Effect of cycloalkene structure on ¯uorination with 1-chloromethyl-4-¯uoro-1,4-diazonia[2.2.2]octane bistetra¯uoroborate) F-TEDA) Marko Zupan, p Primoz ÏS Ï kulj and Stojan Stavber Laboratory of Organic and Bioorganic Chemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana and J. Stefan Institute, As Ïkerc Ïeva 6, SI-1000 Ljubljana, Slovenia Received 20 June 2001; revised 13 September 2001; accepted 11 October 2001 Abstract ÐLiquid phase ¯uorination of norbornene with 1-chloromethyl-4-¯uoro-1,4-diazonia[2.2.2]octane bistetra¯uoroborate)ÐF- TEDA resulted in the formation of two rearranged Ritter type products: 2-exo-acetamido-7-syn-¯uoro norbornane and 2-exo-acetamido- 7-anti-¯uoro norbornane in 1:1 ratio in acetonitrile, while the presence of an external nucleophile, e.g. water or methanol resulted in formation of two additional rearranged products: 2-exo-hydroxy or methoxy -7-syn-¯uoro norbornane and 2-exo-hydroxy or methoxy-7- anti-¯uoro norbornane. Fluorination of cycloalkenes obeys a simple second order rate equation, relative rates close to unity were found for norbornene/cyclohexene and cyclopentene/cyclohexene pairs. Activation parameters were determined for cycloalkenes in acetonitrile±water DH ³ 14 kcal mol 21 and DS ³ 220 cal mol 21 K 21 for norbornene), while the Winstein±Grunwald solvent polarity variation had negligible effect. q 2001 Elsevier Science Ltd. All rights reserved. 1. Introduction Bicyclo[2.2.1]heptene norbornene) is one of the most versatile model ole®ns for studying the role of the structure of electron acceptor type E±L reagents in determining the course of addition reactions. 1±4 From these studies, two types of information can be obtained. Firstly, the structures of the products and their distributions inform us about the type of electron shift from the p electron system to the acceptor E±L reagent. 5,6 Secondly, the relative rate of func- tionalisation of norbornene compared with cyclohexene appears to be very dependent on the geometry of the rate determining transition state: 2 close to unity in the case of a three-centred intermediate mercuric acetate 7 and perben- zoic acid 8 ), while a ratio of up to 8000 was observed in four-centred or larger intermediates picryl azide 9 ). The reactivities of almost all F±L reagents for mild ¯uorine introduction into organic molecules have been tested on norbornene. The type of products and their distribution depend strongly on the reagent and on the reaction con- ditions. In the reaction with caesium ¯uoroxysulphate the initially formed ¯uorocarbonium ion underwent proton loss to yield ¯uoro nortricyclane and Meerwein±Wagner rearrangement resulted in 7-syn-¯uoro-norbornenene in nearly equal amounts at room temperature in dichloro- methane 10 while low temperature reaction with ¯uorine gave only rearranged 7-syn-¯uoro-norbornenene. 11 Intro- duction of ¯uorine with xenon di¯uoride however is very sensitive to solvent CH 2 Cl 2 , CCl 4 , CH 3 CN), the catalyst used HF, BF 3 OEt, C 6 F 5 SH) and photochemical initiali- sation, and up to six products were isolated. 12±17 The N±F class of reagents are easy to handle and commer- cially available, while their reactivity depends on their type, which might be of R 1 R 2 NF type, N-¯uoropyridinum and related salts or FN 1 R 1 R 2 R 3 type. 18±22 Kinetic evaluation of ¯uorine transfer from F±L type reagents is rather scarce, due mainly to their high reactivity and the high sensitivity to the reaction conditions. Many of these dif®culties can be overcome by using some N±F reagents whose reactions could be followed by iodometric titration and reproducible data have been obtained. 23±25 We report here our studies of mild ¯uorine introduction to norbornene, cyclopentene and cyclohexene with F-TEDA in acetonitrile in the presence of water or methanol. 2. Results and discussion In a typical experiment, 1 mmol of norbornene 1) was dissolved in 5 ml of acetonitrile, 1.2 mmol F-TEDA 2) was added and stirred at room temperature for 4 h. The crude reaction mixture showed two signals in the 19 F NMR spectrum d 2207, 2201 ppm) and after GC Tetrahedron 57 2001) 10027±10031 Pergamon TETRAHEDRON 0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved. PII: S0040-402001)01031-6 Keywords: bicyclic aliphatic compounds; cycloalkenes; halogenation; kinetics. p Corresponding author; e-mail: marko.a.zupan@uni-lj.si