iridium-catalyzed regioselective silylation of secondary ...ccc.chem.pitt.edu/wipf/current...
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Yongzhao Yan Wipf Group Current Literature 5-10-2014
Iridium-Catalyzed Regioselective Silylation of Secondary Alkyl C−H Bonds for the Synthesis of 1,3-Diols
Bijie Li, Matthias Driess, and John F. Hartwig.J. Am. Chem. Soc. 2014, ASAP.
dx.doi.org/10.1021/ja5026479
OSi
Et Et
H[Ir] O Si
EtEtOH[O]
H+
OH
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Aliphatic C-H Activation
✤ One the greatest challenges in complex-molecules synthesis
✤ Inherently reactive C-H bond (Benzylic position and etc.)
✤ Directing group not present in desired target.
1. Chen, M. S. & White, M. C. Science 318, 783–787 (2007).2. Lyons, T. W. & Sanford, M. S. Chem. Rev. 110, 1147–1169 (2010)3. Newhouse, T. & Baran, P. S. Angew. Chem. Int. Ed. 50, 3362–3374 (2011).Yongzhao Yan @ Wipf Group Page 2 of 10 6/8/2014
Si-H Directing Group
✤ Hydrosilane as a directing group.
1. Boebel, T. A. & Hartwig, J. F. J. Am. Chem. Soc. 130, 7534–7535 (2008).
XSiMe2H
[Ir(COD)Cl]2, dtbpyB2pin2, 80oC
X= CH2, O, NR
XSiMe2H
Bpin
Meta selectivity
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1. Cho, S. H.; Hartwig, J.F., J. Am. Chem. Soc., 2013, 135, 8157-8160
Si-H Directing Group
✤ Recent example:
SiMe2H[Ir(COD)OMe]2, Me4phen
B2pin2, 80oC
X= CH2, O, NR
HR
SiMe2H
BpinR
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Intramolecular C-H Silylation
1. Tsukada, N.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 5022–5023.
✤ Platinum as catalyst:SiMe2H
SiMe2
TpMe2Pt(Me)2(H)
200oC, 48h
HSi3
Bu2SiTpMe2Pt(Me)2(H)
200oC, 72h
70%
80-88%
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Intramolecular C-H Silylation
1. Simmons, E. M.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132, 17092-17095.
✤ Iridium catalyzed ortho-silylation
OSiEt2H
R1R2
OSiEt2
R1R2
[Ir(COD)OMe]2/phennorbornene, 80oC
61-86%norbornene
OSiEt2
R1R2 Pd(OAc)2, dcpe,
2 M aq. NaOH
dioxane, 65 oCOH
R1R2
ArArI, ArBr or ArCl
OSiEt2
R1R2 KHCO3, H2O2,
THF/MeOH,rt.OH
R1R2
OH
Norbornene H2 absorbant
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Aliphatic C-H Silylation
1. Simmons, E. M.; Hartwig, J. F. Nature 2012, 483, 70.
✤ 1,3-diol formation sequence
OH
R1R2 H
Et2SiH2[Ir]
O
R1R2 H
SiEt
H
Et
[Ir] O
R1R2
SiEt Et
[O] OH
R1R2 OH
✤ Ligand screening[Ir(COD)OMe]2 0.5 mol%/ligand 1.2 mol%
norbornene (1.2 equiv.)
80oC
OSi
Et Et
H O SiEt Et
N
N
Gc yield
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Aliphatic C-H Silylation
1. Simmons, E. M.; Hartwig, J. F. Nature 2012, 483, 70.
✤ Examples in complex molecules synthesis
O
Ir-catalyzed silylationKHCO3, H2O2
then Ac2O, Et3NOAc
OActotal yield 66%(+)-camphor
1 kg/$50
3 steps
64%
O
(+)-Ketopinic acid1 g/$40
HO
H
MeO2C
HH
O Ir-catalyzed silylationKHCO3, H2O2
total yield 51%HO
H
MeO2C
HH
O
OHmethyl glycyrrhetinate
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Aliphatic C-H Silylation
1. Frihed, T. G.; Heuckendorff, M.; Pedersen, C. M.; Bols, M. Angew. Chem., Int. Ed. 2012, 51, 12285.
✤ Application in sugar synthesis
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Silylation of Secondary Alkyl C-H✤ Ligand screening
120oC higher than 80oC
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