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W. Goldeman et al. / Tetrahedron 62 (2006) 4506–4518
(3a; 2.02 g, 10 mmol). The whole mixture was left for 24 h
and filtered. Filtrate was evaporated to dryness and an oily
residue was kept at 60 8C for 2 h to finish up the reaction.
Solidified products were crystallized from acetone (25 mL);
(4-pyridyl derivatives), or from a mixture of toluene and
hexane (1:1 v/v, 25 mL); (2-pyridyl derivatives). After
cooling separated crystals were filtered off, washed with
hexane and dried to give the racemic pyridine aminophos-
phine oxides 4a–d.
4-pyridyl derivative, the product 4g was crystallized from a
mixture of methylene chloride and hexane (1:1, v/v), while
in the case of 2-pyridyl derivative 4f, the crude product was
treated first with warm acetone (5 mL) in order to remove an
unsoluble by-product (the 1-hydroxy-1-(2-pyridyl)-methyl-
diphenyl-phosphine oxide). The filtrate was evaporated to
dryness and the residue was recrystallized from methylene
chloride and hexane (1:1, v/v).
The remaining mother solution was evaporated to give a
product, composed with two stereoisomers, in which the R,R
stereoisomer was predominant over of the S,R one.
4.2.1. Compound 4a. White solid, 3.50 g, yield 88%, mp
120–122 8C, lit.8 102–104 8C. Spectroscopic data consistent
with that reported.8
4.3.1. Compound 4e. White solid, 1.36 g, yield 36%, mp
162–165 8C. 1H NMR; dH (CDCl3; 300 MHz): 8.55 (2H, d,
JZ5.9 Hz, 2,6-PyH); 7.60 (2H, m, 3,5-PyH); 7.50–6.86
(10H, m, ArH); 4.05 (1H, d, JZ7.6 Hz, CH–P); 3.62 (1H, d,
JZ13.4 Hz, NCH2); 3.22 (1H, d, JZ13.4 Hz, NCH2); 2.22
(1H, br s, NH), 0.79 (9H, d, JZ14.6 Hz, t-Bu). 31P NMR; dP
(CDCl3; 121.5 MHz): 50.15 (s). IR, nmax (KBr): 3350; 3259
(NH); 3028; 2961; 2868; 1593; 1495; 1437; 1165 (P]O);
4.2.2. Compound 4b. White solid, 2.87 g, yield 72%, mp
158–160 8C, lit.8 148–149 8C. Spectroscopic data consistent
with that reported.8
4.2.3. Compound 4c. White solid, 2.95 g, yield 81%, mp
100–102 8C. 1H NMR; dH (CDCl3; 300 MHz): 8.37 (1H, d,
JZ4.8 Hz, 6-PyH); 7.84–7.08 (13H, m, PyH, ArH); 4.72
(1H, d, JZ13.3 Hz, CH–P); 2.59–2.43 (2H, m, NCH2); 1.41
(2H, m, CH2); 1.23 (2H, m, CH2); 0.81 (3H, t, JZ7.3 Hz,
CH3). 31P NMR; dP (CDCl3; 121.5 MHz): 29.62 (s). IR, nmax
(KBr): 3387 (NH); 3039; 2916; 2806; 1578; 1471; 1428;
1146 (P]O); 1108; 1037; 990; 831; 744; 733 (P–C); 690;
634; 611; 549; 511 cmK1. Anal. Calcd for C22H25N2OP,
requires C, 72.51; H, 6.92; N, 7.69; P, 8.45. Found: C,
72.21; H, 6.98; N, 7.54; P, 8.43%.
1105; 818; 743 (P–C); 699; 640; 554; 490 cmK1. [a]20
D
C2.1 (c 0.7, CHCl3). Anal. Calcd for C23H27N2OP, requires
C, 72.99; H, 7.19; N, 7.40; P, 8.18. Found: C, 72.81; H, 7.28;
N, 7.25; P, 8.22%.
4.3.2. Compound 4f. White solid, 1.73 g, yield 42%, mp
135–137 8C. 1H NMR; dH (CDCl3; 300 MHz): 8.34 (1H, d,
JZ4.8 Hz, 6-PyH); 7.95–7.87 (4H, m, PyH, ArH); 7.55–
7.40 (9H, m, ArH); 7.20–7.15 (2H, m, ArH); 7.13–7.05 (3H,
m, ArH); 4.76 (1H, d, JZ13.5 Hz, CH–P); 3.51 (1H, q,
JZ6.5 Hz, CH); 3.23 (1H, br s, NH); 1.30 (3H, d,
JZ6.5 Hz, CH3). 31P NMR; dP (CDCl3; 121.5 MHz):
31.37 (s). IR, nmax (KBr): 3439 (NH); 3053; 3005; 2926;
2875; 2808; 1601; 1584; 1566; 1470; 1447; 1437; 1431;
1375; 1309; 1262; 1186 (P]O); 1119; 1101; 1067; 1048;
1038; 1030; 993; 912; 831; 747; 738 (P–C); 722 (P–C); 693;
639; 606; 555; 515; 487 cmK1. [a]20D C29 (c 1.0, CHCl3).
