B. F. Bonini et al.
FULL PAPER
J2 ϭ 11.4 Hz, 1 H), 2.88 (br. d, J ϭ 4.0 Hz, 1 H ϩ m, 1 H), 4.26
(s, 5 H), 4.32 (br. s, 2 H), 4.39 (br. s, 2 H), 7.7 (br. s, 2 H) ppm.
13C NMR: δ ϭ 25.85 (CH3), 32.9 (C), 37.1 (CH2) 60.15, 69.9, 70.2,
70.6, 73.75, 74.2 (CH), 76.2 (C) ppm. IR (CCl4): ν˜ ϭ 1519, 3450
cmϪ1. EI-MS: m/z: 317 [Mϩ], 232, 218, 121, 86. C16H23FeNS
(317.09): calcd. C 60.55, H 7.31, N 4.42 found C 60.31, H 7.58,
N 4.28.
76.2, 82.3 (C) ppm. IR (CCl4): ν˜ ϭ 1475, 3390 cmϪ1. EI-MS:
m/z ϭ 343 [Mϩ], 286, 244, 132, 91, 56. C18H25FeNS (343.11) calcd.
C 62.95, H 7.34, N 4.08; found C 62.68, H 7.44, N 4.19. A suitable
crystal for X-ray analysis was obtained by crystallization from eth-
20
anol. (RFc,S)-22b: M.p. 58Ϫ60 °C (ethanol). [α]D ϭ Ϫ201.4 (c ϭ
1
0.78, CHCl3). H NMR: δ ϭ 0.95 (s, 9 H), 2.50 (s, 3 H), 2.63 (dd,
J1 ϭ 12, J2 ϭ 3.2 Hz, 1 H), 2.95 (dd, J1 ϭ 15, J2 ϭ 3.2 Hz, 1 H),
3.42 (d, J ϭ 16.4 Hz, 1 H), 3.54 (br. t, 1 H), 3.96 (br. s, 1 H), 4.03
(br. s, 1 H), 4.15 (s, 5 H), 4.19 (d, J ϭ 16.4 Hz, 1 H), 4.24 (br. s, 1
H) ppm. EI-MS: m/z ϭ 343 [Mϩ], 286, 244, 132, 56.
(S)-2-Amino-1-(ferrocenylthio)-3-methylbutane (21c): Light brown
20
oil that crystallized at below 0 °C (0.57 g, 95%). [α]D ϭ ϩ69.7
1
(c ϭ 1.58, CHCl3). H NMR: δ ϭ 0.85, (d, J ϭ 6.7 Hz, 3 H), 0.87
In a separate experiment, performed for a shorter reaction time
(1 h), it was possible to isolate (beside the two diastereoisomers of
22b) product (SFc,S)-25b as a single diastereoisomer in 23% yield.
(d, J ϭ 6.7 Hz, 3 H), 1.61 (br. s, 2 H), 1.65 (m, 1 H), 2.42 (dd, J1 ϭ
9.4, J2 ϭ 12.8 Hz, 1 H), 2.58 (m, 1 H), 2.75 (dd, J1 ϭ 12.8, J2 ϭ
16.0 Hz, 1 H), 4.11 (m, 2 H ϩ s, 5 H), 4.25 (m, 2 H) ppm. 13C
NMR: δ ϭ 17.4, 19.1 (CH3), 32.5 (CH), 43.95 (CH2), 55.4, 68.85,
69.0, 69.3, 73.3, 73.5 (CH), 79.4 (C) ppm. IR (CCl4): ν˜ ϭ 3388
cmϪ1. EI-MS: m/z ϭ 303 [Mϩ], 232, 218, 72. HRMS calcd. for
C15H21FeNS: 303.0744 found 303.0732.
1
25b: H NMR: δ ϭ 0.89 (s, 9 H), 2.12 (dd, J1 ϭ 14, J2 ϭ 10 Hz, 1
H), 2.64 (dd, J1 ϭ 10 J2 ϭ 1.5 Hz, 1 H), 2.84 (dd, J1 ϭ 14 J2 ϭ
1.5 Hz, 1 H), 3.85 (d, J ϭ 14.8 Hz, 1 H), 3.94 (br. t, 1 H), 4.01 (d,
J ϭ 14.8 Hz, 1 H), 4.10 (s, 5 H), 4.13 (br. s, 1 H), 4.14 (br. s, 1 H)
ppm. 13C NMR: δ ϭ 27.05 (CH3), 35.5 (C), 36.9, 49.2 (CH2), 64.9,
68.9, 69.5, 69.8, 75.4 (CH), 83.1, 95.8 (C) ppm. EI-MS: m/z ϭ 329
[Mϩ], 245, 91, 56. This product was subsequently methylated by
the standard procedure to provide (SFc,S)-22b in 85% yield.
