M. Potácˇek et al.
FULL PAPER
Ethyl 4-Ethylidene-5,5-dimethyl-2-phenyl-5,6-dihydro-4H-pyrrolo-
[1,2-b]pyrazole-3-carboxylate (4d): Yield 26 mg, 34% (16.5 h; from
fluorinated allenyl azine 1b) and 30 mg, 39% (24 h; from non-fluo-
rinated allenyl azine 1d); white solid; m.p. 98.5–100.5 °C. Rf = 0.06
275.0 Hz, CF3), 78.1 (s, NCH), 61.8 (s, OCH2CH3), 53.1 (s,
CHC=O), 48.0 (s, H3CCCH3), 27.1 (s, H3CCCH3), 24.4 (s,
3
H3CCCH3), 18.8 (q, JC,F
= 1.3 Hz, F3CCCH3), 17.8 (s,
=CCH2CH3), 14.4 (s, =CCH2CH3), 14.2 (s, OCH2CH3) ppm. IR
1
(AcOEt/PE, 5:95). Isomer ratio ca. 3:1. H NMR (major isomer):
(KBr): ν
= 1114, 1167, 1273, 1293, 1386, 1736 (C=O), 2873,
˜
max
3
δ = 7.58–7.65 (m, 2 H, Ph), 7.30–7.37 (m, 3 H, Ph), 5.65 (q, JH,H
2933, 2967 cm–1. GC–MS: m/z (%) = 420 (100) [M]+, 405 (82), 347
(92), 333 (24), 244 (52), 174 (27), 145 (40), 103 (76), 91 (28), 77
(37). HRMS: calcd. for C23H28F3N2O2+ 421.2103; found 421.2090.
3
= 7.1 Hz, 1 H, =CHCH3), 4.22 (q, JH,H = 7.1 Hz, 2 H, CH2CH3),
3.97 (s, 2 H, NCH2), 1.82 (d, 3JH,H = 7.1 Hz, 3 H, =CHCH3), 1.35
3
(s, 6 H, H3CCCH3), 1.18 (t, JH,H = 7.1 Hz, 3 H, CH2CH3) ppm.
Supporting Information (see also the footnote on the first page of
this article): Isolated heterocyclic products, experimental details
and spectroscopic data for allenyl azines 1 and criss-cross products
13C NMR: δ = 165.5 (s, C=O), 155.9 (s, N=C), 145.0 (s, NC=),
137.9 (s, C=CHCH3), 133.5 (s, C, Ph), 128.8 (s, 2ϫ CH, Ph), 128.3
(s, CH, Ph), 128.1 (s, 2ϫ CH, Ph), 120.9 (s, =CHCH3), 107.4 (s,
CC=O), 61.1 (s, NCH2), 60.9 (s, CH2CH3), 47.5 (s, H3CCCH3),
1
2 with some H NMR spectra and crystal structures.
1
27.8 (s, H3CCCH3), 16.5 (s, =CHCH3), 14.2 (s, CH2CH3) ppm. H
NMR (minor isomer): δ = 7.58–7.65 (m, 2 H, Ph), 7.30–7.37 (m, 3
Acknowledgments
3
3
H, Ph), 7.28 (q, JH,H = 7.7 Hz, 1 H, =CHCH3), 4.16 (q, JH,H
=
=
3
7.1 Hz, 2 H, CH2CH3), 4.03 (s, 2 H, NCH2), 2.00 (d, JH,H
The authors acknowledge Marek Necˇas for the crystallographic
measurements and Dominique Harakat for HR mass spectra. The
Grant Agency of the Czech Republic (grant number 203/09/1345)
financially supported this research.
3
7.7 Hz, 3 H, =CHCH3), 1.53 (s, 6 H, H3C-C-CH3), 1.12 (t, JH,H
= 7.1 Hz, 3 H, CH2CH3) ppm. 13C NMR δ = 164.5 (s, C=O), 158.6
(s, N=C), 149.5 (s, NC=), 137.1 (s, C=CHCH3), 134.1 (s, C, Ph),
129.6 (s, 2ϫ CH, Ph), 128.2 (s, CH, Ph), 127.7 (s, 2ϫ CH, Ph),
126.2 (s, =CHCH3), 104.7 (s, CC=O), 63.2 (s, CH2CH3), 60.2 (s,
NCH2), 45.9 (s, H3CCCH3), 27.5 (s, H3CCCH3), 14.4 (s,
[1] a) N. Krause, A. S. K. Hashmi, in: Modern Allene Chemistry,
Wiley-VCH, Weinheim, 2004, vol. 1 and 2; b) R. Zimmer, Syn-
thesis 1993, 165–168; c) B. A. Trofimov, J. Heterocycl. Chem.
