1-(2-diazo-1,3-dioxobutyl)-2-pyrrolidinone | 126685-93-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-(2-diazo-1,3-dioxobutyl)-2-pyrrolidinone
• 英文别名: (2E)-2-diazo-1-(2-oxopyrrolidin-1-yl)butane-1,3-dione
• CAS: 126685-93-6
• 化学式: C₈H₉N₃O₃
• 分子量: 195.178
• InChiKey: WBOUINZGMYOWOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  56.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-diazo-1,3-dioxobutyl)-2-pyrrolidinone 在 dirhodium tetraacetate 作用下， 以 苯 为溶剂， 生成 dimethyl 2-acetyl-5-(3-isocyanatopropyl)furan-3,4-dicarboxylate
  参考文献：
  名称：

  Synthesis of nitrogen-containing polycycles via rhodium(II)-induced cyclization-cycloaddition and insertion reactions of N-(diazoacetoacetyl)amides. Conformational control of reaction selectivity

  摘要：

  A series of diazoacetoacetamides, when treated with a catalytic quantity of a rhodium(II) carboxylate, were found to afford products derived from both a carbonyl ylide intermediate and intramolecular C-H insertion. With 3-(N-(diazoacetoacetyl)amino)propanoate derivatives, the rhodium(II)-catalyzed carbenoid reactions exhibit a strong preference for formation of a beta-lactam ring. This is attributed to a conformational preference that juxtaposes the carbenoid center and the less sterically encumbered amide substituent and is consistent with an activating influence on the C-H bond adjacent to the amide nitrogen atom. Carbonyl ylide products derived from carbenoid cyclization onto the ester carbonyl group are also formed, and their relative yields are dependent on electronic influences from the bridging ligands of rhodium(II). Treatment of a series of cyclic diazoimides with rhodium(II) acetate resulted in cyclization of the rhodium carbenoid onto the adjacent imide carbonyl group to produce an isomunchnone dipole. Cyclization onto the imide carbonyl group occurs exclusively even when C-H insertion or aromatic substitution reactions of the carbenoid intermediate are favorable, and this selectivity is also attributed to conformational preferences that juxtapose the carbenoid center and imide carbonyl group. The isomunchnone dipole readily undergoes cycloaddition with several different dipolarophiles to give 1,3-dipolar cycloadducts. When acetylenic dipolarophiles were used as the trapping agents, the initial cycloadducts were found to undergo a [4 + 2]-cycloreversion, producing substituted furans in high yield. The generality of the method was demonstrated by varying the ring size of the cyclic imide. An analogous cyclization-cycloaddition reaction also occurred using diazoacetoacetyl-substituted ureas.

  DOI：

  10.1021/jo00002a058
• 作为产物：
  描述：

  1-(2-氧代吡咯烷-1-基)丁烷-1,3-二酮 在 4-乙酰氨基苯磺酰叠氮 、 三乙胺 作用下， 以 乙腈 为溶剂， 生成 1-(2-diazo-1,3-dioxobutyl)-2-pyrrolidinone
  参考文献：
  名称：

  异构体与亚甲基吲哚酮的催化不对称 [3+2] 环加成

  摘要：

  使用手性N , N '-二氧化物/Zn( II ) 络合物作为路易斯酸，通过将羰基原位分子内加成到卡宾铑上，实现了异明酮与亚甲基吲哚酮的有效对映选择性 [3+2] 环加成反应. 以高产率获得了一系列手性氧杂桥联的 3-螺哌啶，具有优异的 dr 和优异的 ee 值。

  DOI：

  10.1039/d1cc03685h

文献信息

• Compounds and methods for treating tumors, cancer and hyperproliferative diseases
  申请人：Yale University

