β-amino alcohol derived β-hydroxy- and β-(o- diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides: An ester-amide ligand structural model for the palladium-catalyzed allylic alkylation reaction

Article abstract of DOI:10.1021/jo9016474

(Chemical Equation Presented) A commercially available collection of β-amino alcohols have been converted to their corresponding β-hydroxy- and β-(o-diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides 11a-f and 12a-f and have been employed in the

Full text of DOI:10.1021/jo9016474

pubs.acs.org/joc
β-Amino Alcohol Derived β-Hydroxy- and β-
(o-Diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides: An
Ester-Amide Ligand Structural Model for the Palladium-Catalyzed
Allylic Alkylation Reaction
Geetanjali S. Mahadik, Stanley A. Knott, Lisa F. Szczepura, Steven J. Peters,
Jean M. Standard, and Shawn R. Hitchcock*
Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160
hitchcock@ilstu.edu
Received July 29, 2009
A commercially available collection of β-amino alcohols have been converted to their corresponding
β-hydroxy- and β-(o-diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides 11a-f and
12a-f and have been employed in the Tsuji-Trost asymmetric alkylation reaction with 1,3-diphenyl-
propenyl acetate. With the exception of ligands 11b and 11f, the β-hydroxybenzoyloxy
(o-diphenylphosphino)benzamideligands 11a-f primarily affordedthe (R)-enantiomer of the product.
In contrast, the bis(phosphine) ligands 12a-f consistently afforded the (S)-enantiomer. The best ligand
(12c) was derived from cis-(1R,2S)-2-amino-1,2-diphenyl-1-ethanol, and when applied in the asym-
metric allylic alkylation reaction, it yielded the product in an enantiomeric ratio of 97.8.22 favoring the
(S)-enantiomer. A computational study was conducted on the conformation that this ligand might
adopt in the palladium-catalyzed alkylation reaction as compared to that of the Trost ligand 1a.
1. Introduction
reaction, the Trost modular phosphine ligands (1a,b)3 have
proven to be the benchmark for evaluating the efficacy of newly
developed phosphine ligands in the asymmetric allylic alkyla-
tion reaction. In fact, on the basis of their successful use in a
variety of applications, many of these modular ligands are
commercially available.4 The success of these ligands has
encouraged the synthesis and application of structurally novel
phosphines based on the binaphthyl type ligands,5 tartrate
derived systems,6 carbohydrates,7 paracyclophanes,8 and
The palladium-catalyzed asymmetric allylic alkylation reac-
tion1 known as the Tsuji-Trost reaction has been the subject of
intense studies2 directed toward the design, synthesis, and
application of a myriad of chiral, nonracemic ligand scaffolds.
Of the ligands that have been prepared and applied in this
(1) Tsuji, J. In Palladium Reagents and Catalysts: New Perspectives for the
21st Century; John Wiley & Sons: Chichester, UK, 2004; pp 431-518.
(2) (a) Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258. (b) Trost, B.
M. J. Org. Chem. 2004, 69, 5813. (c) Trost, B. M.; Crawley, M. L. Chem. Rev.
2003, 103, 2921. (d) Trost, B. M.; Machacek, M. R.; Aponick, A. Acc. Chem.
Res. 2006, 39, 747. (e) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96,
395. (f) Trost, B. M. Acc. Chem. Res. 1980, 13, 385. (g) Trost, B. M.; Breit, B.;
Organ, M. G. Tetrahedron Lett. 1994, 35, 5817.
(4) (a) Trost, B. M.; Fandrick, D. R. Aldrichim. Acta 2007, 40, 59.
(5) Feng, J.; Bohle, D. S.; Li, C. Tetrahedron: Asymmetry 2007, 18, 1043–
1047.
(6) Marques, C. S.; Burke, A. J. Tetrahedron: Asymmetry 2007, 18, 1804–
1808.
ꢀ
ꢀ
(3) (a) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J. Am. Chem. Soc.
1992, 114, 9327. (b) Trost, B. M.; Van Vranken, D. L. Angew. Chem., Int. Ed.
1992, 31, 228.
(7) Khiar, N.; Navas, R.; Alvarez, E.; Fernandez, I. ARCHIVOC 2008, 8,
211-224.
(8) Jiang, B.; Lei, Y.; Zhao, X. J. Org. Chem. 2008, 73, 7833–7836.
8164 J. Org. Chem. 2009, 74, 8164–8173
Published on Web 10/07/2009
DOI: 10.1021/jo9016474
r
2009 American Chemical Society

Mahadik et al.
JOCArticle
TABLE 1. Asymmetric Allylic Alkylation with Ligands 11a-f
time
(h)
13:ligand:
Pd
yield
(%)a
er (R:S),
(ee)b
entry ligand
config c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
11a
11a
11a
11a
11a
11b
11b
11c
11c
11c
11d
11d
11e
11f
11f
24
6
24
6
24
24
6
24
6
24
6
24
24
6
25:1:1
25:1:1
25:1:2
25:1:2
25:2:1
25:1:2
25:1:2
25:1:2
25:1:2
25:1:1
25:1:2
25:1:2
25:1:2
25:1:2
25:1:2
29
66
70
53
85
73
66
51
65
89
58
80
ndd
58
80
87.1:13.0 (74)
86.2:13.8 (72)
89.7:10.3 (79)
86.2:13.8 (72)
89.3:10.7 (79)
37.5:62.5 (25)
6.4:93.6 (87)
81.4:18.6 (63)
64.2:35.8 (28)
82.0:18.0(64)
81.9:18.1 (64)
82.5:17.5 (65)
ndd
R
R
R
R
R
S
FIGURE 1. Phosphine ligands.
S
R
R
R
R
R
ndd
S
19.1:80.9 (62)
20.5:79.5 (59)
24
S
aIsolated yield after flash chromatography. bEnantiomeric ratios
determined by CSP HPLC (Chiralcel AD column). cThe identity of
the enantiomer was based on elution from the CSP HPLC column.
See ref 10. dNot determined.
level of asymmetric induction provided by some of the
ligands in Figure 1, there was still the possibility for further
enhancing the effectiveness of this ligand family by changing
the nature of the ligand template.
We report on our efforts in the synthesis and application of
series of β-hydroxy- and β-(o-diphenylphosphino)-
FIGURE 2. β-Hydroxy- and β-(o-diphenylphosphino)benzyloxy-
(o-diphenylphosphino)benzamides.
a
benzyloxy(o-diphenylphosphino)benzamides derived from
a series of commercially available β-amino alcohols in the
asymmetric allylic alkylation reaction with 1,3-diphenylpro-
penyl acetate and dimethyl malonate. In addition, a compu-
tational study concerning the interaction between the best
ligand of this series bound to palladium and 1,3-diphenyl-
propenyl acetate is carried out.
biphenyl systems9 (Figure 1). Many of these ligands afford very
high enantiomeric excesses when employed in the asymmetric
allylic alkylation reaction between 1,3-diphenylpropenyl acet-
ate and dialkyl malonates. However, many of these ligands
require significant synthetic efforts to prepare from either
chiral, nonracemic materials or racemic materials through
resolution.
