Stereoselective Friedel-Crafts Research Articles

Concise synthesis and confirmation of the absolute configurations of naturally occurring bioactive 2,7′-cyclolignans

A concise asymmetric synthesis of naturally occurring bioactive 2,7′-cyclolignans, namely 4,4′-dihydroxy-3′,5,5′-trimethoxy-2,7′-cyclolignan and 4,4′-dihydroxy-3,3′,5-trimethoxy-2,7′-cyclolignan, possessing the uncommon 8,8′-syn dimethyl stereochemistry and unsymmetrical C-6 units with 7′,8′-anti-orientation is described using a substrate-controlled stereoselective Friedel-Crafts cyclization as the key step. The products were obtained in good yields with high stereoselectivity. The absolute configurations of natural 4,4′-dihydroxy-3′,5,5′-trimethoxy-2,7′-cyclolignan and those of natural 4,4′-dihydroxy-3,3′,5-trimethoxy-2,7′-cyclolignan were assigned as (7′S,8S,8′S) and (7′R,8R,8′R), respectively, based on the experimental circular dichroism (CD) spectra of the corresponding synthesized compounds.

A Large Scale Formal Synthesis of CoQ10: Highly Stereoselective Friedel-Crafts Allylation Reaction of Tetramethoxytoluene with (E)-4-Chloro-2-methyl-1-phenylsulfonyl-2-butene in the Presence of Montmorillonite K-10

Ubiquinone, as its name represents, exists ubiquitously in human body, particularly in the heart. It mediates the electron transfer process in mitochondria and also exerts strong antioxidant effect in its reduced form. In clinical trial, it showed beneficial effect on heart-related diseases such as myocardial infarction, angina, and other related symptoms to cause decreased mortality compared to the placebo group. These interesting biological effects have induced various synthetic efforts towards Coenzyme Q10 (CoQ10). Among them, two approaches seem practical for a large scale production in terms of the supply of the starting material, solanesol and their synthetic efficiency: for the construction of its complete carbon framework, Koo’s synthesis used the coupling of the sulfone 2 with solanesyl bromide (3) and Lipsultz group employed nickel catalyzed cross coupling reaction of 4 with vinyl aluminum reagent 5 as the key steps, respectively (Figure 1). Earlier in our synthetic study towards CoQ10, we investigated the reproducibility of the Koo’s synthetic procedure toward 2 obtained from the Friedel-Crafts reaction of (E)-4chloro-2-methyl-1-phenylsulfonyl-2-butene (7) with tetramethoxytoluene 6. Surprisingly, the reaction itself was pretty complicated with the formation of many side products in much lowered E:Z selectivity of ca. 3:1 to 7:1 than reported. Use of zinc chloride and bromide resulted in 3.3:1 and 7.4:1 E:Z ratio, respectively (Table 1, entries 1-2) with yields usually less than 20%. Best ratio of 7.6:1 was obtained by the use of boron trifluoride etherate, however with low conversion of ca. 20%. Aluminum chloride also showed marginal conversion of 21% with 3.4:1 E:Z selectivity. Details of the HPLC profiles of these reaction mixtures were provided in Figure 2. Other Lewis acid such as MgBr2, AlEt3, TiCl4, FeCl3 led to complete decomposition of starting materials and no sign of the formation of the desired product was observed by HPLC analysis. To improve the yield and stereoselectivity of the reaction, we turned our attention to the use of montmollironite K-10 (MK-10), in which the reaction partners might be confined in the layered space, thus rendering the stereoselectivity increased. First we tested commercial MK-10 for the reaction of 6 with 7. Happily, first attempt led to much cleaner reaction profile with significantly improved E:Z selectivity (Table 2, entry 1). However, the reaction did not complete in prolonged reaction time – the maximum conversion was accomplished in 18 h (74%). We speculated that the low conversion might be caused by residual water in clay (6.9% for commercial MK-10). In this respect, we tested a series of

