Bismuth triflate-chiral bipyridine complexes as water-compatible chiral lewis acids

Article abstract of DOI:10.1021/ol051965w

(Chemical Equation Presented) Catalytic asymmetric hydroxymethylation of silicon enolates with an aqueous formaldehyde solution has been developed using a chiral bismuth complex. This is the first example of highly enantioselective reactions using a chira

Full text of DOI:10.1021/ol051965w

Bismuth Triflate-Chiral Bipyridine Complexes as Water-Compatible Chiral Lewis
Acids
_
*
Shu Kobayashi, Tsuyoshi Ogino, Haruka Shimizu, Shunpei Ishikawa, Tomoaki
Hamada, and Kei Manabe
Graduate School of Pharmaceutical Sciences, The University of Tokyo, The
HFRE Division ERATO, Japan Science and Technology Agency (JST), Hongo,
Bunkyo-ku, Tokyo 113-0033, Japan.
Supporting Information
Table of Contents
Pages
S-1
Experimental
Typical Experimental Procedures for the Hydroxymethylation
S-2
Characterization Data of the Hydroxymethylated Adducts
S-2
Crystallization of [BiBr •1]•(H O) •DME Complexes
S-6
3
2
2
NMR Analyses of the Catalyst Structures
References
S-6
S-8
Experimental
1
13
General: Melting points were uncorrected. H and C NMR spectra were recorded on
a JEOL JNM-LA300, JNM-LA400, ECX-400 or ECX-600 spectrometer in CDCl3
unless otherwise noted. Tetramethylsilane (TMS) served as an internal standard (δ = 0
1
13
ppm) for H NMR and CDCl as an internal standard (δ = 77.0 ppm) for C NMR.
3
Preparative thin-layer chromatography was carried out using Wakogel B-5F. An
aqueous solution of formaldehyde was purchased from Wako Pure Chemical Industries,
Ltd.
S-1

Typical
Experimental
Procedure
for
the
Hydroxymethylation
of
Propiophenone-derived Silicon Enolate: A mixture of Bi(OTf) (14 mg, 0.020
3
mmol) and 1 (20 mg, 0.060 mmol) in DME (1 mL) was stirred at room temperature for
3
0 min to afford 20 mM of a catalyst solution. A reaction vessel charged with the
catalyst solution (150 µL) was cooled at 0 °C for 10 min, and an 81 mM solution of
,2’-bipyridine in DME (185 µL) was added. Then an aqueous solution of
2
formaldehyde (129 mg, 35% w/w, 1.5 mmol) and the silicon enolate (62 mg, 0.30
mmol) were added to the mixture. The whole was stirred until the silicon enolate
disappeared completely (checked by TLC). The reaction was quenched with saturated
aqueous NaHCO3. The resultant mixture was extracted with dichloromethane (3
times), and the combined organic layers were dried over anhydrous Na SO . The
2
4
solvents were evaporated, and the residue was purified by preparative TLC (silica gel,
hexane/ethyl acetate (2/1)) to give the hydroxymethylated adduct. The enantiomeric
excess of the product was determined by chiral HPLC analysis.
Characterization Data of the Hydroxymethylated Adducts
1
(
S)-3-Hydroxy-2-methyl-1-phenylpropan-1-one
1
H NMR (CDCl ) δ 1.24 (d, 3H, J = 7.1 Hz), 2.35 (brs), 3.68 (ddq, 1H,
O
3
J = 4.3, 7.0, 7.1 Hz), 3.80 (dd, 1H, J = 4.3, 11.1 Hz), 3.94 (dd, 1H, J =
.0, 11.1 Hz), 7.48 (dd, 2H, J = 7.3, 8.5 Hz), 7.58 (t, 1H, J = 7.3 Hz),
HO
Ph
7
1
3
7
1
.97 (d, 2H, J = 8.5 Hz); C NMR (CDCl ) δ 14.5, 42.9, 64.5, 128.4, 128.7, 133.3,
3
36.1, 204.4; HPLC (Daicel Chiralpak AD-H, hexane/i-PrOH = 19/1, flow rate = 1.0
mL/min) t = 17.5 min (major, S), t = 20.3 min (minor, R).
R
R
3
2
-(Hydroxymethyl)-1-phenylbutan-1-one
1
H NMR (CDCl ) δ 0.95 (t, 3H, J = 7.4 Hz), 1.61-1.83 (m, 2H),
3
O
!
2.40 (brs), 3.52-3.58 (m, 1H), 3.84 (dd, 1H, J = 3.9, 11.0 Hz), 3.98
HO
(
dd, 1H, J = 6.8, 11.0 Hz), 7.45-7.50 (m, 2H), 7.56-7.60 (m, 1H),
1
3
7
1
.95-7.97 (m, 2H); C NMR (CDCl ) δ 11.8, 22.3, 49.5, 62.6, 128.3, 128.7, 133.2,
3
–
1
36.8, 204.6; IR (neat) 3435, 2966, 1678, 1043, 704 cm ; HRMS (ESI-TOF) calcd for
+
2
4
C H O Na ([M+Na] ): 201.0891, found: 201.0889; [α]
–0.6 (c 0.75, CHCl ) (91%
3
11
14
2
D
ee); HPLC (Daicel Chiralpak AD-H, hexane/i-PrOH = 19/1, flow rate = 1.0 mL/min) tR
18.8 min (major), t = 22.4 min (minor).
=
R
S-2

