PAPER
Boronic Acid Mannich Reactions of a,a-Dichloro- and a,a,w-Trichloroaldehydes
439
1
13
H NMR (250 MHz, CDCl ): d = 0.86 (d, J = 6.6 Hz, 3 H,
C NMR (62.90 MHz, CDCl ): d = 14.8 (OCH CH ), 26.5
3 2 2 2 3 2
3
3
2
3
CH CHCH ), 1.04 (d, J = 7.0 Hz, 3 H, CH CHCH ), 2.28–2.48 (m,
(CH CO), 52.0 (CH –N–CH ), 63.5 (OCH CH ), 66.8 (CH –O–
3
3
3
3
4
H, CH –N–CH ), 2.70 [sept, J = 6.8 Hz, 1 H, (CH ) CH)], 3.70–
CH ), 81.5 (CHN), 114.9 (Co-Ar), 126.3 (Cquat-Ar), 130.2 (Cm-Ar),
2
2
3 2
2
3
.74 (m, 4 H, CH –O–CH ), 4.10 (s, 1 H, CHN), 7.22–7.37 (m, 5 H,
159.2 (Cquat-Ar–OC H ), 206.7 (CO).
2
2
2
5
C H ).
+
6
5
MS (EI, 70 eV): m/z (%) = 263 (0.5) [M ], 220 (100), 192 (77), 177
1
3
C NMR (62.90 MHz, CDCl ): d = 19.3 and 18.1 [(CH ) CH], 38.6
(5), 121 (56), 107 (52), 103 (35), 91 (33), 78 (29), 77 (51).
3
3 2
[
(CH ) CH], 52.1 (CH –N–CH ), 66.8 (CH –O–CH ), 79.8 (CHN),
3 2 2 2 2 2
Anal. Calcd for C H NO : C, 68.42; H, 8.04; N, 5.32. Found: C,
1
5
21
3
1
28.6 (Cp-Ar), 128.8 (Cm-Ar), 129.7 (Co-Ar), 134.4 (Cquat-Ar), 211.4
6
8.60; H, 7.99; N, 5.35.
(
CO).
MS (EI, 70 eV): m/z (%) = 247 (0.3) [M ], 176 (100), 117 (43), 105
59), 103 (25), 91 (64), 89 (31), 79 (10), 77 (37), 65 (28), 63 (11),
4 (16), 51 (12).
Anal. Calcd for C H NO : C, 72.84; H, 8.56; N, 5.66. Found: C,
+
1-Morpholino-1-(4-tolyl)propan-2-one (4ac)
Yield: 304 mg (44%), 85 mg (12%); yellow oil; R = 0.17 (EtOAc–
(
5
f
hexane, 3:7).
–
1
IR (ATR): 1712 (CO), 1511, 1451 (C=C) cm .
15
21
2
7
2.92; H, 8.42; N, 5.75.
1
H NMR (250 MHz, CDCl ): d = 2.09 (s, 3 H, CH CO), 2.34 (s, 3
3
3
H, Cquat-ArCH ), 2.36–2.46 (m, 4 H, CH –N–CH ), 3.74 (t, J = 4.7
Hz, 4 H, CH –O–CH ), 3.87 (s, 1 H, CHN), 7.16 (d, J = 8.0 Hz, 2
H, CHm-Ar), 7.27 (d, J = 8.0 Hz, 2 H, CHo-Ar).
1
3
2
2
1
-Morpholino-1-phenylheptan-2-one (4d)
2
2
Yield: 593 mg (54%), 269 mg (24%); yellow oil; R = 0.18 (EtOAc–
f
hexane, 2:8).
3
C NMR (62.90 MHz, CDCl ): d = 21.1 (C
3 2 2 2 2
–CH ), 26.5
3
–
1
3
quat-Ar
IR (ATR): 1713 (CO), 1492, 1450 (C=C) cm .
(
CH CO), 52.1 (CH –N–CH ), 66.8 (CH –O–CH ), 81.9 (CHN),
1
H NMR (250 MHz, CDCl ): d = 0.81 (t, J = 7.0 Hz, 3 H, CH ),
129.0 (Cm-Ar), 129.6 (Co-Ar), 131.6 (Cquat-Ar–CH ), 138.4 (Cquat-Ar),
206.7 (CO).
