Zirakzadeh Afrooz, Herlein Alexander, Groß Manuela A, Mereiter Kurt, Wang Yaping, Weissensteiner Walter
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.
Institute of Organic Chemistry, University of Vienna , Währinger Straße 38, A-1090 Vienna, Austria.
Organometallics. 2015 Aug 10;34(15):3820-3832. doi: 10.1021/acs.organomet.5b00464. Epub 2015 Jul 29.
The -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 into -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 efficiently -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 by -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 be -deprotonated selectively, but in neither case was scrambling of a chloro substituent observed. As a further application of this -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-RFc; R = CHO, COOEt, CN, CH=CH).
通过用四甲基哌啶锂（LiTMP）处理，研究了卤代二茂铁的去质子化反应。碘代、溴代和氯代二茂铁在卤代取代基相邻位置很容易发生去质子化。然而，该反应的合成适用性受到限制，因为根据温度和卤代取代程度，二茂铁核心上的碘和溴取代基会发生重排。碘代二茂铁不能选择性地转化为取代碘代二茂铁，因为在LiTMP存在下，即使在-78°C时碘代取代基也会有效重排，并且这个过程在加入亲电试剂之前就已经发生了。然而，溴代二茂铁和某些单溴代衍生物在低温下可以有效地去质子化，并与多种亲电试剂反应，得到1,2-和1,2,3-取代的二茂铁衍生物。例如，通过溴代二茂铁的去质子化反应，分别与亲电试剂二碘乙烷和二碘四氟乙烷反应，合成了2-溴-1-碘二茂铁。在这种及相关情况下，通过在低温下以反向模式进行反应，可以有效地抑制由于过量LiTMP导致的碘化物重排过程和进一步的产物去质子化。与低温过程相反，在室温下，溴代二茂铁中的溴代取代基在LiTMP存在下会发生重排。氯代和1,2-二氯二茂铁可以选择性地去质子化，但在这两种情况下都未观察到氯代取代基的重排。作为这种去质子化反应的进一步应用，开发了一种合成1,3-二取代二茂铁的路线。1,3-二碘二茂铁可以通过溴代二茂铁分四步得到。在多克规模上，总产率达到41%。1,3-二碘二茂铁进一步转化为对称的1,3-二取代二茂铁（1,3-RFc；R = CHO、COOEt、CN、CH=CH）。
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