Preparation of Polyfunctional Arylzinc Organometallics in Toluene by Halogen/Zinc Exchange Reactions

Article abstract of DOI:10.1002/anie.201906898

A wide range of polyfunctional diaryl- and diheteroarylzinc species were prepared in toluene within 10 min to 5 h through an I/Zn or Br/Zn exchange reaction using bimetallic reagents of the general formula R′₂Zn?2 LiOR (R′=sBu, tBu, pTol). Highly sensitive functional groups, such as a triazine, a ketone, an aldehyde, or a nitro group, were tolerated in these exchange reactions, enabling the synthesis of a plethora of functionalized (hetero)arenes after quenching with various electrophiles. Insight into the constitution and reactivity of these bimetallic mixtures revealed the formation of highly active lithium diorganodialkoxyzincates of type [R′₂Zn(OR)₂Li₂].

Full text of DOI:10.1002/anie.201906898

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International Edition: DOI: 10.1002/anie.201906898
German Edition: DOI: 10.1002/ange.201906898
Exchange Reactions Very Important Paper
Preparation of Polyfunctional Arylzinc Organometallics in Toluene by
Halogen/Zinc Exchange Reactions
Moritz Balkenhohl, Dorothꢀe S. Ziegler, Alexandre Desaintjean, Leonie J. Bole,
Alan R. Kennedy, Eva Hevia,* and Paul Knochel*
Abstract: A wide range of polyfunctional diaryl- and dihetero-
arylzinc species were prepared in toluene within 10 min to 5 h
through an I/Zn or Br/Zn exchange reaction using bimetallic
reagents of the general formula R’2Zn·2LiOR (R’ = sBu, tBu,
pTol). Highly sensitive functional groups, such as a triazine,
a ketone, an aldehyde, or a nitro group, were tolerated in these
exchange reactions, enabling the synthesis of a plethora of
functionalized (hetero)arenes after quenching with various
electrophiles. Insight into the constitution and reactivity of
these bimetallic mixtures revealed the formation of highly
active lithium diorganodialkoxyzincates of type [R’2Zn-
(OR)2Li2].
For preparing related organomagnesium derivatives, the
exchange reagent iPrMgCl·LiCl (“turbo-Grignard”) has been
extensively used and leads to high rates of Br/Mg exchange.[7]
This exchange can be accelerated further by replacing LiCl
with a stronger donor additive, namely a lithium alkoxide
(ROLi; R = 2-ethylhexyl). Furthermore, this exchange could
be performed in the industrially friendly solvent toluene.[8]
Opening new ground in this evolving area, we herein
report a new I/Zn and Br/Zn exchange in toluene based on
the use of a novel bimetallic combination sBu2Zn·2LiOR (1),
which allows the generation of a wide range of polyfunctional
aryl- and heteroarylzinc reagents from the corresponding
organic iodides or bromides.
O
rganozinc reagents are key intermediates in organic
First, Et2Zn reacted in toluene with two equivalents of
a variety of alcohols ROH (258C, 4 h), affording the relevant
ethylzinc alkoxides co-complexed with the corresponding
alcohol (ROZnEt·ROH) of type 2.[9] These ethylzinc alk-
oxides (2) further reacted with sBuLi (2.0 equiv, in cyclohex-
ane) to produce the bimetallic reagent tentatively represented
synthesis as they tolerate many functional groups and readily
participate in transition-metal-catalyzed carbon–carbon
bond-forming reactions.[1] Aryl- and heteroarylzinc halides
have been particularly widely used as organometallic reagents
for preparing complex organic molecules.[2] Two recently
developed alternative synthetic strategies granting access to
these valuable organometallics are the direct insertion of zinc
powder into organic halides[3] and deprotonative metalation
using TMP-zinc bases (TMP = 2,2,6,6-tetramethylpiper-
idyl).[4] Lithium alkylzincates such as “lower-order” R3ZnLi
and “higher-order” R4ZnLi2 have been shown to be able to
promote halogen/zinc exchange reactions towards aryl hal-
ides.[5] Furthermore, an I/Zn exchange of aryl and heteroaryl
iodides can be accomplished by adding substoichiometric
amounts of Li(acac) to iPr2Zn in NMP.[6] Contrasting with the
enhanced reactivity of these mixed-metal combinations,
monometallic R2Zn reagents on their own fail to promote
these type of transformations.
