Benzylic Organometallics Research Articles

Herstellung von benzylischen Natrium‐Metallorganylen im kontinuierlichen Durchfluss

AbstractWir beschreiben eine laterale Natriierung von Alkali(hetero)arenen mittels bedarfsgerecht generiertem, in Hexan löslichem (2‐Ethylhexyl)natrium (1) in Gegenwart von TMEDA. (2‐Ethylhexyl)natrium (1) wird mittels eines Natrium‐Festbettreaktors hergestellt und für Metallierungen bei Umgebungstemperatur sowohl im Kolben als auch im kontinuierlichem Durchfluss genutzt. Die entstehenden benzylischen Natriumspezies werden nachfolgend mit verschiedenen Elektrophilen, unter anderem Carbonylverbindungen, Epoxiden, Oxetan, Allyl/Benzylchloriden, Alkylhalogenen und ‐tosylaten abgefangen. Wurtz‐Typ‐Kopplungen mit sekundären Alkylhalogenen und Tosylaten laufen unter kompletter Inversion der Stereochemie ab. Des Weiteren wird die Nützlichkeit dieser lateralen Natriierung durch die Synthese pharmazeutisch relevanter Verbindungen demonstriert. So wird Fingolimod durch die zweifache Anwendung der lateralen Natriierung ausgehend von p‐Xylol hergestellt. Zusätzlich ist 7‐fach Isotopen angereichertes Salmeterol‐d7 und Fenpiprane, sowie Ausgangsmaterialien zu super linearen Alkylbenzyl (SLAB) Tensiden hergestellt worden.

6,12‐Diphenyldibenzo[b,f][1,5]diazocine as an Electron‐Capture Agent: Efficient Mechanistic Probe for SET Processes and Reagent for the Oxidative Dimerization of Benzylic Organometallics

AbstractIn the present study, 6,12‐diphenyldibenzo[b,f][1,5]diazocine, which X‐ray diffraction measurements have now shown to possess a tub‐shaped, eight‐membered central ring, has been treated with sodium or lithium metal at 25 °C in THF, in an attempt to form the planar, Hückel‐aromatic dianion by the addition of two electrons to the central diazocine. Hydrolysis of such an aromatic dianion should have led to the isomeric 5,12‐ or 5,6‐dihydro derivative of the original diazocine. In actuality, the only product obtained quantitatively upon hydrolytic workup was the interesting quadricyclic transannular reduction product, 4b,9b‐diphenyl‐4b,5,9b,10‐tetrahydroindolo[3,2‐b]indole, whose 3D structure has now been confirmed by X‐ray crystallography and 13C NMR spectroscopy. Preferential SET transannular reduction of the diazocine to yield the quadricyclic indolo[3,2‐b]indole dianion, rather than the planar, Hückel‐aromatic anion, is ascribed to the transannular electronic stabilization operative in the tub‐shaped diazocine radical‐anion. The quantitative generation of the indolo[3,2‐b]indole dianion can be employed for the oxidative dimerization of the organic groups in benzylic lithium reagents. Thus treating one equivalent of the diazocine with two equivalents of benzyllithium, benzhydryllithium, or trityllithium yields quantitatively bibenzyl, 1,1,2,2‐tetraphenylethane, or (4‐benzhydrylphenyl)triphenylmethane, respectively. This oxidative dimerization is potentially of practical preparative scope, since the hydrolysis byproduct, the indolo[3,2‐b]indole, is conveniently reconverted into the starting diazocine reagent by oxidation with chromium trioxide in acetic acid. The formation of the indolo[3,2‐b]indole as a byproduct in the carbometalation of the diazocine by various RLi and Grignard reagents offers a clue as to the SET mechanism of carbometalation.

New Preparation of Benzylic Aluminum and Zinc Organometallics by Direct Insertion of Aluminum Powder

The reaction of commercial Al-powder (3 equiv) and InCl(3) (1-5 mol %) with benzylic chlorides provides various functionalized benzylic aluminum sesquichlorides under mild conditions (THF, 20 °C, 3-24 h) without homocoupling (<5%). These new benzylic organometallics reacted smoothly with various electrophiles (Pd-catalyzed cross-couplings, or Cu-mediated acylations, allylations, or 1,4-addition reactions). Electron-poor benzylic chlorides or substrates prone to Wurtz coupling can be converted to benzylic zinc compounds by the reaction of Al-powder in the presence of ZnCl(2).

ChemInform Abstract: Preparation and Reactions of Functionalized Benzylic Organometallics of Zinc and Copper.

The reaction of zinc dust with primary or secondary benzylic halides 1 bearing various functional groups such as an ester, halide, cyano, or even a ketone group, in THF or, in the case of benzylic chlorides, in THF:DMSO (4:1), furnishes the corresponding zinc organometallics 2 in high yields. The reaction is accompanied by less than 10% of Wurtz coupling products. The benzylic copper organometallics 3, obtained after a transmetalation of 2 with the THF-soluble copper salt CuCN•2LiCl at −20 o C, react in excellent yields (70-95%) with various electrophiles such as acid chlorides, enones, aldehydes, allylic bromides, ethyl propiolate, and tributyltin chloride

ChemInform Abstract: A Facile Synthesis of Functionalized 4-Benzylpyridines by Using Mixed Copper, Zinc Benzylic Organometallics.