1999, 36, 1469–1490; d) L. Brandsma, Eur. J. Org. Chem. 2001,
4569–4581; e) L. Brandsma, N. A. Nedolya, Synthesis 2004,
735–745; f) M. Brasholz, H.-U. Reissig, R. Zimmer, Acc. Chem.
Res. 2009, 42, 45–56.
[2] a) S. Man, P. Kulhánek, M. Potácˇek, M. Necˇas, Tetrahedron
Lett. 2002, 43, 6431–6433; b) S. Man, J.-P. Bouillon, M. Necˇas,
M. Potácˇek, Tetrahedron Lett. 2004, 45, 9419–9421; c) S. Man,
M. Necˇas, J.-P. Bouillon, H. Baillia, D. Harakat, M. Potácˇek,
Tetrahedron 2005, 61, 2387–2393; d) S. Man, M. Necˇas, J.-P.
Bouillon, C. Portella, M. Potácˇek, Eur. J. Org. Chem. 2006,
3473–3478; e) J. Galeta, S. Man, M. Potácˇek, Arkivoc 2009, 6,
=CHCH ), 14.1 (s, CH CH ) ppm. IR (KBr): ν = 1053, 1161,
˜
max
3
2
3
1283, 1371, 1443, 1541, 1707 (C=O), 2868, 2930, 2962, 2978 cm–1.
GC–MS: m/z (%) = 310 (60) [M]+, 264 (82), 249 (100), 77 (23).
+
HRMS: calcd. for C19H23N2O2 311.1760; found 311.1760.
(3S*,4R*)-Ethyl 4,4,5-Trimethyl-2-phenyl-6-(3,3,3-trifluoro-2-meth-
ylpropenyl)-3a,4-dihydro-3H-pyrrolo[1,2-b]pyrazole-3-carboxylate
(9a): Yield 56 mg, 55% (16.5 h); white solid; m.p. 112.5–116.0 °C.
Rf = 0.20 (AcOEt/PE, 1:9). 19F NMR: δ = –69.5 (s) ppm. 1H NMR:
δ = 7.55–7.65 (m, 2 H, Ph), 7.20–7.35 (m, 3 H, Ph), 6.55 (br. s, 1
3
H, CH=CCF3), 4.32 (d, JH,H = 3.4 Hz, 1 H, CHC=O), 4.25 (d,
3
3JH,H = 3.4 Hz, 1 H, NCH), 4.07 (q, JH,H = 7.1 Hz, 2 H,
CH2CH3), 2.09 (s, 3 H, H3CCCF3), 1.59 (s, 3 H, =CCH3), 1.11 (s,
245–259.
3
ˇ
3 H, H3CCCH3), 1.08 (t, JH,H = 7.1 Hz, 3 H, CH2CH3), 0.91 (s,
ˇ
[3] R. Marek, I. Stastná-Sedlácˇková, J. Tousˇek, J. Marek, M. Potá-
3 H, H3CCCH3) ppm. 13C NMR: δ = 171.0 (s, C=O), 150.9 (s,
N=C), 136.1 (s, NC=), 134.7 (s, =CCH3), 131.6 (s, C, Ph), 129.4 (s,
cˇek, Bull. Soc. Chim. Belg. 1997, 106, 645.
[4] A. Koziara, K. Turski, A. Zwierzak, Synthesis 1986, 298–301.
[5] a) J. R. Bailey, N. H. Moore, J. Am. Chem. Soc. 1917, 39, 279–
291; b) J. R. Bailey, A. T. McPherson, J. Am. Chem. Soc. 1917,
39, 1322–1338.
[6] R. Huisgen, Angew. Chem. Int. Ed. Engl. 1963, 2, 565–598.
[7] A. Padwa, in: 1,3-Dipolar Cycloaddition Chemistry, John
Wiley & Sons, New York, 1984.
