ortho-Directing Chromium Arene Complexes as Efficient Mediators for Enantiospecific C(sp2)–C(sp3) Cross-Coupling Reactions

Article abstract of DOI:10.1002/anie.201711816

A new strategy for the coupling of a broad scope of electronically diverse aromatics to boronic esters is reported. The coupling sequence, which relies on the directed ortho-lithiation of chromium arene complexes followed by boronate formation and oxidation, occurs with complete ortho-selectivity and enantiospecificity to give the coupling products in excellent yields and with high functional group tolerance. An intermediate chromium arene boronate complex was characterized by X-ray, NMR, and IR experiments to elucidate the reaction mechanism.

Full text of DOI:10.1002/anie.201711816

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Accepted Article
Title: ortho-Directing Chromium Arene Complexes as Efficient
Mediators for Enantiospecific sp2-sp3 Cross-Coupling Reactions
Authors: Raphael Bigler and Varinder Kumar Aggarwal
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201711816
Angew. Chem. 10.1002/ange.201711816
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10.1002/anie.201711816
Angewandte Chemie International Edition
COMMUNICATION
ortho-Directing Chromium Arene Complexes as Efficient Media–
tors for Enantiospecific sp2-sp3 Cross-Coupling Reactions
Raphael Bigler and Varinder K. Aggarwal*
A) Coupling with electron-rich aromatics (previous work)
Abstract: A new strategy for the coupling of a broad scope of
[Nu–]
OMe
OMe
OMe
[Br+]
OMe
electronically diverse aromatics to boronic esters is reported. The
coupling sequence, which relies on the directed ortho-lithiation of
chromium arene complexes followed by boronate formation and
oxidation, occurs with complete ortho-selectivity and enantio-
specificity to give the coupling products in excellent yields and with
high functional group tolerance. An intermediate chromium arene
boronate complex was characterized by X-ray, NMR and IR to
elucidate the reaction mechanism.
Br
Br
Bpin
R'
R'
B(pin)
R'
B(pin)
R'
R
R
R
R
activation
1,2-migration
elimination
B) Coupling with phenols (previous work)
[Nu–]
Ph Ph
S
RO
O
O
HO
O
S
Ph Ph
RO
OR
Bpin
R'
R'
B(pin)
R'
B(pin)
R'
R
R
R
R
activation
elimination
1,2-migration
C) Coupling with pyridines (previous work)
While the coupling of aromatic building blocks via the Suzuki-
Miyaura cross-coupling is well established in organic and
medicinal chemistry, the enantiospecific coupling of secondary
and tertiary alkyl boronic esters to aromatics through transition
metal catalyzed processes is considerably more challenging.1
Even though substantial progress has been made over the last
two decades, most processes are not generally applicable with
erosion of enantiomeric purity often observed.2,3
O
O
O
R
Cl
N
N
R
N
R
N
R'
Bpin
R'
B(pin)
R'
B(pin)
R'
R
R
R
R
oxidation/hydrolysis
and elimination
activation
1,2-migration
D) Coupling with ortho-lithiated chromium arene complexes (this work)
R'
R' R'
R'
R
R
R'
Bpin
R'
Bpin
[Nu–]
CO
Bpin
As an alternative to these palladium catalyzed processes,
we4 and Ready5 have recently reported a series of transition
metal-free, stereospecific couplings of chiral alkyl boronic esters
with aryl lithium reagents (Scheme 1a-1c). These processes rely
on four basic steps: (i) boronate formation, (ii) activation of the
aromatic group, (iii) stereospecific 1,2-migration of the alkyl
group, and (iv) elimination and rearomatization. Suitable
activators were found for aromatics with electron-donating
groups in the meta-positions and electron rich heterocycles
(Scheme 1a),4a,4b phenols (Scheme 1b),4f and pyridines
Cr0
Cr0
CrII
Cr0
OC
OC
CO
OC
OC
1,2-migration
OC
OC
OC
OC
CO
CO
elimination
oxidation
Scheme 1. Enantiospecific sp2-sp3 coupling of electron-rich aromatics (A),
phenols (B) or pyridines (C) and (D) proposed coupling work.
chromium arene complex. Further oxidation would lead to
removal of the Cr(CO)3 fragment to give the decomplexed
coupled product. An additional attractive feature of chromium
arene complexes is that they significantly acidify Ar–H bonds,8a
facilitating lithiation including ortho-lithiation,7b,8 thereby enabling
the possibility for ortho-selective cross-coupling. In this paper we
report our success in achieving this coupling reaction, although it
ultimately differed mechanistically from the planned pathway.
