1.2- diamino-cyclohexane

The reductive amination of ketones can be carried out under hydrogen pressure in the presence of palladium catalysts. However, if enantiopure Q -aminoketones are used, partial racemization of the intermediate a-amino imine can occur, owing to the equilibration with the corresponding enam-ine [102]. Asymmetric hydrogenation of racemic 2-amidocyclohexanones 218 with Raney nickel in ethanol gave a mixture of cis and trans 1,2-diamino cyclohexane derivatives 219 in unequal amounts, presumably because the enamines are intermediates, but with excellent enantioselectivity. The two diastereomers were easily separated and converted to the mono-protected cis- and trans- 1,2-diaminocyclohexanes 220. The receptor 221 has been also synthesized by this route [103] (Scheme 33). 

Diamine chelate complexes are more stable than the monodentate amine heterocycles and, therefore, can be studied under physiological conditions. The imidazole complexes are unstable in aqueous solution and decompose rapidly to technetium oxide hydrate. Six-membered ring chelates are significantly less stable than five-membered ones. Lesser flexibility of the ligand, such as 1.2-diamino-cyclohexane, parallels somewhat lower stability of the complex [53] ... 

Figure 58 Partial 13C NMR spectra for (R,R)-trans-1,2- diaminocyclohexane-( )-irani-l, 2-cyclopentanediol and (R)-l,l -bi-2-naphthol adducts. Left (a) (R,R)-trans-1, 2-diaminocy-clohexane (b) inms-( )cyclopentanediol (c) 1 1 adduct between (R,R)-trans-1, 2-diamino-cyclohexane and tranx-( )-cyclopentanediol (d) 0.5 1 adduct between (R,R)-trans-1, 2-diaminocyclohexane and Znms-(+/-)-cyclopentanediol. Right (a) (R,R)-trans-1, 2-diami-nocyclohexane (b) 1 1 adduct between (i )-l,l -bi-2-naphthol and trans-( )-1, 2-diaminocyclohexane (c) 1 1 adduct between R,R)-trans-1, 2-diaminocyclohexane and (2 )-1,1 -bi-2-naphthol (e.e. 35%) showing molecular recognition and chiral discrimination of the diastereomeric supraminols (d) 1 1 adduct between (R)-l,l -bi-2-naphthol and (R,R)-trans-1, 2-diaminocyclohexane [60],...

Others CPSs have been prepared in a similar way and characterized at different steps by physicochemical methods. For example, the structure of the chiral selector iV-[2 -(5)-hydroxypropyl]-Ar, /V -bis(3,5- dichlorobenzoyl)-(f ,f )-tra i- 1,2-diamino-cyclohexane was solved by X-ray analysis and its absolute configuration confirmed unambiguously [73]. These CPS phases were used to resolve a large number of racemic mixtures belonging to different classes of organic compounds, such as a-aryloxyacetic acids, alcohols, sulfoxides, selenoxides, phosphinates, amino acids, amino alcohols, etc. 

As we have seen in Chapter 1, it is very difficult to introduce chirality in the inamedi-ate vicinity of the carbene centre [23,24,46], An elegant way to circumnavigate this is to introduce a functional group on the carbene that can act as the carrier of chirality in the metal complex (see Figure 2.6). Excellent examples are a Cp scaffold for planar chiraUty [47 9] or the binaphthyl group for axial chirahty [50-52], The tether itself can be used as the chiral backbone as is the case in functionalised carbenes derived from 1,2-diamino cyclohexane [53,54],... 

Figure 3.47 Synthesis of a chiral imino functionalised NHC ligand from a 1,2-diamino cyclohexane scaffold.

The 2-chloro-imidazolium salt is accessible from the corresponding thione that can be synthesised by Kuhn s method [260] from the diamine. Using a chiral 1,2-diamino-cyclohexane scaffold produces a chiral samrated carbene. 

