Enantiopure -diaminocyclohexane

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). 

Scheme 43 Synthesis of enantiopure ring-substituted 1,2-diaminocyclohexanes by transition metal catalyzed and promoted cyclization of 1,7-octadienes...

In 1994, Hanessian and co-workers [50] reported the first examples of metal-free three-dimensional triple-stranded helicates through spontaneous self-assembly of chiral C2-symmetrical diols and chiral C2-symmetrical diamines. The initial observation resulted from the utilization of enantiopure C2-symmetrical vicinal trans-1,2-diaminocyclohexane [51,52] as ligands in the asymmetric dihydroxylations of olefins [53] and as reagents for asymmetric synthesis [54], When equimolar amounts of (5,5)-frfl x-l,2-diaminocyclohexane (28) and its (i ,i )-enantiomer (29) were individually mixed with (5,5)-frfl x-l,2-cyclohexanediol and heated in refluxing benzene, crystals of the respective supraminol complexes 28 30 and 29 30 were formed quantitatively (Scheme 12). This was the physical basis for the separation of racemic diols with tr[Pg.104]

Preparative Methods The enantiopure sulfonamide la is prepared via sulfonylation of (7 ,7 )-l,2-diaminocyclohexane 2 in the presence of an excess of triethylamine (eq 1). Use of excess amine base is essential for obtaining a high yield of the bis-sulfonamide. Synthesis of related bis-sulfonamides is easily accomplished by substituting the desired sulfonyl chloride in the former procedure. Recrystallization of the bis-sulfonamide la from hexane/ethyl acetate and drying over P2O5 allows for isolation of the analytically pure reagent. Methanesulfonyl chloride and (7 ,/ )-l,2-diaminocyclohexane 2 are commercially available from a number of sources. However it should be noted that racemic 1,2-diaminocyclohexane 2 can be resolved via formation of the tartrate salt. Typically, the diamine can be obtained in >99 1 enantiomeric ratio (er) after two crystallizations from water. Determination of the enantiopurity of the diamine is accomplished via formation of the bis-3-toluyl amide and anal-... 

Trans-N,N-didecyl diaminocyclohexane was also applied by Cheng et al. to the asymmetric aldolisation of pyruvic derivatives with benzaldehydes, providing the corresponding aldol products with excellent syn diastereoselectivities and enantioselectivities of up to 99% ee (Scheme 2.31). It is important to note that enantioselectivities of up to 99% ee combined with syn diastereoselectivities of up to 90% de were also observed in the case of using aliphatic aldehydes, albeit with low yields (<32%). A synthetic application of this methodology was found in the synthesis of enantiopure furanoses, which are important precursors for the synthesis of bioactive compounds. 

Differences in A6cf2i and A5cf2Bi values reported in Table 2 clearly show that perfluoroalkylbromides are weaker electron acceptors than perfluoroalkyliodides. This is consistent with the fact that no solid co-polymer was obtained starting from racemic 1,2-dibromohexafluoropropane (Ig) and several chiral and enantiopure diamines (e. g, (-)-l,2-diaminocyclohexane, (+)-Troger s base, (-)-sparteine). The desired co-crystal formation was obtained when better electron donors were available as was the case in the solid system 12 formed between (-)-sparteine hydrobromide (13) and (5)-1,2-... 

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