10.1002/anie.201905934
Angewandte Chemie International Edition
COMMUNICATION
chiral ligand.[11,21] Enantiomeric ratios as high 97:3 have been
achieved for this enantioselective C(sp3)–Si bond formation.
CuCl (10 mol%)
(R,SP)-15 (15 mol%)
BF3·OEt2 (2.0 equiv)
Me2PhSiMgHal
(Hal = Cl/Br, 1.5 equiv)
N
N
SiMe2Ph
R1
R1
R2
R2
O
O
toluene/Et2O
–78 °C for 12 h
Acknowledgements
1d n
(S)-8d v
heteroaryl substitution
SiMe2Ph
This research was supported by the China Scholarship Council
through predoctoral fellowships to W.M. (2017–2021) and W.X.
(2015–2019). M.O. is indebted to the Einstein Foundation Berlin
for an endowed professorship. We thank the Solvias AG for the
generous donation of (R,Sp)-15.
aryl substitution
N
O
SiMe2Ph
N
O
S
R1
(S)-8d (R1 = H): 65%, e.r. 96.5:3.5
(S)-8e (R1 = iPr): 76%, e.r. 93:7
(S)-8f (R1 = OMe): 45%, e.r. 95.5:4.5
(S)-8g (R1 = F): 51%, e.r. 90:10[a]
(S)-8h (R1 = Cl): 63%, e.r. 80.5:19.5
(S)-8k: 80%, e.r. 85:15
N
SiMe2Ph
Conflict of interest
O
X-ray for (S)-8d
X
The authors declare no conflict of interest.
(S)-8l (X = O): 62%, e.r. 87.5:12.5
(S)-8m (X = S): 75%, e.r. 91:9
N
SiMe2Ph
R1
Keywords: asymmetric catalysis • conjugate addition • copper •
O
N
SiMe2Ph
magnesium • silicon
(S)-8i (R1 = Me): 77%, e.r. 88:12
O
(S)-8j (R1 = OMe): 70%, e.r. 87.5:12.5
X
[1]
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(S)-8n (X = O): 79%, e.r. 86:14
(S)-8o (X = S): 88%, e.r. 95:5
benzoxazole substitution
R2
R2
N
SiMe2Ph
[2]
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2409.
N
SiMe2Ph
O
O
(S)-8t (R2 = Me): 73%, e.r. 95:5
(S)-8u (R2 = F): 76%, e.r. 89.5:10.5
(S)-8p (R2 = Me): 82%, e.r. 90:10
(S)-8q (R2 = Ph): 50%, e.r. 85:15
(S)-8r (R2 = F): 70%, e.r. 88:12
(S)-8s (R2 = Cl): 58%, e.r. 90:10
Me
Me
N
SiMe2Ph
O
[3]
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(S)-8v: 35%, e.r. 91.5:8.5[a]
Scheme 3. Copper-catalyzed enantioselective addition of the silicon Grignard
reagent to various alkenyl-substituted benzoxazole derivatives. [a] 5.0 equiv of
BF3·OEt2 used.
An important synthetic application of the silyl group is that it
can be used as an equivalent of the hydroxy group.[1c] Tamao–
Fleming oxidation[20] of (S)-8a yielded alcohol (S)-16a in 67%
yield and with retention of configuration (Scheme 4). The
absolute configuration of 16 was assigned as S by X-ray
diffraction.[19]
[4]
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[7]
[8]
[9]
For an authoritative perspective, see: D. Best, H. W. Lam, J. Org.
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Scheme 4. Enantiospecific oxidative degradation of the C(sp3)–Si bond.
[10] See also: R. Amengual, V. Michelet, J.-P. Genêt, Tetrahedron Lett.
2002, 43, 5905–5908.
[11] a) R. P. Jumde, F. Lanza, M. J. Veenstra, S. R. Harutyunyan, Science
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To conclude, we accomplished a copper-catalyzed, highly β-
selective addition of silicon Grignard reagents to alkenes
activated by azaaryl groups. An enantioselective version was
developed for benzoxazole-derived substrates with a Josiphos
[12] a) W. Xue, R. Shishido, M. Oestreich, Angew. Chem. Int. Ed. 2018, 57,
12141–12145; Angew. Chem. 2018, 130, 12318–12322; these silicon
Grignard reagents have already been applied to allylic substitution and
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