We began our study by reacting Li[Cr(CO)3(C6H5)] (1.25
equiv, generated by lithiation of [Cr(CO)3(C6H6)] (1a) with n-
BuLi) with boronic ester rac-2a in THF to give the corresponding
boronate. After 4 h at –78 °C, I2 (10 equiv) was added and the
solution was warmed to rt overnight. To our delight, the
decomplexed cross-coupled product rac-3aa was isolated in
21% yield. The major fraction contained a mixture of boron-
incorporated products, indicating inefficient elimination of the
boronic ester moiety in step (iv). By adding I2 as a suspension in
MeOH, the yield of rac-3aa dramatically increased to 83% and
the only observed side product was the SN2 iodination product 4-
(4-methoxyphenyl)butan-2-yl iodide in 6% yield.9 The formation
of this side product was reduced to 3% by changing form MeOH
to n-PrOH, and rac-3aa was obtained in 90% isolated yield.
Importantly, when enantioenriched 2a (er = 96:4) was used, 3aa
was obtained with identical enantiomeric excess indicating that
the reaction occurs with perfect enantiospecificity (Table 1).
(Scheme 1c)4c,5a
.
However, aromatics without particular functional groups to
react with an activating agent could not undergo such couplings
(e.g. the simplest phenyl group). We reasoned that such
couplings could be achieved if step (ii) in these transformations
occurred spontaneously upon formation of the boronate complex.
This could be realized if the aromatic possessed a strong
electron sink. We therefore considered the possibility of using
chromium arene complexes of the type [Cr(CO)3(arene)], which
are easily prepared6 and known to react readily with
organometallic reagents.7 We queried whether they were
sufficiently electron withdrawing to trigger the 1,2-migration
without external activation (Scheme 1d). Subsequent oxidation
of the resulting cyclohexadienyl anion to the corresponding
cation and elimination of the boronic ester moiety would give the
[a]
Dr. R. Bigler, Prof. Dr. V. K. Aggarwal
School of Chemistry
University of Bristol
Cantock’s Close, Bristol, BS8 1TS, United Kingdom
E-mail: v.aggarwal@bristol.ac.uk
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201711816
Angewandte Chemie International Edition
COMMUNICATION
Table 1. Substrate scope of chromium arene complexes 1 for enantiospecific sp2-sp3 coupling to access ortho-cross-coupled aromatics.a
DG
Li
Cr
OC
DG
Bpin
Bpin
CO
OC
(1.25 equiv)
DG
OMe
I2 (10 equiv)
Cr
OC
OC
MeO
n-PrOH
–78 °C to rt, o/n
THF or Et2O
–78 °C, 4 h
CO
MeO
2a
3
CF3
Cl
OTIPS
iPrO
MeO
EtO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
3aeb
86%, er: n.d.
3aa
90%, er: 96:4
es: 100%
3ab
92%, er: 96:4
es: 100%
3ac
90%, er: 96:4
es: 100%
3ad
96%, er: 96:4
es: 100%
3af
50%, er: 96:4
es: 100%
3ag
65%, er: 96:4
es: 100%
OMe
OMe
OMe
NMe2
OMe
NMe2
O
O
O
O
MeO
OMe
OMe
MeO
MeO
H
H
MeO
MeO
MeO
H
H
H
H
MeO
MeO
MeO
MeO
3ak’d
84%, dr > 20:1
3ah
80%, er: 96:4
es: 100%
3aj
41%, er: 96:4
es: 100%
3am
71%, er: 96:4
es: 99%
3aic
55%, er: 96:4
es: 100%
3ak
87%, dr > 20:1
3al
78%, er: 96:4
es: 100%
CF3
F
OMe
EtO
O
HO
F
F
HO
HO
HO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
3ane
52%, er: 97:3
es: 100%
3aof
83%, er: 96:4
es: 100%
3aqf
3apf
3arf
77%, er: 96:4
es: 100%
3as
76%, er: 96:4
es: 100%
3at
84%, er: 96:4
es: 99%
56%, er: 96:4
es: 100%
92%, er: 96:4
es: 100%
F
OMe
NMe2
CF3
OTIPS
F
Cl
F
F
F
F
Cl
MeO
MeO
MeO
MeO
MeO
MeO
MeO
3azb
80%, er: n.d.