  公开号：US07304092B1

  公开（公告）日：2007-12-04

  The present invention relates to novel compounds, pharmaceutical compositions and methods for treating tumors, cancer and hyperproliferative diseases including psoriasis, genital warts and hyperproliferative cell growth diseases, including hyperproliferative keratinocyte diseases such as hyperkeratosis, ichthyosis, keratoderma or lichen planus. These compounds are described according to the chemical structure: where R1 is H, OH, F, Cl, Br, I, a C1-C6 optionally substituted alkyl or alkenyl group, an optionally substituted aryl group or a  group; Ra is a H, OH, C1-C10, optionally substituted alkyl or alkenyl group, an optionally substituted O—(C1-C7 alkyl group) or O-aryl group, an amine group which is optionally substituted with at least one C1-C10 alkyl group which may be optionally substituted, or a single optionally substituted aryl group, biphenyl group, (C1-C6) alkylenearyl group, (C1-C6) alkylenebiphenyl group, heteroaryl group, heterocyclic group, (C1-C6) alkylene heteroaryl group or (C1-C6) alkylene heterocyclic group; R2 is a  group; Rb is a H, OH, C1-C10, optionally substituted alkyl or alkenyl group, an optionally substituted O—(C1-C7 alkyl group) or O-aryl group, an amine group which is optionally substituted with at least one C1-C10 alkyl group which may be optionally substituted, or a single optionally substituted aryl group, biphenyl group, (C1-C6) alkylenearyl group, (C1-C6) alkylenebiphenyl group, heteroaryl group, heterocyclic group, (C1-C6) alkylene heteroaryl group or (C1-C6) alkylene heterocyclic group; R3 and R6 are each independently selected from H, OH, F, Cl, Br, I, a C1-C6 optionally substituted alkyl or alkenyl group, an optionally substituted aryl group, a carbamate, alkylene carbamate, urethane or alkylene urethane; R4 is a  group, wherein Rb is as described above; and R5 is a  group, wherein Rb is as described above, with the proviso that at least one of R1 and R2 or R4 and R5 contains an Ra or Rb group which is an amine group which is optionally substituted with at least one C1-C10 alkyl group which may be optionally substituted, or a single optionally substituted aryl group, biphenyl group, (C1-C6) alkylenearyl group, (C1-C6) alkylenebiphenyl group, heteroaryl group, heterocyclic group, (C1-C6) alkylene heteroaryl group or (C1-C6) alkylene heterocyclic group; or a stereoisomer, pharmaceutically acceptable salt, solvate, and polymorph thereof.

  本发明涉及新化合物、药物组合物和治疗肿瘤、癌症和高增殖性疾病的方法，包括银屑病、生殖器疣和高增殖性细胞生长疾病，包括高增殖性角质细胞疾病，如角化症、鱼鳞病、角皮病或扁平苔藓病。这些化合物根据其化学结构描述如下：其中R1为H、OH、F、Cl、Br、I、C1-C6可选择取代的烷基或烯基基团、可选择取代的芳基团或a 基团；Ra为H、OH、C1-C10、可选择取代的烷基或烯基基团、可选择取代的O—(C1-C7烷基基团)或O-芳基团、可选择取代的胺基团，该胺基团可选择取代至少一个C1-C10烷基基团，该基团可选择取代，或者单一可选择取代的芳基团、联苯基团、(C1-C6)烷基芳基团、(C1-C6)烷基联苯基团、杂环芳基团、杂环基团、(C1-C6)烷基杂环芳基团或(C1-C6)烷基杂环基团；R2为a 基团；Rb为H、OH、C1-C10、可选择取代的烷基或烯基基团、可选择取代的O—(C1-C7烷基基团)或O-芳基团、可选择取代的胺基团，该胺基团可选择取代至少一个C1-C10烷基基团，该基团可选择取代，或者单一可选择取代的芳基团、联苯基团、(C1-C6)烷基芳基团、(C1-C6)烷基联苯基团、杂环芳基团、杂环基团、(C1-C6)烷基杂环芳基团或(C1-C6)烷基杂环基团；R3和R6各自独立地选择自H、OH、F、Cl、Br、I、C1-C6可选择取代的烷基或烯基基团、可选择取代的芳基团、碳酸酯、烷基碳酸酯、脲或烷基脲；R4为a 基团，其中Rb如上所述；和R5为a 基团，其中Rb如上所述，但至少其中之一的R1和R2或R4和R5含有Ra或Rb基团，该基团为可选择取代的胺基团，该胺基团可选择取代至少一个C1-C10烷基基团，该基团可选择取代，或者单一可选择取代的芳基团、联苯基团、(C1-C6)烷基芳基团、(C1-C6)烷基联苯基团、杂环芳基团、杂环基团、(C1-C6)烷基杂环芳基团或(C1-C6)烷基杂环基团；或其立体异构体、药用可接受的盐、溶剂化合物和多晶形式。
• Copper‐Catalyzed Formal [4+2] Cycloaddition of Enoldiazoimides with Sulfur Ylides
  作者：Qing‐Qing Cheng、Lynée A. Massey、Brook S. Willett、Yongming Deng、Hadi Arman、Michael P. Doyle

  DOI：10.1002/anie.201805323

  日期：2018.8.6

  silyl‐protected enol, since the corresponding acetyldiazoimide failed to provide any cross‐products in metal‐catalyzed reactions with sulfur ylides. This copper‐catalyzed cycloaddition is initiated with the generation of enol‐substituted carbonyl ylides and sulfur ylides from enoldiazoimides and sulfonium salts, respectively, and proceeds through stepwise six‐membered ring formation, C−O and C−S bond cleavage, and