Another interesting approach to an NHC ligand with a chiral, bridging wingtip group was introduced by Perry et al. [45] and uses enantiomerically pure 1,2-diamino-cyclohexane as the scaffold. Reaction with chloroacetic acid chloride and subsequently with DIPP-imidazole yields the imidazolium salt that can be reacted with silver(I) oxide [46] to the respective silver(I) NHC complex. Subsequent carbene transfer to palladium(II) renders the chiral palladium(II) carbene transfer that can be used in catalysis (see Figure 5.9). 

Boron was removed from distilled water by using a column of Dowex-1 (OH -form). For the photometric determination as a boron-curcumin complex, interfering ions were removed on small columns of Dowex-1 (formiate) and Dowex-50 (Na ) For the evaporation and ashing step, calcium hydroxide was used (recovery of one ng ca. 80%). By complexation of bivalent ions with 1,2-diamino-cyclohexane-NJ, N, N -tetra-acetic acid, water samples at pH 5.5 passed through a colunm of Dowex 50 W-X 8 (NH4) for the determination of barium Elution followed with 4 M nitric acid. Particular references for the separation of barium from sodium, calcium and sulfate are given. 

A standard method used to separate single polyamine components from these fractions involves neutralization of the amines with a mineral acid and subsequent fractional crystallization of the salt adducts. Some purified polyethylene polyamines have been obtained from DETA (8), TETA (9), and TEPA (10), as well as from technical grade 1,2-diamino-cyclohexane, DACH (11), using this procedure. Fractional crystallization of certain polyamine hydrates has also been reported (12). The difficulties associated with these methods—poor yields and low separation selectivi-ties—appear in the literature, however (13, 14). 

The most studied catalytic system is the one derived from 1,2-diamino-cyclohexane-derived Schiff base, presented for the first time by North and Belokon in 1998 for the cyanosilylation of aldehydes. In contrast to many catalysts known to date that require more than 10 mol% of loading and low temperatures, the catalyst 18 employed here was efficient at 0.1 mol% for a complete conversion at room temperature (0.01 mol% for 80% conversion. Scheme 7.14). Enantiomeric excesses from 30 to 86% were obtained from aromatic aldehydes and lower 44-46% enantiomeric excesses were observed from aliphatic ones (propanal and pivalaldehyde). 

An asymmetric approach to differentially substituted cw-1,2-diamino cyclohexanes also utilized the Curtius rearrangement. The chiral diamine products are components of biologically active small molecules and useful as conformationally restricted peptide-like scaffolds. y Amino acid 54 was prepared in enantiomerically pure form using asymmetric reductive amination and converted to phthaloyl-protected y -amino acyl azide 56. Curtius rearrangement, followed by addition of benzyl alcohol and further heating provided chiral c/5-1,2-diamine 57 with orthogonal A-protection. 

A similar strategy was developed by Kureshy et al. [45]. In 1998, Sherrington et al. [46] reported the application of polymer-bound Mn(lll)-salen catalyst in the epoxidation of 1-phenylcyclohex-l-ene, resulting in 49% yield and 91% ee, which are comparable to results obtained with the nonimmobilized Jacobsen catalyst. The synthesis of these catalysts started from polymer-bound salicy-laldehyde derivatives, which were first treated with 1,2-diamino cyclohexane and then with a second salicylaldehyde derivative. In the last step, the manganese complex was formed. Polymethacrylate was used as polymeric backbone. A similar approach was employed by Peukert and Jacobsen [47] to immobilize this catalyst to polystyrene. 

More importantly the amines are also responsible for activity in cisplatin-resistant cells (Figure 2.4). This has important clinical implications and the demonstration of the lack of cross resistance in 1,2-diamino-cyclohexane complexes [51] is responsible for much of the interest in developing these particular complexes. This ligand is also of interest from a mechanistic point of view because of the demonstration that different stereoisomers also have different biological properties. 

Figure 2.46 Cycloaliphatic amines (a) isophorone diamine, (b) 1,2-diamino-cyclohexane, (c) 4,4 -diaminodicyclohexylmethane, (d) N-aminoethylpipera zine, (e) m-xylylenediamine...

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