β-硝基苯乙烯系列物與親核性試劑反應之研究及金剛烷衍生物與穩定的親核性試劑反應之立體化學探討

The study of the reactions of β-nitrostyrenes and nucleophilic reagents and the stereochemistry of the reactions of derivatives of adamantan-2-ones and stable nucleophilic reagents

林文偉(Wen-Wei Lin)

指導教授 ： 姚清發

國立臺灣師範大學/理學院/化學系/碩士(1999年)

摘要

第一部份：
4-Pentene-1-magnesium bromide 2a或3-butene-1-magnesium bromide 2b可和β-硝基苯乙烯系列物1進行加成反應（Michael addition reactions）生成中間產物3或4（nitronates）。在室溫的條件下將ethyl chloroformate及催化量的4-dimethylaminopyridine（DMAP）加入3或4之溶液中（one-pot）即可得到中等至高產率的isoxazolidines衍生物9或10，trans-9：cis-9從1：3.00到1：4.06，而trans-10：cis-10大於99：1。在產物之純化的過程中也同時分離到經由ethyl chloroformate捕捉住nitrile oxides而生成的化合物14a-d，所以化合物9推論是經由INOC（intramolecular nitrile oxide-olefin cycloadditions）反應機構而產生。化合物10生成的機構則是推論經由IAOC（intramolecular alkoxycarbonyl nitronate-olefin cycloadditions）形成中間體N-(ethoxycarbonyl)isoxazolidines 13，然後脫去EtOH和CO2（or EtOCO2H）而得到最終產物10。
第二部份：
在三乙基胺（Et3N）的作用下allyl mercaptan 2可和β-硝基苯乙烯系列物1在室溫下進行1,4-加成反應（Michael addition reactions）生成化合物3（nitro sulfides）。將methyl chloroformate（MCF）加入化合物3的溶液中後加熱迴流即可得到[3.3.0]雙環化合物6，而trans-6：cis-6從1.1：1到1.8：1。在產物之純化的過程中也同時分離到經由methyl chloroformate捕捉住nitrile oxides而生成的化合物7和8。經由產物的分析判斷化合物6生成的機構推論是先形成5（nitrile oxides）然後再經由INOC（intramolecular nitrile oxide-olefin cycloadditions）得到最終產物6。
第三部份：
5-Substituted adamantan-2-ones 1-X和硝基甲烷（nitromethane）2、thiophenol 3、piperidine 4反應可生成1,4-加成產物5-X；而在此一系列中的取代基（-X）有六種：分別為-H、-F、-Cl、-Br、-I和-Ph。3從zu-face或en-face進行親核性加成所得到的異構物5-X（X = F、Cl、Br、I和Ph）的比例幾乎是固定（約3：2）。當4-substituted-1-nitromethylene-adamantanes 6-X和3、4一起反應也可得到相同的結果，而此一結果可用靜電場作用理論（the electrostatic field influence）討論之。另外亦發現不僅可藉由將所合成的5-X先行氧化再進行β-脫去反應以生成6-X，同時也可以將5-X和silica gel加熱反應進行β-脫去反應而生成相同的產物6-X。

關鍵字

β-硝基苯乙烯系列物 ； 金剛烷衍生物 ； HASH(0x8bf7588) ； HASH(0x8bf7600) ； HASH(0x8bf7678)

並列摘要

Part 1:
The Michael addition reactions of β-nitrostyrenes 1 with 4-pentene-1-magnesium bromide 2a or 3-butene-1-magnesium bromide 2b generated nitronates 3 or 4. Medium to high yields of isoxazolidine derivatives 9 and 10 were obtained when nitronates 3 or 4 were treated with ethyl chloroformate in the presence of catalytic amount of 4-dimethylaminopyridine (DMAP) at room temperature in one-pot and the ratios of trans-9:cis-9 were from 1:3.00 to 1:4.06 and the ratios of trans-10:cis-10 were >99:1. The formation of compounds 9 is proposed to proceed through intramolecular nitrile oxide-olefin cycloadditions (INOC) because compounds 14a-d, obtained from the trapping of the nitrile oxides by ethyl chloroformate, could be isolated. The mechanism of the generation of compounds 10 is proposed to proceed through intramolecular alkoxycarbonyl nitronate-olefin cycloaddtions (IAOC) to form intermediates N-(ethoxycarbonyl)isoxazolidines 13 and then eliminate EtOH and CO2 (or EtOCO2H) to yield the final products.
Part 2:
Reactions of β-nitrostyrenes 1 with allyl mercaptan 2 in the presence of triethylamine generated unsaturated nitro sulfides 3 and then the solution was treated with methyl chloroformate (MCF) and was refluxed to obtain [3.3.0] bicyclic products trans-6 and cis-6 in one-pot. The ratios of trans-6:cis-6 were from 1.1:1 to 1.8:1 and the mechanism of the formation 6 is proposed to proceed through the formation of nitrile oxides 5 to undergo intramolecular nitrile oxide-olefin cycloaddition (INOC).
Part 3:
Reactions of 5-substituted adamantan-2-ones 1-X with nitromethane 2, thiophenol 3, and piperidine 4 generated the 1,4-addition products 5-X. A variety of substituents X were used: hydro, fluoro, chloro, bromo, iodo and phenyl groups. The ratios of the different isomeric products 5-X generated from the zu-face or en-face by the nucleophilic addition of 3 were nearly 3:2. The same results were observed while reactions of 4-substituted-1-nitromethylene-adamantanes 6-X with thiophenol 3 and piperidine 4 were in process and were discussed in terms of the electrostatic field influence. The method of synthesis of 6-X via oxidation of 5-X and β-elimination was discussed, as well as the other method via direct β-elimination of 5-X on silica gel was developed.

並列關鍵字

β-nitrostyrenes ； 5-substituted adamantan-2-ones ； 4-substituted-1-nitromethylene-adamantanes ； adamantan-2-ones ； 2-nitromethyleneadamantanes

參考文獻

(f) Yao, C.-F.; Kao, K.-H.; Liu, J.-T.; Chu, C.-M.; Wang, Y.; Chen, W.-C.; Lin ,Y.-M; Lin, W.-W.; Yan, M.-C.; Liu, J.-Y.; Chuang, M.-C.; Shiue, J.-L. Tetrahedron 1998, 54, 791.

(b) Gottlieb, L.; Hassner, A. J. Org. Chem. 1995, 60, 3759.

(3) (a) Mukaiyama, T.; Hoshino, T. J. Am. Chem. Soc. 1960, 82, 5339.

(b) Basel, Y.; Hassner, A. Synthesis 1997, 309.

(c) Maugein, N.; Wagner, A.; Mioskowski, C. Tetrahedron Lett. 1997, 38, 1547.