Metallotropic equilibrium and configurational stability of 3-chloro-1-(trimethylsilyl)propargyl and -allenyl metals: Comparative study among lithium, titanium, and zinc

Article abstract of DOI:10.1021/om300420q

A comparative study of the metallotropic equilibrium between 1-chloro-3-(trimethylsilyl)propargyl and -allenyl metals was undertaken by means of lithio-, titano-, and zinco-carbenoids. The lithium and zinc species were shown to react mainly in their allenic metallotropic forms, whereas the titanium species proved to react in both its propargylic and allenic forms. The configurational stability of these organometallics was next examined using a modification of the Hoffmann test. In each case, the organometallic was reacted with a chiral enantiopure electrophile. A comparison of the diastereomeric ratios obtained at low and high conversion rates of the reagent allows assessment of its configurational stability. The lithium species thus exhibited a configurational lability at -125 °C in Trapp mixture on the time scale of its reaction with (+)-camphor, while the titanium analogue proved to be configurationally stable at -40 °C in THF/Et₂O on the time scale defined by its reaction with (S)-N-tritylprolinal. In the context of its reaction with the same electrophile, the zinc bromide species was proven to be partially labile from -80 °C in THF and its dynamic kinetic resolution was investigated.

Full text of DOI:10.1021/om300420q

Article
pubs.acs.org/Organometallics
Metallotropic Equilibrium and Configurational Stability of
3-Chloro-1-(trimethylsilyl)propargyl and -allenyl Metals:
Comparative Study among Lithium, Titanium, and Zinc
Joseph Bejjani,† Candice Botuha, Fabrice Chemla,* Franck Ferreira,* Sarah Magnus,
and Alejandro Perez-Luna
́
UPMC-Univ Paris 06, UMR CNRS 7201, Institut Parisien de Chimie Molec
Case 183, 4 place Jussieu, F-75252 Paris Cedex 05, France
́ ́
ulaire, Institut de Chimie Moleculaire (FR 2769),
S
* Supporting Information
ABSTRACT: A comparative study of the metallotropic equilibrium between
1-chloro-3-(trimethylsilyl)propargyl and -allenyl metals was undertaken by
means of lithio-, titano-, and zinco-carbenoids. The lithium and zinc species
were shown to react mainly in their allenic metallotropic forms, whereas the
titanium species proved to react in both its propargylic and allenic forms. The
configurational stability of these organometallics was next examined using a
modification of the Hoffmann test. In each case, the organometallic was
reacted with a chiral enantiopure electrophile. A comparison of the diastereo-
meric ratios obtained at low and high conversion rates of the reagent allows assessment of its configurational stability. The
lithium species thus exhibited a configurational lability at −125 °C in Trapp mixture on the time scale of its reaction with
(+)-camphor, while the titanium analogue proved to be configurationally stable at −40 °C in THF/Et2O on the time scale
defined by its reaction with (S)-N-tritylprolinal. In the context of its reaction with the same electrophile, the zinc bromide species
was proven to be partially labile from −80 °C in THF and its dynamic kinetic resolution was investigated.
thermal sensitivity.30 For the past decade, our group has been
INTRODUCTION
■
interested in the preparation of 3-chloro-1-(trimethylsilyl)allenyl
metals and their reactions with electrophiles. In racemic form,
these reagents have proven highly useful for the stereoselective
preparation of acetylenic epoxides and aziridines.31 In order to
extend the scope of our developed methodology, we envisioned
preparing these species in enantioenriched form. Achievement
of this prospect requires first investigating their configurational
stability. A study was thus conducted using the Hoffmann test,
which is based on the kinetic resolution of the organometallic by
a chiral electrophile and has the advantage of not requiring use
of enantiomerically pure organometallics.32 Two experiments
are needed for this test. The first is carried out with 1 equiv of
the racemic electrophile. The diastereomeric ratio thus observed
is the intrinsic selectivity s of the reaction and corresponds to
the upper attainable stereoselectivity under the reaction
conditions used. The second experiment is carried out under
the same conditions with the enantiopure electrophile. The level
of configurational stability of the organometallic reagent on the
time scale defined by its reaction with the electrophile used is
inferred from a comparison of the diastereomeric ratios obtained
in the two experiments.33,34
Reactions of propargyl and allenyl metals with electrophiles
have been extensively investigated and provide synthetically
useful intermediates.1−6 The regio- and stereoselectivities of
these reactions are both sensitive to the metal itself and the
bulkiness of its substituents. For example, allenyl stanannes,7
indiums,7 and zincs8−13 react with aldehydes in a highly regio-
and stereoselective manner, while the magnesium,14 chromium,15
boron,16−19 and titanium20 analogues generally react less
selectively. Particularly interesting are configurationally stable
chiral propargyl and allenyl metals.2,7,8,21−27 The racemization
process involves intra- or intermolecular dissociative carbon−
metal bond pathways, and thus the level of the configurational
stability is specific to each species. The existence of a metallo-
tropic equilibrium between the propargylic (P) and allenic (A)
forms may also have an impact on the configurational stability of
the organometallic (Scheme 1).23c,28
Scheme 1. Metallotropic Equilibrium between Propargyl (P)
and Allenyl (A) Metals
Herein, we report a comparative study on 3-chloro-1-
(trimethylsilyl)-substituted lithio-, titano-, and zinco-carbenoids
M-1. First, the addition reaction of the racemic species M-1
Little information is available on the configurational stability
of propargyl and allenyl metallo-carbenoids, reagents for which
R1 is a leaving group in Scheme 1,29 probably due to their
Received: May 16, 2012
Published: June 28, 2012
© 2012 American Chemical Society
4876
dx.doi.org/10.1021/om300420q | Organometallics 2012, 31, 4876−4885

Organometallics
Article
with achiral aldehydes has been studied in order to gain insight
into the rate of the metallotropic equilibrium. Then, their con-
figurational stabilities have been investigated by means of the
Hoffmann test using chiral enantiopure aldehydes (Scheme 2).
the configurational stability of M-1, we were not able to
determine their role.39 In addition, metallo-carbenoids M-1,
and more particularly the lithio-carbenoid Li-1, should form
aggregates associated through carbon−metal bonds. However,
throughout this paper, reagents M-1 will only be considered as
monomeric species for a simplified view.40
Scheme 2. Our Work
Study of the Metallotropic Equilibrium Involving
Metallo-Carbenoids M-1. With carbonyl functions, in most
cases it is believed that the reaction of propargyl and allenyl
metals proceeds by a cyclic SE2′ process, giving allenic and
homopropargylic alcohols, respectively.2,41,42 The regioselectiv-
ity of the reaction, i.e. the ratio between allenic and acetylenic
products obtained, is thus highly informative as to the rate of
the metallotropic equilibrium. The reaction of lithio-, titano-,
and zinco-carbenoids M-1 with achiral aldehydes was then
investigated (Scheme 4).
Scheme 4. Addition of Metallo-Carbenoids M-1 to
Aldehydes
RESULTS AND DISCUSSION
■
Preparation of Metallo-Carbenoids M-1. Usually
propargyl- and allenylmetals are prepared by the reduction of
propagylic or allenic halides with metals or by the metalation of
the corresponding hydrocarbons with alkyllithiums.1a,35 As for
us, we succeeded in preparing the lithio-carbenoid Li-1 (Met = Li)
in racemic form by the deprotonation of (3-chloroprop-1-
ynyl)trimethylsilane36 with 1 equiv of nBuLi in the presence of 1
equiv of TMEDA within 15 min at −95 °C in Et2O (Scheme 3).37
Scheme 3. Preparation of Metallo-Carbenoids M-1
When the lithio-carbenoid Li-1 was reacted with aldehydes
for 1 h at −95 °C, mixtures of homopropargylic and allenic
alcohols, 2 and 3,38 respectively, were obtained in high yields
(Table 1, entries 1−5).37 Except for the reaction with
benzaldehyde (Table 1, entry 5), homopropargylic alcohols 2
were obtained with good to high anti selectivity, explained by
the favored “Chodkiewicz−Yamamoto”-type transition state
model M1.43 The relative configuration of the minor allenic
alcohols 3, which could arise from transition state model M2,
could not be determined. Even though products 2 were always
formed as the major isomers, a variation of the 2:3 ratio
depending on the aldehyde was observed. This variation is a
good indication that the Curtin−Hammett principle applies.