as
the
trinuclear
monozinc–dilithium
complexes
sBu2Zn·2LiOR (1, see below). Removal of the solvents and
subsequent redissolution in toluene provided a light yellow
solution of 1 (c = 0.6–1.0m in toluene; Scheme 1), which can
Scheme 1. Preparation of mixed-metal reagents of type 1.
be stored at 258C for months without significant loss of
reactivity. Initial studies showed that the complex
sBu2Zn·2LiOR (R = 2-octyl; 1a) reacted with 3-iodoanisole
(4a) in toluene[10] within 30 min at 258C, forming putative
bis(anisyl)zinc complexed with 2LiOR (5a) in 23% yield, as
determined by GC analysis of reaction aliquots (Table 1,
entry 1). Interestingly, a striking effect was observed upon
varying the alkoxide component of 1. Using alcohols bearing
N-coordination sites[11] led to a significant improvement in the
efficiency of the I/Zn exchange process. Thus complex 1b
(R = CH2CH2N(Et)2) produced the diarylzinc species 5a in
95% GC yield (entry 2) while the use of 1c (R = CH2CH2N-
[*] M. Balkenhohl, Dr. D. S. Ziegler, A. Desaintjean, Prof. Dr. P. Knochel
Ludwig-Maximilians-Universitꢀt Mꢁnchen
Department Chemie
Butenandtstrasse 5–13, Haus F, 81377 Mꢁnchen (Germany)
E-mail: paul.knochel@cup.uni-muenchen.de
Prof. Dr. E. Hevia
Department fꢁr Chemie und Biochemie
Universitꢀt Bern
3012 Bern (Switzerland)
E-mail: eva.hevia@dcb.unibe.ch
L. J. Bole, Dr. A. R. Kennedy
Department of Pure and Applied Chemistry
University of Strathclyde
(CH3)CH2CH2N(CH3)2), where OR contains
a second
N-coordination site, accelerated the I/Zn exchange process,
affording 5a in 99% GC yield after just 1 min (entries 3 and
4). Contrastingly, replacing the sBu group on 1c with other
alkyl groups such as Et, nBu, or tBu had very little effect on
Glasgow, G1 1XL (UK)
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.201906898.
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Negishi cross-coupling[14] took place, generating biaryl 6c in
76% yield. 4-(Trifluoromethoxy)iodobenzene underwent
a smooth I/Zn exchange with 1c, giving the corresponding
diarylzinc reagent 5b. Reaction of 5b with ethyl 2-(bromo-
methyl)acrylate or a palladium-catalyzed cross-coupling with
4-iodothioanisole gave the functionalized arenes 6d and 6e in
48 and 67% yield, respectively. Various electron-poor aryl
iodides bearing, for example, ester or nitrile groups readily
reacted with 1c, and quenching of the zinc reagents of type 5
with various electrophiles gave products 6 f–l in 59–98% yield
(Scheme 2).[15]
Table 1: Optimization of the reaction conditions for the I/Zn exchange
using dialkylzinc reagents of type 1.
Entry
sBu2Zn·2LiOR (1)
Time [min]
Yield [%][a]
1
2
30
30
23
95
To demonstrate the versatility of 1c, this approach was
extended to a wide collection of heteroaromatic substrates to
yield synthetically valuable bis(heteroaryl)zinc organometal-
lics (Scheme 3). Thus, bis(thienyl)zinc reacted with either 3-
bromocyclohexene or 2-bromobenzoyl chloride to provide 7a
and 7b in 71 and 61% yield, respectively. Benzyl-protected 3-
iodopyrazole reacted with 1c to give, after allylation, 7c in
80% yield. Also, various iodopyridines, -pyrimidines, and
-quinolines were converted into the corresponding zinc
reagents using 1c, which were quenched with several electro-
philes, including acid chlorides and allyl bromides to produce
the heterocyclic products 7d–m in 56–96% yield. Reactions
3
4
30
1
99
99
1c
[a] Yield of 5a determined by GC analysis of reaction aliquots quenched
with water.
the overall conversions after 30 min (ranging from 80 to
89%).[12]
Thus 3-iodoanisole (4a) reacted with sBu2Zn·2LiOR (1c)
in toluene at 258C for 10 min to produce the bis(anisyl)zinc
reagent 5a. Reaction of 5a with allyl bromide in the presence
of CuI (20 mol%) gave the allylated arene 6a in 67% yield
(Scheme 2). Transmetalation of 5a to copper using CuI
(0.6 equiv), followed by addition of 4-chlorobenzoyl chloride,
gave the acylated anisole 6b in 86% yield. When the zinc
species 5a was mixed with ethyl 4-iodobenzoate, Pd(OAc)2
(3 mol%), and SPhos (6 mol%),[13] a palladium-catalyzed
Scheme 2. Reaction of various aryl iodides with sBu2Zn·2LiOR (1c),
followed by electrophilic functionalization.
