Bifunctional Thiourea‐Catalyzed Asymmetric Addition of Anthrones to Maleimides

Abstract

For the first time, the addition of anthrones to maleimides catalyzed by bifunctional thiourea catalysts is reported. The thiourea moiety is able to activate the maleimide and the tertiary amine deprotonates the anthrone, furnishing the final DielsAlder or Michael adducts in excellent yields and enantioselectivities.Keywords: anthrones; Diels-Alder cycloaddition; enantioselective; maleimides; Michael addition; organocatalysis Anthrones are important compounds in natural products and in medicinal chemistry.[1] They are isolated, either in the free form or as O-or C-glycosides, from a wide variety of natural sources (plants, shrubs), such as rhubarb, Cassia, and "Cµscara sagrada" bark, among others.[2] From the chemical standpoint, anthrones and their enol tautomers, the 9-anthrols, play a central role in the chemistry of anthracenes, because by oxidation of the central ring they afford 9,10-anthraquinones, extremely valuable compounds as pigments or anticancer agents.[3] On the other hand, the reduction of anthrones provides anthracenes, useful in the preparation of dyestuffs and of optoelectronic materials.[4]The parent anthrone, namely 9A C H T U N G T R E N N U N G (10H)-anthracenone, has been classically used as a reagent for the analytical determination of sugars and many of its derivatives have interesting biological properties: antimicrobial, laxative, antipsoriatic or as telomerase inhibitors.[5] Recently, it has been found that some anthrone derivatives may display potent and selective antitumour activity. [6] Anthrone has been used as the diene component in Diels-Alder cycloadditions with a variety of dienophiles. [7,8] Kinetic studies performed by Koerner and Rickborn [8] on the reaction between anthrone and Nmethylmaleimide showed that a substantial acceleration took place in basic solvents such as DMF, pyridine or triethylamine, or upon the addition of a small quantity of triethylamine to a chloroform or THF solution of the reactants.[8] These results were interpreted by a catalytic oxyanion acceleration of the process, probably via the anthrone enolate (Scheme 1).Building upon these results, Riant and Kagan investigated the effect of chiral bases in the same reaction, [9] finding that quinidine and prolinol were the most enantioselective catalysts (up to 61% ee was achieved with a 10 mol% loading of quinidine in chloroform at À50 8C). Later on, Yamamoto and coworkers [10] described the asymmetric cycloaddition of anthrone and maleimides catalyzed by C 2 -chiral 2,5-bis(hydroxymethyl)pyrrolidines, obtaining good enantioselectivities in some instances (up to 87% ee). The enantioselective Diels-Alder cycloaddition of substituted anthrones with maleimides catalyzed by chiral bicyclic guanidines, which takes place with excellent yields and enantioselectivities (85-99% ee) when run in dichloromethane solution at À20 8C, was reported in 2006 by Tan and co-workers.[11] This reaction showed, however, a very strong temperature dependence, and the enantiomeric purity of the Diels-Alder adduct was much...

Recent Advances in Organocatalytic Methods for Asymmetric CC Bond Formation

“…A chiral thiourea catalyst 53 gives excellent results. The N‐protecting group has an essential influence on selectivity and on the reaction pathway (Scheme ) 169…”

“…The N-protecting group has an essential influence on selectivity and on the reaction pathway (Scheme 79). [169] Deng et al deployed a cinchona derivative 154 catalyst for cycloadditions between nitroalkenes and 2-pyrones. The [2.2.2]-bicyclic reaction products containing a quaternary carbon center are achieved in good yields and up to very high selectivity (Scheme 80).…”

Enantioselective Michael reaction of anthrone catalyzed by chiral tetraoxacalix[2]arene[2]triazine derivatives

“…In this eld of study, similar to the case of a Michael donor, various carbon-centered nucleophiles such as aldehydes and ketones, [15][16][17][18][19] malonate esters, [20][21][22] ketoesters, 23 and 1,3-diketones [24][25][26] have been comprehensively studied; in contrast, not much development has taken place in the improvement of the usage of anthrone as a nucleophile for the Michael addition reaction. [27][28][29][30][31][32][33] Calixarenes and macromolecules bearing one or more calixarene platforms are known as efficient supramolecular materials. Heteroatom-bridged calixaromatics, also called heteroaromatic calixarenes, are a novel group of macrocyclic host compounds in supramolecular chemistry.…”

Urea Derivative Catalyzed Enantioselective Hydroxyalkylation of Hydroxyindoles with Isatins

“…Takemoto’s catalyst is the commercially available chiral organocatalyst, which was first synthesized by Takemoto in 2003 [58]. Then, they were used efficiently for a wide range of diastereoselective and enantioselective reactions [59,60,61,62,63,64,65]. We herein first reported the enantioselective hydroxyalkylation of hydroxyindoles with isatins by employing Takemoto-type catalysts 1a–1h bearing (thio)urea-tertiary amine moiety (Figure 1).…”