Palladium catalyzed asymmetric sulfonylation mediated chiral β-hydroxy- and β-(o-diphenylphosphino)benzoyloxy (o-diphenyl phosphino)benzamides

Article abstract of DOI:10.1016/j.tetasy.2010.10.022

The palladium catalyzed asymmetric allylic sulfonylation reaction has been investigated employing β-hydroxy- and β-(o-diphenylphosphino) benzoyloxy (o-diphenyl phosphino)benzamides as chiral, non-racemic ligands. The bisphosphine β-benzoyloxybenzamide ligands proved to be the best ligands for this process. Competitive transition states for the (1S,2R)-norephedrine derived ligand 14 are compared and a rationale is provided for the observed enantioselectivities.

Full text of DOI:10.1016/j.tetasy.2010.10.022

Tetrahedron: Asymmetry 21 (2010) 2690–2695
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Tetrahedron: Asymmetry
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Palladium catalyzed asymmetric sulfonylation mediated chiral b-hydroxy-
and b-(o-diphenylphosphino)benzoyloxy (o-diphenyl phosphino)benzamides
⇑
Jesse A. Wolfe, Shawn R. Hitchcock
Department of Chemistry, Illinois State University, Normal, IL 61790-4160, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The palladium catalyzed asymmetric allylic sulfonylation reaction has been investigated employing b-
hydroxy- and b-(o-diphenylphosphino)benzoyloxy (o-diphenyl phosphino)benzamides as chiral, non-
racemic ligands. The bisphosphine b-benzoyloxybenzamide ligands proved to be the best ligands for this
process. Competitive transition states for the (1S,2R)-norephedrine derived ligand 14 are compared and a
rationale is provided for the observed enantioselectivities.
Received 24 September 2010
Accepted 26 October 2010
Available online 20 November 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
The substrate was added to a solution containing the palladium
pre-catalyst [(g
3-(C3H5)PdCl)]2 and triphenylphosphine. Finally,
The remarkable success of Tsuji-Trost palladium catalyzed
asymmetric reactions with allylic substrates has spurred the devel-
opment and application of a broad range of phosphorus containing
ligand frameworks.1–4 Burke et al.5 recently developed a series of
monophosphine ligands 1 that were successfully employed in the
asymmetric alkylation of 1,3-diphenylpropenyl acetate with mal-
onate nucleophiles (Fig. 1). This work inspired our group to explore
the use of Ephedra derivatives and commercially available b-amino
alcohols as templates for making both b-hydroxy(o-diphenylphos-
phino)benzamides 2 and b-(o-diphenylphosphino)benzoyloxy (o-
diphenylphosphino)benzamides 3.6,7 We learned that these easily
prepared mono- and bisphosphine ligands could indeed serve as
effective ligands in the palladium catalyzed asymmetric allylic
alkylation of dimethyl malonate and afforded enantioselectivities
of up to 96% ee.8
We became interested in determining the efficacy of the Ephe-
dra based phosphines and other related b-amino alcohol derived
phosphines in the asymmetric allylic sulfonylation reaction that
was pioneered by Hiroi and Makino (Fig. 2).9 Eichelmann and
Gais10 as well as Bondarev et al have also made contributions in
this field.11,12 We describe herein our efforts to employ b-hydroxy-
and b-(o-diphenylphosphino)benzoyloxy(o-diphenyl phosphino)
benzamides as chiral, non-racemic ligands in this area.
the nucleophile (either anhydrous sodium p-toluenesulfinate or
the monohydrate of sodium p-toluenesulfinate) was added to the
reaction mixture. The anhydrous material gave a better yield
(42%) of target compound 9 to reactions involving the hydrated
salt. The catalysis reactions involving the ligands 2a and 2b did
not yield any product when either nucleophile was applied. It is
postulated that the b-hydroxy component of ligands 2a and 2b is
responsible for deactivation of the catalytic system. The origin of
this deactivation is not clear as these same ligands afforded the
product in good yield and enantiomeric excess when the asymmet-
ric alkylation of 1,3-diphenylpropenyl acetate with dimethyl mal-
onate was carried out.7
To determine why the catalysis process was unsuccessful,
(1S,2R)-norephedrine was acylated with o-(diphenylphos-
phino)benzoic acid (Scheme 1). The resultant amide was esterified
at the benzylic alcohol by treatment with benzoyl chloride to yield
the target compound in 49% isolated yield. This ‘capped’ variant of
the b-hydroxy(o-diphenylphosphino)benzamide ligand was then
employed in the asymmetric sulfonylation reaction with [(g3
-
(C3H5)PdCl)]2 and 1,3-diphenylpropenyl acetate to afford the sulf-
onylated product 9 in 46% yield and 78% ee favoring the (R)-enan-
tiomer. Interestingly, the application of the related O-naphthoyl
capped variant in the asymmetric sulfonylation process afforded
9 in only 5% yield and 23% ee favoring the (S)-enantiomer.
