Organic Letters
Letter
were obtained in high yields and with excellent selectivity in all
cases, even when the highly hindered 2,4,6-triisopropylphenyl-
lithium was used (2j).
Importantly, substrate 5a could be efficiently arylated with 2,6-
dimethoxyphenyllithium. To the best of our knowledge, the
synthesis of the corresponding 3,3′-diaryl BINOL 6d has no
precedent in the literature. Besides the bulkiness given by the two
ortho-substituents in the aryl groups, this BINOL offers the
possibility of an additional coordination of the methoxy groups
to e.g. a metallic center.22 A bulky trisubstituted aryllithium
reagent such as mesityllithium was also readily coupled under
these conditions. In this case substrate 5a gave rise to poor yield
and it was necessary to use (S)-3,3′-dichloro-2,2′-bis(methoxy)-
1,1′-binaphthalene 5b as a coupling partner in order to obtain
3,3′-dimesityl BINOL 6e in high yield. Remarkably, 3,3′-
bis(2,4,6-triisopropylphenyl)-2,2′-dimethoxy-1,1′-binaph-
thalene 6f could be synthesized by the Pd-catalyzed cross-
coupling of 2,4,6-triisopropylphenyllithium. Despite the large
steric hindrance of both coupling partners, the reaction could be
successfully carried out under these mild conditions (40 °C, 2 h)
achieving high yield (76%) and selectivity. Importantly, the
reaction could be also performed on a larger scale (1.6 mmol)
with a similar result. It is important to note that binaphthalene 6f
is the precursor of 3,3′-bis(2,4,6-triisopropylphenyl)-1,1′-
binaphthyl-2,2′-diyl hydrogen phosphate (TRIP) which has
emerged as a very powerful catalyst in terms of activity and
enantioselectivity for several asymmetric transformations.23 The
present methodology gives straightforward access to this
precursor with high efficiency in a very short reaction time.
In summary, we have developed a palladium-catalyzed cross-
coupling of aryllithium reagents with 2-alkoxy-substituted aryl
chlorides. The reaction proceeds under mild conditions in short
reaction times and affords 2-alkoxy-substituted biaryls in very
good yields with high selectivity. The use of a chloride as a
substrate is key to avoiding the undesired formation of side
products as the competing lithium−halogen exchange is
suppressed. In addition, this highly practical methodology gives
ready access to chiral 3,3′-diaryl 1,1′-bi-2-naphthols which are
key compounds for asymmetric catalysis. As far as we know, this
methodology represents the first example of the synthesis of
these compounds from the corresponding 3,3′-dichloro 1,1′-bi-
2-naphthols.
Chiral 3,3′-diaryl-1,1′-bi-2-naphthols (BINOLs) represent a
very important class of 2-alkoxy substituted biaryls. These
compounds,3 and the corresponding phosphorus derivatives,
such as phosphoramidites17 and phosphoric acids,18 have been
successfully used as ligands or catalysts in a variety of catalytic
asymmetric reactions. The importance of the aryl substituents at
the 3,3′-positions is due to the fact that their electronic and steric
properties play a crucial role in the performance of the catalyst
resulting from their proximity to the catalytic center. The
development of new, simple, and versatile complementary
methods for the introduction of different aryl groups in the
3,3′-positions of the binaphthol backbone is highly desirable.
Methods for the synthesis of 3,3′-diaryl BINOLs include
Kumada coupling,19 Suzuki coupling,20 and Negishi coupling.21
However, these protocols involve either reactive aryl iodides or
bromides and frequently require high temperatures and/or long
reaction times. We envisioned that the palladium-catalyzed cross-
coupling of organolithium reagents and 2-alkoxy-substituted aryl
chlorides might be applied to the synthesis of 3,3′-diaryl BINOLs
providing a useful alternative. This would represent a fast and
mild protocol and the first example of the use of an aryl chloride
for the synthesis of these important compounds. To our delight,
this new methodology proved to be very efficient for this
coupling, and a range of different 3,3′-diaryl BINOLs could be
obtained in very good yield and selectivity from the
corresponding aryllithium reagents and 3,3′-dichloro BINOLs
(Scheme 3).
Scheme 3. Synthesis of 3,3′-diaryl BINOLs by Pd-Catalyzed
a
Cross-Coupling with Aryllithium Reagents
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and characterization data. This material
AUTHOR INFORMATION
Corresponding Authors
■
Notes
a
Conditions: ArLi (0.6 mmol) added over 2 h to a solution of 5 (0.2
mmol) in toluene (1 mL). Yield values refer to isolated products after
purification. Yield in brackets refers to the reaction run on a 1.6
b
The authors declare no competing financial interest.
mmol (613 mg) scale.
ACKNOWLEDGMENTS
■
The coupling between phenyllithium and (S)-3,3′-dichloro-
2,2′-bis(methoxymethoxy)-1,1′-binaphthalene 5a could be
performed in high selectivity using the optimized catalytic
system and afforded BINOL 6a in 86% yield. Similarly, the use of
3-trifluoromethylphenyllithium and [1,1′-biphenyl]-4-yllithium
gave rise to the corresponding 3,3′-diaryl BINOLs 6b and 6c in
excellent yields. Diortho-substituted aryllithium reagents were
also efficient coupling partners for this transformation.
The Netherlands Organization for Scientific Research (NWO−
CW), the National Research School Catalysis (NRSC-C), the
European Research Council (ERC Advanced Grant 227897 to
B.L.F.), the Royal Netherland Academy of Arts and Sciences
(KNAW), and the Ministry of Education Culture and Science
(Gravitation program 024.601035) are acknowledged for
financial support. C.V. was supported by an Intra-European
Marie Curie fellowship (FP7-PEOPLE-2011-IEF) (Contract
C
dx.doi.org/10.1021/ol5032409 | Org. Lett. XXXX, XXX, XXX−XXX