Ring Expansions of 2-Alkenylazetidinium Salts
FULL PAPER
a 54:46 ratio; yield: 68%, oil. The following data are characteristic
of the major isomer. Rf = 0.67 (Et2O/PE, 4:6). H NMR (CDCl3):
58:42 ratio; overall yield: 72%, oil. Isolated major isomer: Rf = 0.65
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(Et2O/PE, 9:1). [α]2D0 = –53 (c = 0.3, CH2Cl2). H NMR (CDCl3):
δ = 7.55–6.82 (m, 15 H, Ph), 5.19 (s, 1 H, C=CHH), 5.14 (s, 1 H, δ = 7.33–7.07 (m, 10 H, Ph), 5.55 (tdd, J = 1.6, 8.1 and 15.4 Hz, 1
C=CHH), 3.92 (d, J = 8.1 Hz, 1 H, 2-H), 3.70–3.39 (m, 3 H, 4-H, H, CH=CH), 5.14 (tdd, J = 0.96, 5.6 and 15.4 Hz, 1 H, CH=CH),
5-H, 5Ј-H), 3.06 (t, J = 9.4 Hz, 1 H, 3-H), 2.58 (s, 3 H, NMe) ppm.
3.84 (dd, J = 0.96 and 5.6 Hz, 2 H, CH2O), 3.27 (dd, J = 3.3 and
13C NMR: δ = 147.3 (C-q), 143.0, 142.2, 141.6 (C-ipso Ph), 129.5– 9.6 Hz, 1 H, 5-H), 3.07–3.00 (m, 1 H, 4-H), 2.95 (d, J = 9.5 Hz, 1
126.3 (CHPh), 115.6 (CH2), 74.3 (C-2), 63.7 (C-5), 55.1 (C-3), 49.9
H, 2-H), 2.79 (t, J = 9.6 Hz, 1 H, 5Ј-H), 2.62 (q, J = 8.1 Hz, 1 H,
3-H), 2.09 (s, 3 H, NMe) ppm. 13C NMR: δ = 145.9 (CH), 140.8
(CH), 131.4, 131.0 (C-ipso Ph), 128.6, 128.4, 128.2, 128.1, 127.6,
127.5, 126.3 (CHPh), 78.2 (C-2), 63.7 (C-5), 63.3 (CH2O), 61.6 (C-
3), 49.1 (C-4), 40.7 (C-6) ppm. MS (ESI, pos.): m/z = 294.1 [M+H]
+. C20H23NO (293.4): calcd. C 81.87, H 7.90, N 4.77; found C
81.74, H 7.83, N 4.89. Isolated minor isomer: Rf = 0.55 (Et2O/PE,
(C-4), 40.7 (Me) ppm. MS (ESI, pos.): m/z = 340.1 [M+H]+.
(2R,3S,4R)- and (2S,3S,4R)-3-Isopropenyl-1-methyl-2,4-diphenyl-
pyrrolidine (32): This compound was purified by flash chromatog-
raphy (Et2O/PE, 2:98, 5:95, 10:90), mixture of two isomers at C-2
in a 86:14 ratio; overall yield: 94%, oil. Isolated major isomer: Rf
= 0.71 (Et2O/PE, 3:7). [α]2D0 = –16 (c = 0.6, CH2Cl2). 1H NMR
(CDCl3): δ = 7.35–7.09 (m, 10 H, Ph), 4.64–4.56 (m, 1 H,
C=CHH), 4.55–4.53 (m, 1 H, C=CHH), 3.65 (d, J = 10.2 Hz, 1 H,
2-H), 3.56–3.42 (m, 2 H, 4-H, 5-H), 3.11 (t, J = 9.2 Hz, 1 H, 3-H),
2.49 (td, J = 0.96 and 8.5 Hz, 1 H, 5Ј-H), 2.24 (s, 3 H, NMe), 1.13
(s, 3 H, Me) ppm. 13C NMR: δ = 144.3, 142.6 (C-ipso Ph), 140.6
(C-q), 129.0, 128.6, 128.5, 128.4, 127.9, 127.7, 127.6, 127.5, 127.4,
126.8 (CHPh), 113.9 (CH2), 74.4 (C-2), 64.0 (C-5), 59.3 (C-3), 47.0
(C-4), 41.2 (Me), 22.4 (Me) ppm. MS (ESI, pos.):m/z = 300.1
[M+Na]+, 278.1 [M +H]+. C20H23N (277.4): calcd. C 86.59, H
8.36, N 5.05; found C 86.47, H 8.25, N 4.92. Isolated minor isomer:
9:1). [α]2D0 = –34 (c = 0.6, CH2Cl2). H NMR (CDCl3): δ = 7.26–
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7.08 (m, 10 H, Ph), 5.19–5.04 (m, 2 H, CH=CH), 3.62–3.57 (m, 32
H, CH2O, 2-H), 3.44 (dd, J = 6.7 and 9.1 Hz, 1 H, 5-H), 3.17 (td,
J = 7.5 and 10.5 Hz, 1 H, 4-H), 2.95 (q, J = 8.5 Hz, 1 H, 3-H),
2.50 (dd, J = 9.1 and 10.4 Hz, 1 H, 5Ј-H), 2.22 (s, 3 H, NMe) ppm.
