N-Allyl-N-benzyl-2,2-dichloro-2-methylacetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-Allyl-N-benzyl-2,2-dichloro-2-methylacetamide
• 英文别名: N-benzyl-2,2-dichloro-N-prop-2-enylpropanamide
• 化学式: C₁₃H₁₅Cl₂NO
• 分子量: 272.174
• InChiKey: QEUCZOAWZHQLGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-Allyl-N-benzyl-2,2-dichloro-2-methylacetamide 在 Cu(tris(2-methylpyridyl)amine)(2+) 、 N,N,N,N-tetraethylammonium tetrafluoroborate 作用下， 以 乙腈 为溶剂， 反应 1.83h， 生成 trans-N-Benzyl-4-chloromethyl-3-chloro-3-methylpyrrolidin-2-one 、 cis-N-Benzyl-4-chloromethyl-3-chloro-3-methylpyrrolidin-2-one
  参考文献：
  名称：

  铜催化逆原子转移自由基环化的电化学方法

  摘要：

  电化学介导的原子转移自由基环化（e ATRC）已被开发为一种易于清洁的方法，可合成卤代环状化合物。该方法已成功地用于铜与三（2-吡啶基甲基）胺（TPMA）的铜配合物在乙腈（CH 3 CN）中的某些N-烯丙基-α，α-二氯酰胺的铜催化原子转移自由基环化反应中金属含量为1％。催化剂以[Cu（II）TPMA] 2+的形式引入，并通过在铂（Pt）电极上还原而被活化并连续再生为活性铜（I）形式。在ATRC过程中，新的铜（II）络合物[ClCu（II）TPMA] +的还原电势约为。形成比起始[Cu（II）TPMA] 2+负的电压多0.350V 。因此，选择施加的电势至关重要，并且应注意将所有铜（II）物种还原为铜（I）。这些化合物在电解数小时后会经历很高的转化率（79–100％），以两种异构体的混合物形式生成环状γ-内酰胺（收率60–98％），并具有良好的顺-非对映选择性[ dr（cis / trans）=

  DOI：

  10.1002/adsc.201400587
• 作为产物：
  描述：

  N-烯丙基苄胺 、 2,2-二氯丙酰氯 以 二氯甲烷 为溶剂， 生成 N-Allyl-N-benzyl-2,2-dichloro-2-methylacetamide
  参考文献：
  名称：

  Halogen atom transfer radical cyclization of N-allyl-N-benzyl-2,2-dihaloamides to 2-pyrrolidinones, promoted by Fe0-FeCl3 or CuCl-TMEDA

  摘要：

  The halogen atom transfer radical cyclization of a N-allyl-N-benzyl-2,2-dihaloamides to 2-pyrrolidinones has been carried out in high yields under mild conditions, in a reaction promoted by CuCl-TMEDA or Fe-0-FeCl3 in acetonitrile or N,N-dimethylformamide, respectively. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(97)00908-3

文献信息

• Atom transfer radical cyclisations of activated and unactivated N-allylhaloacetamides and N-homoallylhaloacetamides using chiral and non-chiral copper complexes
  作者：Andrew J. Clark、Floryan De Campo、Robert J. Deeth、Robert P. Filik、Sylvain Gatard、Nicola A. Hunt、Dominique Lastécouères、Gerard H. Thomas、Jean-Baptiste Verlhac、Hathaichanuk Wongtap

  DOI：10.1039/a909666c

  日期：——

  Activated N-tosyl-2,2,2-trichloroacetamide 6a, N-benzyl-2,2,2-trichloroacetamide 6d, 2,2-dichloroacetamides 6b–c and 6e–f and 2-monohaloacetamides 11a–g undergo efficient 5-exo atom transfer radical cyclisations at room temperature mediated by CuCl or CuBr in the presence of tris(N,N-dimethylaminoethylene)amine 3 (trien-Me6). The efficiency and stereoselectivity of these cyclisations was found to be greater than existing published atom transfer procedures based upon CuCl(bipyridine), RuCl2(PPh3)3 and CuCl(TMEDA)2. The product distribution for the cyclisation onto alkyne 11g was found to be solvent dependent. Attempts to make larger ring sizes by endo cyclisation of N-tosylacetamides 19a–c led to a competing 5-exoipso aromatic substitution into the N-tosyl group followed by re-aromatisation and loss of SO2 to furnish an amidyl radical. Cyclisation of N-homoallylacetamides 25a–d proceeded smoothly to give δ-lactams with a range of catalysts based upon ligands 2 and 26. The stereoselectivity of cyclisation to give γ lactams could be somewhat influenced by using chiral enantiopure copper complexes 28–30 suggesting that the reactions may involve metal-complexed radicals.

