金(I)催化8-芳香環-2-烯-7-炔-1-辛醇進行分子內克來森類型重排反應合成非鏡像選擇性1,2-雙取代環戊烷衍生物

Abstract

摘要 環戊烷結構為許多天然物中常見的單位，本論文以簡便的方法合成具有立體選擇性的環戊烷衍生物。本文旨在利用金銀共催化系統對帶有炔基的烯醇化物進行分子內克萊森類型重排反應，得到具非鏡像選擇性帶有乙烯基和酮基的1,2-雙取代環戊烷衍生物。

5-己炔-1-醇與芳香環碘化物在鈀金屬催化下進行Sonogashira反應得到6-芳香環-5-己炔-1-醇，以2-碘酰基苯甲酸 (IBX, 2- iodoxybenzoic acid)氧化劑氧化得到6-芳香環-5-己炔-1-醛後，再和溴化2-乙氧-2-側氧乙基三苯基鏻((2-ethoxy-2-oxoethyl)triphenylphosphonium bromide)進行Wittig 反應得到8-芳香環-2-烯-7-炔辛酸乙酯，以二異丁基氫化鋁還原得到8-芳香環-2-烯-7-炔-1-辛醇。

將此帶有炔基的烯醇化合物與0.10當量的氯化三苯基磷金/三氟甲磺酸銀 (Ph3PAuCl/AgOTf)溶於甲苯溶劑，在迴流中，進行分子內克萊森類型重排反應得到帶乙烯基和酮基的-1,2-雙取代環戊烷。以X-ray繞射分析證明環化產物中的乙烯基和酮基為反式的1,2-雙取代環戊烷。

The cyclopentanes are frequently found in a variety of natural products. Therefore, the development of practical and facile synthetic routes for the synthesis of stereoselective five-membered ring derivatives is important. In the thesis, we report that gold and silver cocatalyzed intramolecular Claisen-type rearrangement of (E)-8-phenyloct-2-en-7-yn-1-ol (enynol) produces 1-phenylcarbonyl-2-vinylcyclopentanes in diastereoselective fashion.

Reaction of hex-5-yn-1-ol with aryl iodine catalyzed by palladium(0)under Sonogashira reaction conditions produces 6-arylhex-5-yn-1-ol. Oxidation of 6-arylhex-5-yn-1-ol with IBX (2- iodoxybenzoic acid) affords 6-arylhex-5-yn-1-al. The resulting aldehyde was treated with (2-ethoxy-2-oxoethyl)triphenylphosphonium bromide to afford (E)-ethyl 8-phenyloct-2-en-7-ynoate. Reduction of the (E)-ethyl-8-phenyloct-2-en-7-ynoate using DIBAL(Diisobutylaluminium hydride) generated (E)-8-phenyloct-2-en-7-yn-1-ol.

Treatment of the enynol with 10 mol % Ph3PAuCl / AgOTf in toluene at reflux produced 1-phenylcarbonyl-2-vinylcyclopentanes. The formation of the cyclopentane derivative is believed to undergo intramolecular Claisen-type rearrangement. The X-ray diffraction analysis reveals that the relative stereochemistry of the vinyl and the keto is trans.