Stereoselective Friedel–Crafts alkylation catalyzed by squalene hopene cyclases

In organic synthesis the Friedel–Crafts alkylation is of eminent importance, as it is a key reaction in many synthetic routes. A general access to enzymatic Friedel–Crafts alkylations would be very beneficial due to the high selectivity of biocatalysts. We used designed polyprenyl phenyl ethers to specifically address this reaction by using squalene hopene cyclases as catalysts. Polycyclic products with aromatic rings constituting important biological active compounds were obtained. Our results demonstrate that squalene hopene cyclases can be utilized for Friedel–Crafts alkylations and reveal the potential of these enzymes for chiral Brønsted acid catalysis.

Synthesis of quaternary stereogenic centres via stereoselective intermolecular Friedel–Crafts reactions

Highly stereoselective Friedel-Crafts reactions have been performed using a chiral anthracene template to control the selectivity of the reaction. In the case of additions to fully substituted N-acyliminium ions, competitive elimination and condensation reactions were observed. Retro-Diels-Alder reaction of one of the reaction products led to a precursor that could be used for the construction of pyroglutamic acids bearing quaternary stereogenic centres.

ChemInform Abstract: Triflic Acid Catalyzed Highly Stereoselective Friedel—Crafts Aminoalkylation of Indoles and Pyrroles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.

Mild and Stereoselective Friedel-Crafts Alkylation of Phenol Derivatives with Vinyloxiranes: A New Access to Cycloalkenobenzofurans

The ring opening of vinyloxiranes with aryl borates under very mild and neutral conditions affords new hydroxyphenols with interesting levels of regio- and stereoselectivity. The subsequent Mitsunobu-type cyclodehydration proceeds with a good yield giving a new and easy access to cycloalkenobenzofurans.

Metal Triflate Catalyzed Regio‐ and Stereoselective Friedel—Crafts Alkenylation of Arenes with Alkynes in an Ionic Liquid: Scope and Mechanism.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Metal Triflate‐Catalyzed Regio‐ and Stereoselective Friedel–Crafts Alkenylation of Arenes with Alkynes in an Ionic Liquid: Scope and Mechanism

AbstractIn the metal triflate‐catalyzed hydroarylation of alkynes, employing an ionic liquid dramatically enhanced the catalytic activities, resulting in broadening the scope of substrates (arenes and alkynes). In some cases, even reactions that were not possible in conventional organic solvents proceeded smoothly in ionic liquids. Moreover, the ionic liquid phase containing catalyst could be readily recovered by simple decantation of the organic layer after reaction and reused for the following runs without any significant loss of activity. Mechanistic studies including 13C NMR analysis of reaction intermediates and isotope experiments confirmed for the first time that this type of reaction proceeds via vinyl cationic intermediates.

A Journey Across Recent Advances in Catalytic and Stereoselective Alkylation of Indoles

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Journey Across Recent Advances in Catalytic and Stereoselective Alkylation of Indoles

In this Account our recent results in relation to the catalytic and stereoselective Friedel-Crafts (FC) alkylation of indoles are described. Over the last decade, remarkable efforts have been devoted towards the replacement of the primal approaches with new more efficient, reliable, and environmentally benign strategies for the functionalization of indoles. Moreover, the emerging area of catalytic asymmetric FC processes is addressed and some examples of enantioselective alkylations of indoles via 1,4-additionto α,β-un-saturated systems and asymmetric ring-opening reaction of aromatic epoxides are described.

New Catalytic Approaches in the Stereoselective Friedel—Crafts Alkylation Reaction

AbstractFor Abstract see ChemInform Abstract in Full Text.

New catalytic approaches in the stereoselective Friedel-Crafts alkylation reaction.

