Ti-mediated intramolecular cyclopropanation of N-alkenyl thioamides: Scope and mechanistic study

Article abstract of DOI:10.1016/j.tet.2014.04.006

Although thioamides generally undergo a reductive alkylation process when they are treated with a Grignard reagent in the presence of Ti(OiPr) ₄, substrates fitted with a but-3-enyl substitution at the nitrogen atom are shown to be converted into bicyclic aminocyclopropanes. These reactions are compared with the similar cyclisations of the corresponding carboxylic amide substrates. A mechanistic study is provided. Coincidently, new reagent systems are identified for the mediation of the same transformation.

Full text of DOI:10.1016/j.tet.2014.04.006

Tetrahedron xxx (2014) 1e7
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ti-mediated intramolecular cyclopropanation of N-alkenyl
thioamides: scope and mechanistic study
,
Fabien Hermant a, Emmanuel Nicolas b, Yvan Six a
*
a
ꢀ
Laboratoire de Synthese Organique (DCSO), UMR 7652 CNRS/Ecole Polytechnique, Route de Saclay, 91128 Palaiseau Cedex, France
Laboratoire de Chimie Moleculaire (LCM), UMR 9168 CNRS/Ecole Polytechnique, 91128 Palaiseau Cedex, France
b
ꢁ
a r t i c l e i n f o
a b s t r a c t
Article history:
Although thioamides generally undergo a reductive alkylation process when they are treated with
a Grignard reagent in the presence of Ti(OiPr)4, substrates fitted with a but-3-enyl substitution at the
nitrogen atom are shown to be converted into bicyclic aminocyclopropanes. These reactions are com-
pared with the similar cyclisations of the corresponding carboxylic amide substrates. A mechanistic
study is provided. Coincidently, new reagent systems are identified for the mediation of the same
transformation.
Received 10 January 2014
Received in revised form 1 April 2014
Accepted 3 April 2014
Available online xxx
Keywords:
Kulinkovich-type reactions
Thioamides
Ó 2014 Elsevier Ltd. All rights reserved.
Aminocyclopropanes
Grignard reagents
Diastereoselectivity
1. Introduction
Since the seminal report by Kulinkovich et al. on the synthesis of
cyclopropanols,1 methods that rely on the combined use of
Grignard reagents and titanium(IV) alkoxide derivatives have
emerged as a whole family of valuable reactions.2e5 In this context,
we have recently investigated the behaviour of thioamides 1 and
found that they generally undergo a reductive alkylation process to
afford tertiary amines 2 (Scheme 1).6 This is in sharp contrast with
the behaviour of the corresponding carboxylic amides under the
same conditions. Indeed, these compounds undergo the
Kulinkovich-de Meijere aminocyclopropanation.3 To explain our
results, a ligand exchange process can be proposed, taking place
from the initially generated titanacyclopropane A to afford the
thiatitanacyclopropane species B. The latter would presumably be
in equilibrium with the metallated iminium zwitterion C. Alkyl-
ation of C by the Grignard reagent employed would then operate
and the observed amine 2 would be obtained after hydrolysis.6
Scheme 1. Titanium-mediated reductive alkylation of thioamides with Grignard
reagents.6
A
particular case was represented by the N-but-3-enyl
substituted thioamide 1a. Indeed, the major product, starting
from this substrate, was the bicyclic aminocyclopropane 3a, either
using cyclopentylmagnesium chloride or cyclohexylmagnesium
chloride as the Grignard reagent (Scheme 2).6
* Corresponding author. Fax: þ33 (0) 1 6933 5972; e-mail addresses: yvan.six@
Scheme 2. Reaction of thioamide 1a.6
polytechnique.edu, six@dcso.polytechnique.fr (Y. Six).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.04.006
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2
F. Hermant et al. / Tetrahedron xxx (2014) 1e7
Interestingly, the cyclopropane 3a is also the ‘normal’ expected3
of the solvent and of the rate of the Grignard reagent addition were
put under scrutiny. The results are presented in Table 2, along with
the outcomes of experiments performed, for comparison purposes,
from the carboxylic amides 4bei.
