2,2-Disubstituted Oxazolidines, New Chiral Auxiliaeies Based on the Conformational Control at the Amide Linkage.

2,2-二取代恶唑烷，基于酰胺键构象控制的新型手性助剂。

• 批准号: 05453139
• 负责人: KANEMASA Shuji
• 金额: $ 4.74万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05453139/
• 关键词: Oxazolidines; Chiral Auxiliary; Nitrile Oxide; Conjugate Addition; Cuprates; Alkylation; Michaei Addition; Lithium Enolates; アミド結合の配座制御; 立体選択性; 2,2-ジメチルオキサゾリジン; キラル補助基; キラルアミト; 配座解析; キュブラード; 共役付加; Michael 付加反応; アルドール反応

The 2,2-disubstituted oxazolidines bearing a chiral center at 4-position act as effective chiral auxiliaries with respect to the following points : 1) They are readily available in optically pure form from naturally occurring alpha-amino acids, 2) their alpha, beta-unsaturated amide derivatives are stabilized in Z-/s-cis conformers so that the unsaturated reaction cite is located close to the 4-shielding substituent, 3) such conformational stability is confirmed by the dynamic ^1H NMR spectra, 4) a nitrile oxide cycloaddition to the alpha, beta-unsaturated amide derivatives of 2,2-disubstituted oxazolidines shows the exclusive diastereofacial selectivity, 5) a cuprate conjugate addition to the alpha, beta-unsaturated amides is also absolutely diastereoselective, 6) the reactions affording the major stereoisomers occur at the diastereofaces opposite to the 4-substituent in their Z-/s-cis conformers, 7) the lithium Z-enolates derived from the oxazolidine amides undergo highly diastereoselective alkylations, 8) Michael additions using these lithium Z-enolate donors are also highly diastereoselective, 9) Z-/s-cis conformers again participate in these reactions, 10) these chiral auxiliaries are effective for asymmetric aldol reactions, 11) as a result, the 2,2-disubstituted oxazolidines act as excellent chirality-controlling auxiliaries in the reactions not only with nucleophiles (as alpha, beta-unsatutated amide derivatives) but also with electrophiles (as lithium Z-enolates).

在4-位带有手性中心的2，2-二取代恶唑烷在以下方面作为有效的手性助剂：1）它们容易以光学纯的形式从天然存在的α-氨基酸中获得，2）它们的α，β-不饱和酰胺衍生物稳定在Z-/s-顺式构象异构体中，使得不饱和反应位点位于4-屏蔽取代基附近，3）这种构象稳定性通过动态1H NMR光谱证实，4）与2，2-二取代恶唑烷的α，β-不饱和酰胺衍生物的腈氧化物环加成显示出唯一的非对映体选择性，5）与α，β-不饱和酰胺的铜酸盐缀合物加成也是绝对非对映体选择性的，6）提供主要立体异构体的反应发生在与其Z-顺式构象异构体中的4-取代基相对的非对映面，7）衍生自恶唑烷酰胺的Z-烯醇化锂进行高度非对映选择性烷基化，8）使用这些锂Z-烯醇化物供体的Michael加成也是高度非对映选择性的，9）Z-/s-cis构象体再次参与这些反应，10）这些手性助剂对于不对称Aldol反应是有效的，11）因此，2，2-二取代恶唑烷不仅在与亲核试剂的反应中充当优良的手性控制助剂（作为α，β-不饱和酰胺衍生物），而且还与亲电子试剂（作为Z-烯醇化锂）反应。

项目成果

Shuji Kanemasa: "New Chiral Auxiliaries Based on Conformation Control,a C2-Symmetric 2,2-Dimethylimidazolidine and 4-Chiral 2,2-Dialkyloxazolidines.Synthesis and Conformational Analysis of Acrylamide Derivatives" Tetrahedron. 48. 8631-8644 (1992)

Shuji Kanemasa：“基于构象控制的新型手性助剂，C2-对称 2,2-二甲基咪唑烷和 4-手性 2,2-二烷基恶唑烷。丙烯酰胺衍生物的合成和构象分析”四面体。

S.Kanemasa, T.Mori, and A.Tatsukawa: "Asymmetric anti-Selective Aldol Reactions of Titanium Z-Enolates Derived from N-Alkylideneglycinamides Bearing a 2,2-Dimethyloxazolidine Chiral Controller." Tetrahedron Lett.34 (51). 8293-8296 (1993)

S.Kanemasa、T.Mori 和 A.Tatsukawa：“源自带有 2,2-二甲基恶唑烷手性控制器的 N-亚烷基甘氨酰胺的钛 Z-烯醇化物的不对称反选择性羟醛反应”。

S.Kanemasa: "Effective Enantiocontrol in Conjugate Additions of Organocuprates.Highly Selective 1,5-Chiral Induction in the Conjugate Additions of Cuprates to Unsaturated Amide Derivatives of 2,2-Dimethyloxazolidine Chiral Auxiliaries" The Journal of Orga

S.Kanemasa：“有机铜酸盐共轭加成中的有效对映体控制。铜酸盐与 2,2-二甲基恶唑烷手性助剂的不饱和酰胺衍生物共轭加成中的高度选择性 1,5-手性诱导”Orga 杂志

S.Kanemasa, and O.Tsuge: "N-Metalated Azomethine Ylides." Advances in Cycloaddition. 3. 99-159 (1993)

S.Kanemasa 和 O.Tsuge：“N-金属化甲亚碱叶立德”。

S.Kanemasa: "C2-Symmetric 1,2-Diamine/copper(II)trifluoromethanesulfonate complexes as chiral catalysts.Asymmetric Cyclopropanations of Styrene with Diazo Esters" Tetrahedron Letters. 35. 7985-7988 (1994)

S.Kanemasa：“C2-对称 1,2-二胺/三氟甲磺酸铜 (II) 络合物作为手性催化剂。苯乙烯与重氮酯的不对称环丙烷化”四面体快报。