A. Lattanzi, A. Russo / Tetrahedron 62 (2006) 12264–12269
12267
overnight, the reaction was quenched with saturated ammo-
nium chloride solution (50 mL) extracted with CHCl3
4.3. General procedure for the hydrolysis of carbamates
to (S)-diaryl-2-pyrrolidinemethanols 2
(
3ꢃ50 mL). The combined organic layer was washed with
brine and dried over anhydrous sodium sulfate and concen-
trated under reduced pressure. Purification by flash chroma-
tography typically eluting with mixtures of PE/ethyl acetate
A solution of 1 (2.2 mmol), KOH (2.4 g, 43 mmol), EtOH
ꢁ
(10 mL) and H O (2.0 mL) was heated overnight at 80 C
2
(in some examples up to two days time was necessary to
complete conversion of starting material as assessed by
TLC analysis). After cooling to room temperature, EtOH
was removed under reduced pressure, and the aqueous layer
9
0/10 to 50/50 afforded the corresponding carbamate 1.
4
.2.1. Carbamate 1d. Compound 1d was obtained in 48%
2
4
yield as white gum; [a] ꢂ118.1 (c 1.25, CHCl ); nmax/
was extracted with CHCl (3ꢃ50 mL). The combined or-
D
3
3
ꢂ1
cm 2945, 1743, 1463, 1209, 798, 750; dH (400 MHz,
CDCl ) 7.36 (1H, d, J¼8.5 Hz), 6.94 (1H, d, J¼8.5 Hz),
ganic layer was washed with brine and dried over anhydrous
sodium sulfate and concentrated under reduced pressure. Pu-
rification by flash chromatography typically eluting with
mixtures of PE/ethyl acetate 80/20 to pure ethyl acetate
afforded compounds 2.
3
6
.51–6.43 (3H, m), 6.39–6.34 (1H, m), 4.53 (1H, dd,
J¼9.6, 6.6 Hz), 3.82 (3H, s), 3.78 (3H, s), 3.74 (3H, s),
3
2
1
1
9
.73 (3H, s), 3.67–3.59 (1H, m), 3.30–3.22 (1H, m), 2.09–
.00 (1H, m), 1.98–1.89 (1H, m), 1.75–1.68 (1H, m),
.50–1.42 (1H, m); dC (100 MHz, CDCl ) 160.6, 159.8,
4.3.1. Bis(2,4-dimethoxyphenyl)((S)-pyrrolidin-2-yl)me-
thanol 2d. Compound 2d was obtained in 25% yield as yel-
3
57.6, 129.7, 128.3, 124.1, 120.6, 103.9, 103.5, 99.1,
9.0, 86.7, 69.4, 55.4, 55.2, 55.1, 44.9, 28.0, 25.9; MS
2
4
ꢂ1
low gum; [a]D ꢂ83.5 (c 1.08, CHCl ); nmax/cm 3463,
3
+
+
+
(
ESI , m/z): 422 [(M+Na ), 28%], 438 [(M+K ), 35%],
2938, 1462, 1209, 1031, 833, 754; d (400 MHz, CDCl )
H
3
+
4
C, 66.15; H, 6.31; N, 3.51. Found: C, 66.29; H, 6.20; N,
3
00 [(M+H ), 20%]; Anal. Calcd (%) for C H NO :
7.67 (1H, d, J¼8.7 Hz), 7.54 (1H, d, J¼8.7 Hz), 6.56–6.51
(1H, m), 6.49–6.45 (1H, m), 6.36–6.25 (2H, m), 5.13 (1H,
t, J¼8.4 Hz), 3.75 (3H, s), 3.73 (3H, s), 3.63 (3H, s), 3.51
2
2
25
6
.42.
(3H, s), 3.09–3.00 (2H, m), 1.91–1.76 (3H, m), 1.58–1.55
4
.2.2. Carbamate 1e. Compound 1e was obtained in 59%
(1H, m); d (100 MHz, CDCl ) 160.1, 157.6, 156.5, 131.4,
C 3
2
4
yield as dark yellow gum; [a] ꢂ134.3 (c 1.06, CHCl );
129.6, 127.8, 127.6, 124.4, 123.1, 104.3, 103.7, 99.8, 99.1,
76.9, 62.0, 55.7, 55.4, 55.2, 47.4, 26.8, 25.2; MS (ESI ,
D
3
ꢂ1
+
nmax/cm 2940, 1749, 1418, 1128, 756; dH (400 MHz,
+
CDCl ) 6.73 (2H, s), 6.58 (2H, s), 4.47 (1H, dd, J¼10.5,
m/z): 374 [(M+H ), 18%], 356 [(Mꢂ17), 100%]; Anal.
3
5
3
1
.4 Hz), 3.84 (12H, s), 3.83 (6H, s), 3.80–3.71 (1H, m),
.30–3.25 (1H, m), 2.06–1.98 (1H, m), 1.93–1.86 (1H, m),
.79–1.73 (1H, m), 1.25–1.15 (1H, m); dC (100 MHz,
Calcd (%) for C H NO : C, 67.54; H, 7.29; N, 3.75.
2
1
27
5
Found: C, 67.68; H, 7.20; N, 3.61.
CDCl ) 160.3, 153.2, 153.0, 138.7, 138.1, 137.3, 135.6,
3
4.3.2. Bis(3,4,5-trimethoxyphenyl)((S)-pyrrolidin-2-yl)-
methanol 2e. Compound 2e was obtained in 83% yield as
1
2
3
03.6, 102.8, 85.8, 77.3, 69.3, 60.8, 56.3, 56.2, 46.1, 29.0,
4.8; MS (ESI , m/z): 498 [(M+K ), 12%], 460 [(M+H ),
5%]; Anal. Calcd (%) for C H NO : C, 62.73; H, 6.36;
+
+
+
23
ꢂ1
yellow gum; [a]D ꢂ60.3 (c 1.17, CHCl ); nmax/cm
3
3450, 2940, 1458, 1128, 756; d (400 MHz, CDCl ) 6.81
H 3
2
4
29
8
N, 3.05. Found: C, 62.60; H, 6.49; N, 3.14.
