Diastereoselective Friedel-Crafts Research Articles

Enantioselective Synthesis of Pyrrolizin-1-ones via Lewis Base Catalyzed N-Allylation of N-Silyl Pyrrole Latent Nucleophiles.

Pyrrolizidine alkaloids and their derivatives often feature interesting biological activities. A class of substituted 2,3-dihydro-1H-pyrrolizin-1-one derivatives has been explored as a potential treatment for Alzheimer's disease, but enantioselective synthesis of these molecules is still elusive. We report that enantioselective N-allylation of N-silyl pyrrole latent nucleophiles with allylic fluorides followed by hydrogenation and diastereoselective Friedel-Crafts cyclization constitute an efficient synthetic route to access enantioenriched substituted 2,3-dihydro-1H-pyrrolizin-1-ones.

Cationic Cascade for Building Complex Polycyclic Molecules from Simple Precursors: Diastereoselective Installation of Three Contiguous Stereogenic Centers in a One-Pot Process.

An expedient strategy for the synthesis of polycyclic small molecules is described. The method first joins together two achiral building blocks (an enyne and an aldehyde or a ketone) using an alkynyl halo-Prins protocol. Then, in the same reaction vessel, acidic conditions initiate a cationic cascade that includes a stereospecific halo-Nazarov electrocyclization and a diastereoselective Friedel-Crafts allylation. The entire sequence forms three carbon-carbon bonds and a carbon-halogen bond, generating halocyclopentene adducts in one pot from simple precursors. The process occurs with excellent diastereocontrol, providing highly functionalized polycycles containing three tertiary or quaternary stereogenic centers in a linear array. It is even possible to install three contiguous all-carbon quaternary centers using this method.

Total Synthesis of Adunctin B.

Total synthesis of (±)-adunctin B, a natural product isolated from Piper aduncum (Piperaceae), has been achieved using two different strategies, in seven and three steps. The efficient approach features highly atom economical and diastereoselective Friedel-Crafts acylation, alkylation reaction and palladium catalyzed Wacker type oxidative cyclization.

Diastereoselective Synthesis of 5-Heteroaryl-Substituted Prolines Useful for Controlling Peptide-Bond Geometry.

A versatile diastereoselective Friedel-Crafts alkylation reaction of heteroaryl systems with a cyclic enecarbamate for the preparation of 5-heteroaryl-substituted proline analogues in good yields has been developed. These heterocyclic tethered cyclic amino acid building blocks constitute important structural motifs in many biologically active molecules. The impact of the substitution on proline cis/trans isomerization was explored by carrying out solution conformational studies by NMR on 5-furanyl-substituted proline-containing peptides. Conformational analysis revealed that the peptide bond is constrained in an exclusively trans conformation.

A Ruthenium/Phosphoramidite-Catalyzed Asymmetric Interrupted Metallo-ene Reaction.

Allylic chlorides prepared from commercially available trans-1,4-dichloro-2-butene were converted to trans-disubstituted 5- and 6-membered ring systems with perfect diastereoselectivity and high enantioselectivity under chiral ruthenium catalysis. These products contain stereodefined secondary and tertiary alcohols that originate from the trapping of an alkylruthenium intermediate with adventitious water. Key to the success of this transformation was the development of a new BINOL-based phosphoramidite ligand containing bulky substitution at its 3- and 3'-positions. As a demonstration of product utility, diastereoselective Friedel-Crafts reactions were performed on the chiral benzylic alcohols in high yield and stereoselectivity.

Epoxy and aziridinyl enolsilanes in diastereoselective inter- and intramolecular Friedel–Crafts alkylations

Diastereoselective Friedel–Crafts reactions of optically pure epoxy enolsilanes afford enantiomerically-enriched β-hydroxy-α-arylketones. Aziridinyl enolsilanes react in an analogous manner.

ChemInform Abstract: A Highly Diastereoselective Friedel—Crafts Reaction of Indoles with Isatin‐Derived N‐Sulfinyl Ketimines Towards the Efficient Synthesis of Chiral Tetrasubstituted 3‐Indolyl‐3‐aminooxindoles.

AbstractThis method can be extended to dihydroindole (IX) and pyrrole (XI) as coupling partner.

A highly diastereoselective Friedel-Crafts reaction of indoles with isatin-derived N-sulfinyl ketimines towards the efficient synthesis of chiral tetrasubstituted 3-indolyl-3-aminooxindoles.

A Lewis acid promoted highly diastereoselective asymmetric Friedel-Crafts alkylation of indoles with isatin-derived N-tert-butanesulfinyl ketimines is described. The reaction can be accomplished with ease in the presence of a catalytic amount of Bi(OTf)3, providing a series of 3-indolyl-3-aminooxindoles in excellent diastereoselectivities (up to 98% de) and yields (up to 99%).

ChemInform Abstract: Sc(OTf)3‐Catalyzed Diastereoselective Friedel—Crafts Reactions of Arenes and Hetarenes with 3‐Phenylglycidates.

AbstractIt is assumed that a benzylic cation is involved as intermediate.

Sc(OTf)3-catalyzed diastereoselective Friedel–Crafts reactions of arenes and hetarenes with 3-phenylglycidates

Five different para-substituted 3-phenylglycidates (3-phenyloxirane-2-carboxylates) were prepared and subjected to reactions with arenes and hetarenes under Lewis acid catalysis. Sc(OTf)(3) was found to effectively (5 mol%) promote a Friedel-Crafts reaction in nitromethane as the solvent. The reaction was shown to proceed stereoconvergently, which makes the intermediacy of a benzylic cation likely. The diastereoselectivities varied depending on the choice of the nucleophile and 3-arylglycidate. Best results were obtained with tert-butyl 3-anisylglycidate, which delivered the respective products with high syn-preference in diastereomeric ratios (d.r.) between 82 : 18 and >95 : 5. The observed selectivity can be explained by a model, according to which the intermediate benzylic cations adopt a preferred conformation, which allows for diastereoface-differentiation by the adjacent stereogenic center.

