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A. Baskakova et al.
PAPER
yellow solid. This was purified by flash chromatography on silica
gel (60 g, column 18 cm × 3 cm); elution with EtOAc–PE (20:80,
v/v) yielded 0.67 g (‘42%’) of a spectroscopically pure colorless
solid; mp 131–132 °C. According to the 13C NMR spectra, the ratio
3/4 (erythro/threo) was >95:5; [a]D20 +31 (c = 0.67, CHCl3).
stirred overnight (17 h) at r.t., and the solid was filtered off. The fil-
trate was evaporated and the residue recrystallized from EtOAc–PE
to give the nitrone product 8 as a spectroscopically and analytically
pure solid (1.65 g, 74%); mp 97–100 °C (Lit.31 mp 88–89 °C);
[a]D20 +79 (c = 1.28, EtOH) {Lit.31 [a]D20 +82.5 (c = 1.00, EtOH)}.
IR (neat): 3417 (w, OH), 2899 (s), 2843 (s, NH2), 1447 (m), 1113
(vs, C–O), 1008 (s), 909 (s), 695 cm–1 (s).
IR (neat): 2929 (s), 2852 (m, C = N–O), 1443 (s), 1273 (s, N–O),
1198 (s), 1168 (s), 1102 (vs, C–O), 1024 (s), 927 (vs, N–O), 706
(vs), 664 (s), 589 cm–1 (s).
1H NMR (500.1 MHz, CDCl3): d = 1.39 and 1.48 [2 s, 3 H each,
C(CH3)2], 1.68 (m, 6 H, 4¢-H, 6¢-H, 9-H), 1.78 (m, 6 H, 2¢-H, 8¢-H,
1H NMR (300.1 MHz, CDCl3): d = 1.40 (m, 2 H, 4¢-H), 1.58 (m, 8
3
3
10¢-H), 1.98 (m, 3 H, 3¢-H, 5¢-H, 7¢-H), 2.58 (‘d’, J2,3 = 5.6 Hz,
H, 2¢-H, 3¢-H, 5¢-H, 6¢-H), 3.88 (‘dd’, J2,3a = 5.7 Hz,
1 H, 3-H), 3.96 (A of AB, 2JA,B = 13.7 Hz, 1 H, CHAHBC6H5), 4.20
2J3a,3b = 8.6 Hz, 1 H, 3-Ha), 4.38 (‘dd’, J2,3b = 7.0 Hz,
3
2
3
(‘dd’, J1a,2 = 6.4 Hz, J1b,2 = 8.1 Hz, 2 H, 1-Ha, 1-Hb), 4.24 (B of
2J3a,3b = 8.6 Hz, 1 H, 3-Hb), 4.87 (‘s’, 2 H, A, B of CHAHBC6H5),
5.15 (‘ddd’, 3J1,2 = 4.2 Hz, 3J2,3a = 5.7 Hz, 3J2,3b = 7.0 Hz, 1 H, 2-H),
6.86 (‘d’, 3J1,2 = 4.2 Hz, 1 H, 1-H), 7.39–7.41 (m, 5 H, o-, m-, p-H
of C6H5).
AB, 2J = 13.7 Hz, 1 H, CHAHBC6H5), 4.39 (br s, 1 H, NOH), 4.46
(‘ddd’, J1a,2 = 6.4 Hz, J1b,2 = 8.1 Hz, J2,3 = 5.6 Hz, 1 H, 2-H),
7.24–7.40 (m, 5 H, o-, m-, p-H of C6H5).
2
3
3
13C NMR (125.8 MHz, CDCl3): d = 25.7 and 26.9 [2 q, C(CH3)2],
28.7 (d, C-3¢, C-5¢, C-7¢), 37.1 (t, C-4¢, C-6¢, C-9¢), 40.4 (t, C-2¢, C-
8¢, C-10¢), 38.0 (s, C-1¢), 64.6 (t, CH2C6H5), 68.1 (t, C-1), 74.8 (d,
C-3), 75.0 (d, C-2), 107.1 [s, C(CH3)2], 127.1 (d, p-C of C6H5),
128.3 and 128.9 (2 d, o-, m-C of C6H5), 139.3 (s, i-C of C6H5).
