Chiral Lithium Amido Zincates for Enantioselective 1,2-Additions: Auto-assembling Reagents Involving a Fully Recyclable Ligand

Article abstract of DOI:10.1002/chem.201802044

A methodology consisting in carrying out enantioselective nucleophilic 1,2-additions (ee values up to 97 %) from cheap, easily accessible, and never described before, chiral lithium amido zincates is presented. These multicomponent reactants auto-assemble when mixing, in a 1:1 ratio, a homoleptic diorganozinc (R₂Zn) with a chiral lithium amide (CLA). The latter, obtained after a single reductive amination, plays the role of the chiral inductor and is fully recoverable thanks to a simple acid–base wash, allowing being recycled and re-use without loss of stereochemical information.

Full text of DOI:10.1002/chem.201802044

A Journal of
Accepted Article
Title: Chiral Lithium Amido Zincates for Enantioselective 1,2-Additions:
Auto-assembling Reagents Involving a Fully Recyclable Ligand
Authors: Anne Harrison-Marchand, Mathieu Rouen, Pauline
Chaumont, Gabriella Barozzino-Consiglio, and Jacques
Maddaluno
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To be cited as: Chem. Eur. J. 10.1002/chem.201802044
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Chiral Lithium Amido Zincates for Enantioselective 1,2-Additions:
Auto-assembling Reagents Involving a Fully Recyclable Ligand
Mathieu Rouen, Pauline Chaumont, Gabriella Barozzino-Consiglio, Jacques Maddaluno, and Anne
Harrison-Marchand*
Abstract: A methodology consisting in carrying out enantioselective
nucleophilic 1,2-additions (ees up to 97%) from cheap, easily
accessible, and never described before, chiral lithium amido zincates
is presented. These multicomponent reactants auto-assemble when
mixing, in a 1 : 1 ratio, a homoleptic diorganozinc (R2Zn) with a chiral
lithium amide (CLA). The latter, obtained after a single reductive
amination, plays the role of the chiral inductor and is fully
recoverable thanks to a simple acid-base wash, allowing being
recycled and re-use without loss of stereochemical information.
i. exploring and taking advantage of the very promising, but
still understudied, potential of simple chiral lithium zincates as
powerful nucleophiles, both in terms of reactivity and inductions.
ii. developping an attractive methodology for an easy use of
these tools on a large scale and involving a cheap and
recyclable chiral inductor.
For the sake of simplicity and low cost, we focused on chiral
lithium triorganozincates[6a] that auto-assemble when mixing
equimolar amounts of
commercially available, and
a
homoleptic R2Zn, preferably
chiral organolithium Y*-Li
At the turn of this century, a sustained attention has been
devoted to the use, in organic synthesis, of organo(bi)metallic
“ate-complex” species, which combine, in a synergic operation,
specific properties of two organometallic compounds. Long
standing problems related to the chemo-, regio-, and
stereoselectivities of general reactions, such as the
deprotonation or the creation of C−C bonds, have been
elegantly solved thanks to these tools.[1] Several combinations
such as those associating two of the Li-, Mg-, Al-, and Zn-
derivatives have thus emerged, having shown a strong capacity
to both effectively allow dehalogenative metalations[1],[2] or react
as bases for aromatic deprotonation reactions.[1],[3] But less is
a
requiring little synthetic steps. The applications currently
reported in literature, and involving such species in nucleophilic
1,2-additions towards carbonyl derivatives, rely on the
combination of a dialkylzinc with a chiral lithium alkoxide (Y*-Li =
R*O-Li).[5] We preferred combining a R2Zn to a chiral lithium
(mono) amide (Y*-Li = R*2N-Li, CLA). To our knowledge, only a
single study by Falorni et al. involving such a chiral amido
zincate is known to date,[6f] and unfortunately, this work afforded
disappointing enantioselectivities. Nevertheless, the undeniable
advantage brought by using a lithiated amido partner is that after
hydrolysis of the nucleophilic addition reaction of the
corresponding lithium amido zincate on the carbonyl substrate,
expected to provide an enantioenriched alcohol, the recovery of
the chiral inductor as an amine requires no more than a simple
acid-base wash. This practical operation, not possible engaging
R*O-Li, is of importance because it ensures to re-use efficiently
the chiral ligand and thus provide a genuine turnover to the
chiral inductor (Scheme 1).
known
multicomponent reactants, and very few studies involving chiral
lithium and
magnesates,[1],[4] zincates[1],[4a,b],[5],[6]
about
the
nucleophilic
properties
of
these
aluminates[1],[4a,b],[7] to run enantioselective nucleophilic additions
are mentioned in the literature. Yet, this underexplored side of
ate-complexes reactivity deserves attention, if we refer to
Armstrong et al’s statements presented in a Nature Chem.
