Synthesis of allenylzinc reagents by 1,2-rearrangement of alkynyl(disilyl)zincates derived from acetylenic epoxides and acetylenic aziridines

Article abstract of DOI:10.1016/j.crci.2017.02.001

Lithium alkynyl(disilyl)zincates obtained from metalated ethynyloxiranes, as well as from N-tert-butanesulfinyl(ethynyl)aziridines or N-tert-butanesulfonyl(ethynyl)aziridines, undergo 1,2-migration of the organosilyl group with ring opening of the oxirane or aziridine ring by S_Ni displacement. A developed protocol that involves nBuLi for the metalation step offers a straightforward approach to the corresponding δ-oxy- and δ-amino α-silyl allenylzinc intermediates. The reagents derived from the epoxides are amenable to subsequent in situ condensation with aldehydes or ketones to provide 1,3-diols but not those derived from aziridines that only react sluggishly in similar condensations.

Full text of DOI:10.1016/j.crci.2017.02.001

C. R. Chimie xxx (2017) 1e8
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Full paper/M eꢀ moire
Synthesis of allenylzinc reagents by 1,2-rearrangement of
alkynyl(disilyl)zincates derived from acetylenic epoxides and
acetylenic aziridines
**
***
Valentin N. Bochatay, Laurent Debien, Fabrice Chemla , Franck Ferreira
Olivier Jackowski, Alejandro Perez-Luna
,
*
Sorbonne Universit ꢀe s, UPMC Universit ꢀe Paris-6, CNRS UMR 8232, Institut parisien de chimie mol ꢀe culaire, 75005, Paris, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Lithium alkynyl(disilyl)zincates obtained from metalated ethynyloxiranes, as well as from
N-tert-butanesulfinyl(ethynyl)aziridines or N-tert-butanesulfonyl(ethynyl)aziridines, un-
dergo 1,2-migration of the organosilyl group with ring opening of the oxirane or aziridine
Received 4 November 2016
Accepted 2 February 2017
Available online xxxx
ring by S
N
i displacement. A developed protocol that involves nBuLi for the metalation step
-oxy- and -amino -silyl alle-
offers a straightforward approach to the corresponding
d
d
a
Keywords:
Alkynes
nylzinc intermediates. The reagents derived from the epoxides are amenable to subsequent
in situ condensation with aldehydes or ketones to provide 1,3-diols but not those derived
from aziridines that only react sluggishly in similar condensations.
Carbenoids
Rearrangement
Silicon
©
2017 Académie des sciences. Published by Elsevier Masson SAS. This is an open access
article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/
Zinc
).
1
. Introduction
the propargylic form) or alkynes (from the allenic form).
Lack of regioselectivity is thus a common drawback for
such condensations [2].
Allenylmetal reagents [1], including allenylzincs [2], are
versatile organometallic species that have been used
intensively in organic synthesis. For more than a decade,
work from our laboratories [3] and others [1,2] have
A key feature of
is that the organosilyl group geminal to the carbonezinc
bond stabilizes the allenic form ( -silicon effect) and
a-silylesubstituted allenylzinc reagents
a
demonstrated that
a
-silylesubstituted allenylzincs are a
thereby shifts the propargyl/allenyl metallotropic equilib-
rium toward the latter form (Scheme 1) [4]. Hence,
condensation with carbonyl derivatives occurs with exqui-
site regioselectivity and affords exclusively the propargylic
adducts [3,5]. Furthermore, in cases where two stereogenic
centers are created during the condensation event, excel-
lent levels of diastereocontrol are usually observed. In
addition, their high functional-group tolerance and the fact
that they lead to silylated alkynes that can be easily pro-
todesilylated to unmask a terminal alkyne that then serves
as handle for further synthetic elaboration are also impor-
tant qualities of these propargylating reagents [6].
particularly useful substrate class of this family. Typically,
allenylzinc reagents exist in a solution as mixture of two
rapidly interconverting metallotropic forms: the prop-
argylic and the allenic one. When opposed to carbonyl
derivatives (i.e., aldehydes, ketones, or imines), each form
has the potential to undergo electrophilic substitution
0
through an S
E
2 mechanism providing either allenes (from
*
Corresponding author.
*
*
* Corresponding author.
** Corresponding author.
a-Substituted allenylmetals can be conveniently
E-mail addresses: fabrice.chemla@upmc.fr (F. Chemla), franck.
ferreira@upmc.fr (F. Ferreira), alejandro.perez_luna@upmc.fr (A. Perez-
Luna).
accessed by the 1,2-metalate rearrangement of alkynylo-
gous carbenoids. Commonly, migration of alkyl groups is
http://dx.doi.org/10.1016/j.crci.2017.02.001
1631-0748/© 2017 Académie des sciences. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: V.N. Bochatay, et al., Synthesis of allenylzinc reagents by 1,2-rearrangement of alkynyl(disilyl)
zincates derived from acetylenic epoxides and acetylenic aziridines, Comptes Rendus Chimie (2017), http://dx.doi.org/10.1016/
j.crci.2017.02.001

2
V.N. Bochatay et al. / C. R. Chimie xxx (2017) 1e8
previous work on acetylenic epoxides [10e] and recent re-
sults on the ring-opening of N-tert-butanesulfinylaziridines
and N-tert-butanesulfonylaziridines.
2. 1,2-Rearrangement of alkynyl(disilyl)zincates
derived from acetylenic epoxides
Our first foray in this field was the result of our studies
on the rearrangement of lithiated ethynylepoxides by re-
action with dialkylzinc reagents [10e]. As part of this work,
it was found that lithiated acetylenic epoxides also under-
ꢁ
went transmetalation with (Me
2
PhSi)
2
Zn at ꢀ60 C to
Scheme 1. Condensation of aldehydes with a-silylesubstituted propargyl/
allenyzinc reagents.
afford lithium alkynyl(disilyl)zincates 2 (Scheme 3). 1,2-
Silyl migration inducing opening of the oxirane ring
ꢁ
occurred on warming the reaction mixture to ꢀ20 C and
involved and
tained [7e10]. However, the approach is also suitable to
access -silyl allenylmetals, but this prospect has remained
so far virtually unexplored [10b,11]. In seminal studies,
Harada et al. demonstrated that zincate complexes II, ob-
tained from bromopropargyl mesylates I by halogenemetal
a-alkylesubstituted allenylmetals are ob-
afforded the corresponding
a-silyl allenylzinc in-
termediates. After acidic aqueous workup, a mixture of
homopropargylic (3) and allenic (3′) alcohols was obtained.