In 2008, Burke and co-workers,10 inspired by the earlier
work of Mino and co-workers,11 developed a series of
β-hydroxy(diphenylphosphino)benzamides (7a,b) based on
L-phenylglycinol and L-phenylalaninol and applied these
systems in the asymmetric alkylation reaction with 1,3-
diphenylpropenyl acetate with dimethyl malonate. The pro-
ducts were obtained with enantiomeric excesses that ranged
from 17% to 62% ee. Our research group has recently been
involved in the application of β-amino alcohols from the
genus Ephedra and have developed a series of mono- and
bis(phosphines) ligands (8a,b, 9a,b) for application in the
Tsuji-Trost reaction (Figure 2). We were gratified to learn
that the use of these ligands afforded products with enantio-
mer excesses ranging from 54% to 88% ee.12 While not at the
2. Results and Discussion
A series of β-amino alcohols (10a-f), both acyclic and
cyclic, were coupled with o-(diphenylphosphino)benzoic
acid, 1 equiv of 1-ethyl-3-(3-dimethylaminopropyl)carbodi-
imide (EDC), and a catalytic amount of dimethylaminopyridine
(DMAP) to afford the β-hydroxy(o-diphenylphosphino)-
benzamides 11a-f (Scheme 1). In like fashion, β-amino alco-
hols (10a-f) were also treated with 2 equiv of EDC and
catalytic DMAP to generate the corresponding β-(o-diphenyl-
phosphino)benzyloxy(o-diphenylphosphino)benzamides 12a-f
in yields ranging from 40% to 65%. With these compounds
in hand, the asymmetric allylic alkylation reaction was pursued
with a catalytic amount of allylpalladium chloride dimer {[(η3-
C3H5)PdCl]2}, 1,3-diphenylpropenyl acetate, and dimethyl
malonate. Potassium acetate and N,O-bis(trimethylsilyl)-
acetamide (BSA) were also employed to facilitate the deproto-
nation of dimethyl malonate.
(9) Lai, H.; Huang, Z.; Wu, Q.; Qin, Y. J. Org. Chem. 2009, 74, 283–288.
(10) Marinho, V. R.; Rodrigues, A. I.; Burke, A. J. Tetrahedron: Asym-
metry 2008, 19, 454–458.
(11) Mino, T.; Kashihara, K.; Yamashita, M. Tetrahedron: Asymmetry
2001, 12, 287.
(12) Mahadik, G. S.; Knott, S. L.; Szczepura, L. F.; Hitchcock, S. R.
Tetrahedron: Asymmetry 2009, 20, 1132–1137.
The first set of reactions that were carried out were focused
on the application of the β-hydroxy benzamides 11a-f
(Table 1). The ratio of the palladium precatalyst, ligand
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SCHEME 1. Synthesis of (o-Diphenylphosphino)benzamides 11a-f and 12a-f
and substrate, and time were varied for the sake of finding an
optimal ratio that would afford the best enantioselection.
The only related reports on β-hydroxybenzamides being
employed in the catalytic asymmetric alkylation did not
provide a definitive guide to an optimized ratio.10-12
palladium-bound ligand with the result that that region of
the benzylic alcohol is ultimately responsible for the ob-
served asymmetric induction. There may be other reaction
pathways but any viable pathways would need to take into
account the influence of the stereochemistry at the carbon
bearing the alcohol group.
Benzamides 11a and 11c-e are structurally related to the
(1R,2S)-norephedrine-based β-hydroxybenzamide 8a and
all of these systems afford the same configuration in the
end product, the (R)-enantiomer. In contrast, benzamides
11b and 11f afforded the (S)-enantiomer of the product.
These two benzamides (11b, 11f) are related to the diastereo-
meric (1S,2S)-pseudonorephedrine-based β-hydroxybenza-
mide 8b, which yielded the (R)-enantiomer when applied in
the asymmetric alkylation.12 The change in configuration for
the malonate product resulting from the application of
(1R,2R)-11f was expected as the absolute stereochemistry
was opposite to that of the (1S,2S)-pseudonorephedrine 8b
employed in the earlier study. Yet, the β-hydroxybenzamide
11b has the same configuration as the (1S,2S)-pseudo-
norephedrine benzamide 8b, but yielded the oppositely
configured enantiomer. The origin of the change in enantio-
selection may be associated with a change in the conforma-
tion for 11b as compared to 8b. The result of the application
of the benzamide 11b in the asymmetric catalysis reaction is
perhaps best evaluated in the context of its diastereomeric
counterpart 11c (Scheme 2). These two ligands afford the
malonate product 14 in opposite configurations. For each
ligand the stereocenter bearing the amido functional group is
the same. On the basis of this observation, the argument can
be made that the carbon bearing the alcohol functional
group, which is the point of difference for the diastereomers
11b and 11c, must have a significant influence over the
stereochemical course of the reaction. It is proposed
that the alcohol functional group might exert an influence
in the approach of the malonate nucleophile to the
The benzamide 11e failed to react after multiple attempts
to employ this material as a catalyst in the asymmetric allylic
alkylation. There was a noticeable darkening of the reaction
mixture when ligand 11e was employed as compared to
11a-d and 11f (Figure 3). The reason for this low reactivity
is not clear. It is proposed that the poor reactivity of this
particular ligand may have been associated with the ready
deactivation of the palladium through the proximity of the
alcohol moiety. This is the one ligand that has the alcohol
group in a locked syn-configuration aspect with the
(diphenylpshosphino)benzamide.
The bis(phosphine) ligands 12a-f were also employed in
the asymmetric allylic alkylation reaction with dimethyl
malonate (Table 2). In contrast to the mono(phosphine)
ligands 11a-f, all of the bis(phosphine) ligands (12a-f)
afforded the alkylation product as the (S)-enantiomer with-
out deviation. Some of these ligands yielded very good
enantiomeric excesses of the product while others did not
perform well in the asymmetric process.
The application of ligand 12a afforded a poor enantio-
selectivity in product formation (9-11% ee). It is believed
that the absence of substitution at the carbon bearing the
amino group gives rise to a high level of conformational
freedom that may be detrimental to the success of the process
of asymmetric induction. In the course of characterizing
ligands 12a-f by 31P{1H} NMR spectroscopy it was deter-
mined that the 31P spectrum of 12a was unique among the
diphosphine ligands (see the Supporting Information).
Due to the two different electronic environments of each
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SCHEME 2. Proposed Reaction Mechanisms for Catalysis with 11b and 11c
phosphorus atom in the diphosphine ligands 12a-f, it was
anticipated that each ligand would have two observable signals
in their corresponding spectra. This was indeed the case.