It is proposed that the origin of the difference in the chemical
yield and enantioselectivity occurs during the course of the respec-
tive transition states and intermediates of the catalytic process
(Fig. 3). In the case of the O-benzoyl ligand 12a, it is believed that
the ligand coordinates with palladium through the phosphino
group and through the carbonyl of the benzoyl group. The potential
bonding of the palladium center with the carbonyl is supported by
the earlier mechanistic studies of Lloyd-Jones et al.13 as well as by
2. Results and discussion
We began our investigation by employing triphenylphosphine
as a ligand in the palladium catalyzed allylic sulfonylation of the
substrate 1,3-diphenylpropenyl acetate as a test reaction (Table 1).
⇑
Corresponding author. Tel.: +1 309 438 7854.
E-mail address: Hitchcock@ilstu.edu (S.R. Hitchcock).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.10.022

J. A. Wolfe, S. R. Hitchcock / Tetrahedron: Asymmetry 21 (2010) 2690–2695
2691
R2
R1
N
R2
R1
H3C
R1
H3C
N
O
O
O
O
N
OH
OCH3
O
H
H
H
PPh2
PPh2
PPh2
Ph2P
1a: R1 = -i-Pr (Burke et al.)1
1b: R1 = -Ph
2a: R1 = -Ph, R2 = -H
2b: R1 = -H, R2 = -Ph
3a: R1 = -Ph, R2 = -H
3b: R1 = -H, R2 = -Ph
Figure 1. Chiral, non-racemic phosphine ligands 1–3.
Table 1
O
N
Catalysis with triphenylphosphine and attempted catalysis with ligands 10–11
O
O
Ph2P
Ph2P
Me
Me
SO2p-Tol
OAc
ligand, nucleophile
Ph2P
[(η3-C3H5)2PdCl]2, THF
Ph
Ph
Ph
Ph
5 Eichelmann and Gais10
4 Hiroi and Makino9
8
9
Entry
Ligand
Nucleophile
% Yielda
H
O
1
2
3
4
5
6
Ph3P
Ph3P
2a
2a
2b
NaSO2p-Tol-H2O
NaSO2p-Tol
NaSO2p-Tol-H2O
NaSO2p-Tol
NaSO2p-Tol-H2O
NaSO2p-Tol
29
42
NR
NR
NR
NR
N
N
P
N
Ph
Me O
Me
O
N
2b
P
O
Me
a
O
Me
Isolated yields were determined after flash chromatography.
O
Ph
6 Bondarev et al.11
Me
7 Bondarev et al.12
At this time, we became interested in applying the bisphos-
phine ligands that we had developed earlier for palladium cata-
lyzed asymmetric allylic alkylations with diethylmalonate.8 Prior
to our application of these ligands, the Trost ligand 13 was em-
ployed in the palladium catalyzed sulfonylation reaction (Table 2).
This ligand was excellent in affording a near quantitative yield of
the product with 93% enantiomeric excess in the formation of
the (R)-enantiomer of homoallylic sulfone 9.
The b-aminoalcohol derived bisphosphines were not as success-
ful as in their application but still afforded results that were con-
sidered to be of interest (Table 2). For the bisphosphine ligands
14–18, the use of anhydrous sodium p-toluenesulfinate provided
a greater chemical yield and higher enantioselectivity than that
of the monohydrate. This was consistent with the findings from
the monophosphines. The most noteworthy item from the applica-
Figure 2. Phosphorodiamidate and phosphite ligands employed in asymmetric
sulfonylation reactions.
