Hydrogen-mediated reductive coupling of conjugated alkynes with ethyl (N-sulfinyl)iminoacetates:: Synthesis of unnatural α-amino acids via rhodium-catalyzed C-C bond forming hydrogenation
Hydrogen-mediated reductive coupling of conjugated alkynes with ethyl (N-sulfinyl)iminoacetates:: Synthesis of unnatural α-amino acids via rhodium-catalyzed C-C bond forming hydrogenation
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DOI：
10.1021/ja051104i
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发表时间：
2005-08-17
影响因子：
15
通讯作者：
Krische, MJ
中科院分区：
文献类型：
--
作者：
Kong, JR;Cho, CW;Krische, MJ
铑催化1,3-炔1a-8a和1,3-二炔9a-13a在室温和常压下，分别在乙基（n -叔丁基亚磺酸基）亚乙酸酯和乙基（n -2,4,6三异丙基苯基亚磺酸基）亚乙酸酯的存在下进行加氢反应，产生还原偶联反应，以优异的收率获得不饱和α -氨基酸酯1b-13b，具有优异的区域和立体控制水平。在常温常压下，使用威尔金森催化剂对含有α -氨基酸酯1b-8b的二烯进行进一步加氢，结果是区域选择性还原，从而获得β， γ -不饱和α -氨基酸酯1c-8c，收率很高。Boc-和fmoc保护的烯和二炔偶联产物14b-16b的衍生物的不饱和侧链在室温和常压下使用Crabtree's催化剂进行详尽的氢化反应，产生具有饱和侧链的α -氨基酸酯14d-16d，产率很高。最后，boc保护的还原偶联产物14b与顺式-1,4-二乙酰氧基-2-丁烯容易发生交叉复合反应，得到烯丙基乙酸14e。同位素标记研究涉及在单质氘气氛下炔1a和二炔9a的还原偶联，证实了一种催化机制，其中炔和亚胺残基的氧化偶联随后是产生的金属循环的氢解裂解。提供了一个考虑所观察到的不对称感应感的立体化学模型。这些研究首次使用亚胺作为氢介导的还原碳-碳键形成的亲电伙伴。
Rhodium-catalyzed hydrogenation of 1,3-enynes 1a-8a and 1,3-diynes 9a-13a at ambient temperature and pressure in the presence of ethyl (N-tert-butanesulfinyl)iminoacetate and ethyl (N-2,4,6triisopropylbenzenesulfinyl)iminoacetates, respectively, results in reductive coupling to afford unsaturated alpha-amino acid esters 1b-13b in good to excellent yields with exceptional levels of regio- and stereocontrol. Further hydrogenation of the diene containing alpha-amino acid esters 1b-8b using Wilkinson's catalyst at ambient temperature and pressure results in regioselective reduction to afford the beta,gamma-unsaturated alpha-amino acid esters 1c-8c in good to excellent yields. Exhaustive hydrogenation of the unsaturated side chains of the Boc- and Fmoc-protected derivatives of enyne and diyne coupling products 14b-16b occurs in excellent yield using Crabtree's catalyst at ambient temperature and pressure providing the alpha-amino acid esters 14d-16d, which possess saturated side chains. Finally, cross-metathesis of the Boc-protected reductive coupling product 14b with cis-1,4-diacetoxy-2-butene proceeds readily to afford the allylic acetate 14e. Isotopic labeling studies that involve reductive coupling of enyne 1 a and diyne 9a under an atmosphere of elemental deuterium corroborate a catalytic mechanism in which oxidative coupling of the alkyne and imine residues is followed by hydrogenolytic cleavage of the resulting metallacycle. A stereochemical model accounting for the observed sense of asymmetric induction is provided. These studies represent the first use of imines as electrophilic partners in hydrogen-mediated reductive carbon-carbon bond formation.