用于合成多官能团环己酮的三取代迈克尔受体的非对映选择性(3 + 3)环化反应
Diastereoselective (3 + 3)-Annulations of Trisubstituted Michael Acceptors for Access to Polyfunctional Cyclohexanones.
作者信息
Kitzinger Katelyn M, Giordano Mitchell T, de Jesús Cruz Pedro, Johnson Jeffrey S
机构信息
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, United States.
出版信息
J Org Chem. 2024 Apr 19;89(8):5878-5882. doi: 10.1021/acs.joc.4c00157. Epub 2024 Mar 19.
Abstract
Michael-aldol domino reactions are powerful tools for rapidly assembling carbocyclic scaffolds. We herein disclose a base-catalyzed Michael-aldol domino reaction of trisubstituted Michael acceptors with β-keto ester nucleophiles. The cyclohexanone products are obtained in excellent diastereoselectivity (up to >20:1 dr) and good yields (up to 84%). An attractive practical consideration is that pure products are isolated directly via filtration of the unpurified reaction mixtures. Further functionalization of the cyclohexanones is achieved without perturbation of stereocenters installed through the preceding annulation.
摘要
迈克尔-羟醛串联反应是快速构建碳环骨架的有力工具。我们在此披露一种三取代迈克尔受体与β-酮酯亲核试剂的碱催化迈克尔-羟醛串联反应。环己酮产物以优异的非对映选择性（高达>20:1的dr值）和良好的产率（高达84%）得到。一个吸引人的实际考虑是，通过过滤未纯化的反应混合物可直接分离出纯产物。环己酮的进一步官能化在不干扰通过先前环化所构建的立体中心的情况下得以实现。
相似文献
1
Diastereoselective (3 + 3)-Annulations of Trisubstituted Michael Acceptors for Access to Polyfunctional Cyclohexanones.用于合成多官能团环己酮的三取代迈克尔受体的非对映选择性(3 + 3)环化反应
J Org Chem. 2024 Apr 19;89(8):5878-5882. doi: 10.1021/acs.joc.4c00157. Epub 2024 Mar 19.
2
Domino Michael-Michael and Aldol-Aldol Reactions: Diastereoselective Synthesis of Functionalized Cyclohexanone Derivatives Containing Quaternary Carbon Center.多米诺迈克尔-迈克尔反应和羟醛-羟醛反应：含季碳中心的官能化环己酮衍生物的非对映选择性合成
J Org Chem. 2015 Oct 2;80(19):9700-12. doi: 10.1021/acs.joc.5b01768.
3
A triple cascade approach towards the diastereoselective synthesis of spiro -decalinol scaffolds.三重级联策略在手性螺环[3.3]壬醇骨架的立体选择性合成中的应用。
Chem Commun (Camb). 2022 Sep 15;58(74):10400-10403. doi: 10.1039/d2cc03562f.
4
Catalytic, Asymmetric Michael-Aldol Annulations via a Stereodivergent/Stereoconvergent Path Operating under Curtin-Hammett Control.通过受 Curtin-Hammett 控制的立体发散/立体协同途径进行的催化不对称迈克尔-羟醛缩合反应。
J Am Chem Soc. 2023 Jun 7;145(22):12370-12376. doi: 10.1021/jacs.3c03373. Epub 2023 May 22.
5
Copper(II)-Catalyzed Tandem Decarboxylative Michael/Aldol Reactions Leading to the Formation of Functionalized Cyclohexenones.铜（II）催化的串联脱羧迈克尔/Aldol 反应导致功能化环己烯酮的形成。
Org Lett. 2018 Apr 6;20(7):2067-2070. doi: 10.1021/acs.orglett.8b00607. Epub 2018 Mar 21.
6
N-Heterocyclic carbene-catalyzed diastereoselective synthesis of sulfenylated indanes via sulfa-Michael-Michael (aldol) cascade reactions.通过硫代-迈克尔-迈克尔（羟醛）串联反应实现N-杂环卡宾催化的亚磺酰化茚满的非对映选择性合成。
Org Biomol Chem. 2019 May 15;17(19):4700-4704. doi: 10.1039/c9ob00210c.
7
Organocatalytic Enantioselective Michael-Michael-Michael-Aldol Condensation Reactions: Control of Six Stereocenters in a Quadruple-Cascade Asymmetric Synthesis of Polysubstituted Spirocyclic Oxindoles.有机催化对映选择性迈克尔-迈克尔-迈克尔-Aldol 缩合反应：在四重级联不对称合成多取代螺环吲哚酮中控制六个立体中心。
Org Lett. 2017 Nov 17;19(22):6112-6115. doi: 10.1021/acs.orglett.7b02962. Epub 2017 Nov 1.
8
One-pot Fluorination and Organocatalytic Robinson Annulation for Asymmetric Synthesis of Mono- and Difluorinated Cyclohexenones.一锅法氟代和有机催化的 Robinson 环化反应用于不对称合成单氟和二氟环己烯酮。
Molecules. 2018 Sep 4;23(9):2251. doi: 10.3390/molecules23092251.
