Organic Letters
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data for this paper. These data can be obtained free of charge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK; fax: +44 1223 336033.
Figure 1. Assignment of absolute configuration: molecular structure of
compound (S)-5i.
AUTHOR INFORMATION
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Corresponding Author
ORCID
Scheme 3. Stereospecific Copper-Catalyzed Nucleophilic
Substitution of Enantioenriched α-Triflyloxy Esters with
Inversion of the Configuration
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This research was supported by the Deutsche Forschungsge-
meinschaft (Oe 249/15-1) and the Alexander von Humboldt
Foundation (Georg Forster Research Fellowship to H.H.,
2016−2018). M.O. is indebted to the Einstein Foundation
(Berlin) for an endowed professorship.
REFERENCES
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(1) Cinderella, A. P.; Vulovic, B.; Watson, D. A. J. Am. Chem. Soc.
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a
Erosion of the enantiomeric purity occurred during the triflation of
11652.
the corresponding α-hydroxy ester.
(5) For recent reviews of Si−B chemistry, see: (a) Delvos, L. B.;
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(6) For the preparation of the Si−B reagents, see: Suginome, M.;
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(7) Secondary alkyl triflates without a geminal electron-withdrawing
group were not stable, even at temperatures below 0 °C: Scharfbier, J.;
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(8) For the catalytic generation of racemic α-silylated nitriles by
hydrosilylation see: (a) Ojima, I.; Kumagai, M.; Nagai, Y. J. Organomet.
Chem. 1976, 111, 43−60. (b) Dong, H.; Jiang, Y.; Berke, H. J.
Organomet. Chem. 2014, 750, 17−22. (c) Komine, N.; Abe, M.; Suda,
R.; Hirano, M. Organometallics 2015, 34, 432−437. For the synthesis
of α-silylated nitriles by a cuprate addition−migration sequence, see:
(d) Kondo, J.; Ito, Y.; Shinokubo, H.; Oshima, K. Angew. Chem., Int.
Ed. 2004, 43, 106−108. (e) Kondo, J.; Inoue, A.; Ito, Y.; Shinokubo,
H.; Oshima, K. Tetrahedron 2005, 61, 3361−3369.
(9) Stereospecific Suzuki−Miyaura cross-coupling of α-triflyloxy
nitriles: (a) He, A.; Falck, J. R. J. Am. Chem. Soc. 2010, 132, 2524−
2525. Stereoconvergent Negishi coupling of racemic α-bromo nitriles:
(b) Choi, J.; Fu, G. C. J. Am. Chem. Soc. 2012, 134, 9102−9105.
Enantioselective reductive coupling of racemic α-chloro nitriles and
hetereoaryl iodides: (c) Kadunce, N. T.; Reisman, S. E. J. Am. Chem.
Soc. 2015, 137, 10480−10483.
nitriles (cf. 1 → 5, Scheme 2 and Table 2). However, the
enantiospecificity was again excellent throughout, thus
providing a convenient and practical access to this class of
compounds.17,18 The low enantiomeric excess of α-triflyloxy
ester 6e is due to racemization during triflation of the sterically
unhindered α-hydroxy ester. The absolute configuration of the
α-silylated esters (R)-7 was secured by comparison with the
literature-known optical rotation of (R)-7e.17a
We have shown here that a range of α-triflyloxy nitriles and
esters undergo copper-catalyzed C(sp3)−Si cross-coupling with
inversion of the configuration. The resulting enantioenriched α-
silylated nitriles had not been accessible before while the
present formation of α-silylated esters complements the
existing approach by enantioselective carbenoid insertion into
Si−H bonds.17,19
ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge on the
(10) Breit and co-workers developed a methodology based on
stereospecific zinc-catalyzed nucleophilic substitution of α-triflyloxy
esters with Grignard reagents: (a) Studte, C.; Breit, B. Angew. Chem.,
Int. Ed. 2008, 47, 5451−5455. (b) Brand, G. J.; Studte, C.; Breit, B.
General procedures, experimental details, and character-
ization/spectral data for all new compounds (PDF)
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