The 3/3′ ratio was found to be highly dependent on the
quench conditions and difficult to control. Ultimately, it
was possible to find conditions to prepare regioselectively
a
2 3
exchange with (Me PhSi) ZnLi, provided a-silyl allenylzinc
intermediates III after 1,2-migration of the organosilyl
ꢁ
homopropargylic alcohols 3 using MeOH (0 C) to quench
the reaction mixture after rearrangement. This optimized
protocol was suitable for di- and tri-substituted acetylenic
epoxides having either alkyl or aryl substituents and the
corresponding alcohols 3 were obtained in 64e86% yield
with good to excellent regioselectivity (3/3′ > 84:16).
The possibility to use this chemistry to access 1,3-diols
was also demonstrated. Condensation of propionaldehyde
group with displacement of the propargylic leaving group
through an S i mechanism (Scheme 2, top) [10b,12].
N
Inspired by these results and as part of our longstanding
interest in ring-opening reactions of acetylenic epoxides
[13] and aziridines [14], we reasoned that implementation
of a similar approach with lithium alkynyl(disilyl)zincates
V derived from those substrates and disilylzinc reagents
would lead to d-heteroatom substituted a-silyl allenylzinc
intermediates VI that could offer an expeditious stereo-
selective access to valuable 1,3-diols (VII, X ¼ O) or 1,3-
aminoalcohols (VII, X ¼ NR) on condensation with alde-
hydes (Scheme 2, bottom). In this article, we describe our
research endeavors in this area combining an overview of
with the
a
-silyl allenylzinc intermediate 2a′ (obtained from
ꢁ
epoxide 1a) was achieved at ꢀ40 C and led to diol 4 [15] in
a remarkable 78% yield with excellent regio- and stereo-
selectivity (Scheme 4). Trapping with acetone was less
efficient and tertiary alcohol 5 was obtained in a lower 42%
yield, still with excellent stereoselectivity. Interestingly, in
the latter case, the presence of allenic regioisomers was
also detected to some extent.
3. 1,2-Rearrangement of alkynyl(disilyl)zincates
derived from acetylenic aziridines
Following on these results, we considered the rear-
rangement of acetylenic aziridines and focused on N-tert-
Scheme 2. Formation of
a-silylesubstituted propargyl/allenyzinc reagents
by 1,2-metalate rearrangement of alkynylogous carbenoids.
Scheme 3. Rearrangement of lithium alkynyl(disilyl)zincates.
Please cite this article in press as: V.N. Bochatay, et al., Synthesis of allenylzinc reagents by 1,2-rearrangement of alkynyl(disilyl)
zincates derived from acetylenic epoxides and acetylenic aziridines, Comptes Rendus Chimie (2017), http://dx.doi.org/10.1016/
j.crci.2017.02.001

V.N. Bochatay et al. / C. R. Chimie xxx (2017) 1e8
3
with meta-Chloroperoxybenzoic acid (m-CPBA) afforded
the corresponding N-tert-butanesulfonylethynylaziridines
7aec in excellent yields.
First, the lithiation step was examined (Table 1). To this
end, substrate 6a (representative of N-tert-butanesulfiny-
ꢁ
lethynylaziridines) was treated with nBuLi in THF at ꢀ80 C
for 15 min and the reaction mixture was then quenched
with MeOD. After workup, [ H]-6a was obtained in low 25%
2a
2
yield along with 71% of unreacted 6a (entry 1). To drive the
metalation to completion, the reaction time was then
2
increased to 1 h: [ H]-6a was obtained in 57% yield along
with 7% of 6a (entry 2). Hence, although the deuteration
grade was significantly improved (89%), the overall lith-
iation yield remained modest because around 30% of the
starting material had been consumed unproductively to
yield unidentified material. Sulfoxide 8 was also isolated
from this reaction in 5% yield, suggesting that substitution
at the sulfur atom of the tert-butanesulfinyl moiety was at
the origin of the starting material degradation. To minimize
this possible side reaction, changing nBuLi for other alkyl-
lithium reagents was considered. When tBuLi was used
Scheme 4. Preparation of 1,3-diols 4 and 5.
butanesulfinylethynylaziridines (6) and N-tert-butane-
sulfonylethynylaziridines (7) (Scheme 5). Model substrates
aec were prepared as pure stereoisomers in two steps
(entry 3), sulfoxide 9 was isolated in a higher 16% yield and
6
some starting material was lost. In contrast, degradation
did not occur using MeLi or PhLi (entries 4 and 5). Yet,
complete metalation was not achieved (65e68% deutera-
tion grades) even after prolonged reaction times (3 h).
Following these failures, we contemplated deprotona-
from N-tert-butanesulfinylimines, according to a procedure
previously reported by our group [14,16]. Oxidation of 6aec
ꢁ
tion of 6a with LDA. On reaction at ꢀ80 C for 1 h, only
partial metalation was obtained, but without any signifi-
cant starting material degradation (entry 6). Finally, add-
ing HMPA (2.0 equiv) as additive and performing the
ꢁ
reaction at ꢀ30 C allowed for convenient lithiation of 6a
2
as [ H]-6a was obtained in 81% yield (entry 7). An addi-
tional solution for the metalation of 6a came out of
Scheme 5. Preparation of N-tert-butanesulfonyl(ethynyl)aziridines 7aec.
Table 1
Deprotonation studies of 6a.
