Brønsted Acids as AdditiVes for Aldol Reaction
(
q, JCF ) 291 Hz), 126.9, 127.7, 128.7, 149.7, 162.2, 195.9. Anal.
Calcd for C15 S: C, 51.71; H, 5.50; F, 16.36; N, 8.04; S,
.20. Found: C, 51.74; H, 5.64; F, 16.52; N, 8.08; S, 9.02.
AcOH‚1: Obtained as white crystals in 55% (43 mg). Mp 82-
4 °C (from Et +40.7° (c 0.88 in CH Cl ). IR
O/hexanes); [R]22
ICH
77-79 °C (from Et
3201, 3041, 2981, 2953, 2442, 1618, 1586, 1548 cm . H NMR
(500 MHz; CDCl
2
COOH‚1: Obtained as white crystals in 91% (88 mg). Mp
H
19
F N
3 2
O
2
2
O); [R]22
D
-0.55° (c 1.07 in CH Cl ). IR (KBr)
2
2
-
1 1
9
3
) 1.64 (d, 3 H, J ) 6.7 Hz), 1.85-1.95 (m, 3 H),
8
2
D
2
2
2.45-2.55 (m, 1 H), 3.17-3.24 (m, 1 H), 3.25-.32 (m, 1 H), 3.55
-
1 1
(
KBr) 3167, 2977, 2933, 2754, 1588, 1450 cm ; H NMR (500
MHz; CDCl ) 1.61 (d, 3 H, J ) 7.0 Hz), 1.76-1.84 (m, 2 H),
.93-2.00 (1 H, m), 1.99 (s, 3 H), 2.42 (ddt, 1 H, J ) 13.3, 8.7,
(s, 2 H), 4.77-4.82 (m, 1 H), 5.59 (m, 1 H), 7.21-7.40 (m, 5 H),
7.35-8.10 (m, 2 H), 10.68 (brs, 1 H). 13C NMR (125 MHz; CDCl
)
3
3
1
6
6
2
20.7, 25.3, 33.8, 46.7, 56.0, 63.9, 127.0, 127.7, 128.7, 141.0, 173.7,
197.8. Anal. Calcd for C15 S: C, 42.87; H, 5.04; N, 6.67.
Found: C, 42.96; H, 5.00; N, 6.58.
HCl‚1: Obtained as white crystals in 96% (90 mg). Mp 177-
.8 Hz), 3.07 (dt, 1 H, J ) 10.6, 6.7 Hz), 3.18 (dt, 1 H, J ) 10.5,
.7 Hz), 4.57 (dd, 1 H, J ) 8.7, 6.4 Hz), 5.65 (m, 1 H), 6.35 (brs,
H), 7.24-7.28 (m, 2 H), 7.30-7.34 (m, 3 H), 10.35 (bs, 1 H);
2 2
H21IN O
13
22
C NMR(125 MHz; CDCl
26.5, 127.5, 128.7, 141.5, 176.5, 201.1. Anal. Calcd for
S: C, 61.19; H, 7.53; N, 9.52. Found: C, 61.04; H,
.54; N, 9.46.
CHCO H‚1: Obtained as white crystals in 99% (93 mg). Mp
46-149 °C (from Et -24.6° (c 0.89 in CH Cl ). IR
O); [R]22
3
) 20.6, 21.6, 25.8, 34.1, 47.0, 54.3, 66.2,
178 °C (from Et
3391, 3160, 3010, 2970, 2737, 1551, 1441 cm . H NMR (500
MHz; CDCl ) 1.67 (d, 3 H, J ) 7.0 Hz), 1.80-1.90 (m, 1 H),
2
O); [R]
D
+70.9° (c 0.53 in MeOH). IR (KBr)
-
1 1
1
C
7
15
H N O
22 2 2
3
1.92-2.03 (m, 2 H), 2.74 (m, 1 H), 3.25-3.34 (m, 1 H), 3.43-
3.52 (m, 1 H), 5.00 (m, 1 H), 5.49 (quintet, 1 H, J ) 7.1 Hz), 7.20
(m, 1 H), 7.26 (m, 2 H), 7.38-7.41 (m, 2 H), 7.96 (brs, 1 H),
F
2
2
1
(
(
2
D
2
2
-
1
1
13
KBr) 3186, 3027, 2978, 1638, 1562, 1455, 1435 cm ; H NMR
500 MHz; CDCl ) 1.59 (d, 3 H, J ) 7.0 Hz), 1.81-1.90 (m, 3 H),
.93 (m, 1 H), 3.22-3.28 (m, 1 H), 3.30-3.35 (m, 1 H), 4.83 (dd,
H, J ) 8.6, 6.4 Hz), 5.53 (m, 1 H), 5.64 (t, 1 H, J ) 55.7 Hz),
10.84 (brs, 1 H), 11.54 (d, 1 H, J ) 7.4 Hz). C NMR (125 MHz;
