二异丙基胺锂介导的 2,6-二氟吡啶取代反应的机理。
Mechanism of lithium diisopropylamide-mediated substitution of 2,6-difluoropyridine.
机构信息
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301, USA.
出版信息
J Am Chem Soc. 2010 May 12;132(18):6361-5. doi: 10.1021/ja910834b.
Abstract
Treatment of 2,6-difluoropyridine with lithium diisopropylamide in THF solution at -78 degrees C effects ortholithiation quantitatively. Warming the solution to 0 degrees C converts the aryllithium to 2-fluoro-6-(diisopropylamino)pyridine. Rate studies reveal evidence of a reversal of the ortholithiation and a subsequent 1,2-addition via two monomer-based pathways of stoichiometries [ArH*i-Pr(2)NLi(THF)](double dagger) and [ArH*i-Pr(2)NLi(THF)(3)](double dagger). Computational studies fill in the structural details and provide evidence of a direct substitution without the intermediacy of a Meisenheimer complex.
摘要
用二异丙基胺锂在四氢呋喃溶液中处理 2,6-二氟吡啶，在-78°C 下定量进行邻位锂化。将溶液加热至 0°C，将芳基锂转化为 2-氟-6-(二异丙基氨基)吡啶。速率研究表明，存在邻位锂化的反转和随后通过两种基于单体的途径进行 1,2-加成的证据，其化学计量比为ArH*i-Pr(2)NLi(THF)和ArH*i-Pr(2)NLi(THF)(3)。计算研究填补了结构细节，并提供了直接取代而没有 Meisenheimer 络合物中间体的证据。
相似文献
1
Mechanism of lithium diisopropylamide-mediated substitution of 2,6-difluoropyridine.二异丙基胺锂介导的 2,6-二氟吡啶取代反应的机理。
J Am Chem Soc. 2010 May 12;132(18):6361-5. doi: 10.1021/ja910834b.
2
Lithium diisopropylamide-mediated ortholithiation of 2-fluoropyridines: rates, mechanisms, and the role of autocatalysis.二异丙基胺锂促进 2-氟吡啶的正锂化反应：速率、机制和自催化作用。
J Org Chem. 2013 May 3;78(9):4214-30. doi: 10.1021/jo302408r. Epub 2013 Feb 8.
3
Autocatalysis in lithium diisopropylamide-mediated ortholithiations.二异丙基锂酰胺介导的邻位锂化反应中的自催化作用。
J Am Chem Soc. 2008 Dec 31;130(52):18008-17. doi: 10.1021/ja807331k.
4
Lithium diisopropylamide-mediated ortholithiation and anionic fries rearrangement of aryl carbamates: role of aggregates and mixed aggregates.二异丙基氨基锂介导的芳基氨基甲酸酯的邻位锂化和阴离子弗里斯重排：聚集体和混合聚集体的作用
J Am Chem Soc. 2006 Oct 25;128(42):13753-60. doi: 10.1021/ja064655x.
5
Sodium Diisopropylamide in Tetrahydrofuran: Selectivities, Rates, and Mechanisms of Arene Metalations.四氢呋喃中的二异丙基胺钠：芳基金属化的选择性、速率和机理。
J Am Chem Soc. 2017 Oct 25;139(42):15197-15204. doi: 10.1021/jacs.7b08734. Epub 2017 Oct 16.
6
Mechanism of Lithium Diisopropylamide-Mediated Ortholithiation of 1,4-Bis(trifluoromethyl)benzene under Nonequilibrium Conditions: Condition-Dependent Rate Limitation and Lithium Chloride-Catalyzed Inhibition.非平衡条件下二异丙基氨基锂介导的1,4-双（三氟甲基）苯邻位锂化反应机理：条件依赖性速率限制及氯化锂催化抑制作用
J Am Chem Soc. 2015 May 20;137(19):6292-303. doi: 10.1021/jacs.5b01668. Epub 2015 May 6.
7
Regioselective lithium diisopropylamide-mediated ortholithiation of 1-chloro-3-(trifluoromethyl)benzene: role of autocatalysis, lithium chloride catalysis, and reversibility.区域选择性锂二异丙基酰胺介导的 1-氯-3-(三氟甲基)苯的邻位锂化反应：自催化、氯化锂催化和可逆性的作用。
J Am Chem Soc. 2011 May 11;133(18):7135-51. doi: 10.1021/ja200906z. Epub 2011 Apr 18.
8
Lithium diisopropylamide-mediated lithiation of 1,4-difluorobenzene under nonequilibrium conditions: role of monomer-, dimer-, and tetramer-based intermediates and lessons about rate limitation.非平衡条件下二异丙基氨基锂介导的1,4-二氟苯锂化反应：基于单体、二聚体和四聚体的中间体的作用及速率限制相关经验教训
J Org Chem. 2014 Dec 19;79(24):11885-902. doi: 10.1021/jo501392r. Epub 2014 Aug 8.
9
Lithium diisopropylamide solvated by hexamethylphosphoramide: substrate-dependent mechanisms for dehydrobrominations.由六甲基磷酰胺溶剂化的二异丙基氨基锂：脱氢溴化反应的底物依赖性机制
J Am Chem Soc. 2006 Dec 6;128(48):15399-404. doi: 10.1021/ja060964b.
10
Sodium Diisopropylamide-Mediated Dehydrohalogenations: Influence of Primary- and Secondary-Shell Solvation.二异丙基胺钠介导的脱卤化氢反应：主壳层和次壳层溶剂化的影响。
J Org Chem. 2019 Sep 6;84(17):10860-10869. doi: 10.1021/acs.joc.9b01428. Epub 2019 Aug 22.
