Efficient chiral monophosphorus ligands for asymmetric Suzuki-Miyaura coupling reactions

Article abstract of DOI:10.1021/ol300659d

A series of novel P-chiral monophosphorus ligands exhibit efficiency in asymmetric Suzuki-Miyaura coupling reactions, enabling the construction of an array of chiral biaryl products in high yields and excellent enantioselectivities (up to 96% ee) under mild conditions. The carbonyl-benzooxazolidinone moiety in these chiral biaryl products allows facile derivatization for further synthetic applications. A computational study has revealed that a π-π interaction between the two coupling partners can enhance the enantioselectivity of the coupling reaction.

Full text of DOI:10.1021/ol300659d

Supporting Information
For
Efficient Chiral Monophosphorus Ligands for Asymmetric Suzuki-Miyaura
Coupling Reactions
,
†
‡
†
†
Wenjun Tang,* Nitinchandra D. Patel, Guangqing Xu, Xiaobing Xu, Jolaine Savoie,
‡
‡
Shengli Ma, Ming-Hong Hao, Santosh Keshipeddy, Andrew G. Capacci, Xudong
‡
‡
‡
‡
‡
‡
‡
‡
Wei, Yongda Zhang, Joe J. Gao, Wenjie Li, Sonia Rodriguez, Bruce Z. Lu, Nathan
‡
‡
K. Yee, and Chris H. Senanayake
‡
State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai
Institute of Organic Chemistry,345 Ling Ling Road, Shanghai 200032,China, and
Chemical Development, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield,
CT06877, USA
1
2
3
4
5
6
7
8
9
. General methods-------------------------------------------------------------------------S2
. Synthetic procedures for ligand 1-4-----------------------------------------------S2-5
. Procedures for substrate preparation --------------------------------------------S5-6
. General procedure of asymmetric Suzuki-Miyaura couplings-----------------S6
. Analytical data of the Suzuki-Miyaura coupling products------------------S6-22
. Derivatization of chiral biaryl coupling product 6d------------------------S 22-24
. Computational study-------------------------------------------------------------- S24-28
. References----------------------------------------------------------------------------S28-29
. NMR spectra-------------------------------------------------------------------------S30-85
S1

1. General Methods. All reactions were carried out under a nitrogen atomosphere unless
otherwise specified. THF (<0.02% water content), CH Cl , hexane, n-butanol, dioxane
2
2
and toluene were purchased from J. T. Baker and used directly without further
purifications. Commercialized reagents were used without further purifications. Chiral
[
1]
triflate
2
were prepared according to our reported procedure.
Tf
=
trifluoromethylsulfonate, dba = dibenzylideneacetone, Cy = cyclohexyl, S-Phos = 2-
dicylohexylphosphino-2’,6’-dimethoxybiphenyl, PMHS = polymethylhydrosiloxane,
1
31 13
H, P and C NMR data were recorded on a Bruker-Biospin DRX500 or DRX400
1
NMR Spectrometer with CDCl or CD Cl as the solvent. H shifts were referenced to
3
2
2
3
CDCl at 7.26 ppm and CD Cl at 5.32 ppm. P shifts were referenced to 85% H PO in
1
3
2
2
3
4
1 13
D O at 0.0 ppm as external standard and obtained with H decoupling. C shifts were
2
referenced to CDCl at 77 ppm and CD Cl at 54 ppm and obtained with 1H decoupling.
2
3
2
MS was measured on Agilent 1100 Series LC/MSD mass spectrometer. Chiral HPLC
analyses wee performed on a Hewlett-Packard 1100 system using a Chiralcel OD-H or
Chiralpak AD-H column. Racemic compounds were prepared by reaction using S-Phos
[
2]
o
or racemic BI-DIME as the ligand at 65 C. The optical rotations were recorded on a
Rudolph Research Automatic Polarimeter.
2. Synthetic procedures for ligand 1a-d
a. Synthesis of ligand 1 ((S)-BI-DIME)
1
The synthesis of ligand 1 ((S)-BI-DIME) was carried out from chiral triflate a
through a Suzuki coupling with 2,6-dimethoxyphenylboronic acid to form b followed by
a stereospecific reduction of the phosphane oxide b mediated by PMHS/Ti(OiPr) . The
4
synthetic procedures were similar to those for racemic BI-DIME published in our
2
previous paper.
2
D
0
o
= -66.4 (c = 0.64, CHCl ); Chiral
Phosphane oxide b: white solid; >99% ee; [
3
o
HPLC conditions: Chiralcel AD-H, heptane/n-propanol = 90:10, 1 mL/min, 25 C, 4.93
min (S-enantiomer), 10.22 min (R-enantiomer, b).
2
D
0
o
1
((S)-BI-DIME): white solid; >99% ee; [
= -175.3 (c = 0.3, CHCl ); The
3
enantiomeric excess was determined by converting to its phosphine oxide via
stereospecific oxidation with H O as the oxidant.
2
2
S2

b. Synthesis of ligand 2
The synthesis of ligand 2 was carried out from chiral phosphane oxide b through
methylation to form c followed by a stereospecific reduction of the phosphane oxide c
under conditions of PMHS/Ti(OiPr) . The synthetic procedures were similar to those for
4
3
its racemic form published in our previous paper. The relative configuration between P
chirality and C chirality was determined by NOE experiments.
2
D
0
o
= -12.8 (c = 0.53, CHCl ).
Phosphane oxide c: white solid; [
2
3
0
o
= -121.6 (c = 0.55, CHCl ).
Phosphane 2: white solid; [
D
3
c: Synthesis of ligand 3
To
dihydrobenzo[d][1,3]oxaphosphole oxide (b, 5.0 g, 14.4 mmol) in THF ( 50 mL) at -70
a
solution
of
(R)-3-tert-butyl-4-(2,6-dimethoxyphenyl)-2,3-
o
C was charged LDA (9.6 mL, 1.8 M, 17.3 mmol, 1.2 equiv) over 5 min. The mixture
o
was kept at -70 C for 1 h. To the mixture was charged BnBr (2.96 g, 17.3 mmol, 1.2
o
equiv) over 5 min while controlling the reaction temperature below -60 C. The resulting
o
mixture was stirred at -70 C for additional 1 h and then allowed to warm to rt over 2 h.
Water (50 mL) and dichloromethane (50 mL) was charged. The dichloromethane layer
was separated, washed with brine (50 mL), dried over sodium sulfate, and concentrated.
The residue was purified by silica gel column chromatography (eluent: hexane to EtOAc)
2
D
0
to provide the desired product d as white solid (5.0 g, 11.5 mmol, 80% yield). d: [α]
=
o
1
+
55.9 (c = 0.42, CHCl ); H NMR (400 MHz, CDCl ) δ 7.48 (t, J = 7.8 Hz, 1H), 7.20-
3
3
7
1
.40 (m, 6H), 6.90 (m, 2H), 6.67 (d, J = 8.4 Hz, 1H), 6.57 (d, J = 8.3 Hz, 1H), 4.54 (m,
3
H), 2.91 (s, 3H), 2.95 (s, 3H), 3.10-3.30 (m, 2H), 0.83 (d, J = 15.6 Hz, 9H); P NMR
1
13
(
162 MHz, CDCl ) δ 59.9; C NMR (100 MHz, CDCl ) δ 163.5 (d, J = 18.6 Hz), 158.7,
57.3, 138.4 (d, J = 4.7 Hz), 138.3 (d, J = 9.4 Hz), 134.1 (d, J = 1.6 Hz), 129.8, 129.4,
3
3
1
S3