(2H, s), 6.73 (2H, s), 4.14 (1H, t, J¼7.8 Hz), 3.85 (6H, s),
.84 (6H, s), 3.80 (6H, s), 3.04–2.90 (2H, m), 1.77–1.53
(4H, m); d (100 MHz, CDCl ) 152.9, 152.7, 143.5, 140.7,
3
4
.2.3. Carbamate 1f. Compound 1f was obtained in 65%
C
3
2
5
yield as yellow gum; [a] ꢂ82.2 (c 1.0, CHCl ); nmax/
136.7, 136.5, 103.7, 103.2, 102.8, 72.9, 64.8, 60.7, 56.2,
D
3
ꢂ1
+
+
cm 2963, 1749, 1476, 1248, 754; d (400 MHz, CDCl )
H
56.1, 46.6, 26.4, 25.3; MS (ESI , m/z): 434 [(M+H ),
10%], 416 [(Mꢂ17), 100%]; Anal. Calcd (%) for
C H NO : C, 63.73; H, 7.21; N, 3.23. Found: C, 63.62,
3
7
(
5
.38 (2H, d, J¼1.4 Hz), 7.35–7.33 (1H, m), 7.30–7.28
1H, m), 7.24 (2H, d, J¼1.4 Hz), 4.48 (1H, dd, J¼10.5,
.3 Hz), 3.77–3.70 (1H, m), 3.26–3.20 (1H, m), 2.01–1.95
2
3
31
7
H, 7.30; N, 3.15.
(
(
1H, m), 1.94–1.85 (1H, m), 1.84–1.74 (1H, m), 1.29
36H, s), 1.16–1.10 (1H, m); d (100 MHz, CDCl ) 160.9,
4.3.3. Bis(3,5-di-tert-butylphenyl)((S)-pyrrolidin-2-yl)-
methanol 2f. Compound 2f was obtained in 48% yield as
C
3
1
1
50.7, 150.4, 143.4, 139.6, 122.1, 122.0, 121.0, 119.7,
19.6, 86.8, 70.7, 45.9, 34.9, 31.4, 29.3, 24.8; MS (ESI ,
+
22
ꢂ1
yellow gum; [a]D ꢂ58.2 (c 1.01, CHCl ); nmax/cm
3
+
+
m/z): 526 [(M+Na ), 12%], 504 [(M+H ), 35%]; Anal.
Calcd (%) for C H NO : C, 81.06; H, 9.80; N, 2.78.
Found: C, 81.18; H, 9.68; N, 2.66.
3417, 2963, 1392, 1248, 757; d (400 MHz, CDCl ) 7.52
H 3
(2H, d, J¼1.4 Hz), 7.35 (2H, d, J¼1.4 Hz), 7.26 (1H, s),
3
4
49
2
7.18 (1H, s), 4.73 (1H, t, J¼7.8 Hz), 2.33–2.27 (1H, m),
2.25–2.15 (1H, m), 1.94–1.88 (1H, m), 1.75–1.55 (3H, m),
4
.2.4. Carbamate 1g. Compound 1g was obtained in 84%
1.32 (18H, s), 1.24 (18H, s); d (100 MHz, CDCl ) 150.7,
C 3
2
4
yield as yellow gum; [a] ꢂ168.8 (c 1.54, CHCl ); nmax/
150.4, 143.1, 142.4, 122.1, 120.5, 119.9, 119.2, 78.2, 66.2,
46.2, 35.0, 34.9, 31.6, 26.6, 24.7; MS (ESI , m/z): 478
D
3
ꢂ1
+
cm 2947, 1752, 1484, 1227, 1012, 756; dH (400 MHz,
CDCl ) 7.14 (2H, s), 6.98 (2H, s), 4.50 (1H, dd, J¼10.5,
+
[(M+H ), 100%], 460 [(Mꢂ17), 60%]; Anal. Calcd (%)
3
5
.5 Hz), 3.75–3.68 (1H, m), 3.69 (6H, s), 3.26–3.20 (1H,
for C H NO: C, 82.96; H, 10.76; N, 2.93. Found: C,
3 51
3
m), 2.27 (6H, s), 2.25 (6H, s), 2.01–1.94 (1H, m), 1.93–
.82 (1H, m), 1.70–1.55 (1H, m), 1.14–1.07 (1H, m); dC
100 MHz, CDCl ) 160.7, 156.7, 156.1, 138.6, 135.6,
82.85; H, 10.66; N, 2.85.
1
(
4.3.4. Bis(3,5-dimethyl-4-methoxyphenyl)((S)-pyrrol-
idin-2-yl)methanol 2g. Compound 2g was obtained in
3
1
1
1
7
30.8, 130.6, 126.2, 125.7, 85.5, 59.6, 46.0, 28.9, 24.7,
+
+
+
25
6.3; MS (ESI , m/z): 434 [(M+K ), 15%], 396 [(M+H ),
00%]; Anal. Calcd (%) for C H NO : C, 72.89; H,
.39; N, 3.54. Found: C, 72.73; H, 7.27; N, 3.44.
81% yield as pale yellow gum; [a]D ꢂ48.1 (c 1.15,
ꢂ1
CHCl ); nmax/cm 3446, 2946, 1484, 1224, 1136, 756; dH
3
2
4
29
4
(400 MHz, CDCl ) 7.18 (2H, s), 7.09 (2H, s), 4.18 (1H, t,
3