Scheme 3. Reaction of various heteroaryl iodides with sBu2Zn·2LiOR
(1c), followed by electrophilic functionalization.
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of more complex iodinated N-heterocycles, namely pyrazo-
(0.8 equiv) at 258C for 5 h in toluene (1m) provided the
lone, uracil, or 5,6-dihydropyridone, gave the expected bis-
zinc reagents of type 5, which, after allylation or acylation,
provided 7n–q in 74–85% yield (Scheme 3).[16]
Expanding even further the scope of this approach, the
I/Zn exchange process proved tolerant to different highly
sensitive functional groups. Thus mixing an aryl iodide
bearing a triazine moiety with 1c, followed by allylation,
gave arene 8a in 72% yield (Scheme 4). Next, the diarylzinc
species generated from 4-iodobenzophenone was allylated,
desired bis(aryl)zinc reagent of type 5, which, after quenching
with iodine, gave 4-iodobenzonitrile (11a) in 77% yield
(Scheme 5). The reaction of the same zinc reagent with
4-iodoanisole under palladium catalysis gave the desired
Scheme 4. The I/Zn exchange reaction on various (hetero)aryl iodides
bearing highly sensitive functional groups.
Scheme 5. Reaction of various aryl bromides with sBu2Zn·2LiOR (1),
followed by electrophilic functionalization.
providing ketone 8b in 83% yield. In the case of nitro-
substituted aryl iodides, pTol2Zn·2LiOR (9) gave the best
result.[17] Hence, the mild exchange reagent pTol2Zn·2LiOR
(9, R = CH2CH2N(CH3)CH2CH2N(CH3)2; pTol = p-tolyl) was
prepared by mixing the alkoxide 2c with tolyllithium
(2.0 equiv).[18] Treatment of 2,4-dinitroiodobenzene or
3-iodo-4-nitrobenzonitrile with 9 (0.6 equiv) at À158C for
15 min, followed by a copper-mediated allylation reaction,
afforded nitroarenes 8c and 8d in 79 and 71% yield,
respectively. For the conversion of an iodo-substituted
benzaldehyde into the corresponding zinc species, a short
screening showed that the best exchange reagent was
tBu2Zn·2LiOR (10). Thus alkoxide 2c was treated with
tBuLi (2.0 equiv), and the resulting less nucleophilic reagent
tBu2Zn·2LiOR (10, R = CH2CH2N(CH3)CH2CH2N(CH3)2)
was obtained as a 1m solution in toluene. Reaction of
5-iodo-veratraldehyde with 10 (0.8 equiv; 08C, 10 min)
afforded a diarylzinc organometallic of type 5, which, after
allylation, provided the vanillin derivative 8e in 48% yield. 4-
Iodofuraldehyde was also treated with tBu2Zn·2LiOR (10),
and the resulting zinc reagent reacted with 3-bromocyclohex-
ene in the presence of CuI to give the furfural derivative 8 f in
66% yield (Scheme 4).
biaryl 11b in 64% yield.[19] Various bromoarenes bearing, for
example, an ester functional group underwent smooth Br/Zn
exchange, which, after allylation or cross-coupling, produced
arenes 11c–f in 60–79% yield. Additionally, bromopyridines
and a bromoquinoline were treated with 1c. Allylation of the
resulting zinc reagents gave the functionalized heteroarenes
11g–i in 61–70% yield. Finally, 2-bromobenzothiazole was
mixed with 1c, and the resulting metal species reacted with
iodine to give 11j in 75% yield (Scheme 5).[15]
Intrigued by the unique reactivity of these systems, we
sought to gain some information on the constitution of 1c.
