Wang et al.
JOCArticle
leading to a bis-tertiary amine product by exhaustive reduc-
tion is shown as an outlook.
29.3, 29.9, 33.9, 38.0, 39.8, 43.9, 53.5, 54.7, 55.4, 55.7, 60.4, 67.8,
76.9, 77.1, 77.3, 101.8, 110.4, 120.6, 127.2, 127.9, 130.4, 157.5,
173.5, 177.4.
Compound 29: C20H30N2O5, Mw 378.46 g/mol; HRMS (ESI-
TOF) m/z calcd for C20H30N2O5Na 401.2052, found 401.2081; 1H
NMR (CDCl3, 600 MHz) δ 1.49 (3H, s), 1.56-1.58 (1H, m), 1.65
(3H, m), 2.24 (1H, m), 2.37 (2H, m), 2.81 (1H, m), 2.89 (1H, m),
3.09 (1.0H, dd, J=6.09, 13.95 Hz), 3.38 (3H, s), 3.42 (3H, s), 3.62
(1H, m), 3.85 (3H, s), 5.00 (1H, d, J=11.04 Hz), 6.87 (1H, d, J =
8.16 Hz), 6.90 (1H, d, J=14.76 Hz), 6.90 (1H, t, J=7.38 Hz), 7.13
(1H, dd, J=1.41, 7.35 Hz), 7.22 (1H, dt, J=1.50, 7.80 Hz), 7.30
(1H, w); 13C NMR (CDCl3, 150.92 MHz) δ 17.2, 24.6, 30.0, 32.7,
36.5, 39.9, 47.8, 55.4, 55.6, 56.0, 66.7, 76.8, 77.0, 77.2, 102.8, 110.4,
127.3, 127.9, 130.4, 157.6, 172.9, 173.5.
Compound 30: C22H26N2O5, Mw 398.45 g/mol; HRMS (ESI-
TOF) m/z calcd for C22H26N2O5Na 421.1739, found 421.1747; 1H
NMR (CDCl3, 600 MHz) δ 2.64-2.81 (2H, m), 3.19 (1H, s),
3.25(1H, s), 3.26(1H, s), 3.27 (2H, m), 3.37(3H, s) 3.38(3H, s),
3.44-3.48 (2H, m), 3.78 (2H, s), 3.83-3.88(2H, m), 4.73-
4.78(1H, m), 5.16 (1H, s), 6.52 (1H, s), 6.79 (2H, dd, J=7.73,
15.27 Hz), 6.83-6.93 (3H, m), 7.16(1H, d, J=17.34 Hz), 7.24 (1H,
m), 7.53 (2H, dd, J=7.41, 14.91 Hz), 7.58 (2H, dt, J = 1.10, 7.52
Hz), 7.68(1H, dd, J=0.60, 7.56 Hz), 7.84 (1H, d, J=7.44Hz);13C
NMR (CDCl3, 150.92 MHz) δ 29.5, 40.1, 44.0, 53.4, 55.4, 65.7,
102.0, 110.4, 120.7, 123.1, 123.6, 126.8, 128.0, 128.9, 130.5.
Compound 31: C23H28N2O5, Mw 412.49 g/mol; HRMS (ESI-
TOF) m/z calcd for C23H28N2O5Na 435.1896, found 435.1932;
HPLC-MS tR 10.39, m/z [M þ Na]þ 434.9, [M - H]- 411.1; 1H
NMR (CDCl3, 600 MHz) δ 1.72 (3H, s), 2.60 (1H, m), 2.76 (1H,
m), 3.19(1H, q, J=7.06Hz), 3.27 (1H, d, J=7.14 Hz), 3.32 (1H, s),
3.36 (3H, s), 3.47 (3H, s), 3.68 (1H, dd, J=4.47, 14.07 Hz), 3.73
(3H, s), 5.25 (1H, dd, J = 4.41, 7.05 Hz), 6.70 (2H, d, J=4.32 Hz),
6.75 (1H, d, J=8.16 Hz), 7.12 (1H, dd, J=4.23, 8.49 Hz), 7.50 (1H,
t,J=7.77Hz), 7.51 (1H, d, J = 6.84 Hz), 7.58 (1H, t, J= 7.50 Hz),
7.70 (1H, d, J=7.62 Hz), 7.81 (1H, d, J=7.50 Hz); 13C NMR
(CDCl3, 150.92 MHz) δ 14.2, 29.7, 39.8, 44.5, 55.1, 55.2, 56.1,
60.4, 101.9, 103.0, 110.2, 120.4,122.6, 123.3, 127.0, 127.7, 128.8,
129.4, 130.1, 130.4, 132.6, 148.0, 157.3, 169.8.