This means that the metallotropic equilibrium is faster than the
reactions of (P)-Li-1 and (A)-Li-1 with the aldehydes so that
2:3 = kA:kP. In order to explain both the variation in the 2:3
ratio and the predominant formation of 2, the rate constants
should be such that ke ≫ kA > kP at −95 °C in Et2O.
The reaction of titano-carbenoid Ti-1 was first investigated
with cyclohexanecarboxaldehyde at different temperatures in
THF/Et2O. In each case, the corresponding homopropargylic
and allenic adducts 2 and 3 were obtained with modest regio-
selectivities and variable stereoselectivities (Table 1, entries
6−10). The best regio- and stereoselectivities, however, were
attained within 3 h at −40 °C (Table 1, entry 8). Note that
partial thermal decomposition of Ti-1 was observed above −20 °C.
This initially gave the racemic propargyllithium (P)-Li-1, which
isomerized into its metallotropic allenic form (A)-Li-1 (vide
infra), thereby producing a mixture of (P)-Li-1 and (A)-Li-1
forms in equilibrium. Under these conditions, no detectable self-
coupling product was observed.
The lithio-carbenoid Li-1 exhibits a limited stability at
−95 °C but can still be transmetalated with 1 equiv of
Ti(OiPr)4 and ZnBr2 to give Ti-1 (Met = Ti(OiPr)3) and
Zn-1 (Met = ZnBr), respectively, as mixtures of the two
corresponding metallotropic forms. Alternatively, the zinco-
carbenoid Zn-1 could be prepared in THF at −80 °C by the
lithiation of (3-chloroprop-1-ynyl)trimethylsilane using 2 equiv
of LDA in the presence of 2 equiv of ZnBr2.31a
Attempts to characterize metallo-carbenoids M-1 by low-
temperature NMR experiments were unsuccessful. Although
the TMEDA required for the formation of M-1 and the lithium
salt (LiBr or LiOiPr) generated during the preparation should
have an influence on both the metallotropic equilibrium and
4877
dx.doi.org/10.1021/om300420q | Organometallics 2012, 31, 4876−4885

Organometallics
Article
the metallotropic equilibrium might be totally displaced in favor of
(A)-Zn-1. Alternatively, it might be that a rapid equilibrium occurs
but the exclusive formation of 2 is the result of a Curtin−Hammett
situation with rate constants such that ke ≫ kA ≫ kP.
In conclusion, for each of the three metallo-carbenoids M-1
the regioselectivity of the reaction appears to depend only on
2:3 = kA:kP (Scheme 5).
Table 1. Study of the Metallotropic Equilibrium Involving
M-1 (Scheme 4)
yield
d
a
b
c
c
entry M-1
R
T (°C)
−95
2:3
dr of 2 dr of 3
(%)
1
2
3
4
5
6
7
8
9
Li-1 cHex
Li-1 iPr
89:11
82:18
96:04
83:17
69:31
52:48
35:65
30:70
38:62
71:29
30:70
65:35
50:50
75:25
59:41
71:29
72:28
90:10
69:31
65:35
98:02
98:02
92:08
80:20
68:32
92:08
92:08
85:15
82:18
91:09
68:32
66:34
80:20
58:42
58:42
98:02
98:02
98:02
93:07
75:25
98:02
83
87
75
−95
−95
−95
−95
−80
−60
−40
−20
Li-1 tBu
Li-1 nBu
Li-1 Ph
60
Scheme 5. General Trends of the Metallotropic Equilibrium
Involving M-1
e
79
Ti-1 cHex
Ti-1 cHex
Ti-1 cHex
Ti-1 cHex
80
90
67
74
50
59
63
f
f
10 Ti-1 cHex
11 Ti-1 iPr
12 Ti-1 tBu
13 Ti-1 nBu
14 Ti-1 Ph
0
−40
−40
−40
−40
>98:02
96:04
75:25
79:21
76
e
75
e
15 Ti-1 (E)-crotyl −40
61
16 Zn-1 cHex
17 Zn-1 iPr
18 Zn-1 tBu
19 Zn-1 nBu
20 Zn-1 Ph
21 Zn-1 crotyl
−80 to
>98:02 83:17
>98:02 95:05
>98:02 >98:02
>98:02 86:14
>98:02 64:36
>98:02 84:16
76
75
82
81
83
82
−20
−80 to
−20
Study of the Configurational Stability of Metallo-
Carbenoids M-1. In order to examine the configurational
behavior of metallo-carbenoids M-1, we used a modified version
of the Hoffmann test that only required the use of an enantiopure
electrophile. To this end, the first experiment was carried out at a
low conversion rate (CG) of the organometallic. In practice, to
have good control of CG, the reaction was run using 0.1−0.2
equiv of electrophile. These conditions mimic the reaction of the
organometallic with 1 equiv of the racemic electrophile according
to Hoffmann calculated curves plotting the variation of the
diastereomeric ratio (dr) against the conversion rate of a
configurationally stable organometallic.46 These curves allow us
to know the intrinsic selectivity s of the reaction, which is very
close to the observed dr at low CG (Figure 1).
The configurational stability of lithio-carbenoid Li-1 was first
examined at −125 °C in a 4/4/1 THF/Et2O/pentane mixture
as solvent (Trapp mixture47) using (+)-camphor (4) as the
electrophile. Under these conditions within 1 h, the reaction of
Li-1 with 0.2 equiv of 4 led to a CG value of 20%. Exo acetylenic
epoxides 5 were obtained with dr(5a:5b) = 92:08 (Scheme 6).
The exclusive formation of acetylenic adducts 5 was explained
by the reaction of (A)-Li-1 with 4 being much faster than that
of (P)-Li-1. Thus, in a simplified view only the reaction of (A)-
Li-1 was taken into consideration. The exo stereochemistry and
the S configuration of carbon atom C11 of the major isomer 5a
were assigned by NOE experiments, indicating a significant
effect of 4% between H3α and H11 (Scheme 6).
The stereochemistry of the minor isomer 5b could not be
determined. However, on the basis of reported works showing
that the addition of organometallics occurs from the less
hindered face of camphor, i.e. the endo face,48 5b was assumed
to be also exo but with an R configuration for carbon atom C11.
The predominant formation of 5a could be rationalized by the
nucleophilic attack of the aR enantiomer of (A)-Li-1 via
the favored transition state model M3a, wherein the chlorine
atom and the camphor ring adopt an anti relationship in order
to minimize steric interaction. On the other hand, the aS
enantiomer of (A)-Li-1 approaches via disfavored transition
state model M3b, giving the minor isomer 5b (Scheme 6).
Following the equations developed by Hoffmann, an
observed 5a:5b ratio of 92:08 at a CG value of 20% is
−80 to
−20
−80 to
−20
−80 to
−20
−80 to
−20
a
Conditions: Li-1 (Met = Li), reactions carried out for 1 h at −95 °C
in Et2O; Ti-1 (Met = Ti(OiPr)3), reactions carried out for 3 h at the
indicated temperature in THF/Et2O; Zn-1 (Met = ZnBr), reactions
carried out for 1 h at −80 °C and then 45 min at −20 °C in THF.
b
1
Determined by H NMR analysis at 400 MHz of the crude reaction
c
1
mixture. dr of products 2 and 3 determined by H NMR analysis at
400 MHz of the crude reaction mixture; for product 2, dr = anti:syn
d
ratio. Combined isolated yield in 2 and 3. Unless otherwise stated,
analytically pure 2 and 3 could be isolated by flash chromatography.