3
-(Hydroxy)-2-methyl-1-(4-methoxyphenyl)propan-1-one
1
H NMR (CDCl ) δ 1.22 (d, 3H, J = 7.1 Hz), 2.60 (brs), 3.62
O
3
!
(
ddq, 1H, J = 4.3, 7.0, 7.1 Hz), 3.78 (dd, 1H, J = 4.3, 11 Hz),
.87 (s, 3H), 3.91 (dd, 1H, J = 7.0, 11 Hz), 6.95 (d, 2H, J =
HO
3
OMe
1
3
8
1
8
6
.9 Hz), 7.95 (d, 2H, J = 8.9 Hz); C NMR (CDCl ) δ 14.7, 42.4, 55.4, 64.6, 113.8,
3
29.0, 130.7, 163.6, 202.9; IR (neat) 3438, 2933, 1667, 1597, 1251, 1173, 1047, 975,
–1
+
43 cm ; MS m/z 194 (M ); Anal. Calcd for C H O : C, 68.02; H, 7.27. found: C,
11
14
3
7.88; H, 7.33; [α]24 +4.2 (c 1.5, CHCl ) (88% ee); HPLC (Daicel Chiralpak AD-H,
D
3
hexane/i-PrOH = 19/1, flow rate = 1.0 mL/min) t = 30.7 min (major), t = 38.9 min
R
R
(
minor).
3
-(Hydroxy)-2-methyl-1-(4-chlorophenyl)propan-1-one
1
H NMR (CDCl ) δ 1.21 (d, 3H, J = 7.3 Hz), 2.52 (brs), 3.62
O
3
!
(
ddq, 1H, J = 4.3, 7.2, 7.3 Hz), 3.77 (dd, 1H, J = 4.3, 11 Hz),
HO
3
.87 (s, 3H), 3.93 (dd, 1H, J = 7.2, 11 Hz), 7.44 (d, 2H, J = 8.5
Cl
13
Hz), 7.90 (d, 2H, J = 8.5 Hz); C NMR (CDCl ) δ 14.4, 43.0, 64.4, 129.0, 129.8, 134.4,
3
–
1
1
39.7, 203.0; IR (neat) 3424, 2937, 1682, 1590, 1401, 1092, 976, 841 cm ; MS m/z 198
+
2
4
(
M ); Anal. Calcd for C H ClO : C, 60.48; H, 5.58. found: C, 60.18; H, 5.85; [α]
10
11
2
D
+
4.1 (c 1.05, CHCl ) (89% ee); HPLC (Daicel Chiralpak AD-H, hexane/i-PrOH = 19/1,
3
flow rate = 1.0 mL/min) t = 18.6 min (major), t = 28.7 min (minor).
R
R
3
-Hydroxy-1-(2-methoxynaphthalen-6-yl)-2-methylpropan-1-one
1
H NMR (CDCl ) δ 1.28 (d, 3H, J = 6.9 Hz), 2.60 (s,
O
3
!
1
H), 3.78-3.86 (m, 2H), 3.93 (s, 3H), 3.98 (m, 1H), 7.13
m, 1H), 7.20 (m, 1H), 7.75 (m, 1H), 7.83 (m, 1H), 7.98
m, 1H), 8.40 (m, 1H); C NMR (CDCl ) δ 14.8, 42.7, 55.4, 64.7, 105.7, 119.7, 124.7,
HO
(
OMe
3
1
(
3
1
1
27.2, 127.8, 130.1, 131.2, 131.4, 137.4, 159.8, 204.1; IR (neat) 3444, 1665, 1622, 1477,
-
1
+
268, 1187, 1028 cm ; HRMS (ESI-TOF) calcd for C H O ([M+H] ): 245.1178,
15
17
3
found: 245.1166; [α]24 +2.3 (c 1.84, CHCl ) (92% ee); HPLC (Daicel Chiralcel OD,
D
3
hexane/i-PrOH = 19/1, flow rate = 1.0 mL/min) t = 30.7 min (minor), t = 36.6 min
R
R
(
major).
S-3