However, the only exception was compound 12a, which dis-
played four resonance signals. Upon inspection, these sig-
nals appear to be two sets of doublets centered at -5.29 and
-8.85 ppm. However, since the related monophosphine pre-
cursor (11a) only showed a singlet at -9.92 ppm in its 31P {1H}
NMR spectrum, it is unlikely that the apparent splitting is due
to 1H coupling with protons that were not fully decoupled. In
addition to this, all of the other diphosphine ligands 12a-dand
12f only exhibit two resonances under similar conditions.
Therefore, coupling between the two nonequivalent phos-
phorus atoms can be ruled out. It is more likely that compound
12a exists in two different structural conformations that are in
equilibrium undergoing slow interconversion on the NMR
time scale; each conformer would have two unique 31P reso-
nances which would lead to four resonances overall. If this
proposal is valid, then increasing the temperature of the
solution containing 12a would increase the exchange rate
between these two conformers and the individual pairs of
two resonances would coalesce into broadened singlets. To
test this hypothesis, a variable-temperature NMR study was
pursued. Figure 4 shows the 31P {1H} spectrum of 12a at 298
and 383 K (in toluene-d8). The high-temperature spectrum
clearly shows that the pairs of peaks have coalesced into two
broad singlets, indicative of two conformers undergoing rapid
FIGURE 4. The 202.5 MHz 31P{1H} NMR spectra of a toluene-d8
solution containing 12a recorded at 298 and 383 K in a sealed NMR
tube. The splitting observed for each resonance in the top spectrum
disappears as the temperature is increased to 383 K. The resulting
two broad singlets observed at the high temperature strongly
suggest the presence of two conformers of 12a undergoing rapid
exchange on the NMR time scale.
FIGURE 3. Comparison of typical asymmetric catalysts with li-
gands 11a-d (A) vs. ligand 11e (B).
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TABLE 2. Asymmetric Allylic Alkylation with 12a-f
entry
ligand
solvent
time (h)
13:ligand:Pd
yield (%)a
er (R:S), (ee)b,c
config d
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
12a
12a
12b
12b
12b
12c
12c
12c
12c
12d
12d
12d
12e
12f
12f
12f
12f
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
toulene
THF
THF
THF
THF
THF
24
6
25:1:1
25:1:1
25:1:1
25:2:1
25:1:2
25:1:1
25:1:1
25:2:1
25:1:2
25:1:1
25:1:1
25:1:2
25:1:1
25:1:1
25:1:1
25:2:1
25:1:2
88
89
90
82
67
43
63
79
84
74
61
88
86
<5
78
<5
73
45.2:54.8 (11)
45.4:54.6 (9)
7.3:92.7 (85)
5.5:94.5 (89)
4.8:95.2 (91)
5.5:94.5 (89)
2.2:97.8 (96)
12.8:87.2 (74)
3.2:96.8 (94)
12.7:87.3 (75)
8.9:91.1 (82)
23.0:77.0 (54)
44.6:55.4 (11)
41.6:58.4 (17)
43.4:56.6 (13)
48.1:51.9 (4)
46.9:53.1 (6)
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
24
24
24
24
6
6
6
6
24
24
24
6
24
24
24
aIsolated yield after flash chromatography. bEnantiomeric ratios determined by CSP HPLC (Chiralcel AD column). cThe identity of the enantiomer
was based on elution from the CSP HPLC column. See ref 10. dNot determined.
SCHEME 3. Trost Ligand 1b in the Asymmetric Allylic Alkylation
exchange on the NMR time scale. The fact that this ligand can
exist in these different conformational forms may explain the
low enantioselection observed in the alkylation reaction with
ligand 12a (Table 2).
that the palladium-bound ligands 12e and 12f must experi-
ence significant steric hindrance when interacting with the
1,3-diphenylpropenyl acetate substrate. In contrast to poor
enantioselection obtained from the use of 12e and 12f, the
application of the diphosphine 12d, the diastereomer of 12e,
afforded enantioselectivities that were significantly better.
Because of the stereochemical relationship between trans-
diastereomer 12d and the cis-diastereomer 12e, it is proposed
that the cis-diastereomer must have the diphenylphosphino
groups in such a configuration that the phenyl rings of the
phosphorus atoms are not well-positioned for the transfer of
asymmetry from the chiral scaffold.
The benzamide ligand 12c afforded the best level of enantio-
selection for all of the ligands that were prepared. When applied in
the asymmetric alkylation reaction, the bisester 14 was obtained
with an enantiomeric ratio of 2.2:97.8 (95.6% ee). A model for
the asymmetric induction leading to the observed enantio-
selection was developed by using the Trost “wall/flap” model14
The β-hydroxybenzamides 12e and 12f also yielded low
levels of enantioselection in the asymmetric allylic alkylation
reaction. The rationale for the failure of these two ligands in
this process is attributed to structural dynamics associated
with the chiral cavity created by the interaction of the
palladium(II) with the bis(phosphine) ligands. It has been
established by Trost13 that his ligand 1b affords low enan-
tioselectivity in the alkylation reaction with methyl 1,3-
diphenylpropenylcarbonate, but high enantioselectivity
when the smaller allylic substrate methyl 3-penten-2-ylcar-
bonate was employed (Scheme 3). The rationalization for
these observations was that the “chiral pocket” created by
the ligand bound palladium catalyst exhibits optimal cata-
lytic and asymmetric efficiency when the allylic substrate is of
a smaller size. On the basis of this argument, it is presumed
(14) (a) Trost, B. M.; Machacek, M. R.; Aponick, A. Acc. Chem. Res.
2006, 39, 747. (b) Trost, B. M. Chem. Pharm. Bull. 2002, 50, 1. (c) Yamaguchi,
M.; Yabuki, M.; Yamagishi, T.; Sakai, K.; Tsubomura, T. Chem. Lett. 1996,
241.
(13) Trost, B. M.; Krueger, A. C.; Bunt, R. C.; Zambrano, J. J. Am.
Chem. Soc. 1996, 118, 6520.
8168 J. Org. Chem. Vol. 74, No. 21, 2009

Mahadik et al.
JOCArticle
FIGURE 5. Trost model for asymmetric induction in the allylic alkylation pathway.
FIGURE 6. Lloyd-Jones-Norrby model asymmetric induction in the allylic alkylation reaction.
(Figure 5) and the newly developed Lloyd-Jones-Norrby
model15 that involves hydrogen bonding of the ligand with the
incoming nucleophile. In the context of both of these models, it is
important to note that the diastereomeric ligands 12b and 12c16
yielded enantioselectivities that were in the g90% ee range. This
would suggest that the stereochemistry at the carbon bearing the
amide is one of the key facilitators of the asymmetric induction.17
The Trost model assumes the use of a C2-symmetric ligand as the
scaffold for the asymmetric process. The palladium-bound ligands
12b and 12c are β-benzoyloxyamides that would be expected to
exhibit more conformational freedom than the Trost ligands 1a
and 1b, potentially leading to lower enantioselectivities.2f Despite
this, the conveyance of the asymmetry from these ligands
is successfully transmitted to the prochiral allylic substrate as
evidenced by the moderately high level of enantioselection.