others.14 The toluenesulfinate anion is believed to approach exter-
nally from this coordinated system.9b,c In contrast, the use of the O-
1-naphthoyl ligand 12b is proposed to lead to a palladium bound
system, wherein the 1-naphthoyl group is omitted from the coor-
dination sphere. It is believed that this is due to the steric environ-
ment of the C8 proton of the naphthyl substituent. Under these
circumstances, it would be feasible that the toluenesulfinate anion
becomes bound to the palladium, leading to an internal delivery of
the nucleophile as a viable reaction pathway among others.15
CO2H
Ph2P
HN
Ph2P
HN
CH3
Ar
HO
Ph
NH2
CH3
PPh2
HO
Ph
ArCOCl
O
O
EDC, DMAP, CH2Cl2
O
O
TEA, DMAP, DMF
49%
CH3
11
Ph
69%
10
12a: R = -C6H5 (49%)
12b: R = -1-C10H7 (23%)
SO2p-Tol
Ph
[(η3-C3H5)2PdCl]2, 12
NaSO2p-Tol, THF
OAc
Ph
Ph
Ph
8
9
for 12a: 46% yield, 78% ee (R)
for 12b: 5% yield, 23% ee (S)
Scheme 1. Synthesis and application of the phosphine ligands 12 in asymmetric sulfonylation.

2692
J. A. Wolfe, S. R. Hitchcock / Tetrahedron: Asymmetry 21 (2010) 2690–2695
TS-Pd-12a-SO2Tol
H3C
O
Ph
O
O
S
N
H
O
Tol
Ph
[(η3-C3H5)2PdCl]2
O
Tol
S
P
12a
Ph
O
O
(R)-9 (78%ee)
Ph
Pd
Ph
8
H3C
Ph
O
O
N
H
O
O
[(η3-C3H5)2PdCl]2
O
Tol
8
S
H
P
12b
Ph
Ph
Pd
Tol
O
(S)-9 (23%ee)
S
O
Ph
TS-Pd-12b-SO2Tol
Figure 3. Proposed transition states for the application of 12a and 12b.
Ph
tion of the bisphosphine ligands was the application of the (1S,2R)-
norephedrine derived bisphosphine 14. This was the only entry,
other than the test case of the Trost ligand, that yielded the (S)-
enantiomer of the product (23% ee) when applied to the palladium
catalyzed sulfonylation reaction. From the standpoint of the ste-
reochemical constitution of 14, the carbon bearing the amido
proposed to be active. If an equilibrium between these two states
were present (TS-14-A-Pd-suflinate vs TS-14-B-Pd-sulfinate), there
would be a compromised level of enantioselection. It is noteworthy
that the diastereomeric pseudonorephedrine derived ligand 15
afforded the sulfone product 9 in 84% ee favoring the (R)-enantio-
mer (Table 2). The significantly higher selectivity was attributed to
the conformational differences between the ligands; apparently
the anti-configured 15 does not exhibit the same level of competi-
tion between external and internal delivery of the toluenesulfinate
nucleophile.
group possesses an (R)-stereochemistry versus that the
a-amino
acid derived systems where the stereochemistry of the carbon
bearing the amido group is the (S)-stereochemistry. Based on this
assessment, it is logical that ligand 14 and ligands 15–18 would
form 9 as opposing enantiomers.
There was a concern that 14 might be compromised based on the
low level of enantioselection; as a result a test reaction was carried
out (Table 3). Thus, the (1S,2R)-norephedrine based ligand 14 was
applied to the asymmetric alkylation of allylic acetate 8 and dim-
ethylmalonate. The result was compared to our earlier work involv-
ing the use of the (1R,2S)-norephedrine derived ligand 3a. The
results were virtually identical with those of the original observa-
tion; the formation of the opposite enantiomer was the only differ-
ence. This suggested that ligand 14 (ent-3a) was not compromised
and that the observed result of the palladium catalyzed sulfonyla-
tion was valid. Ultimately, this would suggest that the palladium
catalyzed alkylation with dimethyl malonate and the palladium
catalyzed sulfonylation with sodium toluenesulfinate must have
divergent pathways during the asymmetric induction event.
We propose that the coordination of the palladium with the bis-
phosphine and the ionized 1,3-diphenylpropenyl system is the
same in both catalytic processes (Fig. 4). The key difference is in
the type of nucleophile employed. In the case of the malonate
nucleophile, the Lloyd-Jones–Norrby model16 of amide-mediated
external attack is proposed to be the dominant mode of attack.
