Synthesis of Sterically Constrained R,R-Disubstituted R-Amino Acids
Ni(II) Com p lex of r,r-Diben zylglycin e Sch iff Ba se
(1H, m), 7.43-7.52 (5H, m), 7.91 (1H, m), 8.01 (1H, m), 8.24
1
13
w ith P ABP (13b): R
f
) 0.62; mp 295.2-296.6 °C; H NMR δ
.78 (2H, d, J ) 15.9 Hz), 3.37 (2H, d, J ) 15.9 Hz), 6.65-
.67 (2H, m), 6.82-6.85 (2H, m), 6.96-7.02(2H, m), 7.20-7.34
(1H, d, J ) 4.8 Hz), 8.93 (1H, d, J ) 8.1 Hz); C NMR δ 9.7,
2
6
(
28.4, 72.0, 121.1, 123.2, 123.8, 126.5, 126.7, 126.7, 127.5, 128.5,
128.9, 129.5, 133.1, 133.6, 134.2, 140.2, 142.7, 146.6, 153.0,
169.6, 171.5, 179.0; HRMS [M + Na ] calcd for C23
+
12H, m) 7.50 (1H, m), 7.75 (1H, m), 7.82-7.92 (2H, m), 8.52
H
19
N
3
-
1
3
(
1H, m); C NMR δ 30.88, 82.70, 120.95, 122.94, 123.46,
3
NaNiO 467.0986, found 467.2276.
1
1
1
25.86, 126.26, 127.22, 127.40, 127.70, 128.01, 128.28, 128.67,
29.35, 129.59, 132.37, 134.17, 135.70, 136.40, 139.42, 142.13,
46.59, 152.75, 168.70, 171.53, 178.48; HRMS [M + H ] calcd
Ni(II) Com p lex of r,r-Di-n -p r op ylglycin e Sch iff Ba se
1
w ith P ABP (13e): R ) 0.63; mp 282.5-283.3 °C; H NMR δ
f
+
0.91 (6H, t, J ) 7.5 Hz), 1.35-1.45 (2H, m), 1.57-1.95 (6H,
m), 6.69-6.74 (2H, m), 7.19-7.23 (2H, m), 7.30 (1H, m), 7.41-
7.56 (4H, m), 7.89 (1H, m), 7.98 (1H, m), 8.38 (1H, m), 8.70
(1H, m); 13C NMR δ 14.27, 18.62, 42.32, 83.78, 121.51, 123.93,
123.97, 127.02, 127.79, 127.84, 129.13, 129.93, 132.87, 134.67,
36 30 3 3
C H N NiO 597.3014, found 597.1463.
Ni(II) Com p lex of 2-Am in o-3-p h en ylp r op ion ic Acid
Sch iff Ba se w ith P ABP (14b): R ) 0.65; mp 262.7-264.0
C; H NMR δ 2.86, 3.13 (2H, ABX, J ) 13.5, 5.9, 3.2 Hz), 4.36
1H, dd, J ) 5.9, 3.2 Hz), 6.76-6.88 (3H, m), 7.13-7.26 (3H,
m), 7.28-7.42 (5H, m), 7.52-7.61 (3H, m), 7.68 (1H, m), 7.77
f
1
°
(
136.98, 140.57, 142.46, 147.44, 153.36, 170.12, 173.43; HRMS
+
[M + H ] calcd for C27
28 3 3
H N NiO 501.2158, found 501.1381.
(
1H, m), 7.90 (1H, m), 8.71 (1H, d, J ) 8.7 Hz); 13C NMR δ
Ni(II) Com p lex of 2-Am in op en ta n oic Acid Sch iff Ba se
1
4
1
1
0.1, 72.9, 121.3, 123.4, 123.5, 126.2, 127.0, 127.1, 127.3, 127.5,
28.0, 129.0, 129.2, 130.0, 131.0, 133.2, 133.5, 134.2, 135.6,
w ith P ABP (14e): R ) 0.63; mp 252.1-252.8 °C; H NMR δ
f
0.80 (3H, t, J ) 7.2 Hz), 1.57-1.69 (2H, m), 2.02 (1H, m), 2.17
(1H, m), 4.02 (1H, dd, J ) 8.4; 3.0 Hz), 6.75-6.81 (2H, m),
7.07 (1H, m), 7.32 (1H, m), 7.42-7.52 (5H, m), 7.91 (1H, m),
8.01 (1H, m), 8.23 (1H, d, J ) 5.4 Hz), 8.92 (1H, d, J ) 8.1
39.7, 143.0, 146.5, 153.0, 169.0, 171.0, 177.8; HRMS [M +
+
H ] calcd for C28
21 3 3
H N NaNiO 529.1680, found 529.0767.
