Asymmetric Catalysis Using Self-Assembled Chiral Bidentate P,P-Ligands

Article abstract of DOI:10.1021/ja049873+

A strategy is described for modular catalyst development based upon metal-directed self-assembly of bifunctional subunits around a structural metal to form a heteroleptic complex in which a second set of ligating groups are now suitably disposed to bind a

Full text of DOI:10.1021/ja049873+

Published on Web 03/23/2004
Asymmetric Catalysis Using Self-Assembled Chiral Bidentate P,P-Ligands
James M. Takacs,* D. Sahadeva Reddy, Shin A. Moteki, Di Wu, and Hector Palencia
Department of Chemistry, UniVersity of NebraskasLincoln, Lincoln, Nebraska 68588-0304
Received January 8, 2004; E-mail: jtakacs1@unl.edu
The need for advances in asymmetric catalysis fuels the search
for new ligand and catalyst designs, especially those using
combinatorial and modular approaches.1 Recently, several reports
have appeared wherein self-assembly is used to generate novel
bidentate ligands2-7 and catalyst systems.8-10 We now report a
remarkably effective strategy for modular catalyst development
based upon self-assembly of bifunctional subunits around a
structural metal to form a heteroleptic complex in which a second
set of ligating groups are now suitably disposed to bind a second
metal to form a catalytic site (Figure 1). Most modular approaches
to ligand design attach ligating groups as substituents to a preformed
backbone template. Here, metal-directed self-assembly generates
Figure 1. Metal-directed self-assembly of bimetallic catalysts incorporating
the backbone as the final step and, as such, offers the opportunity
to rapidly assemble a diverse set of backbones and more thoroughly
explore and exploit the influence of template structure.
structural (Ms) and catalytic metals (Mc).
Mixing a “racemic mixture” of monosubstituted bisoxazoline
(box) ligands (e.g., (S,S)- and (R,R)-1) with Zn(OAc)2 results in
the rapid formation of a neutral (box)2Zn complex. While three
2:1 complexes are possible, two homoleptic and one heteroleptic,
the tetrahedral coordination geometry of zinc(II) favors the het-
eroleptic complex 2, and only the latter is observed in solution by
NMR analysis or upon crystallization (Figure 2). These (box)2Zn
complexes are proving to be quite remarkable compounds and
provide an extraordinarily simple, efficient method to prepare new
chiral bidentate P,P-ligands.
A series of monosubstituted box derivatives were prepared, each
member bearing a pendant TADDOL-derived monophosphite11
(Figure 3, 3A-M). The synthetic route is straightforward, the key
step being mono-alkylation12 of the box subunit with a substituted
benzyl bromide bearing a pendant silyl-protected hydroxyl sub-
stituent. Deprotection of the silyl ether followed by phosphorylation
with ((R,R)-TADDOL)PCl13 affords the desired box-(TADDOL)-
phosphite conjugate 3.
Treating complementary combinations of the bifunctional ligands
in Figure 3 with Zn(OAc)2 provides a simple way to prepare a
library of new heteroleptic (box)2Zn complexes bearing two free
chiral phosphite moieties.14 For example, the combination of (S,S)-
3F and (R,R)-3F) affords the pseudo-C2-symmetric diphosphite 4FF
(Figure 4). Mass spectral and NMR data support the structural
assignment. The 31P NMR spectrum of 4FF shows a single reso
nance at 130.2 ppm, similar to that of the precursor (S,S)-3F (130.7
ppm). To test whether the pendant phosphites can coordinate a
second metal, 4FF was treated with an equivalent of [(cod)2Rh]BF4.
The 31P NMR signal at 130.2 ppm is lost and a new doublet appears
at 112.7 ppm (JRh,P ) 248.6 Hz),15 consistent with the formation
of a chiral heterobimetallic complex with rhodium.16
Figure 2. Preparation and crystal structure of (box)2Zn complex 2.
3A-M and screened them in the palladium-catalyzed asymmetric
allylic amination17-21 of racemic carbonate 5 with N-methyl-p-
toluenesulfonamide. Chiral diphosphites have been employed in a
wide range of asymmetric reactions, including palladium-catalyzed
allylations;22 the latter are frequently used as a testing ground for
new chiral ligand motifs.
The chiral diphosphites screened differ only in the structure of
the ligand backbone, and while each gives predominantly (R)-6
(R ) Me), the variation in enantioselectivity is striking. As Figure
5 illustrates, the enantiomeric excess varies quite smoothly over a
wide range, 20-97% ee, as a function of the combination of
subunits A-M employed. The striking variations in enantiomeric
excess demonstrate the ability to employ very subtle changes in
the structural backbone to manipulate the ligand topography around
palladium. For reference, the corresponding amination using ((R,R)-
TADDOL)POPh gives (R)-6 (R ) Me) in 48% ee.
Preferential formation of the heteroleptic (box)2Zn complex is
driven by the complementary chirality of the box subunits and is
largely independent of the nature of the remote substituents on the
box ligand. We prepared 50 combinations of SAL 4 from subunits
Nine combinations of 4 effect the asymmetric allylation in 90%
ee or higher (Table 1). Each contains one of two closely related
subunits, F or H. The most successful ligand, 4FH, contains both
and affords 6 (R ) Me) in 97% ee (entry 1). Surprisingly, the
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10.1021/ja049873+ CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Partial Summary of Screening SALs 4 in the
Palladium-Catalyzed Allylic Amination Reaction of 5 with TsN(H)R
entry
R in TsN(H)R
SAL 4
% yield
% ee
1
2
3
4
5
6
7
8
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
n-Bu
Bn
FH
FM
FJ
82
88
74
85
85
81
80
86
84
88
83
84
77
80
83
95
74
92
97
94
93
93
92
92
92
90
90
87
87
84
80
80
90
91
95
88
HJ
HL
FL
EH
HM
GH
HH
FG
FF
EF
FI
FF
FH
HH
FF
9
10
11
12
13
14
15
16
17
18
i-Pr
Ph
Figure 3. Series of bifunctional box-(TADDOL)phosphite conjugates,
3A-M ((TDO)2 ) (R,R)-TADDOL), used to prepare chiral diphosphites.
Acknowledgment. Support from the University of Nebraska
Research Initiative is gratefully acknowledged. We thank J. M.
Atkins and P. M. Hrvatin for preliminary studies, Joanna Clark for
determining the crystal structure of 2, and Dipanjan Nag for
assistance with NMR studies.
Supporting Information Available: Experimental details for 4FF,
6, and the crystal structure of 2 (PDF, CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
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as an important structural element and palladium as a catalytic metal
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