Job/Unit: O20806
/KAP1
Date: 24-09-12 17:12:45
Pages: 15
E. Villemin, M.-F. Herent, J. Marchand-Brynaert
FULL PAPER
3J1,2 = 5.9, 4J2,4Ј = 4J2,4 = 1.5 Hz, 1 H, C(2)-H], 4.19 [q, 3J = 7.1 Hz, Diethyl
2-(6-Cyanohexyl)-1,3-dioxo-2,3,3a,4,7,7a-hexahydro-1H-
2 H, PO(OCH2CH3)2], 4.09 [q, 3J = 7.3 Hz, 2 H, PO(OCH2-
isoindole-4-phosphonate (5c): N-(6-Cyanohexyl)maleimide (3c,
0.658 g, 3.19 mmol) and 1-diethoxyphosphoryl-1,3-butadiene
(0.607g, 3.19 mmol) gave 5c as a yellow oil (0.607 g, 48%), after
purification by column chromatography on silica gel (ethyl acetate
then acetonitrile). Rf = 0.3 (ethyl acetate). 1H NMR (500 MHz,
CDCl3): δ = 6.12–6.06 [m, 1 H, C(3)-H], 6.02–5.94 [m, 1 H, C(2)-
3
3
CH3)2], 3.46 (m, 2 H, NCH2), 3.33 [ddd, J6,P = 18.8, J5,6 = 9.4,
3J1,6 = 6.4 Hz, 1 H, C(6)-H], 3.11 [td, J5,6
4.2 Hz, 1 H, C(5)-H], 2.97 [dt, J1,P = 22.8, J1,6 = J1,2 = 6.0 Hz,
=
3J4Ј,5 = 9.3, J4,5
=
3
3
1
3
3
2
3
1 H, C(1)-H], 2.72 [dqd, J4,4Ј = 16.3, J4,5
=
5J4,P
=
3J3,4 = 4.0,
2
3
4J2,4 = 1.0 Hz, 1 H, C(4)-H], 2.25 [dddq, J4,4Ј = 16.3, J4Ј,5 = 8.3,
3J3,4Ј = 5.3, J2,4Ј = J4Ј,6 = J1,4Ј = 1.7 Hz, 1 H, C(4)-HЈ], 1.56 (tt,
H], 4.24–4.12 [m, 2 H, PO(OCH2CH3)2], 4.11–4.04 [m, 2 H,
4
4
5
3J = 7.2, J = 7.0 Hz, 2 H, NCH2CH2), 1.32 [t, J = 6.9 Hz, 3 H, PO(OCH2CH3)2], 3.49–3.44 (m, 2 H, NCH2), 3.32 [ddd, J6,P
=
3
3
3
PO(OCH2CH3)2], 1.31 [t, 3J = 6.9 Hz, 3 H, PO(OCH2CH3)2], 1.28– 18.9, 3J5,6 = 9.4, 3J1,6 = 7.2 Hz, 1 H, C(6)-H], 3.11 [td, 3J5,6 = 3J4Ј,5
3
1
3
1.24 [m, 6 H, N(CH2)2CH2(CH2)2CH3, N(CH2)3CH2CH2CH3, and
= 9.2, J4,5 = 4.3 Hz, 1 H, C(5)-H], 2.98 [ddd, J1,P = 22.9, J1,6 =
3
2
N(CH2)4CH2CH3], 0.87 [t, 3J = 6.9 Hz, 3 H, N(CH2)4CH2- 6.3, J1,2 = 5.6 Hz, 1 H, C(1)-H], 2.76–2.68 [m, J4,4Ј = 16.4 Hz, 1
CH3] ppm. 13C NMR (125 MHz, CDCl3): δ = 179.2 (s, C=O), 176.5
H, C(4)-H], 2.40–2.35 [m, 1 H, C(4)-HЈ], 2.34 (t, J = 7.1 Hz, 2 H,
3
(d, 3J = 4.4 Hz, C=O), 130.3 [d, J3,P = 12.3 Hz, C(3)], 124.3 [d, CH2CN), 1.64 (m, 2 H, NCH2CH2), 1.64 (tt, 3J = 7.5, 3J = 7.3 Hz,
3
2J2,P = 7.7 Hz, C(2)], 63.1 [d, J = 6.6 Hz, PO(OCH2CH3)2], 61.9
