(3S,4'S)-2-benzyl-4-benzyloxy-3-(2',2'-dimethyl-1',3'-dioxolan-4'-yl)-3,6-dihydro-2H-1,2-oxazine | 852210-28-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3S,4'S)-2-benzyl-4-benzyloxy-3-(2',2'-dimethyl-1',3'-dioxolan-4'-yl)-3,6-dihydro-2H-1,2-oxazine
• 英文别名: (3S,4'S)-4-benzyloxy-2-benzyl-3-(2',2'-dimethyl-1',3'-dioxolan-4'-yl)-3,6-dihydro-2H-1,2-oxazine；(3S)-2-benzyl-3-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-4-phenylmethoxy-3,6-dihydrooxazine
• CAS: 852210-28-7
• 化学式: C₂₃H₂₇NO₄
• 分子量: 381.472
• InChiKey: DRWSRFYBLFBOJS-FGZHOGPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  40.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,4'S)-2-benzyl-4-benzyloxy-3-(2',2'-dimethyl-1',3'-dioxolan-4'-yl)-3,6-dihydro-2H-1,2-oxazine 在 钯 、 环己烯 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 2.0h， 以59%的产率得到(3S,4'S)-2-benzyl-3-(2',2'-dimethyl-1',3'-dioxolan-4'-yl)-3,4,5,6-tetrahydro-2H-1,2-oxazin-4-one
  参考文献：
  名称：

  Convenient Syntheses of Enantiopure 1,2-Oxazin-4-yl Nonaflates and Phosphates and Their Palladium-Catalyzed Cross-Couplings

  摘要：

  Efficient methods to prepare enantiopure 1,2-oxazin-4-yl nonaflates and phosphates were elaborated. The corresponding 1,2-oxazin-4-ones were transformed into their enolates and then quenched with nonafluorobutanesulfonyl fluoride or diphenyl chlorophosphate to provide the title compounds. Alternatively, the corresponding -bromo ketones were subjected to Perkow reactions efficiently leading to the respective enol phosphates. A variety of palladium-catalyzed cross-couplings such as Kumada-Corriu, Sonogashira, Heck reactions or borylation reactions were studied, which delivered the expected new 4-substituted 1,2-oxazine derivatives generally in satisfactory yields. A few typical subsequent transformations were studied including a copper-catalyzed [3+2] cycloaddition with a galactose-derived azide. They demonstrate the synthetic potential of the newly prepared enantiopure 4-substituted 1,2-oxazines.

  DOI：

  10.1055/s-0033-1339509
• 作为产物：
  描述：

  1-benzyloxyallene 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.0h， 生成 (3S,4'S)-2-benzyl-4-benzyloxy-3-(2',2'-dimethyl-1',3'-dioxolan-4'-yl)-3,6-dihydro-2H-1,2-oxazine
  参考文献：
  名称：

  New Polyhydroxylated Pyrrolidines Derived from Enantiopure 3,6-Dihydro-2H-1,2-oxazines

  摘要：

  [GRAPHICS]Diastereoselective hydroborations of enantiopure 3,6-dihydro-2H-1,2-oxazines led to dihydroxy-substituted 1,2-oxazines. Samarium diiodide-induced N-O bond cleavage generated 1,4-amino alcohols which were recyclized to polyhydroxylated pyrrolidines which are potential glycosidase inhibitors.

  DOI：

  10.1021/ol0260573

文献信息

• Stereodivergent Syntheses of Highly Substituted Enantiopure 4-Alkoxy-3,6-dihydro-2H-1,2-oxazines by Addition of Lithiated Alkoxyallenes to Carbohydrate-Derived Aldonitrones
  作者：Matthias Helms、Wolfgang Schade、Robert Pulz、Toshiko Watanabe、Ahmed Al-Harrasi、Lubor Fišera、Iva Hlobilová、Gernot Zahn、Hans-Ulrich Reißig

  DOI：10.1002/ejoc.200400627

  日期：2005.3

  Additions of lithiated alkoxyallenes to D-glyceraldehyde-based nitrones 1 and 2 did not provide the expected hydroxylamine derivatives. Instead, a novel [3+3] cyclization process furnished 4-alkoxy-3,6-dihydro-2H-1,2-oxazines 9–14 with excellent syn selectivities and in moderate to good yields. Through precomplexation of the nitrones the corresponding anti-configured 1,2-oxazines 9, 10 and 13 could

