Cyclohexane-1,2-diamines

Dynamic polymeric systems utilizing the C=N exchange reaction have been reported by Lehn s group. They have suggested a polymerization system consisting of a fluorene-based dialdehyde monomer 4, cyclohexane diamine 5, and fluorene-based diamine 6 as a comonomer (Scheme 8.2) [20,21]. In principle, a 1 1 1 mixture of all monomers in ethanol was expected to yield the two-component polymers 7 and 8 together with all component-mixed polymers. However, polymer 7 was dominantly yielded (80%) due to the nucleophilicity of diamines. The nucleophilic-ity of aliphatic diaminocyclohexane is much higher than that of aromatic... 

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 scope of Michael additions with catalysts containing cyclohexane-diamine scaffolds was broadened by Li and co-workers [95]. When screening for a catalyst for the addition of phenylthiol to a,p-nnsatnrated imides, the anthors fonnd that thiourea catalyst 170 provided optimal enantioselectivities when compared to Cinchon alkaloids derivatives (Scheme 41). Electrophile scope inclnded both cyclic and acyclic substrates. Li attributed the enantioselectivity to activation of the diketone electrophiles via hydrogen-bonding to the thiourea, with simultaneous deprotonation of the thiol by the tertiary amine moiety of the diamine (170a and 170b). Based on the observed selectivity, the anthors hypothesized that the snbstrate-catalyst... 

The asymmetric conjugate additions with thiol nucleophiles was further expanded to 2-mercaptobenzaldehydes [98]. Wang had previously developed a domino Michael-aldol reaction promoted by Cinchona alkaloids, and now illustrated the utihty of cyclohexane-diamine bifunctionalized catalysts for the domino... 

Takemoto and co-workers designed a small hbrary of thiourea cyclohexane-diamine derived catalysts for the Michael reaction of malonates to nitrolefins [15]. The authors observed an interesting trend in catalysis the reaction only proceeded enantioselectively and in decent yields when the catalyst possessed both thiourea... 

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. 

Fig. 7 Proposed role of cyclohexane-diamine thiourea 166 for the asymmetric aza-Henry reaction...

Jacobsen et al. found that cyclohexane-diamine bifunctional catalyst 216 promoted the enantioselective hydrophosphonylation of A-benzyl imines [110]. Using a modified... 

Berkessel and co-workers have demonstrated the utility of the bifunctional cyclohexane-diamine catalysts in the dynamic kinetic resolution of azalactones (Schemes 60 and 61) [111, 112]. The authors proposed that the urea/thiourea moiety of the catalyst coordinates and activates the electrophilic azlactone. The allyl alcohol nucleophilicity is increased due to the Brpnsted base interaction with the tertiary amine of the catalyst. 

Wang and co-workers reported a novel class of organocatalysts for the asymmetric Michael addition of 2,4-pentandiones to nitro-olefms [131]. A screen of catalyst types showed that the binaphthol-derived amine thiourea promoted the enantiose-lective addition in high yield and selectivity, unlike the cyclohexane-diamine catalysts and Cinchona alkaloids (Scheme 77, Table 5). 

A comparison of the rotatory dispersion curves of (+ )s46[Co-( — )-PDTA] and ( + )546[Co-( —)-CDTA] indicates that these ions have the same configuration around the cobalt ion (25). It follows then that (- cyclohexane-diamine has the configuration of Fig. 8. These procedures for fixing configurations will be utilized in subsequent sections for studying the properties of the conformations. 

The treatment of complex ion equilibria in solution is analogous to the treatment of weak acids. One of the best known chelators is the well-known EDTA (ethylene diamine tetraacetic acid). The metal stability constants for EDTA are very high, which indicates strong complexes. Various other compounds are available with high metal-stability constants for agricultural or environmental uses. Some of the more important ones are DPTA (diethylene triamine pentaacetic acid), CyDTA (cyclohexane diamine tetraacetic acid), EDDA [ethylene diamine di (0-hydroxyphenyl acetic acid], or Chel-138. 

Several novel clathrochelate complexes have also been prepared via the oxidation of preformed sarcophaginates. The cyclohexane-diamine fragments of char sarcophaginate underwent oxidation with mercury(II) acetate in acetic acid to give the diamide complex (Reaction 28). In addition, one of the cyclohexane rings has also been aromatized ... 

Beside the cross aldol reaction, the Mannich reaction, too, has been the object of successful efforts using organocatalysis. The use of small organic molecules such as proline, cyclohexane diamine and Cinchona alkaloid-derived catalysts has proven extraordinarily useful for the development of asymmetric Mannich reactions in traditional polar solvents such as DMSO, DMP, DMF, etc. However, very few studies have been conducted so far in non-conventional solvents. 

The effect of solvent was also studied and complexing solvents such as THF or Et20 inhibited the cyclopropanation reaction. Furthermore, the presence of an unprotected allylic alcohol was found to be essential, since the methyl or benzyl ether derived from cinnamyl alcohol afforded almost racemic cyclopropanes. This method has also been extended to the enantioselective cyclopropanation of vinylsilanes and -stannanes (Scheme 4) [13]. The corresponding optically active silyl- and stannyl-substituted cyclopropyhnethanols were obtained in the presence of the chiral N,iV-bis(p-nitrobenzenesulfonyl)-l,2-cyclohexane-diamine 9. 

This reaction has been applied for preparative purposes mainly in the hydroaromatic series. For instance, according to Wallach,75 the thujone obtained from thuja oil gives with ammonium formate an aminothujone whose hydrochloric acid salt affords thujene on dry distillation and Harries and Antoni76 obtained 2,3-dihydrotoluene analogously from 1 -methyl-1 -3-cyclohexane-diamine. 

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