Organic Letters
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and electron-donating substituents lead to improved results. In
the series of five-membered heteroaryl groups, pinacol
boronates tend to give higher yields than MIDA boronates
and 3-pyrrolyl, thienyl, and furanyl derivatives produce the best
results. For 2-boronated pyrrolyl, thienyl, and furanyl
compounds, yields vary greatly with the heteroaryl group.
Good to excellent results are obtained for electron-rich 2-
pyrrolylboronates, while thienyl and furanyl reagents at best
give moderate yields. The asymmetric reaction is even more
sensitive toward the substrate. Of the pyridine series, only the
methoxy-substituted 3-pyridinyl derivative gives the desired
product. For five-membered heteroaryl residues, high yields are
obtained with 3-thienyl and pyrrolyl derivatives, while those for
3-furanylboronates are moderate. 2-Thienyl and furanyl
derivatives produce modest yields, and for 2-pyrrolylboronates,
only the electron-rich substrate was successful. Further, it
should be noted that all but three of the asymmetric reactions
gave more than 90% ee.
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The modest yields for many reactions from Table 2 may be
caused by two distinctive factors: (1) Protodeboration of the
heteroarylboronic acids liberated from the respective boronate
may be faster than transmetalation to the rhodium catalyst or
(2) after transmetalation, protoderhodation of the heteroaryl-
rhodium complex may become a competing side reaction to the
desired 1,4-addition. We are currently conducting NMR studies
to elucidate which of these factors is crucial for 1,4-additions
with heterorarylboronates. Adjusting the decomposition rate of
the boronate reagent may to some extent avoid unproductive
protodeboration of the liberated heteroaylboronic acid. The
transmetalation and/or the carborhodation steps may become
faster by employing modified catalysts, e.g. rhodium complexes
of electron-deficient phosphines.26
(12) Sakuma, S.; Sakai, M.; Itooka, R.; Miyaura, N. J. Org. Chem.
2000, 65, 5951.
(13) Tajuddin, H.; Shukla, L.; Maxwell, A. C.; Marder, T. B.; Steel, P.
G. Org. Lett. 2010, 12, 5700.
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(16) (a) Yu, S.-Q; Yamamoto, Y.; Miyaura, N. Synlett 2009, 994.
(b) Yu, X.-Q.; Shirai, T.; Yamamoto, Y.; Miyaura, N. Chem.Asian J.
2011, 6, 932.
(17) Knapp, D. M.; Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2009,
131, 6961.
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2011, 17, 9508.
(19) Pattison, G.; Piraux, G.; Lam, H. W. J. Am. Chem. Soc. 2010, 132,
14373.
(20) A single report has described the stereoselective 1,2-addition of
a heteroaryl MIDA to an imine: Brak, K.; Ellman, J. A. J. Org. Chem.
2010, 75, 3147.
(21) Minuth, M.; Boysen, M. M. K. Org. Lett. 2009, 11, 4212.
(22) Grugel, H.; Minuth, T.; Boysen, M. M. K. Synthesis 2010, 3248.
(23) Grugel, H.; Albrecht, F.; Minuth, T.; Boysen, M. M. K. Org. Lett.
2012, 14, 3780.
In conclusion, we have presented an extensive study on
heteroarylboronates in racemic and stereoselective rhodium-
catalyzed 1,4-additions. Further studies, aiming to improve
product yields and the scope of the asymmetric version, are
currently in progress in our laboratory.
ASSOCIATED CONTENT
* Supporting Information
■
(24) Grugel, H.; Albrecht, F.; Boysen, M. M. K. Adv. Synth. Catal.
2014, DOI: 10.1002/adsc.201400459.
S
Full experimental details, characterization data, copies of
spectra and chromatograms. This material is available free of
(25) Preparation of pinacol boronate 4o from pyrrole: (a) Muchow-
ski, J. M.; Solas, D. R. Tetrahedron Lett. 1983, 24, 3455. (b) Morrison,
M. D.; Hanthorn, J. J.; Pratt, D. A. Org. Lett. 2009, 11, 1051. (c) Ayats,
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C.; Soley, R.; Albericio, F.; Alvarez, M. Org. Biomol. Chem. 2009, 7,
860.
(26) Genet
2014, 114, 2824.
AUTHOR INFORMATION
Corresponding Author
■
̂
, J. P.; Ayad, T.; Ratovelomanana-Vidal, V. Chem. Rev.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support by the DFG (BO 1938/5-1), Rodos
BioTarget GmbH, and a DFG Heisenberg Fellowship for
M.M.K.B. (BO 1938/4-1) is gratefully acknowledged. The
authors thank BSc. Nicola Steinke (Leibniz University of
Hannover) for studies on MIDA boronate 7c during her
project work.
REFERENCES
■
(1) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.; Miyaura, N. J.
Am. Chem. Soc. 1998, 120, 5579.
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dx.doi.org/10.1021/ol502630w | Org. Lett. XXXX, XXX, XXX−XXX