Compound 32: C18H26N2O4, Mw 334.41 g/mol; HRMS (ESI-
TOF) m/z calcd for C18H26N2O4Na 357.1790, found 357.1796; 1H
NMR (CDCl3, 600 MHz) δ 1.45 (3H, s), 1.90-1.95 (1H, m),
2.23-2.29 (3H, m), 2.79-2.84 (2H, m), 2.88 (1H, dd, J=6.36,
14.16 Hz), 3.35 (3H, s), 3.40 (3H, s), 3.53 (1H, dd, J=4.55, 14.01
Hz), 3.64 (1H, dt, J=6.71, 13.51 Hz), 4.93 (1.0H, dd, J=4.59, 6.33
Hz), 7.18 (2H, d, J=6.80 Hz), 7.21 (1H, t, J=7.41 Hz), 7.30 (2H, t,
J=7.53Hz), 7.43 (1H, w);13CNMR(CDCl3, 150.92 MHz) δ22.0,
29.3, 33.9, 35.4, 40.8, 43.9, 53.5, 54.8, 56.2, 67.9, 101.8, 126.5,
128.6, 128.7, 138.9, 173.6, 177.4.
Compound 33: C19H28N2O4, Mw 348.44 g/mol; HRMS (ESI-
TOF) m/z calcd for C19H28N2O4Na 371.1946, found 371.1937; 1H
NMR (CDCl3, 600 MHz) 1.48 (3H, s), 1.53-1.59 (1H, m),
1.63-1.67 (2H, m), 2.23-2.27 (1H, m), 2.34-2.37 (2H, m), 2.84
(2H, t, J=7.18 Hz), 2.97 (1H, dd, J = 6.45, 13.98 Hz), 3.35 (3H, s),
3.36-3.39 (1H, m), 3.42 (3H, s), 3.52 (1H, dd, J = 4.74, 13.98 Hz),
3.69 (1H, dt, J =6.80, 6.73 Hz), 5.04 (1H, dd, J=4.83, 6.33 Hz),
7.20 (2H, d, J=7.68 Hz), 7.23 (1H, d, J=7.20 Hz), 7.31 (2H, t, J=
7.52 Hz), 7.50 (1H, s); 13C NMR (CDCl3, 150.92 MHz) δ 17.2,
24.4, 32.7, 35.5, 36.5, 41.0, 47.9, 55.7, 56.5, 66.8, 102.9, 126.5,
128.6, 128.7, 139.0, 173.0, 173.6.
Experimental Section
General Procedure for Ugi Reaction. A 1 mmol portion of
aldehyde or ketone acid was dissolved in 1 mL of MeOH, and
1 mmol of isocyanide and 1 mmol of amino acetal were added
into the solution. The solution was stirred for 24 h at rt. The
MeOH solvent was evaporated, and the residue was purified by
SiO2 column chromatography to give the Ugi product.
