954
N. Meyer et al.
PAPER
J = 8.1, 1.7 Hz, H-6¢), 6.64 (d, J = 1.7 Hz, H-2¢), 4.00 (pseudo-t, 1
H, J = 8 Hz, H-5), 3.77–3.89 [AB-system, 2 H, (MeO)2PhCH2],
3.85, 3.73 (2 s, 6 H, OCH3), 3.35 (mc, 1 H, H-2), 3.08 (dt, 1 H,
Jd = 8.7 Hz, Jt = 6.4 Hz, H-3), 2.93 (dd, 1 H, J = 13.9, 6.2 Hz,
PhCH2-a), 2.82 (dd, J = 13.9, 4.6 Hz, PhCH2-b), 2.13 (ddd, 1 H,
J = 12.8, 7.8, 6.4 Hz, H-4a), 1.99 (ddd, 1 H, J = 12.8, 8.7, 7.5 Hz,
H-4b). The sample contains small amounts of the 2,3-trans-3,5-cis
product.
IR (ATR): 2961, 1514, 1465, 1264, 1233, 1029, 908, 733, 702 cm–1.
1H NMR, COSY (400 MHz, CDCl3): d (cis/trans mixture) = 7.28–
7.45 (m, 8 H, C6H5), 7.19–7.25 (m, 2 H, C6H5), 6.82–6.87 (m, 2 H,
H-2¢t, H-6¢t), 6.77 (d, 1 H, J = 7.9 Hz, H-5¢t), 6.74 (d, 1 H, J = 8.1
Hz, H-5¢c), 6.70 (dd, 1 H, J = 8.1, 1.6 Hz, H-6¢c), 6.67 (d, 1 H,
J = 1.6 Hz, H-2¢c), 3.80–3.91 (m, 13 H, H-2t, 4 OCH3), contained in
this multiplet: 3.86, 3.86, 3.84, 3.81 (4 s, OCH3), 3.76 (d, 1 H,
J = 14.4 Hz, PhCH2-ac), 3.53–3.61 (m, 2 H, H-2c, PhCH2-at), con-
tained in this multiplet: 3.58 (d, 1 H, J = 13.5 Hz, PhCH2-at), 3.34–
3.47 (m, 3 H, H-5t, PhCH2-bc, PhCH2-bt), contained in this multip-
let: 3.44 (d, 1 H, J = 14.4 Hz, PhCH2-bc), 3.37 (d, 1 H, J = 13.5 Hz,
PhCH2-bt), 2.78 (mc, 1 H, H-5c), 2.32 (mc, 1 H, H-3at), 2.17 (mc, 1
H, H-4at), 1.96–2.07 (m, 1 H, H-3ac), 1.86–1.96 (m, 1 H, H-4ac),
1.59–1.77 (m, 2 H, H-3bt, H-3bc), 1.41–1.56 (m, 2 H, H-4bt, H-4bc),
Irradiation at 3.35 ppm (H-2) enhanced the signals at 4.00 ppm (H-
5, 2.7%), 3.87 ppm [(MeO)2PhCH2-a, 1.3%], 3.77 ppm
[(MeO)2PhCH2-b, 2.7%], 2.93 ppm (PhCH2-a, 2.2%), 2.82 ppm
(PhCH2-b, 3.0%). Irradiation at 3.08 ppm (H-3) enhanced the sig-
nals at 3.35 ppm (H-2, 0.9%), 2.93 ppm (PhCH2-a, 0.6%), 2.82 ppm
(PhCH2-b, 1.1%), 2.13 ppm (H-4a, 0.9%), 1.99 ppm (H-4b, 5.0%).
Irradiation at 4.00 ppm (H-5) enhanced the signals at 3.87 ppm
[(MeO)2PhCH2-a, 1.3%], 3.77 ppm [(MeO)2PhCH2-b, 1.1%], 3.35
ppm (H-2, 2.2%), 2.13 ppm (H-4a, 6.8%).
c
t
1.08 (d, 3 H, J = 6.1 Hz, CH3 ), 0.98 (d, 3 H, J = 6.4 Hz, CH3 ).