Recently, Lloyd-Jones and Norrby proposed that the
Trost model may be limited in terms of relaying a more
comprehensive analysis of the key events that occur in the
process of enforcing the formation of the new chiral center in
the substrate.15 The collected research suggested that hydro-
gen bonding from the amide contained in the ligand to the
approaching nucleophile was also important in terms of
determining the stereochemical outcome of the reaction.
Figure 6 illustrates this model with ligands 12b and 12c with
(15) (a) Butts, C. P.; Filali, E.; Lloyd-Jones, G. C.; Norrby, P.; Sale, D. A.;
Schramm, Y. J. Am. Chem. Soc. 2009, 131, 9945–9957. (b) Lloyd-Jones, G.
C.; Stephen, S. C.; Fairlamb, I. J.; Martorell, A.; Dominguez, B.; Tomlin, P.
M.; Murray, M.; Fernandez, J. M.; Jeffrey, J. C.; Riis-Johannessen, G. T.
Pure Appl. Chem. 2004, 76, 589–601. (c) Fairlamb, I. J.; Lloyd-Jones, G. C.
Chem. Commun. 2000, 2447. (d) Butts, C. P.; Crosby, J.; Lloyd-Jones, G. C.;
Stephen, S. C. Chem. Commun. 1999, 1707.
(16) No attempt was made to isolate the palladium complexes of 12b or
12c. The preparation of independent stoichiometric mixtures of 12b and 12c
with the palladium precatalyst has been inconclusive and will be the subject
of future studies.
(17) The Trost model of the asymmetric induction was originally designed
for (1R,2R)-diamine. The ligands described in Figures 3 and 4 possess the
S-configuration at the carbon bearing the amide.
J. Org. Chem. Vol. 74, No. 21, 2009 8169

Mahadik et al.
JOCArticle
exclusively yielded the S-enantiomer. The observed stereo-
chemistry of the products of these reactions was rationalized
based on the Trost model and the Lloyd-Jones-Norrby
model. On the basis of the results obtained here, there is the
potential for the development of even more effective β-
(o-diphenylphosphino)benzoyloxy(o-diphenylphosphino)ben-
zamide ligands in the palladium-catalyzed asymmetric allylic
reaction. Research is underway in this area.
4. Experimental Section
(R)-2-(Diphenylphosphino)-N-(2-hydroxy-2-phenylethyl)-
benzamide (11a). To a 250 mL nitrogen-purged round-bottomed
flask were added (R)-(-)-2-amino-1-phenyl-1-ethanol (0.350 g,
2.55 mmol), DMAP (0.062 g, 0.510 mmol), dichloromethane
(7 mL), 2-(diphenylphosphino)benzoic acid (0.781 g, 2.55 mmol),
and EDC (0.538 g, 2.80 mmol). The reaction mixture was allowed
to stir for 24 h and then quenched with the addition of 3 M HCl
(2 ꢀ 50 mL). The organic layer was diluted with dichloromethane
(100 mL), washed with brine (50 mL), and dried with magnesium
sulfate (MgSO4). The solvents were removed via rotary evapora-
tion and the product was isolated by flash column chromatogra-
phy (hexanes:EtOAc, 6:4). Viscous wax (37%), [R]24 -32.1
D
(c 0.50, CHCl3); IR (nujol) (cm-1) 3312, 1634, 1581, 1310, 1160,
744, 698; 1H NMR (500 MHz, CDCl3) δ(ppm) 3.20(ddd,J=4.9,
8.6,12.4 Hz, 1H), 3.6 3 (ddd, J=3.2, 7.0, 12.4 Hz, 1H), 3.65 (d, J=
3.9 Hz, 1H), 4.63-4.66 (m, 1H), 6.56 (t, J = 5.2 Hz, 1H),
6.94-6.98 (m, 1H), 7.19-7.31 (m, 17H), 7.47-7.51 (m, 1H);
13C NMR (CDCl3) δ 47.8, 72.8, 125.7, 127.5, 127.6, 127.7, 128.3,
128.47, 128.49, 128.52, 128.54, 128.7, 128.8, 130.1, 133.6, 133.7,
133.80, 133.84, 134.0, 135.8, 136.0, 136.5, 136.6, 136.7, 136.8,
140.8, 141.0, 141.5, 169.9; 31P{1H} NMR (CDCl3) -9.92 ppm;
ESI-HRMS calcd for C27H24NO2P (M þ Hþ) 426.1623, found
426.1620.
FIGURE 7. Semiempirical PM3 modeled ligand Trost modular
ligand 1a and β-benzoyloxy amide 12c. Red = oxygen, blue =
nitrogen, gold=phosphorus, green=palladium.
the ligand adopting a similar conformation about the palla-
dium complex as was depicted in the Trost model of Figure 3.
A computational study was conducted with the objective
of evaluating the conformational aspects of the palladium-
bound 12c versus that of the palladium-bound Trost ligand
1a. Thus, a conformational search was conducted. Confor-
mation searching of ligands 12c and 1a was carried out by
using the MMFF force field. Low-energy conformers of
ligands which met acceptable end-to-end distance criteria
were then bound to palladium and subjected to additional
conformation searching by using the Semiempirical PM3
methodology. The lowest energy conformers were obtained
and the structures for the palladium complexes 12c and 1a
are shown in Figure 7. The palladium-bound Trost ligand 1a
has an element of C2-symmetry imparted by the ligand,
whereas the palladium-bound complex 12c deviated from a
symmetrical structure.
This deviation from a more symmetric form is believed to
be due, in some part, to the syn-configuration of the phenyl
rings and the presence of the conformationally flexible ester
functional group. Computationally, there was another con-
former for 12c that was within 1 kcal/mol that was similar in
structure. At room temperature, there are most likely a
number of conformers that, on average, converge to the
conformer depicted. It is proposed that this distortion away
from the C2-symmetry allows for complex 12c to interact
with large substrates such as the 1,3-diphenylpropenyl acet-
ate to give good enantiomeric excesses. It must be noted that
the calculations were conducted in the gas phase and
that there may be solvent effects that are not taken into
account.
(R)-2-(2-(Diphenylphosphino)benzamido)-1-phenylethyl
2-(Diphenylphosphino)benzoate (12a). To a 250 mL nitrogen-
purged round-bottomed flask were added (R)-(-)-2-amino-
1-phenylethanol (0.300 g, 2.19 mmol), DMAP (0.267 g, 2.19 mmol),
dichloromethane (10 mL), 2-(diphenylphosphino)benzoic
acid (1.34 g, 4.37 mmol), and EDC (0.838 g, 4.37 mmol).
