Chiral Ligands On A Spiro
Scaffold for Transition-MetalCatalyzed Asymmetric
Reactions
Work by Prof. Zhou Qi-Lin
Ye Zhu
09/02/10
Burgess’s Group Meeting
Ubiquitous
Spirocyclic
Framework
in 1900, von Baeyer introduced the name “spirocyclane” for bicyclic
hydrocarbons having two rings with a common carbon atom (spiro carbon)
the two rings of the spiro compounds lie in perpendicular planes, which not only
gives rise to an axial chirality in spiro compounds having substituents on the
rings but also increases molecular rigidity
the spirocyclic framework is considerably more rigid than that of
biaryls, since conformational changes involve distortion of the entire molecule
racemization of chiral spiro compounds virtually impossible
very few applications despite these excellent characteristics
2
Spiro[4,4]nonane-1,6-diol As
Chiral Auxiliaries in the
Reduction of Ketones
Kumar, A., et al, Chem. Commun. 1992, 493.
2 eq. (+) 1, 2 eq. LAH, -80 °C, 80%, 98% ee
2 eq. (+) 1, 2 eq. LAH, -20 °C, 75%, 89% ee
3
Spiro[4,4]nonane-1,6-diol As
Chiral Auxiliaries in the
Reduction of Ketones
Kumar, A., et al, Chem. Commun. 1992, 493.
2 eq. (+) 1, 2 eq. LAH, -80 °C, 80%, 98% ee
2 eq. (+) 1, 2 eq. LAH, -20 °C, 75%, 89% ee
4
Monodentate Spiro
Phosphoramidite Ligand
5
Xumu, Zhang, et al, Org. Lett. 2004, 3565.
Synthesis of Chiral Monodentate Spiro
Ligand via
9,9’-Spirobixanthene-1,1’-Diol
6
Xumu, Zhang, et al, Org. Lett. 2004, 3565.
Synthesis of
1,1’Spirobiindane-7,7’-diol
7
Birman, V.B., et al, Tetrahedron Asymmetry 1999, 125.
Synthesis of
1,1’Spirobiindane-7,7’-diol
8
Birman, V.B., et al, Tetrahedron Asymmetry 1999, 125.
Highly efficient and practical resolution of
1,1-spirobiindane-7,7-diol by inclusion
crystallization with
N-benzylcinchonidinium chloride
A highly efficient and practical
resolution of racemic
1,1-spirobiindane-7,7-diol (±)-1 has
been achieved,
with the (S)-(−)- and (R)-(+)-forms of
1 obtained with
>99% e.e. in 82% yield from the
inclusion complex and
75% yield from the mother liquor,
respectively
9
Zhou, Qi-Lin, et al, Tetrahedron Asymmetry 2002, 1363.
Synthesis of 9,9’Spirobifluorene-1,1’-diol
Zhou, Qilin, et al,
10
Synthesis of 9,9’Spirobifluorene-1,1’-diol
SBIFOL was conveniently synthesized from 1,2dibromobenzene and 3-bromoanisole in high yield. Both
enantiomers of SBIFOL were obtained in 99% ee by inclusion
resolution with 2,3-dimethoxy-N,N,N’,N’
tetracyclohexylsuccinamide
11
Synthesis of SDP Ligands
12
Zhou, Qi-Lin, et al, J. Am.Chem.Soc., 2003, 4404.
Zhou, Q.-L. et al, Angew. Chem., Int. Ed. 2002, 41, 2348.
Zhou, Q.-L. et al, Org. Lett. 2006, 8, 1479.
Zhou, Q.-L. et al, J. Org. Chem. 2004, 69, 8157.
Zhou, Q.-L. et al, J. Am.Chem. Soc. 2006, 128, 11774.
Zhou, Q.-L. et al, Org. Lett. 2005, 7, 2333.
Zhou, Qi-Lin, et al, Angew. Chem.
Int. Ed., 2005, 1118.
13
Crystal Structures of Pd-complexes
14
Synthesis of Chiral Spiro
Phosphine-Oxazoline Ligands
Zhou, Q.-L. et al, J. Am.Chem. Soc. 2006, 128, 12886
.
15
Applications: Asymmetric
Hydrogenation
ketones
Zhou, Q.-L. et al, J. Am. Chem. Soc. 2006, 128, 11774
a new chiral scaffold and their application in the rutheniumcatalyzed asymmetric hydrogenation of simple ketones with
high activity (S/C up to 100 000) and excellent enantioselectivity
16
(ee up to 99.5%)
Highly Enantioselective and
Diastereoselective Synthesis of
Chiral Amino Alcohols
Zhou, Qi-Lin, et al, J. Am. Chem. Soc., 2010, 4222.
