A novel heterobicyclic framework by successive ene reactions

Full text of DOI:10.1021/jo000079q

J . Org. Chem. 2000, 65, 3569-3570
3569
electron demand, where the nitrilium ion acts as the ene
and the arene as the enophile.
A Novel Heter obicyclic F r a m ew or k by
Su ccessive En e Rea ction s
Resu lts a n d Discu ssion
J oachim Henninger,† Kurt Polborn, and Herbert Mayr*
N-Isopropylbenzonitrilium hexachloroantimonate (1-
SbCl6), obtained from benzonitrile, isopropyl chloride, and
antimony pentachloride,13 reacts with 2-methylthiophene
(2) in acetonitrile at 20 °C to yield 90% of the bicyclic
product 3-SbCl6 (eq 2), which was characterized by X-ray
crystallography14 (see the Supporting Information).
Department Chemie der Ludwig-Maximilians-Universita¨t
Mu¨nchen, Butenandtstrasse 5-13 (Haus F),
D-81377 Mu¨nchen, Germany
Received J anuary 19, 2000
In tr od u ction
Nitrilium ions are intermediates in numerous reac-
tions, e.g., in the Beckmann rearrangement1 and in the
Ritter,2 von-Braun,3 Bischler-Napieralski,3 Houben-
Hoesch,4 Gattermann,5 and Schmidt reactions.6 Isolated
nitrilium salts undergo various types of reactions with
alkenes,7 alkynes,8 carbonyl compounds,9 and 1,3-di-
poles.10 Arenes react with N-aryl- or N-alkylnitrilium
salts to give iminium ions7a,11 where the incoming aryl
group is located in the position cis to the N-substituent
(Houben-Hoesch reaction, eq 1).7a,12
(2)
The reaction of 1+ with 2 is suggested to proceed via
concerted or stepwise ene reaction with the formation of
an intermediate 2-azoniaallene7b,8a (4+). Since only sig-
nals of the reactants 1+ and 2 and of the product 3+ were
detectable when monitoring the reaction by 1H NMR
spectroscopy, the formation of long-lived intermediates
is ruled out. We, therefore, conclude that 4+ cyclizes
immediately to yield 5+, which gives 3+ by a proton shift
(Scheme 1). Alternatively, the formation of 3+ from 4+
can be considered as a concerted 6-(3,5) ene cyclization,15
a variation of Oppolzer’s intramolecular ene reaction type
I,16a classified as type IV by Snider.16b
(1)
In this paper, we report on a novel reaction mode of
nitrilium ions with arenes, an ene reaction with inverse
Sch em e 1
* To whom correspondence should be addressed. Fax: +49-89/2180-
7717. E-mail: hmy@cup.uni-muenchen.de.
† Present address: Ems-Dottikon, Dottikon, Switzerland.
(1) (a) Craig, D. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Ley, S. V., Eds.; Pergamon Press: Oxford, 1991; Vol. 7,
Chapter 5.2, pp 689-702. (b) Gawley, R. E. Org. React. 1988, 35,
1-420.
(2) (a) Bishop, R. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Winterfeldt, E., Eds.; Pergamon Press: Oxford, 1991; Vol.
6, Chapter 1.9, pp 261-300. (b) Benz, G. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Winterfeldt, E., Eds.; Pergamon
Press: Oxford, 1991; Vol. 6, Chapter 2.3, pp 381-417. (c) Krimen, L.
I.; Cota, D. J . Org. React. 1969, 17, 213-325. (d) J ohnson, F.;
Madron˜ero, R. Adv. Heterocycl. Chem. 1966, 6, 95-146.
(3) Fodor, G.; Nagubandi, S. Tetrahedron 1980, 36, 1279-1300.
