4408
J. Clayden et al. / Tetrahedron 60 (2004) 4399–4412
CDCl3) 164.9 (CvO), 146.0 (NCC5H5), 104.0, 143.8,
136.0, 129.0, 128.0, 126.9, 123.4, 115.9, 112.1, 80.1
(CHNN), 60.6 (NCHCH2), 53.2 (NCH2CH2), 52.5
(PhNCH2), 43.2 (NCH2CH3), 38.4 (NCH2CH3), 28.0
(NCH2CH2), 25.4 (CH2CH3), 23.9 (NCH2CH2CH2), 14.7
(NCH2CH3), 13.1 (NCH2CH3), 13.0 (CH2CH3); nmax(thin
film)/cm21 2963–2931 (CH3), 1627 (CvO); m/z (CI)
392 (100%, MþHþ); m/z (EI) 394 (8.9%, MþHþ).
Found: MþHþ 392.5641; C25H33N3O requires MþHþ
392.5692.
4.1.13. (M,20S,40S,50R)-N,N-Diisopropyl-2-[3,4-dimethyl-
5-phenyl-1,3-oxazolan-2-yl]-1-naphthamide 16a. 2-For-
myl-N,N-diisopropyl-1-naphthamide 1a (251 mg, 0.89 mmol)
and (1R,2S)-ephedrine 13 (165 mg, 1.0 mmol, 1.1 equiv.)
were heated to reflux in toluene (25 mL) for 16 h. The
mixture was concentrated under reduced pressure and
purified by flash chromatography on silica, eluting with
petrol/EtOAc (11:1) to afford the oxazolidine 16a
(328.1 mg, 86%) as a white crystalline solid, mp 214.0–
217.1 8C; [a]2D0¼2157.1 (c¼0.252, CHCl3); dH (300 MHz;
CDCl3) 8.08 (1H, d, J¼9 Hz, ArH), 7.95 (1H, d, J¼9 Hz,
ArH), 7.94–7.86 (2H, m, ArH), 7.57–7.52 (4H, m, ArH),
7.42 (2H, t, J¼7 Hz, ArH), 7.35 (1H, d, J¼7 Hz, ArH), 5.18
(1H, d, J¼8 Hz, OCHPh), 4.99 (1H, s, CHOCHPh), 3.68
(2H, septet, 2£NCH), 3.01 (1H, d quintet, J¼2, 9 Hz,
CHPhCHCH3), 2.23 (3H, s, NCH3), 1.82 (3H, d, J¼7 Hz,
NCHCH3), 1.75 (3H, d, J¼7 Hz, NCHCH3), 1.15 (3H, d,
J¼7 Hz, NCHCH3), 0.99 (3H, d, J¼7 Hz, NCHCH3), 0.86
(3H, d, J¼7 Hz, CHCH3); dC (75 MHz, CDCl3) 168.4
(CvO), 139.6, 137.3, 133.9, 130.8, 129.2, 128.4, 128.1,
127.9, 127.9, 127.6, 126.6, 126.5, 125.3, 125.0 (aromatics),
94.8 (CHNCH3), 82.4 (OCHPh), 64.1 (CHPhCHCH3), 51.3
(NCH), 46.2 (NCH), 35.8 (NCH3), 20.9, 20.5, 20.3, 20.3
(CNHCH3CH3), 15.3 (CHCH3); nmax(thin film)/cm21
3062–2756 (CH3), 1626 (CvO); m/z (CI) 431 (100%,
MþHþ), 313 (7.7%, MþHþ–C6H14ON); m/z (EI) 431
(28%, MþHþ), 313 (7.7%, MþHþ–C6H14ON), 212
(100%, MþHþ–C11H14NO and C3H7), 155 (9%, MþHþ–
C15H14NO and C6H14N), 127 (10.2%, C15H14NO and
C6H14NOC). Found: MþHþ 431.2700; C28H34N2O2
requires MþHþ 431.2699. Anal. Calcd for C28H34N2O2:
C, 78.1; H, 7.96; N, 6.51. Found C, 77.73, H, 7.72, N, 6.31.