Diastereoselective Friedel–Crafts Alkylation of Hydronaphthalenes

An efficient and versatile synthesis of chiral tetralins has been developed using both inter- and intramolecular Friedel-Crafts alkylation as a key step. The readily available hydronaphthalene substrates were prepared via a highly enantioselective metal-catalyzed ring opening of meso-oxabicyclic alkenes followed by hydrogenation. A wide variety of complex tetracyclic compounds have been isolated with high levels of regio-, diastereo-, and enantioselectivity.

Highly diastereoselective Friedel–Crafts reaction of arenes with N-tert-butanesulfinylimino ester towards the efficient synthesis of α-arylglycines

Lewis acid-catalyzed highly diastereoselective asymmetric Friedel-Crafts alkylation of arenes with a chiral N-tert-butanesulfinylimino ester is described. The reaction can be accomplished with ease in the presence of a catalytic amount of In(OTf)(3) at room temperature, providing a series of enantiomerically enriched α-arylglycines in good yields and with excellent diastereoselectivities (up to 99% de). Highly stereoselective double Friedel-Crafts alkylation to afford dialkylation product was also investigated.

Furan Approach to Vitamin D Analogues. Synthesis of the A-Ring of Calcitriol and 1α-Hydroxy-3-deoxyvitamin D3

The A-rings of calcitriol (1α,25-dihydroxyvitamin D(3)) and 1α-hydroxy-3-deoxyvitamin D(3) were synthesized using the furan approach. The critical steps in the synthesis of the A-ring of calcitriol involved an asymmetric carbonyl-ene reaction of 3-methylene-2,3-dihydrofuran with 3-(tert-butyldimethylsiloxy)propanal, a diastereoselective Friedel-Crafts hydroxyalkylation, an oxidation of the 2,3-disubstituted furan to give a γ-hydroxybutenolide, and a Peterson olefination. The A-ring (Z)-dienol of calcitriol was synthesized in 12 steps from 3-(tert-butyldimethylsiloxy)propanal in 17% yield.

ChemInform Abstract: Highly Regio- and Diastereoselective Friedel-Crafts Alkylation of Phenols. Synthesis of 2-Hydroxymandelic Esters.

Abstract Ortho-hydroxyalkylation of phenol substrates was performed via coordinative complexes of metal phenolates with chiral glyoxylates: optically active 2-hydroxymandelic esters have been obtained with good yields and very high diastereoselectivity (up to 94% d.e.).

Highly diastereoselective Friedel–Crafts reaction of indoles with an N-tert-butanesulfinylimino ester: an efficient and practical approach to enantiomerically enriched α-(3-indolyl)glycines

An efficient, mild and general method for the preparation of highly enantiomerically enriched alpha-(3-indolyl)glycines by the transition-metal-based Lewis acid-catalyzed diastereoselective Friedel-Crafts reaction of indoles with an N-tert-butanesulfinylimino ester has been developed.

ChemInform Abstract: Diastereoselective Friedel—Crafts Alkylation of Indoles with Chiral α‐Phenyl Benzylic Cations. Asymmetric Synthesis of anti‐1,1,2‐Triarylalkanes.

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.

ChemInform Abstract: Highly Diastereoselective Friedel—Crafts Alkylation Reactions via Chiral α‐Functionalized Benzylic Carbocations.

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.

Highly Diastereoselective Friedel–Crafts Alkylation Reactions via Chiral α‐Functionalized Benzylic Carbocations

A series of chiral 1-aryl-1-alkanols, which carry different functional groups (FGs) at the 2-position, were subjected to an acid (HBF4)-catalyzed reaction with various arenes. An S(N)1 substitution reaction was observed, in the course of which 1,1-diarylalkanes were formed. In most cases (40 out of 51 reactions), yields were very good to excellent (75-99 %). The diastereoselectivity of the reaction was heavily dependent on the FG at the 2-position. If the FG was methoxycarbonyl, nitro, hydroxy, cyano, trimethylsilylethynyl, or chloro, the corresponding anti products were favored and with a decreasing preference in this order. The methoxycarbonyl-substituted substrates gave the anti products with diastereomer ratios (d.r.) that exceeded 92:8 (16 examples). Nitro- and hydroxy-substituted products were obtained in most instances with d.r. > or = 90:10, whereas cyano-, trimethylsilylalkynyl-, or chloro-substituted substrates delivered only with certain arenes products with high selectivity (d.r. > or = 90:10). The sterically more demanding FGs ethylsulfonyl, ethoxysulfonyl, and diethoxyphosphonyl induced diastereofacial selectivity in favor of the corresponding syn products, with diethoxyphosphonyl being the most effective. The substrate with FG = PO(OEt)2 delivered, with eight different arenes, the corresponding syn substitution products (d.r. = 80:20 - >95:5). The relative configuration of the products was elucidated by spectroscopic and synthetic methods. On selected examples, the reactions were shown to proceed stereoconvergently, under kinetic control, and without racemization. Depending on the functional group, the onset of the reactions between 2-methylthiophene and some representative alcohols was found to occur at a temperature Theta between -78 and -40 degrees C. There was no correlation between the selectivity and theta. A model is suggested to explain the facial diastereoselectivity based on a preferred conformation of the putative intermediate carbocation.

An Aldol Approach to the Synthesis of the anti‐Tubercular Agent Erogorgiaene.

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.

Highly Diastereoselective Friedel—Crafts Reaction of Furans with 8‐Phenylmenthyl Glyoxylate.

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.