General Procedure for the Reaction with HCO2H/HCHO: A solu-
tion of 21 (2 mmol) in formic acid (98%, 20 mmol) and aqueous
formaldehyde (37%, 12 mmol) was heated at reflux for 2 h. Upon
cooling, the mixture was basified with aqueous NaOH (1 , pH ϭ
10) and extracted with Et2O. The combined organic layers were
dried (Na2SO4) and concentrated in vacuo.
Isopropyl Derivatives: The 1H NMR spectrum of the crude reaction
mixture showed the presence of the bicyclic product 22c as a mix-
ture of two diastereoisomers in a 2.4:1 ratio (de ϭ 40%), and also
the presence of the N,N-dimethylated product. Purification of the
crude reaction mixture by column chromatography (ethyl acetate/
light petroleum ether, 10:1 and then 3:1) gave as the first fraction
the cyclic product 22c (500 mg) as a brown solid in 75% yield as a
mixture of two diastereoisomers and as the second fraction product
14c as an orange solid (125 mg, 22%). The two isomers of 22c were
isolated by a second chromatography column (light petroleum
ether/ethyl acetate, 10:1). (SFc,S)-22c: M.p. 93Ϫ94 °C (ethanol).
1
Phenyl Derivatives: The H NMR spectrum of the crude reaction
mixture showed the presence of the bicyclic product 22a as a mix-
ture of two diastereoisomers in a 7:1 ratio (de ϭ 75%) and the
absence of the N,N-dimethylated product. Purification by column
chromatography (light petroleum ether/ethyl acetate, 2:1) of the
crude product gave, as the first Rf fraction, the minor diastereo-
isomer (RFc,S)-22a as a yellow/orange solid and, as the second Rf
fraction, the major diastereoisomer (SFc,S)-22a as a yellow/orange
solid with a total yield of 62% (0.45 g). (SFc,S)-22a: M.p. 70Ϫ71
[α]D ϭ ϩ119.2 (c ϭ 0.775, CHCl3).1H NMR (400 MHz): δ ϭ
20
20
1
°C (ethanol). [α]D ϭ ϩ233.3 (c ϭ 0.925, CHCl3). H NMR: δ ϭ
1.86 (s, 3 H), 2.66 (dd, J1 ϭ 14.6, J2 ϭ 1.8 Hz, 1 H), 2.98 (dd, J1 ϭ
14.6, J2 ϭ 10 Hz, 1 H), 3.78 (d, J ϭ 14.4 Hz, 1 H), 4.03 (br. t, 1
H), 4.10 (m, 1 H), 4.14 (m, 1 H), 4.16 (s, 5 H), 4.20 (m, 1 H), 4.48
(d, J ϭ 14.4 Hz, 1 H) 7.19Ϫ7.36 (m, 5 H) ppm. 13C NMR: δ ϭ
33.6 (CH2), 35.6 (CH3), 57.0 (CH2), 65.3, 69.4, 69.85, 70.5, 74.3
(CH), 83.15, 91.4 (C), 127.0, 127.7, 128.2 (CH), 143.5 (C) ppm. IR
(CCl4): ν˜ ϭ 1475, 3390 cmϪ1. EI-MS: m/z ϭ 363 [Mϩ], 348, 244,
121, 91, 56. C20H21FeNS (363.07) calcd. C 66.10, H 5.83, N 3.86;
found C 65.89, H 5.99, N 3.46. (RFc,S)-22a: 1H NMR: δ ϭ 2.26 (s,
3 H), 3.01Ϫ3.21 (m, 2 H), 3.48 (d, J ϭ 15.2 Hz, 1 H), 4.03 (br. t,
1 H), 4.09 (br. t, 1 H), 4.14 (m, 2 H), 4.15 (s, 5 H), 4.20 (m, 1 H),
7.22Ϫ7.54 (m, 5 H) ppm. EI-MS: m/z ϭ 363 [Mϩ], 348, 244, 121,
91, 56.