13C NMR, HMQC (75.5 MHz, CDCl3): d (cis/trans mixture) =
148.7, 148.3, 147.6, 147.6 (C-3¢, C-4¢), 145.3, 145.0 (C-1¢¢), 133.0,
131.4 (C-1¢), 128.2, 127.6 (C-2¢¢,6¢¢, C-3¢¢,5¢¢), 126.7 (C-4¢¢), 121.2
(C-6¢c), 120.1 (C-6¢t), 112.8 (C-2¢c), 111.6 (C-2¢t), 110.7 (C-5¢t),
110.4 (C-5¢c), 68.8 (C-2c), 65.0 (C-2t), 58.8 (C-5c), 55.8, 55.7
DEPT (100.6 MHz, CDCl3): d = 130.0, 128.1, 128.1, 127.9, 127.8,
127.4, 126.0, 121.5, 112.9, 110.4 (Ar), 71.1 (C-2), 66.6 (C-5), 55.8,
55.6 (OCH3), 55.0 [(MeO)2PhCH2], 47.6 (C-3), 42.9 (C-4), 39.5
(PhCH2). Two aromatic signals are missing due to low S/N-ratio.
c
t
(OCH3), 54.7 [(MeO)2PhCH2 ], 54.0 (C-5t), 50.8 [(MeO)2PhCH2 ],
33.9 (C-3c), 33.4 (C-3t), 32.2 (C-4c), 31.3 (C-4t), 21.1 (CH3 ), 14.4
c
HRMS: m/z calcd for [M + H]+: 464.2591; found: 464.2585.
t
(CH3 ).
2,3-cis-3,5-cis-9g
Yield: 11.3 mg; colorless oil; Rt 12.0 min; Rf 0.62 (cyclohexane–
ESI-MS: m/z (%) = 312.1 ([M
+
H]+, 100), 150.9
([(MeO)2PhCH2]+, 42}.
EtOAc, 1:1 + 1% EtNMe2).
HRMS: m/z calcd for [M + H]+: 312.1964; found: 312.1961.
IR (film): 2932, 2253, 1602, 1513, 1452, 1260, 1140, 1030, 911,
759, 732, 700 cm–1.
1-(3¢,4¢-Dimethoxybenzyl)-5-ethyl-2-phenylpyrrolidine (9i)
Compound 9i was obtained according to the general procedure from
6d (310 mg, 1.10 mmol) and ethyl vinyl ketone (120 mL, 1.21
mmol). Extractive work-up (1 N HCl) gave a 1.4:1 mixture of cis-
and trans-9i (275 mg, 76%) as a light yellow oil; Rf 0.47 (cyclohex-
ane–EtOAc, 3:1 + 1% EtNMe2).
1H NMR (400 MHz, CDCl3): d = 7.50–7.54 (m, 2 H, C6H5), 7.35 (t,
2 H, J = 7.5 Hz, C6H5), 7.16–7.30 (m, 6 H, C6H5), 7.05–7.16 (m, 3
H, C6H5), 6.85 (mc, 2 H, C6H5), 6.73 (d, 1 H, J = 8.1 Hz, H-5¢), 6.67
(dd, 1H, J = 8.1, 1.7 Hz, H-6¢), 6.59 (d, 1 H, J = 1.7 Hz, H-2¢), 3.83–
3.90 (m, 1 H, H-5), 3.84, 3.80 (2 s, 6 H, OCH3), 3.59 [d, 1 H,
J = 14.2 Hz, (MeO)2PhCH2-a], 3.53 (pseudo-q, 1 H, J = 7.0 Hz, H-
2), 3.46 [d, 1 H, J = 14.2 Hz, (MeO)2PhCH2-b], 3.33 (dd, J = 10.0,
7.8 Hz, H-3), 2.67 (dd, 1 H, J = 13.6, 7.0 Hz, PhCH2-a), 2.44 (dt, 1
H, Jd = 12.4 Hz, Jt = 6.8 Hz, H-4a), 2.33 (dd, 1 H, J = 13.6, 7.2 Hz,
PhCH2-b), 2.10 (td, Jd = 12.4 Hz, Jt = 10.0 Hz, H-4b).
IR (ATR): 2970, 1514, 1264, 1234, 1140, 1029, 908, 731, 704
cm–1.
1H NMR, COSY (400 MHz, CDCl3): d (cis/trans mixture) = 7.40–
7.45 (m, 2.4 H, C6H5), 7.27–7.35 (m, 7.2 H, C6H5), 7.18–7.24 (m,
2.4 H, C6H5), 6.78–6.83 (m, 2 H, H-2¢t, H-6¢t), 6.76 (d, 1 H, J = 7.9
Hz, H-5¢t), 6.73 (d, 1.4 H, J = 8.0 Hz, H-5¢c), 6.65–6.70 (m, 2.8 H,
Irradiation at 3.33 ppm (H-3) enhanced the signals at 3.85 ppm (H-
5, 4.7%), 3.53 ppm (H-2, 4.1%), 2.44 ppm (H-4a, 3.4%), 2.33 ppm
(PhCH2-b, 0.4%), 2.10 ppm (H-4b, 0.7%). Irradiation at 2.67 ppm
(PhCH2-a) enhanced the signals at 3.59 ppm ((MeO)2PhCH2-a,
1.8%), 3.53 ppm (H-2, 2.9%), 3.46 ppm ((MeO)2PhCH2-b, 0.9%),
2.33 ppm (PhCH2-b, 28.3%), 2.10 ppm (H-4b, 2.2%). Irradiation at
2.44 ppm (H-4a) enhanced the signals at 3.85 ppm (H-5, 7.0%),
3.80 ppm (OCH3, 0.4%), 3.53 ppm (H-2, 0.6%), 3.33 ppm (H-3,
6.7%), 2.10 ppm (H-4b, 28.2%).