1
1
28.5, 126.6, 124.9 (d, J = 8.3 Hz), 117.5, 114.5 (d, J = 89.9 Hz), 112.6 (d, J = 5.5 Hz),
04.5, 103.1, 75.0 (d, J = 60.4 Hz), 55.1, 56.4, 35.8, 33.3 (d, J = 70.8 Hz), 23.7; ESI-MS:
+
m/z 437 [M +H] .
To a solution of (2S,3R)-2-benzyl-3-tert-butyl-4-(2,6-dimethoxyphenyl)-2,3-
dihydrobenzo[d][1,3]oxaphosphole oxide (d, 3.0 g, 6.87 mmol, 1.0 equiv) in THF (30
mL ) at rt was added PMHS (3 g) and Ti(OiPr) (1.95 g, 6.87 mmol, 1.0 equiv). The
4
mixture was stirred at reflux for 24 h and then distilled under reduced pressure to remove
most THF. To the residue was charging carfully 30% NaOH solution (30 mL). Gas was
generated during the addition. To the mixture at rt was charged Me-THF (30 mL). The
o
resulting mixture was stirred at 60 C for 0.5 h. The organic layer was separated and the
most of the aqueous slurry was discarded. To the organic layer was charged water (30
mL). The aqueous layer was discarded. The organic layer was further washed with water
(30 mL X2) and 5% NaCl solution (30 mL), and then concentrated at rt. The residue was
purified by passing through a neutral alumina plug to provide 3 as white solid (2.5 g, 5.95
2
0
o
1
mmol, 87% yield). 3: [α]D = -16.2 (c = 0.49, CHCl ); H NMR (500 MHz, CDCl ) δ
3
3
7
.10-7.30 (m, 7H), 6.79 (m, 2H), 6.56 (d, J = 8.4 Hz, 1H), 6.49 (d, J = 8.4 Hz, 1H), 4.87
t, J = 7.7 Hz, 1H), 3.71 (s, 3H), 3.61 (s, 3H), 3.00 (m, 1H), 2.77 (m, 1H), 0.58 (d, J =
(
31
13
1
1
1
8
2.0 Hz, 9H); P NMR (202 MHz, CDCl ) δ 5.84; C NMR (125 MHz, CDCl ) δ 162.6,
57.8, 157.0, 138.8 (d, J = 17.2 Hz), 138.5 (d, J = 10.0 Hz), 130.6, 129.6, 129.5, 129.0,
28.3, 126.4, 124.2 (d, J = 14.9 Hz), 123.8 (d, J = 4.1 Hz), 119.6, 109.9, 104.4, 103.6,
3
3
4.2 (d, J = 26.4 Hz), 55.8 (d, J = 1.8 Hz), 53.4, 41.4 (d, J = 28.1 Hz), 31.0 (d, J = 18.4
+
Hz), 26.6 (d, d, J = 14.3 Hz); ESI-MS: m/z 421 [M +H] .
d: Synthesis of ligand 4
Br
O
O
O
P
PMHS, Ti(OiPr)4
P O
P O
tBu
tBu
tBu
THF
MeO
OMe
MeO
OMe
MeO
OMe
LDA
b
e
4
The synthesis of compound e from compound b was carried out following a
procedure similar to the preparation of compound d for the synthesis of ligand 3. e: 85%
2
0
o
1
yield (white solid); [α]D = +43.4 (c = 0.35, CHCl ); H NMR (400 MHz, CDCl ) δ 8.06
3
3
(
d, J = 7.8 Hz, 1H), 7.89 (d, J = 7.7 Hz, 1H), 7.79 (d, J = 8.2 Hz, 1H), 7.40-7.60 (m, 5H),
7
4
9
1
1
8
.32 (t, J = 8.2 Hz, 1H), 6.90 (m, 2H), 6.69 (d, J = 8.4 Hz, 1H), 6.58 (d, J = 8.4 Hz, 1H),
.68 (m, 1H), 3.87 (s, 3H), 3.82 (m, 1H), 3.71 (s, 3H), 3.55 (m, 1H), 0.82 (d, J = 16.0 Hz,
3
1
13
H); P NMR (162 MHz, CDCl ) δ 60.5; C NMR (100 MHz, CDCl ) δ 163.5 (d, J =
3
3
8.8 Hz), 158.7, 157.4, 138.5 (d, J = 5.1 Hz), 134.2 (d, J = 1.5 Hz), 133.9, 131.9, 129.9,
28.9, 128.0, 127.5, 126.0, 125.6, 125.5, 125.0 (d, J = 8.3 Hz), 123.6, 117.4, 114.2 (d, J =
9.5 Hz), 112.7 (d, J = 5.5 Hz), 104.5, 103.0, 74.3 (d, J = 59.7 Hz), 56.1, 55.4, 35.4, 33.4
+
(d, J = 70.6 Hz), 23.6; ESI-MS: m/z 487 [M +H] .
S4