Highlight and appropriately entitled: “Chiral nucleophiles: Ate
complex is the answer”.[8] The results presented in this paper
echo this call by depicting the use of chiral lithium zincates to
perform enantioselective nucleophilic 1,2-additions onto
electrophilic carbonyl derivatives.
chiral lithium
O
amidozincate
R2
R1
R2(R*2N)ZnLi
R2Zn
3
2
Organozinc chemistry is probably the most common
hanging-point to open new asymmetric organometallic routes.
This is assigned to the dramatic change of reactivity when going
from “unreactive” sp linear R2Zn to “reactive” sp2 or sp3 zinc
complexes formed thanks to coordinative interactions between
lone pairs of a chiral ligand and empty orbitals of the zinc atom
in R2Zn.[9] Given that literature is extremely profuse about
examples of chiral σ-donor coordinating entities (such as
diamines) providing dative covalent zinc complexes,[10] it
appears necessary to make it clear at this point that we are not
aiming to propose “one more” chiral σ-donor ligand for neutral
organozinc species. The work and results reported here are
related to a fully different goal and consists in:
R*2N-Li
R*2N
+
1
O
n-BuLi
R1
R2
R*2NH
R
"M"
1-H
OH
*
aqueous
acid-base
wash
("M" = Li and Zn)
R2
R1
R
Scheme 1. Recycling of
a CLA type inductor (R*2N-Li 1) during 1,2-
nucleophilic additions of a chiral lithium amido zincate on R1R2C=O.
Our study started with diethylzinc Et2Zn 2a as the homoleptic
organozinc reference entity. We also took advantage of our
experience in the field of running enantioselective nucleophilic
additions on aromatic aldehydes using dilithiated mixed
aggregates[11] to choose ortho-tolualdehyde 3a (R1 = o-Tol and
R2 = H) as model aromatic electrophile. In order to ensure that
the entire process is carried out under anhydrous conditions, all
experiments were run with a slight excess of organo(bi)metallic
reagent (1.2 equiv) relative to aldehyde (1 equiv).
Dr M. Rouen, P. Chaumont, Dr G. Barozzino-Consiglio, Dr J. Maddaluno
and Dr A. Harrison-Marchand
Normandie Université, UNIROUEN, INSA de Rouen, CNRS
Laboratoire COBRA (UMR 6014 & FR 3038) - 76000 Rouen, France
E-mail: anne.harrison@univ-rouen.fr
Supporting information for this article is given via a link at the end of the
document.((Please delete this text if not appropriate))
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Table 1. Enantioselective nucleophilic 1,2-additions of Et2(1a-l)ZnLi onto 3a
NMe
O
S
R
S
R
R
N
H
N
H
N
H
entry
CLA 1
Yield (%)
Ee (%)[a],[b]
1a-H
1b-H
1c-H
1
2
1a
1b
1c
1d
1e
1f
87
26
65
69
78
87
38
47
66
24
51
61
45
23
30
19
18
11
23
22[c]
70
81
11
90
N
3
R
R
R
N
H
N
H
N
H
4
1f-H
1d-H
1e-H
5
SMe
NMe2
OMe
6
R
R
R
N
H
N
H
N
H
7
1g
1h
1i
1h-H
1g-H
1i-H
8
9
O
O
O
10
11
12
1j
R
R
R
N
H
N
H
N
H
1k
1l
1l-H
1j-H
1k-H
O
[a]Determined by chiral HPLC; [b]major alcohol: 4-R; [c]major alcohol: 4-S.
