · New York

PAPER
S-Allyl Thiocarbamates from Allylic Alcohols
2733
HRMS: m/z [M + Na]+ calcd for C10H14N2OS: 233.0719; found:
233.0722.
(E)-S-4-Cyclohexylbut-3-en-2-yl 1H-Imidazole-1-carbothioate
(10f)25
General procedure A was followed using (E)-1-cyclohexylbut-2-
en-1-ol (1.0 g, 6.48 mmol), TCDI (2.31 g, 12.97 mmol), DMAP (79
mg, 0.65 mmol), and CH2Cl2 (40 mL). The crude product was puri-
fied by column chromatography (PE–EtOAc, 9:1, then, 85:15, then
8:2) to afford the title compound as a yellow oil (1.55 g, 90%); Rf =
0.51 (PE–EtOAc, 8:2); [α]D20 –48.0 (c 0.07, CHCl3).
(E)-S-Hexa-1,4-dien-3-yl 1H-Imidazole-1-carbothioate (10c)25
General procedure A was followed using hexa-2,4-dien-1-ol (500
mg, 5.1 mmol), TCDI (1.8 g, 10.1 mmol), DMAP (62 mg, 0.51
mmol), and CH2Cl2 (50 mL). The crude product was purified by fil-
tration over silica gel (PE–EtOAc, 1:1) to afford the title compound
as a yellow oil (689 mg, 65%); Rf = 0.64 (PE–EtOAc, 1:1).
HPLC: er 6:94; Chiralpak AD-H, hexane–i-PrOH (97:3), 214.4 and
254.4 nm, 1 mL/min; R-enantiomer (minor), tR = 15.3 min; S-enan-
tiomer (major), tR = 20.3 min.
IR (film): 1689, 1212, 882 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.16 (s, 1 H), 7.43 (d, J = 1.0 Hz,
1 H), 7.07 (s, 1 H), 5.73 (dd, J = 15.5, 7.0 Hz, 1 H), 5.47 (ddd, J =
15.5, 7.0, 1.0 Hz, 1 H), 4.34 (quint, J = 7.0 Hz, 1 H), 1.99–1.91 (m,
1 H), 1.74–1.62 (m, 4 H), 1.52 (d, J = 7.0 Hz, 3 H), 1.31–1.01 (m, 6
H).
13C NMR (100 MHz, CDCl3): δ = 165.6, 139.6, 135.4, 130.7, 126.2,
115.8, 43.6, 40.3, 32.6/32.6, 26.0/25.9, 20.6.
MS (ES+): m/z (%) = 265 ([M + H]+, 100), 287 ([M + Na]+, 55).
HRMS: m/z [M + H]+ calcd for C14H20N2OS: 265.1370; found:
IR (film): 1690, 1468, 1212 cm–1.
1H NMR (400 MHz; CDCl3): δ = 8.17 (br s, 1 H), 7.43 (t, J = 1.5
Hz, 1 H), 7.08 (m, 1 H), 5.96 (ddd, J = 17.20, 10.0, 7.0 Hz, 1 H),
5.84 (dqd, J = 15.0, 6.5, 1.0 Hz, 1 H), 5.59 (ddq, J = 15.0, 7.0, 1.5
Hz, 1 H), 5.36 (ddd, J = 17.0, 1.0, 1.0 Hz, 1 H), 5.24 (ddd, J = 10.0,
1.0, 1.0 Hz, 1 H), 4.87 (br t, J = 7.0 Hz, 1 H), 1.74 (d, J = 6.5 Hz, 3
H).
13C NMR (100 MHz, CDCl3): δ = 164.9, 135.4, 134.9, 130.9, 130.5,
126.8, 118.0, 115.8, 50.5, 17.9.
MS (ES+): m/z = 209 ([M + H]+, 90), 231 ([M + Na]+, 40), 263 ([M
+ Na + MeOH]+, 100).
HRMS: m/z [M + H]+ calcd for C10H12N2OS: 209.0743; found:
209.0726.
265.1369.
S-4-Methylpent-1-en-3-yl 1H-Imidazole-1-carbothioate (10d)25
General procedure A was followed using 4-methylpent-2-en-1-ol
(25 mg, 0.25 mmol), TCDI (89 mg, 0.50 mmol), DMAP (3 mg,
0.025 mmol), and CH2Cl2 (52.5 mL). The crude product was puri-
fied by filtration over silica gel (PE–EtOAc, 8:2) to afford the title
compound as a pale yellow oil (47 mg, 88%); Rf = 0.27 (PE–EtOAc,
8:2).