13C NMR: δ = 142.3 (CH), 140.2 (CH), 134.5, 130.1 (C-ipso Ph),
128.7, 128.5, 128.1, 127.8, 127.0, 126.6 (CHPh), 75.3 (C-2), 64.3
(C-5), 63.2 (CH2O), 55.2 (C-3), 50.3 (C-4), 40.9 (NMe) ppm. MS
(ESI, pos.): m/z = 294.1 [M+H]+.
Ethyl (2R,6R)- and (2S,6R)-1-Benzyl-4,6-diphenyl-2,3,6,7-tetra-
hydro-1H-azepane-2-carboxylate (35): This compound was purified
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Rf = 0.57 (Et2O/PE, 3:7). [α]2D0 = –22 (c = 0.3, CH2Cl2). H NMR
(CDCl3): δ = 7.46–7.23 (m, 10 H, Ph), 4.74 (s, 1 H, C=CHH), 4.65 by flash chromatography (Et2O/PE, 5:95, 10:90, 15:85), mixture of
(s, 1 H, C=CHH), 3.76 (d, J = 10.1 Hz, 1 H, 2-H), 3.66–3.52 (m, two isomers at C-2 in a 60:40 ratio; overall yield: 93%, oil. Isolated
2 H, 4-H, 5-H), 3.21 (t, J = 9.6 Hz, 1 H, 3-H), 2.69–2.56 (m, 1 H,
major isomer: Rf = 0.56 (Et2O/PE, 3:7). [α]2D0 = +6 (c = 0.4,
5Ј-H), 2.34 (s, 3 H, NMe), 1.23 (s, 3 H, Me) ppm. 13C NMR: δ = CH2Cl2). 1H NMR (CDCl3): δ = 7.41–7.20 (m, 15 H, Ph), 6.04 (d,
144.3, 142.6 (C-ipso Ph), 140.7 (C-q), 129.0, 128.6, 128.5, 128.4,
127.9, 127.7, 127.6, 127.5, 127.4, 126.5 (CHPh), 113.1 (CH), 76.2
J = 4.1 Hz, 1 H, 5-H), 4.19 (q, J = 7.1 Hz, 2 H, CH2O), 4.09 (t, J
= 4.0 Hz, 1 H, 2-H), 3.95–3.82 (m, 3 H, 6-H, NCH2Ph), 3.26–3.08
(C-2), 64.1 (C-5), 59.3 (C-3), 47.6 (C-4), 40.8 (NMe), 20.5 (Me) (m, 4 H, 3-H, 3Ј-H, 7-H, 7Ј-H), 1.22 (t, J = 7.1 Hz, 3 H, Me) ppm.
ppm. MS (ESI, pos.): m/z = 300.1 [M+Na]+, 278.1 [M+H]+.
13C NMR: δ = 173.9 (CO), 144.7, 144.3, 138.9 (C-ipso Ph, C-4),
133.4 (C-5), 128.9–126.2 (CHPh), 64.3 (C-2), 60.8 (CH2O), 59.4
(NCH2), 57.2 (C-3), 46.3 (C-6), 32.1 (C-7), 14.3 (Me) ppm. MS
(IC, NH3): m/z = 412 [M+H]+. Minor isomer (not isolated pure):
(2R,3S,4R)- and (2S,3S,4R)-1-Methyl-2,4-diphenyl-3-vinylpyrroli-
dine (33): This compound was purified by flash chromatography
(Et2O/PE, 5:95, 10:90, 15:85), mixture of two isomers at C-2 in a
53:47 ratio; overall yield: 83%, oil. Isolated major isomer: Rf = 0.78
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Rf = 0.55 (Et2O/PE, 3:7). H NMR (CDCl3): δ = 7.33–7.11 (m, 15
H, Ph), 6.04 (d, J = 4.1 Hz, 1 H, 5-H), 5.56–3.88 (m, 5 H, 2-H,
NCH2, CH2O), 3.73 (dd, J = 2.7 and 8.7 Hz, 1 H, 6-H), 3.57 (dd,
J = 10.8 and 11 Hz, 1 H, 3-H), 3.26 (ddd, J = 1.35, 8.7, 15.6 Hz,
1 H, 7-H), 2.99 (dd, J = 2.5 and 15.6 Hz, 1 H, 7Ј-H), 2.74 (dd, J
= 2.7 and 13.7 Hz, 1 H, 3Ј-H), 0.99 (t, J = 7.1 Hz, 3 H, Me) ppm.
13C NMR: δ = 173.2 (CO), 144.9, 144.0, 139.4, 139.0 (C-ipso Ph,
C-4), 134.5 (C-5), 128.8–126.1 (CHPh), 63.0 (C-2), 60.4 (CH2O and
CH2N), 55.1 (C-3), 46.1 (C-6), 34.6 (C-7), 14.1 (Me) ppm. HRMS:
m/z calcd. for C28H30NO2 [M+H]+ 412.2271; found 412.2270.