Inseparable mixtures of 2 and 3 were obtained. Partial decomposition
of Ti-1 was observed.
e
f
The titano-carbenoid Ti-1 was thus reacted with other
aldehydes for 3 h at −40 °C (Table 1, entries 11−15). In all
cases, the expected adducts 2 and 3 were isolated in good yields
with low 2:3 ratios but quite good stereoselectivities for both 2
and 3. The anti configuration observed for 2 could again be
explained by transition state model M1. Although still low,
the regioselectivity of the reaction was highly impacted by the
aldehyde itself, as seen by the variation in both the level and the
sense of the 2:3 ratio. As for Li-1, this is characteristic of
Ti-1 existing in its two metallotropic forms that interconvert
much more quickly than they react with aldehydes at −40 and
−80 °C in THF−Et2O, meaning that 2:3 = kA:kP with rate
constants such as ke ≫ kA ≈ kP. These results are in sharp
contrast with the reported reactivity of 3-alkyl-substituted
propargyl/allenyl titanium(IV) species with aldehyde.43b,44
Finally, the reaction of the zinco-carbenoid Zn-1 with
aldehydes was examined (Table 1, entries 16−21).38 In all
cases, the reaction was complete within 2 h between −80 and
−20 °C and only homopropargylic alcohols 2, obtained via M1,
were formed in excellent yields and mostly with high anti:syn
ratios. This result could be explained in two ways. Along the lines
of the works of Gaudemar on 3-alkyl-substituted allenylzincs,42a,b,45
4878
dx.doi.org/10.1021/om300420q | Organometallics 2012, 31, 4876−4885

Organometallics
Article
Figure 1. Modified Hoffmann test.
Scheme 6. Addition of Racemic Li-1 to Enantiopure
(+)-Camphor (4)
than it is trapped by 4. This situation corresponds to the best
possible dynamic kinetic resolution with rate constants such
that kr ≫ kaR > kaS. This result is in accordance with the
configurational behavior reported for 3-alkyl-1-silyl-substituted
allenyllithiums,23c which are labile below −93 °C in Et2O, and
can be correlated to the rapid metallotropic equilibrium
involving Li-1.
The configurational stability of racemic titano-carbenoid Ti-1
was next evaluated by means of the modified Hoffmann test.
(S)-N-Tritylprolinal (6), known to react with various organo-
metallics with high diastereoselectivities,49 was used as the
electrophile. The study was conducted in a THF/Et2O mixture
at −40 °C, conditions for which the best regio- and stereo-
selectivities were observed in reactions with aldehydes (see
Table 1). When Ti-1 was reacted with 0.1 equiv of 6, a CG value
of 10% was reached. The two allenic products 7a,b were
obtained in a 7a:7b ratio of 66:34, corresponding to the low
intrinsic selectivity s = 2 according to Hoffmann equations
(Scheme 7).
The configuration of the newly created stereogenic carbon atom
in both isomers was assumed to be S from the coupling constant
Scheme 7. Addition of Racemic Ti-1 to Enantiopure (S)-N-
Tritylprolinal (6)
associated with the intrinsic selectivity s = kaR:kaS = 14.1 at
−125 °C in Et2O. It also represents the upper theoretical limit
that can be reached at complete conversion of Li-1, under
identical reaction conditions.
When the reaction was carried out with 1.1 equiv of 4, a CG
value of 77% was observed within 1 h at −125 °C on the basis
of recovered unreacted 4 upon hydrolysis. Exo acetylenic
epoxides 5 were isolated in 62% combined yield with an
unchanged 5a:5b ratio of 92:08. Interestingly, this result
strongly suggests that Li-1 is already configurationally labile at
−125 °C in Trapp mixture: it racemizes much more quickly
4879
dx.doi.org/10.1021/om300420q | Organometallics 2012, 31, 4876−4885

Organometallics
Article
of 2.8 Hz between Ha and Hb and earlier works on additions of
organometallics to 6.49 The configuration of the allenic moiety in
both products could not, however, be determined.
Scheme 8. Addition of Zn-1 to Enantiopure (S)-N-
Tritylprolinal (6)
As allenic alcohols 7a,b were exclusively obtained, (P)-Ti-1
was assumed to react much more quickly than (A)-Ti-1 (kP ≫ kA).
Everything thus happened as if only the propargylic metallotropic
form (P)-Ti-1 were present.
When the reaction was conducted under the same conditions
with 1.2 equiv of 6, Ti-1 was completely consumed (CG = 100%),
affording adducts 7a,b in 60% combined yield with no selectivity
(7a:7b = 50:50). This result suggests that (P)-Ti-1 is configura-
tionally stable at −40 °C in THF/Et2O on the time scale defined
by its reaction with 6. Interestingly, despite the rapid equilibrium
between its two metallotropic forms, the configurational stability
of Ti-1 is maintained so that kr ≪ kR and kS. A study of the
configurational stability of Ti-1 could not be undertaken at higher
temperatures due to its partial thermal decomposition.
As a general trend, organozincs are thought to be more
covalently bonded with a barrier of inversion higher than that
of their lithium and titanium analogues.50 We have recently
shown that zinco-carbenoid Zn-1 is partially configurationally
stable at 20 °C in Et2O but configurationally stable at −15 °C
in the presence of HMPA in the time scale defined by its
reaction with enantiopure N-tert-butanesulfinimines.51 How-
ever, no information is available on the configurational stability
of Zn-1 in THF, which is the solvent of choice for its reaction
with aldehydes.37 To this end, we carried out the modified
Hoffmann test at −80 °C in THF, using 0.2 equiv of (S)-N-
tritylprolinal (6) (Scheme 8). Under these conditions, within
2 h, a CG value of 20% was reached. A mixture of the two
diastereomeric acetylenic chlorohydrins 9a,b was obtained with
dr = 90:10 in favor of 9a (Table 2, entry 1). As before, the
exclusive formation of acetylenic adducts 9 was rationalized by
the reactivity of (A)-Zn-1 being greater than that of (P)-Zn-1
(kA ≫ kP), and thus everything happened as if (A)-Zn-1 were
the only existing metallotropic form. The anti and syn relative
configurations of the two newly created stereogenic carbon
atoms of 9a,b were deduced from chemical correlations (see
the Supporting Information).
The anti stereoselectivity of the reaction was explained by
transition state models M4a,b, analogous to those postulated
and validated by PM3 calculations for the nucleophilic addition
reaction of organometallics to 6.49 In M4a,b the organometallic
attacks from the re face of the aldehyde that lies over the
pyrrolidine ring and adopts a pseudo-axial position in a trans
relationship with the trityl group. Accordingly, the aR
enantiomer of (A)-Zn-1 leads to 9a via the favored transition
state model M4a, in which the chlorine atom is not interacting
with the pyrrolidine cycle. The minor isomer 9b iself could
result from the approach of the aS enantiomer via the
disfavored transition state model M4b.
Table 2. Study of the Configurational Stability of Zn-1
(Scheme 8)
amt of 6
(equiv)
T
(°C)
time
(h)
C
yield
c
Ga
b
entry
(%)
dr
(%)
1
2
3
4
5
6
0.20
0.80
1.50
0.15
1.30
1.30
−80
−80
−80
−20
−20
−20
2
7
7
1
1
7
20
75
90:10
70:30
66:34
77:23
63:37
81:19
100
70
d
80
nd
15
100
56
100
100
65
a
Measured by 1H NMR analysis at 400 MHz on the basis of recovered
unreacted 6 in the crude reaction mixture. dr = (9a + 10a):(9b +
10b), determined by H NMR analysis at 400 MHz on the crude
reaction mixture. Combined yield of purified 9a,b and 10a,b. Not
b
1
c
d
determined.