product starting from the corresponding carboxylic amide 4a,
where the sulfur atom of 1a is replaced with an oxygen atom.7 Since
the production of 3a from 1a is rather peculiar in the light of the
results obtained with the other thioamides studied so far, we de-
cided to investigate the generality and mechanism of this intra-
molecular cyclopropanation of N-alk-3-enyl thioamides. In
addition, we wished to evaluate whether this process could be of
some advantage compared to the reactions of the corresponding
carboxylic amides.
The thioamides 1bei evaluated were all successfully converted
into the corresponding bicyclic aminocyclopropanes 3bei. Rela-
tively little influence of the addition time of the Grignard reagent
was observed, although a slow addition (30e60 min) gave some-
what better results than a typical dropwise addition (2e3 min) in
the syntheses of aminocyclopropanes 3c, 3d and 3g (entries 3, 4
and 7). tBuOMe generally proved to be the best solvent with respect
to the yields and the diastereoselectivities. These were markedly
better than in THF in almost all cases (entries 3e6, 8e9). A similar
observation had been made in an earlier study carried out with
related carboxylic amide substrates, where higher diaster-
eoselectivities were generally obtained in Et2O rather than in THF.10
The case of the synthesis of 3b (entry 2) can be considered as an
exception. Indeed, either starting from 1b or from 4b, the reaction
mixtures appeared heterogeneous in Et2O and in tBuOMe and fairly
large variations in the yields and diastereoselectivities were ob-
served when the experiments were repeated, which suggests
a problem of solubility.
2. Results and discussion
2.1. Syntheses of the substrates
For the purpose of this study, several homoallylamines were
prepared by zinc-mediated Barbier-type imine allylation8 and di-
rectly acylated, without purification, to afford the carboxylic am-
ides 4beh. The amide 4i, bearing the chiral centre on another
substituent of the nitrogen atom, was synthesised following an-
other route.9 The amides 4bei were then converted into the cor-
responding thioamides 1bei using the Lawesson reagent. The
results are summarised in Table 1.
Overall, comparative analysis of the results gathered starting
from the carboxylic amide substrates 4bei indicates that they
produce the desired cyclopropanes 3 more cleanly, often in
higher yields (entries 1, 4, 6, 8 and 9). The diastereoselectivities of
these reactions are also consistently more sharply in favour of the
Table 1
Syntheses of the N-but-3-enylamide and N-but-3-enylthioamide substrates
b
diastereoisomers,11 under otherwise identical conditions (en-
tries 2e4 and 6e8). This stereochemical assignment is supported
by NMR analysis of the isolated products and is unambiguously
illustrated by the crystallographic structure of the major di-
astereoisomer of cyclopropane 3g (Fig. 1).13 Most interestingly,
there are a few instances where the diastereoselectivities of
intramolecular cyclopropanations of thioamides 1 are reversed
compared to the those of the same transformations carried out
from the corresponding amides 4: this is the case for the syn-
Entry
1
Substituents
Amide 4 (yield)
4b (84%)a
Thioamide 1 (yield)
1b (41%)
R1¼Bn
R2¼4-(OMe)C6H4
R3¼Me
t
theses of 3c and 3d in THF (entries 3 and 4), of 3h in BuOMe
(entry 8) and of 3i in THF (entry 9). In the latter case, where
the chiral centre of the substrates is not included in the
chain linking the olefin and the (thio)amide moieties, this dif-
ference is especially significant with a 3 to 1 selectivity obtained
starting from 1i versus an almost non-selective reaction starting
from 4i.
