各校計畫成果

中文:
1-烷基-2,3-烯烴酯(α-alkyl β,γ-alkenyl esters)是複雜生物分子結構中的重要單體，同時也是天然物全合成路徑中的關鍵中間體。其獨特的結構與反應特性促使我們對其進行方法學開發。傳統不對稱合成方法中一般不是在嚴苛的反應條件下進行，就是使用對環境較不友善的金屬試劑進行鏡像誘導，使得要能精確控制酯類α-位點碳的立體選擇性一直面臨挑戰。為了克服這些挑戰，我們團隊採用了逆熱力學的光催化策略來合成1-烷基-2,3-烯烴酯。在紫外光的照射下，對起始物 1,2-不飽和酯(α,β-unsaturated esters)進行諾里什重排反應(Norrish type II rearrangement)產生烯醇，接著烯醇在掌性磷酸的作用下進行1,3-質子轉移，順利建構出不對稱的1-烷基-2,3-烯烴酯。透過上述策略我們成功得到超過50個例子，並且最高可以獲得高達96%的鏡像超越值(enantiomeric excess)。此外，我們也將上述開發策略應用於3-丁內酯類(γ-butyrolactone-type)海洋代謝物的形式合成(formal synthesis)上。最後，我們也嘗試將催化級別反應透過光流體技術進行量級放大至克級反應，仍能保持優異的立體選擇性(最高 92% ee)，說明該策略在未來部分具備工業化生產的發展潛力。

英文:

    1-Alkyl-2,3-alkenyl esters (α-alkyl β,γ-alkenyl esters) are important monomers in the architecture of complex biomolecules and serve as key intermediates in the total synthesis of natural products. Their unique structural and reactive features motivated us to develop new synthetic methodologies for their preparation. Conventional asymmetric synthesis approaches often require harsh reaction conditions or employ environmentally unfriendly metal reagents for chiral induction, making it challenging to precisely control the stereoselectivity at the ester α-carbon. To address these challenges, we adopted an anti-thermodynamic photocatalytic strategy for the synthesis of 1-alkyl-2,3-alkenyl esters. Under ultraviolet irradiation, α,β-unsaturated esters underwent a Norrish type II rearrangement to generate the corresponding enols, which subsequently underwent a 1,3-proton transfer promoted by a chiral phosphoric acid, thereby constructing the desired asymmetric 1-alkyl-2,3-alkenyl esters. Using this approach, we successfully synthesized over 50 examples, achieving enantiomeric excesses of up to 96%. Furthermore, we applied this methodology to the formal synthesis of a γ-butyrolactone-type marine metabolite. Furthermore, we demonstrated that the catalytic-scale reaction could be scaled up to gram quantities via a photo-flow technique, while maintaining excellent stereoselectivity (up to 92% ee), highlighting the potential of this strategy for future industrial applications.