The results of multinuclear (1H, 13C, 7Li) NMR studies
1
including H DOSY NMR experiments in [D8]toluene are
consistent with the formation of the contact ion pair lithium
zincate [sBu2Zn(OR)2Li2] (1c) as the major species in
solution, along with a minor ethyl complex tentatively
assigned as the complex [Et(sBu)Zn(OR)2Li2].[12] The pres-
ence of this ethyl species can be rationalized by considering
the residual Et group present in 2 (Scheme 1) in going from
1
type 2 to type 1. Interestingly, H NMR monitoring of the
reaction of this zincate mixture with 2-iodoanisole showed
that both bimetallic complexes are active towards the I/Zn
exchange as evidenced by the almost immediate consumption
of the aryl iodide, affording an arylzinc species,[20] with
concomitant formation of EtI and sBuI. [sBu2Zn(OR)2Li2]
The excellent reactivity of these bimetallic exchange
reagents led us to examine the corresponding Br/Zn exchange
reaction. Treatment of 4-bromobenzonitrile with 1c
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(1c) can be envisaged as a co-complex of sBu2Zn and 2 equiv
of LiOR; in fact, this combination of single-metal reagents in
toluene showed very similar reactivity towards I/Zn exchange
with 3-iodoanisole to that found for 1c.[12]
excellent functional group tolerance through the activation of
both R’ groups on Zn. Quenching of the in situ generated zinc
organometallics with various electrophiles produced a range
of functionalized (hetero)arenes, demonstrating the extensive
synthetic scope of this approach. Structural and spectroscopic
studies probing the constitution of these bimetallic systems
support the formation of highly reactive lithium bis(alkyl)bis-
(alkoxy)zincates and shed light on the key role of each
component in the mixture for the success of the I/Zn
exchange. Further extensions of this bimetallic research are
currently being studied in our laboratories.
Co-complexation reactions of n equiv of LiOR (n = 1 and
2) with several R’2Zn (R’ = Me, Et, sBu) reagents in toluene
were investigated spectroscopically, demonstrating in all cases
the formation of mixed-metal complexes (see the Supporting
Information). Further evidence was obtained from X-ray
crystallographic studies of the lithium diorganoalkoxyzincate
[Me2Zn·LiOR] (12, R = CH2CH2N(CH3)CH2CH2N(CH3)2;
Figure 1).[21] This structure contains an eye-catching 5,5,4,5,5
fused ring system where each zinc in 12 binds to two methyl
groups and one alkoxide ligand. Both Li atoms are connected
Acknowledgements
We thank the DFG (SFB749) for financial support. We also
thank Albemarle (Hoechst, Germany) for the generous gift of
chemicals. L.J.B. thanks the University of Strathclyde for the
award of the George Fraser scholarship.
Conflict of interest
The authors declare no conflict of interest.
Keywords: alkoxides · lithium · metal/halogen exchange ·
organozinc reagents · toluene
Figure 1. Molecular structure of [Me2Zn·LiOR] (12). Hydrogen atoms
are omitted for clarity. Thermal ellipsoids set at 50% probability.
[1] a) E.-i. Negishi, Acc. Chem. Res. 1982, 15, 340 – 348; b) P.
Knochel, R. D. Singer, Chem. Rev. 1993, 93, 2117 – 2188; c) P.
Knochel, N. Millot, A. L. Rodriguez, C. E. Tucker in Preparation
and Applications of Functionalized Organozinc Compounds.
Organic Reactions, Vol. 58, Wiley-VCH, Weinheim, 2004,
pp. 417 – 759; d) P. Knochel, H. Leuser, L.-Z. Cong, S. Perrone,
F. F. Kneisel in Handbook of Functionalized Organometallics,
Wiley-VCH, Weinheim, 2008; e) E.-i. Negishi, Angew. Chem.
Int. Ed. 2011, 50, 6738 – 6764; Angew. Chem. 2011, 123, 6870 –
6897; f) Metal-Catalyzed Cross-Coupling Reactions, Second
Edition, Wiley-VCH, Weinheim, 2008; g) Y.-H. Chen, M.
Ellwart, V. Malakhov, P. Knochel, Synthesis 2017, 49, 3215 – 3223.
[2] a) T. J. Greshock, K. P. Moore, R. T. McClain, A. Bellomo, C. K.
Chung, S. D. Dreher, P. S. Kutchukian, Z. Peng, I. W. Davies, P.
Vachal, M. Ellwart, S. M. Manolikakes, P. Knochel, P. G.
Nantermet, Angew. Chem. Int. Ed. 2016, 55, 13714 – 13718;
Angew. Chem. 2016, 128, 13918 – 13922; b) Y. H. Chen, M.
Ellwart, G. Toupalas, Y. Ebe, P. Knochel, Angew. Chem. Int. Ed.
2017, 56, 4612 – 4616; Angew. Chem. 2017, 129, 4683 – 4687;
c) Y. H. Chen, C. P. Tꢀllmann, M. Ellwart, P. Knochel, Angew.
