Chiral imidazolines

Imidazole nitrones 127 reacted with dimethyl acetylenedicarboxylate to yield imidazo[l,5-fc]isoxazoles 128, which in the presence of base afforded imidazoles 129 <00TL5407>. Chiral imidazoline nitrone 130 participated in a [3+2] cycloaddition reaction with various dienophiles to furnish imidazoisoxazoles 131 <00SL967>. A convenient synthesis of AyvyV -trisubstituted ethylenediamine derivatives from 2-methyl-2-imidazoline has been reported <00SC3307>. Dehydrogenation of 1,3-di- and 1,2,3-trisubstituted imidazolidines afforded l//-4,5-dihydroimidazolium salts <00SC3369>... 

Chiral imidazoline nitrone (88) was synthesized by condensation of hydrochloride a-amino oxime (87) with triethyl orthoformate according to Scheme 2.33... 

Alternatively, the remaining sulfate ester of 70 may serve as a leaving group for a second nucleophilic displacement reaction. When this displacement is by an intramolecular nucleophile, a new ring is formed, as was first shown in the synthesis of a cyclopropane with malonate as the nucleophile [68] and of aziridines with amines as the nucleophiles [76]. The concept is further illustrated in the double displacement on (/J,/ )-stilbenediol cyclic sulfate (72) by benzamidine (73) to produce the chiral imidazoline 74 [79]. Conversion of the imidazoline (74) to (.V,.S )-stilbenediaminc 75 demonstrates an alternative route to optically active 1,2-diamines. Acylation of 75 with chloroacetyl chloride forms a bisamide, which, after reduction with diborane, is cyclized to the enantiomerically pure trans-2,3-diphenyl- 1,4-diazabicy-clo[2.2.2]octane (76) [81],... 

The cyclic sulfates undergo ring opening with a wide variety of nucleophiles, such as hydride, azide, fluoride, benzoate, amines, and Grignard reagents. The reaction of an amidine with a cyclic sulfate provides an expeditious entry to chiral imidazolines 21 and 1,2-diamines (Scheme 9.27).169... 

Chiral imidazolines such as 4, obtained by condensation of iminoether hydrochlorides with (15,25)-1,2-diaminocyclohexane, may be metalated and alkylated with high stereoselectivity. This process is highly efficient for the stereoselective synthesis of quaternary benzylic stereogenic centers, and has been applied to a total synthesis of mesembrine (eq 6). (15,25)-1,2-Diaminocyclohexane here again gives higher diastereomeric excesses than 1,2-diphenyl ethylenediamine in this reaction. 

CD spectroscopy is useful in determining the absolute configuration of chiral imidazolines. In methanol, 116 shows a positive Cotton effect, whereas 117 shows a negative Cotton effect at 370nm (Figure 27) <1997T5359>. 

Oi,R.and Sharpless, K.B. (1991) Stereospecific conversion ofchirall,2-cyclic sulfates to chiral imidazolines. Tetrahedron Letters, 32, 999-1002. 

In 2013, chiral imidazoline-aminophenol ligands 138 combined with copper salts were successfully applied by the same group in the AFC reaction of indoles with isatin-derived nitroalkenes 139. By employing the appropriate catalyst, CuOTf/138a or Cu(OTf)2/138a, the reaction of isatin-derived nitroalkene with indole proceeded smoothly to afford 3,3 -bisindole derivatives 140 in up to 99% yield with 92% ee. l,l,l,3,3,3-Hexafluoro-2-propanol (HFIP) was found to be crucial to this transformation, with a positive effect on catalyst activity (Scheme 6.61). 

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. 

In 2006, Tan and co-workers [88] synthesized a series of chiral imidazolines and found 38 was suitable catalyst for asymmetric BH reactions of vinyl alkyl ketones with aryl aldehydes, which afforded the BH adducts in moderate to high yields and with up to 78% ee in toluene. Recently, Bugarin and Connell [89] applied the Fu s chiral DMAP 39 as catalyst in the MgL-mediated enantioselective BH reaction of cyclopentenone and aldehydes, giving the adducts in good yields and enantioselectivities. 

The complex Ru( -methallyl)2(cod)-PhTRAP [using (R,R)-(5, 5)-PhTRAP (220) and (5,S)-(R,R)-PhTRAP (221)] catalysed asymmetric hydrogenation of the substituted imidazoles and oxazoles into the corresponding chiral imidazolines and oxazolines, respectively. The optically active products (up to 99% ee) could be converted to chiral... 

Metal Catalysis Arai and Yokoyama have developed a chiral imidazoline-aminophenol-CuOTf complex-catalyzed three-component tandem reaction to create acyclic products 146 with three contiguous stereocenters (Scheme 6.20) [47]. Product 146 is mainly formed along with 147, as the minor product. The yield can be enhanced by the addition of HFIP, as weU as the stereoselectivity of the major product. Interesting fuUy substituted tetrahydro-p-carbolines (THBCs) 148 can be obtained after reduction of the nitro group of 146 and subsequent Pictet-Spengler cyclization [48]. 

In 2014, Arai and Yamamoto described asymmetric nickel-catalysed domino Michael/Henry reactions between 2-sulfanylbenzaldehydes and aromatic nitroalkenes to give the corresponding chiral 2-aryl-3-nitrochroman-4-ols, in most cases in almost quantitative yields and with good to high diastereo- and enantioselectivities of up to >98% de and 95% ee, respectively (R = H, Scheme 4.4). These reactions were promoted by an in situ generated catalyst from 10-11 mol% of chiral imidazoline-aminophenol ligand 1 and... 

Dianions derived from chiral imidazolines have been reported to undergo selective one-electron oxidation reactions followed by stereoselective radical coupling. ... 

A novel chiral imidazoline-substituted phosphoric acid catalyst (274) has been successfully applied for highly enantioselective desymmetrisa-tion of aziridines (273) with trimethylsilyl isothiocyanate (TMSNCS) (Scheme 74). ... 

Catalysts In the last decade, several catalysts have been developed based on the concept of chiral secondary amines bearing a bulky substituent. MacMillan and coworkers have developed a family of chiral imidazolines derived from a-amino acids (Scheme 33.3). 

Based on this biological approach, the research group of MacMillan [11] and List [74] reported at the same time the reduction of enals catalyzed by chiral imidazolines 26. In both cases the key to success is the use of Hantzsch ester (92) as reducing agent. The Hantzsch ester can transfer simultaneously a hydride and a proton to the enal in a 1,4-addition process. 

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