Published on Web 09/15/2009
Optically Active (aR)- and (aS)-Linear and Vaulted Biaryl
Ligands: Deracemization versus Oxidative Dimerization
Gang Hu, Daniel Holmes, Brina Fay Gendhar, and William D. Wulff*
Department of Chemistry, Michigan State UniVersity, East Lansing, Michigan 48824
Received May 11, 2009; E-mail: wulff@chemistry.msu.edu
Abstract: The copper-mediated deracemization of the C2-symmetric vaulted biaryl ligands VANOL and
VAPOL has been investigated. In the course of the studies that have led to a more reliable procedure for
this process, an unprecedented oxidative dimerization of these ligands has been uncovered. The structures
of these oxidative dimerization products were elucidated by a series of NMR experiments, and these
assignments were supported by other spectroscopic techniques as well as their chemical reactivity. This
oxidative dimerization process was not observed for the linear biaryl ligands BANOL and BINOL, although
the new deracemization procedure was effective for the generation of BINOL with high optical purity. The
(aS)-enantiomers of BINOL, VANOL and VAPOL were accessible with a copper complex of (-)-sparteine,
and the (aR)-enantiomeric series were accessible with a copper complex of O’Brien’s diamine. Both (-)-
sparteine and O’Brien’s diamine give higher optical purities with VANOL and VAPOL than with BINOL,
and this is consistent with the steric congestion present in the matched and mismatched copper complexes
of these diamines with the biaryl ligands.
reactions,8 heteroatom Diels-Alder reactions,9 the amidation10
Introduction
and imidation11 of imines, the asymmetric reduction of imines,12
C2-Symmetric biaryl compounds are among the most versatile
and efficient ligands in asymmetric synthesis with BINOL 4a
as undoubtedly the most important ligand in this class.1 Much
effort has been focused on the modification of BINOL 4a to
afford a larger and more defined chiral pocket in order to
improve enantioselectivity with the majority of the most
successful BINOL derivatives bearing substituents in the 3- and
3′-positions (4, R * H).2 We have developed a new class of
C2-symmetrical biaryl ligands in which the conjugated π-aro-
matic fused-ring systems of the ligand serve to define the chiral
pocket. The two prototypes of this class of vaulted biaryl ligands
are VANOL 2a and VAPOL 3 (Scheme 1).3,4 The term vaulted
biaryl is used as a descriptor for VANOL and VAPOL since
the aromatic ring systems curve around the nascent active site
as opposed to BINOL, a linear biaryl, where the two aromatic
ring systems are parallel to each other and thus linearly disposed.
As a consequence of this design, the VANOL and VAPOL
ligands have proven to be superior to BINOL in many important
catalytic asymmetric reactions including Diels-Alder reactions,5
aziridination reactions,6 Mannich reactions,7 Baeyer-Villiger
desymmetrization of aziridines,13 the Petasis reaction,14 and the
hydroarylation of alkenes.15 We have also previously developed
a method for the copper(II)-mediated deracemization of the
VANOL and VAPOL ligands, which in the presence of (-)-
sparteine constitutes a method for the conversion of the racemate
of either VANOL or VAPOL into the corresponding (aS)-
ligands with high mass conversion and >99% ee in each case.16
Unfortunately, (+)-sparteine is not a naturally occurring ma-
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9
10.1021/ja903820m CCC: $40.75 2009 American Chemical Society
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