Intramolecular Michael Addition of N- and O-Centred Nucleophiles to Tethered Acrylates. The Role of Double-Bond Geometry in Controlling the Diastereo- selectivity of Cyclizations Leading to 2,6-Disubstituted Tetrahydropyrans and Piperidines.
Intramolecular Michael Addition of N- and O-Centred Nucleophiles to Tethered Acrylates. The Role of Double-Bond Geometry in Controlling the Diastereo- selectivity of Cyclizations Leading to 2,6-Disubstituted Tetrahydropyrans and Piperidines.
复制标题
N-和 O-中心亲核试剂与束缚丙烯酸酯的分子内迈克尔加成。
DOI：
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
G. Simpson
中科院分区：
文献类型：
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作者：
M. Banwell;Brett D. Bissett;C. Bui;H. T. Pham;G. Simpson
由羟基丙烯酸酯E-(5)衍生的氧负离子顺利地进行分子内迈克尔加成，生成反式-2,6-二取代四氢吡喃(7)作为主要反应产物。相反，从异构体Z-(5)获得的氧负离子环化生成顺式-2,6-二取代四氢吡喃(6)作为主要产物。这种化学方法已扩展到(+)-(6)的对映选择性合成，(+)-(6)的获得构成了酸(+)-(2)的正式全合成，酸(+)-(2)是灵猫（Viverra civetta）腺体分泌物的一种成分。酮丙烯酸酯(12)的还原胺化得到一种中间体胺，它原位环化生成顺式-2,6-二取代哌啶(26)。化合物(13)的类似处理得到异构体反式-2,6-二取代哌啶(27)作为唯一的反应产物。已提出过渡态结构来解释在所有环化反应中观察到的非对映选择性。
The oxyanion derived from hydroxyacrylate E-(5) undergoes smooth intramolecular Michael addition to give the trans-2,6-disubstituted tetrahydropyran (7) as the major product of reaction. In contrast, the oxyanion obtained from isomer Z-(5) cyclizes to give the cis-2,6-disubstituted tetrahydropyran (6) as the major product. Such chemistry has been extended to the enantioselective synthesis of (+)-(6) the acquisition of which constitutes a formal total synthesis of acid (+)-(2), a constituent of the glandular secretion from the civet cat (Viverra civetta). Reductive amination of keto acrylate (12) affords an intermediate amine which cyclizes, in situ, to give the cis-2,6-disubstituted piperidine (26). Analogous treatment of compound (13) delivers the isomeric trans-2,6-disubstituted piperidine (27) as the exclusive product of reaction. Transition state structures have been proposed to account for the diastereoselectivities observed in all of the cyclization reactions.