ORGANIC
LETTERS
2011
Vol. 13, No. 6
1366–1369
Efficient Monophosphorus Ligands for
Palladium-Catalyzed Miyaura Borylation
Wenjun Tang,* Santosh Keshipeddy, Yongda Zhang, Xudong Wei, Jolaine Savoie,
Nitinchandra D. Patel, Nathan K. Yee, and Chris H. Senanayake
Chemical Development, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield,
Connecticut 06877, United States
Received January 7, 2011
ABSTRACT
In combination with the Bedford Pd precursor, the new biaryl monophosphorus ligand 5 was efficient for palladium-catalyzed Miyaura borylation
of sterically hindered aryl bromides at low catalyst loadings.
Arylboronic acids or esters are key chemical building
blocks in synthetic organic chemistry that have been
utilized for a variety of chemical transformations.1 Of
particular importance are their applications in transition-
metal-catalyzed cross-coupling reactions, of which are the
well-known Suzuki-Miyaura coupling reactions.2 The
syntheses of aryl boronic acids or esters have thus gained
a great deal of attention, and a few methods have emerged.3
One of the most common methods includes the transmeta-
lation of aryl lithium or Grignard reagents with trialkyl
borates.4 However, this method generally requires harsh
reaction conditions and is incompatible with sensitive
functional groups. By using aryl halides and bis(pinacolato)-
diboron as the reagents, the palladium-catalyzed Miyaura
borylation is more functionality-tolerable and has become
an important alternative for the synthesis of arylboronic
esters.5 A recent modification using pinacolborane as the
reagent is attractive albeit with more limitations of the
substrate scope.6 Despite these progresses,7,8 Miyaura bor-
ylation of sterically hindered aryl halides remains a very
challenging task. For example, only a modest yield (72%)
was achieved on the palladium-catalyzed borylation of
2-bromo-1,3,5-triisopropylbenzene at a high catalyst load-
ing (5 mol %).6d We herein report the application of biaryl
monophosphorus ligands 1and 5(Figure 1) in the palladium-
catalyzed Miyaura borylation. Excellent reactivities have
been achieved on a series of sterically hindered aryl
bromides.
We have developed a series of conformationally rigid
biaryl monophosphorus ligands containing a 2,3-dihydro-
benzo[d][1,3]oxaphosphole substructure 1-4 and have
(1) For recent reviews, see: (a) Merino, P.; Tejero, T. Angew. Chem.,
Int Ed. 2010, 49, 7164. (b) Kotha, S.; Lahiri, K.; Kashinath, D.
Tetrahedron 2002, 58, 9633.
(2) (a) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979,
36, 343. (b) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(3) For rhodium- and iridium-catalyzed borylation of arene C-H
bonds, see a recent review: Mkhalid, I. A. I.; Barnard, J. H.; Marder,
T. B.; Murphy, J. C.; Hartwig, J. F. Chem. Rev. 2010, 110, 890.
(4) Suzuki, A.; Brown, H. C. Organic Syntheses via Boranes; Aldrich
Chemial Company: Milwakee, 2003; Vol. 3.
(5) (a) Ishiyama, T.; Murata, M.; Miyaura, N. J. Org. Chem. 1995,
60, 7508. (b) Ishiyama, T.; Ishida, K.; Miyaura, N. Tetrahedron 2001, 57,
9813. (c) Furstner, A.; Seidel, G. Org. Lett. 2002, 4, 541. (d) Billingsley,
K. L.; Barder, T. E.; Buchwald, S. L. Angew. Chem., Int. Ed. 2007, 46,
5359. (e) Xu, C.; Gong, J.-F.; Song, M.-P.; Wu, Y.-J. Transition Met.
Chem. 2009, 34, 175.
(6) (a) Murata, M.; Watanabe, S.; Masuda, Y. J. Org. Chem. 1997,
62, 6458. (b) Murata, M.; Oyama, T.; Watanabe, S.; Masuda, Y. J. Org.
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Chem. 2000, 65, 164. (c) Broutin, P.-E.; Cerna, I.; Campaniello, M.;
Leroux, F.; Colobert, F. Org. Lett. 2004, 6, 4419. (d) Murata, M.;
Sambommatsu, T.; Watanabe, S.; Masuda, Y. Synlett 2006, 1867. (e)
Billingsley, K. L.; Buchwald, S. L. J. Org. Chem. 2008, 73, 5589. (f) Lam,
K. C.; Marder, T. B.; Lin, Z. Organometallics 2010, 29, 1849.
(7) For Ni-catalyzed borylation, see: (a) Rosen, B.; Huang, C .;
Percec, V. Org. Lett. 2008, 10, 2597. (b) Moldoveanu, C.; Wilson,
D. A.; Wilson, C. J.; Leowanawat, P.; Resmerita, A.-M.; Liu, C.; Rosen,
B. M.; Percec, V. J. Org. Chem. 2010, 75, 5438. (c) Wilson, D. A.; Wilson,
C. J.; Moldoveanu, C.; Resmerita, A.-M.; Corcoran, P.; Hoang, L. M.;
Rosen, B. M.; Percec, V. J. Am. Chem. Soc. 2010, 132, 1800.
(8) With tetrahydroxydiboron as the reagent, see: Molander, G. A.;
Trice, S. L. J.; Dreher, S. D. J. Am. Chem. Soc. 2010, 132, 17701.
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10.1021/ol2000556
Published on Web 02/14/2011
2011 American Chemical Society