3
3
CDCl ) 21.1, 25.4, 34.0, 47.0, 57.0, 63.3, 127.1, 127.6, 128.6, 141.0,
1
1
7
195.3. Anal. Calcd for C13H19ClN S: C, 57.65; H, 7.07; N, 10.34.
2
Found: C, 57.61; H, 7.09; N, 10.34.
13
.17-7.30 (m, 5 H), 11.42 (d, 1 H, J ) 6.9 Hz); C NMR (125
) 20.2, 25.2, 33.5, 46.6, 56.6, 63.0, 109 (t, JCF ) 248.1
Hz), 126.9, 127.6, 128.7, 140.9, 168.5 (t, JCF ) 24 Hz), 196.3.
Anal. Calcd for C15 S: C, 54.53; H, 6.10; N, 8.48.
Found: C, 54.63; H, 6.37; N, 8.34.
ClCH
Mp 110-112 °C (from Et
IR (KBr) 3185, 3027, 2976, 2481, 1619, 1598, 1564, 1455 cm
HBr‚1: Obtained as white crystals in 87% (55 mg). Mp 178-
MHz; CDCl
3
180 °C (from Et
2
O/hexanes); [R]22
+60.6° (c 0.99 in MeOH). IR
1
D
-
(KBr) 3469, 3165, 3024, 2970, 2921, 2734, 2684, 1547, 1458 cm
.
1
H
20
F N O
2 2 2
3
H NMR (500 MHz; CDCl ) 1.69 (d, 3 H, J ) 7.0 Hz), 1.80-1.91
(m, 1 H), 1.99 (m, 2 H), 2.81 (m, 1 H), 3.30 (m, 1 H), 3.52 (m, 1
2
COOH‚1: Obtained as white crystals in 99% (67 mg).
H), 5.09 (m, 1 H), 5.51 (m, 1 H), 7.19-7.30 (m, 3 H), 7.40-7.45
O); [R]22
-11.08° (c 0.77 in CH
Cl
).
2
D
2
2
(m, 2 H), 8.17 (brs, 1 H), 10.02 (brs, 1 H), 11.02 (d, 1 H, J ) 7.5
-
1
13
;
Hz). C NMR (125 MHz; CDCl
3
) 21.2, 25.3, 34.1, 47.1, 57.2,
1
H NMR (500 MHz; CDCl
m, 3 H), 2.45-2.55 (m, 1 H), 3.20-3.31 (m, 2 H), 3.92 (s, 2 H),
3
) 1.63 (d, 3 H, J ) 7.0 Hz), 1.83-1.95
63.0, 127.2, 127.7, 128.6, 140.8, and 195.2. Anal. Calcd for C13
BrN S: C, 49.53; H, 6.07; N, 8.89. Found: C, 49.73; H, 5.93; N,
8.74.