引用本文的文献
1
Case for Lithium Tetramethylpiperidide-Mediated Ortholithiations: Reactivity and Mechanisms.四甲基哌啶锂介导的邻位锂化反应案例：反应性和机理。
J Am Chem Soc. 2018 Apr 11;140(14):4877-4883. doi: 10.1021/jacs.8b00590. Epub 2018 Mar 28.
2
Sodium Diisopropylamide in Tetrahydrofuran: Selectivities, Rates, and Mechanisms of Arene Metalations.四氢呋喃中的二异丙基胺钠：芳基金属化的选择性、速率和机理。
J Am Chem Soc. 2017 Oct 25;139(42):15197-15204. doi: 10.1021/jacs.7b08734. Epub 2017 Oct 16.
3
Sodium Diisopropylamide in N,N-Dimethylethylamine: Reactivity, Selectivity, and Synthetic Utility.二异丙基胺基钠在 N,N-二甲基乙胺中的反应性、选择性和合成实用性。
J Org Chem. 2016 Nov 18;81(22):11312-11315. doi: 10.1021/acs.joc.6b02287. Epub 2016 Nov 2.
4
Lithium diisopropylamide-mediated ortholithiation of 2-fluoropyridines: rates, mechanisms, and the role of autocatalysis.二异丙基胺锂促进 2-氟吡啶的正锂化反应：速率、机制和自催化作用。
J Org Chem. 2013 May 3;78(9):4214-30. doi: 10.1021/jo302408r. Epub 2013 Feb 8.
5
Computational studies of lithium diisopropylamide deaggregation.双异丙基胺锂解聚的计算研究。
J Org Chem. 2011 Oct 7;76(19):7985-93. doi: 10.1021/jo2015642. Epub 2011 Sep 2.
6
Regioselective lithium diisopropylamide-mediated ortholithiation of 1-chloro-3-(trifluoromethyl)benzene: role of autocatalysis, lithium chloride catalysis, and reversibility.区域选择性锂二异丙基酰胺介导的 1-氯-3-(三氟甲基)苯的邻位锂化反应：自催化、氯化锂催化和可逆性的作用。
J Am Chem Soc. 2011 May 11;133(18):7135-51. doi: 10.1021/ja200906z. Epub 2011 Apr 18.
7
1,4-addition of lithium diisopropylamide to unsaturated esters: role of rate-limiting deaggregation, autocatalysis, lithium chloride catalysis, and other mixed aggregation effects.1,4-二异丙基酰胺锂与不饱和酯的加成反应：限速解聚、自催化、氯化锂催化以及其他混合聚集效应的作用。
J Am Chem Soc. 2010 Nov 10;132(44):15610-23. doi: 10.1021/ja105855v.
本文引用的文献
1
Nickel(0)-catalyzed [2 + 2 + 2] cycloaddition of diynes and 3,4-pyridynes: novel synthesis of isoquinoline derivatives.镍（0）催化的二炔与3,4-吡啶炔的[2 + 2 + 2]环加成反应：异喹啉衍生物的新合成方法
Chem Commun (Camb). 2009 Sep 21(35):5245-7. doi: 10.1039/b912022j. Epub 2009 Aug 3.
2
In situ FTIR reaction analysis of pharmaceutical-related chemistry and processes.药物相关化学与过程的原位傅里叶变换红外光谱反应分析
Curr Opin Drug Discov Devel. 2000 Nov;3(6):734-42.
3
Ruthenium Vinyl Carbene Intermediates in Enyne Metathesis.烯炔复分解反应中的钌乙烯基卡宾中间体
Coord Chem Rev. 2007 Mar 1;251(5):671-701. doi: 10.1016/j.ccr.2006.09.008.
4
C-F bond activation in organic synthesis.有机合成中的碳-氟键活化
Chem Rev. 2009 May;109(5):2119-83. doi: 10.1021/cr800388c.
5
Autocatalysis in lithium diisopropylamide-mediated ortholithiations.二异丙基锂酰胺介导的邻位锂化反应中的自催化作用。
J Am Chem Soc. 2008 Dec 31;130(52):18008-17. doi: 10.1021/ja807331k.
6
A study of BF3-promoted ortho lithiation of anilines and DFT calculations on the role of fluorine-lithium interactions.关于BF₃促进苯胺邻位锂化的研究以及氟-锂相互作用作用的密度泛函理论计算。
Angew Chem Int Ed Engl. 2008;47(25):4703-6. doi: 10.1002/anie.200705967.
7
Structural and rate studies of the formation of substituted benzynes.取代苯炔形成的结构与速率研究。
J Am Chem Soc. 2008 Mar 19;130(11):3406-12. doi: 10.1021/ja0754655. Epub 2008 Feb 23.
8
Fluorinated diarylamido complexes of lithium, zirconium, and hafnium.
Inorg Chem. 2008 Apr 21;47(8):3298-306. doi: 10.1021/ic702293d. Epub 2008 Feb 23.
9
Fluorine... and pi...alkali metal interactions control in the stereoselective amide enolate alkylation with fluorinated oxazolidines (Fox) as a chiral auxiliary: an experimental and theoretical study.以氟化恶唑烷（Fox）为手性助剂的立体选择性酰胺烯醇盐烷基化反应中氟与π……碱金属相互作用的控制：一项实验与理论研究
Chemistry. 2008;14(11):3363-70. doi: 10.1002/chem.200701604.
10
Two-dimensional acetylenic scaffolding: extended donor-substituted perethynylated dehydroannulenes.
Chem Asian J. 2006 Sep 18;1(3):479-89. doi: 10.1002/asia.200600131.
Zotero 插件