2
3
4
5
6
7
8
R1¼Ph
4c (75%)a
4d (90%)b
4e (n.d.)c
4f (80%)10
4g (53%)a
4h (86%)e
1c (80%)
1d (69%)
1e (41%)d
1f (59%)
1g (58%)
1h (78%)
1i (56%)
R2¼Ph
R3¼Me
R1¼4-(OMe)C6H4
R2¼Ph
R3¼Me
R1¼4-(OMe)C6H4
R2¼Ph
R3¼nPr
2.3. Mechanistic aspects
R1¼4-(OMe)C6H4
R2¼CF3
A straightforward explanation for the formation of the bicyclic
aminocyclopropane products 3 is intramolecular 1,2-insertion of
the alkene group into the putative thiatitanacyclopropane complex
B (Scheme 3, hypothesis a). This would lead to a thiatitanacyclo-
pentane intermediate D. This complex is analogous to the in-
termediate involved in the cyclisation of the carboxylic amides 4,
the only difference being the sulfur atom in place of an oxygen
atom. The next elementary steps can thus be put forward following
this analogy: cleavage of the carbonesulfur bond and cyclopropane
ring-closure according to an SE2(back) mechanism after adoption of
a W-shaped conformation.14
R3¼Me
R1¼4-(Cl)C6H4
R2¼4-(OMe)C6H4
R3¼Me
R1¼4-(Cl)C6H4
R2¼4-(OMe)C6H4
R3¼H
R1¼CH(Me)Ph
R2¼H
4i (prepared by
another route)9
R3¼Me
a
Conditions: Ac2O, pyridine, 20 ꢀC.
b
c
Conditions: Ac2O, DMAP (cat.), pyridine, 20 ꢀC.
Conditions: nPrCOCl, Et3N, CHCl3 20 ꢀC. The yield was not determined because
Another consideration worth taking into account is the close
structural similarity between the metallated iminium species C,
likely to be in equilibrium with B, and the corresponding zincated
iminium E, the proposed key-organometallic intermediate involved
this amide was only partially purified and engaged as such in the next step.
d
Yield for the whole sequence from the imine.
Conditions: HCO2H/Ac2O, HCO2Na, CH2Cl2, 20 ꢀC. The yield given is for the
e
formylation step only.
in the conversion of
a-N-homoallylamino nitriles 5 into bicyclic
2.2. Titanium-mediated cyclisations
aminocyclopropanes 3, as described by the group of Chemla
(Scheme 4).15 In that work, careful mechanistic studies have pro-
vided evidence that a carbenoid insertion pathway and/or a process
involving an aza-Cope rearrangement can operate, depending on
The new thioamide substrates 1bei were submitted to the
titanium-mediated cyclisation procedure. The effects of the nature
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Table 2
Titanium-mediated cyclisations of N-but-3-enylthioamide derivatives 1aei, compared with the reactions of the corresponding amides 4aei. The best results are displayed in bold
Entry
1
Product 3
Substrate
Solvent
Conditionsa
Yieldb
b/a
ratio11
1a
4a
THF
Ac
Ac
Ac
64%6
62%
d
d
d
tBuOMe
THF
75%7
2
3
1b
THF
A
A
A
B
A
A
66%
54%
51%
46% (35%)
29%
88:12
70:30
71:29
65:35
84:16
80:20
Et2O
tBuOMe
4b
1c
Et2O
tBuOMe
54% (49%)
THF
A
A
A
B
C
A
A
A
40%
43%
53%
69% (55%)
70%
68%
60%
51%
48:52
72:28
76:24d
77:23e
77:23
86:14
98:02
98:02
Et2O
tBuOMe
4c
THF
Et2O
tBuOMe
4
1d
4d
THF
A
A
44%
50% (46%)
55%
45:55
84:16
85:15
88:1210
tBuOMe
B
THF
Ac
84% (77%)
5
6
1e
THF
A
A
35%
60% (50%)
46:54
85:15
tBuOMe
1f
4f
THF
A
32%
44% (37%)
>95% (40%)
59:41
tBuOMe
THF
A
73:27
Ac
75:2510
7
8
1g
4g
tBuOMe
tBuOMe
A
B
A
B
60%
77% (68%)
67%
77:23
73:27
96:04
95:05
60%
1h
4h
THF
A
A
B
D
A
<5%
28%
30%
22%
n.d.