2 H, NCH2CH2), 1.58 (tt, 3J = 8.0, 3J = 7.5 Hz, 2 H, CH2CH2CN),
2
[d, 2J = 7.0 Hz, PO(OCH2CH3)2], 40.7 [d, J6,P = 3.4 Hz, C(6)],
1.46 [tt, 3J = 7.6, 3J = 7.5 Hz, 2 H, N(CH2)2CH2(CH2)3Cl or
2
3
1
39.0 (s, NCH2), 39.0 [d, J5,P = 9.0 Hz, C(5)], 34.1 [d, J1,P
=
N(CH2)3CH2(CH2)2Cl], 1.30 [m, 8 H, PO(OCH2CH3)2 and
146.4 Hz, C(1)], 31.4 [s, N(CH2)3CH2CH2CH3], 27.5 (s, N(CH2)2CH2(CH2)3Cl or N(CH2)3CH2(CH2)2Cl] ppm. 13C NMR
NCH2CH2), 26.5 [s, N(CH2)2CH2], 22.9 [s, C(4)], 22.5 [s, N(CH2)4- (125 MHz, CDCl3): δ = 179.1 (s, C=O), 176.5 (d, 3J = 3.6 Hz,
CH2CH3], 16.4 [d, 3J = 5.8 Hz, PO(OCH2CH3)2], 16.4 [d, 3J =
C=O), 130.3 [d, J3,P = 12.2 Hz, C(3)], 124.3 [d, J2,P = 7.7 Hz,
3
2
6.0 Hz, PO(OCH2CH3)2], 14.0 [s, N(CH2)5CH3] ppm. 31P NMR C(2)], 119.7 (s, CN), 63.0 [d, 2J = 6.4 Hz, PO(OCH2CH3)2], 61.9
2
3
(202 MHz, CDCl ): δ = 25.90 ppm. IR: ν = 2930 (w), 2858 (w),
[d, J = 7.0 Hz, PO(CH2CH3)2], 40.7 [d, J6,P = 2.9 Hz, C(6)], 38.8
˜
3
3
1
1778 (w, C=O), 1697 (s, C=O), 1439 (m), 1402 (m), 1254 (m, P=O),
[d, J5,P = 8.8 Hz, C(5)], 38.6 (s, NCH2), 34.0 [d, J1,P = 146.0 Hz,
1056 (m), 1024 (s, P–O), 960 (s, P–O), 754 (w) cm–1. MS [APCI C(1)], 28.1 (s, NCH2CH2), 27.2 [s, N(CH2)2CH2], 25.9 [s, N(CH2)3-
(atmospheric pressure chemical ionization), positive mode]: m/z (%)
= 373.12 (19) [M + H], 372.11 (100) [M], 345.12 (2) [M + H –
CH2=CH2], 344.11 (13) [M – CH2=CH2], 317.18 (1) [M + H –
CH2(CH2)3CN], 25.2 [s, N(CH2)4CH2CH2CN], 22.8 [s, C(4)], 17.0
3
3
(s, CH2CN), 16.4 [d, J = 6.4 Hz, PO(OCH2CH3)2], 16.3 [d, J =
6.9 Hz, PO(OCH2CH3)2] ppm. 31P NMR (202 MHz, CDCl3): δ =
2CH2=CH2], 316.16 (6) [M – 2CH2=CH2], 298.04 (1) [M – 25.98 ppm. IR: ν = 2970 (m), 2945 (m), 2858 (m), 2243 (w, CN),
˜
2CH2=CH2 – H2O]. HRMS (MALDI-TOF, positive mode): calcd.
for C18H31NO5P (100) [M + H] 372.1940; found 372.1928.
1737 (s, C=O), 1708 (s, C=O), 1357 (m), 1217 (s, P=O), 1051 (s),
1024 (s, P–O), 962 (s, P–O), 754 (m) cm–1. HRMS (MALDI-TOF,
positive mode): calcd. for C19H29N2O5NaP (100) [M + Na]
419.1712; found 419.1692.
