Abstract
A new and high yielding synthetic route to monosubstituted cyclotribenzylenes 6 via the cyclocondensation of benzene with a suitably monosubstituted diol 20 , obtained from ozonolysis of the corresponding dibenzosuberene precursor 19 , was developed for the first time! The dibenzosuberene itself could be readily prepared in large quantities from inexpensive starting materials in five steps. Using this synthetic approach, a mono bromosubstituted cyclotribenzylene 12a was synthesized on large scale. Another four monosubstituted cyclotribenzylenes 21 -24 were also prepared either via bromine/lithium exchange followed by subsequent quenching with external electrophiles or a copper mediated reaction with cyanide. These molecules adopt a rigid crown conformation as shown by X-ray analysis and temperature dependent NMR studies. The barrier to inversion is quite high, requiring temperatures well above 120 °C before inversion takes place. Futhermore, such monosubstituted cyclotribenzylenes are planar chiral and after optical resolution, using HPLC, we were able to obtain the first planar chiral C1-symmetric cyclotribenzylenes in form of the optically pure enantiomers of 12a , the CD spectra of which are exact mirror images over the entire spectral range.
Key words
carbocycles - cyclophanes - CD spectroscopy - planar chirality
References 1 Former address: Institut für Organische Chemie, Universität zu Köln, Greinstrasse 4, 50939 Köln, Germany.
2a Steed JW.
Atwood JL. In Supramolecular Chemistry
Wiley;
Chichester:
2000.
2b Lehn J.-M. In Supramolecular Chemistry, Concepts and Perspectives
VCH;
Weinheim:
1995.
2c Vögtle F. In Supramolecular Chemistry
Wiley & Sons;
Chichester:
1991.
3a Sato T.
Uno K.
J. Chem. Soc., Chem. Commun.
1972,
579
3b Sato T.
Uno K.
J. Chem. Soc., Perkin Trans. 1
1973,
895
4 Vögtle F. In Cyclophane Chemistry
Wiley & Sons;
Chichester:
1993.
5 Diedrich F.
Angew. Chem., Int. Ed. Engl.
1988,
27:
362
6 Collet A.
Tetrahedron
1987,
43:
5725
7 Collet A.
Dutasta J.-P.
Lozach B.
Canceil J.
Top. Curr. Chem.
1993,
165:
103
8 Sato T.
Akima T.
Uno K.
J. Chem. Soc., Perkin Trans. 1
1973,
891
9 Yamato T.
Sakaue N.
J. Chem. Res. (M)
1997,
12:
2614
10 Tellenbröker J.
Kuck D.
Angew. Chem. Int. Ed.
1999,
38:
919
1 see:
11a Lee WY.
Sim W.
Choi KD.
J. Chem. Soc., Perkin Trans. 1
1992,
881
11b Kodomari M.
Taguchi S.
J. Chem. Res. (S)
1996,
240
11c Yamamoto T.
Sakaue N.
Furusawa T.
Tashiro M.
Surya Prakash GK.
Olah GA.
J. Chem. Res. (S)
1991,
242
11d Canceill J.
Collet A.
Gottarelli G.
J. Am. Chem. Soc.
1984,
106:
5997
11e Canceill J.
Collet A.
J. Chem. Soc., Chem. Commun.
1983,
1145
4 see also:
12a Lee WY.
Park CH.
Kim YD.
J. Org. Chem.
1992,
57:
4074
12b Bergmann ED.
Pelchowicz Z.
J. Am. Chem. Soc.
1953,
75:
4281
13 Platzek J.
Snatzke G.
Tetrahedron
1987,
43:
4947
14 Renaud RN.
Layton RB.
Fraser RR.
Can. J. Chem.
1973,
51:
3380
15 Campbell TW.
Ginsig R.
Schmid H.
Helv. Chim. Acta
1953,
36:
1489
16 Gringauz A. In Medicinal Chemistry
Wiley-VCH;
New York:
1997.
17a Thompson WJ.
Anderson S.
Britcher SF.
Lyle TA.
Thies JE.
J. Med. Chem.
1990,
33:
789
17b Weiler-Feilchenfeld H.
Solomonovici A.
J. Chem. Soc. B
1971,
869
17c Jung ME.
Miller SJ.
J. Am. Chem. Soc.
1981,
103:
1984
17d Inoue J.
Cui Y.-S.
Rodriguez L.
Chen Z.
Kador PF.
Eur. J. Med. Chem. Chim. Ther.
1999,
34:
399
18a Fraser RR.
Renaud RN.
Can. J. Chem.
1971,
49:
746
18b Renaud RN.
Bovenkamp JW.
Fraser RR.
Capoor R.
Can. J. Chem.
1977,
55:
2642
19a Engelhardt EL.
Zell HC.
Saari WS.
Christy ME.
Colton CD.
Stone CA.
Stavorski JM.
Wenger HC.
Ludden CT.
J. Med. Chem.
1965,
8:
829
19b Remy DC.
Rittle KE.
Hunt CA.
Anderson PS.
Arison BH.
Engelhardt EL.
Hirschmann R.
Clineschmidt BV.
Lotti VJ.
Bunting PR.
Ballentine RJ.
Papp NL.
Flataker L.
Witoslawski JJ.
Stone CA.
J. Med. Chem.
1977,
20:
1013
19c Davis DA.
de Paulis T.
Janowsky A.
Smith HE.
J. Med. Chem.
1990,
33:
809
20 Mikotic-Mihun Z.
Dogan J.
Litvic M.
Cepanec I.
Karminski-Zamola GM.
Synth. Commun.
1998,
28:
2191
21 Manning C.
McClory MR.
McCullough JJ.
J. Org. Chem.
1981,
46:
919
22a Slates HL.
Wendler NL.
J. Med. Chem.
1965,
8:
886
22b Looker JJ.
J. Org. Chem.
1966,
31:
3599
23 Wendler NL, Taub D, and Hoffsommer RD. inventors; U. S. Patent 2,247,272. In analogy to a patented procedure:
24 LiAlH4 even in equimolar amounts at low temperatures caused substantial debromination and gave only 23%, at most, of the desired bromosubstituted diol 20 . Other reducing agents such as sodium boronate or lithium boronate only gave complex product mixtures in which the desired diol 20 was only present in small amounts (according to TLC and GC-MS analysis), no matter which reaction conditions we tried (e.g. by variation of temperature and solvent, respectively). Borane in THF did not react at all.
25a Thiem J. In Houben-Weyl: Methoden der Organischen Chemie
Vol. VI/1a:
Thieme;
Stuttgart:
1980.
p.853
25b Brown HC.
Narasimhan S.
Choi YM.
J. Org. Chem.
1982,
47:
4702
26 Flippin LA.
Gallagher DW.
Jalali-Araghi K.
J. Org. Chem.
1989,
54:
1430
27a Canceill J.
Collet A.
Gotarelli G.
Plamieri P.
J. Am. Chem. Soc.
1987,
109:
6454
27b Canceill J.
Collet A.
New J. Chem.
1986,
10:
17
27c Canceill J.
Lacombe L.
Collet A.
J. Am. Chem. Soc.
1985,
107:
6993
27d Canceill J.
Collet A.
Gabard J.
Gotarelli G.
Spada GP.
J. Am. Chem. Soc.
1985,
107:
1299
27e Collet A.
J. Am. Chem. Soc.
1981,
103:
5912
