(3R,4R)-3-(naphthalen-1-yl)-4,6-diphenyl-1-tosyl-3,4-dihydropyridin-2(1H)-one | 1380402-63-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (3R,4R)-3-(naphthalen-1-yl)-4,6-diphenyl-1-tosyl-3,4-dihydropyridin-2(1H)-one
• CAS: 1380402-63-0
• 化学式: C₃₄H₂₇NO₃S
• 分子量: 529.659
• InChiKey: CVYPRHBBNKAZBD-WEZIJMHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.29
• 重原子数：
  39.0
• 可旋转键数：
  5.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  54.45
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  1-萘乙酸 、 N-(p-tolylsulfonyl)-1,3-diphenyl-2-propen-1-imine 在 三甲基乙酰氯 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以66%的产率得到(3R,4R)-3-(naphthalen-1-yl)-4,6-diphenyl-1-tosyl-3,4-dihydropyridin-2(1H)-one
  参考文献：
  名称：

  A Recyclable, Immobilized Analogue of Benzotetramisole for Catalytic Enantioselective Domino Michael Addition/Cyclization Reactions in Batch and Flow

  摘要：

  A polystyrene-supported, enantiopure benzote-tramisole (BTM) analogue (5) has been synthesized from (2S,3S)-phenylglycidol through a five-step sequence involving a copper-catalyzed alkyne azide cycloaddition (CuAAC) reaction as the final, immobilization step. The functional resin 5 (f = 0.9 mmol g(-1)) has been successfully used as a highly active and enantioselective catalyst in the domino Michael addition/cyclization reaction of in situ activated arylacetic acids (7) with chalcone-type tosylimines (6), leading to dihydropyridinones 8 (17 examples) to afford the products with excellent yields and very high enantioselectivity (mean ee 97.4%). The deactivation of 5 by species present during the catalytic process has been studied, and pivaloyl chloride (required for the activation of the arylacetic acid) has been identified as the main source of deactivation. A simple experimental protocol taking this fact into account has allowed the multiple recycling of 5 with only a marginal decrease in catalytic activity and the implementation of a continuous flow process where the activation of phenylacetic acid (residence time 14.2 min), the asymmetric domino Michael addition/cydization reaction (residence time 7.5 min), and aqueous workup are performed sequentially, delivering the dihydropyridinone product as a clean dichloromethane solution (0.54 mmol catalyst sample; 11 h operation; 8a (4.44 g, >99.9% ee)). The supported catalyst 5 has also been used in a new domino Michael addition/cydization reaction involving saccharin-derived tosylimines 9 as electrophiles, leading to 8,9-dihydro-7H-benzo[4,5]isothiazolo [2,3-[a]pyridin-7-one 5,5-dioxides 10 (8 examples) in high isolated yields and diastereoselectivities and excellent enantioselectivities (mean ee 98%). A single sample of 5 (0.5 g, 0.45 mmol) has been used for the sequential preparation in batch of a library of 7 different derivatives 10 at the gram scale (ca. 10 g, accumulated TON = 51), the whole process being performed without any column chromatographic purification. The increased diastereoselectivity recorded with 5 in reactions involving sterically congested arylacetic acids (with respect to homogeneous BTM) has been rationalized through the occurrence of steric interactions between the sulfonylimine and the linker plus support catalyst fragments leading to additional destabilization of the transition state leading to the minor, cis diastereomer of products 8/10.

  DOI：

  10.1021/acscatal.5b02121

文献信息

• Dihydropyridones: Catalytic Asymmetric Synthesis, N- to C-Sulfonyl Transfer, and Derivatizations
  作者：Carmen Simal、Tomas Lebl、Alexandra M. Z. Slawin、Andrew D. Smith

  DOI：10.1002/anie.201109061

  日期：2012.4.10

  promotes the reaction of ammonium enolates derived from arylacetic acids with N‐tosyl‐α,β‐unsaturated ketimines, thus giving dihydropyridones with high diastereo‐ and enantiocontrol (see scheme). These products readily undergo N‐ to C‐sulfonyl photoisomerization and are derivatized to afford stereodefined piperidines and tetrahydropyrans.

  苯并四咪唑（1）促进了从芳酸中衍生出来的烯醇铵盐与N-甲苯磺酰基-α，β-不饱和酮亚胺的反应，从而使二氢吡啶酮具有非对映异构和对映异构控制性（见方案）。这些产品容易进行N-至C-磺酰基的光异构化，并衍生化得到立体定义的哌啶和四氢吡喃。
• An Upstream By-product from Ester Activation via NHC-Catalysis Catalyzes Downstream Sulfonyl Migration Reaction
  作者：Runfeng Han、Liwenze He、Lin Liu、Xingang Xie、Xuegong She

  DOI：10.1002/asia.201500959

  日期：2016.1

  A sequential reaction combining N‐heterocyclic carbene (NHC) and N‐hydroxyphthalimide (NHPI) catalysis allowed for the upstream by‐product NHPI, which was generated in the NHC‐catalyzed cycloaddition reaction, to act as the catalyst for a downstream nitrogen‐to‐carbon sulfonyl migration reaction. Enantiomeric excess of the major product in the cycloaddition reaction remained intact in the follow‐up

  N-杂环卡宾（NHC）和N-羟基邻苯二甲酰亚胺（NHPI）催化相结合的顺序反应允许上游副产物NHPI在NHC催化的环加成反应中生成，充当下游氮到氮的催化剂碳磺酰基迁移反应。在后续的磺酰基迁移反应中，环加成反应中主要产物的对映体过量保持完整。
• Enantioselective Activation of Stable Carboxylate Esters as Enolate Equivalents <i>via</i> N-Heterocyclic Carbene Catalysts
  作者：Lin Hao、Yu Du、Hui Lv、Xingkuan Chen、Huishen Jiang、Yaling Shao、Yonggui Robin Chi

  DOI：10.1021/ol300676w

  日期：2012.4.20

  The first N-Heterocyclic Carbene (NHC) mediated activation of stable carboxylate esters to generate enolate intermediates is disclosed. The catalytically generated arylacetic ester enolates undergo enantioselective reactions with α,β-unsaturated imines.

  公开了第一种由N-杂环卡宾（NHC）介导的稳定羧酸酯的活化以生成烯醇酸酯中间体的方法。催化生成的芳酯酸酯烯酸酯与α，β-不饱和亚胺进行对映选择性反应。
• Catalytic Generation of C1 Ammonium Enolates from Halides and CO for Asymmetric Cascade Reactions
  作者：Lu‐Lu Li、Du Ding、Jin Song、Zhi‐Yong Han、Liu‐Zhu Gong

  DOI：10.1002/anie.201901501

  日期：2019.6.3

  the design of asymmetric cascade reactions using readily available halides and carbon monoxide (CO) as substrates is developed. The key is the catalytic generation of C1‐ammonium enolates for the subsequent asymmetric cascade reactions through the combination of palladium‐catalyzed carbonylation and chiral Lewis base catalysis. Utilizing this strategy, we have established asymmetric formal [1+1+4]

  提出了使用不易获得的卤化物和一氧化碳（CO）作为底物设计不对称级联反应的一般策略。关键是通过钯催化的羰基化和手性Lewis碱催化相结合，可为随后的不对称级联反应催化生成C1-氨基烯醇盐。利用这种策略，我们建立了不对称的形式[1 + 1 + 4]和[1 + 1 + 2]反应，从而以高收率，高对映体和非对映体选择性提供了手性二氢吡啶酮和β-内酰胺。