3au
91%, er: 97:3
es: 100%
3av
83%, er: 96:4
es: 100%
3ay
72%, er: 96:4
es: 100%
3aα
51%, er: 96:4
es: 100%
3aw
91%, er: 96:4
es: 100%
3ax
62%, er: 96:4
es: 100%
a Reactions were carried out with 0.30 mmol of boronic ester, 1.25 equiv of lithiated chromium arene complex, and 10.0 equiv of I2. Yields recorded are those of
isolated material. b No separation achieved by HPLC. c Reaction warmed to rt after addition of boronic ester. d ent-2a was used. e K2HPO4 added with I2 in MeOH.
f Ethoxymethyl acetal employed and no base used during oxidation.
When the [Cr(CO)3(anisole)] (1b) was employed under
identical conditions, 3ab was obtained in excellent yield and as a
single regioisomer. Perfect ortho-selectivity was also observed
for products 3ac and 3ad containing ethoxy and isopropoxy
directing groups, respectively. A series of functional groups (i.e.
alkyl (3ad), CF3 (3ae), Cl (3af), OTIPS (3g), OMe (3h), and
NMe2 (3j)) were well tolerated and the sp2-sp3 cross-coupling
occurred selectively ortho to the methoxy substituent.6b,10
Interestingly, the 4-substituted product 3ai was obtained as a
single regioisomer in the case of the resorcinol derived
chromium complex 1i, indicating that the initially formed 2-
lithiated arene is too hindered to form the boronate complex and
rearranges to the 4-lithiated isomer, which is selectively trapped
by 2a.11
To highlight the synthetic utility of this method for late
stage modification, the estradiol-derived chromium complex 1k
was selectively coupled in the 6-position with boronic esters 2a
and ent-2a to give the diastereomeric products 3ak and 3ak’ in
high yields and complete diastereoselectivity.12 Furthermore,
complexes 1l and 1m containing the benzodioxole motif, which
is widely found in natural products and drugs, were selectively
mono-lithiated and coupled to give products 3al and 3am in high
yield and complete enantiospecificity.13
as shown for products 3ap–3ar. Even when other directing
groups such as fluoro or methoxy were present, the ortho-
phenols were obtained selectively.
As halogenated aromatics are important motifs in drugs
and agrochemicals,14 we next investigated the use of fluoro and
chloro aromatics. To our delight, the reaction with fluorobenzene
complex 1s worked similarly well, and the desired product 3as
was obtained in 76% yield as a single regioisomer and with
complete enantiospecificity. Again, functional groups such as
methyl (3t and 3u), OTIPS (3av), OMe (3aw), NMe2 (3ax), and F
(3ay) were well tolerated and the cross-coupling occurred
selectively ortho to the fluoro substituent. Finally, the ability of
chloride to act as a directing group was exemplified for the
chlorinated chromium complexes 1z and 1α, which selectively
afforded ortho-cross-coupled products 3az and 3aα in 80% and
51% isolated yield. Our results indicate that the order of ortho-
directing ability decreases along the series: OCH2OEt > F > OR
> Cl > alkyl, CF3, NMe2, and OTIPS.7b
The scope of boronic esters was investigated next (Table
2). Boronic esters containing larger alkyl substituents such as
ethyl (2b), isopropyl (2c) or cyclopropyl (2d) were well tolerated
and the coupled products 3ba–3da were isolated in 79–93%
yield. An OTBS group was well tolerated when KH2PO4 was
added with iodine as shown for 3ea, which was obtained in 74%
yield. Similarly to the OCH2OEt group (vide supra), the OTBS
group was cleaved in the absence of base and the free alcohol
3fa was obtained in similar yield. Using KH2PO4 as additive,
other functional groups such as acetal (3ga), ester (3ha), nitrile
(3ia), azide (3jb), or olefin (3kb) were tolerated as well and the
Besides ethers, acetal groups were also found to be
effective directing group as exemplified by 3an, which was
obtained in 52% yield when KH2PO4 was added to quench HI
formed during the reaction. In the absence of base, the free
ortho-phenol 3ao was isolated in 83% and with complete
enantiospecificity. Again, functional groups were well tolerated
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10.1002/anie.201711816
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COMMUNICATION
Table 2. Substrate scope of boronic esters 2 for enantiospecific sp2-sp3 coupling to access ortho-cross-coupled aromatics.a
DG
Li
R
DG
Cr
OC
OC
(1.25 equiv)
CO
R’
Bpin
Bpin
DG
I2 (10 equiv)
Cr
R
R’
R
R’
OC
OC
n-PrOH
–78 °C to rt, o/n
THF or Et2O
–78 °C, 4 h
CO
2
3
OTBS
OH
O
6
6
O
MeO
MeO
3aa
90%, er: 96:4
es: 100%
3ba
93%, er: 99:1
es: 100%
3cab
85%, er: n.d.