0.92 (d, J ϭ 6.6 Hz, 3 H), 0.96 (d, J ϭ 6.6 Hz, 3 H), 1.51 (m, 1 H),
1.80 (s, 3 H), 2.38 (dd, J1 ϭ J2 ϭ 14.4 Hz, 1 H), 2.39 (dd, 1 H,
J1 ϭ J2 ϭ 14.7 Hz), 2.69 (br. t, J ϭ 8.7 Hz, 1 H) 3.74 (d, J ϭ
14.8 Hz, 1 H), 3.96 (br. t, 1 H), 4.08 (m, 1 H). 4.10 (s, 5 H), 4.14
(m, 1 H), 4.31 (d, J ϭ 14.8 Hz, 1 H) ppm. 13C NMR (100 MHz):
δ ϭ 20.65, 20.8 (CH3), 28.25 (CH2), 30.6 (CH3), 31.0 (CH), 56.9
(CH2), 64.9, 69.5, 69.7, 70.5 (FcCH), 76.75 (CH), 82.2, 92.2 (FcC)
ppm. IR (CCl4): ν˜ ϭ 1480, 3399 cmϪ1 . EI-MS: m/z ϭ 329 [Mϩ],
286, 244, 91, 56. C17H23FeNS (329.09) calcd. C 61.99, H 7.04, N
4.26; found C 61.52, H 7.37, N 4.09. (RFc,S)22c: 1H NMR
(400 MHz): δ ϭ 0.90 (d, J ϭ 6.5 Hz, 3 H), 1.07 (d, J ϭ 6.5 Hz, 3
H), 2.14 (s, 3 H), 2.34Ϫ2.55 (m, 2 H) 2.59 (m, 1 H), 2.77 (dd, J1 ϭ
J2 ϭ 14.7 Hz, 1 H), 3.29 (d, J ϭ 14.9 Hz, 1 H), 3.96 (br. t, 1 H),
4.06 (m, 1 H). 4.11 (s, 5 H ϩ m, 1 H), 4.42 (d, J ϭ 14.9 Hz, 1 H)
ppm. 13C NMR (100 MHz): δ ϭ 20.5 (CH3), 27.1 (CH), 29.9
(CH2), 40.3 (CH3), 48.0 (CH2), 65.3, 69.5, 70.0 (FCH), 70.4 (CH),
70.9 (FcCH) ppm. IR (CCl4): ν˜ ϭ 1480, 3399 cmϪ1 . EI-MS:
tert-Butyl Derivatives: The 1H NMR spectrum of the crude reaction
mixture showed the presence of the bicyclic product 22b as a mix-
ture of two diastereoisomers in a 5.7:1 ratio (de ϭ 70%) and the
absence of the N,N-dimethylated product. Purification by column
chromatography (ethyl acetate/light petroleum ether, 2:1) of the
crude product gave, as the first fraction, the minor diastereoisomer
(RFc,S)-22b as an orange solid and, as the second fraction, the ma-
jor diastereoisomer (SFc,S)-22b as an orange solid and with a total
yield of 58% (0.40 g). (SFc,S)-22b: M.p. 68Ϫ70 °C (ethanol).
m/z ϭ 329 [Mϩ], 286, 244, 91, 56. (S)-2-(Dimethylamino)-1-(ferro-
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cenylthio)-3-methylbutane (14c): M.p. 39Ϫ41 °C (Et2O). [α]D
ϭ
1
ϩ22.4 (c ϭ 1.04, CHCl3). H NMR: δ ϭ 0.92, (d, J ϭ 6.5 Hz, 6
H), 1.82 (m, 1 H), 2.25 (s, 6 H), 2.30 (m, 1 H), 2.55 (dd, J1 ϭ 4.7,
J2 ϭ 13 Hz, 1 H), 2.77 (dd, J1 ϭ 6.5, J2 ϭ 13 Hz, 1 H), 4.18 (m, 2
H), 4.19 (s, 5 H), 4.30 (m, 2 H) ppm. 13C NMR: δ ϭ 19.9, 21.2
(CH3), 29.7 (CH), 36.3 (CH2), 41.4, 68.9, 68.9, 69.4, 69.7, 73.3,
73.35 (CH), 78.6 (C) ppm. IR (CCl4): ν˜ ϭ 1480, 2780 cmϪ1. EI-
MS: m/z ϭ 331 [Mϩ], 217, 100, 58. C17H25FeNS (331.11) calcd. C
61.61, H 7.61, N 4.23; found C 61.58, H 7.64, N 4.28.
20
1
[α]D ϭ ϩ208.4 (c ϭ 0.80, CHCl3). H NMR: δ ϭ 0.94 (s, 9 H),
1.93 (s, 3 H), 2.3 (d, J ϭ 14.5 Hz, 1 H), 2.58 (dd, J1 ϭ 14.5, J2 ϭ
10.5 Hz, 1 H), 2.89 (d, J ϭ 10.5 Hz, 1 H), 3.74 (d, J ϭ 1 5.0 Hz, 1
H), 3.97 (br. t, 1 H), 4.07 (m, 1 H), 4.10 (s, 5 H), 4.14 (m, 1 H),
4.26 (d, J ϭ 15.0 Hz, 1 H) ppm. 13C NMR: δ ϭ 26.9 (CH2), 28.4 General Procedure for the Synthesis of β-Iminoalkyl Sulfides 23: A
33.1 (CH3), 36.1 (C), 58.8 (CH2), 65.0, 69.6, 69.8, 70.6, 79.3 (CH), mixture of 21 (1 mmol) and freshly distilled benzaldehyde
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Eur. J. Org. Chem. 2002, 2776Ϫ2784