In contrast, the argument developed by Trost15 in which the het-
eronucleophilic system of the toluenesulfinate nucleophile is capa-
ble of external and internal (palladium bound sulfinate) attack is
3. Conclusion
We have applied a series of monophosphine and bisphosphine
ligands in the palladium catalyzed asymmetric sulfonylation reac-
tion. The alcohol bearing monophosphines were ineffective in the
catalysis process. It is believed that the appendant alcohol inhib-
ited the process and prevented the formation of the product. The
‘capped’ monoligands proved to offer a better catalysis process
although the acyl group bound to oxygen influences the overall le-
vel of enantioselection. The bisphosphines were the most effective
ligands and generated enantioselectivities that ranged from 9% to
84% ee.
4. Experimentals
4.1. General remarks
Anhydrous THF was purchased as an anhydrous reagent and
used without further purification. All reactions were run under a
nitrogen atmosphere. Unless otherwise noted, all 1H spectra were
recorded in CDCl3 using NMR spectrometer operating at
500 MHz. Chemical shifts were reported in parts per million (d
scale), and coupling constant (J values) are listed in Hertz (Hz). Tet-

J. A. Wolfe, S. R. Hitchcock / Tetrahedron: Asymmetry 21 (2010) 2690–2695
2693
Table 2
Palladium catalyzed sulfonylation with phosphinobenzamides 14–19
[(η3-C3H5)2PdCl]2
ligand
SO2p-Tol
8
NaSO2p-Tol, THF
Ph
Ph
9
PPh2 Ph2P
PPh2 Ph2P
PPh2 Ph2P
HN
CH2Ph
PPh2 Ph2P
NH HN
O
HN
CH3
O
HN
CH3
O
O
O
O
O
O
O
O
O
Ph
Ph
14
15
16
13 (Trost)
PPh2 Ph2P
HN
Ph
PPh2 Ph2P
HN
C(CH3)3
O
O
O
O
O
O
17
18
Entry
Ligand
Nucleophile
%Yielda
%eeb
Abs Config.c
1
2
3
4
5
6
7
9
10
11
13
14
15
15
16
16
17
17
18
18
NaSO2p-Tol
NaSO2p-Tol
99
33
37
81
39
14
33
96
36
53
90
23
49
84
9
51
59
76
59
75
(S)
(S)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
NaSO2p-TolꢁH2O
NaSO2p-Tol
NaSO2p-TolꢁH2O
NaSO2p-Tol
NaSO2p-TolꢁH2O
NaSO2p-Tol
NaSO2p-TolꢁH2O
NaSO2p-Tol
a
b
c
Isolated yields were determined after flash chromatography and recrystallization.
Enantiomeric excesses were determined by chiral stationary phase HPLC (Chiralcel OD-H).
The identity of the enantiomer was based on the elution from the CSP HPLC column.
ramethylsilane (TMS) was used as internal standard (d = 0 ppm).
determined using chiral stationary phase HPLC using AD or OD-H
column. High resolution mass spectra were obtained from the
mass spectrometry laboratory, School of Chemical Science, Univer-
sity of Illinois, Urbana-Champaign. Anhydrous THF was used for
the catalysis reaction. Ligands 15, 17, and 18 were characterized
and previously described.7,8
Infrared spectra are reported in reciprocal centimeters (cmꢀ1
)
and are measured either as nujol mull or as neat liquid. Melting
points were recorded on a Mel-Temp apparatus and are uncor-
rected. Optical activities were measured at 589 nm using digital
polarimeter. Enantiomeric ratios of the asymmetric catalyses were
Table 3
Palladium catalyzed alkylation with 3a and 14 (ent-3a)
MeO2C
CO2Me
Ph
OAc
[(η3-C3H5)PdCl]2, CH2(CO2Me)2
cat. KOAc, BSA,THF
Ephedra ligand 3a or 14
Ph
Ph
Ph
rac-8
19
c
Entry
Ligand
Yieldb (%)
e.r. (% ee)
Enantiomerd
1
2
3a
14
51
50
94.0:6.0 (88)
6.0:94.0 (86)
(S)
(R)
a
All reactions were conducted in THF at 25 °C.
b
Isolated yield after flash chromatography.
Enantiomeric ratios determined by CSP HPLC (Chiralcel AD column).
c
d
The identity of the enantiomer was based on elution from the CSP HPLC column.

