3672
V. Stockmann et al. / Tetrahedron 65 (2009) 3668–3672
4
.3. (Z)-4-Isocyano-2-(thiophen-3-yl)but-2-enenitrile (3)
126.8 (pyrrole-C5), 125.0 (pyrrole-C2), 119.6 (pyrrole-C3), 115.3 (C1,
CN), 114.4 (C2), 107.2 (pyrrole-C4), 41.7 (t, J 7.0, CH –NC), 17.7 (TIPS-
CH ). 11.5 (TIPS–CH); NMR assignments are based on HSQC, HMBC
and NOESY experiments; IR (film) max 2948s, 2869s, 2215w, 2147s,
2
The title compound was isolated as a yellow solid (16 mg, 27%),
pure by NMR; R 0.37 (CH Cl ); R 0.47 (0.5% MeOH/CH Cl ); mp 61–
2 C; H NMR (300 MHz, CDCl 7.60 (1H, dd, J 3.0, 1.2, thienyl-
H2), 7.42 (1H, dd, J 5.1, 3.0, thienyl-H5), 7.26 (1H, dd, J 5.1, 1.2,
3
f
2
2
f
2
2
n
ꢁ
1
6
3
)
d
H
1624m, 1491m, 1463m, 1264m, 1227m, 1130s, 1097s, 884s,
795s cm ; ESI-HRMS calcd for [MþNa]þ
ꢀ
1
18 27 3
C H N NaSi: 336.1867;
1
3
thienyl-H4), 6.64 (1H, t, J 6.9, H3), 4.51 (2H, d, J 6.9, –CH
NMR (100 MHz, CDCl 159.5 (br s, CH –NC), 133.3 (thienyl-C3),
32.5 (C3),128.2 (thienyl-C5),125.8 (thienyl-C2),123.8 (thienyl-C4),
2
, H4);
C
obsd 336.1882.
3
)
d
C
2
1
4.7. (Z)-N-(3-Cyano-3-(1-(triisopropylsilyl)-1H-pyrrol-3-
yl)allyl)-formamide (7a)
1
15
1
14.9 (C2), 114.6 (CN, C1), 41.7 (t, J 7.0, CH
600 MHz, CDCl ) showed correlation between both H3/H4 and
NC ( 165 ppm). NMR assignments are based on ATP, HSQC,
NOESY and HMBC experiments; IR (KBr) max 3080w, 2231w, 2154s,
624w, 1437m, 1359w, 1276m, 1103w, 955m, 930m, 777s cm
2
–NC, C4); H– N HMBC
(
–
3
d
N
HCl (1.0 mL, concd) and H O (1.0 mL) were added to compound
2
n
7 (10.0 mg, 31.9 mmol) to form a heterogeneous mixture. The orig-
ꢀ
1
1
;
inal solid turned into a brown oil after 1 h. Water (10.0 mL) was
added and the oil was dissolved in CH Cl (20 mL). The organic
þ
EIMS m/z (%) 174 (M , 100), 149 (38), 147 (48), 134 (12), 122 (52), 111
2
2
þ
(
1
29), 104 (14), 97 (21); ESI-HRMS calcd for [MþNa]
C
H
9 6
N
2
NaS:
2 4
extracts were dried over Na SO and concentrated in vacuo. The
97.0143; obsd 197.0145; calcd for [MþH]þ
C
S: 175.0324;
9
7
H N
2
product was obtained as a brown oil (10 mg, 95%). Full conversion
1
obsd 175.0327.