3da
79%, er: 95:5
es: 100%
3eac
74%, er: 96:4
es: 100%
3fad
85%, er: 96:4
es: 100%
3gac
83%, er: 97:3
es: 100%
MeO
MeO
MeO
MeO
N3
CO2tBu
CN
3iac
71%, er: 97:3
es: 100%
3jbc
91%, er: 98:2
es: 100%
3hac
79%, er: 96:4
es: 100%
3mb
74%, dr > 20:1
3na
0%
3kb
93%, er: 97:3
es: 100%
3lb
78%
a Reactions were carried out with 0.30 mmol of boronic ester, 1.25 equiv of lithiated chromium arene complex, and 10.0 equiv of I2. Yields recorded are those of
isolated material. b No separation achieved by HPLC. c K2HPO4 added with I2 in MeOH. d TBS ether employed and no base used during oxidation.
products were obtained in high yield and with perfect
enantiospecificity. Finally, while the sterically demanding
menthyl boronic ester 2m was successfully coupled to afford
3mb in 74% and >20:1 dr, the coupling was unsuccessful with
tertiary boronic esters such as AdBpin (2n), possibly because of
the increased steric bulk leading to inefficient boronate formation.
To shed light on the reaction mechanism of this new
transformation, chromium benzene complex 1a was treated with
n-BuLi and MeBpin and the solution was stirred for 4 h at –78 °C
in THF, at which point the 11B NMR spectrum showed a singlet
at 3.0 ppm characteristic of boronate complex 4 (Scheme 2). To
our surprise, the 11B NMR spectrum did not change upon stirring
overnight at rt indicating that the chromium tricarbonyl group
was not sufficiently electron-withdrawing for the 1,2-migration to
occur. Complex 4 was isolated in 73% after trituration with Et2O
and the structure was unambiguously proven by X-ray
crystallography as the monohydrate THF adduct (Figure 1).15
Li
Li
O
B
Me
Figure 1. X-ray structure of 4 (ellipsoids are set at 30% probability (hydrogen
atoms and a THF molecule omitted for clarity). Selected bond lengths [Å]: Cr–
C1 1.810(2), C1–O1 1.166(3), Cr–C2 1.837(2), C2–O2 1.159(3), Cr–C3
1.837(3), C3–O3 1.156(3).
O
THF, –78 °C to rt
73%
+
MeBpin
Cr
OC
OC
(prepared from 1a)
CO
Cr
OC
OC
CO
4
Scheme 2. Isolation of surprisingly stable chromium boronate complex 4.
To explain the observed reactivity we propose the
mechanism outlined in Scheme 3. Two reaction pathways are
feasible when boronate 4 is treated with I2. In the minor pathway,
it reacts as an organometallic-type nucleophile at the sp3 carbon
to give the SN2 iodination product (vide supra).9 In the major
pathway however, oxidation occurs at the electron-rich
chromium center. This would render the Cr(CO)3 motif more
electron-withdrawing, triggering the 1,2-migration leading to the
cyclohexadienyl complex. In the presence of alcoholic solvent,
the boronic ester is eliminated (with formation of H+) to give the
cross-coupled chromium arene complex. Finally, the arene is
decomplexed in the presence of excess iodine.
The crystal structure of 4 shows a planar arrangement of
the six-membered ring with aromaticity clearly intact. The lithium
counterion coordinates to an oxygen of the pinacol moiety, two
solvent molecules (water and thf), as well as end-on to a CO
ligand of the Cr(CO)3 fragment. When this fragment is compared
to the related complex [Cr(CO)3(C6H5CH(OEt)2)],16 the average
C–O (carbon monoxide) bond length in 4 is slightly longer (1.160
Å vs. 1.152 Å) and the average Cr–C bond length is slightly
shorter (1.828 Å vs. 1.840 Å). This indicates a stronger back-
donation from the metal center, which can be attributed to
greater electron donation from the electron rich aromatic ring.
This is in agreement with IR spectroscopy, where the CO bands
are at considerably lower frequency when compared to the
parent chromium complex 1a (1940 and 1825 cm–1 vs. 1982 and
1915 cm–1),17 indicating an electron-rich chromium center.
In conclusion, we have developed a new sp2-sp3 cross-
coupling reaction, which relies on the use of easily accessible,
electronically diverse chromium arene complexes, which act as
traceless mediators to give the desired products in high yield,
excellent ortho-selectivity and complete enantiospecificity.