Anal. Calcd for C25H23N2OP, requires N, 6.79; P, 7.51.
Found: N, 6.49; P, 7.28%.
4.2.4. Compound 4d. White solid, 3.13 g, yield 86%, mp
145–147 8C. 1H NMR; dH (CDCl3; 300 MHz): 8.43 (2H, d,
JZ5.9 Hz, 2,6-PyH); 7.85 (2H, m, 3,5-PyH); 7.62–7.21
(10H, m, ArH); 4.56 (1H, d, JZ12.7 Hz, CH–P); 2.53–2.41
(2H, m, NCH2); 1.40 (2H, m, CH2); 1.23 (2H, m, CH2); 0.83
(3H, t, JZ7.3 Hz, CH3). 31P NMR; dP (CDCl3; 121.5 MHz):
30.52 (s). IR, nmax (KBr): 3297 (NH); 3046; 3006; 2973;
2808; 1582; 1493; 1455; 1326; 1154 (P]O); 1112; 987;
835; 772; 732 (P–C); 681; 641; 558; 512; 491 cmK1. Anal.
Calcd for C22H25N2OP, requires C, 72.51; H, 6.92; N, 7.69;
P, 8.45. Found: C, 72.31; H, 7.08; N, 7.55; P, 8.52%.
4.3.3. Compound 4g. White solid, 2.02 g, yield 49%, mp
174–176 8C. 1H NMR; dH (CDCl3; 300 MHz): 8.39 (2H, d,
JZ4.7 Hz, 2,6-PyH); 7.96 (2H, dd, JZ4.7, 3.1 Hz, 3,5-
PyH); 7.64–7.02 (15H, m, ArH); 4.61 (1H, d, JZ11.2 Hz,
CH–P); 3.62 (1H, q, JZ6.4 Hz, CH); 2.59 (1H, br s, NH);
1.29 (3H, d, JZ6.4 Hz, CH3). 31P NMR; dP (CDCl3;
121.5 MHz): 32.22 (s). IR, nmax (KBr): 3337 (NH); 3057;
3026; 2973; 2848; 2808; 1590; 1560; 1494; 1469; 1451;
1436; 1378; 1326; 1176 (P]O); 1121; 1102; 1070; 1025;
991; 833; 795; 773; 742 (P–C); 723 (P–C); 691; 639; 603;
559; 531; 514; 495 cmK1. [a]20D C79 (c 1.0, CHCl3). Anal.
Calcd for C25H23N2OP, requires N, 6.79; P, 7.51. Found: N,
6.60; P, 7.77%.
4.3. Procedure for preparation of optically active
pyridine aminophosphine oxides 4e–h
To a solution of pyridine aldehyde (1a or 1b; 1.07 g,
10 mmol) in dichloromethane (25 mL) benzylamine (2a;
1.07 g, 10 mmol), or (R)-(C)-a-methylbenzylamine (2c;
1.21 g, 10 mmol) was added, respectively, and a mixture
was left for 48 h at room temperature. Then, the solution
was dried (anh. Na2SO4), filtered, and diphenylphosphine
oxide (3a; 2.02 g, 10 mmol), or (S)-(K)-tert-butylphenyl-
phosphine oxide11 3b, 1.82 g, 10 mmol, [a]20 K24.8
D
(c 1.0, CHCl3), or (R)-(C)-tert-butylphenylphosphine11 3c,
1.82 g, 10 mmol, [a]20 C24.6 (c 1.0, CHCl3) was added,
D
respectively. The formed solution was left for 24 h and
evaporated to dryness to give an oily residue, which was
kept for 2 h at 60 8C. After this, the oil turned to a whitish
solid. The solid was dissolved in warm acetone (25 mL) and
the solution was kept at room temperature for several hours.
The product crystallized out from the solution. The product
was collected by filtration and dried. If necessary, the
crystallization from acetone was repeated. In the case of
4.3.4. Compound 4h. White solid, 2.12 g, yield 54%, mp
210–212 8C. 1H NMR; dH (CDCl3; 300 MHz): 8.21 (2H, d,
JZ5.9 Hz, 2,6-PyH); 7.44 (2H, d, JZ5.9 Hz, 1.7 Hz, 3,5-
PyH); 7.20–7.05 (10H, m, ArH); 4.51 (1H, d, JZ8.3 Hz,
CH–P); 3.43 (1H, q, JZ6.4 Hz, CH); 2.65 (1H, br s, NH);
1.31 (9H, d, JZ15.0 Hz, t-Bu); 1.24 (3H, d, JZ6.4 Hz,
CH3). 31P NMR; dP (CDCl3; 121.5 MHz): 48.97 (s). IR, nmax
(KBr): 3351 (NH); 3064; 2967; 2868; 1592; 1557; 1459;