  将锂化烷氧基丙二烯添加到基于 D-甘油醛的硝酮 1 和 2 中并没有提供预期的羟胺衍生物。相反，一种新的 [3+3] 环化工艺提供了具有优异顺式选择性和中等至良好产率的 4-烷氧基-3,6-二氢-2H-1,2-恶嗪 9-​​14。通过硝酮的预络合，可以以高立体选择性获得相应的反构型 1,2-恶嗪 9、10 和 13。衍生自 D-赤藓糖或 D-苏糖的硝酮 3-6 的反应通常进行较少的非对映选择性，但在路易斯酸下可以获得合理的反构型 1,2-恶嗪，如抗 17 和抗 19促销条件。D-阿拉伯糖衍生的硝酮 7 的反应也是如此，它提供了抗 1、2-恶嗪 23 和 24 具有优异的非对映选择性和良好的产率。双硝酮 8 和锂化甲氧基丙二烯提供了六种化合物的混合物，其中主要成分是 C2 对称的 Syn/syn-1,2-恶嗪 29。这些反应的非对映选择性是根据 Dondoni 之间的反应模型来解释的。有机锂化合物和硝酮。讨论了
• Ring Enlargement of Carbohydrate-Derived 1,2-Oxazines to Enantiopure 5-Bromo-1,2-oxazepines and Subsequent Palladium-Catalyzed Reactions
  作者：Hans-Ulrich Reissig、Ahmed Al-Harrasi、Sebastian Fischer、Reinhold Zimmer

  DOI：10.1055/s-0029-1217126

  日期：2010.1

  palladium-catalyzed C-C bond forming processes (Sonogashira, Suzuki, Stille, and Heck reactions). These transformations led to a series of new highly substituted 1,2-oxazepine derivatives syn-5 or anti-5-11 being of considerable interest for further synthetic elaborations. 1,2-oxazines - carbene additions - cyclopropanes - ring enlargement - 1,2-oxazepines - palladium catalysis - alkynes

  二溴卡宾除了d甘油醛衍生的1,2- -恶嗪顺式 -1和反 -1提供dibromocyclopropane中间体顺式- 3和抗- 3，其平滑地与甲醇配料5-溴-1,2-反应下扩环-氧氮杂衍生物syn -4和anti -4。相关的1,2-恶嗪类化合物（如阿拉伯糖衍生的化合物）提供了1,2-恶氮平衍生物syn - 4e和anti - 4f具有相当的功效。然后，通过钯催化的CC键形成过程（Sonogashira，Suzuki，Stille和Heck反应），利用1,2-氧杂氮杂卓衍生物syn -4和anti -4的烯基溴化物部分引入新的取代基。这些变换导致了一系列新的高度取代的1,2-氧氮杂衍生物的顺式- 5或抗- 5 - 11感用于进一步合成阐述相当大的兴趣。 1,2-恶嗪-卡宾加法-环丙烷-扩环- 1,2- -氧氮杂-钯催化-炔
• Lewis Acid Promoted Rearrangements of 1,3-Dioxolanyl-Substituted 1,2-Oxazines into Novel Products with 1,3,6-Trioxa-7-azacyclopenta[<i>cd</i>]indene Skeletons
  作者：Hans-Ulrich Reissig、Fabian Pfrengle、Ahmed Al-Harrasi

  DOI：10.1055/s-2006-956463

  日期：2006.12

  Lewis acid promoted rearrangements of 4-methoxy- and 4-benzyloxy-substituted 1,2-oxazines syn-1b and syn-1c furnished novel tricyclic products 5 and 6. A mechanistic rationale is suggested for the different rearrangement pathways depending on the configuration and the nature of the 4-alkoxy groups of the precursor 1,2-oxazines. Short period hydrogenolyses of these rearrangement products afforded tetrahydrofuranyl-annulated 5,6-dihydro-4H-1,2-oxazines 10 and 11, whereas longer reduction times led to formation of tetrahydrofuran derivatives 14, 15 and 16, 17 in good yields.