2694
J. A. Wolfe, S. R. Hitchcock / Tetrahedron: Asymmetry 21 (2010) 2690–2695
Ph
O
H3C
O
P
O
N
H3CO2C
CO2CH3
Ph
H
H3CO2C
CO2CH3
P
BSA, KOAc
Ph
Pd
9, 88% ee (S)
good enantioselection
Ph
Ph
TS-14-Pd-malonate
Ph
O
Ph
O
H3C
N
H3C
N
PPh2
O
P
O
O
O
H
H
Tol
S
P
P
SO2Tol
O
Pd
O
Pd
Ph
Ph
19, 23% ee (S)
Tol
S
O
low enantioselection
Ph
Ph
Ph
Ph
O
TS-14-A-Pd-sulfinate
TS-14-B-Pd-sulfinate
external delivery
internal delivery
Figure 4. Proposed transitions states involving 14.
4.2. 2-(Diphenylphosphino)-N-((1S,2R)-1-hydroxy-1-phenyl-2-
propyl)benzamide 11
with HCl (2 ꢂ 50 mL), and brine (50 mL). The organic layer was
dried over magnesium sulfate (MgSO4). The solvents were re-
moved via rotary evaporation and the product was recrystallized
(hexanes/CH2Cl2, 3:1). White solid (49%), mp: 188–190 °C.
In a 100 mL flame dried nitrogen purged round bottom flask
were added (1S,2R)-norephedrine (0.500 g, 3.31 mmol), dichloro-
methane (16.5 mL), DMAP (0.161 g, 1.32 mmol), 2-(diphenylphos-
phino)benzoic acid (1.011 g, 3.31 mmol), and EDC (0.634 g,
3.31 mmol). The reaction mixture was allowed to stir for 72 h
and then quenched with the addition of 3 M HCl (50 mL ꢂ 2). The
organic layer was diluted with dichloromethane (100 mL), washed
with brine (50 mL), and dried over magnesium sulfate (MgSO4).
The solvents were removed via rotary evaporation and the product
was purified by trituration (hexanes/EtOAc, 3:1). White solid (69%),
½
a 2D3
ꢃ
¼ ꢀ31:0 (c 0.98, CHCl3). IR (nujol mull) (cmꢀ1): 3337, 1713,
1645, 1524, 1273, 744, 701. 1H NMR (500 MHz, CDCl3) d (ppm):
1.05 (d, J = 6.8 Hz, 3H), 4.59–4.66 (m, 1H), 6.09 (d, J = 3.6 Hz, 1H),
6.18 (d, J = 6.8 Hz, 1H), 6.89–6.91 (m, 1H), 7.18–7.37 (m, 17H),
7.45–7.48 (m, 2H), 7.51–7.54 (m, 1H), 7.58–7.61 (m, 1H), 8.09–
8.11 (m, 2H). ESI-HRMS calcd for C35H30NO3P (M+H)+: 544.2042.
Found: 544.2033.
4.4. (1S,2R)-2-(2-(Diphenylphosphino)benzamido)-1-
phenylpropyl 1-napthoate 12b
mp: 170–173 °C. ½a D23
ꢃ
¼ þ34:9 (c 0.38, CHCl3). IR (nujol mull)
(cmꢀ1): 3324, 1623, 1525, 1008, 749, 699. 1H NMR (500 MHz,
CDCl3) (ppm): 0.85 (d, J = 6.9 Hz, 3H), 3.20 (s (br), 1H), 4.29 (dp,
J = 2.7, 7.0 Hz, 1H), 4.89 (d, J = 2.6 Hz, 1H), 6.01 (d, J = 5.7 Hz, 1H),
6.97 (ddd, J = 1, 4.3, 7.6 Hz, 1H), 7.23–7.42 (m, 17H), 7.60–7.62
(m, 1H). ESI-HRMS calcd for C28H26NO2P (M+H)+: 440.1779. Found:
440.1784.
