A Novel, Simple and Efficient Synthesis of Ferrocenyl Enones and Alkynols

Abstract

A mild and efficient alkoxide-catalyzed addition of ferrocenylacetylene to diverse ketones and aldehydes is described. Some new propargyl alcohols containing ferrocenyl moieties were obtained by addition of ferrocenylacetylene to ketones. When aromatic aldehydes were used, trans-enones such as ferrocenyl chalcone derivatives were obtained in high yields via base-catalyzed addition-isomerization.Propargylic alcohols are versatile precursors to many organic molecules including natural products 1 and pharmaceutical compounds 2 . The most commonly employed method to obtain propargylic alcohols is the nucleophilic addition of metalated terminal alkynes to ketones and aldehydes. Whereas the reactive alkynylides are generally prepared from a terminal alkyne and stoichiometric amounts of alkynylmetals (Li, Na, K and Mg). 3 However, these alkynylmetals commonly possess high reactivity and strong basicity, and sometimes undergo undesired side reactions. Several improved procedures employing alkynyl-B, 4 Al, 5 Ce, 6 and V 7 are not straightforward as the alkyne deprotonation must be necessarily carried out as a separate step. Balber 8 and Knochel 9 have made a significant contribution to simplify this process by use of catalytic bases t-BuOK and CsOH for the in situ generation of metal acetylides under mild condition. However, they are mostly applicable only to ketones and aliphatic aldehydes. Aromatic aldehydes seem to undergo complex side reactions and are not suited for t-BuOK 8 and CsOH 9 catalysis.Ferrocenylacetylene has been successfully used as starting material for the synthesis of conjugated redox-active ligands, 10 new materials with defined magnetic and electronic properties, 11 compounds with large optical nonlinearities 12 and polymers. 13 In our continuing interest in the development of practical methods for synthesis of ferrocene derivatives, we decided to investigate the efficiencies of ferrocenylacetylene addition to aromatic aldehydes under t-BuOK catalyzed conditions. 8 Interestingly, we found that the usually reliable coupling reaction between terminal alkynes of type 1 and aromatic aldehydes of type 2 does not furnish the expected propargylic alcohols 4, but that the isomeric aryl enones 3 are formed in high yield and very short reaction time (Scheme 1). This provided a promising protocol for preparation of ferrocenyl chalcones in a practical, economical and mild sense compared with the traditional method 14 To the best of our knowledge, this unusual reaction was first observed for the addition of terminal acetylene to aldehyde in a base-catalyzed manner. Scheme 1A typical experimental procedure is as follows. To a solution of 1 (0.4 mmol) and 2 (0.4 mmol) in DMSO (1.5 mL) was added t-BuOK (0.02-0.04 mmol) at room temperature under Ar atmosphere. After several minutes, the usual workup and column chromatography offered the desired product. Table 1 summarizes our results.The products 3a-3l were kept unchanged for the initial 30 minutes when the starting material 1 and 3 disappeared (TLC examination) and ...