Beta-環糊精與其衍生物對5取代金剛酮還原反應的面選擇性研究

Abstract

碳5取代金剛酮與NaBH4進行還原反應,將會受到取代基推或拉電子效應的 影響而改變親核基的anti或syn方位攻擊.本論文以此反應當做架構,將反 應移到含beta-環糊精的環境中,利用beta- 環糊精孔洞會與碳5取代基有 較大的凡得瓦力而形成錯合物,使金剛酮分子倚靠beta-環糊精對syn-pi面 造成立體阻礙 ,改變面選擇性.我們除了利用以前用過的氟,氯,溴,苯等取 代基外也加入更大的取代基如三甲基錫以及在苯環上另外再加取代基的化 合物.從實驗中發現小的取代基如氟,beta-環糊精並不影響面向選擇性,當 取帶基過大如三甲基錫時syn-pi面攻擊反而有利.本論文並使用各種修飾 的beta-環糊精,對取代基大小與beta-環糊精孔洞深淺進行探討,發現當孔 洞變小或變窄時,對面向選擇性影響會變差.此外我們發現在水溶液中進行 還原反應時2-Br及2-Cl會有SN1反應產生,Br及 Cl會被置換成OH.我們發現 不管何種beta-環糊精及其對面向選擇的大小如何,均可以保護2-Br及2-Cl 使之不進行SN1反應.我們也以氫核磁共振方法證明,所有碳5上有不同取代 苯環的金剛酮與beta-環糊精形成錯合物. The reduction of 5-substituted-adamantan-2-one (5-X-ADs) by NaBH4 is found to favor the syn-pi-face attack of nucleophile due to electronwithdrawing substituents. In the present of beta- cyclo- n(beta-CD),5-X-AD can form an inclusion complex with the hydrophibic cavity of CD.This leads to the protection of syn- pi- face of 5-X-AD and a reversed face selectivity was observed. Beside Cl and Br substituents, we also added bigger substituents as SnMe3 and different substituted phenyl groups. Our results show that, for small substituent (such as F), beta-CD has almost no effect on pi-face selectivity, however, for large substituent such as SnMe3, enhanced syn- attack was found. In this work, we also use seneral modified beta-CDs in combination with different 5-X-ADs to study their size and shape relationships for inclusion complexes and their effects on face selectivity. 2-Br and 2-Cl are found to undergo SN1 rection in the process of basic reduction (NaBH4 and 0.01 N NaOH);i.e. Br- and Cl- substituents arereplaced by -OH. All beta-CDs studied here can protect 2-Br and 2-Cl form SN1 reaction no matter whether they change the face-selectivity or not. H-NMR was used to prove the inclusion complex formation of 5-acryl-ADs with beta-CDs.