13C NMR, DEPT (100.6 MHz, CDCl3): d = 129.1, 128.7, 128.1,
127.7, 127.6, 127.3, 126.7, 125.9, 125.2 (Ar), 121.0 (C-6¢), 112.6,
110.3 (C-2¢, C-5¢), 67.8 (C-2), 67.6 (C-5), 55.6, 55.4 [OCH3,
(MeO)2PhCH2], 46.1 (C-3), 41.3 (C-4), 38.5 (PhCH2).
t
c
H-2¢c, H-6¢c), 3.84–3.88 (m, 11.2 H, H-2t, 2 OCH3 , OCH3 ), con-
t
tained in this multiplet: 3.86, 3.85 (2 s, 6 H, 2 OCH3 ), 3.84 (s, 4.2
c
c
H, OCH3 ), 3.80 (s, 4.2 H, OCH3 ), 3.75 (d, 1.4 H, J = 14.1 Hz,
PhCH2-ac), 3.57–3.64 (m, 2.4 H, H-2c, PhCH2-at), contained in this
multiplet: 3.61 (d, 1 H, J = 13.8 Hz, PhCH2-at), 3.45 (d, 1.4 H,
J = 14.1 Hz, PhCH2-bc), 3.43 (d, 1 H, J = 13.8 Hz, PhCH2-bt), 3.11
(mc, 1 H, H-5t), 2.70 (mc, 1.4 H, H-5c), 2.27 (mc, 1 H, H-4at), 2.10
(mc, 1 H, H-3at), 1.97–2.05 (m, 1.4 H, H-4ac), 1.83–1.93 (m, 1.4 H,
H-3ac), 1.51–1.78 (m, 7.2 H, H-3b, H-4b, CH2Me-a), 1.16–1.35 (m,
c
2.4 H, CH2Me-b), 0.87 (t, 4.2 H, J = 7.4 Hz, CH3 ), 0.82 (t, 1 H,
t
J = 7.4 Hz, CH3 ).
13C NMR, HMQC (75.5 MHz, CDCl3): d (cis/trans mixture) =
148.6, 148.2, 147.6, 147.4 (C-3¢, C-4¢), 145.2, 145.0 (C-1¢¢), 133.2,
131.5 (C-1¢), 128.2, 127.5 (C-2¢¢,6¢¢c, C-3¢¢,5¢¢c), 128.1, 127.7 (C-
2¢¢,6¢¢t, C-3¢¢,5¢¢t), 126.7 (C-4¢¢c), 126.6 (C-4¢¢t), 121.1 (C-6¢c), 120.0
(C-6¢t), 112.7 (C-2¢c), 111.5 (C-2¢t), 110.7 (C-5¢t), 110.4 (C-5¢c),
ESI-MS: m/z = 464.4 ([M + H]+, 100%).
HRMS: m/z calcd for [M + H]+: 464.2591; found: 464.2610.
The 2,3-cis-3,5-trans-diastereomer could not be obtained in suffi-
cient quantity.
t
68.8 (C-2c), 65.5 (C-2t), 64.6 (C-5c), 61.0 (C-5t), 55.8 (OCH3 ), 55.8
c
t
c
c
(OCH3 ), 55.7 (OCH3 ), 55.6 (OCH3 ), 55.1 [(MeO)2PhCH2 ], 50.5
[(MeO)2PhCH2 ], 34.3 (C-4c), 33.3 (C-4t), 29.0 (C-3c), 28.1 (C-3t),
27.7 (MeCH2 ), 21.7 (MeCH2 ), 10.6 (CH3 ), 10.2 (CH3 ).
t
1-(3¢,4¢-Dimethoxybenzyl)-5-methyl-2-phenylpyrrolidine (9h)
Compound 9h was obtained according to the general procedure
from 6d (322 mg, 1.15 mmol) and methyl vinyl ketone (105 mL,
1.26 mmol). Extractive work-up (1 N HCl) gave a 1:1 mixture of
cis- and trans-9h (301 mg, 84%) as a light yellow oil; Rf 0.44 (cy-
clohexane– EtOAc, 3:1 + 1% EtNMe2).
c
t
t
c
ESI-MS: m/z (%) = 326.0 ([M
+
H]+, 100), 150.9
([(MeO)2PhCH2]+, 20).
HRMS: m/z calcd for [M + H]+: 326.2120; found: 326.2133.
Synthesis 2005, No. 6, 945–956 © Thieme Stuttgart · New York