Cyclohexane-diamine catalysts, chiral

The asymmetric Mannich addition of carbon nucleophiles to imines catalyzed by the cyclohexane-diamine catalysts has developed significantly in the past decade. List and co-workers reported the asymmetric acyl-cyanantion of imines catalyzed by a cyclohexane-diamine catalyst [103], Using a derivative of Jacobsen s chiral urea catalyst, the authors optimized reaction conditions and obtained chiral iV-acyl-aminonitriles in high yield and enantioselectivities (Scheme 51). The scope of the reaction was explored with both aliphatic and aromatic imines, providing good to high selectivities for a variety of substrates. 

In this section, examples of transformations mediated by chiral bifunctional catalysts are presented, focusing on cinchona alkaloids, cinchona-alkaloid-derived thioureas, and cyclohexane-diamine catalysts (Figure 11). 

The asymmetric conjugate addition with thiol nucleophiles was demonstrated using 2-mercaptobenzaldehydes. The utiUty of the same chiral cyclohexane-diamine catalysts 35 mediated the domino Michael-aldolof 2-sulfanylbenzaldehydes with maleimides (Scheme 13.10) [28]. The products of the reaction consist of fused heterocycles in high yield and high enantiomeric ratios. The stereochemical outcome sheds insight into the proposed mechanism whereby the catalyst simultaneously activates the thiol group via the cyclohexyl tertiary amine while the maleimide is stabilized by the thiourea component... 

Keywords Asymmetric organocatalysis Bifunctional catalyst Brpnsted base Chiral scaffold Cinchona akaloid Cyclohexane-diamine Guanidine... 

Bifunctional catalysts have proven to be very powerful in asymmetric organic transformations [3], It is proposed that these chiral catalysts possess both Brpnsted base and acid character allowing for activation of both electrophile and nucleophile for enantioselective carbon-carbon bond formation [89], Pioneers Jacobsen, Takemoto, Johnston, Li, Wang and Tsogoeva have illustrated the synthetic utility of the bifunctional catalysts in various organic transformations with a class of cyclohexane-diamine derived catalysts (Fig. 6). In general, these catalysts contain a Brpnsted basic tertiary nitrogen, which activates the substrate for asymmetric catalysis, in conjunction with a Brpnsted acid moiety, such as urea or pyridinium proton. 

The synthetic utility of the bifunctional catalysts in various organic transformations with chiral cyclohexane-diamine derived thioureas was estabhshed through the works of Jacobsen, Takemoto, Johnston, Li, Wang, and Tsogoeva. In the last decade, asymmetric conjugate-type reactions have become popular with cinchona alkaloid derived thioureas. The next section presents non-traditional asymmetric reactions of nitroolefins, enones, imines, and cycloadditions to highhght the role of chiral Br0nsted base derived thiourea catalysts. 

Chiral irara-cyclohexane- 1,2-diamine was used as the bridging diamine and this led to a successful catalyst [14], often referred to as Jacobsen s catalyst (Figure 14.12). The oxidising agent is household bleach ( ) diluted and buffered... 

Among several chiral cyclic and acyclic diamines, (R,R)-cyclohexane-l,2-diamine-derived salen ligand (which can adopt the gauche conformation) was most effective in providing high enantioselectivity [38]. Further, the introduction of substituents at the 3,4, 5 and 6 positions on the aromatic ring of catalyst 39c was not advantageous, and resulted in low enantioselectivity [32,37,39]. The metal ions from first-row transition metals - particularly copper(II) and cobalt(II) - that could form square-planar complexes, produced catalytically active complexes for the asymmetric alkylation of amino ester enolates [38]. 

The A, A -bis(arenesulfonyl)cyclohexane-1,2-diamines used as chiral controllers (see also Houben-Weyl, Vol. E21, pp 1327, 3895) can also be employed as their aluminum complexes to catalyze the cyclopropanation of allylic alcohols with diethylzinc and diiodomethane. ° The bis(sulfonamide)aluminum complex was first prepared in situ in 1,2-dichloroethane and after removal of the solvent in vacuo, cyclopropanation was carried out in dichloromethane at — 20 °C. The enantioselectivities are similar to those obtained with the chiral zinc catalyst described above. However, the most characteristic feature of the chiral aluminum complex catalyzed reaction is that no decrease in the enantioselectivity was observed even at a higher concentration. An electron-withdrawing group on the benzene ring of the sulfonamide or the... 

In 2009, these same authors applied a closely related preformed nickel catalyst 9 derived from another chiral cyclohexane-l,2-diamine in the enanti-oselective a-amination of cyclic p-keto esters (Scheme 6.12). The reaction of various cyclic p-keto esters with tert-butyl azodicarboxylate provided the... 

Relatively soft, late transition-metal Lewis acids are also suitable catalysts for electrophilic fluorination. Indeed, the cationic chiral mthenium(II)-(15,25)-A,/V -bis(o-(diphenyl-phosphino)benzylidene)cyclohexane-1,2-diamine complex is a powerful catalyst for the enantioselective fluorination of (3-keto esters (Scheme 44.25). ... 

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