香豆素衍生物於 Wittig 反應及有機不對稱催化的應用

The application of coumarin derivatives in Wittig reactions and asymmetric organocatalysis

楊玫春(Mei-Chun Yang)

指導教授 ： 林文偉

國立臺灣師範大學/理學院/化學系/碩士(2012年)

摘要

本論文主要分為兩個部分: 第一部份以香豆素衍生物為起始物製備新型雜環化合物經由分子內 Wittig 反應； 第二部份發展有機催化 Michael 加成反應，以香豆素衍生物作為 Michael 受體與環己酮或丙醛進行反應。
第一部份，設計三種香豆素衍生物作為 Michael 受體與醯氯、三丁基膦以及三乙基胺進行分子內 Wittig 反應，合成多官能性的呋喃[3,4-c]香豆素、呋喃[3,2-c]香豆素以及具有呋喃分子取代的香豆素化合物。
第二部分，設計具有 Michael 受體的香豆素衍生物，以香豆素衍生物為起始物與環己酮、丙醛進行有機催化 Michael 加成反應，合成以香豆素為主結構的一種新型的 Michael 加成產物，具高立體選擇性 (非鏡像選擇性 20:1，鏡像超越值 91% ee ) 以及良好的產率 80%。如果將環己酮置換為丙醛，以丙醛與 具 Michael 受體的香豆素衍生物進行有機催化 Michael 加成反應，得到的 Michael 加成產物可進一步與 PCC 進行氧化反應，產物為新類型且具兩個掌性中心的多官能性內酯衍生物。

關鍵字

Wittig 反應 ； 呋喃香豆素

並列摘要

The dissertation is divided into two parts: preparation of new types of heterocycles bearing coumarin moieties via intramolecular Wittig reactions as key steps (part I) and development of organocatalytic Michael addition reactions of cyclohexanone or propionaldehyde towards the designed Michael acceptors with coumarin moieties (part II).
In part I, three kinds of designed coumarin derivatives as Michael acceptors are proposed and successfully react with a wide variety of acid chlorides, tributylphosphine, and triethylamine via intramolecular Wittig reactions to provide functional furo[3,4-c]coumarins, furo[3,2-c]coumarins, and furyl coumarins (Figure 1).
In part II, investigation of organocatalytic Michael addition reactions of cyclohexanone or propionaldehyde towards the designed Michael acceptors with coumarin moieties is carried out. A new type of Michael adducts with high stereoselectivities (up to 20:1 dr, 91% ee) and good yields (up to 80% yield) can be generated starting from cyclohexanone and Michael acceptors with coumarin as the core structure. While propionaldehyde, instead of cyclohexanone, is employed in organocatalytic Michael addition reactions with Michael acceptors bearing coumarin moieties, the Michael adducts can further undergo oxidation reactions with PCC to afford a new class of functional lactone derivatives with two stereogenetic centers.

並列關鍵字

Wittig reaction ； fuorocoumarin

參考文獻

(1) Schiedel, M.-S.; Briehn, C. A.; Bäuerle, P. Angew. Chem. Int. Ed. 2001, 40, 4677.

(2) Inagaki, S.; Ohtani, O.; Goto, Y.; Okamoto, K.; Ikai, M.; Yamanaka, K.-i.; Tani, T.; Okada, T. Angew. Chem. Int. Ed. 2009, 48, 4042.

(4) Kathuria, A.; Priya, N.; Chand, K.; Singh, P.; Gupta, A.; Jalal, S.; Gupta, S.; Raj, H. G.; Sharma, S. K. Bioorg. Med. Chem. 2012, 20, 1624.

(5) Carta, F.; Maresca, A.; Scozzafava, A.; Supuran, C. T. Bioorg. Med. Chem. 2012, 20, 2266.

(6) Sashidhara, K. V.; Kumar, A.; Kumar, M.; Sarkar, J.; Sinha, S. Bioorg. Med. Chem. Lett. 2010, 20, 7205.