tBuOMe
23:77
33:67
41:59
64:36
tBuOMe
42% (37%)
9
1i
4i
THF
A
33%
40% (32%)
(63%)
33:67f
tBuOMe
THF
A
25:75f
Ac
54:4612 f
a
Conditions: A: cyclopentylmagnesium chloride (4.0 equiv) was added within 2e3 min, at 0 ꢀC, to a solution of the substrate 1 or 4 (1.0 equiv) and Ti(OiPr)4 (1.5 equiv) in the
specified solvent; B: same as A, except the Grignard reagent was added during z30 min; C: same as A, except the Grignard reagent was added during z60 min; D: same as B,
except the Grignard reagent was added at ꢁ30 ꢀC.
b
Yield estimated by NMR. Yields in parentheses are those of the isolated products.
c
The addition of the Grignard reagent was performed at 20 ꢀC.
d
Using cC6H11MgCl instead of cC5H9MgCl under otherwise identical conditions, the yield dropped to 30% (dr 73:27).
e
Using 0.5 equiv of Ti(OiPr)4 and 3.0 equiv of cC5H9MgCl, the yield dropped to 17% (dr 70:30).
f
The relative configurations of the chiral centres of the two diastereoisomers were not determined and the b/a naming does not apply in this case.
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4
F. Hermant et al. / Tetrahedron xxx (2014) 1e7
In the documented syntheses of nitrogen-substituted cyclo-
propanes by the reaction of a carbenoid species with an olefin, the
insertion of the carbenoid usually tends to proceed in a concerted
fashion, which results in retention of stereochemistry when di-
substituted alkene substrates are engaged.16 Therefore, we pre-
pared the (E)- and (Z)-N-alkenylthioamides 1j and 1k and
submitted them to the reaction conditions. In both cases, the major
products were the secondary amines resulting from loss of the
thiocarbonyl group and the reductive alkylation products 2j and 2k.
The cyclopropanes 3j and 3k were produced in poor yields but with
exclusive inversion of configuration (Scheme 5). This result dis-
qualifies the carbenoid pathway (hypothesis b). Indeed, even as-
suming that the carbenoid insertion could have proceeded in
a stepwise manner,17 inversion should not have been observed both
from (E) and (Z) alkenes. In contrast, this is consistent with hy-
pothesis a, with the inversion resulting from the SE2(back) process
operating in the final ring-closure.
In order to investigate a possible aza-Cope pathway (hypothesis
c), the substrates 1l and 1m were next evaluated (Scheme 6). The
results show that with increasing spacer length between the thi-
oamide and the alkene functions, the yields decrease rapidly:
56e64%, 7% and 0% from 1a, 1l and 1m, respectively. From com-
pounds 1l and 1m, the structures of the corresponding metallated
iminiums Cl and Cm are not suitable for an aza-Cope rearrange-
Fig. 1. Single-crystal X-ray diffraction structure of the major
Ellipsoids are displayed at the 75% probability level.
b diastereoisomer of 3g.
Scheme 3. Hypotheses for the formation of 3aei from 1aei.
ment to take place and yet, the aminocyclopropane 3l is produced,
notwithstanding the low yield. This rules out the possibility that
pathway c may operate alone and further supports hypothesis a:
intramolecular insertion of an alkene into the titanacycle B is ex-
pected to be the easiest when a five-membered ring is formed, then
a six-membered ring and last, a seven-membered ring.