Entry
Base
Conditions
[2H]-6a (%)a
6aa (%)
tBuS(O)Ra (%)
1
2
3
4
5
6
7
8
nBuLi
nBuLi
tBuLi
MeLi
PhLi
ꢀ80 ꢁC, 15 min
25
57
52
62
63
47
81
89
71
7
8: eb
8: 5
9: 16
10: eb
11: 7
e
ꢁ
ꢀ80 C, 1 h
ꢁ
ꢀ80 C, 1 h
11
34
30
39
9
ꢁ
ꢀ80 C, 3 h
ꢁ
ꢀ80 C, 3 h
ꢁ
LDA
ꢀ80 C, 1 h
c
ꢁ
LDA
HMPA , ꢀ30 C, 2 h
e
8: eb
ZnLid
0
ꢁ
C, 2 h
11
nBu
3
LDA, Lithium diisopropylamide; HMPA, Hexamethylphosphoramide.
a
b
c
1
Yield determined by H NMR spectroscopy using biphenyl as an internal standard.
Product not detected.
2.0 equiv.
d
2.2 equiv.
Please cite this article in press as: V.N. Bochatay, et al., Synthesis of allenylzinc reagents by 1,2-rearrangement of alkynyl(disilyl)
zincates derived from acetylenic epoxides and acetylenic aziridines, Comptes Rendus Chimie (2017), http://dx.doi.org/10.1016/
j.crci.2017.02.001

4
V.N. Bochatay et al. / C. R. Chimie xxx (2017) 1e8
serendipity. Although studying the ring-opening of ethy-
3
obtained using nBu ZnLi for the metalation step (entry 3).
nylaziridines with triorganozincates [17], we found that
In this case, a mixture of 12a and 12a′ in a 12a/12a′ ¼
66:34 ratio was isolated in 63% yield. Quite unexpectedly,
given the apparent moderate efficiency of the lithiation
step (see above), similar yields (60e65%) in rearranged
products were obtained when nBuLi was used as base
(entries 4e6). Here, mixtures of 12a/12a′ were isolated in
regio- and stereoselectivities that were difficult to control
and varied with the workup conditions [19]. Importantly,
these substantial disparities provided good evidence for
2
[
2
H]-6a could be obtained in 89% yield by treatment with
ꢁ
.2 equiv nBu
3
ZnLi at 0 C for 2 h followed by quenching
with MeOD (entry 8) [18].
Unlike for N-tert-butanesulfinylethynylaziridine 6a,
lithiation of 7a (representative of N-tert-butanesulfonyla-
ziridines) was not problematic and occurred readily at
ꢁ
ꢀ
80 C on treatment with nBuLi (1.1 equiv). This was
2
confirmed by the isolation of [ H]-7a in 89% yield after
addition of MeOD to the reaction mixture and aqueous
workup (Scheme 6).
the intermediate formation of a
nylzinc intermediate VI and, in-line with the behavior of
the related -oxy -silyl allenylzinc reagents obtained
d-amino a-silyl alle-
With suitable metalation procedures in hand for 6 and 7,
the 1,2-metalate rearrangement of the corresponding
alkynyl(disilyl)zincates (V) arising from reaction with
d
a
from ethynylepoxides, are likely the result of the diffi-
culty to control the selectivity of the protodemetalation
reaction.
(
2 2
Me PhSi) Zn was investigated. N-tert-butanesulfinylethy-
nylaziridines 6 were considered first (Table 2).
Trace amounts of rearrangement products were ob-
tained with the initial set of conditions involving LDA as
The 1,2-metalate rearrangement also occurred effi-
ciently in the case of ethynylaziridine 6b having a secondary
alkyl substituent (entry 7). Interestingly, with the protocol
relying on nBuLi for the metalation step, the exclusive for-
ꢁ
base, addition of 1.1 equiv (Me
2
PhSi)
2
Zn at ꢀ60 C, and
ꢁ
warming the reaction mixture to ꢀ30 C (Table 2, entry
mation of d-amino allenylsilane 12b′ (97:3 dr) was obtained
ꢁ
1
). After addition of MeOH (at ꢀ30 C) and work up,
in 75% yield. On the contrary, ring-opening by 1,2-metalate
rearrangement did not occur for the alkynyl(disilyl)zincate
derived from cis-configured ethynylaziridine 6c and the
starting material was recovered (entry 8) [20].
N-tert-Butanesulfonylethynylaziridines 7 were consid-
ered next (Table 3). The rearrangement of the alkynyl(di-
around 80% of the starting aziridine 6a was recovered. To
our delight, when a larger amount of (Me PhSi) Zn was
introduced (2.2 equiv), complete ring opening of 6a was
observed and -amino allenylsilane 12a′ was isolated in
7% yield as a 68:32 mixture of diastereomers (entry 2).
2
2
d
5
ꢁ
1,2-Rearrangement also occurred at 0 C with the zincate
silyl)zincate derived from lithiated 7a and (Me
2
PhSi)
2
Zn
ꢁ
(
1.5 equiv) occurred fully at ꢀ30 C and a mixture of
products 13a and 13a′ (13a/13a′ ¼ 78:22) was isolated after
methanolysis and workup in 54% yield (entry 1). Perform-
ꢁ
ing the rearrangement at 0 C led to a better 70% yield
(entry 2).
In the case of substrate 7b having a secondary alkyl
substituent, the yield in rearranged products 13b and
13b′ was already good when the rearrangement was
Scheme 6. Deprotonation of 7a.
Table 2
Rearrangement of N-tert-butanesulfinylethynylaziridines 6.
Entry
6
Base
(Me
2
PhSi)
2
Zn [equiv], T
Product
12/12′a
12′(dr)a
Yieldb (%)
1
2
3
4
5
6
6a
6a
6a
6a
6a
6a
6b
6c
LDA/HMPA
LDA/HMPA
1.1, ꢀ30 ꢁ
C
C
12a/12a′
12a/12a′
12a/12a′
12a/12a′
12a/12a′
12a/12a′
12b/12b′
12c/12c′
ncc
ncc
<5
57
63
60
64
65
75
ꢁ
2.2, ꢀ30
<2:98
66:34
84:16
<2:98
90:10
<2:98
e
68:32
91:9
33:67
77:23
54:46
97:3
e
d
ꢁ
(nBu)
3
ZnLi
2.2, 0
1.5, 0
1.5, 0
1.5, 0
1.5, 0
1.5, 0
C
C
C
C
C
C
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
nBuLi
nBuLi
nBuLi
nBuLi
nBuLi
e
f
7
8
g
e
a
Measured by 1H NMR spectroscopy before purification.
