臺灣博碩士論文加值系統

中 文 摘 要
橋頭雙環醇類化合物在適當的條件下易於發生重排而形成各種雙環酮類化合物。有趣地，我們已經發現ㄧ些 [2.2.1] 雙環醇類衍生物，例如：化合物53, 60, 67能夠經由擴環烷基化反應形成[3.2.1] 雙環雙醇化合物來替代雙環酮類化合物。
首先化合物53, 60, 67是由起始物camphor (1), camphene (2), norcamphor (3)製備而得。[2.2.1]雙環醛醇化合物53, 60, 67 接著與各種格林鈉試劑( RMgX )和烷基鋰試劑( RLi )反應，分別得到各種不同取代的擴環烷基化產物。此外，化合物53, 60, 67 在甲氧化鈉或醋酸存在下亦會進行簡單的擴環反應。而這些反應證明具有高度的化學選擇性、立體選擇性和位置選擇性。而這反應的機制在本篇論文中亦會討論。

Abstract

Bridged bicyclic alcohols are prone to rearrangement to

form various bicyclic ketones under appropriate

conditions. Interestingly, we have found that some

[2.2.1] bicyclic alcohol derivatives, such as

compounds 53, 60 and 67, could undergo ring expansion-

alkylation reaction to form [3.2.1] bicyclic diols instead

of ketones.

At first, compounds 53, 60 and 67, was prepared using

camphor (1), camphene (2), and norcamphor (3) as the

starting materials. The formylsubstituted [2.2.1]

bicyclic carbinol ( compounds 53, 60 and 67 ), then,

reacted with various Grignard reagents ( RMgX ) and alkyl

lithium reagents ( RLi ) , individually. In addition, (

compounds 53, 60 and 67 ) did undergo simple ring

expansion reaction in the presence of sodium

methoxide or acetic acid. These reactions turned out to

be highly chemoselective、stereoselective and

regioselective. The mechanism of these reactions will be

also discussed.

目錄：
中文摘要 .............................................. Ⅰ

英文摘要 .............................................. Ⅱ

謝 誌 .............................................. Ⅲ

目 錄 .............................................. Ⅳ

圖 目 錄 .............................................. Ⅵ

表 目 錄 .............................................. Ⅷ

反應流程目錄 ........................................... Ⅸ

緒 論 ............................................... 1

結果與討論 ............................................. 17

藥品與儀器 ............................................. 67

實驗步驟與數據 ......................................... 69

參考文獻 .............................................. 153

附錄 1H光譜 ............................................ 155

13C光譜............................................ 188

X-ray數據資料....................................... 217

圖目錄 ：
圖一 樟腦衍生物之結構圖................................. 2
圖二 擴環反應應用於天然物合成實例....................... 4
圖三 以溴化烷基環烷醇類衍生物與格林鈉試劑進行擴環反應之
機制............................................... 5
圖四 以溴化苯甲基雙環醇類衍生物與格林鈉試劑進行擴環反應
之流程圖............................................ 6
圖五 以溴化苯甲基單環醇類衍生物與格林鈉試劑進行擴環反應
之流程圖............................................ 7
圖六 McKinney以降樟腦氨醇衍生物為起始物，藉由Tiffeneau-
Demjaniou重排進行擴環反應........................... 8
圖七 McKinney以降樟腦氨醇衍生物，藉由Tiffeneau-Demjaniou
重排擴環之機制...................................... 9
圖八 Grigg以Palladium(II)-catalysed進行擴環反應的機制圖..... 10
圖九 Grigg以Palladium(II)-catalysed進行擴環反應流程圖....... 11
圖十 McIntosh以樟腦衍生物進行擴環反應流程圖............. 12
圖十一 Paquette以[2.2.2]雙環醛醇衍生物進行擴環研究流程圖... 13
圖十二 以天然物樟腦合成出樟腦醛醇衍生物之擴環烷基化反應
研究流程圖....................................... 15
圖十三 樟腦醛醇衍生物之擴環烷基化反應研究機制........... 16
圖十四 化合物 55的 X-ray 繞射圖......................... 20
圖十五 化合物61的 X-ray 繞射圖.......................... 27
圖十六 化合物65的 X-ray 繞射圖.......................... 32
圖十七 相轉移試劑的氧化反應機構......................... 34
圖十八 化合物68的 X-ray 繞射圖譜........................ 37
圖十九 化合物85的 X-ray 繞射圖譜........................ 54
圖二十 化合物88的 X-ray 繞射圖譜........................ 60
圖二十一 由天然物降樟腦製備環戊烷衍生物................. 65


