ORGANIC
LETTERS
2011
Vol. 13, No. 8
2094–2097
Activation of the SiÀB Linkage:
Copper-Catalyzed Addition of
Nucleophilic Silicon to Imines
†
,†
Devendra J. Vyas,†,‡ Roland Frohlich, and Martin Oestreich*
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Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat Munster,
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Corrensstrasse 40, 48149 Mu€nster, Germany
Received February 24, 2011
ABSTRACT
Activation of the SiÀB bond through copper-catalyzed transmetalation quickly developed into a practical method to generate CuÀSi reagents.
These silicon nucleophiles cleanly add to aldehyde-derived imine electrophiles to form R-silylated amines in protic media, and no carbon-to-
nitrogen Brook-type rearrangement of the intermediate anion is observed. Aside from electron-withdrawing groups at the imine nitrogen atom, for
example, SO2Tol and P(O)Ph2, previously delicate nitrogen substituents such as phenyl or benzhydryl are tolerated. The same protocol also
allows the unprecedented addition to representative ketone-derived imines.
The SiÀB bond serves as a source of nucleophilic silicon,1
and its heterolytic cleavage is mediated by transition metalÀ
alkoxide complexes, corresponding to a transmetalation of
the silicon group from the boron atom to the transition metal.
The recent development of rhodium(I)-2 and copper(I)-
catalyzed3 protocols for SiÀB bond activation and subse-
quent selective CÀSi bond formation is currently garnering
considerable attention. The emerging copper(I) catalysis is
particularly attractive as the catalytically generated CuÀSi
reagent represents an alternative to established silicon-based
cuprates,4 indeed opening the door to enantioselective con-
jugate additions3a,c and regioselective transformations.3e,f
Due to ongoing interest in silicon-containing peptide
isosteres5À7 and R-amino acids,8 a copper-catalyzed
(4) For a review of silicon-based cuprate chemistry catalytic in
copper, see: Weickgenannt, A.; Oestreich, M. Chem.ÀEur. J. 2010, 16,
402–412.
(5) For an authoritative review, see: (a) Sieburth, S. M.; Chen, C.-A.
Eur. J. Org. Chem. 2006, 311–322. (b) Sieburth, S. M.; Nittoli, T.;
Mutahi, A. M.; Guo, L. Angew. Chem., Int. Ed. 1998, 37, 812–814. (c)
Mutahi, M. W.; Nittoli, T.; Guo, L.; Sieburth, S. M. J. Am. Chem. Soc.
2002, 124, 7363–7375.
(6) Organ, M. G.; Buon, C.; Decicco, C. P.; Combs, A. P. Org. Lett.
2002, 4, 2683–2685.
†
€
€
Westfalische Wilhelms-Universitat M€unster.
‡ NRW Graduate School of Chemistry.
(1) For a recent summary of SiÀB chemistry, see: Ohmura, T.;
Suginome, M. Bull. Chem. Soc. Jpn. 2009, 82, 29–49.
(2) Conjugate addition: (a) Walter, C.; Auer, G.; Oestreich, M.
Angew. Chem., Int. Ed. 2006, 45, 5675–5677. (b) Walter, C.; Oestreich,
€
M. Angew. Chem., Int. Ed. 2008, 47, 3818–3820. (c) Walter, C.; Frohlich,
(7) (a) Nielsen, L.; Lindsay, K. B.; Nielsen, N. C.; Skrydstrup, T. J.
Org. Chem. 2007, 72, 10035–10044. (b) Nielsen, L.; Skrydstrup, T. J. Am.
R.; Oestreich, M. Tetrahedron 2009, 65, 5513–5520. (d) Hartmann, E.;
Oestreich, M. Angew. Chem., Int. Ed. 2010, 49, 6195–6198. Propargylic
substitution: (e) Ohmiya, H.; Ito, H.; Sawamura, M. Org. Lett. 2009, 11,
5618–5620.
ꢀ
Chem. Soc. 2008, 130, 13145–13151. (c) Hernandez, D.; Lindsay, K. B.;
Nielsen, L.; Mittag, T.; Bjerglund, K.; Friis, S.; Mose, R.; Skrydstrup, T.
ꢀ
J. Org. Chem. 2010, 75, 3283–3293. (d) Hernandez, D.; Nielsen, L.;
ꢀ
Lindsay, K. B.; Lopez-Garcıa, M. A.; Bjerglund, K.; Skrydstrup, T. Org.
´
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(3) Conjugate addition: (a) Lee, K.-s.; Hoveyda, A. H. J. Am. Chem.
Soc. 2010, 132, 2898–2900. (b) Welle, A.; Petrignet, J.; Tinant, B.;
Wouters, J.; Riant, O. Chem.ÀEur. J. 2010, 16, 10980–10983. (c)
Lett. 2010, 12, 3528–3531. (e) Hernandez, D.; Mose, R.; Skrydstrup, T.
Org. Lett. 2011, 13, 732–735.
ꢀ
Ibrahem, I.; Santoro, S.; Himo, F.; Cordova, A. Adv. Synth. Catal.
(8) For a review of silicon-containing R-amino acids: (a) Mortensen,
M.; Husmann, R.; Veri, E.; Bolm, C. Chem. Soc. Rev. 2009, 38, 1002–
1010. For selected references, see: (b) Bolm, C.; Kasyan, A.; Drauz, K.;
2011, 353, 245–252. Isocyanide addition: (d) Tobisu, M.; Fujihara, H.;
Koh, K.; Chatani, N. J. Org. Chem. 2010, 75, 4841–4847. Allylic substitu-
tion: (e) Vyas, D. J.; Oestreich, M. Angew. Chem., Int. Ed. 2010, 49, 8513–
8515. Alkyne addition: (f) Wang, P.; Yeo, X.-L.; Loh, T. P. J. Am. Chem.
Soc. 2011, 133, 1254–1256.
€
Gunther, K.; Raabe, G. Angew. Chem., Int. Ed. 2000, 39, 2288–2290. (c)
Chen, J.-X.; Tunge, J. A.; Norton, J. R. J. Org. Chem. 2002, 67, 4366–
4369. (d) Sun, H.; Moeller, K. D. Org. Lett. 2003, 5, 3189–3192.
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10.1021/ol200509c
Published on Web 03/18/2011
2011 American Chemical Society