Combined isolated yield of 12 and 12′.
Not calculated.
b
c
d
e
f
2
.2 equiv.
ꢁ
Quenched at ꢀ20 C.
ꢁ
Quenched with 1 M HCl at ꢀ30 C.
g
The starting material was recovered.
Please cite this article in press as: V.N. Bochatay, et al., Synthesis of allenylzinc reagents by 1,2-rearrangement of alkynyl(disilyl)
zincates derived from acetylenic epoxides and acetylenic aziridines, Comptes Rendus Chimie (2017), http://dx.doi.org/10.1016/
j.crci.2017.02.001

V.N. Bochatay et al. / C. R. Chimie xxx (2017) 1e8
5
Table 3
Rearrangement of N-tert-butanesulfonylethynylaziridines 7.
Entry
7
T
Product
13/13'a
13′(dr)a
Yieldb (%)
ꢁ
ꢁ
1
2
3
7a
7a
7b
7c
ꢀ30
C
13a/13a′
13a/13a′
13b/13b′
13a/13a′
78:22
93:7
98:2
90:10
nc
nc
54
70
70
80
ꢁ
0
C
c
ꢀ30
C
C
4
ꢀ30 ꢁ
87:13
74:16
a
Measured by 1H NMR spectroscopy before purification.
Combined isolated yield of 13 and 13′.
b
c
Quench was performed at ꢀ80 ꢁC.
ꢁ
carried out at ꢀ30 C (entry 3). Here, in sharp contrast
4. Conclusion
with N-tert-butanesulfinyl substrates, no significant
reactivity difference was noted between trans and cis
configured ethynylaziridines. Thus, starting from cis-
configured 7c, the ring-opening products 13a and 13a′
were isolated in 80% combined yield after rearrangement
To sum up, lithium alkynyl(disilyl)zincates derived from
ethynylepoxides and ethynylaziridines undergo 1,2-
migration of the organosilyl group with ring opening of the
oxirane or aziridine ring by S i displacement. This protocol,
N
initially developed for the rearrangement of ethynylep-
oxides, was successfully extended to aziridines and thus of-
ꢁ
at ꢀ30 C and treatment with MeOH (entry 4). Again,
evidencing the formation of d-amino a-silyl allenylzinc
intermediates (VI), the regio- and stereoselectivity of the
process was, for all the substrates, somewhat erratic and
dependent on the workup conditions. Nevertheless,
quenching the reactions with MeOH before aqueous
workup favored in general the formation of homo-
propargylamines 13, as indicated in Table 3.
fers a straightforward approach to both
d
-oxy- and
-silyl allenylzinc
d-amino
a
-silyl allenylzinc intermediates. -Oxy a
d
intermediates could undergo condensation with aldehydes
or ketones to provide 1,3-diols in good yields and stereo-
selectivities. In contrast, the d-amino a-silyl allenylzinc in-
termediates only reacted sluggishly. Understanding the
reasons for this lack of reactivity and finding suitable con-
ditions allowing for the preparation of 1,3-aminoalcohols
with satisfactory yields using this chemistry are currently
our research objectives in this promising field.
Finally, the reactivity against aldehydes of the
d-
amino -silyl allenylzinc intermediates (VI) obtained
a
from ethynylaziridines was investigated. Despite exten-
sive experimentation, condensation was not observed to
significant extents (<10e15%) between the allenylzinc
species obtained from N-sulfinylated ethynylaziridines
6
a or 6b and neither propionaldehyde nor acetone. The
5. Experimental section
allenylzinc intermediates arising from N-sulfonylated
ethynylaziridines 7a or 7b were slightly more prone to
react but still satisfactory results were not achieved. The
most promising reaction was that of 7b that afforded
5.1. General methods
Experiments involving organometallic compounds were
carried out in dried glassware under a positive pressure of
dry argon or nitrogen using Schlenk techniques. THF was
dried over Na/benzophenone and distilled before use.
Commercial nBuLi (SigmaeAldrich or Acros) was titrated
1
,3-aminodiol 14 as a single stereoisomer in 30% yield
21], by sequential ring opening by 1,2-metalate rear-
rangement and condensation with benzaldehyde
Scheme 7).
[
(
2
with Sufferts's reagent [22]. Commercial ZnBr was melted
under nitrogen and immediately after cooling to room
temperature dissolved in dry THF. Chloro(dimethyl)phe-
nylsilane (SigmaeAldrich) and all other reagents were of
commercial quality and were used without purification.
Flash column chromatography was performed using the
indicated solvents on silica gel 60 (15e40 or 40e63
mm
1
13
particle size) by Merck. H NMR and C NMR spectra were
recorded with a Bruker AV 400. Chemical shifts are reported
inparts per million (ppm) downfield fromtetramethylsilane
and are referenced to the residual solvent resonance as the
1
internal standard (CHCl
3
:
d
¼ 7.26 ppm for H NMR and
1
3
Scheme 7. Preparation of 1,3-aminoalcohol 14.
CDCl
3
:
d
¼ 77.16 ppm for C NMR). Data are reported as
Please cite this article in press as: V.N. Bochatay, et al., Synthesis of allenylzinc reagents by 1,2-rearrangement of alkynyl(disilyl)
zincates derived from acetylenic epoxides and acetylenic aziridines, Comptes Rendus Chimie (2017), http://dx.doi.org/10.1016/
j.crci.2017.02.001

6
V.N. Bochatay et al. / C. R. Chimie xxx (2017) 1e8
follows: chemical shift, multiplicity (br s ¼ broad singlet,
s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet, and
m ¼ multiplet), coupling constant, and integration. Infrared
1H), 1.94e1.85 (m, 1H), 1.47 (s, 9H), 1.11 (d, J ¼ 6.8 Hz, 3H),
13
0.96 (d, J ¼ 6.8 Hz, 3H). C NMR (100 MHz, CDCl
3
):
d
¼ 77.9,
73.6, 60.5, 53.8, 32.8, 28.7, 24.2 (3C), 20.2, 19.0. IR (neat):
ꢀ
1
(
IR) spectra were recorded on a Bruker Tensor 27 ATR dia-
3245, 2977, 2929, 2361, 1303, 1131, 886, 703, 670 cm
.
