Imidazolidinone. chiral catalyst

Scheme 18.5 Enantioselective reduction of unsaturated aldehydes by Hantzsch ester and imidazolidinone chiral catalysts.

Figure 18.4 Natural products obtained by the use of imidazolidinone chiral catalysts. 

Alder reactions, 1,3-dipolar cycloadditions (Jen et al. 2000), and conjugate additions of electron rich aromatic and heteroaromatic compounds can be catalyzed using chiral amino acid derived imidazolidinones as catalysts (Scheme 17 Eqs. 35-38 Paras and MacMillan 2001, 2002 Austin and MacMillan 2002 Brown et al. 2003b). In addition, highly enantioselective epoxidations (Marigo et al. 2005b) and cyclopropana-tions (Kunz and MacMillan 2005) have recently been developed. 

Analogous alkylations with unsaturated ketones can also be effected with silica-supported benzenesul-fonic acid sodium salt or, with some stereoselectivity, using a chiral imidazolidinone organo-catalyst. Optical induction can also be achieved in the addition of indole to alkyhdene malonates using bisoxazoline copper(II) complexes. ... 

Alternatively, the iminium-activation strategy has also been apphed to the Mukaiyama-Michael reaction, which involves the use of silyl enol ethers as nucleophiles. In this context, imidazolidinone 50a was identified as an excellent chiral catalyst for the enantioselective conjugate addition of silyloxyfuran to a,p-unsaturated aldehydes, providing a direct and efficient route to the y-butenolide architecture (Scheme 3.15). This is a clear example of the chemical complementarity between organocatalysis and transition-metal catalysis, with the latter usually furnishing the 1,2-addition product (Mukaiyama aldol) while the former proceeds via 1,4-addition when ambident electrophiles such as a,p-unsaturated aldehydes are employed. This reaction needed the incorporation of 2,4-dinitrobenzoic acid (DNBA) as a Bronsted acid co-catalyst assisting the formation of the intermediate iminium ion, and also two equivalents of water had to be included as additive for the reaction to proceed to completion, which... 

A-Benzylic sulfonamides, Ar Ar CHNHTs, a-alkylate aldehydes, and ketones (R CH2C0R ) to give products, Ar Ar CH CH (R )-COR, in up to 84% ee, through C-N bond cleavage, using TFA and a chiral imidazolidinone as catalysts. 

Organocatalysts To date, the main classes of organocatalysts that have been used are [42] imidazolidinone, diarylprolinol silyl ether, cinchona alkaloid, and phosphoric acid and thiourea derivatives. Essentially, two modes of activation can be considered the reversible formation of iminiums/enamines (covalent activation) with a,P-unsaturated aldehydes and ketones in the presence of primary or secondary chiral amines (Figure 35.1), and activation via hydrogen-bond formation (non-covalent activation) when chiral catalysts bearing hydrogen-bond donors are used (Figure 35.2). 

We therefore prepared a new chiral ligand, (l ,J )-isopropylidene-2,2 -bis[4-(o-hy-droxybenzyl)oxazoline)], hereafter designated J ,J -BOX/o-HOBn. To our delight, the copper(II) complex catalyst prepared from J ,J -BOX/o-HOBn ligand and Cu(OTf)2 was quite effective (Scheme 7.45). Especially, the reaction of O-benzylhydroxylamine with l-crotonoyl-3-isopropyl-2-imidazolidinone in dichloromethane (0.15 m) at -40°C in the presence of J ,J -BOX/o-HOBn-Cu(OTf)2 (10 mol%) provided the maximum enantioselectivity of 94% ee. 

Several chiral ligands have been developed for use with the rhodium catalysts, among them are pyrrolidinones and imidazolidinones.207 For example, the lactamate of pyroglutamic acid gives enantioselective cyclopropanation reactions. 

By far the greatest advances in enantiocontrolled C-H insertion reactions have been provided by Doyle and co-workers with chiral dirhodium(II) carboxamidate catalysts [7,10]. The key development here is the creation of chiral imidazolidinone-ligated dirhodium catalysts 22 to control diastereoselectivity and enhance enantiocontrol [122]. A significant example of the power of this methodology is the insertion reactions of cycloalkyl diazoacetates. With cyclohexyl diazoacetate, for example, four products are possible via C-H insertion constituted in two pairs of diastereoisomers (Eq. 5.28). 

