.
Angewandte
Communications
DOI: 10.1002/anie.201402293
Tropos Organocatalyst
Selector-Induced Dynamic Deracemization of a Selectand-Modified
Tropos BIPHEPO-Ligand: Application in the Organocatalyzed
Asymmetric Double-Aldol-Reaction**
Frank Maier and Oliver Trapp*
Dedicated to the MPI fꢀr Kohlenforschung on the occasion of its centenary
Abstract: Stereolabile interconverting catalysts open up the
possibility of directing enantioselectivity in asymmetric syn-
thesis by formation of diastereomeric complexes with chiral
auxiliaries and deracemization. However, the stoichiometri-
cally used auxilliaries can significantly limit the potential
applications of such systems. We synthesized a new BIPHEPO
tropos ligand containing achiral selectands in the backbone,
which forms transient diastereomeric associates with amylose-
tris-3,5-dimethylphenyl carbamate as a selector and thus
deracemizes. The enantiomerically enriched BIPHEPO
obtained was successfully used in the organocatalytic asym-
metric double aldol addition of substituted methyl ketones to
form benzaldehyde. This strategy combines an on-column
deracemization with the high stereoinduction of chiral biar-
ylphosphineoxides and opens up new possibilities in the field of
self-amplified asymmetric syntheses.
Scheme 1. Asymmetric reactions using interconverting racemic cata-
lysts. a) Chirality control and activation by the selector and b) chirality
control by the selector.
After aligning the tropos ligands by chiral auxiliary
ligands at elevated temperatures, the enantiomerically
enriched catalysts can be used directly or be split off again
at lower temperatures.[6]
Mikami et al. as well as other groups could apply these
concepts to a number of metal complexes with tropos
BIPHEP ligands and to a variety of asymmetric transforma-
tions.[5b,c,6b,e,f,8]
Another strategy for the deracemization of stereo labile
compounds by means of stopped-flow HPLC (sfHPLC) on
chiral stationary-phases were demonstrated by Pirkle et al.[9]
and Lindner et al.[10] Wolf, Kçnig, and Roussel obtained the
(ꢀ)-2,2’-diiodobiphenyl enantiomer in 90% yield by multiple
separations and re-racemizations by sfHPLC.[11] Cannazza
et al. refined this approach by using a second achiral column
next to the chiral separation column for recycling of the
unwanted enantiomer.[12]
Kotani and Nakajima et al. used chiral biarylphosphine-
oxide successfully as organocatalysts in enantioselective aldol
and double aldol additions,[13] allylations[14] as well as ring-
opening reactions and epoxidations.[15]
D
ynamic stereoisomers constitute an interesting and impor-
tant alternative to classical stereochemically stable ligands.[1]
Among these the fluxional axially chiral 2,2’-bis(diphenyl-
phosphino)biphenyl (BIPHEP) species have a prominent
position as ligands for asymmetric catalysis. In contrast to the
related BINAP ligands[2] the o,o’-disubstituted biphenyl
enantiomers[3] convert dynamically into each other by rota-
tion around the s bond even at room temperature.[4]
Mikami and Noyori et al. took advantage of this dynamic
property and used the unsubstituted BIPHEP as a ligand for
asymmetric catalysis.[5] To deracemize the catalyst complex
Mikami et al. employed stoichiometric amounts of chiral
counterligands (selectors) to selectively align the BIPHEP
tropos ligands in the corresponding diastereomeric complexes
(Scheme 1). By coordination to transition-metal centers the
interconversion barrier may increase, whereby the BIPHEP
ligands show an atropisomeric behavior.[6,7]
The active catalyst is formed by a hypervalent BINAPO-
SiCl3 species. Mechanistic studies on the double-aldol-addi-
tions demonstrate the need and the stereoselective influence
of the employed chiral BINAPO ligands for the formation of
the silyl enol ether (Scheme 2).[13e]
Herein we report on a new strategy for the catalytic
transfer of chiral information, which combines the excellent
stereo-inducing properties of BIPHEP tropos ligands with on-
column deracemization (Scheme 3). Recently, we have stud-
ied in detail the stereo dynamics of tropos 5,5’-disubstituted
BIPHEPO ligands.[16] These compounds show an ideal
[*] Dr. F. Maier, Prof. Dr. O. Trapp
Ruprecht-Karls-Universitꢀt Heidelberg
Organisch-Chemisches Institut
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
E-mail: trapp@oci.uni-heidelberg.de
[**] We thank the European Research Council (ERC) for financial
support in the form of a Starting Grant (Nr. 258740, AMPCAT).
Supporting information for this article is available on the WWW
8756
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 8756 –8760