利用對掌N-乙醛醯胺與-酮醯胺衍生物進行不對稱烯丙基加成反應
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2004
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Abstract
利用烯丙基金屬化合物(allylmetal)與醛基化合物進行不對稱烯丙基加
成反應(allylation),乃是有機合成中相當重要的合成方式。反應所得到之產
物─烯丙醇,於有機合成上之應用亦相當廣泛,藉由各種不同的反應條件,
可以製備醛基、酮基、環氧化合物、γ-內酯、δ-內酯……等不同的官能基化
合物;再者,烯丙醇在許多天然物的分子(如:Laulimide(21)、LY426965
(22)……等)結構中亦為重要的一種官能基。因此,若能有效掌握產物─
烯丙醇的「立體化學中心」,必更能增進烯丙基加成反應的應用。
本研究以對掌輔助劑camphorpyrazolidinone(112)為主架構,利用其衍
生物125 與126,進行不對稱烯丙基加成反應,並探討其立體化學中心的控
制,均獲致不錯的結果。
首先,利用N-glyoxyloyl camphorpyrazolidinone(125)進行之不對稱烯
丙基加成反應,篩選出以一當量的路易士酸Eu(OTf)3 進行催化的最佳反應條
件,亦探討溶劑的影響情況。本實驗的最高產率可達90 %,雖然立體選擇性
方面不甚理想,以非鏡像超越值為48 % de 最高。
接著,再利用-keto amide(126)之不同官能基取代化合物進行不對稱
烯丙基加成反應,更成功地篩選出以一當量路易士酸Sn(OTf)2 進行催化的最
佳反應條件,且發現不同的路易士酸會使產物的立體化學中心反轉,並就反
應機構加以推測及探討;其最高產率達95 %,非鏡像超越值更可高達95 % de
以上。
Asymmetric carbonyl allylation represents one of the most useful tools for the construction of regio- and stereodefined carbon framework. The alkene functionality is readily available for further functional group transformation to give epoxides, γ-lactam, δ-lactam, ect. The Lewis acid-mediated allylation of aldehydes is a highly useful synthetic operation to form chiral secondary homoallyl alcohols and has been studied extensively. Diastereoselective allylation of camphorpyrazolidinone derived N-glyoxylate (125) and α-keto amides (126) was examined by using allyltributyltin in the presence of various Lewis acids. The chiral camphor pyrazolidinone (112) can be easiliy prepared from the known (S)-ketopinic acid (118) in three steps in total 80 % yield. This research is to study the asymmetric allylation by using camphorpyrazolidinone derived N-glyoxylate (125) as a substrate. Treatment of compound 125 with various of Lewis acids gave good chemical yield (up to 90 %) in presence of allyltributyltin but unsatisfied diastereoselectivity. On the other hand, Then camphorpyrazolidinone phenylate (126c) was used as a substrate, to our surprise, a high stereoselectivity was achieved (up to 95 % de). The absolute stereochemistry of the newly generated steregenic center was assigned as R-configuration by single crystal X-ray analysis of 126c. Therefore, the effect between diastereoselectivity and reaction rate of various α-keto amides (126a-d) were studied. A reasonable mechanism was proposed.
Asymmetric carbonyl allylation represents one of the most useful tools for the construction of regio- and stereodefined carbon framework. The alkene functionality is readily available for further functional group transformation to give epoxides, γ-lactam, δ-lactam, ect. The Lewis acid-mediated allylation of aldehydes is a highly useful synthetic operation to form chiral secondary homoallyl alcohols and has been studied extensively. Diastereoselective allylation of camphorpyrazolidinone derived N-glyoxylate (125) and α-keto amides (126) was examined by using allyltributyltin in the presence of various Lewis acids. The chiral camphor pyrazolidinone (112) can be easiliy prepared from the known (S)-ketopinic acid (118) in three steps in total 80 % yield. This research is to study the asymmetric allylation by using camphorpyrazolidinone derived N-glyoxylate (125) as a substrate. Treatment of compound 125 with various of Lewis acids gave good chemical yield (up to 90 %) in presence of allyltributyltin but unsatisfied diastereoselectivity. On the other hand, Then camphorpyrazolidinone phenylate (126c) was used as a substrate, to our surprise, a high stereoselectivity was achieved (up to 95 % de). The absolute stereochemistry of the newly generated steregenic center was assigned as R-configuration by single crystal X-ray analysis of 126c. Therefore, the effect between diastereoselectivity and reaction rate of various α-keto amides (126a-d) were studied. A reasonable mechanism was proposed.
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Keywords
N-乙醛醯胺, 酮醯胺, 烯丙基