In a 100 mL flame dried nitrogen purged round bottom flask
were added 2-(diphenylphosphino-N-((1S,2R)-1-hydroxy-1-phe-
nyl-2-propyl)benzamide (0.450 g, 1.02 mmol), dimethylformamide
(5 mL), DMAP (0.024 g, 0.20 mmol), 1-naphthoyl chloride (0.389 g,
2.04 mmol), and triethylamine (0.28 mL, 2.04 mmol). The reaction
mixture was heated at reflux and allowed to stir overnight. The
reaction mixture was diluted with ethyl acetate (50 mL), washed
with 1 M HCl (2 ꢂ 50 mL), and brine (50 mL). The organic layer
was dried over magnesium sulfate (MgSO4). The solvents were re-
moved via rotary evaporation. The crude mixture was purified by
column chromatography (hexane/EtOAc, 80:20) and was recrystal-
lized twice (hexanes/CH2Cl2, 3:1). 1H NMR contamination with 1-
napthoic acid (ꢄ20%). White solid (23%), mp: 163–165 °C.
4.3. (1S,2R)-2-(2-(Diphenylphosphino)benzamido)-1-
phenylpropyl benzoate 12a
In a 50 mL flame dried nitrogen purged round bottom flask were
added 2-(diphenylphosphino-N-((1S, 2R)-1-hydroxy-1-phenylpro-
pan-2-yl)benzamide (0.500 g, 1.14 mmol), dimethylformamide
(7 mL), DMAP (0.028 g, 0.23 mmol), benzoyl chloride (0.26 mL,
2.28 mmol), and triethylamine (0.32 mL, 2.28 mmol). The reaction
mixture was heated at reflux and allowed to stir overnight. The
reaction mixture was diluted with ethyl acetate (50 mL) washed
½
a 2D3
ꢃ
¼ ꢀ10:5 (c 0.35, CHCl3). IR (nujol mull) (cmꢀ1): 3349, 1706,
1643, 1524, 1277, 1247, 778, 741, 700. 1H NMR (500 MHz, CDCl3)
(ppm): 1.05 (d, J = 6.8 Hz, 3H), 4.52–4.71 (m, 1H), 6.21–6.25 (m,

J. A. Wolfe, S. R. Hitchcock / Tetrahedron: Asymmetry 21 (2010) 2690–2695
2695
1H), 6.90 (dd, J = 4.1, 7.6 Hz, 1H), 7.16–7.66 (m, 16H), 7.86–7.89 (m,
1H), 8.05 (d, J = 8.3 Hz, 1H), 8.34–8.37 (m, 1H), 8.90–8.93 (m, 1H).
ESI-HRMS calcd for
594.2203.
dissolved in THF (1 mL) and added to the reaction mixture. The
mixture was allowed to stir for an additional 30 min. Sodium p-tol-
uenesulfinate (0.595 g, 3.34 mmol) was added and the reaction
mixture was allowed to stir overnight at room temperature. The
reaction was diluted with dichloromethane (50 mL), washed with
water (3 ꢂ 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,
9:1) and recrystallized (hexanes/CH2Cl2, 3:1). The products were
analyzed by HPLC using a Chiralcel OD-H column (hexanes/i-PrOH,
95:5, 0.5 mL/min). White solid (29%), mp: 161–163 °C. IR (nujol
mull) (cmꢀ1): 1596, 1494, 748, 700, 666. 1H NMR (500 MHz, CDCl3)
d (ppm): 2.38 (s, 3H), 4.82 (d, J = 8.2 Hz, 1H), 6.59–6.60 (m, 2H),
7.19 (d, J = 8.1 Hz, 2H), 7.24–7.27 (m, 1H), 7.29–7.36 (m, 9H),
7.53 (d, J = 8.3 Hz, 2H). 13C NMR (125 MHz, CDCl3): 21.6, 75.4,
120.3, 126.8, 128.46, 128.64, 128.69, 128.87, 129.31, 129.34,
129.73, 132.5, 134.5, 136.0, 138.0. ESI-HRMS calcd for C22H20O2S
(M+Na+): 371.1082. Found: 371.1082.
C
39H32NO3P (M+H+): 594.2198. Found:
4.5. (1S,2R)-2-(2-(Diphenylphosphino)benzamido)-1-
phenylpropyl 2-(diphenylphosphino) benzoate 14
In a 100 mL flame dried nitrogen purged round bottom flask
was added (1S,2R)-norephedrine (0.500 g, 3.31 mmol), dichloro-
methane (16.5 mL), DMAP (0.161 g, 1.32 mmol), 2-(diphenylphos-
phino)benzoic acid (2.223 g, 7.28 mmol), and EDC (1.396 g,
7.28 mmol). The reaction mixture was allowed to stir for 24 h
and was quenched with the addition of 3 M HCl (50 mL ꢂ 2). The
organic layer was diluted with dichloromethane (100 mL), washed
with brine (50 mL), and dried over magnesium sulfate (MgSO4).