13C NMR (75.5 MHz, CDCl3): d = 23.7 (t, C-4¢), 23.9 and 25.0 (2 t,
C-3¢ and C-5¢), 34.3 and 35.9 (2 t, C-2¢, C-6¢), 67.5 (t, C-3), 69.0 (t,
CH2C6H5), 71.7 (d, C-2), 110.6 (s, C-1¢), 129.2 (d, p-C of C6H5),
129.0 and 129.4 (2 d, o-, m-C of C6H5), 132.1 (s, i-C of C6H5), 139.4
(d, C-1).
Anal. Calcd for C23H33NO3 (371.5): C, 74.36; H, 8.95; N, 3.77.
Found: C, 74.54; H, 8.99; N, 3.63.
Anal. Calcd for C16H21NO3 (275.3): C, 69.79; H, 7.69; N, 5.09.
Found: C, 69.75; H, 7.72; N, 5.05.
(2S,3S)-3-(1-Adamantyl)-3-(tert-butoxycarbonylamino)-1,2-O-
isopropylidene-1,2-propanediol (5)
(2S,3S)-3-(1-Adamantyl)-3-(N-benzylhydroxylamino)-1,2-O-
cyclohexylidene-1,2-propanediol (9)
Diastereomerically pure N-benzylhydroxylamine
3
(320 mg,
1-Adamantylmagnesium bromide was prepared as described above.
In analogy to literature reports,20b,d,e to a well-stirred solution of the
N-benzylnitrone 8 (1.42 g, 5.2 mmol) in absolute Et2O (60 mL) was
added Et2AlCl (ca. 5.2 mmol) in one portion at r.t. The resulting
mixture was stirred for 15 min under N2, cooled to –60 °C, treated
with adamantylmagnesium bromide (ca. 10.4 mmol), and stirred for
17 h at this temperature. The reaction was quenched by the addition
of sat. aq NH4Cl (ca. 40 mL) and allowed to stir for 20 min. The
aqueous layer was then separated and extracted with Et2O
(3 × 20 mL). The combined ethereal layers were washed with brine
(2 × 30 mL), dried (Na2SO4), and concentrated in vacuo (40 °C/15
mbar, then 0.05 mbar) to give the crude product as a yellowish semi-
solid, 2.50 g (‘117%’). Only one diastereomer of 9 was detected ac-
cording to the 13C NMR spectrum, as well as 10–15% of the starting
nitrone 8. The crude material was purified by flash chromatography
on silica gel (40 g, column 14 cm × 3 cm), eluting with PE (ca. 100
mL) followed by PE–EtOAc (80:20, v/v). The product 9 was isolat-
ed as a colorless, analytically pure solid; mp 129–132 °C (1.29 g,
61%); [a]D20 +21 (c = 1.00, CHCl3).
0.86 mmol) was dissolved in anhyd MeOH (10 mL), then di-tert-
butyl dicarbonate (282 mg, 11.5 mmol) was added, and the resulting
solution was transferred into a hydrogenation vessel. This was
flushed with N2 and Pd(OH)2/C (40 mg) was added. The reaction
was carried out under H2 pressure (4.8 bar) for 3 days. The resulting
suspension was filtered through a pad of Celite/silica gel (ca. 1 cm,
Celite on top) and the adsorbent was washed with EtOAc (2 × 10
mL). The filtrate was concentrated in vacuo (40 °C/15 mbar) to give
a colorless semi-solid, which was purified by column chromatogra-
phy on silica gel (10 g, column 1 cm × 4 cm), eluting with EtOAc–
PE–Et3N (50:50:2, v/v/v). From this, 192 mg (61%) of 5 was isolat-
ed as an analytically pure, colorless solid; mp 109–114 °C;
[a]D20 +20 (c = 1.54, MeOH).
IR (neat): 2902 (vs, b), 2849 (vs), 1678 (vs, amide I), 1525 (s, amide
II), 1452 (m), 1365 (s), 1242 (s), 1161 (vs), 1049 (vs, b, C-O), 1011
(vs, C–O), 940 (s), 827 cm–1 (s).
1H NMR (500.2 MHz, CDCl3): d = 1.34 and 1.38 [2 s, 3 H each,
C(CH3)2], 1.44 [s, 9 H, C(CH3)3], 1.51–1.71 (m, 12 H, 2¢-H, 4¢-H,
6¢-H, 8¢-H, 9¢-H, 10¢-H), 1.98 (br s, 3 H, 3¢-H, 5¢-H, 7¢-H), 3.55
IR (neat): 3417 (w, OH), 2899 (s), 2843 (s, NH2), 1447 (m), 1113
(vs, C–O), 1008 (s), 909 (s), 695 cm–1 (s).