Ni(II) Com plex of r,r-Di-(tr a n s)-cin n am ylglycin e Sch iff
1
13
Ba se w ith P ABP (13c): R
NMR δ 2.46 (2H, dd, J ) 15.2, 6.0 Hz), 2.73 (2H, dd, J ) 15.2,
.0 Hz), 6.63-6.76 (7H, m), 7.12-7.41 (13H, m), 7.49-7.58
f
) 0.79; mp 247.5-249.3 °C; H
Hz); C NMR δ 13.7, 18.4, 37.3, 70.9, 121.1, 123.2, 123.8,
126.5, 126.7, 126.8, 127.5, 128.5, 128.8, 129.5, 133.0, 133.6,
6
134.2, 140.2, 142.7, 146.6, 153.0, 169.6, 171.2, 179.1; HRMS
1
3
+
(4H, m), 7.76 (1H, m), 8.13 (1H, m) 8.61 (1H, m); C NMR δ
[M + H ] calcd for C24
H
22
N
3
NiO
3
459.1361, found 459.0934.
4
1
1
1
6
2.13, 83.56, 121.11, 123.22, 123.52, 123.74, 125.91, 126.15,
27.00, 127.52, 127.60, 128.15, 128.94, 129.68, 132.52, 134.04,
Ni(II) Com p lex of r,r-Di-n -bu tylglycin e Sch iff Ba se
1
w ith P ABP (13f): R ) 0.67; mp 221.7-222.5 °C; H NMR δ
f
34.10, 136.13, 136.72, 139.58, 142.22, 146.55, 152.42, 169.14,
0.93 (6H, t, J ) 7.4 Hz), 1.21-1.34 (4H, m), 1.39-1.49 (2H,
m), 1.59-1.87 (6H, m), 6.65-6.74 (2H, m), 7.19-7.23 (2H, m),
7.31 (1H, m), δ 7.42-7.55 (4H, m), 7.90 (1H, m), 7.99 (1H, m),
8.39 (1H, m), 8.72 (1H, m); 13C NMR δ 14.46, 23.10, 27.33,
40.20, 83.75, 121.49, 123.93, 123.96, 127.02, 127.79, 127.87,
129.12, 129.92, 132.87, 134.71, 136.96, 140.58, 142.51, 147.47,
+
72.76, 179.46; HRMS [M + H ] calcd for C39
34 3 3
H N NiO
49.3753, found 649.1760.
Ni(II) Com p lex of 2-Am in o-5-p h en ylp en t-4-en oic Acid
Sch iff Ba se w ith P ABP (14c): R ) 0.43; mp 182.1-183.7
C; H NMR δ 2.56-2.71 (2H, bm), 4.22 (1H, m), 6.69-6.81
3H, m), 7.04-7.06 (3H, m), 7.12 (1H, m), 7.24-7.39, (5H, m),
f
1
°
(
+
153.36, 170.19, 173.41, 182.60; HRMS [M + H ] calcd for
7
8
1
1
1
.53-7.56 (4H, m), 7.77 (1H, t, J ) 7.5 Hz), 7.97 (1H, bm),
.79 (1H, d, J ) 8.7 Hz); 13C NMR δ 30.10, 71.07, 121.68,
23.79, 124.07, 126.35, 126.72, 127.08, 127.44, 127.58, 127.75,
27.98, 128.67, 128.78, 129.28, 129.58, 130.29, 133.63, 133.82,
29 32 3 3
C H N NaNiO 529.2680, found 529.1837.
Ni(II) Com p lex of 2-Am in oh exa n oic Acid Sch iff Ba se
1
w ith P ABP (14f): R ) 0.62; mp 249.7-250.6 °C; H NMR δ
f
0.82 (3H, t, J ) 7.2 Hz), 1.11-1.32 (2H, m), 1.49-1.70 (2H,
m), 1.96-2.09 (2H, m), 4.00 (1H, q, J ) 3.7 Hz), 6.74-6.80
(2H, m), 7.06 (1H, m), 7.27-7.37 (2H, m), 7.41-7.54 (4H, m),
7.90 (1H, m), 8.00 (1H, m), 8.23 (1H, d, J ) 5.4 Hz), 8.92 (1H,
d, J ) 8.4 Hz); 13C NMR δ 14.16, 22.73, 27.41, 35.46, 71.53,
121.62, 123.65, 124.26, 127.01, 127.16, 127.32, 128.00, 128.96,
129.35, 130.00, 133.53, 134.10, 134.69, 140.70, 143.19, 147.14,
34.66, 135.86, 136.97, 140.25, 143.44, 146.92, 153.00, 169.65;
+
HRMS [M + Na ] calcd for C30
5
23 3 3
H N NaNiO 555.2052, found
55.0589.
Dia lk yla tion of Ni(II) Com p lex 2 w ith Non a ctiva ted
Iod id es 12d -h Yield in g Com p lexes 13d -h . Gen er a l
P r oced u r e. To a solution of sodium tert-butoxide (3.5 equiv)
in DMF (10 mL per 1 g of complex 2), cooled in an ice bath to
+
153.50, 170.13, 171.76, 179.66; HRMS [M + Na ] calcd for
4
°C, were added complex 2 (1 equiv) and the corresponding
25 23 3 3
C H N NaNiO 495.1517, found 495.1092.
alkylating reagent 12d -h (3.5 equiv). The reaction was stirred
at 4 °C for 5 min, after which time the ice bath was removed
and the reaction mixture was allowed to warm to room
temperature. After an additional 10 min (monitored by TLC),
the reaction was poured into ice-water, and the resulting solid
was filtered and washed with water and n-hexane to afford
the products 13d -h of greater than 99% purity. For the
chemical yields, see Table 1, entries 11-15.