H
In contrast, amides 1d-1i (entries 4 to 9) that result from a
simple reductive amination synthetic sequence, all led to 4 in
satisfying to good yields (38% to 87%). Among all, CLA 1i
showed the best inductive effect, providing 4 in a 66% yield and
70% ee in favor of alcohol R (entry 9). Fine tuning of the OR
appendage on the aromatic ring led us to replace the methoxy
group of 1i by Oi-Pr (1j), Ot-Bu (1k) and Oi-Bu (1l) (Scheme 2,
top). These three new CLAs, obtained following the same easy
procedure than 1i (see pages 7S and 8S in SI),[12b] have been
used in the enantioselective nucleophilic 1,2-addition of 3a in
Et2O in the same conditions as before (Scheme 2, bottom). The
related results gathered in Table 1 (entries 10 to 12) show that
increasing the steric hindrance of the OR appendage is
detrimental on both yield and induction if too crowded, as
observed for OR = Ot-Bu (1k, entry 11). A balanced increase of
the congestion can however have beneficial consequences on
the induction as noticed with 1j for which OR = Oi-Pr (entry 10)
and that leads to an 81% ee. Unfortunatly, with this CLA, the
reactivity remains altered, dropping to 24%. A good compromise
was found with 1l, of which OR = Oi-Bu (entry 12), and that
leads, after two hours of reaction to enantioenriched alcool 4-R
in 61% yield and 90% ee.
OH
Et
Et2Zn 2a
3a
(1equiv)
n-BuLi
(1.2 equiv)
(1.2 equiv)
Et2(1a-l)ZnLi
1a-l-H
1a-l
(1.2 equiv)
(1.2 equiv)
solvent
-78°C, 2 h
(solvent = THF, Et2O or Tol)
solvent
-20°C
solvent
-20°C, 30 min
-78°C, 30 min
4
20 min
Scheme 2. Enantioselective nucleophilic 1,2-additions of Et2(1a-l)ZnLi onto 3a.
Parameters that have been preliminarily varied are the
nature of CLA 1 and the solvent. Thus, CLAs issued from nine
chiral amines (1a-H to 1i-H, Scheme 2) have been first taken
into consideration (for the preparation of amines 1a-H to 1i-H,
see ref 12 and General Procedure pages 4S to 6S in SI). They
all derive from the very cheap, and commercially available in its
two enantiomeric form, α-methylbenzyl amine, the
R
configuration being randomly chosen for the study. The auto-
assembling of the lithium amido zincate complexes was
preliminarily performed at –20°C, adding successively, and with
an interval of 20 minutes, n-BuLi, then 2a, to amine 1-H in a
1:1:1 ratio (Scheme 2, bottom). After cooling down the reaction
mixture to –78°C, electrophile 3a was introduced. In a first series
of experiments, the efficiency of nine ate complexes (involving
amides 1a to 1i) has been evaluated in three types of solvent,
that are tetrahydrofuran (THF), diethylether (Et2O) and toluene
The scope of application of the lithium amido zincates
incorporating 1l was then explored by first keeping the Et2Zn
partner while varying the nature of the aldehyde (Scheme 3).
(Tol), while fixing
a two hours reaction time and the
concentration at c = 0.034 M (see General Procedure page 9S in
SI). Results obtained (see Table 1S page 15S in SI) put into
evidence that THF is not an appropriate solvent, alcohol 4 being
formed in this solvent with both low yields and low ees, whatever
the amide implicated. By contrast, 4 is obtained in acceptable to
good yields in either Et2O or Tol, but higher ees are generally
obtained in Et2O (Table 1, entries 1 to 9). These results
demonstrate, for the first time, that chiral triorganozincates of
which the inductor is an amido ligand can behave as efficient
enantioselective nucleophiles toward carbonyl substrates.
It turns out that in Et2O, CLA derived from 3-aminopyrrolidine
1a-H, tetrahydrofuran 1b-H and tetrahydrothiophene 1c-H
(Table 1, entries 1 to 3, respectively), did not provide here the
highest ees while they behaved as good chiral ligands (ees up to
80%) for the enantioselective 1,2 and 1,4-additions with [Li,Li]
mixed aggregates.[11],[12]
CF3
O
O
OMe O
H
H
H
H
O
O
3a
3b
3c
Et
O
CN
O
O
8
H
Ph
H
MeO2C
3e : ortho
3f : para
3d
3g
O
i-Bu
O
R
H
Et2Zn 2a
n-BuLi
3a-g
(1equiv)
OH
R
Ph
N
(1.2 equiv) (1.2 equiv)
1l
H
Et2(1l)ZnLi
R
Et
(1.2 equiv)
-20°C, 30 min
-78°C, 30 min
Et2O
-78°C, 3 h
Et2O
-20°C
20 min
Et2O
1l-H
(1.2 equiv)
4-10
Scheme 3. Nucleophilic 1,2-additions of Et2(1l)ZnLi onto 3a-g in Et2O.