4-Methylbenzoic Acid‚1: Obtained as white crystals in 25% (30
mg). Mp 101-103 °C (from Et -5.58° (c 0.97
O/hexanes). [R]22
in CH Cl ). IR (KBr) 3166, 3062, 3032, 2958, 2920, 2879, 1606,
1591, 1551, 1455 cm . H NMR (500 MHz; CDCl
19
H -
(
2
4
5
2
1
.87 (dd, 1 H, J ) 8.3, 6.2 Hz), 5.56 (m, 1 H), 7.20-7.35 (m,
H), 11.42 (brd, 1 H, J ) 5.5 Hz); 13C NMR(125 MHz; CDCl
0.2, 25.0, 33.4, 43.5, 46.3, 56.1, 63.2, 126.7, 127.4, 128.4, 140.6,
72.1, 196.7. Anal. Calcd for C15 S: C, 54.78; H, 6.44;
3
)
2
D
H21ClN O
2 2
2
2
-
1 1
Cl, 10.78; N, 8.52; S, 9.75. Found: C, 54.78; H, 6.51; Cl, 10.86;
N, 8.67; S, 9.45;
3
) 1.63 (d, 3 H,
J ) 7.0 Hz), 1.80-2.00 (m, 2 H), 1.96 (m, 1 H), 2.42 (s, 3 H),
2.52 (m, 1 H), 3.13 (dt, 1 H, J ) 10.7, 6.7 Hz), 3.26 (dt, 1 H, J )
10.7, 6.6 Hz), 4.79 (dd, 1 H, J ) 8.5, 6.6 Hz), 5.62 (brs, 1 H),
7.20-7.30 (m, 5 H), 7.31-7.35 (m, 2 H), 7.65 (brs, 1 H), 7.92-
Cl
Mp 140-142 °C (from Et
IR (KBr) 3195, 3030, 2979, 2567, 1635, 1556, 1455 cm ; H NMR
500 MHz; CDCl ) 1.63 (d, 3 H, J ) 7.0 Hz), 1.79-1.94 (m, 3 H),
2
CHCOOH‚1: Obtained as white crystals in 99% (244 mg).
O); [R]22
-34.5° (c 0.97 in CH Cl ).
2
D
2
2
-1 1
(
3
7.96 (m, 2 H), 10.61 (brs, 1 H). 13C NMR (125 MHz; CDCl
3
) 20.8,
21.7, 25.7, 34.1, 47.0, 54.9, 65.6, 126.6, 127.5, 128.3, 128.7, 129.0,
130.0, 141.4, 143.5, 171.4, 200.0. Anal. Calcd for C21 S:
2
4
7
.51-2.59 (m, 1 H), 3.20-3.27 (m, 1 H), 3.30-3.37 (m, 1 H),
.77 (dd, 1 H, J ) 8.2, 6.5 Hz), 5.55 (m, 1 H), 5.75 (s, 1 H), 7.22-
.39 (m, 5 H), 7.77 (brs, 1 H), 11.24 (d, 1 H, J ) 7.1 Hz), 11.72
26 2 2
H N O
C, 68.08; H, 7.07; N, 7.56. Found: C, 68.09; H, 7.08; N, 7.46.
(
brs, 1 H). 13C NMR (125 MHz; CDCl
3
) 20.5, 25.2, 33.6, 46.8,
3,5-Dinitrobenzoic Acid‚1: Obtained as white crystals in 91%
2
2
5
6.8, 63.2, 69.0, 127.1, 127.7, 128.7, 140.8, 169.0, 196.0. Anal.
S: C, 49.46; H, 5.53; Cl, 19.47; N, 7.69;
S, 9.06. Found: C, 49.45; H, 5.54; Cl, 19.39; N, 7.68; S, 9.07.
Cl CHCOOH‚1: Obtained as white crystals in 95% (87 mg).
Mp 108-109 °C (from Et -37.5° (c 0.93 in CH Cl ).
O); [R]22
IR (KBr) 3216, 3043, 2980, 1660, 1545, 1432 cm . H NMR (500
MHz; CDCl
(69 mg). Mp 159-161 °C dec (from Et O). [R] +42.24° (c 0.54
1
2
D
-
Calcd for C15
H20Cl
N
2 2
O
2
in MeOH). IR (KBr) 3202, 3030, 2980, 2944, 1631, 1544 cm .