þ
mond spectrophotometer equipped with an ATR unit. High-
resolution mass spectra (HRMS) were obtained using a
Bruker micrOTOF instrument equipped with ESI source.
Product characterization data forcompounds 5 [10e]and 12′
aec [14,19b] have been previously reported.
HRMS (ESI): m/z [M þ Na] calcd for
11 2
C H19NNaO S,
252.1029; found, 252.1035.
5.2.3. Preparation of product 7c
The typical procedure was followed with 6c (516 mg,
.42 mmol). Purification by flash column chromatography
2
5
.1.1. Preparation of PhMe
Under argon, Li (557 mg, 80.0 mmol) was washed with
dry THF (3 ꢂ 5 mL). TMSCl (5.1 mL, 40.0 mmol) and THF
20 mL) were added. After 15 min of sonication, Li was
2
SiLi (~0.40 M in THF)
on silica gel (cyclohexane/AcOEt) afforded analytical pure
7c (500 mg, 90%) as a pale yellow oil. H NMR (400 MHz,
1
CDCl
3
):
d
¼ 3.19 (dd, J ¼ 6.8, 1.9 Hz, 1H), 2.86e2.76 (m, 1H),
(
2.24 (d, J ¼ 1.9 Hz, 1H), 1.69e1.59 (m, 2H), 1.57e1.48 (m,
13
washed with dry THF (4 ꢂ 5 mL) and then taken up in dry
2H), 1.48 (s, 9H), 0.98 (t, J ¼ 7.3 Hz, 3H). C NMR (100 MHz,
THF (40 mL). After an additional 5 min of sonication,
CDCl
13.8.
3
):
d
¼ 72.7, 72.6, 59.6, 41.6, 35.0, 30.5, 24.1 (3C), 19.9,
PhMe
2
SiCl (3.3 mL, 20.0 mmol) was added and the result-
ꢁ
ing mixture was sonicated for 2 h at 0 C to give a dark red
THF solution of PhMe
exchange was assumed to be effective at 80% [23]. The
solution was stored at ꢀ18 C and used within 2 weeks.
2
SiLi (~0.40 M). The halogenelithium
5.3. Typical procedure for the rearrangement of
ethynylepoxides and ethynylaziridines (preparation of 13a
(Table 3, entry 2))
ꢁ
5
.1.2. Preparation of (PhMe
To a stirred THF solution of PhMe
.50 mmol) was added dropwise a THF solution of ZnBr
2
Si)
2
Zn (~0.16 M in THF)
nBuLi (2.40 M in hexanes, 0.23 mL, 0.55 mmol) was
ꢁ
2
SiLi (~0.40 M, 3.75 mL,
added dropwise at ꢀ80 C to a THF (5 mL) solution of
1
2
ethynylaziridine 7a (115 mg, 0.50 mmol). The mixture
ꢁ
(
1.0 M, 0.75 mL, 0.75 mmol) at ꢀ20 C giving a dark green
was stirred for 1 h at this temperature, then warmed to
ꢁ
solution within 10 min.
ꢀ60 C, and added via cannula to a THF solution of
ꢁ
(
PhMe
2
Si)
2
Zn (0.16 M, 4.7 mL, 0.75 mmol) at ꢀ60 C. The
ꢁ
5
5
.2. Preparation of N-tert-butanesulfonylaziridines 7aec
reaction mixture was then warmed to 0 C and stirred for
2
h. MeOH (1 mL) was added and the mixture was left to
warm to room temperature. Et O (10 mL) was then added
and the layers were separated. The aqueous layer was
extracted with Et
O (ꢂ2), and the combined organics
4
were washed with water and brine, dried over MgSO ,
.2.1. Typical procedure for the oxidation of N-tert-
2
butanesulfinylaziridines (preparation of 7a)
To a stirred CH Cl (40 mL) solution of N-tert-butane-
sulfinylaziridine 6a (1.54 g, 7.22 mmol) at room tempera-
ture was added m-CPBA (ꢃ77% assay, 1.96 g, 7.94 mmol).
The mixture was stirred for 10 min and an aqueous satu-
2
2
2
and concentrated under reduced pressure. Purification by
flash column chromatography on silica gel (cyclohexane/
AcOEt ¼ 90:10) afforded analytical pure 13a (127 mg, 70%)
2 2 3
rated solution of Na S O (40 mL) was added. After 30 min
of stirring, the layers were separated and the aqueous layer
was extracted with AcOEt (ꢂ2). The combined organics
were washed with an aqueous saturated solution of
NaHCO
MgSO , and concentrated under reduced pressure. Purifi-
cation by flash column chromatography on silica gel
as a yellow oil.
1
H NMR (400 MHz, CDCl
3
):
d
¼ 7.62e7.60 (m, 2H), 7.44
e7.38 (m, 3H), 4.01 (d, J ¼ 9.9 Hz, 1H, NH), 3.55e3.43 (m,
1H), 2.68 (AB system, J ¼ 17.1, 5.7 Hz, 1H), 2.56 (AB system,
J ¼ 17.1, 4.4 Hz, 1H), 1.76e1.65 (m, 2H), 1.46e1.34 (m, 2H),
3
(ꢂ3), water (ꢂ2), and brine, dried over anhydrous
4
13
1.40 (s, 9H), 0.99 (t, J ¼ 7.5 Hz, 3H), 0.41 (s, 6H). C NMR
(
(
cyclohexane/AcOEt ¼ 90:10) afforded analytically pure 7a
(100 MHz, CDCl
3
):
d
¼ 137.2, 133.7 (2C), 129.5, 128.0 (2C),
1
1.32 g, 80%) as a pale yellow solid. H NMR (400 MHz,
104.2, 86.3, 60.0, 54.7, 28.4, 26.9, 24.4 (3C), 10.6, ꢀ0.67,
þ
CDCl
4
3
):
d
¼ 3.00 (dd, J ¼ 4.3, 2.0 Hz, 1H), 2.87 (dt, J ¼ 8.2,
ꢀ0.69 (one C missing). HRMS (ESI): m/z [M þ Na] calcd for
.3 Hz, 1H), 2.33 (d, J ¼ 2.0 Hz, 1H), 2.07e1.97 (m, 1H), 1.70
19 2
C H31NNaO SSi, 388.1737; found, 388.1728.