3
3
3
1
.06–1.26 [m, 3 × 2 H, CH (CH ) CH CO], 1.38–1.51 (m, 2 H,
2
3
2 3
2
CH CO), 2.37–2.44 (m, 4 H, CH –N–CH ), 3.74 (t, J = 4.7 Hz, 4 H,
CH –O–CH ), 3.94 (s, 1 H, CHN), 7.27–7.43 (m, 5 H, C H ).
+
2
2
MS (EI, 70 eV): m/z (%) = 233 (0.5) [M ], 190 (100), 146 (6), 131
(
(52), 65 (32).
2
2
6
5
32), 130 (39), 119 (68), 117 (56), 105 (71), 103 (58), 91 (56), 71
1
3
C NMR (62.90 MHz, CDCl ): d = 13.8 (CH ), 22.3 (CH CH ),
3
3
3
2
2
3.5 (CH CH CH ), 31.2 (CH CH CO), 39.5 (CH CO), 52.1 (CH –
3 2 2 2 2 2 2
Anal. Calcd for C H NO : C, 72.07; H, 8.21; N, 6.00. Found: C,
7
1
4
19
2
N–CH ), 66.8 (CH –O–CH ), 81.7 (CHN), 128.5 (Cp-Ar), 128.9
2
2
2
1.81; H, 8.9; N, 5.94.
(
Cm-Ar), 129.3 (Co-Ar), 134.7 (Cquat-Ar), 208.5 (CO).
+
MS (70 eV): m/z (%) = 275 (0.90) [M ], 176 (100), 117 (35), 105
1-(4-Chlorophenyl)-1-morpholinopropan-2-one (4ad)
(
(
55), 103 (20), 91 (60), 89 (20), 79 (22), 77 (25), 71 (7), 65 (18), 57
7), 56 (10), 54 (14).
Yield: 114 mg (18%), 11 mg (2%); yellow oil; R = 0.15 (EtOAc–
hexane, 3:7).
f
–
1
Anal. Calcd for C H NO : C, 74.14; H, 9.15; N, 5.09. Found: C,
IR (ATR): 1716 (CO), 1487, 1452 (C=C) cm .
17
25
2
7
4.25; H, 9.24; N, 4.91.
1
H NMR (250 MHz, CDCl ): d = 2.10 (s, 3 H, CH ), 2.33–2.45 (m,
3
3
4
1
H, CH –N–CH ), 3.74 (t, J = 4.6 Hz, 4 H, CH –O–CH ), 3.89 (s,
2
2
2
2
1
-(2,5-Dimethoxyphenyl)-1-morpholinopropan-2-one (4aa)
H, CHN), 7.34 (s, 4 H, C H ).
6
4.
Yield: 564 mg (50%), 156 mg (14%); yellow oil; R = 0.12 (EtOAc–
f
1
3
C NMR (62.90 MHz, CDCl ): d = 26.3 (CH ), 52.0 (CH –N–
hexane, 4:6).
3
3
2
CH ), 66.8 (CH –O–CH ), 81.5 (CHN), 129.2 (Co-Ar), 130.3 (Cm-Ar),
1
–
1
2
2
2
IR (ATR): 1718 (CO), 1498, 1451 (C=C) cm .
33.2 (Cquat-Ar), 134.6 (Cquat-Ar–Cl), 206.2 (CO).
1
H NMR (250 MHz, CDCl ): d = 2.05 (s, 3 H, CH CO), 2.44 (t,
+
+
3
3
MS (EI, 70 eV): m/z (%) = 255 (trace) [M + 2] , 253 (0.3) [M ], 210
(
(
J = 4.6 Hz, 4 H, CH –N–CH ), 3.76–3.71 (m, 4 H, CH –O–CH ),
2
2
2
2
100), 166 (6), 141 (11), 139 (54), 127 (26), 125 (59), 103 (58), 89
43), 77 (23).