Ni(II) Com p lex of r,r-Dim eth ylglycin e Sch iff Ba se
1
w ith P ABP (13g): R ) 0.36; mp 328.2-328.9 °C; H NMR δ
f
1.25 (3H, s), 1.44 (3H, s), 6.72-6.74 (2H, m), 7.21-7.25 (2H,
m), 7.31 (1H, m), 7.43-7.52 (4H, m), 7.91 (1H, m), 8.00 (1H,
m), 8.38 (1H, m), 8.72 (1H, m); 13C NMR δ 29.07, 75.21, 121.06,
123.38, 123.51, 126.58, 127.34, 128.35, 128.94, 129.15, 132.50,
134.29, 136.27, 140.15, 141.83, 146.75, 152.94, 169.53, 173.08,
+
182.63; HRMS [M + H ] calcd for C H N NiO 445.1095,
2
3
20
3
3
The corresponding monoalkylated products 14d -h were
prepared under the same conditions except that the base and
the alkylating reagent (bromides) were used in a ratio of 1.5/
found 445.0939.
Ni(II) Com p lex of 2-Am in op r op ion ic Acid Sch iff Ba se
1
w ith P ABP (14g): R ) 0.44; mp 258.2-259.1 °C; H NMR δ
f
1
.1, respectively.
1.58 (3H, d, J ) 7.1 Hz), 4.03 (1H, q, J ) 7.1 Hz), 6.74-6.78
(2H, m), 7.08 (1H, m), 7.27-7.36 (2H, m), 7.42-7.55 (4H, m),
7.90 (1H, m), 8.00 (1H, m), 8.23 (1H, d, J ) 5.1 Hz), 8.92 (1H,
d, J ) 8.4 Hz); 13C NMR δ 21.56, 67.18, 121.20, 123.31, 123.84,
126.42, 126.76, 126.83, 127.67, 128.54, 128.96, 129.58, 133.16,
Ni(II) Com p lex of r,r-Dieth ylglycin e Sch iff Ba se w ith
1
P ABP (13d ): R
(
f
) 0.52; mp 322.1-323.0 °C; H NMR δ 1.27
6H, t, J ) 7.2 Hz), 1.52 (2H, dq, J ) 14.7, 7.2 Hz), 1.71 (2H,
dq, J ) 14.7,7.2 Hz), 6.68 (1H, m), 6.72 (1H, m), δ 7.24-7.34
(
(
3H, m), 7.42-7.55 (4H, m), 7.90 (1H, m), 7.99 (1H, m), 8.40
133.46, 134.25, 140.32, 142.71, 146.64, 153.04, 169.70, 171.65,
1
3
+
1H, m), 8.71 (1H, m); C NMR δ 9.54, 32.79, 84.53, 121.04,
180.36; HRMS [M + Na ] calcd for C22
H
17
N
3
NaNiO
3
454.0720,
1
1
1
23.46, 123.48, 126.55, 127.31, 127.33, 128.71, 129.40, 132.40,
found 454.0523.
34.19, 136.49, 140.10, 142.01, 147.00, 152.88, 169.65, 173.17,
Ni(II) Com p lex of r,r-Di-n -p en tylglycin e Sch iff Ba se
+
1
81.72; HRMS [M + H ] calcd for C25
H
24
N
3
NiO
3
473.1626,
w ith P ABP (13h ): R ) 0.81; mp 221.8-223.4 °C; H NMR δ
f
found 473.1322.
0.89 (6H, t, J ) 7.1 Hz), 1.19-1.47 (10H, m), 1.58-1.88 (6H,
m), 6.66-6.74 (2H, m), 7.19-7.22 (2H, m), 7.31 (1H, m), 7.42-
7.53 (4H, m), 7.89 (1H, m), 7.99 (1H, m), 8.39 (1H, m), 8.72
(1H, m); 13C NMR δ 14.67, 23.00, 24.99, 32.20, 40.43, 83.80,
121.51, 123.93, 123.96, 127.03, 127.81, 127.85, 129.14, 129.91,
Ni(II) Com p lex of 2-Am in obu tyr ic Acid Sch iff Ba se
1
w ith P ABP (14d ): R
.39 (3H, t, J ) 7.5 Hz), 1.73 (1H, m), 1.97 (1H, m), 3.99 (1H,
dd, J ) 7.5; 3.3 Hz), 6.74-6.81 (2H, m), 7.06 (1H, m), 7.32
f
) 0.45; mp 265.4-266.5 °C; H NMR δ
1
J . Org. Chem, Vol. 68, No. 16, 2003 6213