The solvents were removed via rotary evaporation and the product
was isolated by flash column chromatography (hexanes/EtOAc,
8:2). Viscous wax (50%), ½a D23
¼ ꢀ10:8 (c 1.00, CHCl3). IR (nujol
ꢃ
mull) (cmꢀ1): 1715, 1652, 1248, 743, 696. 1H NMR (500 MHz,
CDCl3) d (ppm): 0.81 (d, J = 6.9 Hz, 3H), 4.50–4.57 (m, 1H), 6.10
(d, J = 3.4 Hz, 1H), 6.77 (d, J = 8.7 Hz, 1H), 6.92–6.95 (m, 1H), 7.01
(dd, J = 3.9, 7.5 Hz, 1H), 7.11–7.14 (m, 1H), 7.06 (d, J = 6.9 Hz, 2H),
7.16–7.34 (m, 26H), 7.39–7.46 (m, 2H), 7.52–7.57 (m, 1H), 8.10–
8.13 (m, 1H). ESI-HRMS calcd for C47H39NO3P2 (M+H+): 728.2483.
Found: 728.2479.
Acknowledgements
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
CHE-0722385.
4.6. (S)-2-(2-(Diphenylphosphino)benzamido)-3-phenylpropyl
References
2-(diphenylphosphino) benzoate 16
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1457.
In a 100 mL flame dried nitrogen purged round bottom flask
were
3.31 mmol), dichloromethane (16.5 mL), DMAP (0.161 g,
1.32 mmol), 2-(diphenylphosphino)benzoic acid (2.230 g,
added
(S)-2-amino-3-phenyl-1-propanol
(0.500 g,
7.28 mmol), and EDC (1.396 g, 7.28 mmol). The reaction mixture
was allowed to stir for 24 h and was quenched with the addition
of 3 M HCl (50 mL ꢂ 2). The organic layer was diluted with dichlo-
romethane (100 mL), washed with brine (50 mL), and dried over
magnesium sulfate (MgSO4). The solvents were removed via rotary
evaporation and the product was isolated by flash column chroma-
tography (hexanes/EtOAc, 9:1) and recrystallized (hexanes/CH2Cl2,
3:1). White solid (26%), mp: 172–173 °C. ½a D23
¼ þ4:5 (c 1.00,
ꢃ
CHCl3). IR (nujol mull) (cmꢀ1): 3347, 1712, 1636, 1258, 743, 696.
1H NMR (500 MHz, CDCl3) d (ppm): 2.55 (dd, J = 4.7, 13.7 Hz, 1H),
2.74 (dd, J = 8.0, 13.7 Hz, 1H), 4.02 (dd, J = 7.7, 11.4 Hz, 1H), 4.10
(dd, J = 7.1, 11.5 Hz, 1H), 4.48–4.54 (m, 1H), 6.64 (d, J = 8.7 Hz,
1H), 6.91–6.97 (m, 2H), 7.06 (d, J = 6.9 Hz, 2H), 7.14–7.32 (m,
25H), 7.38–7.44 (m, 2H), 7.52–7.56 (m, 1H), 8.10–8.13 (m, 1H).
ESI-HRMS calcd for
728.2443.
C
47H39NO3P2 (M+H+): 728.2483. Found:
15. Trost et al. have proposed that it is possible that both the internal and external
delivery of the sulfinate nucleophile is possible. Trost, B. M.; Schmuff, N. R. J.
Am. Chem. Soc. 1985, 107, 396–405.
16. (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; Guerziz, T. Pure Appl. Chem.
2004, 76, 589–601.
4.7. General procedure for the catalytic asymmetric allylic
sulfonylation reactions 9
In a 100 mL flame dried, nitrogen purged round bottom flask
were added the ligand (0.049 g, 0.067 mmol), anhydrous THF
(4 mL), and [(
was allowed to stir for 15 min. 1,3-Diphenylpropenyl acetate was
g
3-C3H5)PdCl]2 (0.025 g, 0.067 mmol). The mixture