3
2
,3-Dihydro-2-(hydroxymethyl)-2-methylinden-1-one
1
H NMR (CDCl ) δ 1.26 (s, 3H), 2.91 (d, 1H, J = 7.2 Hz), 3.24 (d,
3
O
1
7
H, J = 7.2 Hz), 3.64 (d, 1H, J = 11 Hz), 3.83 (d, 1H, J = 11 Hz),
!
.35-7.41 (m, 1H), 7.45-7.48 (m, 1H), 7.59-7.64 (m, 1H), 7.64-7.77
HO
13
(
m, 1H); C NMR (CDCl ) δ 20.7, 38.0, 50.8, 67.8, 124.2, 126.7, 127.5, 135.2, 135.8,
3
–
1
o
1
53.2, 211.1; IR (KBr) 3473, 2962, 2921, 2866, 1703 cm ; Mp 83-89 C; Anal. calcd
24
for C H O : C, 74.98; H, 6.86. found: C, 74.80; H, 7.05; [α] +1.6 (c 0.95, CHCl3)
D
11
12
2
(
88% ee); HPLC (Daicel Chiralcel OB-H, hexane/i-PrOH = 100/1, flow rate = 1.0
mL/min) t = 39.6 min (major), t = 50.0 min (minor).
R
R
3
3
,4-Dihydro-2-(hydroxymethyl)-2-methylnaphthalen-1(2H)-one
1
H NMR (CDCl ) δ 1.23 (s, 3H), 1.78 (ddd, 1H, J = 3.7, 4.9, 13.4
3
O
Hz), 2.24 (ddd, 1H, J = 5.1, 12.0, 13.4 Hz), 2.77 (brs), 2.94 (ddd,
HO
!
1
H, J = 3.7, 5.1, 17.3 Hz), 3.15 (ddd, 1H, J = 4.9, 12.0, 17.3 Hz),
3
1
6
7
2
.65 (d, 1H, J = 11.2 Hz), 3.74 (d, 1H, J = 11.2 Hz), 7.24-7.26 (m, 1H), 7.29-7.33 (m,
13
H), 7.47-7.50 (m, 1H), 8.00-8.03 (m, 1H); C NMR (CDCl ) δ 18.2, 25.0, 31.3, 46.3,
3
9.0, 126.7, 127.7, 128.7, 131.4, 133.6, 143.4, 204.0; IR (neat) 3456, 2931, 1678, 1047,
–
1
+
42 cm ; HRMS (ESI-TOF) calcd for C H O Na ([M+Na] ): 213.0891, found:
1
2
14
2
13.0881; [α]24 –1.4 (c 1.3, CHCl ) (95% ee); HPLC (Daicel Chiralcel OD,
D
3
hexane/i-PrOH = 100/1, flow rate = 1.0 mL/min) t = 28.6 min (major), t = 34.3 min
R
R
(
minor).
2
-Butyl-3,4-dihydro-2-(hydroxymethyl)naphthalen-1(2H)-one
1
13
H NMR (CDCl ) δ; C NMR (CDCl ) δ 13.9, 23.2, 24.9, 25.8,
3
3
O
n-C H
4
9
2
2
8.0, 29.9, 49.5, 66.5, 126.7, 127.7, 128.7, 131.6, 133.5, 143.4,
HO
!
-
1
04.4; IR (neat) 3443, 1672, 1458, 1227, 1053, 742 cm ; HRMS
+
2
4
(
ESI-TOF) calcd for C H O Na ([M+Na] ): 255.1356, found: 255.1362; [α]
–2.8 (c
D
1
5
21
2
0
.75, CHCl ) (93% ee); HPLC (Daicel Chiralcel OD, hexane/i-PrOH = 100/1, flow rate
3
=
1.0 mL/min) t = 20.6 min (major), t = 23.6 min (minor).
R R
S-4