The reaction mixture was allowed to stir for 24 h and then
quenched with the addition of 3 M HCl (2 ꢀ 50 mL). The
organic layer was diluted with dichloromethane (100 mL),
washed with brine (50 mL), and dried with magnesium
sulfate (MgSO4). The solvents were removed via rotary
evaporation and the product was isolated by flash column
chromatography (hexanes:EtOAc, 6:4). Viscous wax (50%),
[R]24 27.4 (c 0.26, CHCl3); IR (nujol) (cm-1) 1714, 1651,
D
1
1584, 1247, 1108, 743, 696; H NMR (500 MHz, CDCl3)
δ (ppm) 3.18 (ddd, J=3.6, 10.3, 13.0 Hz, 1H), 3.98 (ddd, J =
3.2, 8.6, 13.0, Hz, 1H), 5.93 (dd. J = 3.0, 10.3 Hz, 1H),
6.88-6.90 (m, 1H), 6.93-6.97 (m, 1H), 7.12-7.49 (m, 30 H),
7.65-7.67 (m, 1H), 8.10-8.12 (m, 1H); 13C NMR (CDCl3)
δ 44.2, 126.5, 127.7, 128.2, 128.4, 128.42, 128.5, 128.54,
128.6, 128.7, 128.74, 128.8, 128.82, 128.9, 129.1, 130.1,
132.1, 132.3, 133.4, 133.5, 133.7, 133.8, 133.9, 134.0,
134.15, 134.2, 134.3, 134.9, 135.2, 135.3, 136.9, 137.0,
137.01, 137.1, 137.2, 137.3, 137.45, 137.5, 137.54, 137.6,
137.7, 140.9, 141.1, 166.3, 168.6; 31P{1H} NMR (CDCl3)
-5.28, -5.31, -8.84, -8.86 ppm; 31P NMR also suggests
impurity present in less than 5%; ESI-HRMS calcd for
C46H37NO3P2 (M þ Hþ) 714.2327, found 714.2335.
3. Conclusion
The (mono)phosphine ligands 11a-f primarily afforded
the R-enantiomer and the bis(phosphine) ligands 12a-f
8170 J. Org. Chem. Vol. 74, No. 21, 2009

Mahadik et al.
JOCArticle
2-(Diphenylphosphino)-N-(1S,2S)-2-hydroxy-1,2-dipheny-
lethylbenzamide (11b). To a 250 mL nitrogen-purged round-
bottomed flask were added (S,S)-(-)-2-amino-1,2-diphenyl-
ethanol (0.300 g, 1.41 mmol), DMAP (0.034 g, 0.281 mmol),
dichloromethane (10 mL), 2-(diphenylphosphino)benzoic
acid (0.430 g, 1.41 mmol), and EDC (0.297 g, 1.55 mmol).
The reaction mixture was allowed to stir for 24 h and then
quenched with the addition of 3 M HCl (2 ꢀ 50 mL). The
organic layer was diluted with dichloromethane (100 mL),
washed with brine (50 mL), and dried with magnesium
sulfate (MgSO4). The solvents were removed via rotary
evaporation and the product was isolated by flash column
chromatography (hexanes:EtOAc, 7:3). Viscous wax (52%),
[R]23D -35.4 (c 0.55, CHCl3); IR (nujol) (cm-1) 3343, 1642,
1579, 1314, 1184; 1H NMR (500 MHz, CDCl3) δ (ppm) 3.59
(s, 1H), 4.70 (d, J=7.8 Hz, 1H), 5.18 (dd, J=8.1, 10.0 Hz,
1H), 6.61 (d, J=9.0 Hz, 1H), 6.78-6.80 (m, 1H), 6.85-6.89
(m, 1H), 7.01-7.29 (m, 21H), 7.34-7.37 (m, 1H); 13C NMR
(CDCl3) 60.6, 77.4, 126.5, 127.1, 127.4, 127.5, 128.2, 128.21,
128.3, 128.5, 128.6, 128.7, 128.8, 128.83, 128.9, 128.94, 130.2,
133.55, 133.58, 133.75, 133.78, 134.3, 134.8, 134.9, 136.2,
136.3, 136.7, 136.8, 138.5, 140.4, 141.43, 141.7, 169.2; 31P-
{1H} NMR (CDCl3) -10.98 ppm; ESI-HRMS calcd for
C33H28NO2P (M þ Hþ) 502.1936, found 502.1925.
in ether and hexanes (1:2). Viscous wax (71%), [R]24D -37.9
(c 1.00, CHCl3); IR (nujol) (cm-1) 3350, 1623, 1522, 1220; 1H
NMR (400 MHz, CDCl3) δ (ppm) 5.17(d, J=3.3 Hz, 1H),
5.28(dd, J=5.4 Hz,1H), 6.72 (br s, 1H), 6.81 (d, J=7.5 Hz,
3H), 6.99-7.02 (m, 5H), 7.11 (t, J = 2.86 Hz, 3H), 7.16-7.42
(m, 13H), 7.61-7.64 (m, 1H); 13C NMR (CDCl3) 60.6, 75.7,
126.4, 127.3, 127.5, 127.8, 127.9, 128.2, 128.3, 128.31, 128.7,
128.71, 128.8, 128.9, 129.1, 129.3, 130.4, 133.7, 133.7, 133.8,
133.9, 134.3, 136.2, 139.8, 168.8; 31P{1H} NMR (CDCl3)
-10.73 ppm; ESI-HRMS calcd for C33H29NO2P (M þ Hþ)
502.1936, found 502.1946.
(1R,2S)-2-(2-(Diphenylphosphino)benzamido)-1,2-diphenyl-
ethyl 2-(Diphenylphosphino)benzoate (12c). To a 250 mL
nitrogen-purged round-bottomed flask were added (1R,2S)-
2-amino-1,2-diphenylethanol (0.494 g, 2.32 mmol), DMAP
(0.283 g, 2.316 mmol), dichloromethane (10 mL), 2-(di-
phenylphosphino)benzoic acid (1.42 g, 4.63 mmol), and
EDC (0.888 g, 4.63 mmol). The reaction mixture was allowed
to stir for 24 h and then quenched with the addition of 3 M
HCl (2 ꢀ 50mL). The organic layer was diluted with dichloro-
methane (100 mL), washed with brine (50 mL), and dried with
magnesium sulfate (MgSO4). The solvents were removed via
rotary evaporation and the product was isolated by recrys-
tallization in ether and hexanes (1:2). White solid (43%),
(1S,2S)-2-(2-(Diphenylphosphino)benzamido)-1,2-diphenyl-
ethyl 2-(diphenylphosphino)benzoate (12b). To a 250 mL
nitrogen-purged round-bottomed flask were added (S,S)-
(-)-2-amino-1,2-diphenylethanol (0.494 g, 2.32 mmol),
DMAP (0.283 g, 2.32 mmol), dichloromethane (10 mL),
2-(diphenylphosphino)benzoic acid (1.42 g, 4.63 mmol),
and EDC (1.00 g, 4.63 mmol). The reaction mixture was
allowed to stir for 24 h and then quenched with the addition
of 3 M HCl (2 ꢀ 50 mL). The organic layer was diluted with
dichloromethane (100 mL), washed with brine (50 mL), and
dried with magnesium sulfate (MgSO4). The solvents were
removed via rotary evaporation and the product was isolated
by flash column chromatography (hexanes:EtOAc, 7:3).