Based of the X-ray structure of boronate 4, a mechanism based
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10.1002/anie.201711816
Angewandte Chemie International Edition
COMMUNICATION
Me
Me
P. Conti-Ramsden, J. N. Harvey, D. Leonori, V. K. Aggarwal, J. Am.
Chem. Soc. 2016, 138, 9521; d) V. Ganesh, M. Odachowski, V. K.
Aggarwal, Angew. Chem. Int. Ed. 2017, 56, 9752 – 9756; Angew.
Chem. 2017, 129, 9884; e) S. Aichhorn, R. Bigler, E. L. Myers, V. K.
Aggarwal, J. Am. Chem. Soc. 2017, 139, 9519; f) C. M. Wilson, V.
Ganesh, A. Noble, V. K. Aggarwal, Angew. Chem. Int. Ed. 2017, 56,
DOI: 10.1002/anie.201710777; Angew. Chem. 2017, 129, DOI:
10.1002/ange.201710777.
Me
I2
Bpin
Bpin
Cr0
Cr0
elimination
oxidation
CrII
OC
OC
OC
OC
OC
OC
CO
CO
CO
HOR
1,2-migration
(not observed)
Me
Bpin
Bpin
I2
I
Cr0
+
Cr0
Me
OC
OC
SN2-iodination
(minor)
OC
OC
[5]
a) S. Panda, A. Coffin, Q. N. Nguyen, D. J. Tantillo, J. M. Ready,
Angew. Chem. Int. Ed. 2016, 55, 2205; Angew. Chem. 2016, 128,
2245; b) S. Panda, J. M. Ready, J. Am. Chem. Soc. 2017, 139, 6038.
E. P. Kündig in Topics in Organometallic Chemistry VII (Ed: E. P.
Kündig), Springer, Berlin, 2004, pp. 3 – 20.
CO
CO
4
oxidation
(major)
I2
[6]
[7]
Me
Bpin
Me
Me
I2
a) M. F. Semmelhack in Comprehensive Organometallic Chemistry II
(Eds.: E. W. Abel, F. G. A. Stone, G. Wilkinson), Pergamon, Oxford,
1995, pp. 979 – 1015; b) M. F. Semmelhack, A. Chlenov in Topics in
Organometallic Chemistry VII (Ed: E. P. Kündig), Springer, Berlin, 2004,
pp. 43 – 69.
Bpin
Cr0
CrII
OC
CrII
OC
OC
Me
OC
OC
CO
CO
CO
HOR
elimination
OC
1,2-migration
decomplexation
Scheme 3. Proposed mechanism for chromium arene-mediated coupling.
[8]
[9]
a) P. Ricci, K. Krämer, X. C. Cambeiro, I. Larrosa, J. Am. CHem. Soc.
2013, 135, 13258; b) P. Ricci, K. Krämer, I. Larrosa, J. Am. CHem. Soc.
2014, 136, 18082; c) D. Whitaker, M. Batuecas, P. Ricci, I. Larrosa,
Chem. Eur. J. 2017, 23, 12763.
on selective oxidation of Cr(0) followed by 1,2-migration and
elimination is proposed. Although there has been a recent surge
in stereoselective cross-coupling strategies,2–5 most of the
products presented here are inaccessible by such methods.
Thus, the current method is a valuable addition to the ever-
growing arsenal of cross-coupling reactions.
R. Larouche-Gauthier, T. G. Elford, V. K. Aggarwal, J. Am. Chem. Soc.
2011, 133, 16794.
[10] OTIPS and NMe2 do not act as ortho-directing groups for the lithiation
of chromium arene complexes, see: a) N. F. Masters, D. A. Widdowson,
J. Chem. Soc., Chem. Commun 1983, 955; b) R. J. Card, W. S.
Trahanovsky, J. Org. Chem. 1980, 45, 2560.
[11] H.-G. Schmalz, T. Volk, D. Bernicke, S. Huneck, Tetrahedron 1997, 53,
9219.
[12] For a related substrate, see: J. C. Gill, B. A. Marples, J. R. Traynor,
Tetrahedron Lett. 1987, 28, 2643.
Acknowledgements
[13] M. F. Costa, M. R. G. da Costa, M. J. M. Curto, M. Magrinho, A. M.
Damas, L. Gales, J. Organomet. Chem. 2001, 632, 27.