Compound 24: C20H30N2O6, Mw 394.45 g/mol; HRMS (ESI-
TOF) m/z calcd for C20H29N2O6Na 417.2002, found 417.2020; 1H
NMR (CDCl3, 600 MHz) δ 1.46 (3H, s), 1.95 (1H, m, J=4.78 Hz),
2.19 (1.0H, d, J=11.71 Hz), 2.28 (3H, m, J=5.06 Hz), 2.62 (1H, t,
J=6.42 Hz), 2.77 (2H, t, J=6.97 Hz), 2.90 (1H, dd, J=6.33, 14.19
Hz), 3.36 (1H, m, J=7.37 Hz), 3.40 (3H, s), 3.42 (3H, s), 3.55 (1H,
dd, J=4.52, 14.06 Hz), 3.59 (1H, dt, J=7.06, 6.77 Hz), 3.86 (3H,
s), 3.88 (3H, s), 4.94 (1H, dd, J=4.77, 6.25 Hz), 6.72 (1H, d, J=
7.62 Hz), 6.73 (1H, s), 6.81 (1H, d, J=7.86 Hz), 7.44 (1H, t, J=5.10
Hz); 13C NMR (CDCl3, 150.92 MHz) δ22.0, 29.3, 34.0, 35.1, 41.0,
43.9, 54.9, 55.8, 55.9, 56.1, 67.9, 101.9, 111.2, 111.7, 120.6, 131.3,
147.7, 149.0, 173.7, 177.5.
Compound 25: C21H32N2O6, Mw 408.49 g/mol; HRMS (ESI-
TOF) m/z calcd for C21H32N2O6Na 431.2158, found 431.2169; 1H
NMR (CDCl3, 600 MHz) δ 1.49 (3H, s), 1.67 (1H, m), 2.18 (2H,
m), 2.26 (1H, m), 2.36 (2H, m), 2.77 (2H, m), 3.00 (1H, m), 3.41
(6H, m), 3.49 (1H, m), 3.61 (2H, m), 3.86 (6H, m), 5.03 (1H, m),
6.72 (2H, m), 6.80 (1.0H, t, J=7.18 Hz), 7.44 (1H, s); 13C NMR
(CDCl3, 150.92 MHz) δ 17.2, 24.5, 30.9, 32.7, 35.1, 36.5, 39.3,
41.1, 47.9, 53.4, 55.7, 55.8, 55.9, 56.5, 66.8, 103.0, 111.2, 111.3,
111.8, 120.6, 131.4, 147.7, 149.0, 173.0, 173.6.
Compound 26: C23H28N2O6, Mw 428.48 g/mol; HRMS (ESI-
TOF) m/z calcd for C23H28N2O6Na 451.1845, found 451.1810; 1H
NMR (CDCl3, 600 MHz) δ 2.69 (2H, m), 3.09-3.21 (1H, m), 3.27
(1.0H, m), 3.32-3.45 (6H, m), 3.75 (3H, s), 3.80 (3H, s), 4.69 (1H,
t, J=5.49 Hz), 5.15 (1H, s), 6.52 (1H, d, J=7.92 Hz), 6.58 (1H, s),
6.66 (1H, d, J=8.10 Hz), 7.03 (1H, w), 7.38 (1H, t, J=7.35 Hz),
7.51 (1H, t, J=7.50 Hz), 7.57 (1H, d, J=7.50 Hz), 7.62 (1H, d, J=
7.56 Hz); 13C NMR (CDCl3, 150.92 MHz) δ 14.2, 34.8, 40.8, 44.0,
54.5, 54.7, 55.7, 55.8, 65.7, 102.0, 111.2, 111.7, 120.6, 122.9, 123.4,
128.8, 130.3, 130.9, 132.4, 141.7, 147.6, 148.9, 167.8, 170.1.