At −80 °C in THF, the intrinsic selectivity of the reaction is
then s = kaR:kaS = 9.8 according to Hoffmann equations. The
reaction was next carried out with 0.80 and 1.50 equiv of 6
under the same conditions. In both cases, a longer reaction time
of 7 h was necessary in order to reach CG values of 75% and
80% with dr values of 70:30 and 66:34, respectively (Table 2,
entries 2 and 3). This decrease of dr was a good fit with the
theoretical curve calculated for the variation of dr as a function
of CG for a configurationally stable chiral organometallic
(Figure 2). Thus, it could be concluded that Zn-1 is configura-
tionally stable with s = kaR:kaS = 9.8 at −80 °C in THF on the
time scale defined by its reaction with 6. Subsequently, we
studied the configurational stability of Zn-1 in THF at −20 °C.
Within 1 h, the reaction with 0.15 equiv of 6 led to a mixture of
chlorhydrins 9a,b. They were accompanied by about 15% of
epoxides 10a,b, which came from intermediates 9a,b, respectively,
by intramolecular displacement of the chlorine. The diastereo-
selectivity of the reaction is thus given by dr = (9a + 10a):
(9b + 10b) = 77:23 at CG = 15% (Table 2, entry 4). This cor-
responds to the intrinsic selectivity s = 3.2 according to Hoffmann
equations. At CG = 100%, reached using 1.30 equiv of 6, a dr
value of 63:37 was observed. It significantly deviated from 50:50,
4880
dx.doi.org/10.1021/om300420q | Organometallics 2012, 31, 4876−4885

Organometallics
Article
Figure 2. Study of the configurational stability of Zn-1 in THF at −80 and −20 °C.
the dr which would have been obtained in the case of a configura-
tionally stable organometallic. A partial racemization of Zn-1 on
the time scale of its reaction with 6 was then suspected.
Scheme 9. Synthesis of Enantioenriched Chlorhydrins
To confirm this interpretation, we performed an additional
experiment by slowly adding 1.30 equiv of 6 over a period of
6 h and waiting an additional 1 h prior to hydrolysis. As
expected, slowing down the addition rate of 6 resulted in an
increased dr of 81:19. Under these conditions, a higher kinetic
resolution was attained by giving more time to the mismatched
aS enantiomer of (A)-Zn-1 to racemize into its matched aR
enantiomer. Thus, Zn-1 was shown to be partially configura-
tionally labile from −20 °C in THF. The striking difference in
behavior of Zn-1 in comparison to that of its 3-alkyl-substituted
analogues, which are reported to be configurationally stable up
to 40 °C,3,9,22,25c,d,52 remains unexplained.
We next envisioned running kinetic resolution experiments to
evaluate the time during which Zn-1 is still configurationally stable
at −80 °C in THF. With this aim, the reaction was conducted at
−80 °C between Zn-1 and 2 equiv of 6 for a given time, after
which cyclohexanecarboxaldehyde was added in order to trap the
remaining Zn-1. Upon hydrolysis, 9a and the corresponding
chlorohydrin 2 were obtained with anti:syn ratios of 90:10 and
84:16, respectively (Scheme 9). After 2 h of reaction, under these
conditions, 2:9a = 25:75, giving CG = 25% (Table 3, entry 1). The
enantiomeric ratio (er) of the major anti chlorohydrin, isolated in
25% yield, was assigned to be 63:37 by the use of 50 wt % of
Eu(hfc)3 as a europium shift reagent. The R,S absolute
configuration of the chlorohydrin was deduced from its conversion
into a known homopropargylic alcohol53 via successive treatments
with DBU and LiAlH4 (see the Supporting Information). The
formation of the anti isomer could thus be explained by transition
state model M5, wherein the aS enantiomer of Zn-1 reacts with 6.
All these results indicated that unreacted (A)-Zn-1 was
enantioenriched in its aS enantiomer.
Further experiments were thus carried out under the same
conditions while increasing the reaction time between Zn-1 and
6 (Table 3, entries 2−5). In all cases, the anti chlorohydrin
was isolated as the main isomer in 29−33% yields with up to
78:22 er obtained after 3.5 h of reaction (Table 3, entry 4). Up
to 3.5 h of reaction, the observed er was a good fit with the
theroretical calculated curve er = f(CG) obtained in the case of a
configurationally stable organometallic with s = 9.8 (Figure 3),
suggesting that Zn-1 is configurationally stable over 3.5 h at
−80 °C in THF.
4881
dx.doi.org/10.1021/om300420q | Organometallics 2012, 31, 4876−4885

Organometallics
Article
Trapp mixture on the time scale defined by its reaction with
(+)-camphor, whereas Ti-1 exhibited configurational stability at
−40 °C in THF/Et2O on the time scale defined by its reaction
with (S)-N-tritylprolinal. With the latter electrophile, Zn-1 was
demonstrated to be configurationally stable over 4 h at −80 °C
but partially labile at −20 °C in THF. Further studies and
synthetic applications using metallo-carbenoids M-1 are being
undertaken in our group and will be reported in due course.
Table 3. Kinetic Resolution of Zn-1 (Scheme 9)
a
b
c
entry
time (h)
yield (%)
25
er
1
2
3
4
5
2
63:37
69:31
77:23
78:22
69:31
d
2.5
3
nd
29
d
3.5
4
nd
33
a
Reaction time at −80 °C with 6 prior to addition of cyclo-
b
hexylcarboxaldehyde. Yield in purified chlorohydrin 2 based on cyclo-
hexanecarboxaldehyde. Measured by addition of 50 wt % of Eu(hfc)3
to a CD3Cl solution of purified chlorohydrin 2. Not determined.
EXPERIMENTAL SECTION
c
■
d
General Methods. Experiments involving organometallics were
carried out in dried glassware under a positive pressure of dry nitrogen.
Liquid nitrogen was used as a cryoscopic fluid. A three-necked, round-
bottomed flask equipped with an internal thermometer, a septum cap,
and a nitrogen inlet was used. Anhydrous THF and Et2O were
obtained by distillation over sodium−benzophenone ketyl. CH2Cl2
and TMEDA were obtained by distillation over CaH2. (+)-Camphor
was sublimed prior to use. Commercial zinc bromide was melted
under argon and immediately after cooling to room temperature
dissolved in anhydrous THF or Et2O. n-BuLi (2.50 M commercial
solution in hexane) was titrated with N-pivaloyl-o-toluidine.54 All other
reagents and solvents were of commercial quality and were used
without further purification. Flash chromatography was carried out
over silica gel (230−400 mesh). 1H and 13C NMR spectra were
recorded with a dual probe (13C/1H). Chemical shifts are reported
in δ units relative to an internal standard of residual chloroform
Surprisingly, a drop in the er was noted for a longer reaction
time (Table 3, entry 5), which could not be explained by
racemization of the electrophile, since recovered unreacted 6
showed no loss of its optical purity. Conversely, racemization of
Zn-1 could be invoked. Indeed, the reaction rate between Zn-1
and 6 might become slower and slower while CG increases, which
might give more and more time for Zn-1 to racemize.
Unfortunately, this phenomenon precludes the practical use of
the kinetic resolution of Zn-1 in order to access highly enantio-
enriched allenylzinc species and their use in asymmetric synthesis.
CONCLUSION
■
1
(δ 7.27 ppm for H NMR and δ 77.16 ppm for 13C NMR) or C6D6
3-Chloro-1-(trimethylsilyl)-substituted metallo-carbenoids M-1
were shown to exist in rapid metallotropic equilibria between
propargylic and allenic forms. The allenic form of Li-1 exhibited
a greater reactivity toward aldehydes than the propargylic form,
giving predominantly homopropargylic alcohols at −95 °C in
Et2O. The same behavior was observed for Zn-1 between −80
and −20 °C in THF. On the other hand, the allenic and
propargylic forms of Ti-1 proved to have similar reactivities at
−80 and −40 °C in a THF/Et2O mixture, affording mixtures of
homopropargylic and allenic alcohols.