[R]23 þ9.6 (c 1.00, CHCl3); mp 220-223 °C; IR (nujol)
D
(cm-1) 3350, 1623, 1522, 1220; 1H NMR (400 MHz, CDCl3)
δ (ppm) 5.58 (dd, J=4.1, 8.8 Hz, 1H), 6.21 (d, J=4.1 Hz, 1H),
6.91-6.99 (m, 8H), 7.06-7.31 (m, 26H), 7.38-7.41 (m, 3H),
7.54-7.57 (m, 1H), 7.97-8.00 (m, 1H); 13C NMR (CDCl3)
57.8, 78.6, 126.8, 127.4, 127.9, 128.0, 128.03, 128.1, 128.14,
128.2, 128.4, 128.42, 128.5, 128.6, 128.62, 128.7, 130.1, 130.5,
131.9, 133.6, 133.7, 133.76, 133.8, 133.9, 133.93, 134.0, 134.1,
134.5, 134.8, 135.0, 136.3, 136.4, 136.5, 136.7, 137.0, 137.04,
137.1, 137.2, 137.3, 137.6, 137.7, 139.9, 140.1, 141.0, 141.2,
166.0, 167.9; 31P{1H} NMR (CDCl3) -5.45, -9.72 ppm; ESI-
HRMS calcd for C52H42NO3P2 (M þ Hþ) 790.2640, found
790.2649.
Viscous wax (49%), [R]24 -30.0 (c 0.52, CHCl3); IR
2-(Diphenylphosphino)-N-((1S,2S)-2-hydroxy-2,3-dihydro-1H-
inden-1-yl)benzamide (11d).To a 250 mL nitrogen-purged round-
bottomed flask were added (1S,2S)-(þ)-trans-1-amino-2-indanol
(0.200 g, 1.34 mmol), DMAP (0.033 g, 0.268 mmol), dichloro-
methane (10 mL), 2-(diphenylphosphino)benzoic acid (0.411 g,
1.34 mmol), and EDC (0.283 g, 1.48 mmol). The reaction mixture
was allowed to stir for 24 h and then quenched with the addition
of 3 M HCl (2 ꢀ 50 mL). The organic layer was diluted with
dichloromethane (100 mL), washed with brine (50 mL), and
dried with magnesium sulfate (MgSO4). The solvents were
removed via rotary evaporation and the product was isolated
by flash column chromatography (hexanes:EtOAc, 6:4). Viscous
D
(nujol) (cm-1) 3404, 1716, 1666, 1583, 1338, 1146; 1H
NMR (500 MHz, CDCl3) δ (ppm) 5.65 (t, J=8.3 Hz, 1H),
6.20 (d, J=7.7 Hz, 1H), 6.90-6.95 (m, 1H), 7.00-7.46 (m, 37
H), 8.28-8.29 (m, 1H); 13C NMR (CDCl3) 58.0, 78.6, 127.2,
127.4, 127.9, 127.93, 128.0, 128.1, 128.2, 128.24, 128.3,
128.32, 128.4, 128.43, 128.5, 130.0, 131.8, 132.1, 133.3,
133.4, 133.5, 133.6, 133.7, 133.76, 133.8, 133.84, 134.1,
134.4, 135,6, 135.8, 136.7, 136.9, 137.0, 137.1, 137.2, 137.4,
137.44, 137.6, 137.65, 137.7, 139.9, 140.1, 141.2, 141.5, 165.7,
168.1; 31P{1H} NMR (CDCl3) -4.43, -10.76 ppm; ESI-
HRMS calcd for C52H41NO3P2 (M þ Hþ) 790.2640, found
790.2635.
wax (71%), [R]24 25.7 (c 0.30, CHCl3); IR (nujol) (cm-1
)
D
2-(Diphenylphosphino)-N-(1R,2S)-2-hydroxy-1,2-diphenyl-
ethylbenzamide (11c). To a 250 mL nitrogen-purged round-
bottomed flask were added (1R,2S)-2-amino-1,2-diphenyl-
ethanol (0.494 g, 2.32 mmol), DMAP (0.057 g, 0.463 mmol),
dichloromethane (6 mL), 2-(diphenylphosphino)benzoic
acid (0.709 g, 2.32 mmol), and EDC (0.488 g, 2.55 mmol).
The reaction mixture was allowed to stir for 24 h and was
quenched with the addition of 3 M HCl (2 ꢀ 50 mL). The
organic layer was diluted with dichloromethane (100 mL),
washed with brine (50 mL), and dried with magnesium
sulfate (MgSO4). The solvents were removed via rotary
evaporation and the product was isolated by recrystallization
1628, 1583, 1306, 1154, 742, 723; 1H NMR (500 MHz, CDCl3)
δ (ppm) 2.87(dd, J=8.1, 15.8 Hz, 1H), 3.21 (dd, J=7.9, 15.8 Hz,
1H), 4.24 (dd, J=7.9, 14.2 Hz, 1H), 4.55 (s, 1H), 5.03 (t, J=
5.8 Hz, 1H), 6.59-6.61 (m, 1H), 6.93-6.97 (m, 1H), 7.12-7.39
(m, 16 H), 7.66-7.68 (m, 1H); 13C NMR (CDCl3) 38.3, 64.8,
81.1, 123.0, 125.0, 127.1, 128.3, 128.34, 128.4, 128.66, 128.7,
128.72, 128.74, 128.8, 129.1, 129.14, 130.5, 133.7, 133.8, 133.9,
133.91, 134.0, 135.7, 135.8, 135.9, 136.0, 136.1, 136.2, 138.7,
139.9, 140.1, 140.4, 171.13; 31P{1H} NMR (CDCl3) -9.21
ppm; 31P NMR also suggests impurity present in less than 5%;
ESI-HRMS calcd for C28H24NO2P (M þ Hþ) 438.1623, found
438.1618.
J. Org. Chem. Vol. 74, No. 21, 2009 8171

Mahadik et al.