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Table 2. Yields and ees obtained reacting Et2(1l)ZnLi onto 3a-g in Et2O.
The nature of the organozinc partner, homoleptic dialkyl- and
diaryl- zincs (2a to 2f, Scheme 4), has been modulated next and
the corresponding ates complexes reacted on o-TolCHO 3a in
Et2O keeping 1l as the chiral ligand. The related results gathered
in Table 3 put once more into evidence the flexibility of the
methodology in alkylation since good (76%) to excellent (up to
97%) ees were measured, whatever the alkyl group of R2Zn. The
main difference is at the level of the yields for which logically,
more hindered R appendages such as i-Pr or c-C6H11 require
longer times to complete the reaction. The case of Me2Zn is
particularly remarkable: not only it leads to one of the best ees
(95%) but also the reaction occurs in 41% yield, which is
probably a record since it is well known that, in ate complexes,
the Me group is hardly transferable.[13] With regards to arylation,
a preliminary essay led to a very encouraging 54% ee with
Ph2Zn. The major difficulty encountered with this reactant is its
insolubility in the reaction medium, which probably explains the
low yield (34%). We are currently working to find the best
conditions for this specific reaction.
entry
Aldehyde
Product
Yield (%)
Ee (%)[a],[b]
1
2
3
4
5
6
7
3a
3b
3c
3d
3e
3f
4
5
76
56
90
91
69
63
90
53
75
6
68
7
8[d]
64[c]
40[e]
83
9
3g
10
45[f]
[a]Determined by chiral HPLC; [b]major alcohol: R; [c]+36% of 3d; [d]8
corresponds to the cyclized benzofuranone formed in situ; [e]+60% of 3e;
[f]+55% of 3g.
Aromatic aldehydes (ArCHO) differently substituted on the
ortho position of the Ar appendage by either electrodonor (3a
and 3b) or electron-withdrawing (3c-f) groups have been
involved, including sensitive functions such as a cyano (3d) or
an ester group (3e and 3f). The chemoselectivity of the reaction
was also evaluated testing an enolizable aldehyde
(dihydrocinnamaldehyde 3g). Note that for this set of reactions
(Table 2), the time was increased to 3 hours.
Et2Zn
Me2Zn
n-Bu2Zn
i-Pr2Zn
(c-C6H11)2Zn
Ph2Zn
2a
2b
2c
2d
2e
2f
O
With respect to ortho-tolualdehyde 3a, changing the time did not
alter the enantiomeric excess (90% ee, entry 12 in Table 1 and
entry 1 in Table 2) but increased the yield by about 15% (76%
yield after 3 hours instead of 61% after 2 hours). The induction
level is maintained at 91% when switching the methyl group by a
methoxy at the ortho position (entry 2 in Table 2), at the expense
of a slight drop of the yield. An electron-withdrawing ortho-
substituent such as CF3 (3c, entry 3 in Table 2) did not show a
strong effect on the reactivity, that keeps in the range of 60 to
70% yield. However, the enantioselectivity drops by about 20%.
The other electron-withdrawing substituents such as a cyano (3d,
entry 4) or an ester (3e and 3f, entries 5 and 6) aryl substituent
led, satisfyingly, to the selective formation of products resulting
only from the 1,2-nucleophilic addition of Et2(1l)ZnLi on the
aldehyde. With regards to the cyano derivative, the results, both
in terms of yield and induction, are comparable with those
observed for CF3. With respect to the methoxycarbonyl
derivatives, the ortho isomer 3e led to a benzofuranone (8, 40%
yield) that results from the cyclization of the alkoxide
intermediate. Note that, by reaching a 90% ee, the level of
induction measured for this reaction is quite remarkable. We
checked that the low yield obtained with 3e was resulting from a
steric hindrance of the CO2Me group at the ortho position of the
reactive CHO group by engaging instead the para CO2Me
congener 3f. In this case, the nucleophilic addition, still observed
only on the CHO group, indeed took place with a higher 83%
yield but a lower 53% induction level. Another aspect of the
chemoselectivity was tested with an enolisable aldehyde (3g,
entry 6). Here again, only the formation of the product of 1,2-
alkylation on the CHO was observed in 45% yield, next to 55%
of starting material. We ensured that no competitive
deprotonation at the alpha position occurred by quenching the
reaction in the presence of deuteriated methanol. The NMR
analysis of the crude product put into evidence less than 2% of
deuteriated product.
i-Bu
O
H
3a
(1equiv)
OH
R2Zn 2a-f
n-BuLi
R
Ph
N
H
(1.2 equiv)
(1.2 equiv)
R
R2(1l)ZnLi
1l
Et2O
-20°C
20 min
Et2O
-20°C, 30 min
-78°C, 30 min
(1.2 equiv) Et2O
1l-H
(1.2 equiv)
-78°C, 3 h
4, 11-15
Scheme 4. Nucleophilic 1,2-additions of 2a-f(1l)ZnLi onto 3a in Et2O.