(δ 7.15 ppm for 1H NMR and δ 128.6 ppm for 13C NMR). Elemental
analyses were performed at the Service de Microanalyses de
l’Universite Pierre et Marie Curie-Paris 6, case 55, 4 place Jussieu,
́
75252 Paris Cedex 05.
Typical Procedure for the Reaction of Li-1 with Aldehydes.
At −95 °C, to a solution of (3-chloroprop-1-ynyl)trimethylsilane (0.80 mL,
5.00 mmol) in Et2O (20 mL) and TMEDA (0.75 mL, 5.00 mmol) was
added n-BuLi (2.30 M in hexanes, 2.17 mL, 5.00 mmol) at such a rate
that the internal temperature did not exceed −95 °C. The reaction
mixture was stirred for 15 min while it turned orange. The aldehyde
(5.00 mmol) in Et2O (5 mL) was added to the reaction mixture at
−95 °C over a period of 5 min. After 1 h of stirring at −95 °C, a 1 M
aqueous HCl solution (10 mL) was added, the layers were separated,
The configurational stability of metallo-carbenoids M-1 was
also investigated by means of a modification of the Hoffmann
test. Li-1 proved to be configurationally labile at −125 °C in
Figure 3. Configurational stability of Zn-1 over 4 h at −80 °C in THF.
4882
dx.doi.org/10.1021/om300420q | Organometallics 2012, 31, 4876−4885

Organometallics
Article
and the aqueous layer was extracted with Et2O (3 × 20 mL). The
combined organic layers were dried over anhydrous MgSO4, filtered,
and concentrated in vacuo. Purification of the crude material by flash
chromatography allowed isolation of 2 and 3 (see Table 1, entries 1−5).
(1R,2S,3′S,4R)-1,7,7-Trimethyl-3′-(trimethylsilyl)ethynylspiro-
[bicyclo[2.2.1]heptane-2,2′-oxirane] (5a). The title compound was
obtained following the above procedure by the reaction between
(3-chloroprop-1-ynyl)trimethylsilane (1.61 mL, 10.00 mmol) and
(+)-camphor (4; 1.40 g, 9.00 mmol) in a Trapp mixture. Purification
by flash chromatography (5% Et2O/pentane) afforded a mixture of 5a
and 5b (1.46 g, 5.58 mmol, 5a:5b = 92:08, 62%) as a colorless oil.
found 488.2183; m/z calcd for C30H34(37Cl)NOSi + H+ 490.2162
[M + H+], found 490.2149.
Typical Procedure for the Reaction of Zn-1 with Aldehydes.
At −80 °C, to a 1 M THF solution of ZnBr2 (2.00 mL, 2.00 mmol)
and (3-chloroprop-1-ynyl)trimethylsilane (0.32 mL, 2.00 mmol) in
THF (6 mL) was added dropwise a freshly prepared 2 M THF
solution of LDA (2 mL, 4.00 mmol) over a period of 1 h. After
completion of the addition, the aldehyde (2.00 mmol) was added. The
resulting mixture was stirred at −80 °C for 1 h and then warmed to
−20 °C, at which temperature it was stirred for an additional 45 min.
A 2/1 mixture of a saturated aqueous NH4Cl solution and NH3
(10 mL) was added, the layers were separated, and the aqueous layer
was extracted with Et2O (2 × 10 mL). The combined organic layers
were dried over anhydrous MgSO4 and filtered, and the solvents were
removed in vacuo. Purification by flash chromatography afforded
analytically pure chlorohydrins 2 (see Table 1, entries 16−21).
(−)-(1S,2R)-2-Chloro-4-(trimethylsilyl)-1-((S)-1-tritylpyrrolidin-2-
yl)but-3-yn-1-ol (9a) and (−)-(1S,2S)-2-chloro-4-(trimethylsilyl)-1-
((S)-1-tritylpyrrolidin-2-yl)but-3-yn-1-ol (9b). The title compounds
were obtained following the above procedure by the reaction bet-
ween (3-chloroprop-1-ynyl)trimethylsilane (0.32 mL, 2.00 mmol) and
(S)-N-tritylprolinal (6; 0.82 g, 2.40 mmol) for 7 h at −80 °C. Purifica-
tion by flash chromatography (4.9%/0.1% EtOAc/Et3N/cyclohexane)
afforded analytically pure 9a (0.57 g, 49%) and 9b (0.25 g, 21%) as
white solids.
1
Data for 5a are as follows. H NMR (400 MHz, CDCl3, 25 °C): δ
3.27 (s, 1 H), 1.92 (dt, J = 13.8, 3.9 Hz, 1 H), 1.84−1.75 (m, 2 H),
1.72−1.60 (m, 2 H), 1.55−1.52 (d, J = 13.8 Hz, 1 H), 1.24 (m, 1 H),
0.95 (s, 3 H), 0.92 (s, 3 H), 0.87 (s, 3 H), 0.16 (s, 9 H). 13C NMR
(100 MHz, CDCl3, 25 °C): δ 101.9, 92.3, 73.7, 48.8, 48.2, 46.8, 44.8,
39.4, 30.7, 27.9, 19.7, 19.3, 10.6, −0.3. IR (neat): ν 2959, 2170, 1652,
1242, 1035, 846 cm−1. MS (ESI): m/z (%) 285 (24) [M + Na+], 251
(100), 223 (42). HMRS (ESI): m/z calcd for C16H26OSi + Na+
285.1645 [M + Na+], found 285.1641.
Typical Procedure for the Reaction of Ti-1 with Aldehydes.
At −95 °C, to a solution of TMEDA (0.60 mL, 4.00 mmol) and
(3-chloroprop-1-ynyl)trimethylsilane (0.64 mL, 4.00 mmol) in Et2O
(10 mL) was added dropwise n-BuLi (2.30 M in hexanes, 1.70 mL,
4.00 mmol). The resulting yellow solution was stirred for 2 min at
−95 °C prior to the addition of Ti(O-i-Pr)4 (1.18 mL, 4.00 mmol) in
THF (4 mL). The reaction mixture was stirred at −95 °C for 10 min,
at which time it turned orange, and then warmed to the appropriate
temperature (see Table 1, entries 6−15) over a period of 30 min. The
aldehyde (6.00 mmol) in THF (6 mL) was then added. After 3 h of
stirring at the same temperature, the reaction mixture was hydrolyzed
with a 2/1 mixture of a saturated aqueous NH4Cl solution and NH3
(10 mL). The layers were separated, and the aqueous layer was
extracted with CH2Cl2 (2 × 10 mL). The combined organic layers
were dried over anhydrous Na2SO4 and filtered, and the solvents were
removed in vacuo. Purification of the crude material by flash
chromatography afforded 2 and 3 (see Table 1, entries 6−15).
(1S)-4-Chloro-2-(trimethylsilyl)-1-((S)-1-tritylpyrrolidin-2-yl)buta-
2,3-dien-1-ols (7). The title compound was obtained following the
above procedure by the reaction between (3-chloroprop-1-ynyl)-
trimethylsilane (0.32 mL, 2.00 mmol) and (S)-N-tritylprolinal
(4; 0.82 g, 2.40 mmol). Purification by flash chromatography (4.9%/
0.1% EtOAc/Et3N/cyclohexane) afforded a mixture of 7a and 7b
(0.58 g, 7a:7b = 50:50, 60%). Further purification by flash
chromatography (4.9%/0.1% EtOAc/Et3N/cyclohexane) gave analyti-
cally pure 7a as a white amorphous solid, while a pure sample of 7b
could not be obtained.
