Chiral imidazolidinone

An asymmetric version of this reaction was achieved by the use of complexes derived from chiral imidazolidinones. For example, the reaction of Danishefsky s diene with these chiral complexes occurs with both high exo endo selectivity and high facial selectivity at the dienophile [103] (Scheme 56). 

An enantioselective organocatalytic 1,3-DC reaction, based on the activation of a,fi-unsaturated aldehydes through the reversible formation of iminium ions with chiral imidazolidinones 100, was described. Good levels of asymmetric induction and diastereocontrol were achieved (up to 94% ee and 94 6 dr) <00JA9874>. 

The predicted low enantiocontrol from reactions performed with methallyl diazoacetate (Eq. 5.18) was borne out in reactions catalyzed by Rh2(MEPY)4 and Rh2(MEOX)4, but when chiral imidazolidinone-ligated dirhodium(II) was used, enantioselectivity rose to 89% ee (Table 5.8) [89]. The use of CuPF6/7b also caused relatively high enantiocontrol (87% ee) [92] which, however, decreases to 82% ee when the methyl group of 36 was replaced by n-butyl, whereas with Rh2(4S-MPPIM)4 the enantiopurity of the product corresponding to 37 was 93% ee. The A-3-phenylpropanoyl substituents of Rh2(4S-MPPIM)4 help to create a more conformationally restrictive environment that leads to enhanced enantiocontrol. 

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 chiral imidazolidinone 45 also catalyzes the Mukaiyama-Michael reaction between 2-silyloxy furans and a,/ -unsaturated aldehydes, affording enantiomeri-cally highly enriched y-butenolides (Scheme 4.18) [33]. For optimum catalytic performance, hydroxyl additives are necessary, and addition of 2 equiv. water proved best. 

A highly enantioselective Mukaiyama-Michael addition of silyl ethers, CH2= C(OSiMe3)R1, to a,/9-unsaturated aldehydes, R2CH=CHCHO, catalysed by MacMillan s chiral imidazolidinone (150), in the presence of 2,4-(N02)2C6H3C02H as an acid... 

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. 

For computational studies on the Friedel-Crafts alkylation of pyrroles and indoles catalyzed by chiral imidazolidinones, see R. Gordillo, J. Carter, K.N. Houk, Adv. Synth. Catal. 

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... 

General Procedure for the Intramolecular Michael Addition with Chiral Imidazolidinone Salt [33] (p. 90)... 

Imidazolidinones. The reaction of urea with (- )-ephedrine hydrochloride provides a chiral imidazolidinone (l),1 which can be used as a chiral auxiliary for... 

Chiral Imidazolidinones with Other Substitution Patterns. The intermediate imidazolidinone (2) can also be N-acylated by Benzoyl Chloride or Benzyl Chloroformate, and other substituents on the acetal center and/or on the N(3) nitrogen can be present, depending upon the aldehyde used for the imine formation and upon the glycine amide employed at the beginning of the synthesis. Chiral substituents, such as the 1-phenylethyl group may be placed on N(3), and the imidazolidinone may be derived from a dipeptide. Some examples are collected for (15), with references, in Table fijesg different derivatives... 

Table 1 Chiral Imidazolidinones (15) with Different Substitution Patterns...

The chiral imidazolidinone derived from urea and ephedrine hydrochloride is utilized in a diastereoselective conjugate methylation. Subsequent hydrolysis affords optically pure (—)-citronellic acid (eq 4). 

Alkylation of chiral imidazolidinones with 1,3-dibromopropane in the presence of LDA followed by a second condensation with the anion of the (-)-camphor imine of diethyl aminomethylphosphonate gives access to the phosphonic acid analogues of diaminopimelic acid (DAP) as pure diastereomers. ... 

Chiral imidazolidinones have been kinetically resolved with the aid of homochiral lithium amide... 

Chiral imidazolidinone carbene complexes undergo exo selective Diels-Alder reactions Powers TS, Jiang W,Su J,Wulff WD (1997) J Am Chem Soc 119 6438... 

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. ... 

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... 

The iminium strategy, elegantly illustrated by MacMillan, using chiral imidazolidinones as organocatalysts in a Diels-Alder reaction was then... 

Inspired by the use of chiral imidazolidinones as highly enantioselective catalysts for Diels-Alder, 1,3-dipolar cycloaddition and Friedel-Crafts reactions, Tan et have synthesized a series of novel chiral imidazolines and examined their application in MBH reactions. Up to 54% ee and high yields were obtained by using stoichiometric amounts of imidazoline 175 for the MBH reactions of various aromatic aldehydes with unactivated acrylates. Furthermore, the imidazolines were also suitable promoters for reactions between aromatic aldehydes and alkyl vinyl ketone. Using 50 mol.% of imidazoline 176, which bears a chiral methylnaphthyl group, afforded adducts in high yield with up to 78% ee (Scheme 2.86). These chiral imidazolines are readily prepared from commercially available amino alcohols and can be easily recovered for reuse without loss of product enantioselectivity. 

Some interesting organocatalyzed asymmetric double conjugate additions have been recently reported. For instance, the hydrochloride salt of chiral imidazolidinone... 

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