The synthesis of fluorinated endcaps: Part 2. Preserving the endo,endo configuration in the monohydrolysis of 7-fluorinated nadic diesters David E. Rajsfus, Pessia Gilinsky-Sharon, Aryeh A. Frimer * Ethel and David Resnick Chair in Active Oxygen Chemistry, Bar-Ilan University, Ramat Gan 52900, Israel 1. Introduction The strained norbornene ring has found broad application in assorted fields [1–10] but most famously in the development of high-temperature aerospace polyimides [11–17]. Research has surprisingly shown, however, that the C 7 -bridge of norbornene in these polyimides is the site of much of the oxidative degradation observed on thermal cycling [15,16,18–20]. In the search for improved thermal oxidative stability (TOS), several polymers have been prepared which incorporate fluorinated monomers [21–26]. Nevertheless, the number and variety of fluorinated norbornenes has been limited. To this end we have devoted our recent efforts to the synthesis of 7,7-difluoro and 7-fluoronadic acid esters 5c and 5d, as precursors in the preparation of aerospace polyimides (oligomers 7c and 7d, Scheme 1). Our previous work in this field [27,28] has taught us how to conveniently insert one or two fluorines into the C 7 position of the norbornene system, beginning with 7-ketoanhydride 1a. Treating the corresponding symmetrical dimethylester 3a (R = CH 3 ) with DAST (diethylaminosulfur trifluoride) [28–33] generates the corresponding 7,7-difluoro analog 3c. The reduced 7-hydroxydie- ster 3b (R = CH 3 ), on the other hand, gives us convenient entre ´e to the corresponding 7-fluoro system 3d (R = CH 3 ). We note that both carboxylic acids and anhydrides are reported to react with DAST to yield acyl fluorides and/or CF 3 derivatives [32,33]. Hence, we used diesters 3 – not diacids 2 – as the starting material for these fluorinations. A second consideration in planning an effective synthetic strategy of 2,3-nadic monoacid monoesters 5 is the requirement to generate them specifically in the cis-2,3-endo,endo configuration, rather than the epimeric trans-exo,endo analogs 6. Only the former can cyclize, undergoing imidization to polyimides 7c and 7d [34]. We have previously shown [27] that 7-oxodiacid 2a and its 7- hydroxy analog 2b undergo esterification via diazotization or ultrasonic methylation yielding the respective symmetrical diesters 3a and 3b (R = CH 3 ) in the endo,endo configuration exclusively. Similarly, no inversion of configuration is observed on the treatment of ketones 3a or alcohols 3b with DAST. Thus, only cis-endo,endo symmetrical diesters 3c and 3d are formed, while none of the trans-endo,exo analogs 4c and 4d are observed. However, under the strongly basic conditions required for the subsequent monohydrolysis, the symmetrical dimethyl esters 3c and 3d (R = CH 3 ) undergo partial epimerization. As a result, the nadic monoacid monomethyl esters are obtained as a mixture of both the cis-endo,endo (5c and 5d) and the trans-endo,exo (6c and 6d) configurations [27]. As just noted, the latter resists imide 7 formation. We describe herein our development of an alternate synthetic strategy which successfully allows for the convenient preparation Journal of Fluorine Chemistry 148 (2013) 59–66 A R T I C L E I N F O Article history: Received 28 November 2012 Received in revised form 28 January 2013 Accepted 29 January 2013 Available online 6 February 2013 Keywords: Nadic ester hydrolysis Hydrolysis of symmetric diesters 7-Oxonadic ester 7-Hydroxynadic ester 7-Fluoronadic ester 7,7-Difluoronadic ester A B S T R A C T Fluorination should impart greater thermal-oxidative stability to the versatile norbonenyl system. Anti- 7-Fluoronadic and 7,7-difluoro nadic acid esters (5-norbornenyl-2-endo,3-endo-acid esters) 5c and 5d were synthesized as precursors for a variety of uses including the manufacture of high temperature aerospace polyimides (7c and 7d). Acid ester 5c and 5d cannot be simply prepared by the saponification of symmetrical diesters 3c and 3d because of concomitant epimerization. We have developed an alternative approach, involving the preparation and monohydrolysis of the mixed t-butyl methyl diesters 8c and 8d – while maintaining the cis-endo,endo configuration around the C 2 and C 3 linkage. Selective ester hydrolysis of the mixed esters mediated by formic acid produced the desired acid ester 5c and 5d. ß 2013 Elsevier B.V. All rights reserved. * Corresponding author at: Department of Chemistry, Bar-Ilan University, Ramat Gan 52900, Israel. Tel.: +972 3 5318610; fax: +972 3 7384053. E-mail address: Aryeh.Frimer@biu.ac.il (A.A. Frimer). Contents lists available at SciVerse ScienceDirect Journal of Fluorine Chemistry jo ur n al h o mep ag e: www .elsevier .c om /loc ate/f luo r 0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jfluchem.2013.01.030