20
Data for 9a are as follows. Mp: 58−59 °C. [α]D = −46.0° (c =
1
1.42 in CHCl3). H NMR (CDCl3, 400 MHz, 25 °C): δ 7.56 (d, J =
7.3 Hz, 6 H), 7.26 (t, J = 7.6 Hz, 6 H), 7.17 (t, J = 7.1 Hz, 3 H), 4.25
(dd, J = 8.3, 1.8 Hz, 1 H), 4.20 (d, J = 8.3 Hz, 1 H), 3.78 (ddd, J = 8.8,
3.8, 2.0 Hz, 1 H), 3.30 (dt, J = 12.4, 8.5 Hz, 1 H), 3.02 (ddd, J = 11.9,
8.7, 3.0 Hz, 1 H), 2.90 (bs, 1 H), 1.60−1.54 (m, 1 H), 1.36−1.32
(m, 1 H), 1.03−0.98 (m, 1 H), 0.36−0.29 (m, 1 H), 0.20 (s, 9 H). 13C
NMR (CDCl3, 100 MHz, 25 °C): δ 145.0, 129.8, 127.7, 126.3, 100.8,
93.3, 77.8, 77.3, 61.6, 52.2, 50.0, 25.3, 24.7, −0.1. IR (CHCl3): ν 3460,
3056, 2957, 2361, 2178, 1596, 1489, 1447, 1250, 1010, 844, 758, 707
cm−1. Anal. Calcd for for C30H34ClNOSi: C, 73.82; H, 7.02; N, 2.87.
Found: C, 74.02; H, 7.02; N, 2.67.
Data for 9b are as follows. Mp: 53−54 °C. [α]D20 = −44.8° (c = 0.93
in CHCl3). 1H NMR (CDCl3, 400 MHz, 25 °C): δ 7.56 (d, J = 7.6 Hz,
6 H), 7.26 (t, J = 7.6 Hz, 6 H), 7.18 (t, J = 7.2 Hz, 3 H), 4.27 (d, J = 9.4
Hz, 1 H), 4.23 (bd, J = 9.9 Hz, 1 H), 3.92−3.88 (m, 1 H), 3.28 (ddd, J =
12.1, 9.3, 7.6 Hz, 1 H), 3.07 (ddd, J = 11.8, 8.3, 2.8 Hz, 1 H), 2.99 (bs,
1 H), 1.55−1.45 (m, 1 H), 1.39−1.26 (m, 1 H), 1.14−1.06 (m, 1 H),
0.30−0.18 (m, 1 H), 0.10 (s, 9 H). 13C NMR (CDCl3, 100 MHz,
25 °C): δ 144.8, 129.8, 127.7, 126.4, 99.5, 93.4, 79.2, 78.5, 62.3, 52.9,
52.8, 25.3, 25.2, −0.2. IR (CHCl3): ν 3453, 3058, 2958, 2180, 1596,
1489, 1448, 1250, 1009, 845, 759, 708 cm−1. HMRS (ESI): m/z calcd
for C30H34ClNOSi + H+ 486.2014 [M + H+], found 486.2009.
Data for 7a are as follows. Mp: 115 °C dec. [α]D20 = −9.8° (c = 1.24
in CHCl3). 1H NMR (CDCl3, 400 MHz, 25 °C): δ 7.55 (d, J = 7.3 Hz,
6 H), 7.27 (t, J = 7.6 Hz, 6 H), 7.18 (t, J = 7.2 Hz, 3 H), 6.07 (d, J =
2.8 Hz, 1 H), 4.66 (t, J = 2.8 Hz, 1 H), 3.56 (ddd, J = 8.8, 6.0, 3.0 Hz,
1 H), 3.25 (ddd, J = 12.1, 10.8, 6.8 Hz, 1 H), 3.07 (ddd, J = 11.2, 7.8,
2.5 Hz, 1 H), 2.96 (bs, 1 H), 1.73−1.63 (m, 1 H), 1.33−1.25 (m, 1 H),
1.16−1.07 (m, 1 H), 0.14−0.01 (m, 1 H), −0.11 (s, 9 H). 13C NMR
(CDCl3, 100 MHz, 25 °C): δ 202.5, 144.5, 129.9, 127.8, 126.5, 113.1,
88.5, 78.3, 73.4, 63.9, 53.5, 26.0, 25.0, −1.4. IR (CHCl3): ν 3468, 3084,
3057, 2955, 2874, 1935, 1596, 1489, 1447, 1366, 1320, 1250, 1217,
1104, 1012, 904, 842, 758, 745, 708, 629 cm−1. Anal. Calcd for
C30H34ClNOSi: C, 73.82; H, 7.02; N, 2.87. Found: C, 73.70; H, 7.17;
N, 2.81.
ASSOCIATED CONTENT
■
S
* Supporting Information
Text and figures giving experimental procedures for com-
pounds 3 and the determination of the configurations of
1
compounds 9a,b, H and 13C spectra of all new analytically
1
pure compounds, and H spectra for the determination of the
er of 2 with Eu(hfc)3. This material is available free of charge
via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
1
Data for 7b are as follows. H NMR (CDCl3, 400 MHz, 25 °C): δ
Corresponding Author
*Fax: (+33) 144-27-75-67. E-mail: fabrice.chemla@upmc.fr
(F.C.); franck.ferreira@upmc.fr (F.F.).
7.55 (d, J = 7.3 Hz, 6 H), 7.27 (t, J = 7.6 Hz, 6 H), 7.18 (t, J = 7.2 Hz,
3 H), 5.91 (d, J = 2.6 Hz, 1 H), 4.74 (t, J = 2.7 Hz, 1 H), 3.57 (ddd, J =
8.8, 5.7, 3.0 Hz, 1 H), 3.23 (ddd, J = 12.1, 9.8, 7.0 Hz, 1 H), 3.06 (ddd,
J = 11.4, 8.1, 2.5 Hz, 1 H), 2.93 (bs, 1 H), 1.61−1.51 (m, 1 H), 1.30−
1.21 (m, 1 H), 1.13−1.03 (m, 1 H), 0.14−0.01 (m, 1 H), −0.06 (s, 9 H).
13C NMR (CDCl3, 100 MHz, 25 °C): δ 202.6, 144.5, 129.9, 127.8,
126.5, 113.4, 87.7, 78.3, 73.7, 63.9, 53.5, 26.1, 25.0, −1.2. HMRS
(ESI): m/z calcd for C30H34(35Cl)NOSi + H+ 488.2176 [M + H+],
Present Address
†Universite
́
Saint-Joseph, Dep
Sciences, Campus des Sciences et Technologies Mar Roukos-
Mkalles, P.O. Box 11-514, Riad el Solh Beirut 1107 2050,
Lebanon.
́ ́
artement de Chimie, Faculte des
̀
4883
dx.doi.org/10.1021/om300420q | Organometallics 2012, 31, 4876−4885

Organometallics
Article
Tetrahedron 1995, 51, 11681−11692. (c) Tamaru, Y.; Goto, S.;
Tanaka, A.; Shimizu, M.; Kimura, M. Angew. Chem., Int. Ed. 1996, 35,
878−880. (d) Tomooka, K.; Yamamoto, H.; Nakai, T. Liebigs Ann./
Recl. 1997, 1275−1281. (e) Bertrand, M. P.; Feray, L.; Nouguier, R.;
Perfetti, P. Synlett 1999, 1148−1150. (f) Poisson, J.-F.; Normant, J. F.
Org. Lett. 2001, 3, 1889−1891. (g) Normant, J. F.; Poisson, J. F. J. Am.
Chem. Soc. 2001, 123, 4639−4640.
(24) For allenyl lithiums, see: (a) Hoppe, D.; Dreller, S.; Dyrbusch,
M. Synlett 1991, 397−400. (b) Marshall, J. A.; Wolf, M. A.; Wallace, E.
M. J. Org. Chem. 1997, 62, 367−371. (c) Reich, H. J.; Holladay, J. E.;
Walker, T. G.; Thompson, J. L. J. Am. Chem. Soc. 1999, 121, 9769−
9780. (d) Hoppe, D.; Christoph, G. In The Chemistry of Organolithium
Compounds; Rappoport, Z., Marek, I., Eds.; Wiley: Chichester, U.K.,
2004; Vol. 1, pp 1055−1164.
