Chiral imidazolidin-4-one

Park, J., Sreekanth, P., and Kim, B. (2004) Recycling chiral imidazolidin-4-one catalyst for asymmetric Diels-Alder reactions ... 

Benaglia M, Celentano G, Cinquini M, Cozzi F, Puglisi A (2002) Poly(ethylene glycol)-supported chiral imidazolidin-4-one an efficient organic catalyst for the enantioselective diels-alder cycloaddition. Adv Synth Catal 344 149-152... 

MPEG with chiral imidazolidin-4-one =5,000" =0.2" CH3CN/H2O" En an tios elective Diels-Alder reactions Precipitation (diethyl ether) (r) [139]... 

Chiral imidazolidin-4-ones-chiral secondary amines-had already been successfully used in asymmetric synthesis before they started their own career as organo-catalysts [1]. They were deployed as chiral auxiliaries for alkylation processes [2], Michael additions [3], and aldol reactions [4], For syntheses of this class of catalyst see Reference [5]. The ability to activate both carbonyl compounds by enamine formation as well a, 3-unsaturated carbonyl compounds by intermediate formation of iminium ions makes imidazolidin-4-ones a valuable class of organocatalysts in both series. Thus, they can roughly be divided by their mode of activation into enamine [6] or iminium [7] catalysis (Scheme 4.1). These catalysts were successfully deployed in a wide range of several important enantioselective C-C bond formation and functionalization processes. Figure 4.1 shows the chiral imidazo-lidinones covered in this chapter. 

Chiral imidazolidin-4-ones operate as chiral secondary amines to activate aldehydes by enamine formation. Enamines of imidazolidin-4-one and hydrocinnamaldehyde... 

By treatment of enolizable aldehydes with benzoyl peroxide in the presence of catalytic amounts of chiral imidazolidin-4-one 4 gives direct access to enantioen-riched a-oxybenzoylated aldehydes (Scheme 4.4) [21]. The a-oxygenated aldehydes were isolated as their primary alcohols 19a-d to aid in analysis. 

Allen and MacMillan demonstrated the introduchon of a trifluoromethyl group at the a-position of enolizable aldehydes by a simple deployment of the corresponding iodonium salts [41]. Enamines of enolizable aldehydes and chiral imidazolidin-4-ones react with trifluoromethyl-benziodoxole in the presence of catalytic amounts of Lewis acids to give a-trifluoromethylated aldehydes with high degrees of enantioselectivities (Scheme 4.11). 

Furthermore, N-benzylic sulfonamides can generate stabilized carbocations under conditions of organocatalysis. This was reported for the reactions of ketones and aldehydes in the presence of catalytic amounts of chiral imidazolidin-4-ones [51]. 

Several other asymmetric inter- as well intramolecular Friedel-Crafts alkylation with a,(3-unsaturated aldehydes have been described but without any configurative assignment [91]. Asymmetric carba-Michael additions of aldehydes to enones catalyzed by a chiral imidazolidin-4-one were reported by GeUman et al. [8] (Scheme 4.23). 

Other chiral azomethine ylide precursors such as 2-(ferf-butyl)-3-imidazolidin-4-one have been tested as chiral controllers in 1,3-dipolar cycloadditions (89). 2-(ferf-Butyl)-3-imidazolidin-4-one reacted with various aldehydes to produce azomethine ylides, which then were subjected to reaction with a series of different electron-deficient alkenes to give the 1,3-dipolar cycloaddition products in moderate diastereoselectivity of up to 60% de. 

Masked chiral a-hetero substituted carboxylic acid enolates have also shown utility in dia-stereoselective additions to nitroalkenes. For example, derivatives of a-hydroxycarboxylic acids, e.g. l,3-dioxolan-4-ones (187) a-amino acids, e.g. 1,3-imidazolidin-4-ones (188) and a-amino-fi-hydroxy-carboxylic acids, e.g. methyl 1,3-oxazolidin-4-carboxylates (189) and methyl l,3-oxazolin-4-carboxy-lates (190), have been employed.1S0a Further, diastereoselective additions of chiral (3-hydroxyesters (191), via the enediolates, to nitroalkenes (40) afford predominant anr/ -P-hydroxyesters (192 Scheme... 