Abstract A general approach by use of highly functionalized mixed copper zinc, benzylic organometallics to react with N-ethoxycarbonylpyridinium chloride to give regioselectively 4-benzylpyridines after oxygen oxidation in 30–75% yield is described.

ChemInform Abstract: Regio- and Chemoselective Addition of Mixed Copper, Zinc Benzylic Organometallics to Functionalized Pyridinium Salts: A Facile Synthesis of Functionalized 4-Benzylpyridines.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Diastereoselective electrophilic substitution of α-amino-substituted benzylic organometallics

Reductive metallation of a diastereoisomeric bicyclic 2-phenyloxazolidine derived from 2-hydroxymethylpiperidine occurs with racemization at the benzylic carbon atom. Reaction of intermediate organometallics with alkyl halides affords substituted amino alcohols in a highly syn-selective fashion. Observed diastereoselectivities are rationalized in terms of rapidly equilibrating epimeric intermediate organometallics, one of which reacts preferentially under appropriate reaction conditions. Deuteration of the same intermediates usually leads to deuterated amino alcohols with low diasteroselectivities, unless lithium is employed as the reducing agent and the resulting mixture is allowed to equilibrate before deuteration.

ChemInform Abstract: Studies on Regioselective Addition of Benzylic Organometallics to α‐Oxoketene Dithioacetals in our Aromatic Anellation Protocol

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

New preparation of benzylic zinc reagents via a fragmentation reaction

The fragmentation of sterically hindered homobenzylic zinc alcoholates proceeds readily leading to benzylic zinc reagents free from any Wurtz-coupling product. Reaction of these organometallic intermediates with various aldehydes produces new homobenzylic alcohols in moderate to good yields. A 1,4-addition of these newly prepared benzylic organometallics to an alkylidenemalonate is also reported.

Studies on regioselective addition of benzylic organometallics to α-oxoketene dithioacetals in our aromatic annelation protocol

The α-oxoketene dithioacetals derived from various acyclic and cyclic active methylene ketones are shown to undergo either 1,2- or sequential 1,4- and 1,2-addition with various substituted benzylic Grignard reagents (or benzyl lithium) and 1-/2-(naphthylmethyl) Grignard reagents to give carbinol adducts which on facile BF 3.Et 2O induced cycloaromatization afford a variety of substituted naphthalenes, phenanthrenes and other condensed aromatics. This methodology has emerged as a versatile tool for the regioselective construction of aromatic ring via [3+3] annulation from readily available acyclic precursors. The various substituted benzylic Grignard reagents (or benzyl lithium) and the corresponding 1- and 2-(naphthylmethyl) reagents display diverse regioselectivity in these reactions via either 1,2-addition or sequential 1,4- and 1,2-addition depending on the substituents in the benzylic moiety, nature of the metal and the substrate oxoketene dithioacetals. The benzylic organocopper reagents undergo regioselective conjugate addition-displacement to give β-benzyl-β-methylthiomethylene ketones while the corresponding alkoxy substituted benzyl organocopper reagents gave unexpected results under these conditions. An attempt has been made to generalize some of these observations in terms of charge control 1,2- and orbital control 1,4-addition, although theoretical studies are needed to throw further light for better understanding of these results.

A facile synthesis of functionalized 4-benzylpyridines by using mixed copper, zinc benzylic organometallics

A general approach by use of highly functionalized mixed copper zinc, benzylic organometallics to react with N-ethoxycarbonylpyridinium chloride to give regioselectively 4-benzylpyridines after oxygen oxidation in 30–75% yield is described.

Regio- and Chemoselective Addition of Mixed Copper, Zinc Benzylic Organometallics to Functionalized Pyridinium Salts: A Facile Synthesis of Functionalized 4-Benzylpyridines

2′,3-Disubstituted 4-benzylpyridines 4 were synthesized in good yield by reaction of mixed copper, zinc benzylic organometallics 1 with 3-substituted 1-(ethoxycarbonyl)pyridinium chlorides 2 followed by sulfur oxidation under reflux in decalin.

Preparation and reactions of functionalized benzylic organometallics of zinc and copper

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation and reactions of functionalized benzylic organometallics of zinc and copperScott C. Berk, Ming Chang P. Yeh, Nakcheol Jeong, and Paul KnochelCite this: Organometallics 1990, 9, 12, 3053–3064Publication Date (Print):December 1, 1990Publication History Published online1 May 2002Published inissue 1 December 1990https://doi.org/10.1021/om00162a016RIGHTS & PERMISSIONSArticle Views2786Altmetric-Citations83LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (2 MB) Get e-Alerts Get e-Alerts

ChemInform Abstract: General Approach to Highly Functionalized Benzylic Organometallics of Zinc and Copper.

AbstractReaction of the benzylic bromides (I) with zinc (II) activated by 1,2‐dibromoethane yields the benzylic zinc bromides (III) which are subjected to transmetalation reaction to give the copper organics (V).

Mixed copper, zinc 2-amino benzylic organometallics as efficient reagents for the synthesis of heterocycles

The mixed copper, zinc benzylic organometallics 1a–1c react efficiently with various electrophiles. By the reaction with acyl chlorides, highly functionalized 2-substituted indoles are produced. The treatment of 1a with allylic bromides, 3-iodo-cyclohexenone and ethyl propiolate furnishes polyfunctionalized anilines. Several of them could be converted into five- or seven-membered heterocycles.

General approach to highly functionalized benzylic organometallics of zinc and copper

General approach to highly functionalized benzylic organometallics of zinc and copper