Frontalin is usually used as one of standard molecules to test the usefulness of chiral tertiary alcohol construction. Based on methodology of chiral tertiary alcohols construction via [2,3]-Meisenheimer rearrangement which has been developing on our laboratory, the formal synthesis of (-)-frontalin is finished via successive Wittig reaction, ester reduction, [2,3]-Meisenheimer rearrangement, and etc. The total yield is 34% and the ee value is 94%. The substrate scope is expanded from α,β-conjugated olefins into isolated olefins. This proves the more general characteristic of chiral tertiary alcohol construction via [2,3]-Meisenheimer rearrangement. Keywords (-)-frontalin; chiral tertiary alcohol; [2,3]-Meisenheimer rearrangement; Wittig reaction (-)-Frontalin (1), 其化学结构为(1S,5R)-1,5-二甲 基-6,8-二氧双环[3.2.1]辛烷, 系 Kinzer 等 1969 年从美国 西部松小蠹虫(Dendroctonus frontalis)尾部分离得到, 用 于小蠹虫聚集的信号传递物. 人工合成(-)-Frontalin(1)使由小蠹虫啃食树皮引起的大面积松林死亡已得到 有效控制 [1] . 1996 年, 从几种被子植物的树皮中也分离 得到(-)-Frontalin (1), 但其在植物中的具体作用尚不 清楚 [2] . 2005 年, 英国《自然》杂志报道了在亚洲成年大 象中, 由于脸部颞腺中分泌(-)-Frontalin (1)和其对映 体比例不同, 而引起其性相关行为发生变化 [3] .(-)-Frontalin (1)的 6,8-二氧双环[3.2.1]辛烷分子骨 架, 结构较为独特, 但更为独特的是在该分子骨架中隐 含有合成上具有挑战性的手性三级醇结构 [4] , 因此结合 (-)-Frontalin (1)的实用价值、独特骨架、挑战性手性三 级醇结构这三方面因素, 使(-)-Frontalin (1)成为化学 工作者进行他们手性三级醇构筑方法学测试偏好的基 准分子之一.迄今为止, 至少有 26 条消旋体合成路线, 48 条光学 活性(-)-Frontalin (1)合成路线的报道 [1] . 化学工作者对

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 ...

A Novel, Simple and Efficient Synthesis of Ferrocenyl Enones and Alkynols. -Advantages of the title reaction are short reaction times, mild conditions, easily available reagents and ideal atom economy. -(SUN, M.; SHI, Q.; HUANG*, G.; LIANG, Y.; MA, Y.; Synthesis 2005, 15, 2482-2486; State