of 7 into compound 7a was obtained as shown by NMR; H NMR
(
400 MHz, CDCl
pyrrole-H2), 6.74 (1H, dd, J 2.8, 2.0, pyrrole-H5), 6.46 (1H, t, J 7.2,
CH–), 6.42 (1H, dd, J 2.8, 1.6, pyrrole-H4), 5.85 (1H, s, br, NH), 4.31
3 H
) d 8.24 (1H, s, CH]O), 6.97 (1H, dd, J 2.8, 1.2,
4
.4. (Z)-4-Amino-2-(thiophen-3-yl)but-2-enenitrile (3b)
Typical procedure for the formation of amine 3a; isonitrile 3
]
2 3 2
(2H, dd, J 7.2, 6.4, CH –NH),1.45 (3H, sept, J 7.6, CH(CH ) ),1.10 (18H,
13
(
10 mg) was dissolved in 10% D
2
O/H
2
O (1 mL) in an NMR tube. HCl
d, J 7.6, CH(CH ) ); C NMR (100 MHz, CDCl3)
C
d 161.0 (CH]O),
3
2
(
concd, excess, approx. three drops) was added. Depending on the
132.8 (]CH–), 126.4 (pyrrole-C5), 124.0 (pyrrole-C2), 120.3 (pyr-
role-C3), 116.4 (CN), 112.8 (CH]C–CN), 107.2 (pyrrole-C4), 38.2
(CH –NH), 17.7 (TIPS-CH ), 11.5 (TIPS-CH); NMR assignments are
amount of added HCl, full conversion of 3 to amine 3a was obtained
in 2–30 h. The reaction was monitored by NMR; H NMR (400 MHz,
1
2
3
H
2
2
O/D O/HCl)
d
H
8.31 (2H, br, NH
2
), 7.75 (1H, dd, J 2.8, 1.2, thienyl-
based on HSQC and HMBC experiments; IR (film)
n
max
3319br,
H2), 7.56 (1H, dd, J 5.2, 2.8, thienyl-H5), 7.42 (1H, dd, J 5.2, 1.2,
2947s, 2868s, 2219w, 1668s, 1464m, 1385m, 1227m, 1132s, 1098s,
13
ꢀ1
þ
thienyl-H4), 6.93 (1H, t, J 7.6, H3), 4.10 (2H, d, J 7.6, –CH
NMR (100 MHz, H O/D O/HCl) 136.7 (C3), 136.3 (thienyl-C3),
31.3 (thienyl-C5), 128.8 (thienyl-C2), 127.3 (thienyl-C4), 118.4 (C2),
18.0 (-CN, C1), 42.7 (C4); NMR assignments are based on H,H-
2
; H4);
C
1017m, 884s cm ; ESI-HRMS calcd for [MþH] C18H30N OSi:
3
þ
2
2
d
C
332.2152; obsd 332.2161; calcd for [MþNa] C18H29N ONaSi:
3
1
354.1972; obsd 354.1978.
1
þ
COSY, HSQC and HMBC experiments; ESI-HRMS calcd for [MþH]
Acknowledgements
C
H
8 9
N
2
S: 165.0481; obsd 165.0480.
.5. 2-(Thien-3-yl)-1H-pyrrole-3-carbonitrile (4)
The title compound was isolated as an orange oil (4 mg, 6%),
Trygve Andreassen (Ph.D.), NMR-centre, NT-faculty, NTNU, is
acknowledged for his NMR technical assistance.
4
References and notes
1
pure by NMR; R
f
0.37 (CH
2
Cl
2 f 2 2
); R 0.40 (0.5% MeOH/CH Cl ); H
NMR (400 MHz, DMSO-d
6
)
d
H
12.1 (1H, br s, NH), 7.87 (1H, dd, J 2.8,
1. Stockmann, V.; Fiksdahl, A. Tetrahedron 2008, 64, 7626.
2. Hansen, L. K.; Stockmann, V.; Fiksdahl, A. Acta Crystallogr. 2007, E63, o3290.
3. Hansen, L. K.; Stockmann, V.; Fiksdahl, A. Acta Crystallogr. 2007, E63, o3896.
4. Stockmann, V.; Eriksen, K. L.; Fiksdahl, A. Tetrahedron 2008, 64, 11180.
1.6, thienyl-H2), 7.72 (1H, dd, J 4.8, 2.8, thienyl-H5), 7.59 (1H, dd, J
4
.8, 1.6, thienyl-H4), 6.97 (1H, dd, J 2.8, 2.8 pyrrole-H5), 6.53 (1H,
13
dd, J 2.8, 2.4, pyrrole-H4); C NMR (100 MHz, DMSO-d
6
)
d
C
134.3
5. Bakke, J. M.; Hegbom, I.; Øvreeide, K.; Aaby, K. Acta Chem. Scand. 1994, 48, 1001.
. Bakke, J. M.; Ranes, E. Synthesis 1997, 281.
. Morishima, I.; Mizuno, A.; Yonezawa, T. J. Chem. Soc., Chem. Commun. 1970, 1321.
. Hahn, F. E.; Langenhahn, V.; Pape, T. Chem. Commun. 2005, 5390.
