通过连续不对称烯丙基烷基化和环收缩合成对映体富集的2,2-二取代吡咯烷。
Synthesis of enantioenriched 2,2-disubstituted pyrrolidines via sequential asymmetric allylic alkylation and ring contraction.
作者信息
Goldstein Elizabeth L, Takada Hirokazu, Sumii Yuji, Baba Katsuaki, Stoltz Brian M
机构信息
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
出版信息
Tetrahedron. 2022 Sep 24;123. doi: 10.1016/j.tet.2022.132940. Epub 2022 Aug 6.
Abstract
The synthesis of a variety of enantioenriched 2,2-disubstituted pyrrolidines is described. A stereogenic quaternary center is first formed utilizing an asymmetric allylic alkylation reaction of a benzyloxy imide, which can then be reduced to a chiral hydroxamic acid. This compound can then undergo a thermal "Spino" ring contraction to afford a carbamate protected 2,2-disubstituted pyrrolidine stereospecifically. These pyrrolidines can be further advanced to enantioenriched indolizidine compounds. This reaction sequence allows access to new molecules that could be useful in the development of pharmaceutical agents.
摘要
本文描述了多种对映体富集的2,2-二取代吡咯烷的合成方法。首先利用苄氧基酰亚胺的不对称烯丙基烷基化反应形成一个手性季碳中心，然后将其还原为手性异羟肟酸。该化合物随后可进行热“Spino”环收缩反应，立体专一性地得到氨基甲酸酯保护的2,2-二取代吡咯烷。这些吡咯烷可进一步转化为对映体富集的中氮茚化合物。该反应序列能够获得可用于药物研发的新分子。
相似文献
1
Synthesis of enantioenriched 2,2-disubstituted pyrrolidines via sequential asymmetric allylic alkylation and ring contraction.通过连续不对称烯丙基烷基化和环收缩合成对映体富集的2,2-二取代吡咯烷。
Tetrahedron. 2022 Sep 24;123. doi: 10.1016/j.tet.2022.132940. Epub 2022 Aug 6.
2
Highly Enantioselective, Base-Free Synthesis of α-Quaternary Succinimides through Catalytic Asymmetric Allylic Alkylation.通过催化不对称烯丙基烷基化反应高对映选择性、无碱合成α-季戊四酰亚胺。
Chemistry. 2018 Jun 7;24(32):8076-8080. doi: 10.1002/chem.201800920. Epub 2018 May 14.
3
Synthesis of Enantioenriched -Disubstituted 4-Imidazolidinones by Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation.钯催化脱羧不对称烯丙基烷基化反应合成对映富集的 -二取代 4-咪唑烷酮。
Org Lett. 2021 Aug 20;23(16):6348-6351. doi: 10.1021/acs.orglett.1c02134. Epub 2021 Aug 4.
4
Asymmetric Synthesis of α-Quaternary γ-Lactams through Palladium-Catalyzed Asymmetric Allylic Alkylation.钯催化不对称烯丙基烷基化反应实现α-季碳γ-内酰胺的不对称合成。
Org Lett. 2019 Feb 1;21(3):603-607. doi: 10.1021/acs.orglett.8b03613. Epub 2019 Jan 15.
5
Asymmetric Redox Allylic Alkylation to Access 3,3'-Disubstituted Oxindoles Enabled by Ni/NHC Cooperative Catalysis.镍/氮杂环卡宾协同催化实现的不对称氧化还原烯丙基烷基化反应合成3,3'-二取代氧化吲哚
Angew Chem Int Ed Engl. 2022 May 23;61(22):e202201678. doi: 10.1002/anie.202201678. Epub 2022 Mar 29.
6
Synergistic Ir/Cu Catalysis for Asymmetric Allylic Alkylation of Oxindoles: Enantio- and Diastereoselective Construction of Quaternary and Tertiary Stereocenters.协同 Ir/Cu 催化的吲哚类化合物不对称烯丙基烷基化反应：对映选择性和非对映选择性构建季碳和叔碳中心。
Chemistry. 2021 Jul 16;27(40):10255-10260. doi: 10.1002/chem.202101267. Epub 2021 May 27.
7
Asymmetric organocatalytic allylic alkylation of Reissert compounds: a facile access to chiral 1,1-disubstituted 1,2-dihydroisoquinolines.不对称有机催化烯丙基烷基化反应的 Reissert 化合物：一种获得手性 1,1-二取代 1,2-二氢异喹啉的简便方法。
Org Biomol Chem. 2013 Feb 14;11(6):984-90. doi: 10.1039/c2ob27269e. Epub 2013 Jan 2.