9
CPA-catalyzed asymmetric domino thia-Michael/aldol reactions for simultaneous chiral center and axial chirality formation.CPA催化的不对称多米诺硫代迈克尔/羟醛反应用于同时形成手性中心和轴手性。
Org Biomol Chem. 2023 Aug 23;21(33):6697-6701. doi: 10.1039/d3ob01087b.
10
Tandem Sakurai-aldol addition reactions as a route to structurally complex carbocycles.串联樱井-羟醛加成反应作为构建结构复杂碳环的一条途径。
J Org Chem. 2005 May 27;70(11):4375-9. doi: 10.1021/jo050225y.
本文引用的文献
1
Catalytic, Asymmetric Michael-Aldol Annulations via a Stereodivergent/Stereoconvergent Path Operating under Curtin-Hammett Control.通过受 Curtin-Hammett 控制的立体发散/立体协同途径进行的催化不对称迈克尔-羟醛缩合反应。
J Am Chem Soc. 2023 Jun 7;145(22):12370-12376. doi: 10.1021/jacs.3c03373. Epub 2023 May 22.
2
Bifunctional Iminophosphorane Superbase Catalysis: Applications in Organic Synthesis.双功能亚膦酰胺超强碱催化：在有机合成中的应用。
Acc Chem Res. 2020 Oct 20;53(10):2235-2247. doi: 10.1021/acs.accounts.0c00369. Epub 2020 Sep 4.
3
Phosphine-Catalyzed Chemo- and Diastereoselective [2 + 2 + 2] and [3 + 2] Annulations of γ-Methyl Allenoates with Doubly Activated Olefins: Syntheses of Highly Substituted Cyclohexanes and Cyclopentenes.膦催化的γ-甲基烯丙酸盐与双活化烯烃的化学和立体选择性[2 + 2 + 2]和[3 + 2]环加成反应：高度取代的环己烷和环戊烯的合成。
J Org Chem. 2019 Oct 4;84(19):12490-12498. doi: 10.1021/acs.joc.9b01968. Epub 2019 Sep 24.
4
β-Ketoesters as Mono- or Bisnucleophiles: A Concise Enantioselective Total Synthesis of (-)-Englerin A and B.β-酮酯作为单亲核试剂或双亲核试剂：（-）-恩格勒菌素A和B的简洁对映选择性全合成
Angew Chem Int Ed Engl. 2019 Jun 17;58(25):8346-8350. doi: 10.1002/anie.201900401. Epub 2019 May 10.
5
Environmental analysis of the life cycle emissions of 2-methyl tetrahydrofuran solvent manufactured from renewable resources.由可再生资源制造的2-甲基四氢呋喃溶剂生命周期排放的环境分析。
J Environ Sci Health A Tox Hazard Subst Environ Eng. 2016;51(6):487-94. doi: 10.1080/10934529.2015.1128719. Epub 2016 Feb 18.
6
Asymmetric synthesis of functionalized cyclohexanes bearing five stereocenters via a one-pot organocatalytic Michael-Michael-1,2-addition sequence.通过一锅法有机催化的迈克尔-迈克尔-1,2-加成序列对含有五个立体中心的官能化环己烷进行不对称合成。
Chem Commun (Camb). 2014 Jul 4;50(52):6853-5. doi: 10.1039/c4cc01885k.
7
Enantioselective synthesis of protected nitrocyclohexitols with five stereocenters. Total synthesis of (+)-pancratistatin.具有五个手性中心的保护硝基环己醇的对映选择性合成。(+)- Pancratistatin 的全合成。
J Org Chem. 2012 Dec 21;77(24):11377-82. doi: 10.1021/jo3022567. Epub 2012 Dec 3.
8
2-Methyltetrahydrofuran (2-MeTHF): a biomass-derived solvent with broad application in organic chemistry.2-甲基四氢呋喃（2-MeTHF）：一种源自生物质的溶剂，在有机化学中有广泛的应用。
ChemSusChem. 2012 Aug;5(8):1369-79. doi: 10.1002/cssc.201100780.
9
A highly diastereo- and enantioselective reaction for constructing functionalized cyclohexanes: six contiguous stereocenters in one step.一种构建官能化环己烷的高度非对映和对映选择性反应：一步形成六个相邻的立体中心。
Angew Chem Int Ed Engl. 2012 Jan 27;51(5):1248-51. doi: 10.1002/anie.201107495. Epub 2011 Dec 23.
10
Asymmetric organocatalytic domino Michael/aldol reactions: enantioselective synthesis of chiral cycloheptanones, tetrahydrochromenones, and polyfunctionalized bicyclo[3.2.1]octanes.不对称有机催化多米诺迈克尔/羟醛反应：手性环庚酮、四氢色原酮和多官能化双环[3.2.1]辛烷的对映选择性合成
Angew Chem Int Ed Engl. 2009;48(20):3699-702. doi: 10.1002/anie.200900754.
Zotero 插件