Transcript B3LYP/LANL2DZ Chem. Eur. J. 2003, 9

Asymmetric Iridium-Catalysed
Hydrogenation
New Ligands, New Substrates.
Pher G. Andersson
Uppsala University
Asym hydrogenation of olefins
Rh
Ru
Asym hydrogen non-functionalized olefines
Ru (II) - BINAP
Rh (I) - BINAP
Takaya 1995
Buchwald 1993
Halterman Comprehensive Asymmetric Catalysis Springer 1999, vol.1, 183-195.
Asym hydrogenation, mechanism
Rh
? Ru ?
? Ir ?
Landis & Halpern J. Am. Chem. Soc. 1987, 109, 1746.
DFT study of Ir-hydrogenation
B3LYP/LANL2DZ
Chem. Eur. J. 2003, 9, 339.
axup
eqt-P
Computational chemistry
eqt-N
axdown
Olefin
X-Ray structure vs DFT
DFT results
Path
2
TS(2®3)
3
TS(3®4)
log(rel. rate)
A
1.9
15.1
7.9
19.2
0.0
A’
B
C
C’
D
E´-S
14.3
-2.4
0.4
26.8
-1.6
-1.9
21.5
5.6
15.5
34.4
5.7
0.7
5.0
0.3
1.3
16.5
4.5
-10.2
12.9
12.9
4.6
2.7
19.2
8.6
0.0
7.8
B3LYP/LANL2DZ
Chem. Eur. J. 2003, 9, 339.
DFT results
Path
2
TS(2®3)
3
TS(3®4)
log(rel. rate)
A-H2
-9.1
6.0
-8.8
-7.6
9.7
A'-H2
-3.1
8.4
-7.5
B-H2
-11.6
-3.4
-8.0
5.6
10.0
C-H2
-11.3
1.7
-9.7
-9.0
12.9
C'-H2
-5.0
5.8
-9.7
-9.0
9.9
D-H2
-10.9
-2.8
-4.2
11.9
5.4
E-H2
-9.1
6.1
-8.8
3.5
9.6
E'-H2
-4.8
-0.8
-8.8
3.5
11.6
F'-H2
-3.4
2.7
-1.0
12.7
4.8
Proposed catalytic cycle
Chem. Eur. J. 2003, 9, 339.
Coupled MI and Ox Add
New ligand structures
Synthesis should be:
short and efficient
allow preparation of both enantiomeres
Ligand structure and synthesis
Synthesis
Preparation of catalysts
Evaluation of catalysts
Substrate study
J. Am. Chem. Soc. 2004,126, 14308.
Further improvements of
the ligand strucure
?
?
Oxazole vs Thiazole
Ligand synthesis II
Ligand, absolute configuration
Ligand evaluation
Results
Ligand synthesis III
Ligand synthesis III
Adv.Synth.Cat. 2008, 350, 1168.
Separation of the enantiomeres
by ChiralCel OD
A new class of ligands
Ligand synthesis IV
Org.Lett. 2004, 6, 3825. Chem. Eur. J. 2006, 12, 2318.