The synthesis of ligand 4 from compound e was carried out following a procedure
similar to the preparation of ligand 3 from compound d. 4: 83% yield (white solid); [α]
2
D
0
o
1
=
(
=
-28.6 (c = 0.29, CHCl ); H NMR (400 MHz, CDCl ) δ 7.94 (d, J = 8.1 Hz, 1H), 7.77
3
3
d, J = 7.7 Hz, 1H), 7.67 (d, J = 7.4 Hz, 1H), 7.12-7.50 (m, 6H), 6.80 (m, 2H), 6.59 (d, J
8.2 Hz, 1H), 6.50 (d, J = 8.4 Hz, 1H), 5.05 (t, J = 7.6 Hz, 1H), 3.76 (s, 3H), 3.62 (s, 3H),
3
1
3
.45 (m, 1H), 3.25 (m, 1H), 0.55 (d, J = 12.0 Hz, 9H); P NMR (162 MHz, CDCl ) δ 7.5;
C NMR (100 MHz, CDCl ) δ 162.6, 157.8, 157.0, 138.8 (d, J = 17.0 Hz), 134.6 (d, J =
3
1
3
3
1
1
0.7 Hz), 133.9, 132.1, 130.6, 129.1, 128.9, 127.9 (d, J = 1.8 Hz), 127.3, 125.9, 125.4,
25.3, 123.8 (d, J = 4.1 Hz), 123.8, 119.6, 110.1, 104.4, 103.7, 83.5 (d, J = 26.2 Hz), 55.9
(d, J = 1.5 Hz), 55.4, 38.5 (d, J = 29.3 Hz), 31.0 (d, J = 18.4 Hz), 26.6 (d, J = 14.3 Hz);
ESI-MS: m/z 471 [M +H] .
+
3
. Procedures for substrate preparation
To a suspension of 1-bromo-2-naphthoic acid (1.0g, 4.0 mmol) in DCM (10 mL)
was charged DMF (14.5 mg, 0.2 mmol, 0.05 equiv) followed by slow addition of oxaly
chloride (0.56 g, 4.38 mmol, 1.1 equiv). Gas was generated during the addition and the
resulting mixture was stirred at rt for 1 h. In a separated flask was charged
benzo[d]oxazol-2(3H)-one (0.54 g, 3.98 mmol, 1.0 equiv), triethylamine (1.21 g, 11.9
mmol, 3.0 equiv) and DCM (10 mL). To the mixture at rt was charged the
aforementioned solution. The resulting mixture was stirred at rt overnight. Water (20 mL)
was charged to quench the reaction. The DCM layer was separated, washed with water
(25 mL X 2) and brine (25 mL), dried over sodium sulfate, concentrated and solvent-
switched to EtOAc (10 mL). The slurry was heated to 55 C for 10 min and then cooled
o
to rt. Filtration of the slurry provided the desired product 5d as yellow solid (1.2 g, 3.3
1
mmol, 82% yield). 5d: H NMR (400 MHz, CD Cl ) δ 8.39 (d, J = 8.3 Hz, 1H), 8.23 (m,
2
2
1
1
1
1
H), 8.04 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 7.9 Hz, 1H), 7.74 (m, 2H), 7.52 (d, J = 8.4 Hz,
1
3
H), 7.41 (m, 2H), 7.35 (m, 1H); C NMR (100 MHz, CD Cl ) δ 167.2, 150.5, 143.2,
2
2
35.4, 134.4, 132.0, 129.2, 129.1, 128.9, 128.8, 128.0, 127.9, 126.4, 125.5, 124.2, 120.5,
+
16.1, 110.7; ESI-MS: m/z 390 [M +Na] .
Preparation of 5c was carried out according to a procedure similar to that for the
1
synthesis of 5d. 5c: 85% yield; H NMR (500 MHz, CDCl ) δ 8.30 (d, J = 8.5 Hz, 1H),
3
S5

7
=
.89 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.65 (m, 1H), 7.58 (m, 1H), 7.34 (d, J
1
8.4 Hz, 1H), 4.53 (t, J = 7.8 Hz, 2H), 4.28 (t, J = 8.3 Hz, 2H); C NMR (125 MHz,
3
CDCl ) δ 168.0, 152.1, 134.6, 134.1, 131.6, 128.4, 128.3, 128.2, 127.8, 127.5, 123.6,
3
+
19.8, 62.2, 42.5; ESI-MS: m/z 342 [M +Na] .
1
4
. General procedure for asymmetric Suzuki-Miyaura couplings
To a mixture of aryl bromide (1.0 mmol), arylboronic acid (2.0 mmol), potassium
phosphate (3 mmol, 3 equiv), Pd(OAc) (0.01-0.05 mmol), and ligand 2 or 4 (0.012-0.06
2
mmol, Pd/ligand ratio = 1/1.2) was charged dry THF (2 mL). The mixture was stirred at
o
room temperature or 40 C under nitrogen for 4-36 h and then quenched by addition of
1
0% citric acid solution (4 mL). EtOAc (4 mL) was added and the EtOAc layer was
separated, washed sequentially with water (4 mL) and brine (4 mL), dried over sodium
sulfate, concentrated, and purified by silica gel column chromatography to provide biaryl
products. Their ee’s were determined by chiral HPLC on a chiralcel OD-H or chiralpak
AD-H column.
5
. Analytical data of asymmetric Suzuki-Miyaura coupling products
R)-N,N-Dimethyl-1,1'-binaphthyl-2-carboxamide: white solid
(
20
o
1
(
95% yield); 79% ee; [α]D = +66.0 (c = 0.80, CHCl ); H NMR
3
(
7
500 MHz, CDCl ) δ 8.02 (d, J = 7.3 Hz, 1H), 7.95 (br m, 3H), 7.40-
3
O
1
.75 (m, 5H), 7.29 (m, 4H), 2.20-3.10 (br m, 4H); C NMR (125
3
N
MHz, CDCl ) δ 170.7, 135.1, 134.4, 133.4, 133.2, 132.8, 128.6,
3
128.4, 128.1, 127.1, 126.7, 126.4, 125.8, 123.8, 38.8, 34.3. ESI-MS:
m/z 326 [M +H] . Chiral HPLC conditions: Chiralcel OD-H, 4.6
mm X 250 mm, 30 C, flow rate: 2 mL/min, heptane/isopropanol: 96/4, 254 nm, 9.30 min
S), 12.00 min (R).
+
o
(
S6

(
R)-3-(1,1'-binaphthyl-2-carbonyl)oxazolidin-2-one:
o
20
yellowish solid (96% yield). 87% ee; [α]D = -61.6 (c = 0.55,
1
O
O
CHCl ); H NMR (400 MHz, CD Cl ) δ 8.10 (d, J = 8.4 Hz,
3
2
2
1
(
H), 7.95-8.07 (m, 3H), 7.55-7.70 (m, 3H), 7.52 (m, 2H), 7.38
N
O
13
m, 4H), 3.99 (m, 2H), 3.63 (m, 1H), 3.46 (m, 1H); C NMR
(
100 MHz, CD Cl ) δ 169.9, 153.2, 136.3, 135.6, 134.6, 133.9,
2
2
1
1
4
1
33.7, 133.2, 133.1, 129.0, 128.8, 128.7, 128.5, 127.7, 127.6, 127.4, 127.3, 126.7, 125.7,
+
24.1, 62.9, 43.0; ESI-MS: m/z 390 [M +Na] . Chiral HPLC conditions: Chiralcel OD-H,
o
.6 mm X 250 mm, 30 C, flow rate: 2 mL/min, heptane/isopropanol: 85/15, 225 nm,
1.00 min (S), 13.98 min (R).
(
R)-3-(1,1'-binaphthyl-2-carbonyl)benzo[d]oxazol-2(3H)-
o
20
one: white solid (96% yield); 96% ee; [α]D = -126.1 (c =
.33, CHCl ); H NMR (400 MHz, CD Cl ) δ 8.11 (d, J = 6.7
1
O
1
3
2
2
Hz, 1H), 8.04 (d, J = 6.4 Hz, 1H), 7.79 (m, 2H), 7.72 (d, J =
6.7 Hz, 1H), 7.60 (m, 1H), 7.25-7.50 (m, 8H), 7.14 (t, J = 6.0
N
O
1
3
O
Hz, 1H), 7.04 (m, 2H); C NMR (100 MHz, CD Cl ) δ 168.5,
2
2
1
1
1
2
7
51.0, 142.9, 137.7, 135.1, 135.0, 133.9, 133.3, 133.2, 132.8, 129.0, 128.9, 128.8, 128.7,
28.6, 128.2, 128.0, 127.9, 127.6, 127.0, 126.8, 126.6, 125.6, 125.5, 124.9, 124.1, 114.8,
+
10.1. ESI-MS: m/z 438 [M +Na] ; Chiral HPLC conditions: Chiralcel OD-H, 4.6 mm X
o
50 mm, 30 C, flow rate: 2 mL/min, heptane/isopropanol: 96/4, 254 nm, 6.19 min (S),
.05 min (R).
S7