13
e1.59 (m, 3H), 1.48 (s, 9H), 0.99 (t, J ¼ 7.1 Hz, 3H). C NMR
(
100 MHz, CDCl
3
):
d
¼ 78.3, 72.8, 60.6, 49.1, 34.8, 31.4, 24.1
5.3.1. Preparation of product 12a (Table 2, entry 6)
(
3C), 20.4, 13.8. IR (neat): 3244, 2967, 2935, 2875, 2361,
The typical procedure was followed with 6a (107 mg,
0.50 mmol) but using an aqueous solution of HCl (1.0 M) for
hydrolysis instead of MeOH. Purification by flash column
chromatography on silica gel (cyclohexane/AcOEt ¼ 90:10)
ꢀ1
1301, 1123, 1018, 881, 729, 669 cm . HRMS (ESI): m/z
þ
[
2
M þ Na] calcd for
11 2
C H19NNaO S, 252.1029; found,
52.1020.
afforded 12a contaminated with 12a′ (114 mg, 12a/12a′ ¼
1
5
.2.2. Preparation of product 7b
The typical procedure was followed with 6b (320 mg,
.50 mmol). Purification by flash column chromatography
90:10, 65%). Data for 12a: H NMR (400 MHz, CDCl
3
):
d
¼ 7.64e7.58 (m, 2H), 7.40e7.30 (m, 3H), 3.57 (d, J ¼ 8.1 Hz,
1
1H, NH), 3.39 (m, 1H), 2.72 (ABX system, J ¼ 16.9, 5.8,
0.7 Hz, 1H), 2.56 (ABX system, J ¼ 16.9, 4.7, 0.7 Hz, 1H), 1.65
on silica gel (cyclohexane/AcOEt ¼ 70:30) afforded analyt-
ical pure 7b (340 mg, 99%) as a pale yellow amorphous
e1.51 (m, 2H), 1.48e1.30 (m, 2H), 1.19 (s, 9H), 0.92 (t,
solid. 1H NMR (400 MHz, CDCl
):
d
¼ 2.99 (dd, J ¼ 4.3,
J ¼ 7.4 Hz, 3H), 0.40 (s, 6H). C NMR (100 MHz, CDCl
13
3
3
):
2
.0 Hz, 1H), 2.79 (dd, J ¼ 7.1, 4.3 Hz, 1H), 2.36 (d, J ¼ 2.0 Hz,
d
¼ 137.3, 133.7 (2C), 129.5, 128.0 (2C), 104.8, 86.3, 56.0,
Please cite this article in press as: V.N. Bochatay, et al., Synthesis of allenylzinc reagents by 1,2-rearrangement of alkynyl(disilyl)
zincates derived from acetylenic epoxides and acetylenic aziridines, Comptes Rendus Chimie (2017), http://dx.doi.org/10.1016/
j.crci.2017.02.001

V.N. Bochatay et al. / C. R. Chimie xxx (2017) 1e8
7
5
3
8
4.5, 37.2, 28.2, 22.8 (3C), 19.1, 14.0, ꢀ0.61, ꢀ0.65. IR (neat):
3.14 (d, J ¼ 5.5 Hz, 1H, OH), 2.94 (dd, J ¼ 7.4, 4.2 Hz, 1H), 2.28
209, 3069, 2957, 2870, 2173, 1939, 1457, 1248, 114, 1051,
(septd, J ¼ 6.9, 2.9 Hz, 1H), 1.33 (s, 9H), 0.97 (d, J ¼ 6.9 Hz,
ꢀ
1
13
35, 814, 779, 730, 698 cm
.
3H), 0.94 (d, J ¼ 6.9 Hz, 3H), 0.28 (s, 3H), 0.27 (s, 3H).
C
NMR (100 MHz, CDCl
3
):
d
¼ 141.5, 136.9, 133.7 (2C), 129.5,
5
.3.2. Preparation of product 13b (Table 3, entry 3)
128.3 (2C), 128.0 (2C), 127.8, 126.5 (2C), 105.1, 90.0, 71.8,
60.7, 59.5, 48.1, 31.0, 24.6 (3C), 21.6, 17.2, ꢀ0.8, ꢀ0.9. IR
(neat): 3490, 3278, 3060, 2964, 2170, 1427, 1297, 1115, 1018,
The typical procedure was followed with 7b (115 mg,
ꢁ
0
.50 mmol) but methanolysis was carried out at ꢀ80 C.
ꢀ1
þ
Purification by flash column chromatography on silica gel
907, 819, 727 cm . HRMS (ESI) m/z [M þ Na] calcd for
(
(
cyclohexane/AcOEt ¼ 90:10) afforded analytical pure 13b
C
26
H
37NNaO SSi, 494.2156; found, 494.2166.
3
1
127 mg, 70%) as a pale yellow oil. H NMR (400 MHz,
CDCl
J ¼ 10.0 Hz,1H, NH), 3.36 (dddd, J ¼ 10.1, 6.5, 5.7, 4.6 Hz,1H),
.68 (AB system, J ¼ 17.3, 5.7 Hz, 1H), 2.60 (AB system,
3
):
d
¼ 7.62e7.60 (m, 2H), 7.39e7.35 (m, 3H), 3.92 (d,
Acknowledgments
2
The authors wish to thank the MESR for a grant to V.N.B.
and Omar Khaled from Institut Parisien de Chimie
Mol eꢀ culaire (IPCM) for HRMS analysis.