Chem. Int. Ed. 2017, 56, 9236 – 9239; Angew. Chem. 2017, 129,
9364 – 9368; d) Y. Zhou, C. Liu, L. Wang, L. Han, S. Hou, Q.
Bian, J. Zhong, Synlett 2019, 30, 860 – 862.
to the OR groups via oxygen bridges, and complete their
coordination sphere by binding to the two N atoms present in
the multidentate alkoxide chain. This special coordination to
Li can be influential for the marked alkoxide effect seen in
Table 1 as other OR groups without N donor substituents may
favor formation of higher oligomeric lithium zincates, which
can be expected to be less reactive.
1H NMR monitoring studies with addition of variable
amounts of LiOR to a solution of Et2Zn in [D8]toluene
disclose the importance of the LiOR/alkylzinc ratio for the
success of the I/Zn exchange. While Et2Zn is completely inert
towards exchange with 2-iodoanisole (2 equiv), addition of
1 equiv of LiOR gave a conversion of only 23% after 10 min;
on the other hand, with 2 equiv of LiOR, the reaction is
almost quantitative (95%). This is consistent with the
formation of a more activated diorganodialkoxyzincate
species [sBu2Zn(OR)2Li2], where zinc is formally part of an
electron-rich dianionic moiety. The excellent atom economy
of the reaction, with both ethyl groups on Et2Zn being active
towards the exchange, is particularly remarkable, especially
when compared with the related tris(alkyl) reagent
Et3ZnLi,[22] where only one of the three Et groups can
undergo I/Zn exchange.[12]
[3] a) L. Zhu, R. M. Wehmeyer, R. D. Rieke, J. Org. Chem. 1991, 56,
1445 – 1453; b) A. Krasovskiy, V. Malakhov, A. Gavryushin, P.
Knochel, Angew. Chem. Int. Ed. 2006, 45, 6040 – 6044; Angew.
Chem. 2006, 118, 6186 – 6190; c) N. Boudet, S. Sase, P. Sinha, C.-
Y. Liu, A. Krasovskiy, P. Knochel, J. Am. Chem. Soc. 2007, 129,
12358 – 12359; d) C. Y. Liu, X. Wang, T. Furuyama, S. Yasuike,
A. Muranaka, K. Morokuma, M. Uchiyama, Chem. Eur. J. 2010,
16, 1780 – 1784.
In summary, a new family of bimetallic reagents of type
R’2Zn·2LiOR have been developed that efficiently promote
I/Zn and Br/Zn exchange processes at room temperature with
4
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[4] a) B. Haag, M. Mosrin, H. Ila, V. Malakhov, P. Knochel, Angew.
[12] See the Supporting Information for further details.
Chem. Int. Ed. 2011, 50, 9794 – 9824; Angew. Chem. 2011, 123,
9968 – 9999; b) K. Murakami, S. Yamada, T. Kaneda, K. Itami,
Chem. Rev. 2017, 117, 9302 – 9332; c) M. Balkenhohl, P. Knochel,
SynOpen 2018, 2, 78 – 95; d) S. D. Robertson, M. Uzelac, R. E.
Mulvey, Chem. Rev. 2019, https://doi.org/10.1021/acs.chemrev.
9b00047.
[13] a) T. E. Barder, S. D. Walker, J. R. Martinelli, S. L. Buchwald, J.
Am. Chem. Soc. 2005, 127, 4685 – 4696; b) R. A. Altman, S. L.
Buchwald, Nat. Protoc. 2007, 2, 3115.
[14] a) A. O. King, N. Okukado, E.-i. Negishi, J. Chem. Soc. Chem.
Commun. 1977, 683; b) D. Haas, J. M. Hammann, R. Greiner, P.
Knochel, ACS Catal. 2016, 6, 1540.
[5] a) M. Uchiyama, T. Furuyama, M. Kobayashi, Y. Matsumoto, K.
Tanaka, J. Am. Chem. Soc. 2006, 128, 8404 – 8405; b) T.
Furuyama, M. Yonehara, S. Arimoto, M. Kobayashi, Y. Matsu-
moto, M. Uchiyama, Chem. Eur. J. 2008, 14, 10348 – 10356; c) L.
Melzig, C. R. Diꢁne, C. J. Rohbogner, P. Knochel, Org. Lett.
2011, 13, 3174 – 3177; d) D. Tilly, F. Chevallier, F. Mongin, P. C.
Gros, Chem. Rev. 2014, 114, 1207 – 1257.
[6] F. F. Kneisel, M. Dochnahl, P. Knochel, Angew. Chem. Int. Ed.