In conclusion, the mechanism of the intramolecular thioamide
aminocyclopropanations most likely operates via the thiatitana-
cyclopentane intermediate D, according to pathway a displayed in
Scheme 3.18
2.4. Additional results
A few test experiments were conducted with other reagent
systems. Although none of them performed better than Ti(OiPr)4
associated with a Grignard reagent, these investigations revealed
that FeCl3, ZnBr2, CuCN and CuCN$2LiCl can all, combined with
cC5H9MgCl, mediate to some extent the formation of amino-
cyclopropanes 3, however only from the thioamide substrates 1
and not from the corresponding amides 4. In spite of the low yields
attained so far, it is interesting to note that these transformations
proceed with reversed diastereoselectivity, as illustrated by the
example displayed in Scheme 7, to be compared with the results
obtained from the same substrate 1g with the usual reagent system
Scheme 4. Chemla’s zinc-mediated cyclopropanation of
a-N-homoallylamino
nitriles.15
the substitution pattern. The formation of aminocyclopropanes
3aei from the putative titanium-substituted iminium complex C
could hence be envisaged to proceed by analogous pathways
(Scheme 3, hypotheses b and c).
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F. Hermant et al. / Tetrahedron xxx (2014) 1e7
5
Scheme 5. Reactions of (E)- and (Z)-disubstituted alkene substrates 1j and 1k.
Scheme 6. Reactions of extended-chain substrates 1l and 1m.
Scheme 7. Intramolecular cyclopropanation of 1g mediated by CuCN$2LiCl and cC5H9MgCl.
(Table 2, entry 7). This difference suggests that entirely different
mechanisms operate, perhaps involving radical intermediates.
under nitrogen for several months. Cyclopentylmagnesium
chloride was purchased from SigmaeAldrich or Acros and ti-
trated once a month according to a method described earlier.19
Zinc was activated by washing successively with 1 M HCl aque-
ous solution, H2O, EtOH and dried thoroughly. Other commercial
reagents were used as received, without purification. Tetrahy-
drofuran, diethyl ether, dichloromethane and methanol were
3. Conclusions
Our results demonstrate that 2-azabicyclo[3.1.0]hexane de-
rivatives can be accessed from N-(but-3-enyl)thioamide substrates
by an intramolecular titanium-mediated reaction. From a mecha-
nistic viewpoint, all the experiments support a process operating
similarly to the well-known intramolecular Kulinkovich-de Meijere
reaction of N-(but-3-enyl)carboxylic amides. The latter substrates
tend to give superior results to those obtained with their thioamide
counterparts, with a few exceptions. Moreover, it is worthy of note
that the intramolecular aminocyclopropanations of N-(but-3-enyl)
thioamides can be mediated by other reagent systems, such as
CuCN$2LiCl/cC5H9MgCl, so far with inferior yields but, interestingly,
with reversed diastereoselectivity.
purified using
a MB SPS-800 solvent purification system
(MBRAUN). tert-Butyl methyl ether and cyclopentyl methyl ether
were purchased from Acros or Alfa Aesar and used as received.
All the reactions were carried out under a stream of nitrogen or
argon, unless specified otherwise. The temperatures mentioned
are the temperatures of the cold baths used. Concentration under
reduced pressure was carried out using rotary evaporators at
40 ꢀC.
Flash column chromatography was performed on Merck silica
gel 60 (40e63 mm). NMR spectra were recorded with AM 400 and
AVANCE 400 Bruker spectrometers (1H at 400 MHz, 13C at
100.6 MHz). Infrared spectra were recorded with a PerkineElmer
2000 FT-IR spectrometer. Melting points were determined using
4. Experimental
€
4.1. General information
a Buchi 535 apparatus. Low-resolution mass spectra were recorded
on a HewlettePackard Quad GCeMS engine spectrometer via direct
injection. High-resolution mass spectrometry was performed on
a JEOL GC-mate II spectrometer.
Titanium(IV) isopropoxide (VERTECÒ TIPT) was purchased
from Alfa Aesar, distilled under reduced pressure and stored
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6
F. Hermant et al. / Tetrahedron xxx (2014) 1e7
4.2. X-ray crystal structure of compound
b
-3g13
mixture was filtered through a short pad of Na2SO4 and Celite
(rinsing: Et2O). The solution was concentrated under reduced
pressure. The resulting crude product was analysed by NMR spec-
troscopy before purification.