Diethyl
2-(6-Chlorohexyl)-1,3-dioxo-2,3,3a,4,7,7a-hexahydro-1H-
isoindole-4-phosphonate (5b): N-(6-Chlorohexyl)maleimide (3b,
0.224 g, 1.038 mmol) and 1-diethoxyphosphoryl-1,3-butadiene
(0.198 g, 1.038 mmol) gave 5b as a yellow oil (244 mg, 58%). Rf =
0.3 (ethyl acetate/acetone, 1:1). H NMR (500 MHz, CDCl3): δ =
6.12–6.05 [m, 1 H, C(3)-H], 6.03–5.95 [m, 1 H, C(2)-H], 4.25–4.11
Diethyl
2-(6-tert-Butylhexylcarbamoyl)-1,3-dioxo-2,3,3a,4,7,7a-
hexahydro-1H-isoindole-4-phosphonate (5d): N-[NЈ-(tert-Butyloxy-
carbonyl)-6-aminohexyl]maleimide (3d, 0.229 g, 0.776 mmol) and
1-diethoxyphosphoryl-1,3-butadiene (0.147 g, 0.776 mmol) gave 5d
1
1
[m,
2
H, PO(OCH2CH3)2], 4.08 [q, 3J
=
6.9 Hz,
2
H,
as a yellow oil (256 mg, 68%). Rf = 0.3 (ethyl acetate). H NMR
3
3
3
PO(OCH2CH3)2], 3.51 (t, J = 6.7 Hz, 2 H, CH2Cl), 3.48–3.43 (m, (500 MHz, CDCl3): δ = 6.08 [dtt, J2,3 = 9.3, J3,4Ј
2 H, NCH2), 3.32 [ddd, J6,P = 18.8, J5,6 = 9.3, J1,6 = 6.6 Hz, 1
=
4J3,5 = 4.6,
3
3
3
4
3
3
3J3,4 = J3,P = 1.7 Hz, 1 H, C(3)-H], 5.98 [dtt, J2,3 = 9.3, J2,P
=
3
3
3
4
4
H, C(6)-H], 3.10 [td, J5,6 = J4Ј,5 = 9.2, J4,5 = 4.2 Hz, 1 H, C(5)-
3J1,2 = 6.0, J2,4Ј = J2,4 = 1.9 Hz, 1 H, C(2)-H], 4.73 (br. s, 1 H,
H], 2.97 [dt, 1J1,P = 22.7, 3J1,6 = 3J1,2 = 5.8 Hz, 1 H, C(1)-H], 2.74– NHBoc), 4.23–4.11 [m, 2 H, PO(OCH2CH3)2], 4.07 [q, 3JЈ =
2
2.65 [m, J4,4Ј = 16.5 Hz, 1 H, C(4)-H], 2.39–2.30 [m, 1 H, C(4)- 7.1 Hz, 2 H, PO(OCH2CH3)2], 3.49–3.40 (m, 2 H, NCH2), 3.31
3
3
3
3
3
HЈ], 1.75 (tt, J = 7.3, J = 6.9 Hz, 2 H, CH2CH2Cl), 1.57 (quint,
[ddd, J6,P = 19.2, J5,6 = 9.3, J1,6 = 6.7 Hz, 1 H, C(6)-H], 3.11
3J = 7.5 Hz, 2 H, NCH2CH2), 1.44 [tt, J = 7.7, J = 7.4 Hz, 2 H,
[td, J5,6 = J4Ј,5 = 9.3, J4,5 = 4.3 Hz, 1 H, C(5)-H], 3.07 (t, J =
3
3
3
3
3
3
N(CH2)3CH2(CH2)2Cl], 1.36 [tt, 3J = 7.5, 3J = 7.0 Hz, 2 H, N(CH2)2- 7.2 Hz, 2 H, CH2NHBoc), 2.97 [ddd, 1J1,P = 22.6, J1,6 = 5.9, J1,2
3
3
CH2(CH2)3Cl], 1.31 [t, J = 7.0 Hz, 3 H, PO(OCH2CH3)2], 1.30 [t, = 5.8 Hz, 1 H, C(1)-H], 2.70 [dqd, J4,4Ј = 16.4, 3J4,5 = 5J4,P = 3J3,4
3
2
3J = 6.9 Hz, 3 H, PO(OCH2CH3)2], 1.30–1.22 [m, 2 H, N(CH2) = 4.1, J2,4 = 1.4 Hz, 1 H, C(4)-H], 2.35 [dddq, J4,4Ј = 16.3, J4Ј,5