4.1.11. (P,20R,40S)-N,N-Diisopropyl-2-(1-methoxy-1-
methylethyl)-6-(2-phenylperhydropyrrolo[1,2-c]imida-
zol-3-yl)benzamide 12d. In the same way, aldehyde 2d
gave the imidazolidine 12d (96 mg, 85%) as an amorphous
solid, [a]2D5¼þ34.8 (c¼0.145, CHCl3); dH (300 MHz;
CDCl3) 7.24–7.15 (3H, m, ArH), 7.09 (2H, d, J¼8 Hz,
ArH), 6.74 (2H, d, J¼8 Hz, ArH), 6.62 (1H, t, J¼7 Hz,
ArH), 5.68 (1H, s, CHN), 4.32–4.22 (1H, m, PhNCH2
CHCH2), 3.84–3.76 (1H, m, PhNCH2), 3.74–3.69 (1H, m,
PhNCH2), 3.66–3.54 (2H, m, NCH), 3.37–3.26 (5H, m,
NCH2, NCH2CH2 and NCH2CH2CH2), 2.74–2.62 (1H, m,
NCH2CH2CH2), 3.26 (3H, s, OCH3), 1.70 (3H, d, J¼7 Hz,
NCHCH3), 1.66 (3H, d, J¼7 Hz, NCHCH3), 1.64 (3H, s,
CH3), 1.55 (3H, s, CH3), 0.99 (3H, d, J¼7 Hz, NCHCH3),
0.95 (3H, d, J¼7 Hz, NCHCH3); dC (75 MHz, CDCl3) 170.6
(CvO), 144.4 [NC(C5H5)], 142.8, 140.0, 135.6, 129.0,
127.7, 126.4, 125.4 (aromatics), 120.8, 115.6, 112.2
(aromatics), 79.4 (CHN), 60.4 (NCHCH2), 53.7 (NCH),
52.6 (OCH3), 50.8 (NCH), 49.2 (PhNCH2), 45.9 (NCH2),
29.0 (NCH2CH2), 27.9 (NCH2CH2CH2), 25.7 (CCH3), 23.3
(CH3), 20.9, 20.6, 20.3, 19.6 (NCHCH3); m/z (CI) 464
(100%, MþHþ), 388 (6.4%, MþHþ–C4H9O and CH3); m/z
(EI) 464 (23%, MþHþ), 463 (2%, M), 388 (100%, MþHþ–
C4H9O and CH3). Found: MþHþ 464.3284; C29H41N3O2
requires MþHþ 464.3278.
4.1.14. (M,20S,40S,50R)-N,N-Diethyl-2-[3,4-dimethyl-5-
phenyl-1,3-oxazolan-2-yl]-1-naphthamide 16b. In the
same way, 2-formyl-N,N-diethyl-1-naphthamide 1b gave
the oxazolidine 16b (196.2 mg, 87%) as white needles,
mp 139.1–141.8 8C; [a]2D4¼293.6 (c¼0.588, CHCl3); dH
(300 MHz; CDCl3) 8.12 (1H, d, J¼9 Hz, ArH), 7.95 (1H, d,
J¼9 Hz, ArH), 7.96–7.88 (1H, m, ArH), 7.86–7.79 (1H, m,
ArH), 7.60–7.49 (5H, m, ArH), 7.41 (1H, dt, J¼7, 1 Hz,
ArH), 7.35 (1H, dd, J¼7, 1 Hz, ArH), 5.2 (1H, d, J¼9 Hz,
OCHPh), 4.98 (1H, s, CHOCHPh), 3.79 (2H, m, NCH2),
3.16 (2H, m, NCH2CH3), 3.08 (1H, d quintet, J¼2, 8 Hz,
CHPhCHCH3), 2.25 (3H, s, NCH3), 1.46 (3H, t, J¼7 Hz,
NCH2CH3), 0.97 (3H, t, J¼7 Hz, NCH2CH3), 0.86 (3H, d,
J¼7 Hz, CHCH3); dC (75 MHz, CDCl3) 168.7 (CvO),
139.7, 136.2, 133.8, 131.4, 129.2, 128.9, 128.1, 127.9,
127.9, 127.6, 126.7, 126.7, 125.1, 124.9 (aromatics), 94.9
(CHNCH3), 82.5 (OCHPh), 63.8 (CHPhCHCH3), 43.3
(NCH2), 38.8 (NCH2), 35.6 (NCH3), 15.2, 13.8 (CNCH2-
CH3), 12.8 (CHCH3); nmax(thin film)/cm21 1629 (CvO);
m/z (CI) 403 (100%, MþHþ), 212 (23%, MþHþ–
C11H14NO and CH3); m/z (EI) 403 (19.2%, MþHþ), 254
(7.7%, M2C2H10N),212 (100%, MþHþ–C11H14NO and
CH3), 127 (10.2%, MþHþ–C11H14NO and C2H10NO).