Table 3. Yields and ees obtained reacting 2a-f(1l)ZnLi onto 3a in Et2O.
entry
R2Zn
Product
Yield (%)
Ee (%)[a],[b]
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
4
76
41
66
52
71
34
90
95
89
97
76
54
11
12
13
14
15
[a]Determined by chiral HPLC; [b]major alcohol: R.
The last-but-not-least challenge in this study consisted in
examining the possibility of properly recycling the chiral amido
inductor. The nucleophilic addition of Et2(1l)ZnLi onto 3a, which
provides alcohol 4, was thus chosen to be repeated several
times from a single batch of 1l recycled by carrying out an acido-
basic wash after each essay. Because our aim is also to set up
a methodology adapted to large scales, the reactions were run
with up to 3 mmol of aldehyde instead of 0.75 mmol. This
change implied to increase slightly the excess of ate to 1.5 equiv
with respect to aldehyde. Results in Table 4 show that working
on larger scales leads to a limited decrease of the ee (80% ee
instead of 90%), a result that can most probably be improved
after adjustment of the experimental conditions. Nevertheless,
one can aver that the turn-over of the chiral inductor is excellent
since amine 1l-H is recovered with recycling rates over 95%,
without any loss of optical purity, neither of induction.
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Table 4. Yields and ees obtained reacting Et2(1l)ZnLi (1.5 equiv.) onto 3a in
Et2O after ligand recyclings.
109, 7111-7115; b) K. Soai, M. Nishi, Y. Ito, Chem. Lett. 1987, 2405-
2406; c) E. J. Corey, F. J. Hannon, Tetrahedron Lett. 1987, 28, 5233-
5236; d) S. Niwa, K. Soai, J. Chem. Soc., Perkin Trans. 1 1990, 937-
943; e) K. Soai, Y. Kawase, J. Chem. Soc., Perkin Trans. 1 1990, 3214-
3215; f) G. Chelucci, M. Falorni, G. Giacometli, Tetrahedron:
Asymmetry 1990, 1, 843-849; g) G. M. Ramos Tombo, E. Didier, B.
Loubinoux, Synlett 1990, 547-548; h) W. Oppolzer, R. N. Radinov,
Tetrahedron Lett. 1991, 32, 5777-5780; i) C. A. de Parrodi, E. Juaristi, L.
Quintero-Cortés, P. Amador, Tetrahedron: Asymmetry 1996, 7, 1915-
1918; j) S. Vyskocil, S. Jaracz, M. Smrcina, M. Sticha, V. Hanus, M.
Polasek, P. Kocovsky, J. Org. Chem. 1998, 63, 7727-7737; k) L. Tan,
C.-Y. Chen, R. D. Tillyer, E. J. J. Grabowski, P. J. Reider, Angew.
Chem. Int. Ed. 1999, 38, 711-713; l) A. M. DeBerardinis, M. Turlington,
L. Pu, Angew. Chem. Int. Ed. 2011, 50, 2368-2370.
19
entry
1l % recycle
1l [α]D
4 Yield (%)
4 Ee (%)[a],[b]
1
2
3
4
96
95
98
99
50,9
51.6
53.5
50.7
86
79
81
83
81
Quantitative
68
67
5
96
52.6
77
80
[a]Determined by chiral HPLC; [b]major alcohol: R.
In conclusion, we present here
a
new class of chiral
multicomponent nucleophiles, spontaneously auto-assembled,
to perform efficient enantioselective 1,2-additions on aldehydes.
Mainly alkylation reactions are reported in this work, and the
methodology is general at the level of both the nucleophilic alkyl
moieties, and of the electrophilic substrates. This study shows
that these new ate-complexes exhibit salient advantages such
as i) the chemoselectivity of the reaction, which targets the
aldehyde group even in the presence of other sensitive functions
such as esters and nitriles; ii) the usefulness of the new chiral
ligands that are not only very easily accessible but also
efficiently recovered, without loss of stereochemical information,
thanks to a simple acid-base wash, providing a genuine and
handy turnover to this chiral inductor.