2004, 43, 1017 – 1021; Angew. Chem. 2004, 116, 1032 – 1036.
[7] a) A. Krasovskiy, P. Knochel, Angew. Chem. Int. Ed. 2004, 43,
3333 – 3336; Angew. Chem. 2004, 116, 3396 – 3399; b) L. Shi, Y.
Chu, P. Knochel, H. Mayr, Org. Lett. 2009, 11, 3502 – 3505; c) L.
Shi, Y. Chu, P. Knochel, H. Mayr, J. Org. Chem. 2009, 74, 2760 –
2764; d) T. Klatt, J. T. Markiewicz, C. Sꢂmann, P. Knochel, J.
Org. Chem. 2014, 79, 4253 – 4269; e) R. L.-Y. Bao, R. Zhao, L.
Shi, Chem. Commun. 2015, 51, 6884 – 6900; f) D. S. Ziegler, B.
Wei, P. Knochel, Chem. Eur. J. 2019, 25, 2695 – 2703.
[15] Further examples can be found in the Supporting Information.
[16] Because of the poor solubility of the aryl iodides, the reactions
generating 7g,j,k, and n–q were performed in THF.
[17] When 2,4-dinitroiodobenzene was treated with 1c, decomposi-
tion of the starting material was observed.
[18] pTolyllithium was prepared by a direct lithium insertion into 4-
chlorotoluene; see: C. G. Screttas, B. R. Steele, M. Micha-
Screttas, G. A. Heropoulos, Org. Lett. 2012, 14, 5680 – 5683.
[19] Prior to addition of the catalyst system and the aryl iodide,
TMSCl (0.8 equiv; 08C, 10 min) was added to quench the excess
alkoxide.
[20] The arylzinc complex formed in this reaction has limited
solubility in [D8]toluene but was fairly soluble in [D8]THF. Its
13C NMR spectrum shows
a
diagnostic resonance at d =
À
À
155.71 ppm for Zn C(aryl) (vs. d = 86.4 ppm for C I in 2-
iodoanisole). DOSY NMR studies are consistent with the
formation of a heteroleptic [Ar2Zn(OR)2Li2] species.
[8] D. S. Ziegler, K. Karaghiosoff, P. Knochel, Angew. Chem. Int.
Ed. 2018, 57, 6701 – 6704; Angew. Chem. 2018, 130, 6811 – 6815.
[21] CCDC 1918845 (12) and 1918846 (13, see the Supporting
Information), contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre.
[9] Co-complex
[EtZn(OR)·ROH]
(R = CH2CH2N-
(CH3)CH2CH2N(CH3)2) has been spectroscopically character-
1
ized by H and 13C NMR analysis; see the Supporting Informa-
[22] Et3ZnLi was prepared in [D8]toluene by co-complexation of
EtLi and Et2Zn. Its reaction with three equiv of 2-iodoanisole
tion. The structure of the neutral complex EtZn(OR) has been
previously established by X-ray crystallography; see: M. S. Hill,
G. Kociok-Kçhn, K. C. Molloy, D. C. Stanton, Main Group Met.
Chem. 2015, 38, 61.
1
was monitored by H NMR spectroscopy, revealing the forma-
tion of an ArEt2ZnLi species; see the Supporting Information
for details.
[10] A solvent screen showed that the halogen/zinc exchange cannot
only be performed in hydrocarbons such as toluene or hexane,
but also in other industrially friendly ethereal solvents such as 2-
methyl-THF or MTBE.
Manuscript received: June 3, 2019
[11] D. Sꢂlinger, R. Brꢀckner, Chem. Eur. J. 2009, 15, 6688 – 6703.
Version of record online: && &&, &&&&
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Communications
Exchange Reactions
M. Balkenhohl, D. S. Ziegler,
A. Desaintjean, L. J. Bole, A. R. Kennedy,
E. Hevia,* P. Knochel*
&&&& — &&&&
Preparation of Polyfunctional Arylzinc
Organometallics in Toluene by Halogen/
Zinc Exchange Reactions
Alkoxide is all you need: Atom-economic
I/Zn and Br/Zn exchange reactions were
developed by using dialkylzinc reagents
co-complexed with lithium alkoxides.
Because of the covalent nature of the
carbon–zinc bond, several sensitive
functional groups, including triazines,
ketones, aldehydes, and nitro groups,
were tolerated. Quenching of the diaryl-
zinc species with various electrophiles
produced a plethora of functionalized
(hetero)arenes.
6
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