(R)-3-(4'-Methyl-1,1'-binaphthyl-2-
carbonyl)benzo[d]oxazol-2(3H)-one: white solid (95% yield);
2
0
o
1
9
6% ee; [α]D = -128.8 (c = 0.49, CHCl ); H NMR (500
3
O
MHz, CDCl ) δ 8.07 (d, J = 8.5 Hz, 1H), 7.98 (d, J = 8.3 Hz,
3
1
H), 7.87 (d, J = 8.4 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.56
N
(m, 1H), 7.37-7.48 (m, 4H), 7.32 (m, 3H), 7.25 (d, J = 7.0 Hz,
1H), 7.06 (m, 1H), 6.97 (m, 2H), 2.56 (s, 3H); C NMR (125
O
13
O
MHz, CDCl ) δ 168.3, 150.4, 142.3, 137.5, 134.9, 134.6, 132.8, 132.5, 132.4, 132.3,
3
1
32.1, 128.4, 128.2, 127.9, 127.6, 127.5, 127.3, 127.1, 126.9, 125.9, 125.8, 125.7, 124.7,
+
24.2, 124.1, 123.6, 114.1, 109.4, 19.4; ESI-MS: m/z 452 [M +Na] ; Chiral HPLC
1
conditions: Chiralcel OD-H, 4.6 mm X 250 mm, 30 C, flow rate: 2 mL/min,
heptane/isopropanol: 96/4, 254 nm, 5.82 min (S), 6.52 min (R).
o
S8

(R)-3-(4'-(dimethylamino)-1,1'-binaphthyl-2-
carbonyl)benzo[d]oxazol-2(3H)-one: 95% yield; 96% ee;
N
2
0
o
1
[
α]D = -175.2 (c = 0.65, CHCl ); H NMR (500 MHz,
3
CDCl ) δ 8.09 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.3 Hz, 1H),
3
O
7
.99 (d, J = 8.2 Hz, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.56 (m,
N
2
H), 7.38 (m, 4H), 7.30 (m, 1H), 7.23 (m, 1H), 7.04 (m, 1H),
1
3
O
7.94 (m, 3H), 2.71 (s, 6H); C NMR (125 MHz, CDCl ) δ
3
O
168.6, 151.2, 150.3, 142.2, 137.5, 134.8, 133.6, 132.9, 132.3,
28.5, 128.45, 128.4, 128.3, 128.2, 127.6, 127.5, 127.3, 127.1, 127.0, 126.9, 126.0, 125.2,
1
1
+
24.5, 124.2, 124.1, 123.8, 113.8, 113.0, 109.3, 45.0; ESI-MS: m/z 481 [M +Na] ; Chiral
o
HPLC conditions: Chiralcel AD-H, 4.6 mm X 250 mm, 30 C, flow rate: 2 mL/min,
heptane/isopropanol: 97/3, 254 nm, 5.30 min (R), 8.75 min (S).
S9

O
(R)-3-(4'-methoxy-1,1'-binaphthyl-2-
carbonyl)benzo[d]oxazol-2(3H)-one: white solid (95% yield);
2
0
o
1
9
4% ee; [α]D = -70.6 (c = 0.17, CHCl ); H NMR (400 MHz,
3
O
CD Cl ) δ 8.19 (d, J = 8.3 Hz, 1H), 8.10 (d, J = 8.5 Hz, 1H),
2
2
N
8.03 (d, J = 8.3 Hz, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.59 (t, J =
7.2 Hz, 1H), 7.28-7.50 (m, 7H), 7.15 (t, J = 7.4 Hz, 1H), 7.06
O
O
13
m, 2H), 6.80 (d, J = 7.8 Hz, 1H), 3.94 (s, 3H); C NMR (100
(
MHz, CD Cl ) δ 168.7, 156.2, 151.0, 142.9, 137.8, 135.1, 134.1, 133.6, 133.1, 128.9,
2
2
1
28.8, 128.7, 128.1, 128.0, 127.5, 127.2, 126.9, 125.9, 125.5, 124.9, 124.1, 122.5, 114.8,
+
10.1, 103.8, 56.1; ESI-MS: m/z 468 [M +Na] ; Chiral HPLC conditions: Chiralcel AD-
1
H, 4.6 mm X 250 mm, 30 C, flow rate: 2 mL/min, heptane/isopropanol: 96/4, 225 nm,
o
1
1.53 min (R), 12.78 min (S).
S10

(R)-3-(1-(1,2-dihydroacenaphthylen-5-yl)-2-
naphthoyl)benzo[d]oxazol-2(3H)-one: white solid (96%
2
0
o
1
O
yield); 88% ee; [α]D = -96.8 (c = 0.41, CHCl ); H NMR
3
(
400 MHz, CD Cl ) δ 8.10 (d, J = 8.5 Hz, 1H), 8.03 (d, J =
N
2
2
8.2 Hz, 1H), 7.73 (d, J = 8.5 Hz, 1H), 7.61 (m, 1H), 7.54 (d, J
= 8.6 Hz, 1H), 7.40 (m, 2H), 2.31 (m, 2H), 7.23 (m, 2H), 6.95-
O
O
13
7
1
1
.13 (m, 4H), 3.13-3.42 (m, 4H); C NMR (100 MHz, CD Cl ) δ 168.9, 151.0, 147.4,
2
2
46.8, 142.9, 139.6, 137.7, 135.2, 133.2, 132.7, 131.4, 130.4, 130.1, 128.82, 128.8, 128.7,
28.2, 127.9, 127.5, 125.2, 124.7, 124.3, 121.8, 120.1, 119.3, 114.4, 109.9, 30.8, 30.6;
+
ESI-MS: m/z 464 [M +Na] ; Chiral HPLC conditions: Chiralcel OD-H, 4.6 mm X 250
o
mm, 30 C, flow rate: 2 mL/min, heptane/isopropanol: 96/4, 225 nm, 5.47 min (S), 6.80
min (R).
S11

