Approach to Animated Anthracyclines via an Intramolecular Marschalk Reaction

An anionic cyclization based approach to a novel daunomycin analog is described.     

Intramolecular Wittig Reaction: A New Synthesis of (S)‐Pyrrolam A

A straightforward synthesis of (S)‐pyrrolam A is described. The synthesis involves in situ generation of the phosphorane 3 , followed by an intramolecular Wittig reaction to furnish (S)‐pyrrolam A.     

A New Enantioselective Total Synthesis of Natural Vincamine via an Intramolecular Mannich Reaction of an Silyl Enol Ether

Natural Vincamine ( 1 ) has been synthesized in an enantioselective manner starting from the ethylpentenal 7 . In the key step a mixture of the diastereoisomeric racemates, 14 and 15 , was directly obtained from the silyl enol ether 11 and the dihydro-β-carboline 12 by the way of an intramolecular Mannich reaction of the intermediate 13 (Scheme 4). The undesired stereoisomers, 14 and 15b , were recycled to 15a using the related reversible Mannich reaction 18 ? 14 + 15 , followed by crystallization of the salt from 15a and (+)malic acid. 15a was converted to natural vincamine ( 1 ) in several steps including the known transformation 20→1 .     

Microwave Assisted Intramolecular Wittig Reaction: A Facile Method for the Synthesis of Conjugated Acetylenes

Abstract

A rapid and efficient synthesis of acetylenic compounds by the microwave assisted intramolecular Wittig reaction of β-oxo-alkylidene-triphenylphosphoranes is reported.

     

A Facile One‐Pot Synthesis of Substituted Quinolines via New Multicomponent Reaction

An efficient synthesis of quinoline derivatives is described via the reaction between ethyl chloropyruvate or alkyl 4‐chloroacetoacetate and activated acetylenic compounds in the presence of nucleophilic form of isatin in water as the solvent. Nucleophilic form of isatin is produced from the reaction of isatin and triethylamin.     

Facile Synthesis of New Functionalized Triazacyclopenta[cd]indenones Through a Multicomponent Reaction Followed by an Intramolecular Aminolysis

An efficient tandem route to the synthesis of triazacyclopenta[cd]indenone derivatives of the cyclazine family has been developed. Target compounds were obtained in moderate to good yields by Groebke–Blackburn–Bienaymé reaction involving a potassium carbonate promoted intramolecular aminolysis. This in turn will set the stage for a wide application of this useful reaction for the synthesis of structurally diverse polyheterocyclic skeletons containing the imidazo[1,2‐a]pyridine ring.     

Synthesis of diaryl acetates and oxindoles via a sequential VNS(Ar)-S(N)Ar three-component coupling reaction

[reaction: see text] The VNS and S(N)Ar reactions combine to form an efficient three-component one-pot route to diarylmethanes. The products of selected diaryl acetates provide modular 3-aryloxindole derivatives.     

New Concise and Efficient Synthesis of Rubrolides C and E via Intramolecular Wittig Reaction

A short total synthesis of rubrolides C and E has been achieved in four steps, using readily available 4‐methoxyacetophenone, 2‐bromoacetic acid, and the appropriate aromatic aldehyde, in 46 and 45% yield, respectively. Key reactions involved are α‐tosyloxylation of the aryl methyl ketone, intramolecular Wittig reaction, Knoevenagel condensation, and demethylation.     

A Novel Synthesis of Isoflavones via Copper(I)‐Catalyzed Intramolecular Cyclization Reaction

Isoflavone derivatives were synthesized via intramolecular cyclization of 3‐(2‐bromophenyl)‐3‐oxopropanal derivatives, using CuI as the catalyst, 2‐picolinic acid (=pyridine‐2‐carboxylic acid) as the ligand, K₂CO₃ as the base, and DMF as the solvent, in up to 96% yield. The synthesis is functional group‐tolerant.     

Single-step formation of structurally defined bicyclic peptides via S(N)Ar cyclization

[structure: see text]. A solid-phase methodology for macrocyclization via an S(N)Ar reaction has been developed for the unambiguous formation of bicyclic peptidic compounds in a single cyclization step. The cyclization strategy involves the reaction of a 3,5-dihydroxybenzoyl group with two nitrofluorobenzoyl moieties. The symmetry of the dihydroxy aromatic ring results in a single product, and the remaining nitro groups are subsequently reduced to anilines and acylated.     

A tandem cross-coupling/S(N)Ar approach to functionalized carbazoles

A novel route to functionalized carbazoles utilizing a tandem Suzuki cross-coupling/SNAr protocol is described. This process was found to be compatible with a variety of electron-withdrawing groups including aldehydes, esters, and sulfones. Using this method, a concise total synthesis (four steps, 50% overall yield) of the carbazole alkaloid glycosinine was achieved.     

A Facile Approach for Synthesis of Benzofuro[2,3‐c]pyridines via Intramolecular Cascade Annulations

A facile synthesis of benzofuro[2,3‐c]pyridines has been achieved under mild conditions by using ammonium acetate as the nitrogen source through intramolecular cascade annulation. This reaction could efficiently construct pyridine ring and furan ring in one step. Moreover, the key annulation step was demonstrated through dihydrobenzofuran intermediates.     

