The fluorine atom as a cation-stabilizing auxiliary in biomimetic polyene cyclizations:: Total synthesis of dl-dammarenediol
The fluorine atom as a cation-stabilizing auxiliary in biomimetic polyene cyclizations:: Total synthesis of dl-dammarenediol
复制标题
DOI：
10.1021/jo991196s
复制
发表时间：
1999-12-24
影响因子：
3.6
通讯作者：
Bancroft, KJ
中科院分区：
文献类型：
--
作者：
Johnson, WS;Bartlett, WR;Bancroft, KJ
达马烯二醇I(1a)和II(1b)是通过高效的非酶仿生多烯四环化反应合成的。环化底物五烯醇3含有一个四甲基烯丙醇引发剂、一个烯丙基三甲基硅烷端基和一个位于Pro-C-13的氟原子，以作为阳离子稳定剂(C-S)辅助控制C/D环连接的区域化学。3的合成是通过锂-卤素交换生成醇10和19。3中的Z-氟烯是通过Trost钯催化的乙酸烯丙烷基化反应(Z/E：4.6/1)立体选择性地引入的。3的环化反应最有效(分离产率为62%)，当它在-45℃的二氯甲烷和三氟乙酸的稀溶液中加入时，得到的四环氟二烯24具有丹马烷的反式-反式环立体化学。用Ohsawa-Oishi试剂(Na/K合金和冠醚)完全保留构型，用氢原子取代了24个氟原子。生成的碳氢化合物的瓦克氧化得到酮28，在酮化后，用还原工作臭氧化得到SP-醇30。缩酮水解后与异戊烯基溴化镁发生格氏反应，得到1/3，1a/1b的丹马烯二醇。
Dammarenediols I (1a) and II (1b) were prepared by an efficient nonenzymatic biomimetic polyene tetracyclization route. The cyclization substrate, pentaenol 3, contains a tetramethylallylic alcohol initiator, an allyltrimethylsilane terminating group, and a fluorine atom at pro-C-13 to serve as a cation-stabilizing (C-S) auxiliary controlling the regiochemistry of the C/D ring juncture. The synthesis of 3 employed lithium-halogen exchange to create alcohols 10 and 19. The Z-fluoroalkene in 3 was introduced stereoselectively via the Trost palladium-catalyzed alkylation of allylic acetate 11 (Z/E: 4.6/1). The cyclization of 3 was most efficient (62% isolated yield) when it was added as a dilute solution in dichloromethane to trifluoroacetic acid at -45 degrees C to afford tetracyclic fluoro diene 24 possessing the trans-anti-trans-anti-trans ring stereochemistry of the dammaranes. Replacement of the fluorine atom of 24 with hydrogen with complete retention of configuration was accomplished using the Ohsawa-Oishi reagent (Na/K alloy and crown ether). Wacker oxidation of the resulting hydrocarbon provided ketone 28, which after ketalization was ozonolyzed with a reductive workup to give the SP-alcohol 30. Ketal hydrolysis followed by Grignard reaction with isopentenylmagnesium bromide afforded the dammarenediols (1/3, 1a/1b).