3
.76 (s, 3 H, Cquat-Ar–OCH ), 3.82 (s, 3 H, Cquat-Ar–OCH ), 4.57 (s, 1
3
3
H, COCH), 6.84, 6.92 (2 × d, J = 2.7 Hz, 2 × 1 H, CHarom.), 6.85 (s,
1
Anal. Calcd for C H ClNO : C, 61.54; H, 6.36; N, 5.52. Found: C,
6
H, CH ).
13 16
2
arom.
1.32; H, 6.30; N, 5.61.
1
3
C NMR (62.90 MHz, CDCl ): d = 27.7 (CH CO), 51.6 (CH –N–
3
3
2
CH ), 55.8 (OCH ), 56.1 (OCH ), 66.9 (CH –O–CH ), 72.6 (CHN),
1
2
3
3
2
2
1
-Cyclopropyl-2-morpholino-2-phenylethanone (15)
12.3 (Carom.), 114.5 (Carom.), 115.0 (Carom.), 123.5 (Cquat-Ar), 152.2
Yield: 192 mg (20%), 100 mg (10%); pale yellow oil; R = 0.25
f
(
Cquat-Ar–CH ), 153.9 (C
–CH ), 205.8 (CO).
3
quat-Ar
3
(
EtOAc–hexane, 3:7).
+
MS (EI, 70 eV): m/z (%) = 279 (1) [M ], 236 (100), 220 (40), 206
IR (ATR): 1694 (CO), 1450 (C=C) cm–1.
1
(
(
42), 162 (41), 148 (33), 136 (35), 118 (30), 85 (52), 77 (34), 65
33).
H NMR (250 MHz, CDCl ): d = 0.75–1.07 [m, 4 H, 2 ×
3
(
CH ) CH], 2.30–2.40 [m, 1 H, (CH ) CH], 2.46 (t, J = 4.6 Hz, 4 H,
2
2
2 2
Anal. Calcd for C H NO : C, 64.50; H, 7.58; N, 5.01. Found: C,
6
15
21
4
CH –N–CH ), 3.76 (t, J = 4.6 Hz, 4 H, CH –O–CH ), 4.01 (s, 1 H,
CHN), 7.27–7.45 (m, 5 H, C H ).
2
2
2
2
4.26; H, 7.63; N, 5.05.
6
5
1
3
C NMR (62.90 MHz, CDCl ): d = 11.3 and 12.3 [(CH ) CH], 29.7
1
-(4-Ethoxyphenyl)-1-morpholinopropan-2-one (4ab)
3
2 2
[
1
(
(CH ) CH], 52.1 (CH –N–CH ), 66.9 (CH –O–CH ), 82.3 (CHN),
28.3 (Cp-Ar), 128.8 (Cm-Ar), 129.1 (Co-Ar), 135.1 (Cquat-Ar), 208.8
CO).
Yield: 401 mg (63%), 148 mg (23%); yellow oil; R = 0.12 (EtOAc–
hexane, 3:7).
2 2
2 2 2 2
f
–
1
IR (ATR): 1708 (CO), 1608, 1508 (C=C) cm .
+
MS (EI, 70 eV): m/z (%) = 245 (2) [M ], 178 (18), 176 (100), 118
(
(
1
H NMR (250 MHz, CDCl ): d = 1.41 (t, J = 7.0 Hz, 3 H,
3
2), 117 (10), 115 (2), 105 (25), 103 (5), 92 (2), 91 (32), 89 (6), 79
4), 77 (7), 69 (7), 65 (5), 63 (2), 54 (3), 51 (3).
OCH CH ), 2.09 (s, 3 H, CH CO), 2.31–2.43 (m, 4 H, CH –N–
2
3
3
2
CH ), 3.73 (t, J = 4.6 Hz, 4 H, CH –O–CH ), 3.84 (s, 1 H, CHN),
4
CHo-Ar), 7.28 (d, J = 8.6 Hz, 2 H, CHm-Ar).
2
2
2
Anal. Calcd for C H NO : C, 73.44; H, 7.81; N, 5.71. Found: C,
7
.02 (q, J = 7.0 Hz, 2 H, OCH CH ), 6.87 (d, J = 8.6 Hz, 2 H,
15 19
2
2
3
3.50; H, 7.76; N, 5.75.
Synthesis 2007, No. 3, 433–441 © Thieme Stuttgart · New York