  烯醇重氮亚胺是烯醇重氮化合物的一个新亚类，可生成烯醇取代的羰基叶立德，其与硫叶立德的反应能够实现前所未有的正式[4+2]环加成。所得的多官能化中氮茚酮结合了硫，在温和的反应条件下以良好的产率形成。这种转化的独特性源于甲硅烷基保护的烯醇的作用，因为相应的乙酰基重氮亚胺未能在与硫叶立德的金属催化反应中提供任何交叉产物。这种铜催化的环加成反应是由烯醇二氮亚胺和锍盐分别生成烯醇取代的羰基叶立德和硫叶立德引发的，并通过逐步六元环形成、CO和C-S键断裂以及甲硅烷基和硫基叶立德进行。乙酰基迁移。
• Bimolecular cycloaddition reactions of isomünchnones derived from the rhodium(II) catalyzed cyclization of diazo pyrrolidinones
  作者：Albert Padwa、Donald L. Hertzog

  DOI：10.1016/s0040-4020(01)86338-9

  日期：1993.3

  pyrrolidinones with a catalytic amount of rhodium(II) acetate in refluxing benzene results first in the formation of a rhodium carbenoid which then cyclizes onto the neighboring carbonyl oxygen to produce an isomünchnone ring system. Subsequent cycloaddition across the pi-bond of an added dipolarophile affords 1,3-dipolar cycloadducts in high yield. The isomünchnone derived from 2-diazoacetyl-2-pyrrolidinone reacts

  在回流的苯中用催化量的乙酸铑（II）处理重氮取代的吡咯烷酮，首先导致形成铑类胡萝卜素，然​​后将其环化到相邻的羰基氧上以生成异麦角酮环系统。随后的环加成反应越过所添加的双极性亲和剂的π键，可以高收率获得1,3-偶极环加合物。衍生自2-重氮乙酰基-2-吡咯烷酮的异麦角酮与富电子（二乙基乙烯酮乙缩醛）和缺电子（N-苯基马来酰亚胺，甲基乙烯基酮）的双极性亲和剂容易反应。区域化学结果完全符合FMO理论。通过半经验AMAC计算确定了异辛酮的前沿轨道系数。当使用乙炔双极性亲电子试剂作为捕集剂时，没有分离出预期的偶极环加合物，而是进行了4 + 2-环还原，从而获得了呋喃异氰酸酯。通过与甲醇反应，将异氰酸酯表征为其氨基甲酸酯衍生物。
• Transition‐Metal‐Free [4+3]‐Cycloaddition of <i>ortho</i> ‐Quinone Methides and Isomünchnones: Catalytic and Diastereoselective Assembly of Oxa‐bridged Oxazocine Scaffolds
  作者：Heather Lam、Zafar Qureshi、Marcus Wegmann、Mark Lautens

  DOI：10.1002/anie.201810760

  日期：2018.12.3

  between an in situ generated ortho‐quinone methide and an isomünchnone to yield oxa‐bridged oxazocine cores, generating N2 and H2O as the sole by‐products. Using only catalytic amounts of camphorsulfonic acid, it is possible to generate both reactive intermediates in one step, eliminating the need for rhodium catalysts generally employed for isomünchnone formation. Spectroscopic data and X‐ray crystallography

  环加成是合成复杂的多环支架的强大过程。本文中，我们公开了在原位生成的邻苯二甲酰甲基甲烷和异麦草酮之间的[4 + 3]-环加成反应，生成草桥连的恶唑啉核，生成N 2和H 2 O作为唯一的副产物。仅使用催化量的樟脑磺酸，就可以在一个步骤中生成两种反应性中间体，从而消除了通常用于异丁香酮形成的铑催化剂的需求。光谱数据和X射线晶体学表明顺式非对映异构体的形成，主要副产物由水合物参与竞争的[4 + 2]-环加成途径。
• Chemoselective 1,3-Dipolar CycloadditionReactions of Rhodium(II)-Generated Isomünchnones with 1,4<i>-</i>Quinones: Synthesis of Novel Azapolycycles
  作者：Vijay Nair、V. Santhi、K. C. Sheela、K. V. Radhakrishnan、Nigam P. Rath

  DOI：10.1055/s-2003-40529

  日期：——

  The formation of the hybrid skeletons of oxoprotoberberines and quinonoid natural products is achieved by the cycloaddition of isomünchnones with 1,4-quinones, followed by BF3˙OEt2-catalyzed transformation of the adducts.

  氧化原小檗碱和醌类天然产物的杂化骨架的形成是通过异明酮与1,4-醌的环加成，然后是加合物的BF3-OEt2催化转化来实现的。