[6]
For a definition of tetraorganozincate and triorganozincate, see a) D. R.
Armstrong, C. Dougan, D. V. Graham, E. Hevia, A. R. Kennedy,
Organometallics 2008, 27, 6063-6070. For use of tetraorganozincates
made of a chiral amido moiety, see: b) K. Soai, S. Niwa, Y. Yamada, H.
Inoue, Tetrahedron Lett. 1987, 28, 4841-4842; c) S. Niwa, K. Soai, J.
Chem. Soc., Perkin Trans.
1 1991, 2717-2720; d) D. Pini, A.
Mastantuono, G. Uccello-Barretta, A. Iuliano, P. Salvadori, Tetrahedron
1993, 49, 9613-9624; e) K. Fuji, K. Tanaka, H. Miyamoto, Chem.
Pharm. Bull. 1993, 41, 1557-1561; f) J. Eriksson, P. I. Arvidsson, Ö.
Davidsson, Chem. Eur. J. 1999, 5, 2356-2361. For use of
triorganozincates made of a chiral amido moiety, see g) G. Chelucci, S.
Conti, M. Falorni, G. Giacomelli, Tetrahedron 1991, 47, 8251-8258; h)
D. R. Armstrong, W. Clegg, S. H. Dale, J. Garcia-Alvarez, R. W.
Harrington, E. Hevia, G. W. Honeyman, A. R. Kennedy, R. E. Mulvey, C.
T. O’Hara, Chem. Commun. 2008, 187-189.
Acknowledgements: The authors thank the Agence Nationale
pour la Recherche (MR, ANR-07-BLAN-0294-01), the Labex
SynOrg (PC, ANR-11-LABX-0029), the CNRS (GB and JM) and
the University of Rouen (AHM) for financial supports. The
Région Normandie is also acknowledged for material support
and assistance.
[7]
For use of chiral nucleophilic lithium aluminates, see for instance: a) G.
Boireau, D. Abenhaim, J, Bourdais, E. Henry-Basch, Tetrahedron Lett.
1976, 17, 4781-4782; b) G. Boireau, D. Abenhaim, E. Henry-Basch,
Tetrahedron 1979, 35, 1457-1461; c) D. Abenhaim , G. Boireau, B.
Sabourault, Tetrahedron Lett. 1980, 21, 3043-3046; d) G. Boireau, D.
Abenhaim, A. Deberly, B. Sabourault, Tetrahedron Lett. 1982, 23,
1259-1262; e) A. Deberly, G. Boireau, D. Abenhaim, Tetrahedron Lett.
1984, 25, 655-658; f) D. Vegh, G. Boireau, E. Henry-Basch, J.
Organomet. Chem. 1984, 267, 127-131; g) D. Abenhaim, G. Boireau, A.
Deberly, J. Org. Chem. 1985, 50, 4045-4047.
Keywords: chiral lithium amido zincate
addition recyclable chiral inductor
organo(bi)metallic
•
1,2 nucleophilic
alkylation •
•
•
[8]
[9]
a) G. Armstrong, S. Cantrill, S. Davey, A. Pichon, N. Withers Nature
Chem. 2011, 3, 907-907; b) R. Larouche-Gauthier, T. G. Elford, V. K.
Aggarwal, J. Am. Chem. Soc. 2011, 133, 16794-16797.
[1]
[2]
F. Mongin, A. Harrison-Marchand, Chem. Rev. 2013, 113, 7563-7727.
See for instance: D. Tilly, F. Chevallier, F. Mongin, P. C. Gros, Chem.
Rev. 2014, 114, 1207-1257.
A. Harrison-Marchand, F. Mongin, Chem. Rev. 2013, 113, 7470-7562.
[10] Not being exhaustive, see at least the following unavoidable literature:
a) K. Soai, S. Niwa, Chem. Rev. 1992, 92, 833-856; b) L. Pu, H.-B. Yu,
Chem. Rev. 2001, 101, 757-824. c) Z. Rappoport and I. Marek (Ed),
2006, The chemistry of organozinc compounds, Patai Series: The
Chemistry of Functional Groups, John Wiley & Sons, Ltd. ; d) L. Pu,
Acc. Chem. Res. 2014, 47, 1523-1535.