4
2
3
2CH2(CH2)3Cl] ppm. 13C NMR (125 MHz, CDCl3): δ = 179.2 (s,
C=O), 176.5 (d, 3J = 4.0 Hz, C=O), 130.3 [d, 3J3,P = 12.3 Hz, C(3)],
= 8.4, J3,4Ј = 5.4, J2,4Ј = J4Ј,6 = J4Ј,P = 1.7 Hz, 1 H, C(4)-HЈ],
1.54 (tt, 3J = 7.4, 3J = 7.0 Hz, 2 H, NCH2CH2), 1.48–1.43 (m,
2 H, CH2CH2CN), 1.42 [s, 9 H, CH3(Boc)], 1.33–1.26 [m, 10 H,
3
4
4
5
124.3 [d, J2,P = 7.5 Hz, C(2)], 63.1 [d, 2J = 6.5 Hz, PO(OCH2-
2
CH3)2], 62.0 [d, 2J = 7.0 Hz, PO(OCH2CH3)2], 44.9 (s, CH2Cl), PO(OCH2CH3)2,N(CH2)2CH2(CH2)3CN,andN(CH2)3CH2(CH2)2-
2
3
40.7 [d, J6,P = 3.1 Hz, C(6)], 38.9 [d, J5,P = 9.6 Hz, C(5)], 38.8 (s,
CN] ppm. 13C NMR (125 MHz, CDCl3): δ = 179.2 (s, C=O), 176.5
NCH2), 34.1 [d, J1,P = 146.4 Hz, C(1)], 32.4 (s, CH2CH2Cl), 27.4 (d, 3J = 4.4 Hz, C=O), 156.0 [s, (Boc)C=O], 130.3 [d, J3,P
=
1
3
2
(s, NCH2CH2), 26.4 [s, N(CH2)3CH2(CH2)2Cl], 26.1 [s, N(CH2)2- 12.2 Hz, C(3)], 124.2 [d, J2,P = 7.8 Hz, C(2)], 78.8 [s, Cq(Boc)],
CH2(CH2)3Cl], 22.9 [s, C(4)], 16.4 [d, 3J = 6.1 Hz, PO(OCH2- 63.0 [d, 2J = 6.5 Hz, PO(OCH2CH3)2], 61.8 [d, 2J = 7.0 Hz,
CH3)2], 16.4 [d, 3J = 6.4 Hz, PO(OCH2CH3)2] ppm. 31P NMR PO(OCH2CH3)2], 40.6 [d, J6,P
= 3.3 Hz, C(6)], 40.3 (s,
2
3
(202 MHz, CDCl ): δ = 26.10 ppm. IR: ν = 2988 (m), 2931 (m),
CH2NHBoc), 38.8 [d, J5,P = 8.2 Hz, C(5)], 38.7 (s, NCH2), 33.9
˜
3
1
2860 (w), 1776 (m, C=O), 1699 (s, C=O), 1402 (s), 1047 (s), 1228
(m, P=O), 1022 (s, P–O), 960 (s, P–O), 788 (s), 754 (s, C–Cl), 681
(w) cm–1. HRMS (MALDI-TOF, positive mode): calcd. for
C18H30NO5ClP (100) [M + H] 406.1550; found 406.1530; m/z =
428.1333 (38) [M + Na], 378.1212 (16) [M + H – CH2=CH2],
350.0928 (12) [M + H – 2CH2=CH2].
[d, J1,P = 146.1 Hz, C(1)], 29.7 (s, CH2CH2NHBoc), 28.4 [s,
CH3(Boc)], 27.4 (s, NCH2CH2), 26.3 [s, N(CH2)2CH2(CH2)3-
NHBoc or N(CH2)3CH2(CH2)2NHBoc], 26.2 [s, N(CH2)3CH2-
(CH2)2NHBoc or N(CH2)2CH2(CH2)3NHBoc], 22.8 [s, C(4)], 16.3
3
[d, J6,P
= = 6.8 Hz,
6.5 Hz, PO(OCH2CH3)2], 16.3 [d, 3J
PO(OCH2CH3)2] ppm. 31P NMR (202 MHz, CDCl3):
δ =
8
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