For the first time, the [2,3]-Meisenheimer rearrangement has been developed into a general strategy for the construction of chiral tertiary alcohols. The effectiveness and practicality of this methodology are illustrated by the successful synthesis of (R)-20 and (R)-30, the side chain acids of homoharringtonine and harringtonine, respectively.

The enantiospecific total synthesis of the δ-lactonic marine natural product (+)-tanikolide (1), isolated from Lyngbya majuscula , was achieved using a [2,3]-Meisenheimer rearrangement as the key reaction. During this rearrangement, we discovered that the allylic amine N-oxide could direct the m-CPBA double-bond epoxidation to the syn position. The resulting syn product 8 underwent epoxide ring opening under the m-CBA conditions to give the five- and six-membered cyclic ether amine N-oxides, which we further treated with Zn and conc. HCl to obtain the reduced bisbenzyl tertiary amines 23 and 22, respectively. When 23 and 22 were treated with trichloroisocyanuric acid (TCCA) in dichloromethane, oxidation at the benzyl position occurred, forming iminium ions. These intermediates were trapped by intramolecular reaction with the hydroxyls, and the resulting intermediates were then oxidized or shifted to afford 25 and 24, respectively. The entire one-pot process involves N-debenzylation, N-chlorination, and hemiacetal oxidation. The amine N-oxide-directed epoxidation complements Davies' ammonium-directed epoxidation. Thus, TCCA N-debenzylation is described for the first time and might be a useful N-debenzylation technique.

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

Chlorination. -Tanikolide (I) is synthesized over nine linear steps in 53% overall yield. -(XIE, Y.; SUN, M.; ZHOU, H.; CAO, Q.; GAO, K.; NIU, C.; YANG*, H.; J. Org. Chem. 78 (2013) 20, 10251-10263, http://dx.doi.org/10.1021/jo4016437 ; Sch. Pharm. Sci., Zhengzhou Univ., Zhengzhou, Henan 450001, Peop. Rep. China; Eng.) -M. Zastrow 11-230