JOCArticle
(1S,2S)-1-(2-(Diphenylphosphino)benzamido)-2,3-dihydro-
1H-inden-2-yl 2-(Diphenyphosphino)benzoate (12d). To a
250 mL nitrogen-purged round-bottomed flask were added
(1S,2S)-(þ)-trans-1-amino-2-indanol (0.200 g,1.34 mmol),
DMAP (0.066 g, 0.536 mmol), dichloromethane (10 mL),
2-(diphenylphosphino)benzoic acid (0.821 g, 2.68 mmol),
and EDC (0.514 g, 2.68 mmol). The reaction mixture was
allowed to stir for 24 h and then quenched with the addition
of 3 M HCl (2 ꢀ 50 mL). The organic layer was diluted with
dichloromethane (100 mL), washed with brine (50 mL), and
dried with magnesium sulfate (MgSO4). The solvents were
removed via rotary evaporation and the product was isolated
by flash column chromatography (hexanes:EtOAc, 6:4).
dried with magnesium sulfate (MgSO4). The solvents were
removed via rotary evaporation and the product was isolated
by flash column chromatography (hexanes:EtOAc, 6:4).
Viscous wax (65%), [R]23D 66.9 (c 0.49, CHCl3); IR (nujol)
(cm-1) 3249, 1715, 1660, 1585, 1215, 762, 696; 1H NMR (500
MHz, CDCl3) δ (ppm) 2.67 (d, J=17.6 Hz, 1H), 3.13 (dd, J=
4.6, 17.6 Hz, 1H), 5.88 (d, J=7.0 Hz, 1H), 6.60 (t, J=8.2 Hz,
1H), 6.71 (t, J=7.2 Hz, 1H), 6.83-7.40 (m, 29H), 7.55-7.57
(m, 1H), 7.90 (s, 1H), 8.12-8.14 (m, 1H); 13C NMR (CDCl3)
37.6, 55.6, 77.2, 124.3, 124.3, 124.7, 127.0, 127.8, 127.81,
128.2, 128.21, 128.3, 128.32, 128.34, 128.4, 128.41, 128.5,
128.53, 128.6, 128.7, 129.72, 131.8, 131.9, 132.1, 132.7, 132.9,
133.7, 133.8, 133.9, 133.91, 134.2, 134.7, 135.1, 135.2, 135.27,
135.3, 136.1, 136.3, 136.7, 136.8, 137.1, 137.2, 137.23, 137.3,
137.8, 137.9, 138.9, 140.7, 141.9, 142.1, 166.8, 169.2; 31P{1H}
NMR (CDCl3) -5.73, -10.06 ppm; 31P NMR also suggests
impurity present in less than 5%; ESI-HRMS calcd for
C47H37N O3P2 (M þ Hþ) 726.2327, found 726.2337.
Viscous wax (40%), [R]24 6.9 (c 0.54, CHCl3); IR (nujol)
D
(cm-1) 1707, 1645, 1584, 1252, 742, 695; 1H NMR (500 MHz,
CDCl3) δ (ppm) 2.74 (dd, J=7.0, 16.2 Hz, 1H), 3.25 (dd, J=
7.5, 16.2 Hz, 1H), 5.27 (dd, J = 7.1, 13.9 Hz, 1H), 5.72
(apparent triplet, J=7.1 Hz, 1H), 6.32 (dd, J=1.0, 8.4 Hz,
1H), 6.89-6.95 (m, 1H), 7.08-7.38 (m, 29 H), 7.60-7.62 (m,
1H), 8.11-8.14 (m, 1H); 13C NMR (CDCl3) 36.2, 59.4, 80.7,
124.45, 124.5, 124.6, 127.3, 128.0, 128.02, 128.29, 128.3,
128.33, 128.4, 128.44, 128.5, 128.54, 128.66, 128.7, 128.8,
130.2, 131.15, 131.2, 132.0, 133.65, 133.7, 133.8, 133.9,
133.94, 134.0, 134.03, 134.1, 135.8, 135.9, 136.7, 136.8,
137.0, 137.1, 137.7, 137.8, 138.0, 138.1, 138.7, 139.4, 140.3,
140.5, 140.8, 141.0, 166.6, 169.0; 31P{1H} NMR (CDCl3)
-4.40, -10.17 ppm; ESI-HRMS calcd for C47H37NO3P2
(M þ Hþ) 726.2327, found 726.2313.
2-(Diphenylphosphino)-N-((1R,2R)-2-hydroxycyclohexyl)-
benzamide (11f). To a 250 mL nitrogen-purged round-bot-
tomed flask were added (1R,2R)-trans-2-aminocyclohexanol
(0.350 g, 2.31 mmol), DMAP (0.056 g, 0.462 mmol), dichloro-
methane (10 mL), 2-(diphenylphosphino)benzoic acid
(0.707 g, 2.308 mmol), and EDC (0.487 g, 2.54 mmol). The
reaction mixture was allowed to stir for 24 h and then
quenched with the addition of 3 M HCl (2 ꢀ 50 mL). The
organic layer was diluted with dichloromethane (100 mL),
washed with brine (50 mL), and dried with magnesium
sulfate (MgSO4). The solvents were removed via rotary
evaporation and the product was isolated by flash column
chromatography (hexanes:EtOAc, 6:4). Viscous wax (48%),
[R]24D -32.1 (c 0.50, CHCl3); IR (nujol) (cm-1) 1716, 1270,
1248, 744, 696; 1H NMR (500 MHz, CDCl3) δ (ppm)
0.83-0.98 (m, 2H), 1.07-1.33 (m, 2H), 1.58-1.67 (m, 2H),
1.81-1.84 (m, 1H), 1.95-1.98 (m, 1H), 3.20 (td, J=4.4, 10.4
Hz, 1H), 3.66-3.73 (m, 1H), 6.01 (d, J = 7.6 Hz, 1H),
6.96-6.98 (m, 1H), 7.24-7.36 (m, 13H), 7.60-7.63 (m,
1H); 13C NMR (CDCl3) 23.8, 24.4, 30.9, 33.6, 56.1, 74.3,
128.06, 128.1, 128.5, 128.6, 128.62, 128.7, 128.9, 128.92,
129.0, 130.1, 133.5, 133.6, 133.7, 133.7, 134.0, 134.5, 136.1,
136.2, 136.3, 141.6, 141.9, 170.0; 31P{1H} NMR (CDCl3)
-10.96 ppm; 31P NMR also suggests impurity present in less
than 5%; ESI-HRMS calcd for C25H26 NO2 P (M þ Hþ)
404.1779, found 404.1765.
(1R,2R)-(2-(Diphenylphosphino)benzamido)cyclohexyl
2-(Diphenylphosphino)benzoate (12f). To a 250 mL nitrogen-
purged round-bottomed flask were added (1R,2R)-trans-2-
aminocyclohexanol (0.350 g, 2.31 mmol), DMAP (0.282 g,
2.31 mmol), dichloromethane (10 mL), 2-(diphenylphosph-
ino)benzoic acid (1.41 g, 4.62 mmol), and EDC (0.885 g,
4.62 mmol). The reaction mixture was allowed to stir for 24 h
and then quenched with the addition of 3 M HCl (2 ꢀ 50 mL).