1
H NMR (500 MHz; d -DMSO) 1.52 (d, 3 H, J ) 6.9 Hz), 1.82-
6
3
1.95 (m, 3 H), 2.34-2.42 (m, 1 H), 3.20-3.32 (m, 2 H), 4.51 (m,
2
D
2
2
1 H), 5.54 (m, 1 H), 7.23-7.27 (m, 1 H), 7.30-7.38 (m, 4 H),
8.85 (t, 1 H, J ) 2.2 Hz), 8.91 (d, 2 H, J ) 2.2 Hz), 11.11 (brs, 1
-1 1
) 1.63 (d, 3 H, J ) 7.0 Hz), 1.81-1.96 (m, 3 H),
.58-2.65 (m, 1 H), 3.26 (m, 1 H), 3.38 (m, 1 H), 4.80 (brs, 1 H),
.53 (m, 1 H), 7.23-7.40 (m, 5 H), 7.79 (brs, 1 H), 10.82 (d, 1 H,
H). 13C NMR (125 MHz; d
6
-DMSO) 20.7, 24.2, 32.7, 46.0, 54.3,
3
2
5
64.5, 95.4, 119.4, 126.4, 127.2, 128.3, 128.4, 141.7, 141.8, 147.8,
164.5, 197.8. Anal. Calcd for C20 S: C, 53.80; H, 4.97; N,
22 4 6
H N O
1
3
J ) 7.0 Hz), 11.14 (brs, 1 H); C NMR (125 MHz; CDCl
3
) 20.4,
5.0, 33.4, 46.8, 56.7, 63.2, 95.3, 126.9, 127.6, 128.5, 140.4, 165.1,
95.6. Anal. Calcd for C15 S: C, 45.30; H, 4.82; Cl,
12.55; S, 7.18. Found: C, 53.86; H, 4.81; N, 12.64; S, 7.21.
2
1
2
6
2-Hydroxybenzoic Acid‚1: Obtained as white crystals in 90%
2
2
H
19Cl
N O
3 2 2
(64 mg). Mp 140-142 °C (from Et O); [R] -36.50° (c 0.95 in
2
D
6.74; N, 7.04; S, 8.06. Found: C, 45.35; H, 4.90; Cl, 26.81; N,
.99; S, 7.98.
2 2
CH Cl ). IR (KBr) 3454, 3176, 3066, 2977, 2936, 2897, 1638, 1590,
1550, 1485 cm . H NMR (500 MHz; CDCl ) 1.59 (d, 3 H, J )
6.9 Hz), 1.90-1.98 (m, 3 H), 2.45-2.55 (m, 1 H), 3.19-3.25 (m,
-
1 1
3
BrCH
Mp 76-77 °C (from Et
KBr) 3200, 3038, 2984, 2448, 1616, 1591, 1554, 1458 cm ; H
NMR (500 MHz; CDCl ) 1.63 (d, 3 H, J ) 7.0 Hz), 1.82-1.94
2
COOH‚1: Obtained as white crystals in 91% (61 mg).
O); [R]22
-7.6° (c 0.98 in CH Cl ). IR
1 H), 3.31 (m, 1 H), 4.88 (dd, 1 H, J ) 8.0, 6.4 Hz), 5.57 (quintet,
1 H, J ) 7.0 Hz), 6.80 (m, 1 H), 6.91 (d, 1 H, J ) 7.8 Hz), 7.18-
7.27 (m, 4 H), 7.29-7.36 (m, 3 H), 7.77 (dd, 1 H, J ) 7.8, 1.8
2
D
2
2
-
1 1
(
3
13
(
(
(
m, 3 H), 2.45-2.55 (m, 1 H), 3.16-3.24 (m, 1 H), 3.24-3.30
Hz), 9.05 (brs, 2 H), 10.67 (brd, 1 H, J ) 5.6 Hz). C NMR (125
MHz; CDCl ) 20.3, 25.3, 33.5, 46.7, 56.2, 63.8, 116.9, 118.3, 126.9,
127.8, 128.8, 130.5, 133.9, 140.6, 161.6, 174.8, 197.0; HRMS (ESI)
m, 1 H), 3.74 (s, 2 H), 4.78 (m, 1 H), 5.56 (m, 1 H), 7.20-7.37
3
m, 5 H), 7.35-8.40 (brs, 2 H), 10.94 (brs, 1 H). 13C NMR (125
+
MHz; CDCl
1
4
3
) 20.2, 25.0, 31.0, 33.4, 46.4, 55.9, 63.4, 126.7, 127.4,
S: C,
8.26; H, 5.67; N, 7.50. Found: C, 48.30; H, 5.59; N, 7.61.
19 2
(positive ion) calcd for C13H N S [1 + H] 235.1264; found
28.4, 140.7, 171.9, 197.0. Anal. Calcd for C15
H21BrN O
2 2
7 5 3
235.1268; (negative ion) calcd for C H O 137.0244; found
137.0241.
J. Org. Chem, Vol. 72, No. 3, 2007 969