Chiral secondary amines such as nonracemic imidazolidin-4-ones have been found to be effective asymmetric organocatalysts in the Diels-Alder cyclization of cyclopentadiene and a,p-unsaturated aldehydes [60]. A tyrosine-derived imidazoli-din-4-one was immobilized on PEG to provide a soluble, polymer-supported catalyst 110. In the presence of 110, Diels-Alder cycloaddition of acrolein 112 to 1,3-cyclohexadiene 111 proceeded smoothly to afford the corresponding cycloadduct 113 with high endo selectivity and enantioselectivity up to 92% ee (Scheme 3.31) [61]. 

Very recently, Cozzi et al. successfully demonstrated the application of this methodology for the a-alkylation of the formyl group to enohzable aldehydes. This was achieved by a reaction of benzodithiolylium tetrafluoroborate (a stabilized carbenium ion) in the presence of several different substituted imidazolidin-4-ones [48]. After reductive removal of the benzodithiol group access to chiral a-branched primary alcohol is given. Using this method optically pure arundic acid is obtained by a three-step synthesis. 

The influence of solvents [64] and comparisons with catalysts of the diarylpro-linol series [65] were reported. For theoretical calculations on stereocontrol see Reference [66]. In addition, imidazolidin-4-one catalyzed cycloadditions have been used in several total syntheses of natural products. Intramolecular Diels-Alder reactions (IMDA) were reported as key steps in the synthesis of bicyclo-undecenes [67], amaminols [68], solanapyrones [69], telomerase inhibitor UCS1025A [70], englerin A [71], (-)-nor-platencin [72], and muironolide A [73]. In addition, asymmetric [3-1-2]-cycloadditions of azomethines were accomphshed in the presence of chiral imidazoUdinones [74]. Intermolecular cycloadditions of dihydropyridine 53 and acrolein catalyzed by imidazolidin-4-ones were reported. The chiral azabicyclo-octenol 54 was isolated as the important key intermediate in the total synthesis of lycopodium alkaloids [75] (e.g., ludduline) and oseltamivir (Scheme 4.19) [76]. 

The optically pure bis-naphthalene ortho-methoxy amide 117 cyclized to the l,4-diazepin-5-one 118 in 86% yield and with >95% ee upon refluxing in ethylenediamine for 5 h to provide the first axially chiral 1,4-diazepine derivative (Scheme 64) <2000SL1616>. This example of a type g ring closure in which the leaving group is MeOH, proceeded in lower yield with an ot/ o-hydroxy substituent, with product distribution largely redirected toward an imidazolidine derivative in which the ethylenediamine reacted solely with the ester. In the structurally simpler salicylic acid ester series, activation of the phenol as the trifluoromethanesulfonate facilitated the SnAr reaction <1995TL7595>. 

Enantiomerically pure N,N-disubstituted imidazolidine-2-one-4-carboxylates 332 can also be obtained in a one-step, simple, and highly efficient manner using a Lewis acid-catalyzed ring-expansion reaction of commercially available chiral aziridines with isocyanates. These reactions proceed both regio- and stereospecifically with retention of the configuration at the C-2 carbon of the chiral aziridines <2005CC3062>. The C(2)-N bond of the aziridine... 

The enolates of //-acylimidazolidinones derived from 1.131 generated from ephedrine 1.61 (R = H) are useful in asymmetric alkylations [447, 448] and aldol reactions [449, 450] and cuprate additions to the a,p-unsaturated acyl analogs have recently been described [451], These chiral auxiliaries are cleaved by MeONa/MeOH or LiEtBHj. Recently, Davies and coworkers have suggested the use of symmetrical AyV-diacyl-1,3-imidazolidin-2-ones 1.132, formed from diamines having a C2 axis of symmetry [452], for asymmetric aldol reactions [449]. Juaristi [453] has used peihydropyrimidin-4-ones for related purposes. 

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