2
(
R)-2-(Hydroxymethyl)-2-methylcyclohexanone
1
H NMR (CDCl ) δ 1.19 (s, 3H), 1.54-1.96 (m, 5H), 2.00-2.07 (m, 1H),
3
O
2
.24-2.30 (m, 1H), 2.52 (ddd, 1H, J = 6.1, 12.9, 14.4 Hz), 3.48 (d, 1H, J
HO
13
=
11.5 Hz), 3.52 (d, 1H, J = 11.5 Hz); C NMR (CDCl ) δ 20.2, 20.7,
3
2
7.3, 35.5, 38.9, 50.1, 69.0, 218.1.
3
[
(R)-1-Methyl-2-oxocyclohexyl]methyl benzoate
To a solution of 2-(hydroxymethyl)-2-methylcyclohexanone (14 mg,
O
0
0
.099 mmol) in CH Cl (0.99 mL) were added benzoyl chloride (23 µL,
2 2
BzO
.20 mmol) and pyridine (40 µL, 0.49 mmol) at room temperature.
After stirring for 2 h, the reaction was quenched with water. The resultant mixture
was extracted with CH Cl (twice), and the combined organic layers were washed with
2
2
brine and dried over anhydrous Na SO . The solvents were evaporated, and the
2
4
residue was purified by preparative TLC (silica gel, hexane/ethyl acetate (6/1)) to give
the desired product (75% yield).
1
H NMR (CDCl ) δ 1.26 (s, 3H), 1.73-1.98 (m, 6H), 2.42-2.54 (m, 2H), 4.38 (d, 1H, J =
3
1
2
1
1.0 Hz), 4.46 (d, 1H, J = 11.0 Hz), 7.41-7.45 (m, 2H), 7.53-7.58 (m, 1H), 7.99-8.01 (m,
1
3
H); C NMR (CDCl ) δ 20.8, 21.0, 27.2, 36.4, 38.8, 48.9, 69.1, 128.3, 129.5, 130.0,
3
–
1
33.0, 166.3, 212.9; IR (neat) 2937, 1718, 1274, 1115, 714 cm ; Anal. calcd for
18
C H O : C, 73.15; H, 7.37. found: C, 73.24; H, 7.54; [α]
–0.2 (c 0.50, CHCl ) (for
3
1
5
18
3
D
R, 77% ee); HPLC (Daicel Chiralpak AD-H, hexane/i-PrOH = 100/1, flow rate = 0.5
mL/min) t = 39.7 min (major, R), t = 42.3 min (minor, S).
R
R
3
2
-Benzyl-2-(hydroxymethyl)cyclohexanone
1
H NMR (CDCl ) δ 1.40-1.48 (m, 1H), 1.60-1.78 (m, 3H), 1.91-2.11 (m,
3
Ph
HO
O
2
H), 2.35-2.41 (m, 1H), 2.55-2.80 (m, 2H), 2.88 (d, 1H, J = 13.4 Hz),
.08 (d, 1H, J = 13.4 Hz), 3.34 (d, 1H, J = 11.6 Hz), 3.46 (d, 1H, J =
!
3
1
3
1
1.6 Hz), 7.21-7.31 (m, 5H); C NMR (CDCl ) δ 20.6, 27.0, 31.5, 37.0, 39.3, 53.8, 65.6,
3
–
1
1
26.6, 128.2, 130.5, 135.9, 217.9; IR (neat) 3452, 2941, 1699, 1454, 1061, 706 cm ;
+
HRMS (ESI-TOF) calcd for C H O Na ([M+Na] ): 241.1204, found: 241.1204;
1
4
18
2
[
α]24 –8.2 (c 1.25, CHCl ) (82% ee); HPLC (Daicel Chiralpak AD-H, hexane/i-PrOH
D
3
=
40/1, flow rate = 1.0 mL/min) t = 22.1 min (major), t = 29.8 min (minor).
R R
S-5