17
Enantioselective Hydrogenation of
α-Arylmethylene Cycloalkanones
the asymmetric hydrogenation of exocyclic
α,β-unsaturated ketones is a challenge task
Zhou, Qi-Lin, et al, J. Am. Chem. Soc., 2010, 4538.
18
Applications: Asymmetric
Hydrogenation
aldehydes
Zhou, Q.-L. et al, J. Am. Chem. Soc. 2007, 129, 1868
the first example of asymmetric hydrogenation of aldehyde19via
DKR
Applications: Asymmetric
Hydrogenation
α,β-unsaturated carboxylic acid
Zhou, Q.-L. et al, Angew. Chem. Int.Ed. 2005, 1118
these results are comparable to, or better than, 20
those obtained with [Ru(OAc)2(binap)] and other catalysts
Applications: Asymmetric
Hydrogenation
α,β-unsaturated carboxylic acid
Zhou, Q.-L. et al, Angew. Chem. Int.Ed. 2005, 1118
these results represents the highest level of enantiocontrol reported to
date in the asymmetric hydrogenation of cinnamic acid derivatives 21
Applications: Asymmetric
Hydrogenation
α,β-unsaturated carboxylic acid
Zhou, Q.-L. et al, Adv. Synth, Catal. 2006, 1271
22
Hydrogenations with Chiral Spiro
Phosphine-Oxazoline Ligands
Zhou, Q.-L. et al, J. Am.
Chem. Soc. 2008, 130,
8584
.
Zhou, Q.-L. et al, J. Am.
Chem. Soc. 2010, 132, 1172
.
Zhou, Q.-L. et al, J. Am.
Chem. Soc. 2006, 128,
.
12886
23
Applications: Asymmetric
Hydrogenation
enamines
24
Applications: Asymmetric
Hydrogenation
Zhou, Q.-L. et al, J. Am. Chem. Soc. 2006, 128, 11774
Other ligands such as the diphosphine ligands BINAP, Josiphos, and SDP (6a)
and the monodentate phosphorus ligands Mono- Phos, H-MOP, SIPHOS (9a), and
ShiP (10a) provided the hydrogenation product with very low 25
enantioselectivities under the same reaction conditions
Iridium-Catalyzed
Asymmetric Hydrogenation
of Cyclic Enamines
26
Zhou, Qi-Lin, et al, J. Am. Chem. Soc., 2010, 1366.
Enantioselective Iron-catalysed
O–H Bond Insertions
27
Zhou, Qi-Lin, et al, Natural Chemistry, 2010, 546.
Other Developments
Zhou, Qi-Lin, et al, J. Am. Chem. Soc., 2007, 5834.
Enantioselective Insertion of Carbenoids into N−H Bonds Catalyzed by Copper Complexes of Chiral Spiro Bisoxazolines
Zhou, Qi-Lin, et al, Angew. Chem. Int. Ed., 2008, 932.
Enantioselective Synthesis of a-Hydroxyesters by a Copper–Carbenoid O-H Insertion Reaction
28
Other Developments
Zhou, Qi-Lin, et al, Angew. Chem. Int. Ed., 2008, 8496.
Copper-Catalyzed Highly Enantioselective Carbenoid Insertion into Si-H Bonds
Zhou, Qi-Lin, et al, Angew. Chem. Int. Ed., 2008, 4351.
Enantioselective Rhodium-Catalyzed Addition of Arylboronic Acids to β-Ketoesters
29
Addition of Arylboronic Acids to
Aldehydes and N-Tosylarylimines
30
Ni Catalyzed Reactions
Zhou, Qi-Lin, et al, J. Am. Chem. Soc., 2010, 10955.
Enantioselective Nickel-Catalyzed Reductive Coupling of Alkynes and Imines
Zhou, Qi-Lin, et al, J. Am. Chem. Soc., 2008, 14052.
Enantioselective Nickel-Catalyzed Alkylative Coupling of Alkynes and Aldehydes
31
Asymmetric
hydrovinylation of
Vinylarenes
Zhou, Q.-L. et al, J. Am.
Chem. Soc. 2006, 128,
2780
32
Pd Catalyzed
Carboamination Reactions
John, Wolfe, et al, J. Am. Chem. Soc. 2010, 12157.
33
Possible Works
34
Thanks
35