After more than 125 years, the Friedel-Crafts alkylation is still one of the most studied and most utilized reactions in organic synthesis. What is the secret of this astonishing success? Perhaps the great versatility in scope and applicability continues to justify its crucial role in the synthesis of more and more complex molecules. However, it has taken more than a century for asymmetric catalytic versions of this reaction to be developed and subsequently extended to a range of aromatic compounds and alkylating agents. Herein we review recent developments in the design and use of catalytic and stereoselective strategies for the alkylation of aromatic systems and synthesis of a wide range of polyfunctionalized enantiomerically enriched compounds.

Highly Stereoselective Friedel—Crafts Type Cyclization. Facile Access to Enantiopure 1,4‐Dihydro‐4‐phenyl Isoquinolinones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly stereoselective Friedel–Crafts type cyclization. Facile access to enantiopure 1,4-dihydro-4-phenyl isoquinolinones

The present report describes a stereoselective synthesis of 1,4-dihydro-4-phenyl isoquinolinones 5 based on a stereoselective Friedel–Crafts type cyclization. Cyclization precursors 1 were prepared in two steps, from the readily available ( S)-mandelic acid, in 60–80% overall yield. The stereoselective electrophilic cyclization was accomplished in 20–86% yield and with 20–97% ee. In the course of this work, the presence of the amide carbonyl was found to be particularly important to guarantee a stereospecific process during the electrophilic aromatic substitution.

Highly stereoselective Friedel–Crafts alkylations of unactivated benzenes by episulfonium ion cyclizations

Intermolecular additions of highly enantiomerically enriched episulfonium ions onto activated benzene rings are known to accomplish chiral Friedel–Crafts alkylations. Unactivated benzenes are either unreactive or can give low stereoselectivities. Intramolecular cyclizations should be faster than intermolecular additions; thus, cyclization reactions should be able to avoid undesired episulfonium ion racemization. The work reported here tests that hypothesis and demonstrates that cyclizations of enantiomerically enriched episulfonium ions onto unactivated benzene rings are highly stereoselective.

Asymmetric Friedel–Crafts alkylation using chiral α-acyl-α-chloromethylsulphides

Lewis acid catalysed stereoselective Friedel–Crafts alkylation of aromatic compounds with α-(−)-menthyloxycarbonyl-α-(phenylthio)methyl chloride and α-(−)-8-phenylmenthyloxycarbonyl-α-(phenylthio)methyl chloride is described.

Synthesis of optically active 4-hydroxymandelic acid and derivatives via Regio- and Stereoselective Friedel-Crafts alkylation.

Optically active 4-hydroxymandelic esters were prepared in good yields and very high diastereoselectivity (up to 96% d.e.) via para-hydroxyalkylation of phenolic ethers. Enantiomeric pure 4-hydroxymandelic acid is available by hydrolysis.

Correction. Highly Stereoselective Friedel-Crafts Alkylations via Transannular Reactions

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCorrection. Highly Stereoselective Friedel-Crafts Alkylations via Transannular ReactionsStephen Taylor, Gay Lilley, Kevin Lilley, and Patricia McCoyCite this: J. Org. Chem. 1981, 46, 26, 5460Publication Date (Print):December 1, 1981Publication History Published online27 October 2003Published inissue 1 December 1981https://doi.org/10.1021/jo00339a618RIGHTS & PERMISSIONSArticle Views18Altmetric-Citations-LEARN 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 (151 KB) Get e-Alerts Get e-Alerts

Highly stereoselective Friedel-Crafts alkylations via epoxide transannular reactions

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHighly stereoselective Friedel-Crafts alkylations via epoxide transannular reactionsStephen K. Taylor, Gay L. Lilley, Kevin J. Lilley, and Patricia A. McCoyCite this: J. Org. Chem. 1981, 46, 13, 2709–2712Publication Date (Print):June 1, 1981Publication History Published online1 May 2002Published inissue 1 June 1981https://doi.org/10.1021/jo00326a021RIGHTS & PERMISSIONSArticle Views233Altmetric-Citations16LEARN 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 (559 KB) Get e-Alerts Get e-Alerts