(
R)-3-(1-(phenanthren-9-yl)-2-naphthoyl)benzo[d]oxazol-
2
0
o
2
(3H)-one: white solid (96% yield); 90% ee; [α]D = -91.7 (c
0.36, CHCl ); H NMR (500 MHz, CDCl ) δ 8.61 (d, J =
1
=
3
3
8.3 Hz, 1H), 8.57 (d, J = 8.2 Hz, 1H), 8.11 (d, J = 8.5 Hz, 1H),
8.01 (d, J = 8.3 Hz, 1H), 7.83 (d, J = 7.3 Hz, 1H), 7.78 (s, 1H),
7.74 (d, J = 8.6 Hz, 1H), 7.53-7.65 (m, 4H), 7.40-7.53 (m, 3H),
O
N
O
7.34 (t, J = 7.3 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 6.96 (m, 1H),
1
O
3
6
.85 (m, 2H); C NMR (125 MHz, CDCl ) δ 168.1, 150.6,
3
1
1
1
42.1, 137.1, 134.6, 133.2, 132.8, 132.2, 131.5, 131.0, 130.2, 130.1, 129.1, 128.8, 128.6,
28.3, 127.7, 127.6, 127.5, 127.2, 127.1, 126.9, 126.8, 126.78, 126.77, 124.7, 124.2,
+
23.6, 122.6, 122.4, 114.0, 109.4; ESI-MS: m/z 488 [M +Na] ; Chiral HPLC conditions:
o
Chiralpak AD-3, 4.6 mm X 250 mm, 25 C, flow rate: 1.2 mL/min, heptane/isopropanol:
8
5/15, 254 nm, 20.0 min (R), 21.1 min (S).
S12

(
R)-3-(1-(pyren-4-yl)-2-naphthoyl)benzo[d]oxazol-2(3H)-
o
20
one: white solid (95% yield); 90% ee; [α]D = -129.5 (c =
.44, CHCl ); H NMR (400 MHz, CD Cl ) δ 8.13-8.25 (m,
H), 8.00-8.12 (m, 5H), 7.94 (d, J = 9.2 Hz, 1H), 7.79 (d, J =
.5 Hz, 1H), 7.63 (m, 2H), 7.36 (m, 2H), 7.29 (d, J = 7.9 Hz,
3
H), 6.88 (m, 2H), 6.75 (t, J = 7.8 Hz, 1H); C NMR (100
1
0
4
8
1
3
2
2
O
1
N
O
MHz, CD Cl ) δ 168.5, 151.0, 142.7, 138.2, 135.1, 133.5,
2
2
O
133.2, 132.1, 131.8, 131.7, 131.4, 130.8, 129.0, 128.9, 128.8,
28.32, 128.31, 128.29, 128.1, 127.8, 127.7, 126.8, 126.0, 125.9, 125.9, 125.4, 125.0,
1
1
+
24.93, 124.9, 124.6, 124.2, 114.6, 109.9; ESI-MS: m/z 512 [M +Na] ; Chiral HPLC
o
conditions: Chiralcel AD-H, 4.6 mm X 250 mm, 30 C, flow rate: 2 mL/min,
heptane/isopropanol: 96/4, 254 nm, 10.17 min (R), 13.89 min (S).
S13

H
N
(R)-3-(1-(1H-indol-4-yl)-2-naphthoyl)benzo[d]oxazol-
1
2
(3H)-one: 95%; 68% ee; H NMR (500 MHz, CDCl ) δ 8.05
3
(
d, J = 8.4 Hz, 1H), 8.04 (br, 1H), 7.98 (d, J = 8.3 Hz, 1H),
O
7.72 (d, J = 8.4 Hz, 2H), 7.57 (t, J = 7.2 Hz, 1H), 7.40 (m, 2H),
6.95-7.20 (m, 6H), 6.93 (d, J = 7.9 Hz, 1H), 6.14 (t, J = 2.2 Hz,
N
1
3
O
1H); C NMR (125 MHz, CDCl ) δ 168.9, 150.3, 142.3,
3
O
138.2, 135.5, 134.9, 132.0, 131.2, 128.9, 128.3, 128.2, 127.9,
27.7, 127.5, 126.7, 124.5, 124.4, 124.0, 123.9, 122.8, 121.9, 121.7, 113.9, 110.6, 109.2,
1
1
2
3
+
02.8; ESI-MS: m/z 427 [M +Na] ; Chiral HPLC conditions: Chiralcel OD-H, 4.6 mm X
o
50 mm, 30 C, flow rate: 2 mL/min, heptane/isopropanol: 93/7, 225 nm, 28.5 min (S),
4.2 min (R).
S14

(S)-3-(1-(benzo[b]thiophen-3-yl)-2-
naphthoyl)benzo[d]oxazol-2(3H)-one: 95% yield; 82% ee;
S
2
0
o
1
O
[
D
= -121.8 (c = 0.61, CHCl ); H NMR (500 MHz,
3
CDCl ) δ 8.09 (d, J = 8.5 Hz, 1H), 8.99 (d, J = 8.3 Hz, 1H),
3
N
7
7
1
.71 (m, 2H), 7.64 (d, J = 8.6 Hz, 1H), 7.60 (t, J = 8.0 Hz, 1H),
.54 (d, J = 7.8 Hz, 1H), 7.49 (s, 1H), 7.42 (m, 1H), 7.35 (m,
H), 7.23-7.32 (m, 2H), 7.11 (m, 1H), 7.05 (m, 1H), 6.99 (d, J
O
O
1
3
=
8.0 Hz, 1H); C NMR (125 MHz, CDCl ) δ 168.4, 150.4, 142.3, 139.5, 139.0, 134.7,
3
1
1
32.42, 132.38, 132.3, 129.1, 128.4, 127.7, 127.3, 127.2, 127.0, 126.5, 124.9, 124.7,
+
24.5, 124.4, 123.7, 123.6, 122.4, 114.2, 109.5; ESI-MS: m/z 431 [M +Na] ; Chiral
o
HPLC conditions: Chiralcel AD-H, 4.6 mm X 250 mm, 30 C, flow rate: 2 mL/min,
heptane/isopropanol: 96/4, 225 nm, 10.02 min (S), 13.50 min (R).
S15

(R)-3-(3-methyl-2-(naphthalen-1-
yl)benzoyl)benzo[d]oxazol-2(3H)-one: 85% yield; 70% ee;
2
D
0
o
1
O
[
= -121.8 (c = 0.66, CHCl ); H NMR (400 MHz,
3
CDCl ) δ 7.70 (m, 1H), 7.66 (dd, J = 7.4, 1.6 Hz, 1H), 7.56 (m,
3
N
1
H), 7.51 (m, 3H), 7.42 (m, 2H), 7.27-7.45 (m, 3H), 7.06 (m,
13
O
O
1H), 6.97 (m, 2H), 2.06 (s, 3H); C NMR (100 MHz, CDCl )
3
δ 168.1, 150.4, 142.1, 138.2, 137.6, 135.5, 135.2, 133.3, 133.0, 131.5, 128.1, 128.0, 127.8,
27.3, 127.0, 126.3, 126.0, 125.9, 125.0, 124.99, 124.7, 124.2, 114.1, 109.4, 20.1; ESI-
1
MS: m/z 402 [M +Na] ; Chiral HPLC conditions: Chiralcel OD-H, 4.6 mm X 250 mm,
+
o
0 C, flow rate: 2 mL/min, heptane/isopropanol: 96/4, 225 nm, 6.11 min (S), 9.69 min
R).
3
(
S16