Kinetic Resolution of 1-Cyclohexylbut-2-en-1-ol via Sharpless
Asymmetric Epoxidation27
To a solution of 1-cyclohexylbut-2-en-1-ol (1.00 g, 6.48 mmol) in
CH2Cl2 (25 mL) at r.t. was added (+)-diisopropyl tartrate [(+)-
DIPT, 0.20 mL, 228 mg, 0.97 mmol, 0.15 equiv], followed by pow-
dered 4 Å molecular sieves (250 mg, 20–30 wt% based on allylic al-
cohol, previously dried under reduced pressure at 160 °C
overnight). The reaction mixture was cooled to –20 °C (internal
temperature monitored). Ti(Oi-Pr)4 (0.19 mL, 184 mg, 0.65 mmol,
0.10 equiv) was added and the mixture was stirred at –20 °C for 20–
30 min. Anhyd tert-butyl hydroperoxide (TBHP) (0.71 mL, 5.5 M
in decane, 3.89 mmol, 0.6 equiv) was added dropwise, maintaining
the internal temperature between –21 and –19 °C. The reaction mix-
ture was stirred at –20 °C for 15 h before an aliquot (0.1 mL) was
removed and quenched with 2 mL of an aq solution of FeSO4·7H2O
and citric acid monohydrate (33 g of FeSO4·7H2O, 11 g of citric acid
monohydrate, 100 mL of distilled H2O). 1H NMR of the concentrat-
ed organic fraction of the aliquot showed an allylic alcohol/epoxide
ratio of 1:1.3. The reaction was quenched at –20 °C by adding the
aforementioned ferrous aqueous solution (20 mL) and warming the
reaction to r.t. and vigorously stirring until two clear phases ap-
peared (30 min). The mixture was extracted with CH2Cl2 (2 × 20
mL) and the combined organic layers concentrated to the original
volume, washed with 30% NaOH in brine (6.5 mL, 1 mL/1.0 mmol
of substrate). The mixture was extracted with CH2Cl2 (3 × 30 mL)
and the combined organic layers were washed with brine (2 × 50
mL), dried (MgSO4), filtered, and concentrated down. The crude
was purified by column chromatography (100% PE, then PE–EtO-
Ac, 95:5, then, 9:1, then, 85:15) to afford the R-allylic alcohol as a
colourless oil (296 mg, 30%).
IR (film): 1689, 1467, 1211 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.19 (br s, 1 H), 7.46 (t, J = 1.5
Hz, 1 H), 7.08 (dd, J = 1.5, 1.0 Hz, 1 H), 5.85 (ddd, J = 17.0, 10.0,
9.0 Hz, 1 H), 5.35 (d, J = 17.0 Hz, 1 H), 5.21 (ddd, J = 10.0, 1.0, 1.0
Hz, 1 H), 4.18 (dd, J = 9.0, 6.5 Hz, 1 H), 2.08 (oct, J = 6.5 Hz, 1 H),
1.04 (2 dd, J = 6.5, 1.0 Hz, 6 H).
13C NMR (100 MHz, CDCl3): δ = 165.3, 135.5, 134.8, 130.8, 118.4,
115.9, 56.2, 32.0, 20.0, 19.7.
MS (ES+) m/z (%) = 211 ([M + H]+, 20), 233 ([M + Na]+, 100), 265
([M + Na + MeOH]+, 50).
HRMS: m/z [M + Na]+ calcd for C10H14N2OS: 233.0719; found:
233.0729.
(E)-S-Pent-3-en-2-yl 1H-Imidazole-1-carbothioate (10e)25
General procedure A was followed using pent-3-en-2-ol (50 mg,
0.58 mmol), TCDI (206 mg, 1.16 mmol), DMAP (7 mg, 0.06
mmol), and DCE (6 mL). The reaction mixture was stirred at r.t. for
2 h, then heated to 40 °C, and stirred at 40 °C for 24 h. The crude
product was purified by filtration over silica gel (PE–EtOAc, 8:2) to
afford the title compound as a yellow oil (112 mg, 98%); Rf = 0.30
(PE–EtOAc, 8:2).
IR (film): 1686, 1211, 880 cm–1.
The enantiomeric ratio was determined by chiral GC [chiral column
G-TA, method: 3 min at 50 °C, up to 80 °C by 5 °C/min, up to
102 °C by 1 °C/min, 5 min hold at 102 °C, up to 110 °C by
1 °C/min, up to 180 °C by 10 °C/min; R-enantiomer (major), tR =
29.3 min, S-enantiomer (minor), tR = 31.1 min, er 93:7].
1H NMR (400 MHz, CDCl3): δ = 8.15 (s, 1 H), 7.42 (d, J = 1.5 Hz,
1 H), 7.07 (s, 1 H), 5.80 (dqd, J = 15.0, 6.45, 1.0 Hz, 1 H), 5.54 (ddq,
J = 15.0, 7.5, 1.5 Hz, 1 H), 4.34 (quint, J = 7.5 Hz, 1 H), 1.70 (d, J =
6.5 Hz, 3 H), 1.52 (d, J = 7.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 165.6, 135.4, 130.8, 130.1, 128.5,
115.8, 43.4, 20.5, 17.7.
25
Rf = 0.58 (PE–EtOAc, 8:2); [α]D20 –1.0 (c 0.12, CHCl3) {Lit27 [α]D
–13.33 (c 2.76, EtOH).
MS (ES+): m/z (%) = 197 ([M + H]+, 100), 219 ([M + Na]+, 70), 251
1H NMR (400 MHz, CDCl3): δ = 5.62 (dq, J = 15.0, 6.5 Hz, 1 H),
5.47 (ddq, J = 15.0, 7.0, 1.5 Hz, 1 H), 3.75 (t, J = 7.0 Hz, 1 H), 1.87–
1.83 (m, 1 H), 1.77–1.63 (m, 4 H), 1.70 (dd, J = 6.5, 1.5 Hz, 3 H),
1.43–0.86 (m, 8 H).
([M + Na + MeOH]+, 70).
HRMS: m/z [M + Na]+ calcd for C9H12N2OS: 219.0563; found:
219.0567.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2723–2734

2734
G. Mingat, J. Clayden
PAPER
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Acknowledgment
This work was supported by the EPSRC by way of a studentship (to
G.M.).
(18) Sakamoto, M.; Yoshiaki, M.; Takahashi, M.; Fujita, T.;
Watanabe, S. J. Chem. Soc., Perkin Trans. 1 1995.
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
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Synthesis 2012, 44, 2723–2734
© Georg Thieme Verlag Stuttgart · New York