The MacMillan group has also shown that cycloaddition reactions (see also Chapter 8) can be performed highly diastereo- and enantioselectively. The [3+2]-cycloaddition of nitrones and a,/i-un saturated carbonyl compounds in the presence of 20 mol% of a phenylalanine-derived imidazolidinone acid salt led to products with 99% ee [32]. An example of an enantioselective rearrangement reaction (see also Section 13.6) with 99% ee has been reported by the Fu group [33], who used 2 mol% of a planar chiral DMAP derivative as catalyst. 

As indicated from computational studies, the catalyst-activated iminium ion MM3-2 was expected to form with only the (E)-conformation to avoid nonbonding interactions between the substrate double bond and the gem-dimethyl substituents on the catalyst framework. In addition, the benzyl group of the imidazolidinone moiety should effectively shield the iminium-ion Si-face, leaving the Re-face exposed for enantioselective bond formation. The efficiency of chiral amine 1 in iminium catalysis was demonstrated by its successful application in several transformations such as enantioselective Diels-Alder reactions [6], nitrone additions [12], and Friedel-Crafts alkylations of pyrrole nucleophiles [13]. However, diminished reactivity was observed when indole and furan heteroaromatics where used for similar conjugate additions, causing the MacMillan group to embark upon studies to identify a more reactive and versatile amine catalyst. This led ultimately to the discovery of the second-generation imidazolidinone catalyst 3 (Fig. 3.1, bottom) [14],... 

In line with the mechanistic rationale of LUMO-lowering iminium activation, MacMillan hypothesized that intermediate 2, generated from the secondary amine 1 and an a,/f-un saturated aldehyde, could be activated towards cydoaddi-tion with an appropriate diene (Scheme 3.1). The Diels-Alder reaction would form iminium ion cydoadduct 5 that, in the presence of water, would hydrolyze to yield the enantioenriched product 6 and regenerate the chiral imidazolidinone catalyst 1. 

In 2005, the groups of List and McMillan simultaneously described excellent results in the asymmetric reduction of a,/ -unsaturated aldehydes with a prochiral center in the ft position [14, 15]. (For experimental details see Chapters 14.22.1 and 14.22.2). In both cases the catalyst used was a chiral imidazolidinone (6 or 8), and some representative examples are listed in Tables 11.1 and 11.2. The reactions were run at 10-20 mol% of catalyst, at moderate temperature (13 °C or 4 °C) over several hours. The hydride source (Hantzsch ester) was utilized in stoichiometric quantities, and the chemical yields and enantiomeric excesses proved to be... 

More recently, a fluorous organocatalyst has been used to perform selective Diels-Alder reactions of dienes with oc,(3-unsaturated aldehydes in acetonitrile-water. The chiral fluorous imidazolidinone catalyst can be recovered using fluorous silica (80-90% recovery efficiency) and reused. Figure 7.10. Further organocatalytic reactions are presented later in this chapter. 

The first enantioselective organocatalytic 1,3-dipolar cycloaddition of acyclic nitrones with acrolein and crotonal-dehyde has been reported <2000JA9874>. In particular, the reversible formation of iminium ions from a,/3-unsatu-rated aldehydes and the enantiopure imidazolidinone 535 provided ( A-4-formylisoxazolidines in high yields and ees (Equation 86). A polymer-supported version of catalyst 535 was also prepared <2004EJ0567>. The catalytic performance of various chiral pyrrolidinium salts in the cycloaddition of 1-cycloalkene-l-carboxaldehydes was also evaluated <2003EJO2782>. 

Simple L-alanine, L-valine, L-norvaline, L-isolecucine, L-serine and other linear amino acids [ 121 ] or chiral amino acids with a binaphthyl backbone [ 122] and peptides have also been used as asymmetric catalysts [123,124,125,126]. Solid-supported proline-terminated peptides have been used for heterogeneous catalysis of the asymmetric aldol reaction [ 127]. Apart from proline and derivatives, other cyclic compounds such as 5,5-dimethyl thiazolidinium-4-car-boxylate (DMTC) [128], 2-fert-butyl-4-benzyl imidazolidinones [129], (l/ ,25)-2-aminocy-clopentanecarboxylic acid [130], (5 -5-(pyrrolidin-2-yl)tetrazole, (5)-l,3-thiazolidine-4-car-boxylic acid, (5)-5,5-dimethyl-l,3-thiazolidine-4-carboxylic acid, and (5)-hydroxyproline are effective catalysts in asymmetric aldol reactions [126,131,132,133,134,135]. 

Likewise, [bis(acyloxy)iodo]arenes can be used as the oxidants in organocatalytic, asymmetric epoxidation of a,p-unsaturated aldehydes using chiral imidazolidinone catalyst 207 [266]. In a specific example, the... 

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