  活化的N-托烯基-2,2,2-三氯乙酰酰胺6a、N-苄基-2,2,2-三氯乙酰酰胺6d、2,2-二氯乙酰酰胺6b–c和6e–f以及2-单卤乙酰酰胺11a–g在室温下通过CuCl或CuBr以及三（N,N-二甲氨基乙烯）胺3（trien-Me6）的介导，经历了高效的5-exo原子转移自由基环化反应。这些环化反应的效率和立体选择性比现有的基于CuCl（联吡啶）、RuCl2（PPh3）3和CuCl（TMEDA）2的原子转移程序更高。环化反应在炔烃11g上的产物分布发现依赖于溶剂。尝试通过N-托烯基乙酰酰胺19a–c的内环化生成更大环的过程，导致N-托烯基基团发生竞争性的5-exo环置换，随后发生再芳香化并失去SO2，生成酰基自由基。N-同烯丙基乙酰酰胺25a–d的环化顺利进行，得到了一系列基于配体2和26的催化剂的δ-内酯。通过使用手性恩路全纯铜复合物28–30，γ-内酯的环化立体选择性受到一定影响，表明反应可能涉及金属配位自由基。
• Efficient and Green Route to γ-Lactams by Copper-Catalysed Reversed Atom Transfer Radical Cyclisation of α-Polychloro-<i>N</i>-allylamides, using a Low Load of Metal (0.5 mol%)
  作者：Franco Bellesia、Andrew J. Clark、Fulvia Felluga、Armando Gennaro、Abdirisak A. Isse、Fabrizio Roncaglia、Franco Ghelfi

  DOI：10.1002/adsc.201300132

  日期：2013.5.17

  The cyclisation of N‐allyl‐N‐substituted‐α‐polychloroamides is efficiently obtained through a copper‐catalysed activators regenerated by electron transfer–atom transfer radical cyclisation process, with a metal load of only 0.5 mol%. The redox catalyst is introduced in its inactive form as copper(II) chloride/[nitrogen ligand] complex, and continuously regenerated to the active copper(I) chloride/[nitrogen

  通过电子转移-原子转移自由基环化过程再生的铜催化活化剂，可以有效地实现N-烯丙基-N-取代-α-聚氯酰胺的环化，金属负载量仅为0.5 mol％。氧化还原催化剂以其惰性形式作为氯化铜（II）/ [氮配体]配合物引入，并通过抗坏血酸连续再生为活性氯化铜（I）/ [氮配体]物种。为了保持催化剂的完整性，在每个再生循环后释放的盐酸已被碳酸盐淬灭。溶剂的选择至关重要，在乙酸乙酯-乙醇（3：1）中观察到最佳性能。
• Halogen atom transfer radical cyclization of N-allyl-N-benzyl-2,2-dihaloamides to 2-pyrrolidinones, promoted by Fe0-FeCl3 or CuCl-TMEDA
  作者：Miriam Benedetti、Luca Forti、Franco Ghelfi、Ugo Maria Pagnoni、Roberto Ronzoni

  DOI：10.1016/s0040-4020(97)00908-3

  日期：1997.10

  The halogen atom transfer radical cyclization of a N-allyl-N-benzyl-2,2-dihaloamides to 2-pyrrolidinones has been carried out in high yields under mild conditions, in a reaction promoted by CuCl-TMEDA or Fe-0-FeCl3 in acetonitrile or N,N-dimethylformamide, respectively. (C) 1997 Elsevier Science Ltd.
• A green way to γ-lactams through a copper catalyzed ARGET-ATRC in ethanol and in the presence of ascorbic acid
  作者：Roberto Casolari、Fulvia Felluga、Vincenzo Frenna、Franco Ghelfi、Ugo M. Pagnoni、Andrew F. Parsons、Domenico Spinelli

  DOI：10.1016/j.tet.2010.11.025

  日期：2011.1

  A 'green' ARGET-ATRC, for the CuCl[PMDETA] catalysed cyclo-isomerization of N-allyl-alpha-polychloroamides to gamma-lactams is described. The process works efficiently (yields 78-96%), uses a bio-solvent, as ethanol, and exploits the reducing feature of ascorbic acid to limit, at a low level (2-4%), the amount of catalyst. To preserve the efficacy of the catalytic cycle, addition of Na2CO3 is essential, which quenches the HCl released during the CuCl[PMDETA] regeneration step. Profitable features of the process are: mild reaction temperatures (25-37 degrees C), relatively short reaction times (usually 5 h) and low solvent volumes (2 mmol of substrate/mL of ethanol). The method, upon stoichiometric adjustment, was also used for the synthesis of alpha,beta-unsaturated-gamma-lactams from N-(2-chloroallyl)-alpha-polychloroamides, via a tandem process involving an ATRC and a reductive [1,2]-elimination. (C) 2010 Elsevier Ltd. All rights reserved.
• The influence of benzylic protection and allylic substituents on the CuCl-TMEDA catalyzed rearrangement of N-allyl-N-benzyl-2,2-dihaloamides to γ-lactams. Application to the stereoselective synthesis of pilolactam
  作者：Franco Ghelfi、Franco Bellesia、Luca Forti、Gianluca Ghirardini、Romano Grandi、Emanuela Libertini、Maria C Montemaggi、Ugo M Pagnoni、Adriano Pinetti、Laurent De Buyck、Andrew F Parsons

  DOI：10.1016/s0040-4020(99)00247-1

  日期：1999.4

  A number of N-benzylic protecting groups and allylic substituents have been investigated for the rearrangement, promoted by CuCl-TMEDA, of N-allyl-2,2-dihaloamides to 3,4-disubstituted gamma-lactams. An appreciable chiral induction was observed at the C-4 site when alpha-phenylethylamine was used as a chiral protecting group, while an unexpected Diels-Alder reaction occurred when using a 2-furyl-methyl protection. This rearrangement has been applied to the synthesis of pilolactam, a drug with muscarinic activity. (C) 1999 Elsevier Science Ltd. All rights reserved.