(4) (a) Heaney, H. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Heathcock, C. H., Eds.; Pergamon Press: Oxford, 1991;
Vol. 2, Chapter 3.2, pp 733-752. (b) Ruske, W. In Friedel-Crafts and
Related Reactions; Olah, G. A., Ed.; Wiley: New York, 1964; Vol. 3,
pp 383-497.
To our knowledge, the reaction of 1-SbCl6 with 2 is
the first example of an ene reaction of a nitrilium ion
with an aromatic compound. The scope of this new
reaction type is not yet clear. Since reactions of N-methyl
and N-ethylnitrilium salts with 2-methylthiophene (2)
and other arenes gave exclusively Houben-Hoesch-type
products,12a it is assumed that ene-type reactions are
typical for N-isopropylnitrilium ions, particularly since
J ochims also observed ene reactions when N-isopropyl-
nitrilium salts were combined with alkenes7b and
alkynes.8a
(5) Truce, W. E. Org. React. 1957, 9, 37-72.
(6) Banthorpe, D. V. In The Chemistry of the Azido Group; Patai,
S., Ed.; Wiley: London, 1971; Chapter 7, pp 397-440.
(7) (a) Moustafa, A. H.; Hitzler, M. G.; Lutz, M.; J ochims, J . C.
Tetrahedron 1997, 53, 625-640. (b) Moustafa, A. H.; Wirschun, W.;
Freyhardt, C. C.; J ochims, J . C.; Abu-El-Halawa, R. J . Prakt. Chem.
1997, 339, 615-622. (c) Schmidt, R. R. Angew. Chem. 1973, 85, 235-
247; Angew. Chem., Int. Ed. Engl. 1973, 12, 212-223.
(8) (a) Abu-El-Halawa, R.; J ochims, J . C. Synthesis 1992, 871-874.
(b) Al-Talib, M.; J ochims, J . C.; Wang, Q.; Hamed, A.; Ismail, A. E.
Synthesis 1992, 875-878.
(9) (a) Lukyanov, S. M. In The Chemistry of Enamines - Part 2;
Rappoport, Z., Ed.; Wiley: Chichester, 1994; Chapter 24, pp 1441-
1506. (b) Al-Talib, M.; Zaki, M.; Hehl, S.; Stumpf, R.; Fischer, H.;
J ochims, J . C. Synthesis 1996, 1115-1121.
(10) (a) Quast, H.; Hergenro¨ther, T. Liebigs Ann. Chem. 1992, 581-
590. (b) Abu-El-Halawa, R.; Shrestha-Dawadi, P. B.; J ochims, J . C.
Chem. Ber. 1993, 126, 109-116.
Exp er im en ta l Section
Gen er a l Meth od s. All reactions were run under an atmo-
sphere of dry nitrogen. The nitrilium salt 1-SbCl6 was synthe-
sized from benzonitrile, isopropyl chloride, and SbCl5 according
(13) Meerwein, H.; Laasch, P.; Mersch, R.; Spille, J . Chem. Ber.
1956, 89, 209-224.
(14) Crystallographic data (excluding structure factors) for the
structure reported in this paper have been deposited with the
Cambridge Crystallographic Data Center as supplementary publication
no. CCDC-138484. Copies of the data can be obtained free of charge
on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(Fax: +44-1223/336-033; e-mail: deposit@ccdc.cam.ac.uk).
(15) Mikami, K.; Shimizu, M. Chem. Rev. 1992, 92, 1021-1050.
(16) (a) Oppolzer, W.; Snieckus, V. Angew. Chem. 1978, 90, 506-
516; Angew. Chem., Int. Ed. Engl. 1978, 17, 476-486. (b) Snider, B.
B. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Paquette, L. A., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, Chapter
1.1, pp 1-27.
(11) (a) Eyley, S. C.; Giles, R. G.; Heaney, H. Tetrahedron Lett. 1985,
26, 4649-4652. (b) Amer, M. I.; Booth, B. L.; Noori, G. F. M.; Proenc¸a,
M. F. J . R. P. J . Chem. Soc., Perkin Trans. 1 1983, 1075-1082.
(12) (a) Henninger, J . Dissertation, Ludwig-Maximilians-Universita¨t
Mu¨nchen, 1999. (b) Hegarty, A. F. Acc. Chem. Res. 1980, 13, 448-
454.