9. Hahn, F. E.; Tamm, M. Angew. Chem., Int. Ed. Engl. 1991, 30, 203.
6
7
8
(
pyrrole-C2), 131.0 (thienyl-C3), 127.7 (thienyl-C5), 125.0 (thienyl-
C4),121.5 (thienyl-C2),119.9 (pyrrole-C5),118.0 (CN),112.1 (pyrrole-
C4), 87.7 (pyrrole-C3); NMR assignments are based on H,H-COSY,
HSQC, NOESY and HMBC experiments; IR (film) nmax 3432br m,
1
0. Hahn, F. E.; Tamm, M. Angew. Chem., Int. Ed. Engl. 1992, 31, 1212.
11. Claridge, T. D. W. High-Resolution NMR Techniques in Organic Chemistry; Per-
gamon: Amsterdam, 1999.
ꢀ1
2
962w, 2215s, 1725s, 1653m, 1025s, 1006s, 790m cm ; ESI-HRMS
þ
calcd for [MþH]
C
9
H
7
N
2
S: 175.0324; obsd 175.0324.
12. Stein, A. R.; Lim, Y. Y. Can. J. Chem. 1971, 49, 2455.
1
3. Wentrup, C.; Winter, H.-W. J. Am Chem. Soc. 1980, 102, 6159.
4. Wentrup, C. Top. Curr. Chem. 1976, 51, 173.
5. Chang, C. W. J.; Scheuer, P. J. Top. Curr. Chem. 1993, 167, 33.
16. Chang, C. W. J. Prog. Chem. Org. Nat. Prod. 2000, 80, 1.
7. Garson, M. J.; Simpson, J. S. Nat. Prod. Rep. 2004, 21, 164.
18. Banert, K.; K o¨ hler, F.; Meier, B. Tetrahedron Lett. 2003, 44, 3781.
9. Meier, M.; Ruechardt, C. Tetrahedron Lett. 1984, 25, 3441.
0. Haaf, K.; Ruechardt, C. Chem. Ber. 1990, 123, 635.
21. Marcaccini, S.; Torroba, T. Org. Prep. Proced. Int. 1993, 25, 141.
1
1
4
.6. (Z)-4-Isocyano-2-(1-(triisopropylsilyl)-1H-pyrrol-3-
yl)but-2-enenitrile (7)
1
The title compound was prepared from 5 4 as described for 3
above. Product 7 was separated from the main product 6 (71%) by
flash chromatography (gradient: 0–10% MeOH/CH
1
2
2
Cl
2
)
and
22. Wong, D. M.; Simpson, S. J. Polyhedron 2006, 25, 2303.
23. Villemin, D.; Jullien, A.; Bar, N. Tetrahedron Lett. 2007, 48, 4191.
24. Ojo, W.-S.; Paugam, E.; Petillon, F. Y.; Schollhammer, P.; Talarmin, J.; Muir, K. W.
Organometallics 2006, 25, 4009.
obtained as a yellow solid (20%), pure by NMR; R 0.52 (CH
f
2
Cl
2
); mp
ꢁ
1
7
9–80 C; H NMR (400 MHz, CDCl
pyrrole-H2), 6.77 (1H, dd, J 2.8, 2.0, pyrrole-H5), 6.45 (1H, dd, J 2.8,
.6, pyrrole-H4), 6.37 (1H, t, J 7.2, H3), 4.45 (2H, d, J 7.2, –CH , H4),
.46 (3H, sept, J 7.6, CH(CH ), 1.10 (18H, d, J 7.6, CH(CH
NMR (100 MHz, CDCl 158.3 (t,
3 H
) d 7.01 (1H, dd, J 2.0, 1.6,
2
5. Antinolo, A.; Garcia-Yuste, S.; Lopez-Solera, M. I.; Otero, A.; Perez-Flores, J. C.;
Reguillo-Carmona, R.; Villasenor, E. Dalton Trans. 2006, 1495.
6. Harris, R. K.; Becker, E. D.; Cabral De Menezes, S. M.; Granger, P.; Hoffman, R. E.;
Zilm, K. W. Pure Appl. Chem. 2008, 80, 59.
1
1
2
13
3
)
2
3
)
2
);
C
2
1
3
)
d
C
JCN 4.5, CH –NC), 126.9 (C3),
2