COMMUNICATIONS
system can gain maximal benefit from resonance stabilization.
In the deprotonated species, the system relaxes into a
geometry which is twisted in this region, albeit slightly.[9] In
rhodopsin, the chromophore is certainly not deprotonated.
However, according to two photon spectroscopic measure-
ments the binding site of rhodopsin is neutral;[15] that is the
charge balanced by a negatively charged counter ion, most
probably the carboxylate group of glu113, which interacts
with the chromophore in the C12 ± C13 region[16] and may
cause not only partial fixation of the double bond but also
additional steric distortion.
Selective C ± H Activation of Aliphatic Hydro-
carbons under Phase-Transfer Conditions**
Peter R. Schreiner,* Oliver Lauenstein,
Igor V. Kolomitsyn, Suad Nadi, and Andrey A. Fokin
Â
Dedicated to Professor Paul von Rague Schleyer
The selective activation of aliphatic hydrocarbons,[1] is
mostly achieved with electronically unsaturated transition
metal complexes,[2±6] superacids,[32] or enzymatic processes.[7, 8]
In this paper we present a highly unusual C ± H activation of
aliphatic hydrocarbons by phase-transfer catalysis (PTC) in
mixed aqueous/organic solvents.
Received: February 5, 1998 [Z11439IE]
German version: Angew. Chem. 1998, 110, 1997 ± 2000
When treated with tetrabromomethane and sodium hy-
droxide under standard PTC conditions (catalyst: triethyl-
benzylammonium chloride), adamantane 1[9] gives 1-bromo-
(1a) and 1,3-dibromoadamantane (1b) in 85% conversion
and 70% yield [Eq. (1); Table 1]. The dibromide 1b can also
Keywords: chirality ´ circular dichroism ´ retinal ´ rhodop-
sin
[1] T. Yoshizawa, G. Wald, Nature 1963, 197, 1279.
[2] a) H. Shichi, Biochemistry of Vision, Academic Press, New York, 1983;
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[5] Q. Tan, J. Lou, B. Borhan, E. Karnaukhova, N. Berova, K. Nakanishi,
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[7] W. Stöckenius, R. A. Bogomolni, Ann. Rev. Biochem. 1982, 587.
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[9] a) F. Terstegen, V. Buss, J. Mol. Struct. (Theochem) 1996, 369, 53; b) F.
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Lett. 1997, 272, 335.
be obtained from 1a under the same conditions but with
longer reaction times, which indicates a stepwise incorpora-
tion of bromine into the adamantane core. Although the
synthesis of polybromoadamantanes[10] is straightfor-
ward,[11±15] we have chosen 1 as a model for studying tertiary
C ± H bond activations.[1]
We arrived at these reaction conditions in the course of
derivatizing adamantane 1 to its bridgehead substituted
analogues[9, 10] by dibromocarbene (from HCBr3/50%
NaOH/CH2Cl2/PTC, 16 h, reflux) insertion into the bridge-
head C ± H bond. Apart from the desired dibromomethyl-
adamantane (1c, 33%),[16] we also found 1a (41%), 1b
(16%), and traces of 2-bromoadamantane (1d) (2%). Since
isolated 1c does not form 1a or 1b under the same reaction
:
[11] R. H. Callender, A. Doukas, R. Crouch, K. Nakanishi, Biochemistry
1976, 15, 1621.
conditions, we surmized that it is not the reaction of CBr2
with 1 that yields the bromoadamantanes. Rather, we
reasoned that the halogen may be transferred from CBr4.
This compound is known to equilibrate with HCBr3 under the
reaction conditions used.[17, 18]
The transformation is highly regiospecific for the bridge-
head position of 1 (the methyl groups of methyladamantanes
[12] M. J. Frisch, G. W. Trucks, H. B. Schlegel, P. M. W. Gill, B. G. Johnson,
M. A. Robb, J. R. Cheeseman, T. Keith, G. A. Petersson, A. Mont-
gomery, K. Raghavachari, M. A. Al-Laham, V. G. Zakrzewski, J. V.
Ortiz, J. B. Foresman, C. Y. Peng, P. Y. Ayala, W. Chen, M. W. Wong,
J. L. Andres, E. S. Replogle, R. Gomperts, R. L. Martin, D. J. Fox, J. S.
Binkley, D. J. Defrees, J. Baker, J. J. P. Stewart, M. Head-Gordon, C.
Gonzalez, J. A. Pople, GAUSSIAN 94. RevE.1, Gaussian Inc.,
Pittsburgh, PA, 1995.
[*] Dr. P. R. Schreiner, O. Lauenstein
Institut für Organische Chemie der Universität
Tammannstrasse 2, D-37077 Göttingen (Germany)
Fax: (49)551-399-475
[13] K. Andersson, M. R. A. Blomberg, M. P. Fülscher, G. Karlström, R.
Â
Lindh, P.-. Malmqvist, P. Neogrady, J. Olsen, B. O. Roos, A. J. Sadlej,
Â
M. Schütz, L. Seijo, L. Serrano-Andres, P. E. M. Siegbahn, P.-O.
Widmark, MOLCAS-4, Lund University (Sweden).
[14] P.-O. Widmark, P.-. Malmqvist, B. O. Roos, Theor. Chim. Acta 1990,
79, 291.
[15] R. R. Birge, L. P. Murray, M. B. Pierce, H. Akita, V. Balogh-Nair,
L. A. Findsen, K. Nakanishi, Proc. Natl. Acad. Sci. USA 1985, 82, 4117.
[16] M. Han, B. S. Decker, S. O. Smith, Biophys. J. 1993, 65, 899.
Prof. Dr. A. A. Fokin, I. V. Kolomitsyn, S. Nadi
Department of Organic Chemistry, Kiev Polytechnic Institute
Pr. Pobedy, 37, 252056 Kiev (Ukraine)
Â
[**] The dedication honors the seminal contributions of Paul von Rague
Schleyer to adamantane chemistry. This work was supported by the
Fonds der Chemische Industrie (Liebig-Fellowship for P.R.S.), the
Deutsche Forschungsgemeinschaft, and the Fundamental Research
Foundation of the Ukraine. P.R.S. is grateful to Prof. A. de Meijere for
his support. Critical comments from Dr. J. Belzner were highly
appreciated.
Angew. Chem. Int. Ed. 1998, 37, No. 13/14
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