(Et2O/PE, 3:7). [α]2D0 = +27 (c = 0.1, CH2Cl2). H NMR (CDCl3):
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δ = 7.44–7.21 (m, 10 H, Ph), 5.37 (td, J = 9.8 and 16.8 Hz, 1 H,
CH=CH2), 4.66–4.58 (m, 2 H, CH=CH2), 3.71 (d, J = 9.6 Hz, 1
H, 2-H), 3.55 (dd, J = 6.7 and 8.9 Hz, 1 H, 5-H), 3.28 (td, J = 6.8
and 10.6 Hz, 1 H, 4-H), 3.05 (q, J = 9.1 Hz, 1 H, 3-H), 2.63 (dd,
J = 9.1 and 10.4 Hz, 1 H, 5Ј-H), 2.34 (s, 3 H, NMe) ppm. 13C
NMR: δ = 142.2 (C-ipso Ph), 139.3 (CH), 128.6, 128.4, 128.0,
127.8, 127.4, 126.8, 126.4 (CHPh), 114.9 (CH2), 74.9 (C-2), 64.1
(C-5), 56.8 (C-3), 50.1 (C-4), 40.9 (C-6) ppm. MS (ESI, pos.): m/z
= 286.1 [M+Na]+, 264.1 [M+H]+. HRMS: m/z calcd. for C19H22N
[M+H]+ 264.1747; found 264.1758. Isolated minor isomer: Rf =
0.77 (Et2O/PE, 3:7). [α]2D0 = –63 (c = 0.3, CH2Cl2). 1H NMR
Ethyl (2R,6R)- and (2S,6R)-1-Benzyl-6-phenyl-2,3,6,7-tetrahydro-
1H-azepane-2-carboxylate (36): This compound was purified by
flash chromatography (Et2O/PE, 5:95, 10:90, 15:85), mixture of two
(CDCl3): δ = 7.46–7.19 (m, 10 H, Ph), 5.89–5.71 (m, 1 H, isomers at C-2 in a 90:10 ratio; overall yield: 99%, oil. Major iso-
CH=CH2), 4.90 (dd, J = 1.4 and 10.2 Hz, 1 H, CH=CHH), 4.67 mer (not isolated pure): Rf = 0.55 (Et2O/PE, 3:7). 1H NMR
(dd, J = 0.66 and 17 Hz, 1 H, CH=CHH), 3.41 (dd, J = 3.3 and
9.8 Hz, 1 H, 5-H), 3.22–3.12 (m, 1 H, 4-H), 3.07 (d, J = 9.4 Hz, 1
H, 2-H), 2.91 (t, J = 9.6 Hz, 1 H, 5Ј-H), 2.70 (q, J = 8.3 Hz, 1 H,
3-H), 2.22 (s, 3 H, NMe) ppm. 13C NMR: δ = 146.2, 141.0 (C-
(CDCl3): δ = 7.40–7.15 (m, 10 H, Ph), 5.81–5.74 (m, 2 H, 4-H, 5-
H), 4.21 (q, J = 7.1 Hz, 2 H, CH2O), 3.98–3.94 (m, 1 H, 6-H),
3.84–3.81 (m, 2 H, NCH2Ph), 3.13–2.97 (m, 2 H, 7-H, 7Ј-H), 2.85–
2.73 (m, 2 H, 3-H, 3Ј-H), 1.31 (t, J = 7.1 Hz, 3 H, Me) ppm. 13C
ipso Ph), 138.0 (C-q), 128.6, 128.4, 128.3, 128.1, 127.6, 127.4, 126.2 NMR: δ = 173.7 (CO), 144.1, 139.0 (C-ipso Ph), 135.0, 128.8,
(CHPh), 116.3 (CH2), 78.1 (C-2), 63.7 (C-5), 63.5 (C-3), 48.9 (C-
4), 40.8 (C-6) ppm. MS (ESI, pos.): m/z = 286.1 [M+Na]+, 264.1
[M+H]+.
128.6, 128.4, 128.2, 127.9, 127.6, 127.0, 126.9, 126.3 (CHPh,
CH=CH), 65.3 (C-2), 60.7 (CH2O), 57.7 (C-7), 56.4 (CH2N), 46.4
(C-6), 28.9 (C-3), 14.3 (Me) ppm. MS (IC, NH3): m/z = 336
[M+H]+. HRMS: m/z calcd. for C22H26NO2 [M+H]+ 336.1958;
found 336.1941.
3-[(2R,3S,4R)- and (2S,3S,4R)-1-Methyl-2,4-diphenylpyrrolidin-3-
yl]prop-2-en-1-ol (34): For this compound, 2.2 equiv. of KHMDS
was used. This compound was purified by flash chromatography
(Et2O/PE, 5:95, 10:90, 15:85), mixture of two isomers at C-2 in a
Diethyl (2R,3R,6R)- and (2S,3R,6R)-1-Benzyl-6-phenyl-2,3,6,7-
tetrahydro-1H-azepane-2,3-dicarboxylate (37): This compound was
Eur. J. Org. Chem. 2006, 4214–4223
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