The organic layer was diluted with dichloromethane
(100 mL), washed with brine (50 mL), and dried with
magnesium sulfate (MgSO4). The solvents were removed
via rotary evaporation and the product was isolated by flash
column chromatography (hexanes:EtOAc, 6:4). Viscous wax
(50%), [R]23D 64.3 (c 0.51, CHCl3); IR (nujol) (cm-1) 1698,
1656, 1583, 1256, 1156, 743, 693; 1H NMR (500 MHz,
CDCl3) δ (ppm) 0.83-0.97 (m, 2H), 1.11-1.27 (m, 1H),
1.35-1.43 (m, 1H), 1.55-1.67 (m, 2H), 1.90 (t, J=13.5 Hz,
2H), 4.12 (td, J=4.1, 12.0 Hz, 1H), 4.73 (td, J=4.4, 11.4 Hz,
2-(Diphenylphosphino)-N-((1R,2S)-2-hydroxy-2,3-dihydro-1H-
inden-1-yl)benzamide (11e). To a 250 mL nitrogen-purged
round-bottomed flask were added (1R,2S)-(þ)cis-1-amino-
2-indanol (0.500 g, 3.35 mmol), DMAP (0.082 g, 0.670 mmol),
dichloromethane (10 mL), 2-(diphenylphosphino)benzoic
acid (1.03 g, 3.35 mmol), and EDC (0.707 g, 3.69 mmol).
The reaction mixture was allowed to stir for 24 h and then
quenched with the addition of 3 M HCl (2 ꢀ 50 mL). The
organic layer was diluted with dichloromethane (100 mL),
washed with brine (50 mL), and dried with magnesium
sulfate (MgSO4).The solvents were removed via rotary eva-
poration and the product was isolated by flash column
chromatography (hexanes:EtOAc, 6:4). Viscous wax
(56%); [R]23D 34.4 (c 0.54, CHCl3); IR (nujol) (cm-1) 1716,
1270, 1248, 744, 696; 1H NMR (500 MHz, CDCl3) δ (ppm)
2.81 (dd, J=1.5, 16.6 Hz, 1H), 2.99 (dd, J=5.0, 16.6 Hz, 1H),
3.06 (s, 1H), 4.52 (d, J=3.1 Hz, 1H), 5.35 (dd, J=5.0, 8.3 Hz,
1H), 6.66 (d, J=8.3 Hz, 1H), 6.98-7.01 (m, 1H), 7.09-7.31
(m, 16 H), 7.60-7.62 (m, 1H); 13C NMR (CDCl3) 39.3, 58.1,
73.1, 124.3, 124.9, 126.8, 127.6, 127,64, 127.8, 140.2, 141.2,
141.4, 128.4, 128.5, 128.7, 128.8, 130.1, 133.5, 133.65, 133.7,
133.8, 134.0, 135.4, 135.5, 136.3, 136.4, 136.5, 136.54, 169.4;
31P{1H} NMR (CDCl3) -10.04 ppm; ESI-HRMS calcd for
C28H24NO2P (M þ Hþ) 438.1623, found 438.1618.
(1R,2S)-1-(2-(Diphenylphosphino)benamido)-2,3-dihydro-
1H-inden-2-yl 2-(Diphenylphosphino)benzoate (12e). To a
250 mL nitrogen-purged round-bottomed flask were added
(1R,2S)-(þ)-cis-1-amino-2-indanol (0.108 g, 0.724 mmol),
DMAP (0.088 g, 0.724 mmol), dichloromethane (7 mL),
2-(diphenylphosphino)benzoic acid (0.444 g, 1.45 mmol),
and EDC (0.277 g, 1.45 mmol). The reaction mixture was
allowed to stir for 24 h and then quenched with the addition
of 3 M HCl (2 ꢀ 50 mL). The organic layer was diluted with
dichloromethane (100 mL), washed with brine (50 mL), and
8172 J. Org. Chem. Vol. 74, No. 21, 2009

Mahadik et al.
JOCArticle
1H), 6.04 (d, J=8.9 Hz, 1H), 6.87-6.90 (m, 1H), 7.14-7.46
(m, 26H), 8.15-8.18 (m, 1H); 13C NMR (CDCl3) 23.8, 24.0,
30.7, 31.4, 52.5, 75.3, 127.3, 128.1, 128.11, 128.14, 128.16,
128.2, 128.22, 128.24, 128.3, 128.4, 128.42, 129.7, 131.0,
131.7, 133.4, 133.5, 133.6, 133.64, 133.9, 133.94, 134.1,
135.7, 135.9, 137.1, 137.2, 137.4, 137.5, 137.7, 137.8, 137.9,
138.0, 140.0, 140.2, 140.9, 141.1, 166.7, 168.2; 31P{1H} NMR
(CDCl3) -4.71, -9.84 ppm; ESI-HRMS calcd for
C44H39NO3P2 (M þ Hþ) 692.2483, found 692.2484.
isolated by flash column chromatography (hexanes:EtOAc,
9:1). The products were analyzed by HPLC, using an AD
column. 1H NMR (500 MHz, CDCl3) δ (ppm) 3.44 (s, 3H),
3.62 (s, 3H), 3.88 (d, J=10.9 Hz, 1H), 4.19 (dd, J=8.8, 10.8 Hz,
1H), 6.26 (dd, J=8.60, 15.8 Hz, 1H), 6.40 (d, J=15.8 Hz,
1H), 7.10-7.25 (m, 10 H); 13C NMR (CDCl3) 49.2, 52.4,
52.6, 57.6, 126.4, 127.1, 127.5, 127.9, 128.5, 128.7, 129.1,
131.8, 136.8, 140.2, 167.7, 168.2.
General Procedure for the Catalytic Asymmetric Allylic
Alkylation Reactions (Table 2, Entry 7). To a 50 mL nitrogen-
purged round-bottomed flask were added ligand (0.053 g,
0.067 mmol), [(η3-C3H5)PdCl]2 (0.025 g, 0.068 mmol), KOAc
(0.006 g, 0.068 mmol), THF (4 mL), BSA (1.3 mL, 5.100 mmol),
1,3-diphenylpropenyl acetate (0.456 g, 1.700 mmol), and
CH2(CO2Me)2 (0.6 mL, 5.100 mmol). The reaction mixture
was allowed to stir for 6 h at 25 °C and then quenched with
the addition of 1 M HCl (50 mL) and ammonium chloride
(50 mL). The organic layer was diluted with ether (50 mL),
washed with brine (50 mL), and dried (MgSO4). The solvents
were removed via rotary evaporation and the product was
Acknowledgment. The authors gratefully acknowledge
financial support from the National Science Foundation
(grant CHE-644950). The 500 MHz NMR spectroscopic
data collected in this work are based upon work supported
by the National Science Foundation under grant no.CHE-
0722385.
Supporting Information Available: Copies of 1H, 13C, and
31P NMR spectra for new compounds 11a-f and 12a-f and
HPLC traces for the asymmetric allylic alkylations. This
material is available free of charge via the Internet at http://
pubs.acs.org.
J. Org. Chem. Vol. 74, No. 21, 2009 8173