A colourless crystal of
mounted on a loop. Data were collected at 150.0(1) K with a Bruker
b
-3g was coated in ParatoneÒ-N oil and
ꢂ
Kappa APEX II diffractometer using an Mo-K
source and a graphite monochromator. All data were measured
a
(
l
¼0.71070 A) X-ray
Acknowledgements
using 4- and u-scans. The crystal structures were solved using SIR
9720 and refined using SHELXL 2013.21
We wish to warmly thank Natalia Szwankowska, Aleksander
ꢁ ^
Przybyła and Jerome Deffit for preliminary experiments. We are
4.3. Typical procedure for the syntheses of the carboxylic
amide substrates 4: preparation of 4b
also grateful to Michel Levart for the MS analyses of our com-
pounds and to the Ecole Polytechnique for financial support, in
ꢁ
particular for the research grant attributed to F.H. Funding from
the CNRS is also acknowledged. Finally, Y.S. especially wishes to
thank Prof. S.Z. Zard for his continuous encouragement and valu-
able support.
To a solution of p-anisaldehyde (1.00 equiv, 20.0 mmol, 2.43 mL)
in CH2Cl2 (50 mL) was added benzylamine (1.00 equiv, 20.0 mmol,
2.18 mL) and pTSA (1.00% equiv, 200 mmol, 38.0 mg). The mixture
was stirred at 20 ꢀC for 3 h, then filtered through a pad of silica gel
(rinsing: CH2Cl2). The volatile components were removed under
reduced pressure and THF (50 mL) was added. Allyl bromide
(3.00 equiv, 60.0 mmol, 5.20 mL) and zinc powder (3.00 equiv,
60.0 mmol, 3.90 g) were added and the mixture was stirred at 20 ꢀC
overnight. 1 M HCl aqueous solution (0.10 L) was added. The phases
were separated and the aqueous layer was extracted with EtOAc
(3ꢂ40 mL). The combined organic phases were dried over Na2SO4,
filtered and concentrated under reduced pressure to afford crude
N-benzyl-N-[1-(4-methoxyphenyl)but-3-en-1-yl]ammonium
chloride. This salt was dissolved in pyridine (20 mL). Acetic anhy-
dride (2.00 equiv, 40.0 mmol, 3.78 mL) was added and the mixture
was stirred at 20 ꢀC for 24 h, after, which time more acetic anhy-
dride was added (1.00 equiv, 20.0 mmol, 1.89 mL). After three ad-
ditional days of stirring, 1 M NaOH aqueous solution (40 mL) was
added. The phases were separated and the aqueous layer was
extracted with CH2Cl2 (3ꢂ10 mL). The combined organic layers
were washed successively with water (2ꢂ10 mL), 1 M HCl aqueous
solution (10 mL) and water (10 mL), then dried over MgSO4. The
volatile components were removed under reduced pressure and
the residue was purified by flash chromatography on silica gel
(EtOAc/petroleum ether, gradient from 20 to 50%) to afford pure N-
benzyl-N-[1-(4-methoxyphenyl)but-3-en-1-yl]acetamide 4b as
a yellow oil (5.18 g, 16.7 mmol, 84% over three steps).
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.04.006.
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483e485.
8. (a) Basile, T.; Bocoume, A.; Savoia, D.; Umani-Ronchi, A. J. Org. Chem. 1994, 59,
7766e7773; (b) Wang, D.-K.; Dai, L.-X.; Hou, X.-L.; Zhang, Y. Tetrahedron Lett.
1996, 37, 4187e4188.
Lawesson reagent (0.500 equiv) was added at 20 ꢀC to a solu-
tion of the amide substrate 4 (1.00 equiv) in BuOMe (1.0e4.0 mL
t
per mmol of 4). The mixture was stirred at 20 ꢀC. When the re-
action was finished (as indicated by TLC), the mixture was filtered
through a pad of silica gel (rinsing: Et2O) and the volatile com-
ponents were removed under reduced pressure. The crude prod-
uct was purified by flash chromatography on silica gel (EtOAc/
petroleum ether).