Intramolecular Redox‐Mannich Reactions: Facile Access to the Tetrahydroprotoberberine Core

Cyclic amines such as pyrrolidine undergo redox‐annulations with 2‐formylaryl malonates. Concurrent oxidative amine α‐C?H bond functionalization and reductive N‐alkylation render this transformation redox‐neutral. This redox‐Mannich process provides regioisomers of classic Reinhoudt reaction products as an entry to the tetrahydroprotoberberine core, enabling the synthesis of (±)‐thalictricavine and its epimer. An unusually mild amine‐promoted dealkoxycarbonylation was discovered in the course of these studies.     

A Facile Entry into Naphthopyran Quinones via an Annelation Reaction of Levoglucosenone. The Total Synthesis of (-)-Hongconin(1)

The annelation reactions of levoglucosenone, prepared by pyrolysis of paper, with 3-cyano-1(3H)-isobenzofuranone and 3-cyano-5-methoxy-1(3H)-isobenzofuranone have been studied. Reductive ring-opening of the annelation products with zinc/copper couple and subsequent chemical transformations provide a facile entry into the naphthopyran quinone ring system. Standard chemical transformations of the annelation product from 3-cyano-5-methoxy-1(3H)-isobenzofuranone and levoglucosenone afforded (1R)-5,9,10-trimethoxy-1-methyl-1H-naphtho[2,3-c]pyran-4(3H)-one. The lithium enolate of this compound undergoes an interesting and potentially useful reaction with oxygen to afford (3R)-4,5,9-trimethoxy-3-methylnaphtho[2,3-c]furan-1(3H)-one. When oxygen is rigorously excluded, methylation of the enolate could be performed in good yield using 10 equiv of methyl iodide in the presence of 10 equiv of DMPU. This chemistry culminated in a total synthesis of (-)-hongconin in six steps from levoglucosenone.     

Approaches to the fully functionalized DEF ring system of ristocetin A via highly selective ruthenium-promoted S(N)Ar reaction

Ruthenium-promoted intramolecular S(N)Ar reaction has allowed the construction of the fully functionalized 16-membered DEF macrocycle 4 of ristocetin A that incorporates the required arylglycine and arylserine residues as the F and E ring, respectively.     

A Stereocontrolied Entry to Racemic Eremophilane and Valencane Sesquiterpenes via an Intramolecular Diels-Alder Reaction

A stereocontrolied route to racemic eremophilane and valencane sesquiterpenes is described via a common intermediate 15 , accessible from an intramolecular Diels-Alder reaction. ¹³ C - NMR .-shift assignments of the bicyclic intermediates and products are presented.     

Asymmetric Induction via an Intramolecular Haloetherification Reaction of Chiral Ene Acetals: A Novel Approach to Optically Active 1,4- and 1,5-Diols

An asymmetric synthesis of chiral 1,4- and 1,5-diols has been developed from the ene acetals 1a and 1c, prepared from the corresponding aldehydes and chiral C(2)-symmetric diols, involving remote asymmetric induction as a key step. In the first step, treatment of 1 with I(coll)(2)ClO(4) in the presence of an alcohol afforded the macrocyclic acetals (3-5 and 7) in a highly stereoselective manner. Subsequent nucleophilic substitution of iodide followed by a Grignard reaction with complete retention of stereochemistry and a final deprotection of the diphenylethylene or diphenylpropylene unit successfully gave optically active 1,4- and 1,5-diols in good yields.     

Intramolecular Formal anti‐Carbopalladation/Heck Reaction: Facile Domino Access to Carbo‐ and Heterooligocyclic Dienes

An intramolecular domino process consisting of a formal anti‐carbopalladation followed by Heck reaction is realized. Complex oligo(hetero)cyclic scaffolds are efficiently obtained in one synthetic step from easily obtainable enyne precursors. In contrast to common syn‐carbopalladation reactions of alkyne units, the carbopalladation employed here is designed to afford an anti‐arrangement of the two new substituents across the emerging double bond. A prerequisite is that the residues next to the alkyne should lack any β‐hydrogen atoms. The method paves the way to tri‐ and tetrasubstituted double‐bond systems that have not been accessible by conventional Pd catalysis.     

A Facile Synthesis of Aldehyde and Ketone via Senochemical Barbier Reaction and Oxidation

Methyl ketone is prepared by a sonochemical Barbier reaction of methyl iodide, magnesium powder and aldehyde in Benzene/THF (9/1) solvent in a commercial ultrasonic cleaning bath (39 kHz), followed by the addition of N-chlorosuccinimide (NCS) as an oxidizing agent.     

Facile Synthesis of Azahelicenes and Diaza[8]circulenes through the Intramolecular Scholl Reaction

Carbazole-based aza[7]helicenes and hetero[9]helicenes were successfully obtained via the intramolecular Scholl reaction of 3,6-bis(biphenyl-2-yl)carbazole congeners, while the reaction of 3,6-bis(naphthylphenyl)-appended carbazole gave a triple helicene via an unexpected simultaneous double aryl rearrangement. DFT calculations suggested that the rearrangement proceeded via an arenium cation intermediate. In addition, the reaction of methoxy-appended substrate gave an azahepta[8]circulene via the concurrent C−C bond formation. These helical dyes showed circularly polarized luminescence. The azahepta[8]circulene was further transformed into deeply saddle-distorted dibenzodiaza[8]circulenes as the first example of its solution-based synthesis and unambiguous structural determination.