2
CH, Ph), 128.6 (s, 2ϫ CH, Ph), 127.4 (q, JC,F = 28.5 Hz, CCF3),
1
126.8 (s, 2ϫ CH, Ph), 125.0 (q, JC,F = 273.0 Hz, CF3), 120.6 (q,
3JC,F = 6.6 Hz, CH=CCF3), 77.4 (s, NCH), 61.8 (s, CH2CH3), 52.7
(s, CHC=O), 47.1 (s, H3CCCH3), 26.8 (s, H3CCCH3), 23.6 (s,
H3CCCH3), 14.1 (s, CH2CH3), 12.9 (q, 3JC,F = 1.1 Hz, H3CCCF3),
9.5 (s, =CCH ) ppm. IR (KBr): ν
= 1097, 1160, 1297, 1729
˜
3
max
[8] A. Gieren, P. Narayanan, K. Burger, W. Thenn, Angew. Chem.
Int. Ed. Engl. 1974, 13, 475–476.
(C=O), 2870, 2932, 2966 cm–1. GC–MS: m/z (%) = 406 (100) [M]+,
391 (32), 333 (71), 230 (51), 103 (41). C22H25F3N2O2 (406.44): calcd.
C 65.01, H 6.20, N 6.89; found C 64.94, H 6.31, N 6.78.
[9] P. Kulhánek, M. Potácˇek, J. Kocˇa, Collect. Czech. Chem. Com-
mun. 2004, 69, 231–241.
[10] L. Davis, G. Kuttan, Immunopharmacol. Immunotoxicol. 1999,
(3S*,4R*)-Ethyl 5-Ethyl-4,4-dimethyl-2-phenyl-6-(3,3,3-trifluoro-2-
methylpropenyl)-3a,4-dihydro-3H-pyrrolo[1,2-b]pyrazole-3-carboxyl-
ate (9b): Yield 18 mg, 17% (16.5 h); white solid; m.p. 97.5–101.0 °C.
Rf = 0.11 (AcOEt/PE, 5:95). 19F NMR: δ = –65.5 (s) ppm. 1H
NMR: δ = 7.69–7.73 (m, 2 H, Ph), 7.30–7.38 (m, 3 H, Ph), 6.32–
21, 695–703.
[11] B. Singh, A. K. Saxena, B. K. Chandan, D. K. Gupta, K. K.
Bhutani, K. K. Anand, Phytother. Res. 2001, 15, 311–318.
[12] L. Davis, G. Kuttan, J. Exp. Clin. Cancer Res. 2002, 21, 115–
118.
6.35 (m, 1 H, CH=CCF3), 4.37 (d, 3JH,H = 3.9 Hz, 1 H, CHC=O), [13] B. C. Hamper, Org. Synth. 1992, 70, 246–255.
3
3
[14] SHELXTL, version 5.10, Bruker AXS Inc., Madison, WI,
USA, 1997.
4.32 (d, JH,H = 3.9 Hz, 1 H, NCH), 4.17 (q, JH,H = 7.1 Hz, 2 H,
4
OCH2CH3), 2.08–2.18 (m, 1 H, =CCH2CH3), 2.04 (d, JH,H
=
[15] CCDC-773515 (for 2Dc), -773516 (for 2Ea2), -773517 (for 4c),
-773518 (for 4d), -773519 (for 9a), and -773520 (for 9b) contain
the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
1.5 Hz, 3 H, H3CCCF3), 1.90–2.00 (m, 1 H, =CCH2CH3), 1.22 (s,
3 H, H3CCCH3), 1.17 (t, 3JH,H = 7.1 Hz, 3 H, OCH2CH3), 1.01 (t,
3JH,H = 7.6 Hz, 3 H, =CCH2CH3), 1.00 (s, 3 H, H3CCCH3) ppm.
13C NMR: δ = 171.5 (s, C=O), 150.9 (s, N=C), 134.7 (s, NC=),
2
133.5 (s, =CCH2CH3), 132.0 (s, C, Ph), 130.6 (q, JC,F = 29.6 Hz,
CCF3), 129.3 (s, CH, Ph), 128.6 (s, 2ϫ CH, Ph), 126.8 (s, 2ϫ CH,
Received: July 22, 2010
Published Online: November 24, 2010
3
1
Ph), 126.2 (q, JC,F = 3.3 Hz, CH=CCF3), 123.7 (q, JC,F
=
398
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Eur. J. Org. Chem. 2011, 392–398