J ¼ 17.3, 4.7 Hz, 1H), 2.05 (dq, J ¼ 13.5, 6.8 Hz, 1H), 1.40 (s,
9
6
H), 1.02 (d, J ¼ 6.8 Hz, 3H), 1.00 (d, J ¼ 6.8 Hz, 3H), 0.40 (s,
13
H). C NMR (100 MHz, CDCl
3
):
d
¼ 137.2, 133.7 (2C), 129.5,
128.0 (2C), 104.6, 86.3, 60.2, 58.4, 32.2, 24.9, 24.5 (3C), 19.1
Appendix A. Supplementary data
(
1
C
2C), ꢀ0.7 (2C). IR (neat): 3275, 2959, 2360, 2341, 1939,
ꢀ
1
þ
305, 1122, 814 cm . HRMS (ESI): m/z [M þ Na] calcd for
Supplementary data related to this article can be found
at http://dx.doi.org/10.1016/j.crci.2017.02.001.
19 2
H31NNaO SSi, 388.1737; found, 388.1722.
5
.4. Typical procedure for sequential rearrangemente
References
condensation with aldehydes (preparation of 4)
[
1] For selected recent reviews on the use of allenylmetals in synthesis:
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2] J.A. Marshall, Synthesis and reactions of allenylzinc reagents, in:
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nozinc Compounds (2007), John Wiley & Sons, Ltd, Chichester, 2009.
nBuLi (2.40 M in hexanes, 0.23 mL, 0.55 mmol) was
(
ꢁ
added dropwise at ꢀ80 C to a THF (5 mL) solution of
(
ethynylepoxide 1a (69 mg, 0.50 mmol). The mixture was
[
ꢁ
stirred for 1 h at this temperature, then warmed to ꢀ60 C
and added via cannula to a THF solution of (PhMe
2
Si)
2
Zn
ꢁ
[3] (a) C. Botuha, F. Chemla, F. Ferreira, A. P eꢀ rez-Luna, B. Roy, New J.
(
0.16 M, 4.7 mL, 0.75 mmol) at ꢀ60 C. The reaction mixture
Chem. 31 (2007) 1552;
ꢁ
ꢁ
was warmed to ꢀ20 C for 1.5 h and then to 0 C for 45 min
(
b) C. Botuha, F. Chemla, F. Ferreira, J. Louvel, A. P eꢀ rez-Luna, Tet-
ꢁ
before being cooled to ꢀ80 C. Propionaldehyde (180
mL,
rahedron: Asymmetry 21 (2010) 1147.
[
4] For theoretical support, see: P. Quinio, C. François, A. Escribano
Cuesta, A.K. Steib, F. Achrainer, H. Zipse, K. Karaghiosoff, P. Knochel
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2
.5 mmol) was added at this temperature and the mixture
ꢁ
was warmed to ꢀ40 C and stirred for 2.5 h. After warming
to room temperature, aqueous HCl (1.0 M, 10 mL) and Et
2
O
[5] J. Bejjani, C. Botuha, F. Chemla, F. Ferreira, S. Magnus, A. P eꢀ rez-Luna,
(
10 mL) were added and the layers were separated. The
Organometallics 31 (2012) 4876.
6] Recent applications in synthesis from our group: (a) A. Voituriez,
[
aqueous layer was extracted with Et
2
O (ꢂ2) and the com-
F. Ferreira, F. Chemla, J. Org. Chem. 72 (2007) 5358;
bined organics were washed with water and brine, dried
over MgSO , and concentrated under reduced pressure.
Purification by flash column chromatography on silica gel
(b) A. Voituriez, F. Ferreira, A. Perez-Luna, F. Chemla, Org. Lett. 9
ꢀ
(2007) 4705;
4
(
(
(
c) F. Ferreira, C. Botuha, F. Chemla, A. P eꢀ rez-Luna, J. Org. Chem. 74
2009) 2238;
(
(
n-pentane/Et
129 mg, 78%, 95:5 dr) as a colorless oil. H NMR (400 MHz,
):
¼ 7.66e7.61 (m, 2H), 7.43e7.35 (m, 3H), 3.97 (dd,
2
O ¼ 85:15) afforded analytical pure
4
ꢀ
ꢀ
d) C. Seguin, F. Ferreira, C. Botuha, F. Chemla, A. Perez-Luna, J. Org.
1
Chem. 74 (2009) 6986;
(
(
(
e) B. H eꢀ lal, F. Ferreira, C. Botuha, F. Chemla, A. P eꢀ rez-Luna, Synlett
CDCl
3
d
2009) 3115;
J ¼ 8.7, 3.1 Hz, 1H), 3.84 (m, 1H), 2.74 (dd, J ¼ 8.7, 2.1 Hz, 1H),
f) J. Louvel, C. Botuha, F. Chemla, E. Demont, F. Ferreira, A. P eꢀ rez-
1
3
.75e1.25 (m, 7H), 1.00 (t, J ¼ 7.4 Hz, 3H), 0.94 (t, J ¼ 7.4 Hz,
Luna, Eur. J. Org. Chem. (2010) 2921;
(g) J. Louvel, F. Chemla, E. Demont, F. Ferreira, A. P eꢀ rez-Luna,
13
H), 0.93 (t, J ¼ 7.4 Hz, 3H), 0.40 (s, 6H). C NMR (100 MHz,
):
¼ 137.3, 133.7 (2C), 129.6, 128.0 (2C), 105.7, 88.4,
2.6, 71.8, 44.2, 43.1, 29.0, 22.9, 20.6, 12.4, 11.9, 10.7, ꢀ0.6
2C). IR (neat): 3393, 3070, 2961, 2929, 2876, 2169, 1719,
A. Voituriez, Adv. Synth. Catal. 353 (2011) 2137;
CDCl
3
d
(
h) J. Louvel, F. Chemla, E. Demont, F. Ferreira, A. P eꢀ rez-Luna, Org.
7
(
1
(
Lett. 13 (2011) 6452.
