title: Halide-MediatedOrtho-Deprotonation Reactions Applied to the Synthesis of 1,2- and 1,3-Disubstituted Ferrocene Derivatives.
abstract: Theortho-deprotonation of halide-substituted ferrocenes by treatment with lithium tetramethylpiperidide (LiTMP) has been investigated. Iodo-, bromo-, and chloro-substituted ferrocenes were easily deprotonated adjacent to the halide substituents. The synthetic applicability of this reaction was, however, limited by the fact that, depending on the temperature and the degree of halide substitution, scrambling of both iodo and bromo substituents at the ferrocene core took place. Iodoferrocenes could not be transformed selectively intoortho-substituted iodoferrocenes since, in the presence of LiTMP, the iodo substituents scrambled efficiently even at -78 °C, and this process had occurred before electrophiles had been added. Bromoferrocene and certain monobromo-substituted derivatives, however, could be efficientlyortho-deprotonated at low temperature and reacted with a number of electrophiles to afford 1,2- and 1,2,3-substituted ferrocene derivatives. For example, 2-bromo-1-iodoferrocene was synthesized byortho-deprotonation of bromoferrocene and reaction with the electrophiles diiodoethane and diiodotetrafluoroethane, respectively. In this and related cases the iodide scrambling process and further product deprotonation due to the excess LiTMP could be suppressed efficiently by running the reaction at low temperature and in inverse mode. In contrast to the low-temperature process, at room temperature bromo substituents in bromoferrocenes scrambled in the presence of LiTMP. Chloro- and 1,2-dichloroferrocene could beortho-deprotonated selectively, but in neither case was scrambling of a chloro substituent observed. As a further application of thisortho-deprotonation reaction, a route for the synthesis of 1,3-disubstituted ferrocenes was developed. 1,3-Diiodoferrocene was accessible from bromoferrocene in four steps. On a multigram scale an overall yield of 41% was achieved. 1,3-Diiodoferrocene was further transformed into symmetrically 1,3-disubstituted ferrocenes (1,3-R2Fc; R = CHO, COOEt, CN, CH=CH2).
authors: Institute of Organic Chemistry, University of Vienna , Währinger Straße 38, A-1090 Vienna, Austria ; Institute of Applied Synthetic Chemistry, Vienna University of Technology , Getreidemarkt 9/163, A-1060 Vienna, Austria.
authors: Afrooz
authors: A
authors: Zirakzadeh
authors: Institute of Organic Chemistry, University of Vienna , Währinger Straße 38, A-1090 Vienna, Austria.
authors: Alexander
authors: A
authors: Herlein
authors: Institute of Organic Chemistry, University of Vienna , Währinger Straße 38, A-1090 Vienna, Austria ; Department of Chemistry, University of Cambridge , Lensfield Road, CB2 1EW Cambridge, U.K.
authors: Manuela A
authors: MA
authors: Groß
authors: Institute of Chemical Technologies and Analytics, Vienna University of Technology , Getreidemarkt 9/164, A-1060 Vienna, Austria.
authors: Kurt
authors: K
authors: Mereiter
authors: College of Pharmaceutical Sciences, Capital Medical University, Beijing , No. 10 Xitoutiao, You An Men Beijing 100069, People's Republic of China.
authors: Yaping
authors: Y
authors: Wang
authors: Institute of Organic Chemistry, University of Vienna , Währinger Straße 38, A-1090 Vienna, Austria.
authors: Walter
authors: W
authors: Weissensteiner