Found: MþHþ 403.2388; C26H30N2O2 requires MþHþ
403.2386.
4.1.12. (M,20R,40S)-N,N-Dicylohexyl-2,4-dimethyl-6-(2-
phenylperhydropyrrolo[1,2-c]imidazol-3-yl)benzamide
12e. In the same way, benzamide 2e (88 mg) gave, after
flash chromatography eluting with petrol/EtOAc (8:1;
Rf¼0.42), the imidazolidine 12e (80.1 mg, 62%) as a
white solid, mp 154.5–157.2 8C; [a]2D1¼þ42.1 (c¼0.28,
CHCl3); dH (300 MHz; CDCl3) 7.06 (2H, t, J¼8 Hz, ArH),
6.78 (1H, s, ArH), 6.64 (1H, s, ArH), 6.53 (1H, t, J¼7 Hz,
ArH), 6.40 (2H, d, J¼9 Hz, ArH), 5.60 (1H, s, CHN), 3.82–
3.73 (1H, m, PhNCH2CHCH2), 3.56 (1H, t, J¼8 Hz,
PhNCH2), 3.17–2.84 (5H, m, NCH, NCH, PhNCH2 and
NCH2CH2), 2.78–2.62 (3H, m, NCH2CH2 and NCH2CH2),
2.52–2.43 (2H, m, NCH2CH2CH2), 2.24 (3H, s, ArCH3),
2.11 (3H, s, ArCH3), 2.06–0.65 (20H, m, cyclohexyl-H); dC
(75 MHz, CDCl3) 170.7 (CvO), 146.2, 136.7, 134.8, 133.2,
129.8, 129.0, 128.8, 124.3, 119.2, 115.6, 111.8 (aromatics),
79.6 (CHNN), 60.6 (NCHCH2), 60.1 (NCH), 56.0 (NCH),
52.7 (PhNCH2), 52.0 (NCH2), 30.9 (NCH2CH2), 30.8
(NCH2CH2CH2), 30.7, 29.3, 27.6, 26.7, 26.7, 25.8, 25.8,
25.4, 25.3, 23.4 (cyclohexyl), 21.4 (CH3), 19.3 (CH3);
n
max(thin film)/cm21 3005 (Ar–CH), 1609 (CO); m/z (CI)
500 (100%, MþHþ); m/z (EI) 499 (100%, M), 456 (34.6%,
M2CH3), 319 (28.2%, M2C12H22N), 303 (9%, M2ON
(C6H11)2, 289 (52.6%, MþHþ–ON(C6H11)2 and CH3), 187
(47.4%, M2C6H2ON(C6H11)2 and [CH3]2). Found: M
499.3560; C22H31NO2 requires M 499.3562.
4.1.15. (M,20S,40S,50S)-N,N-Diisopropyl-2-[3,4-dimethyl-
5-phenyl-1,3-oxazolan-2-yl]-1-naphthamide 17. Simi-
larly, 2-formyl-N,N-diisopropyl-1-naphthamide 1a (124 mg,
0.44 mmol) and (1S,2S)-(2)-pseudoephedrine 14 (80 mg,