(R)-3-(3-Methyl-2-(phenanthren-9-
yl)benzoyl)benzo[d]oxazol-2(3H)-one: white solid (90%
2
D
0
o
1
yield); 64% ee; [
= -17.8 (c = 0.45, CHCl ); H NMR
3
(
400 MHz, CDCl ) δ 8.57 (d, J = 8.2 Hz, 1H), 8.51 (d, J =
3
O
7.4 Hz, 1H), 7.80 (m, 1H), 7.50-7.65 (m, 9H), 7.22 (d, J =
7.8 Hz, 1H), 6.93 (t, J = 7.9 Hz, 1H), 6.81(m, 2H), 2.10 (s,
N
1
3
1
H); H NMR (100 MHz, CDCl ) δ 168.1, 150.6, 142.0,
O
3
O
38.4, 137.6, 135.3, 134.4, 133.0, 131.1, 130.6, 130.2, 130.0,
1
1
28.7, 127.9, 127.8, 127.2, 126.9, 126.8, 126.72, 126.7, 125.1, 124.6, 124.1, 122.7, 122.3,
+
13.9, 109.3, 20.1; ESI-MS: m/z 452 [M +Na] ; Chiral HPLC conditions: Chiralcel OD-
o
H, 4.6 mm X 250 mm, 30 C, flow rate: 2 mL/min, heptane/isopropanol: 94/6, 225 nm,
7
.07 min (S), 10.92 min (R).
S17

Diethyl 1-o-tolylnaphthalen-2-ylphosphonate: white solid (95%
2
0
o
1
yield); 80% ee; [
= -5.5 (c = 0.53, CHCl ); H NMR (400
3
D
O
MHz, CDCl ) δ 8.09 (dd, J = 11.8, 8.8 Hz, 1H), 7.92 (m, 2H), 7.55
3
P OEt
OEt
(
t, J = 7.3 Hz, 1H), 7.25-7.43 (m, 5H), 7.21 (d, J = 7.3 Hz, 1H),
3
.82-4.00 (m, 3H), 3.70-3.82 (m, 1H), 1.92 (s, 3H), 1.85 (m, 6H);
1
H NMR (100 MHz, CDCl ) δ 144.9 (d, J = 10.0 Hz), 137.8 (d, J =
3
5
1
6
.2 Hz), 137.6, 134.9 (d, J = 2.6 Hz), 132.4 (d, J = 16.1 Hz), 130.7, 129.3, 128.3, 128.2,
28.0, 127.8, 127.3, 127.2, 127.0, 126.7 (d, J = 1.2 Hz), 124.9, 124.8 (d, J = 129.0 Hz),
+
1.7 (m), 20.0, 16.2 (m); ESI-MS: m/z 355 [M +H] ; Chiral HPLC conditions: Chiralpak
o
AD-3, 4.6 mm X 250 mm, 30 C, flow rate: 1.0 mL/min, heptane/ethanol: 90/10, 220 nm,
2
9.6 min, 31.0 min;
S18

Diethyl 1-(2-isopropylphenyl)naphthalen-2-ylphosphonate: 75%
2
0
o
1
yield; 80% ee; [
= -19.8 (c = 0.4, CHCl ); H NMR (400 MHz,
3
D
iPr
O
CDCl ) δ 8.06 (d, J = 8.5 Hz, 1H), 8.03 (d, J = 8.7 Hz, 1H), 7.92 (dd,
3
P OEt J = 8.5, 3.4 Hz, 1H), 7.88 (d, J = 8.2 Hz, 1H), 7.54 (t, J = 7.6 Hz,
1H), 7.44 (m, 2H), 7.36 (m, 2H), 7.26 (m, 1H), 7.18 (d, J = 7.4 Hz,
H), 3.98 (m, 1H), 3.88 (m, 2H), 3.84 (m, 1H), 2.37 (m 1H), 1.17
OEt
1
1
3
(
m, 9H), 0.91 (d, J = 6.8 Hz, 3H); C NMR (100 MHz, CDCl ) δ 148.0, 144.7 (d, J =
3
1
1
(
0.2 Hz), 136.8 (d, J = 5.1 Hz), 134.8 (d, J = 2.6 Hz), 133.1 (d, J = 16.4 Hz), 130.4,
28.4, 128.0, 127.9, 127.86, 127.8, 127.3, 127.2, 126.3 (d, J = 1.1 Hz), 125.3, 124.8, 61.7
+
t, J = 6.0 Hz), 30.5, 24.6, 23.5, 16.3 (t, J = 6.4 Hz); ESI-MS: m/z 383 [M +H] ; Chiral
o
HPLC conditions: Chiralcel OD-H, 4.6 mm X 250 mm, 30 C, flow rate: 2 mL/min,
heptane/isopropanol: 96/4, 225 nm, 4.04 min , 4.74 min.
S19

Diethyl 1-(biphenyl-2-yl)naphthalen-2-ylphosphonate: 74%
20
Ph
O
o
1
yield; 96% ee; [
= -4.7 (c = 0.6, CHCl ); H NMR (400 MHz,
3
D
P OEt
OEt
CDCl ) δ 7.98 (dd, J = 12.0, 8.8 Hz, 1H), 7.81 (dd, J = 8.4, 3.6 Hz,
3
1
H), 7.73 (d, J = 8.3 Hz, 1H), 7.54 (m, 2H), 7.37-7.49 (m, 3H), 7.33
(
d, J = 8.6 Hz, 1H), 7.25 (t, J = 8.0 Hz, 1H), 7.16 (m, 2H), 6.94 (m,
1
3
3
1
1
H), 3.92 (m, 3H), 3.68 (m, 1H), 1.15 (m, 6H); C NMR (100 MHz, CDCl ) δ 142.0,
3
41.2, 136.9, 134.6, 131.7, 129.7, 129.1, 128.3, 127.9, 127.8, 127.7, 127.68, 127.5, 127.4,
27.3, 127.26, 126.5, 126.3, 126.29, 61.9 (d, J = 5.8 Hz), 61.8 (d, J = 6.6 Hz), 16.3 (d, J
+
6.2 Hz), 16.2 (d, J = 6.5 Hz); ESI-MS: m/z 417 [M +H] ; Chiral HPLC conditions:
=
o
Chiralcel OD-H, 4.6 mm X 250 mm, 30 C, flow rate: 2 mL/min, heptane/isopropanol:
6/4, 225 nm, 6.57 min , 8.21 min.
9
S20