3
3
(‘dd’, J2,3 = 6.2 Hz, J2,NH = 10.8 Hz, 1 H, 3-H), 3.67 (‘dd’,
2J1a,1b = 8.4 Hz, J1a,2 = 7.7 Hz, 1 H, 1-Ha), 3.98 (‘dd’, J1a,1b = 8.4
1H NMR (300.1 MHz, CDCl3): d = 1.41 (m, 2 H, 4¢¢), 1.55–1.70 (m,
14 H, 4¢-H, 6¢-H, 9¢-H, 2¢¢-H, 3¢¢-H, 5¢¢-H, 6¢¢-H), 1.80 (br s, 6 H, 2¢-
H, 8¢-H, 10¢-H), 1.99 (br s, 3 H, 3¢-H, 5¢-H 7¢-H), 2.57 (‘d’,
3
2
3
3
Hz, J1b,2 = 6.4 Hz, 1 H, 1-Hb), 4.23 (‘dt’, J1a,2 = 7.5 Hz,
3J1b,2 = 3J2,3 = 6.3 Hz, 1 H, 2-H), 4.45 (d, J3,NH = 10.8 Hz, 1 H,
3
2
NH).
3J2,3 = 6.3 Hz, 1 H, 3-H), 3.95 (A of AB, JA,B = 13.7 Hz, 1 H,
CHAHBC6H5), 4.14 (dd, 2J1a,1b = 8.1 Hz, 3J1a,2 = 8.8 Hz, 1 H, 1-Ha),
13C NMR (125.8 MHz, CDCl3): d = 25.7 and 26.4 [2 q, C(CH3)2],
28.3 [q, C(CH3)3], 28.4 (d, C-3¢, C-5¢, C-7¢), 35.9 (s, C-1¢), 36.9 (t,
C-4¢, C-6¢, C-9¢), 39.1 (t, C-2¢, C-8¢, C-10¢), 58.1 (d, C-3), 66.8 (t,
C-1), 74.7 (d, C-2), 79.2 [s, C(CH3)3], 108.8 [s, C(CH3)2], 156.2
(C=O).
2
4.21 (B of AB, JA,B = 13.8 Hz, 1 H, CHAHBC6H5), 4.22 (‘dd’,
3
2J1a,1b = 8.1 Hz, 3J1b,2 = 5.7 Hz, 1 H, 1-Hb), 4.45 (‘ddd’, J1a,2 = 8.8
Hz, 3J1b,2 = 5.7 Hz, 3J2,3 = 6.3 Hz, 1 H, 2-H), 7.24–7.36 (m, 5 H, o-,
m-, p-H of C6H5).
13C NMR (75.5 MHz, CDCl3): d = 24.1 (t, C-3¢¢, C-5¢¢), 25.3 (t, C-
4¢¢), 28.8 (d, C-3¢, C-5¢, C-7¢), 35.1 and 36.6 (2 t, C-2¢¢, C-6¢¢), 37.2
(t, C-4 ¢, C-6¢, C-9¢), 38.0 (s, C-1¢), 40.4 (t, C-2¢, C-8¢, C-10¢), 64.6
(t, CH2C6H5), 68.1 (t, C-1), 74.4 (d, C-3), 75.0 (d, C-2), 107.8 (s, C-
1¢¢), 127.1 (d, p-C of C6H5), 128.3 and 128.9 (2 d, o-, m-C of C6H5),
139.4 (s, i-C of C6H5).
Anal. Calcd for C21H35NO4 (365.5): C, 69.01; H, 9.65; N, 3.83.
Found: C, 68.77; H, 9.58; N, 3.57.
2,3-O-Cyclohexylidene-D-glyceraldehyde N-Benzylnitrone (8)
According to Dondoni’s procedure,27 2,3-O-cyclohexylidene-D-
glyceraldehyde (7; 1.38 g, 8.1 mmol) and N-benzylhydroxyl-
amine39 (1.00 g, 8.1 mmol) were dissolved in anhyd CH2Cl2
(20 mL), and MgSO4 (ca. 2 g) was added. The suspension was
Anal. Calcd for C26H37NO3 (411.6): C, 75.87; H, 9.06; N, 3.40.
Found: C, 75.41; H, 9.35; N, 3.31.
Synthesis 2010, No. 21, 3693–3699 © Thieme Stuttgart · New York