表目錄：
表一 Alkyl Lithium for the ring expansion-alkylation result........ 38

表二 norcamphor of Ring Expansion and Alkylation Result........ 45

表三 Ring Expansion Result................................. 63

反應流程目錄：
Scheme 1................................................ 18

Scheme 2................................................ 20

Scheme 3................................................ 21

Scheme 4................................................ 23

Scheme 5................................................ 26

Scheme 6................................................ 29

Scheme 7................................................ 31

Scheme 8................................................ 36

Scheme 9................................................ 41

Scheme 10................................................43

Scheme 11............................................... 44

Scheme 12............................................... 50

Scheme 13............................................... 51

Scheme 14.............................................. 52

Scheme 15.............................................. 53

Scheme 16.............................................. 57

Scheme 17.............................................. 58

Scheme 18.............................................. 59

Scheme 19............................................... 62

參 考 文 獻

1.Wagner, G.; Lampropoulou, M.; Herrmann, R. Tetrahedron 2004, 60, 4635-4643

2.Maleczka, Jr.; Baoyu Mi ; Robert E. Tetrahedron Letters 1999, 40, 2053-2056

3. Maleczka, Jr.; Ruggles Erik L.; Robert E. Organic Letters 2002, 4, 3899-3902

4. Sisiti, A. J.; Rusch, G. M. J. Org. Chem. 1974, 39, 1182-1186

5. Sisiti, A. J. J. Org. Chem. 1968, 33, 453-454

6. Yang,T. -F.; Zhang,Z. -N.; Tseng C. -H.; Chen L. -H. Tetrahedron Letters 2005, 46, 1917-1920

7. Mckinney, M. A.; Patel, P. P. J. Org. Chem. 1973, 38, 4059-4064

8. Grigg, R.; Boontanonda, P. J. C. S. Comm. 1977. 583-584

9. Mcintosh, J. M.; Cassidy, K.C. Can. J. Chem. 1991, 69, 1315-1319

10. Paquette, L. A.; Guevel,R.; Sakamoto,S.; Kim, I. H.; Crawford, J.
J. Org. Chem. 2003, 68, 6096-6107

11. Paquette, L. A.; Andrews, J. F. P.; Vanucci, C.; Lawhorn, D. E.; Negri,
J. T.; Rogers, R. D. J. Org. Chem. 1992, 57, 3956-3965

12. Paquette, L. A.; Pegg, N. A. ; Topps, D. ; Maynard, G. D.; Rogers, R. D.
J. Am. Chem.Soc. 1990, 112, 277-283

13. Paquette, L. A.; Reddy, Y. R.; Haeffner, F.; Houk, K. N. J. Am. Chem. Soc.
2000, 122, 740-741

14. Wittig, G.; Geissler, G.; Justus Liebigs Ann. Chem. 1953, 580, 44-57.

15. Cha, J. K.; Christ, W. J.; Kishi, Y. Tetrahedron 1984, 40, 2247-2255.

16. Cha, J. K.; Christ, W. J.; Kishi, Y. Tetrahedron Lett. 1983, 24, 3943-3946.


17. Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org. Chem. 1987, 52,
2559-2562.

18. Thomas, S. S. J. Chem. Edu. 1991, 68, 1049

19. Vainiotalo, P.; Pohjala, E.; Mälkönen, P. J. Chem. Soc.Perkin Trans. II
1985, 10, 1537-1540

20. Hückel, W.; Schneider, H. -J.; Schneider-Bernlöhr, H. Liebigs Ann. Chem. 1975, 1690-1699

21. Vedejs, E.; Meier, G. P.; Snoble, K. A. J. J. Am. Chem. Soc. 1981, 103, 2823-2831

22. Ranganathan, S.; Singh, B. B. Journal of the Chemical Society [Settion] D : Chemical Communications 1970, 4, 218-219

23. North, M.; Hibbs, D. E.; Hursthouse, M. B.; Jones, I. G.; Jones, W.;
Malik, K. M. A. J. Org. Chem. 1999, 64, 5413-5421.

24. Ruedi, G.; Nagel, M.; Hansen, H.-J. Organic Letters 2003, 5, 2691-2693