(25) For allenyl palladiums, see: (a) Elsevier, C. J.; Stehouwer, P. M.;
Westmijz, H.; Vermeer, P. J. Org. Chem. 1983, 48, 1103−1105.
(b) Marshall, J. A.; Wolf, M. A. J. Org. Chem. 1996, 61, 3238−3239.
(c) Marshall, J. A.; Adams, N. D. J. Org. Chem. 1998, 63, 3812−3813.
(d) Marshall, J. A.; Adams, N. D. J. Org. Chem. 1999, 64, 5201−5204.
(e) Mandai, T. In Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E., Ed.; Wiley: New York, 2002; Vol. 2, pp 1827−
1832. (f) Wei, S.; Guochen, J.; Shengming, M. Org. Lett. 2009, 11,
117−120.
(26) For allenyl stannanes and allenyl indiums, see: (a) Marshall, J.
A.; Wang, X.-J. J. Org. Chem. 1992, 57, 1242−1252. (b) Marshall, J. A.;
Perkins, J. J. Org. Chem. 1994, 59, 3509−3511. (c) Marshall, J. A.;
Palovich, M. R. J. Org. Chem. 1997, 62, 6001−6005. (d) Marshall, J. A.;
Palovich, M. R. J. Org. Chem. 1998, 63, 3701−3705. (e) Marshall, J. A.;
Johns, B. A. J. Org. Chem. 1998, 63, 7885−7892. (f) Marshall, J. A.;
Adams, N. D. J. Org. Chem. 1998, 63, 3812−3813. (g) Marshall, J. A.;
Grant, C. M. J. Org. Chem. 1999, 64, 696−697.
Author Contributions
The manuscript was written through contributions of all authors.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We wish to cordially thank the Lebanese National Concil for
Scientific Research for a grant to J.B.
■
REFERENCES
■
(1) (a) Epzstein, R. The Formation and Transformation of Allenic
and α-Acetylenic Carbanions. In Comprehensive Carbanions Chemistry;
Buncel, E., Durst, T., Eds.; Elsevier: Amsterdam, 1984; Vol. B, pp
107−175. (b) Yamamoto, H. Propargyl and Allenyl Organometallics.
In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: London, 1991; Vol. 2, pp 81−98.
(2) Marshall, J. A.; Gung, B. W.; Grachan, M. L. In Modern Allene
Chemistry; Krause, N., Hashmi, A. S. K., Eds.; Wiley-VCH: Weinheim,
Germany, 2004; Vol. 1, pp 493−592.
(3) Marshall, J. A. Chem. Rev. 2000, 100, 3163−3186.
(4) Panek, J. S. In Comprehensive Organic Synthesis; Schreiber, S. L.,
Ed.; Pergamon Press: Oxford, U.K., 1991; Vol. 1, pp 595.
(5) Brandsma, L.; Zwikker, J. W.; Bilthoven, N. Sci. Synth. 2006, 8a,
271−283.
(6) Ding, C.-H.; Hou, X.-L. Chem. Rev. 2011, 111, 1914−1937.
(7) (a) Achmatowicz, M.; Hegedus, L. S. J. Org. Chem. 2004, 69,
2224−2229. (b) Marshall, J. A. Chem. Rev. 1996, 96, 31−47.
(8) Marshall, J. A., Synthesis and Reactions of allenylzinc compounds.
In The Chemistry of Organozinc Compounds; Rappoport, Z., Marek, I.,
Eds.; Wiley: New York, 2006; Vol. 1, pp 421−455.
(9) Marshall, J. A. J. Org. Chem. 2007, 72, 8153−8166.
(27) For allenyl silanes, see: (a) Kobayashi, S.; Nishio, K. J. Org.
Chem. 1994, 59, 6620−6628. (b) Kobayashi, S.; Nishio, K. J. Am.
Chem. Soc. 1995, 117, 6392−6393. (c) Kobayashi, S.; Yasuda, M.;
Nishio, K. Synlett 1996, 153−154. (d) Marshall, J. A.; Adams, N. D. J.
Org. Chem. 1997, 62, 8976−8977. (e) Marshall, J. A.; Maxson, K. J.
Org. Chem. 2000, 65, 630−633. (f) Buckle, M. J. C.; Fleming, I.; Gil,
S.; Pang, K. L. C. Org. Biomol. Chem. 2009, 2, 749−769. (g) Curtis-
Long, M. J.; Aye, Y. Chem. Eur. J. 2009, 15, 5402−5416.
(10) Harada, T.; Katsuhita, T.; Osada, A.; Iwazaki, K.; Maejima, K.;
Oku, A. J. Am. Chem. Soc. 1996, 118, 11377−11390.
(11) Zweifel, G.; Hahn, G J. Org. Chem. 1984, 49, 4565−4567.
(12) For triorganozincated propargylamines, see: (a) Bernaud, F.;
Vrancken, E.; Mangeney, P. Synlett 2004, 1080−1082. (b) Vrancken,
E.; Alouane, H.; Ger
1770−1779.
́
ard, H.; Mangeney, P. J. Org. Chem. 2007, 725,
(13) Hameury, T.; Guillemont, J.; Van Hijfte, L; Bellosta, V.; Cossy,
J. Org. Lett. 2009, 11, 2397−2400.
(28) (a) Hoffmann, R. W.; Dress, R. K.; Ruhland, T.; Wenzel, A.
Chem. Ber. 1995, 128, 861−870. (b) Dress, R. K.; Rolle, T.; Hoffmann,
R. W. Chem. Ber. 1995, 128, 673−677.
(14) For an example of transmetalation of an allenyl Grignard with
cerium chloride, see: Groth, U.; Kesenheimer, C.; Neidhofer, J. Synlett
̈
(29) (a) Kobrich, G.; Wagner, E. Chem. Ber. 1970, 103, 2515−2525.
̈
2006, 1859−1862.
(15) Place, P.; Vernier, C.; Gore, J. Tetrahedron 1981, 37, 1359−
1368.
(16) Favre, E.; Gaudemar, M. J. Organomet. Chem. 1975, 92, 17−25.
(17) Lai, C.; Soderquist, J. A. Org. Lett. 2005, 7, 5397−5400.
(18) Hernandez, E.; Burgos, C. H.; Alicea, E.; Soderquist, J. A. Org.
Lett. 2006, 8, 4089−4091.
(19) Fandrick, D. R.; Fandrick, K. R.; Reeves, J. T.; Tan, Z.; Johnson,
C. S.; Lee, H.; Song, J. J.; Yee, N. K.; Senanayake, C. H. Org. Lett.
2010, 12, 88−91.
(20) Oshiguro, O.; Ikeda, N.; Yamamoto, H. J. Org. Chem. 1982, 47,
2225−2227.
(21) Basu, A.; Thayumanavan, S. Angew. Chem., Int. Ed. 2002, 41,
716−738.
(b) Kirihara, M.; Takuwa, T.; Takizawa, S.; Momose, T.; Nemoto, H.
Tetrahedron 2000, 56, 8275−8280. (c) Braun, M. Lithium carbenoids.
In The Chemistry of Organolithium Compounds; Rappoport, Z., Marek,
I., Eds.; Wiley: Chichester, U.K., 2004; Vol. 1, pp 829−891. (d) Li, Q.
R.; Gu, C. Z; Yin, H. Chin. J. Chem. 2006, 24, 72−78. (e) Mae, M.;
Hong, J. A.; Xu, B.; Hammond, G. B. Org. Lett. 2006, 8, 479−482.
(30) Boche, G.; Lohrenz, J. C. W. Chem. Rev. 2001, 101, 697−756.
(31) (a) Chemla, F.; Bernard, N.; Ferreira, F.; Normant, J. F. Eur. J.