We thank Dr. Natalie E. Pridmore for X-ray analysis of 4 and the
[14] For recent review articles, see: a) J. Wang, M. Sánchez-Roselló, J. Luis
Aceña, C. del Pozo, A. E. Sorochinsky, S. Fustero, V. A. Soloshonok, H.
Liu, Chem. Rev. 2014, 114, 2432; b) T. Fujiwara, D. O’Hagan, J. Fluor.
Chem. 2014, 167, 16.
University of Bristol for financial support. R.B. thanks the Swiss
National
Science
Foundation
fellowship
program
(P2EZP2_1652).
[15] CCDC 1585569 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Keywords: boronic esters • chromium complexes • aromatics •
arylation • cross-coupling
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.
[16] T. M. Gilbert, C. B. Bauer, R. D. Rogers, J. Chem. Crystallogr. 1996, 26,
[1]
[2]
For recent review articles, see: a) D. Leonori, V. K. Aggarwal, Angew.
Chem. Int. Ed. 2015, 54, 1082; Angew. Chem. 2015, 127, 1096; b) C.-
Y.Wang, J. Derosa, M. R. Biscoe, Chem. Sci. 2015, 6, 5105; c) A. H.
Cherney, N. T. Kadunce, S. E. Reisman, Chem. Rev. 2015, 115, 9587.
a) S.-M. Zhoi, M.-Z. Deng, L.-J. Xia, M.-H. Tang, Angew. Chem. Int. Ed.
1998, 37, 2845; Angew. Chem. 1998, 110, 3061; b) M. Rubina, M.
Rubin, V. Gevorgyan, J. Am. Chem. Soc. 2003, 125, 7198; c) T.
Ohmura, T. Awano, M. Suginome, J. Am. Chem. Soc. 2010, 132,
13191; d) T. Awano, T. Ohmura, M. Suginome, J. Am. Chem. Soc.
2011, 133, 20738; e) B. W. Glasspoole, M. S. Oderinde, B. D. Moore, A.
Antoft-Finch, C. M. Crudden, Synthesis 2013, 45, 1759; f) D. Imao, B.
W. Glasspoole, V. S. Laberge, C. M. Crudden, J. Am. Chem. Soc. 2009,
131, 5024; g) S. C. Matthew, B. W. Glasspoole, P. Eisenberger, C. M.
Crudden, J. Am. Chem. Soc. 2014, 136, 5828; h) L. Chausset-Boissarie,
K. Ghozati, E. LaBine, J. L.-Y. Chen, V. K. Aggarwal, C. M. Crudden,
Chem. Eur. J. 2013, 19, 17698.
355.
[17] C. A. L. Mahaffy, P. L. Pauson, Inorg. Synth. 1979, 19, 154.
[3]
For related trifluoroborates, see: a) G.-H. Fang, Z.-J. Yan, M.-Z. Deng,
Org. Lett. 2004, 6, 357; b) D. L. Sandrock, L. Jean-Gérard, C. Chen, S.
D. Dreher, G. A. Molander, J. Am. Chem. Soc. 2010, 132, 17108; c) J.
C. H. Lee, R. McDonald, D. G. Hall, Nat. Chem. 2011, 3, 894; d) G. A.
Molander, S. R. Wisniewski, J. Am. Chem. Soc. 2012, 134, 16856; e) L.
Li, S. Zhao, A. Joshi-Pangu, M. Diane, M. R. Biscoe, J. Am. Chem. Soc.
2014, 136, 14027; f) Y. Lou, P. Cao, T. Jia, Y. Zhang, M. Wang, J. Liao,
Angew. Chem. Int. Ed. 2015, 54, 12134; Angew. Chem. 2015, 127,
12302.
[4]
a) A. Bonet, M. Odachowski, D. Leonori, S. Essafi, V. K. Aggarwal, Nat.
Chem. 2014, 6, 584; b) J. Llaveria, D. Leonori, V. K. Aggarwal, J. Am.
Chem. Soc. 2015, 137, 10958; c) M. Odachowski, A. Bonet, S. Essafi,
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10.1002/anie.201711816
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ortho-Directing Chromium Arene
Complexes as Efficient Mediators for
Enantiospecific sp2-sp3 Cross-
Coupling Reactions
The sp2-sp3 coupling of chromium arene complexes with boronic esters is reported.
After ortho-selective lithiation of the aromatic and boronate formation, oxidation at
the electron-rich chromium center with I2 triggers the 1,2-migration and Bpin
elimination to directly afford the decomplexed ortho-coupled products in high yield
and with complete enantiospecificity.
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