[3]
See for instance: a) R. E. Mulvey, F. Mongin, M. Uchiyama, Y. Kondo,
Angew. Chem. Int. Ed. 2007, 46, 3802-3524; b) B. Haag, M. Mosrin, H.
Ila, V. Malakhov, P. Knochel, Angew. Chem. Int. Ed. 2011, 50, 9794-
9824; c) F. Chevallier, F. Mongin, R. Takita, M. Uchiyama, in Arene
Chemistry: Reaction Mechanisms and Methods for Aromatic
Compounds, Vol. 31 (Ed.: J. Mortier), John Wiley
Published, 2016, 27, 777-812.
& Sons, Inc.
[11] See for instance a) B. Lecachey, C. Fressigné, H. Oulyadi, A. Harrison-
Marchand, J. Maddaluno, Chem. Commun. 2011, 47, 9915-9917; b) A.
Harrison-Marchand, N. Duguet, G. Barozzino-Consiglio, H. Oulyadi, J.
Maddaluno, Top. Organomet. Chem. 2014, 47, 43-62; c) A. Harrison-
Marchand, G. Barozzino-Consiglio, J. Maddaluno, Chem. Rec. 2017,
17, 1-17.
[4] For use of chiral nucleophilic lithium magnesates, see for instance: a) T.
Sato, K. Soai, K. Suzuki, T. Mukaiyama, Chem. Lett. 1978, 601-604; b)
T. Mukaiyama, K. Soai, T. Sato, H. Shimizu, K. Suzuki, J. Am. Chem.
Soc. 1979, 101, 1455-1460; c) T. Mukaiyama, Tetrahedron 1981, 37,
4111-4119; d) C. G. Screttas, B. R. Steele, J. Organomet. Chem. 1986,
317, 137-144; e) R. Noyori, S. Suga, K. Kawai, S. Okada, M. Kitamura,
Pure & Appl. Chem. 1988, 60, 1597-1606; f) M. R. Luderer, W. F.
Bailey, M. R. Luderer, J. D. Fair, R. J. Dancer, M. Bech Sommer,
Tetrahedron : Asymmetry 2009, 20, 981-998; g) D. Catel, O. Payen, F.
Chevallier, F. Mongin, P. C. Gros, Tetrahedron 2012, 68, 4018-4028; h)
O. Payen, F. Chevallier, F. Mongin, P. C. Gros, Tetrahedron :
Asymmetry 2012, 23, 1678-1682; i) D. Catel, F. Chevallier, F. Mongin,
P. C. Gros, Eur. J. Org. Chem. 2012, 53-57.
[12] For the synthesis of amine 1a-H to 1c-H see a) N. Duguet, S. M. Petit,
P. Marchand, A. Harrison-Marchand, J. Maddaluno, J. Org. Chem.
2008, 73, 5397-5409; for the synthesis of amines 1i-H and 1j-H, also
see b) G. Barozzino-Consiglio, M. Rouen, H. Oulyadi, A. Harrison-
Marchand, J. Maddaluno, Dalton Trans. 2014, 43, 14219-14228.
[13] a) W. Tückmantel, K. Oshima, H. Nozaki, Chem. Ber. 1986, 119, 1581-
1593; b) Y. Kondo, M. Fujinami, M. Uchiyama, T. Sakamoto, J. Chem.
Soc., Perkin Trans. 1 1997, 799-800.
[5]
For use of chiral nucleophilic lithium alkoxy zincates, see for instance:
a) K. Soai, A. Ookawa, T. Kaba, K. Ogawa, J. Am. Chem. Soc. 1987,
This article is protected by copyright. All rights reserved.

10.1002/chem.201802044
Chemistry - A European Journal
COMMUNICATION
COMMUNICATION
This study puts into evidence, for the
first time, that triorganozincates made
of a chiral amido moiety can behave
as efficient chemo- and enantio-
Mathieu Rouen, Pauline Chaumont,
Gabriella Barozzino-Consiglio, Jacques
Maddaluno,
Marchand*
and
Anne
Harrison-
selective
aldehydes.
nucleophiles
These cheap
toward
auto-
Page No. – Page No.
assembled reactants incorporate
a
Chiral Lithium Amido Zincates for
Enantioselective 1,2-Additions: Auto-
chiral inductor based on an amine
easily recycled thanks to a simple
acid-base wash.
assembling Reagents Involving
Fully Recyclable Ligand
a
This article is protected by copyright. All rights reserved.