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(1974) 5620;
462, 1428, 1250, 115, 837, 817, 780, 731, 700 cm . HRMS
(b) G. Zweifel, S.J. Blacklund, T. Leung, J. Am. Chem. Soc. 100 (1978)
þ
ESI): m/z [M þ Na] calcd for C20
H32NaO
2
Si, 355.2064;
5561;
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(c) M.M. Midland, J. Org. Chem. 42 (1977) 2650;
(
d) D. Carri eꢀ , B. Carboni, M. Vaultier, Tetrahedron Lett. 36 (1995)
8
209.
5
.4.1. Preparation of 1,3-aminoalcohol 14
The typical procedure was followed with 7b (115 mg,
.50 mmol) and benzaldehyde (254 L, 2.5 mmol). Purifi-
[
[
8] Allenylaluminium reagents: N.R. Pearson, G. Hanh, G. Zweifel J. Org.
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K. Takagi, G. Wu, J. Am. Chem. Soc. 111 (1989) 3089;
0
m
cation by flash column chromatography on silica gel (n-
pentane/Et
(b) T. Luker, R.J. Whitby, Tetrahedron Lett. 35 (1994) 785;
2
O ¼ 90:10e70:30) afforded analytical pure 14
(c) G.J. Gordon, R.J. Whitby, Chem. Commun. (1997) 1321;
(d) J. Steck, A.R. Henderson, R.J. Whitby, Tetrahedron Lett. 53 (2012)
1
1
(
71 mg, 30%) as a colorless oil. H NMR (400 MHz, CDCl
3
):
12.
d
¼ 7.53e7.51 (m, 2H), 7.42e7.28 (m, 8H), 4.98 (m, 1H), 4.0
[
10] Allenylzinc reagents: (a) T. Katsuhira, T. Harada, K. Maejima,
(
d, J ¼ 10.2 Hz, 1H, NH), 3.43 (ddd, J ¼ 10.2, 7.4, 2.9 Hz, 1H),
A. Osada, A. Oku, J. Org. Chem. 58 (1993) 6166;
Please cite this article in press as: V.N. Bochatay, et al., Synthesis of allenylzinc reagents by 1,2-rearrangement of alkynyl(disilyl)
zincates derived from acetylenic epoxides and acetylenic aziridines, Comptes Rendus Chimie (2017), http://dx.doi.org/10.1016/
j.crci.2017.02.001

8
V.N. Bochatay et al. / C. R. Chimie xxx (2017) 1e8
(
b) T. Harada, T. Katsuhira, A. Osada, K. Iwazaki, K. Maejima, A. Oku,
F. Ferreira, J. Org. Chem. 69 (2004) 8244;
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(
(
(
c) T. Harada, E. Kutsuwa, J. Org. Chem. 68 (2003) 6716;
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e) A. Denichoux, L. Debien, M. Cyklinsky, M. Kaci, F. Chemla,
5269.
[17] The ring opening of ethynyloxiranes on reaction with nBu
3
ZnLi (2.4
0
equiv) has been previously reported and it involves direct S
displacement to some extent, see Ref. [10d].
[18] It is documented that nBu ZnLi can abstract acetylenic protons from
3
N
2
F. Ferreira, A. P eꢀ rez-Luna, J. Org. Chem. 78 (2013) 134.
11] M. Shimizu, T. Kurahashi, H. Kitagawa, T. Hiyama, Org. Lett. 5 (2003)
25.
3
12] The reaction between (Me PhSi) ZnLi and propargylic mesylates
[
[
2
propargylic mesylates and propargylic ethers under similar condi-
tions; 2 equiv of zincate were used, but this issue was not discussed
in any detail, see Ref. [10a].
2
having terminal alkynes was also contemplated. In that case, direct
S
Ref. [10b].
0
N
2 displacement seemed to be the major operating pathway, see
[19] Optimization of the regio- and stereoselectivity was not pushed
further because we have previously disclosed more efficient syn-
thetic strategies to access the same products: (a) (12) M. Cyklinsky,
C. Botuha, F. Chemla, F. Ferreira, A. P eꢀ rez-Luna, Synlett (2011) 2681;
[
13] (a) A. Denichoux, F. Ferreira, F. Chemla, Org. Lett. 6 (2004) 3509;
(
b) A. Denichoux, M. Cyklinsky, F. Chemla, F. Ferreira, A. P eꢀ rez-
0
Luna, Synlett (2013) 1001.
(b) (12 ) V.N. Bochatay, Z. Neouchy, F. Chemla, F. Ferreira,
[
14] V.N. Bochatay, Y. Sanogo, F. Chemla, F. Ferreira, O. Jackowski,
A. Perez-Luna, Adv. Synth. Catal. 357 (2015) 2809.
O. Jackowski, A. Perez Luna, Synthesis 48 (2016) 3287 and Ref. [14].
[20] This surprising difference of reactivity between trans and cis iso-
[
15] The configuration of diol 4 was determined by 1H NMR analysis of
mers was further confirmed by an experiment wherein a 1:1
the cyclic 6-membered acetal obtained from
dimethoxymethane.
4
and
mixture of 6a (0.5 equiv) and 6c (0.5 equiv) was treated under the
rearrangement conditions (0 C): ring opening of 6a was complete,
ꢁ
[
16] Our studies were carried out with racemic N-tert-butanesulfinyle-
thynylaziridines, but these substrates can also be prepared in
enantiomerically pure form starting from enantiopure N-tert-buta-
nesulfinylimines. For relevant references, see: (a) F. Chemla,
whereas 6c was recovered intact.
[21] The relative configurations of product 14 were not determined.
[22] J. Suffert, J. Org. Chem. 54 (1989) 509.
[23] M. Oestrich, B. Weiner, Synlett (2004) 2139.
Please cite this article in press as: V.N. Bochatay, et al., Synthesis of allenylzinc reagents by 1,2-rearrangement of alkynyl(disilyl)
zincates derived from acetylenic epoxides and acetylenic aziridines, Comptes Rendus Chimie (2017), http://dx.doi.org/10.1016/
j.crci.2017.02.001