Compound 27: C24H30N2O6, Mw 442.50 g/mol; HRMS (ESI-
TOF) m/z calcd for C24H30N2O6Na 465.2002, found 465.2023;
HPLC-MS tR 9.72, found m/z [M þ Na]þ464.9, [M - H]- 441; 1H
NMR (CDCl3, 600 MHz) δ 1.71 (3H, s), 1.81 (3H, s), 2.36 (1H, s),
2.60-2.63 (2H, m), 3.16 (1H, dd, J=7.20, 14.10 Hz), 3.24-3.27
(1H, m), 3.31 (3.0H, s), 3.39 (3H, s), 3.46-3.48(1H, m), 3.49 (3H,
s), 3.71 (1H, dd, J=4.49, 14.03 Hz), 4.39 (0.7H, t, J=5.29 Hz),
5.30-5.34 (2H, m), 6.42 (1H, dd, J=1.81, 8.04 Hz), 6.54 (1H, d,
J = 1.68 Hz), 6.64 (1H, d, J = 8.31 Hz), 7.17 (1H, q, J = 6.92 Hz),
7.26 (1H, t, J=6.84 Hz), 7.46 (1H, d, J=16.02 Hz), 7.50 (2H, dd,
J=4.08, 6.72 Hz), 7.52-7.57 (2H, m), 7.68 (1H, dd, J=1.05, 7.46
Hz), 7.71 (1H, d, J=7.62 Hz), 7.78 (1H, d, J=7.44 Hz), 7.87 (1H,
d, J=7.93 Hz); 13C NMR (CDCl3, 150.92 MHz) δ 22.1, 27.4, 34.9,
41.1, 43.3, 44.6, 53.4, 53.6, 55.3, 55.7, 55.9, 56.6, 69.9, 101.1, 102.1,
103.0, 111.1, 111.6, 120.6, 122.3, 122.6, 123.3, 125.3, 125.5, 127.8,
128.2, 128.8, 129.0, 129.3, 130.1, 131.2, 132.7, 134.3, 147.5, 147.8,
148.8, 149.4, 169.0, 170.0, 170.5.
Compound 34: C21H24N2O4, Mw 368.43 g/mol; HRMS (ESI-
TOF) m/z calcd for C21H24N2O4Na 391.1634, found 391.1646;
1H NMR (CDCl3, 600 MHz) δ 2.69-2.78 (2H, m), 3.25 (1H, d,
J=6.42 Hz), 3.37 (3H, s), 3.40 (3H, s), 3.54 (1H, ddd, J=6.43,
0.03, 13.24 Hz), 3.74 (1H, dd, J=5.31, 14.31 Hz), 4.82 (1H, t,
J=5.43 Hz), 5.15 (1H, s), 6.56 (1H, w), 6.95 (2H, dd, J=1.71,
7.29 Hz), 7.18 (2H, d, J=7.14 Hz), 7.53 (1H, t, J=7.55 Hz), 7.61
(1H, dt, J=0.75, 3.75 Hz), 7.71 (1H, d, J=7.62 Hz), 7.82 (1H, d,
J=7.50 Hz); 13C NMR (CDCl3, 150.92 MHz) δ 35.2, 40.7, 44.6,
Compound 28: C19H28N2O5, Mw 364.44 g/mol; HRMS (ESI-
TOF) m/z calcd for C19H28N2O5Na 387.1896, found 387.1914;
1H NMR (CDCl3, 600 MHz) δ 1.45 (3H, s), 1.90 (1H, m), 2.26
(3H, m), 2.83 (2H, m, J=6.97 Hz), 2.94 (1H, dd, J=6.30, 14.16
Hz), 3.50 (1H, dd, J = 4.56, 14.16 Hz), 3.59 (1H, q, J=6.54 Hz),
4.87 (1H, dd, J = 4.71, 6.15 Hz), 6.86 (1H, d, J=8.22 Hz), 6.88
(1H, dt, J=0.75, 7.40 Hz), 7.10 (1H, d, J=7.32 Hz), 7.20 (1H, dt,
J=1.44, 7.80 Hz); 13C NMR (CDCl3, 150.92 MHz) δ 22.1, 27.6,
642 J. Org. Chem. Vol. 76, No. 2, 2011