5
R)-Diethyl 1,1'-binaphthyl-2-ylphosphonate: 88% yield; 90%
(
2
0
o
1
ee; [
= +46.4 (c = 0.29, CHCl ); H NMR (400 MHz,
3
D
CDCl ) δ 8.21 (dd, J = 12.0, 8.7 Hz, 1H), 8.02 (dd, J = 8.6, 3.7
O
3
Hz, 1H), 7.94 (m, 3H), 7.60 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.3
Hz, 1H), 7.49 (d, J = 7.0 Hz, 1H), 7.44 (t, J = 7.4 Hz, 1H), 7.15-
P OEt
OEt
7
.30 (m, 3H), 7.08 (d, J = 8.4 Hz, 1H), 3.80 (m, 1H), 3.69 (m,
13
1
1
1
1
H), 3.58 (m 2H), 0.97 (t, J = 7.0 Hz, 1H); C NMR (100 MHz, CDCl ) δ 135.9, 134.9,
3
33.4, 133.2, 128.73, 128.71, 128.6, 128.3, 128.0, 127.9, 127.8, 127.7, 127.6, 126.72,
26.7, 125.9, 125.6, 124.9, 61.8 (d, J = 6.0 Hz), 61.6 (d, J = 6.0 Hz), 15.9 (d, J = 6.7 Hz),
+
5.4 (d, J = 7.2 Hz); ESI-MS: m/z 391 [M +H] ; Chiral HPLC conditions: Chiralcel AD-
o
H, 4.6 mm X 250 mm, 30 C, flow rate: 2 mL/min, heptane/isopropanol: 96/4, 225 nm,
8
.13 min (R), 11.7 min (S).
S21

(
R)-diethyl 1-(phenanthren-9-yl)naphthalen-2-ylphosphonate:
2
0
o
1
9
0% yield; 82% ee; [
= +30.4 (c = 0.25, CHCl ); H NMR
3
D
(
500 MHz, CDCl ) δ 8.79 (d, J = 8.3 Hz, 2H), 8.26 (dd, J = 12.2,
3
8
7
7
7
7
.6 Hz, 1H), 8.06 (dd, J = 8.6, 3.7 Hz, 1H), 8.96 (d, J = 8.3 Hz, 1H),
.89 (d, J = 7.8 Hz, 1H), 7.77 (s, 1H), 7.74 (m, 1H), 7.65 (m, 2H),
.54 (t, J = 7.0 Hz, 1H), 7.34 (m, 2H), 7.23 (m, 1H), 7.15 (d, J =
.7 Hz, 1H), 3.77 (m, 1H), 3.64 (m, 2H), 3.54 (m, 1H), 0.95 (t, J =
O
P OEt
OEt
1
3
.1 Hz, 3H), 0.61 (t, J = 7.1 Hz, 3H); C NMR (125 MHz, CDCl )
3
δ 143.3 (d, J = 9.3 Hz), 135.0 (d, J = 2.6 Hz), 134.5 (d, J = 5.3 Hz), 133.3 (d, J = 15.7
Hz), 132.6, 131.3, 130.3, 129.9, 129.63, 129.62, 128.9, 128.8, 128.79, 128.0 (d, J = 1.0
Hz), 127.9 (d, J = 1.0 Hz), 127.87, 127.8, 127.7, 127.1, 127.6, 126.9, 126.7 (d, J = 1.4
Hz), 126.5, 126.3, 125.6, 122.63, 122.61, 61.8 (d, J = 6.1 Hz), 61.5 (d, J = 6.1 Hz), 15.9
+
d, J = 7.1 Hz), 15.3 (d, J = 7.2 Hz); ESI-MS: m/z 441 [M +H] ; Chiral HPLC conditions:
(
Chiracel OD-H, 4.6 X150 mm, flow rate: 2 mL/min, Water/Acetonitrile: 50/50; 225 nm,
1
1.70 min (S), 12.50 min (R).
6
. Derivatization of chiral biaryl coupling product 6d
LiOOH
O
O
N
OH
O
O
6d
7
S22

To a solution of 6d (100 mg, 0.24 mmol, 92% ee) in THF/water (4 mL, 3/1 v/v) at
C was charged 30% H O solution (109 mg, 0.96 mmol, 3 equiv) followed by lithium
o
0
2
2
o
hydroxide (11.5 mg, 0.48 mmol, 2 equiv). The resulting mixture was stirred at 0-25 C
for ~ 0.5 h. The starting material was totally consumed. To the mixture was charged 10 %
sodium bisulfite solution (4 mL) and dichloromethane (4 mL). The DCM layer was
separated, washed with brine, concentrated, and purified by column chromatography to
2
D
0
o
provide 7 as white solid (71 mg, 0.238 mmol, 99% yield). 7: 92% ee; [
= +23.6 (c =
1
0
7
.70 , CHCl ); H NMR (400 MHz, CDCl ) δ 8.07 (d, J = 8.7 Hz, 1H), 7.95 (m, 4H),
3
3
.54 (m, 2H), 7.44 (t, J = 7.3 Hz, 1H), 7.31 (d, J = 6.8 Hz, 1H), 7.20-7.28 (m, 3H), 7.13
1
3
(
d, J = 8.3 Hz, 1H); C NMR (100 MHz, CDCl ) δ 171.5, 141.2, 136.5, 135.2, 133.2,
3
1
1
33.1, 132.9, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.2, 127.0, 126.7, 126.1, 126.0,
+
25.7, 125.2; ESI-MS: m/z 299[M +H] ; Chiral HPLC conditions: Chiralcel OD-H, 4.6
o
mm X 250 mm, 30 C, flow rate: 2 mL/min, heptane/isopropanol: 94/6, 225 nm, 15.07
min (S) , 16.88 min (R).
o
To a solution of 6d (100 mg, 0.24 mmol, 94% ee) in THF (5 mL) at 0 C was charged
LiBH (8 mg, 0.36 mmol, 1.5 equiv) in one portion. The mixture was then stirred at 0-25
4
o
C for 1 h and then quenched by addition of water (5 mL) and EtOAc (5 mL). The
organic layer was separated, washed with brine, dried over sodium sulfate, concentrated,
and purified by silica gel column chromatography to provide alcohol 8 as white solid (63
2
0
o
5 1
mg, 0.22 mmol, 94% ee). 8: 94% ee; [
= +46.3 (c = 1.0, CHCl ); H NMR (400
3
D
S23