Org. Chem. 2001, 3295−3300. (b) Chemla, F.; Ferreira, F.; Hebbe, V.;
Stercklen, E. Eur. J. Org. Chem. 2002, 1385−1391. (c) Palais, L.;
Chemla, F.; Ferreira, F. Synlett 2006, 1039−1042. (d) Botuha, C.;
Chemla, F.; Ferreira, F.; Per
1552−1567. (e) Ferreira, F.; Botuha, C.; Chemla, F.; Per
Chem. Soc. Rev. 2009, 38, 1162−1186. (f) Botuha, C.; Chemla, F.;
Ferreira, F.; Louvel, J.; Perez-Luna, A. Tetrahedron: Asymmetry 2010, 21,
1147−1153.
́
ez-Luna, A.; Roy, B. New J. Chem. 2007, 31,
́
ez-Luna, A.
(22) For allenyl titaniums, see: (a) Hoffmann, R. W.; Lanz, J.; Tarara,
G.; Hoppe, D. Angew. Chem. Int. Engl. 1987, 26, 1145−1146.
(b) Hoppe, D.; Dreller, S.; Dyrbusch, M. Synlett 1991, 397−400.
(c) Sato, F.; Urabe, H.; Okamoto, S. Chem. Rev. 2000, 100, 2835−
2886. (d) Song, Y.; Okamoto, S.; Sato, F. Org. Lett. 2001, 3, 3543−3545.
́
(32) Hoffmann, R. W. Top. Stereochem. 2010, 26, 165−188.
(33) (a) Hoffmann, R. W.; Lanz, J.; Metternich, R.; Tarara, G.;
Hoppe, D. Angew. Chem., Int. Ed. 1987, 26, 1145−1146. (b) Hoffmann,
R. W.; Julius, M.; Chemla, F.; Ruhland, T.; Frenzen, G. Tetrahedron
1994, 50, 6049−6060. (c) Hoffmann, R. W.; Harbach, R. J. Liebigs Ann.
Chem. 1992, 725−730.
(34) Hirsch, R.; Hoffmann, R. W. Chem. Ber. 1992, 125, 975−982.
(35) Schuster, H. F.; Coppola, G. M. In Allenes in Organic Synthesis;
Wiley: New York, 1984; pp 57−88.
(e) Schultz-Fademrecht, C.; Wibbeling, B.; Frolich, R.; Hoppe, D. Org.
̈
Lett. 2001, 8, 12221−1224. (f) Song, Y.; Okamoto, S.; Sato, F.
Tetrahedron Lett. 2003, 44, 2113−2115. (g) Apeller, D. C.;
Hammerschmidt, F. J. Am. Chem. Soc. 2008, 130, 2329−2335.
(23) For allenyl/propargyl zincs, see: (a) De Graff, G.; Boersma, J.;
Van Koten, G.; Elsevier, C. J. J. Organomet. Chem. 1989, 378, 115−
124. (b) Utimoto, K.; Shinokubo, H.; Miki, H.; Yokoo, T.; Oshima, K.
4884
dx.doi.org/10.1021/om300420q | Organometallics 2012, 31, 4876−4885

Organometallics
Article
(36) For the preparation of (3-chloroprop-1-ynyl)trimethylsilane,
see: (a) Verkruijsse, H. D.; Brandsma, L. Synth. Commun. 1990, 20,
3375−3378. (b) Komarov, N. N.; Shostakovskii, M. F.; Astaf’eva, L. N.
J. Gen. Chem. USSR 1961, 1963−1964.
(37) Ferreira, F.; Denichoux, A.; Chemla, F.; Bejjani, J. Synlett 2004,
2051−2065.
(38) (a) Compounds 2 were fully characterized.31a (b) For the
characterization of analytically pure compounds 3 see the Supporting
Information.
(39) For example, we have recently shown that (3-(methoxymethoxy)
allenyl)zinc bromide is less configurationally stable in the presence of
TMEDA: Chemla, F.; Ferreira, F. Synlett 2004, 2613−2616.
(40) For recent reviews on the structure and reactivity of
organolithium compounds, see: (a) Gessner, V. H.; Daschlein, C.;
̈
Strohmann, C. Chem. Eur. J. 2009, 15, 3320−3334. (b) Capriati, V.;
Florio, S. Chem. Eur. J. 2010, 16, 4152−4162.
(41) The reaction of propargyl and allenyl metals with non-
coordinating electrophiles, such as water, is assumed to proceed by an
acyclic SE2 process. See for example: (a) Katsuhira, T.; Harada, T.;
Maejima, K.; Osada, A.; Oku, A. J. Org. Chem. 1993, 58, 6166−6168.
(b) Harada, T.; Katsuhira, T.; Osada, A.; Iwazaki, K.; Maejima, K.;
Oku, A. J. Am. Chem. Soc. 1996, 118, 11377−11390.
(42) For relevant examples on reactions of propargyl and allenyl
metals with aldehydes following an SE2′ mechanism, see: (a) Favre, E.;
Gaudemar, M. J. Organomet. Chem. 1974, 76, 297−304. (b) Favre, E.;
Gaudemar, M. J. Organomet. Chem. 1974, 76, 305−317. (c) Creary, X.
J. Am. Chem. Soc. 1977, 99, 7632−7639. (d) Pearson, N. R.; Hahn, G.;
Zweifel, G. T. J. Org. Chem. 1982, 47, 3364−3366.
(43) (a) Saniere-Karila, M.; Capmau, M. L.; Chodkiewicz, W. Bull.
Soc. Chim. Fr. 1973, 3371−3376. (b) Ishiguro, M.; Ikeda, N.;
Yamamoto, H. J. Org. Chem. 1982, 47, 2227−2229.
(44) Okamoto, S. J. Synth. Org. Chem. 2001, 59, 1204−1211.
(45) Moreau, J. L.; Gaudemar, M. Bull. Soc. Chim. Fr. 1970, 2171−
2174.
(46) The conversion rate CG of a racemic chiral organometallic is
related to CR (conversion rate of R enantiomer), CS (conversion rate of
S enantiomer), and s by CG = (CR + CS)/2 with CR = 1 − (1 − CS)s.
The enantiomeric ratio of the remaining organometallic at a given CG
is er = (1 − CS)/(1 − CR) where the R enantiomer of the
organometallic is consumed faster than the S enantiomer.34
(47) Kobrich, G.; Trapp, H. Chem. Ber. 1966, 99, 680−688.
(48) For the addition of allyl metals to (+)-camphor, see: Dimitrov,
V.; Simona, S.; Kostova, K. Tetrahedron 1996, 52, 1699−1706.
(49) Bejjani, J.; Chemla, F.; Audouin, M. J. Org. Chem. 2003, 68,
9747−9752.
(50) Guijarro, A. Dynamic Behavior of Organozinc Compounds. In
The Chemistry of Organozinc Compounds; Rappoport, Z., Marek, I.,
Eds.; Wiley: New York, 2006; Vol. 1, pp 193−236.
(51) Ferreira, F.; Audouin, M.; Chemla, F. Chem. Eur. J. 2005, 11,
5269−5278.
(52) (a) Marshall, J. A.; Schaaf, G. M. J. Org. Chem. 2001, 66, 7825−
7831. (b) Poisson, J. F.; Chemla, F.; Normant, J. F. Synlett 2001, 2,
305−307. (c) Unger, R.; Weisser, F.; Chinkov, N.; Stanger, A.; Cohen,
T.; Marek, I. Org. Lett. 2009, 11, 1853−1856. (d) Unger, R.; Cohen, T .;
Marek, I. Tetrahedron 2010, 66, 4874−4881.
(53) Ikeda, N.; Arai, I.; Yamamoto, H. J. Am. Chem. Soc. 1986, 108,
483−486.
(54) Suffert, J. J. Org. Chem. 1989, 54, 509−510.
4885
dx.doi.org/10.1021/om300420q | Organometallics 2012, 31, 4876−4885