以硫基、胺基為親核試劑之非鏡像共軛加成反應

Diastereoselective conjugate addition of thiol and amine to camphor pyrazolidinone Derived

林峻揮(Chun- Hui Lin)

指導教授 ： 陳焜銘

國立臺灣師範大學/理學院/化學系/碩士(1999年)

摘要

本研究在合成以樟腦架構為主的對掌輔助劑，由此對掌輔助劑衍生之α,β-不飽和醯胺為共軛受質，分別與胺基及硫基等親核試劑反應，在路易士酸催化條件下，可得到共軛加成產物。以胺基為親核試劑時，鑭系金屬的路易士酸催化下反應進行，產率高達90%，不過非鏡像立體選擇性不甚理想(最高為10%　de)。
以含有酯類之硫醇化合物為親核試劑時，在四氯化錫及四氯化鈦為路易士酸的條件下，可得到相當高之的非鏡像立體選擇性(最高可達98% de)，當共軛受質為crotonate衍生物時，在四氯化錫的催化條件下，其所建立之立體化學中心可得到大於99% de的S組態，反之，在四氯化鈦催化條件下，可以得到80% de的R組態。改變路易士酸的種類導致相反組態的產物是相當有趣的發現，我們對此現象亦提出合理的反應機構。除此之外，亦探討在不同溶劑、溫度、不同共軛受質、路易士酸當量數及在鹼性條件下對立體選擇性及反應的影響。

關鍵字

共 軛加成反應 ； 對掌輔助劑 ； 共軛受質

並列摘要

Reaction of Chiral α,β-unsaturated carboxylic acid derivanties derived from a camphor pyrazolidinone 69 with thiols and amines to afford β-mercaptocarboxylic acid derivatives and β-aminocarboxylic acid derivatives, respectively. The chiral camphor pyrazolidinone 69 can be easily prepared from the commerical available (+)-ketopinic acid in 3 steps in a total of 74% yield.
In the presence of Yb(OTf)3, the conjugate addition of O-Benzylhydroxylamine to chiral N-alkenoyl-N-phenyl pyrazolidinones provide the conjugate addition adduct in good chemical yield (90%), with poor diastereoselectivity .
The reaction of methyl 3-mercaptopropionate with crotonate (70b) in the presence of titanium tetrachloride (TiCl4) or tin tetrachloride (SnCl4), the conjugate adducts were isolated in good yield (85-90%) and in excellent diastereomeric excess (70-98% de). When mediated with SnCl4, the absolute configuration of the newly generated stereocenter C(β) is S while the R configuration dominates when mediated with TiCl4. The reversal of stereochemistry as a function of Lewis acid is remarkable. A reasonable mechanism has been proposed. In addition, the effect of diastereoselectivites and reaction rate in the presence of various solvent, conjugate acceptor, the amount of Lewis acid, and additives are studied.

並列關鍵字

camphor pyrazolidinone ； conjugate acceptor ； conjugate addition

參考文獻

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