10.1021/jo000079q CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/27/2000

3570 J . Org. Chem., Vol. 65, No. 11, 2000
Additions and Corrections
to ref 13. 2-Methylthiophene (2) is commercially available and
was distilled prior to use. 1H (400 MHz) and 13C NMR (100.6
MHz) spectra of solutions in CD3CN were calibrated to the
solvent signals (δH 1.93, δC 1.30).
experiments); MS (FAB, Ar, 5-6 kV) m/z 246, 245, 244 (6, 18,
89) [M - SbCl6]. Anal. Calcd for C15H18Cl6NSSb: C, 31.12; H,
3.13; Cl, 36.75; N, 2.42; S, 5.54. Found: C, 31.49; H, 3.21; Cl,
36.47; N, 2.43; S, 5.68.
2,2-Dim e t h yl-7-m e t h yle n e -4-p h e n yl-3-a zon ia -6-t h ia -
bicyclo[3.2.1]octa -3-en e Hexa ch lor oa n tim on a te (3-SbCl6).
2-Methylthiophene (2, 0.83 g, 8.5 mmol) was added to a solution
of 1-SbCl6 (0.96 g, 2.0 mmol) in 3 mL of dry acetonitrile at
ambient temperature. After steering for 15 h, the volatile
components were removed in vacuo, and the residue was
recrystallized from CH2Cl2/pentane to yield 1.04 g of 3 (1.8 mmol,
90%): orange needles; mp 180 °C; 1H NMR (CD3CN) δ 1.54, 1.58
(2 s, 2 × 3 H, 2 × CH3), 2.48-2.54, 2.85-2.88 (2 m, 2 × 1 H,
8-H2), 3.24-3.25 (m, 1 H, 1-H), 4.95 (mc, 1 H, 5-H), 5.27-5.29,
5.46-5.47 (2 m, 2 × 1 H, dCH2), 7.65-7.69 (m, 2 H, Ph), 7.82-
7.86 (m, 3 H, Ph), 10.29 (br t, J N,H ≈ 47 Hz, 1 H, NH); 13C NMR
(CD3CN) δ 27.6, 28.0 (2 q, 2 × CH3), 33.2 (t, C-8), 45.2 (d, C-5),
52.0 (d, C-1), 63.2 (s, C-2), 110.7 (t, dCH2), 129.4 (s, Ph), 130.4,
130.7, 137.3 (3 d, Ph), 145.2 (s, C-7), 183.1 (s, C-4) (signal
assignments are based on 2D NOE, 1H,1H- and 1H,13C-COSY
Crystallization from diethyl ether yields 3-SbCl6 as gold-
yellow needles with approximately 0.75 equiv of ether in the
crystals.
Ack n ow led gm en t. We thank Mrs N. Hampel for
experimental assistance. Financial support by the Deut-
sche Forschungsgemeinschaft and the Fonds der Che-
mischen Industrie is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: ORTEP diagram
and details of the X-ray crystallographic study of 3-SbCl6. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O000079Q
Additions and Corrections
Vol. 65, 2000
Ryo Ta k eu ch i,* Keisu k e Ta n a be, a n d Sh iger u Ta n a k a .
Stereodivergent Synthesis of (E)- and (Z)-2-Alken-4-yn-1-ols from
2-Propynoic Acid: A Practical Route via 2-Alken-4-ynoates.
Page 1558. We inadvertently overlooked the related
work of Uguen and co-workers in ref 12: Zoller, T.;
Uguen, D. Tetrahedron Lett. 1998, 39, 6719.
J O004002D
10.1021/jo004002d
Published on Web 05/03/2000