  在路易斯酸的促进下，4-甲氧基和 4-苄氧基取代的 1,2-噁嗪 syn-1b 和 syn-1c 发生重排，生成了新型三环产物 5 和 6。根据前体 1,2-噁嗪中 4-烷氧基基团的构型和性质，提出了不同重排途径的机理依据。对这些重排产物进行短时间的氢解，可得到四氢呋喃基环化的 5,6- 二氢-4H-1,2-噁嗪 10 和 11，而较长的还原时间则可形成四氢呋喃衍生物 14、15 和 16、17，而且产率很高。
• Unusual Enantiopure Heterocyclic Skeletons by Lewis Acid Promoted Rearrangements of 1,3-Dioxolanyl-Substituted 1,2-Oxazines
  作者：Fabian Pfrengle、Ahmed Al-Harrasi、Irene Brüdgam、Hans-Ulrich Reißig

  DOI：10.1002/ejoc.200800870

  日期：2009.1

  Lewis acid promoted rearrangements of different 4-alkoxy-substituted 1,2-oxazines syn-1 are reported. Depending on the nature of this alkoxy group different reaction pathways are possible either providing bicyclic 1,2-oxazinones 2 or the novel tricyclic products 3–5. A mechanistic rational describing the role of the 4-alkoxy group is presented. The key step for formation of tricyclic skeletons 3–5

  路易斯酸促进了不同 4-烷氧基取代的 1,2-恶嗪 syn-1 的重排。根据该烷氧基的性质，不同的反应途径可能提供双环 1,2-恶嗪酮 2 或新型三环产物 3-5。介绍了描述 4-烷氧基作用的机械原理。形成三环骨架 3-5 的关键步骤是 1,2-烷基转移。这些三环化合物的氢化反应根据氢解时间产生不饱和 1,2-恶嗪 12 和 13 或四氢呋喃 15a-c/16a-c。四氢呋喃环化的 1,2-恶嗪 12 用于进一步转化为复杂的取代四氢呋喃。用氰基硼氢化钠还原，随后通过氢化裂解 N,O-键，得到氨基呋喃衍生物 19。
• Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2<i>H</i>-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions
  作者：Michal Medvecký、Igor Linder、Luise Schefzig、Hans-Ulrich Reissig、Reinhold Zimmer

  DOI：10.3762/bjoc.12.289

  日期：——

  Iodination of carbohydrate-derived 3,6-dihydro-2H-1,2-oxazines of type 3 using iodine and pyridine in DMF furnished 5-iodo-substituted 1,2-oxazine derivatives 4 with high efficacy. The alkenyl iodide moiety of 1,2-oxazine derivatives syn-4 and anti-4 was subsequently exploited for the introduction of new functionalities at the C-5 position by applying palladium-catalyzed carbon–carbon bond-forming reactions such as Sonogashira, Heck, or Suzuki coupling reactions as well as a cyanation reaction. These cross-coupling reactions led to a series of 5-alkynyl-, 5-alkenyl-, 5-aryl- and 5-cyano-substituted 1,2-oxazine derivatives being of considerable interest for further synthetic elaborations. This was exemplarily demonstrated by the hydrogenation of syn-21 and anti-24 and by a click reaction of a 5-alkynyl-substituted precursor.

  使用碘和吡啶在DMF中对碳水化合物衍生的3,6-二氢-2H-1,2-噁啉（oxazines）进行碘化反应，高效地合成了5-碘取代的1,2-噁啉衍生物4。1,2-噁啉衍生物syn-4和anti-4的烯基碘醚基团随后被利用，通过钯催化的碳-碳键形成反应（如Sonogashira、Heck或Suzuki偶联反应以及氰化反应）在C-5位置引入新的官能团。这些交叉偶联反应导致了一系列具有相当重要意义的5-炔基、5-烯基、5-芳基和5-氰基取代的1,2-噁啉衍生物，这些衍生物对于进一步的合成研究具有相当的兴趣。这一点通过对syn-21和anti-24的氢化以及对一种5-炔基取代前体的click反应进行了示范。