通过不对称醇介导的羰基烯丙基化反应实现福司曲星的形式合成。
Formal Synthesis of Fostriecin via Asymmetric Alcohol-Mediated Carbonyl Allylation.
作者信息
Pfaffinger Dana E, Krische Michael J
机构信息
Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States.
出版信息
Org Lett. 2025 May 2;27(17):4501-4506. doi: 10.1021/acs.orglett.5c01026. Epub 2025 Apr 10.
Abstract
A formal synthesis of fostriecin via convergent assembly of two fragments prepared via asymmetric alcohol-mediated C-C coupling is described. One fragment is made by the enantioselective iridium-catalyzed allylation of an allylic alcohol mediated by allyl acetate. The other fragment is made via enantioselective ruthenium-catalyzed reductive -(α-alkoxy)allylation of an aldehyde mediated by an alkoxyallene (where 2-propanol is the hydrogen source), representing the first use of this method in target-oriented synthesis. Metathetic fragment union enables interception of a late-stage compound that previously required a 25 step (LLS) synthesis in only 7 steps (LLS).
摘要
本文描述了通过不对称醇介导的碳-碳偶联制备的两个片段的汇聚组装来实现磷霉素的形式合成。一个片段是通过乙酸烯丙酯介导的对映选择性铱催化的烯丙醇烯丙基化反应制备的。另一个片段是通过烷氧基丙二烯介导的醛的对映选择性钌催化的还原-(α-烷氧基)烯丙基化反应制备的（其中2-丙醇为氢源），这代表了该方法在目标导向合成中的首次应用。复分解片段结合能够截获一种后期化合物，该化合物以前需要25步（线性最长步骤数）合成，现在仅需7步（线性最长步骤数）即可完成。
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1
Catalytic Enantioselective C-C Coupling of Alcohols for Polyketide Total Synthesis beyond Chiral Auxiliaries and Premetalated Reagents.
Chem Rev. 2024 Dec 25;124(24):13715-13735. doi: 10.1021/acs.chemrev.4c00858. Epub 2024 Dec 6.
2
Leveraging the Stereochemical Complexity of Octahedral Diastereomeric-at-Metal Catalysts to Unlock Regio-, Diastereo-, and Enantioselectivity in Alcohol-Mediated C-C Couplings via Hydrogen Transfer.
J Am Chem Soc. 2024 Mar 27;146(12):7905-7914. doi: 10.1021/jacs.4c01857. Epub 2024 Mar 13.
3
Carbonyl Allylation and Crotylation: Historical Perspective, Relevance to Polyketide Synthesis, and Evolution of Enantioselective Ruthenium-Catalyzed Hydrogen Auto-Transfer Processes.
Synthesis (Stuttg). 2023 May;55(10):1487-1496. doi: 10.1055/s-0042-1751420. Epub 2023 Feb 20.
4
Historical perspective on ruthenium-catalyzed hydrogen transfer and survey of enantioselective hydrogen auto-transfer processes for the conversion of lower alcohols to higher alcohols.
Chem Sci. 2022 Oct 26;13(43):12625-12633. doi: 10.1039/d2sc05621f. eCollection 2022 Nov 9.
5
Synthesis of -linked α-Gal and α-GalNAc-1'-hydroxyalkanes by way of C2 functionality transfer.
Tetrahedron Lett. 2021 Jun 8;73. doi: 10.1016/j.tetlet.2021.153109. Epub 2021 Apr 23.
6
From Hydrogenation to Transfer Hydrogenation to Hydrogen Auto-Transfer in Enantioselective Metal-Catalyzed Carbonyl Reductive Coupling: Past, Present, and Future.
ACS Catal. 2021 May 7;11(9):5572-5585. doi: 10.1021/acscatal.1c01109. Epub 2021 Apr 22.
7
Allenes and Dienes as Chiral Allylmetal Pronucleophiles in Catalytic Enantioselective C=X Addition: Historical Perspective and State-of-The-Art Survey.
Chemistry. 2021 Sep 15;27(52):13107-13116. doi: 10.1002/chem.202101890. Epub 2021 Jul 29.
8
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J Am Chem Soc. 2021 Jun 16;143(23):8849-8854. doi: 10.1021/jacs.1c03480. Epub 2021 Jun 1.
9
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Nat Chem. 2021 Jul;13(7):692-697. doi: 10.1038/s41557-021-00706-1. Epub 2021 May 27.
10
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Org Lett. 2021 May 7;23(9):3767-3771. doi: 10.1021/acs.orglett.1c01166. Epub 2021 Apr 23.
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