8
Construction of Quaternary Stereogenic Carbon Centers through Copper-Catalyzed Enantioselective Allylic Alkylation of Azoles.通过铜催化的唑类化合物的对映选择性烯丙基烷基化反应构建四元手性碳中心。
Angew Chem Int Ed Engl. 2016 Apr 4;55(15):4777-80. doi: 10.1002/anie.201600619. Epub 2016 Mar 9.
9
Catalytic Asymmetric Reactions with -Metallated Azomethine Ylides.手性催化不对称反应与 -金属化亚胺叶立德。
Acc Chem Res. 2020 May 19;53(5):1084-1100. doi: 10.1021/acs.accounts.0c00113. Epub 2020 Apr 22.
10
Asymmetric Synthesis of All-Carbon Quaternary Spirocycles via a Catalytic Enantioselective Allylic Alkylation Strategy.通过催化对映选择性烯丙基烷基化策略实现全碳季碳螺环的不对称合成。
Tetrahedron Lett. 2017 Aug 23;58(34):3341-3343. doi: 10.1016/j.tetlet.2017.07.022. Epub 2017 Jul 5.
引用本文的文献
1
Total Synthesis of (-)-Flueggeacosine C.（-）-弗吕格可辛C的全合成
Org Lett. 2024 Sep 6;26(35):7341-7346. doi: 10.1021/acs.orglett.4c02516. Epub 2024 Aug 23.
本文引用的文献
1
Palladium-Catalyzed Enantioselective C-C Cross-Coupling for the Synthesis of (Poly)fluorinated Chiral Building Blocks.钯催化的对映选择性 C-C 交叉偶联反应在（多）氟代手性砌块合成中的应用。
Org Lett. 2018 Sep 21;20(18):5657-5660. doi: 10.1021/acs.orglett.8b02369. Epub 2018 Sep 5.
2
An Efficient Protocol for the Palladium-catalyzed Asymmetric Decarboxylative Allylic Alkylation Using Low Palladium Concentrations and a Palladium(II) Precatalyst.一种使用低钯浓度和钯（II）预催化剂的钯催化不对称脱羧烯丙基烷基化的高效方法。
Adv Synth Catal. 2015 Jul 6;357(10):2238-2245. doi: 10.1002/adsc.201500253. Epub 2015 Jul 14.
3
Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals.分析美国 FDA 批准的药物中氮杂环的结构多样性、取代模式和频率。
J Med Chem. 2014 Dec 26;57(24):10257-74. doi: 10.1021/jm501100b. Epub 2014 Oct 7.
4
A General, Enantioselective Synthesis of 1-Azabicyclo[.0]alkane Ring Systems.1-氮杂双环[.0]烷烃环系的通用对映选择性合成。
Tetrahedron Lett. 2013 Mar 27;54(13):1645-1648. doi: 10.1016/j.tetlet.2013.01.041.
5
Expanding insight into asymmetric palladium-catalyzed allylic alkylation of N-heterocyclic molecules and cyclic ketones.拓展对不对称钯催化的 N-杂环分子和环状酮的烯丙基烷基化反应的认识。
Chemistry. 2013 Apr 2;19(14):4414-8. doi: 10.1002/chem.201300030. Epub 2013 Feb 27.
6
Photochemical and thermal ring-contraction of cyclic hydroxamic acid derivatives.环状羟肟酸衍生物的光化学和热环收缩反应。
J Org Chem. 2012 Dec 21;77(24):11216-26. doi: 10.1021/jo3023507. Epub 2012 Dec 13.
7
Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams.通过钯催化的内酰胺脱羧烯丙基烷基化反应构建手性季碳 N-杂环。
Nat Chem. 2011 Dec 18;4(2):130-3. doi: 10.1038/nchem.1222.
8
Photochemical rearrangement of N-mesyloxylactams: stereospecific formation of N-heterocycles.N-甲氧基邻氨基内酯的光化学重排：N-杂环的立体特异性形成。
J Org Chem. 2011 Jan 7;76(1):164-9. doi: 10.1021/jo101805q. Epub 2010 Dec 3.
9
Rapid synthesis of an electron-deficient t-BuPHOX ligand: cross-coupling of aryl bromides with secondary phosphine oxides.缺电子叔丁基膦恶唑啉配体的快速合成：芳基溴与仲膦氧化物的交叉偶联反应
Tetrahedron Lett. 2010 Oct 20;51(42):5550-5554. doi: 10.1016/j.tetlet.2010.08.039.
10
A palladium-catalysed enolate alkylation cascade for the formation of adjacent quaternary and tertiary stereocentres.钯催化的烯醇化物烷基化级联反应用于形成相邻的季碳和叔碳立体中心。
Nat Chem. 2010 Mar;2(3):192-6. doi: 10.1038/nchem.518.
Zotero 插件