2
-Benzyl-2-(hydroxymethyl)cyclopentanone
1
H NMR (CDCl ) δ 1.56-1.88 (m, 3H), 1.94 (m, 1H), 2.11-2.31 (m, 2H),
3
Ph
O
2
7
.41 (br, 1H), 2.81 (dd, 2H, J = 13, 28 Hz), 3.55 (m, 2H), 7.16 (m, 2H),
HO
!
1
3
.20-7.30 (m, 3H); C NMR (CDCl ) δ 19.0, 29.8, 37.9, 39.1, 54.3, 65.7,
3
-
1
1
26.6, 128.3, 130.2, 136.8, 224.5; IR (neat) 3438, 1727, 1160, 1053, 757, 705 cm ;
+
HRMS (ESI-TOF) calcd for C H O Na ([M+Na] ): 227.1043, found: 227.1040;
1
0
16
2
[
α]24 –4.5 (c 0.85, CHCl ) (79% ee); HPLC (Daicel Chiralpak AD-H, hexane/i-PrOH
D
3
=
19/1, flow rate = 1.0 mL/min) t = 15.1 min (major), t = 19.0 min (minor).
R R
Crystallization of [BiBr •1]•(H O) •DME complexes
3
2
2
Crystallization of [BiBr •1]•(H O) •DME was carried out as follows: To a yellow
3
2
2
solution of BiBr (20.2 mg, 45 µmol) in DME (20 µL) was added 1 (14.8 mg, 45 µmol)
3
at room temperature. The solution was warmed to 75 °C (oil bath temperature).
Then, a white precipitate was gradually formed, and was dissolved by addition of DME
(
630 µL). The resulting solution was allowed to stand at room temperature under
DME vapor to give the crystals.
NMR analysis of the catalyst structure
NMR experiments were conducted to obtain some information about the catalyst
structure when the Bi(OTf) -1 ratio were 1:0.5, 1:1, 1:2 and 1:3 (Figure S-1). When
3
the Bi(OTf) and 1 were combined at the ratio of 1:0.5, a signal at 5.49 ppm was
3
dominant. On the other hand, another signal at 4.72 ppm increased when the ratio of 1
to Bi(OTf) increased, and finally the former signal disappeared when Bi(OTf) was
3
3
combined with three equivalents of 1. These results indicate that two equivalents of
Bi(OTf) and one equivalent of 1 formed complex 3, and that complex 4 consisting of
3
one equivalent of Bi(OTf) and one equivalent of 1 was generated when excess amount
3
of 1 was added (Scheme S-1).
S-6

1
Figure S-1. H NMR analysis of the catalyst structure.
<
<
<
<
<
Bi/L = 1/3 >
Bi/L = 1/2 >
Bi/L = 1/1 >
Bi/L = 1/0.5 >
Ligand only >
0
: 1
0
.4 : 1
2
: 1
1
5 : 1
(bipyridine)
(methine)
8
6
4 (ppm)
Scheme S-1.
*
*
*
N
N
N
N
N
N
1
+
2 Bi
Bi Bi
Bi
HO
OH
HO
OH
HO
OH
1
3
4
Representative Procedure for NMR Experiments: [Bi(OTf) :1 = 1:1] A solution
3
of Bi(OTf) (24 mg, 0.036 mmol) and 1 (12mg 0.036 mmol) in CD CN (900 µL) was
3
3
stirred at 0 °C for 10 min. D O (100 µL) was added to the mixture, and the solution
2
was stirred for 30 min at 0 °C. NMR experiments were conducted at 0 °C using
ECX-600 NMR spectrometer. The deuterated solvents were purchased from Cambridge
Isotope Laboratories, Inc. and used without further purification.
S-7

References
(
(
1) Manabe, K.; Ishikawa, S.; Hamada, T.; Kobayashi, S. Tetrahedron 2003, 59, 10439.
2) Miyaoka, H.; Kajiwara, Y.; Hara, M.; Suma, A.; Yamada, Y. Tetrahedron: Asymmetry 1999,
1
0, 3189.
(
3) Ishikawa, S.; Hamada, T.; Manabe, K.; Kobayashi, S. J. Am. Chem. Soc. 2004, 126, 12236.
S-8