MHz, CDCl ) δ 7.85-8.05 (m, 4H), 7.78 (d, J =8.3 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H),
3
1
3
7
1
1
.33-7.50 (m, 3H), 7.12-7.30 (m, 4H), 4.4 (s, 2H); C NMR (100 MHz, CDCl ) δ 136.7,
3
35.8, 135.7, 133.6, 133.1, 132.9, 132.8, 128.3, 128.1, 127.9, 127.8, 126.6, 126.4, 126.2,
+
26.1, 125.8, 125.7, 125.5, 63.4; ESI-MS: m/z 285[M +H] ; Chiral HPLC conditions:
o
Chiralcel OD-H, 4.6 mm X 250 mm, 30 C, flow rate: 2 mL/min, heptane/isopropanol:
6/4, 254 nm, 9.14 min (S) , 16.30 min (R).
9
7
. Computational studies
6
Both Buchwald and Baudoin have made a reasonable hypothesis that the
7
enantioselectivities in the Suzuki-Miyaura coupling reactions are determined in the
transition state of reductive elimination. The occurrence of a particular conformation of
reaction intermediate is determined by its energy. The chirality of the product follows the
shortest path from the conformation of the transition state. To determine the most
probable conformation of the intermediates, we first sampled all possible conformations
of the palladium complex at the reductive elimination step in the reaction of 5d and 1-
naphthylboronic acid with the Pd-2 catalyst. This was accomplished by fixing the
conformation of the ligand and systematically rotating the bonds between the Pd center
o
and the two reactants in 30 intervals. Two differently probable coordination
configurations were considered as shown in Figure 1S. After eliminating conformations
that have obvious steric clashes, 28 unique conformations were obtained. The geometry
of each of these conformations was then optimized by energy minimized. All calculations
8
were carried out with Gaussian 03 package. The DFT/B3LYP method was used in the
optimization. Because our system consists of bulky aromatic system, non-bonded van der
Walls interactions are expected to make a significant contribution to the relative energy
of different conformations. We therefore employed the MIDI basis set developed by
S24

9
Truhlar and co-workers , supplied by the Gaussian 03 package (MidiX) for the first-row
atoms (H, C, N and O). This functional was reported to produce good results for non-
bonded interactions comparable with higher-order theories. For phosphorus, the 6-31G(d)
basis set was employed; and for palladium, the all-electron basis set from optimization of
1
0
fcc Pd bulk was employed.
Conformer class A (A-01 to A-12)
Naphthyl group is 180 with respect to phosphorus ligand
Conformer class B (B-01 to B-12)
Naphthyl group is 90 with respect to phosphorus ligand
o
o
Figure S1: Two different conformation classes that were sampled
Although there were 28 unique starting conformations, four pairs of
conformations were found to be almost duplicates after full energy minimization for each
conformation. The coordinates of the 24 unique energy-minimized conformations are
provided in the enclosed minimized-conformation.cif file. Figure S2 shows the relative
energy of the 24 conformations. Three lowest-energy conformations were found with
relative energy of 0, 0.51 and 0.78 kcal/mol, respectively. All other conformations have
energy > 2 kcal/mol or higher than the lowest-energy state.
S25

Figure S2: The relative energy of all the sample conformations in the energy-minimized
state
There are two main interesting observations from calculation results. First, all
three lowest-energy conformations turn out to lead to the same chirality in the coupling
product that is in agreement with the inferred axial chirality of 6d. This result suggests
that the energetics of non-bonded -interaction of the aromatic systems indeed dictate the
conformation of the intermediate and the chirality of the product. Secondly, the origin of
the π-stacking interaction in determining the energetics of this system is most clearly seen
nd
in the lowest and 2 lowest-energy conformations. Figure S3 and S4 compare the
conformations of these two conformations. In each case, there is a π-stacking interaction
between the naphthal group and the benzooxazolidinone; and more revealing, in each
case, there is a related energy-minimum conformation in which the naphthal group
rotates by 180 that reverses the chirality of the system and that has higher energy by ~ 2
kcal/mol.
S26

Figure S3: Comparison of the lowest-energy conformation and the local energy minimum
o
in which the napthtyl group approximately flaps by 180 with respect to the first
conformation
Conformer 12
Energy = 0.51 Kcal/Mol
Conformer 10
Energy = 2.45 Kcal/Mol.
nd
Figure S4: Comparison of the 2 lowest-energy conformation and the local energy
o
minimum in which the napthtyl group approximately flaps by 180 with respect to the
first conformation
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rd
Figure S5: The conformation of the 3 lowest-energy conformation. Interestingly, the
chirality of the coupling product from this intermediate conformation is the same as the
st
nd
and 2 lowest energy conformations.
1
8
. References:
(
1) (a) Tang, W.; Qu, B.; Capacci, A. G.; Rodriguez, S.; Wei, X.; Haddad, N.; Narayanan,
B.; Ma, S.; Grinberg, N.; Yee, N. K.; Krishnamurthy, D.; Senanayake, C. H. Org. Lett.
010, 12, 176. (b) Tang, W.; Capacci, A. G.; White, A.; Ma, S.; Rodriguez, S.; Qu, B.;
2
Savoie, J.; Patel, N. D.; Wei, X.; Haddad, N.; Grinberg, N.; Yee, N. K.; Krishnamurthy,
D.; Senanayake, C. H. Org. Lett. 2010, 12, 1104.
(2) Tang, W.; Capacci, A. G.; Wei, X.; Li, W.; White, A.; Patel, N. D.; Savoie, J.; Gao, J.
J.; Rodriguez, S.; Qu, B.; Haddad, N.; Lu, B. Z.; Krishnamurthy, D.; Yee, N. K.;
Senanayake, C. H. Angew. Chem., Int. Ed. 2010, 49, 5879.
(
3) Rodriguez, S.; Qu, B.; Haddad, N.; Reeves, D.; Tang, W.; Krishnamurthy, D.;
Senanayake, C. H. Adv. Asy. Cat. 2011, 353, 533.
4) (a) Yin, J. J.; Buchwald, S. L. J. Am. Chem. Soc. 2000, 122, 12051. (b) Kurz, L.; Lee,
G.; Morgans, D., Jr.; Waldyke, M. J.; Ward, T. Tetrahedron Lett. 1990, 31, 6321.
5) (a) Meyers, A. I.; Lutomski, K. A. J. Am. Chem. Soc. 1982, 104, 879. (b) Aoyagi, N.;
Ohwada, T.; Izumi, T. Tetrahedron Lett. 2003, 44, 8269.
6) Shen, X.; Jones, G. O.; Watson, D. A.; Bhayana, B.; Buchwald, S. L. J. Am. Chem.
Soc. 2010, 132, 11278.
7) Joncour, A.; Décor, A.; Liu, J.M. ; Dau, M. ; Baudoin, O. Chem. Eur. J. 2007, 13,
450.
8) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
(
(
(
(
5
(
Cheeseman, J. R.; Montgomery, Jr., J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani,
G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda,
R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.;
Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.;
Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J.
J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D.
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K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A.
G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.;
Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M.
W.; Gonzalez, C.; and Pople, J. A.; Gaussian 03 ; Gaussian, Inc. ; Wallingford CT, 2004.
(
9) (a) Zhou, Y.; Truhlar, D.G. J. Phys. Chem. A 2006, 110, 10478. (b) Zhou, Y.; Truhlar,
D.G. J. Chem. Theory Comput. 2007, 3, 289.
10) http://www.chimifm.unito.it/teprica/crystal/crystal.html
(
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