9. See Supplementary data for detail.
10. Madelaine, C.; Buzas, A. K.; Kowalska-Six, J. A.; Six, Y.; Crousse, B. Tetrahedron
Lett. 2009, 50, 5367e5371.
11. The diastereoisomer where the C-aryl substituent of the pyrrolidine ring is on
4.5. General procedure for the titanium-mediated intra-
molecular cyclopropanation reactions of the substrates 1 or 4
the same side as the fused cyclopropane ring is named
astereoisomer is named
a. The other di-
b
.
12. Wolan, A.; Soueidan, M.; Chiaroni, A.; Retailleau, P.; Py, S.; Six, Y. Tetrahedron
Lett. 2011, 52, 2501e2504.
To a solution of 1 or 4 (1.00 equiv) in the specified solvent (20 mL
per mmol of substrate) was added Ti(OiPr)4 (1.50 equiv). The re-
action mixture was cooled to 0 ꢀC, then the Grignard reagent
(z2.0 M solution in Et2O, 4.00 equiv) was added dropwise over the
indicated time (using a syringe pump for addition times of 30 min
or more). During the addition, the temperature of the reaction
mixture was maintained at 0 ꢀC. A yellow colour was initially ob-
served that gradually darkened to become black. After 1 h of stir-
ring at room temperature, 25% aqueous NH3 solution (0.50 mL per
mmol of substrate) was added and the flask was exposed to air. The
formation of a white precipitate was observed. After 0.5 h, the
13. CCDC-975129 contains the supplementary crystallographic data for this pub-
lication. Copies of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: þ44-(0)1223-336033 or e-
mail: deposit@ccdc.cam.ac.uk).
14. (a) Ouhamou, N.; Six, Y. Org. Biomol. Chem. 2003, 1, 3007e3009; (b) Casey, C. P.;
Strotman, N. A. J. Am. Chem. Soc. 2004, 126, 1699e1704.
ꢁ
15. (a) Ouizem, S.; Cheramy, S.; Botuha, C.; Chemla, F.; Ferreira, F.; Perez-Luna, A.
Chem. Eur. J. 2010, 16, 12668e12677; (b) Ouizem, S.; Chemla, F.; Ferreira, F.;
ꢁ
Perez-Luna, A. Synlett 2012, 1374e1378.
16. Selected examples: (a) Ogawa, A.; Takami, N.; Sekiguchi, M.; Ryu, I.; Kambe,
ꢁ
N.; Sonoda, N. J. Am. Chem. Soc. 1992, 114, 8729e8730; (b) Begis, G.; Cla-
dingboel, D.; Motherwell, W. B. Chem. Commun. 2003, 2656e2657; (c)
Gharpure, S.; Vijayasree, U.; Reddy, S. R. B. Org. Biomol. Chem. 2012, 10,
1735e1738.
Please cite this article in press as: Hermant, F.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.04.006

F. Hermant et al. / Tetrahedron xxx (2014) 1e7
7
17. Recent example with a diamidocarbene: Moerdyk, J. P.; Bielawski, C. W. Nat.
Chem. 2012, 4, 275e280.
18. The possibility that D could be generated by ligand exchange with the alkene
unit first, followed by insertion of the thiocarbonyl group, cannot be ruled out
and further studies will be carried out in our laboratory to investigate it.
19. Six, Y. Eur. J. Org. Chem. 2003, 1157e1171.
20. Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.; Giacovazzo, C.; Gua-
gliardi, A.; Moliterni, A. G. G.; Polidori, G.; Spagna, R. J. Appl. Cryst. 1999, 32,
115e119.
21. Sheldrick, G. M. Acta Crystallogr. A. 2008, 64, 112e122.
Please cite this article in press as: Hermant, F.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.04.006