Diamines chiral, cyclic

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]. 

Asymmetric esterification of benzoic acid with racemic (l-bromoethyl)benzene was performed with chiral cyclic guanidines as stoechiometric bases4 the ester was obtained with ee below 15%. The chiral guanidines 6 were obtained from a chiral diamine of C2 symmetry which was tranformed first to urea and then to several guanidines through an intermediate chloroformamidinium chloride (Figure 4). 

The iodocyclization of acyclic unsaturated isoureas containing (S )-phenylethylamine as the chiral auxiliary gave chiral cyclic isoureas, which are masked 1,2-diamines. Starting from (S)-phenyl-ethylamine, the corresponding cyanamide was easily obtained, which was then converted, after allylation, to the corresponding isourea. The iodocyclization of the isourea derived from (S)-phenylethylamine afforded an equimolar diastereomeric mixture of 4,5-dihydroimidazoles 4 in 90% yield, which were easily separated by chromatography167. 

Racemization of chiral cyclic N, N-acetal, which is in equilibrium with a mixture of ketone and diamine, was utilized for DKR by intramolecular asymmetric acylation, catalysed by La-linked BINOL, to obtain a key intermediate of antithrombic agent M58163 and M58169 (Scheme 5.38) [111]. 

Diketimines can be prepared by condensation of 1,2-diketones with 2 equiv of an amine, or 1 equiv of a 1,2-diamine, by azeotropic removal of water. Either a chiral diketone or a chiral amine/diamine can be used in order to obtain a chiral diimine. In both cases, the use of 1,2-diamines is expected to provide better stereocontrol, because of the rigidity of the derived cyclic diimines. For example, the reaction of camphor 1,2-diketone 275 and racemic 1,2-diphenylethylenediamine (d,l)-26 gave the diimine 276 as a mixture of two diastereomers (Scheme 45) [138]. Reduction of 276 with sodium borohydride followed by hydrogenolysis of the N substituents afforded the camphordiamine, which was isolated as the dihydrochloride... 

The 1,2-diol is liberated easily from cyclic osmate ester by either reductive or oxidative hydrolysis.213 Importantly, the ligand acceleration has been utilized extensively for the production of chiral 1,2-diols from (achiral) olefins using optically active amine bases (such as L = dihydroquinidine, dihydroquinine and various chiral diamine ligands).215... 

In addition to standard cyclic and acyclic enamides, the effective hydrogenation of several more unusual enamides has been reported (Fig. 24.13). A concise method for the synthesis of chiral yS-amino alcohols, amino oximes and chiral 1,2-diamines has been described by Burk et al. via the enantioselective hydroge-... 

A series of diamine amides based on the phenoxypropyl amine scaffold was reported. Amide 26 displayed an hH3 Ki of 1 nM and was selective versus other histamine receptors [73]. The chirality was removed via cyclic diamines to produce tetrahydroisoquinolines, tetrahydroquinolines, benzazepines and indolines [74]. The benzazepine 27 displayed picomolar hH3 binding affinity. Pharmacokinetic issues were also identified with this diamine series, with i.v. half-lives of 10-12 h in the rat. A strategy to remove the diamine skeleton and prepare new H3... 

Nagao has disclosed bifunctional chiral sulfonamide 69 as being effective for the thiolytic ASD of meso-cyclic anhydrides in up to 98% ee when employed at the 5 mol% level for 20 h at room temperature in ether [228], Catalyst 69 is a 1,2-diamine derivative in which one of the nitrogens presents as an acidic NH group (part of an electron deficient aryl sulfonamide) and the other as a nucleophihc/basic teri-amine group with the intention to act synergistically in activation of the substrate carbonyl function and thiol nucleophile respectively (Fig. 16) [228],... 

Careful inspection of the reported photocatalytic reactions may demonstrate that reaction products can not be classified, in many cases, into the two above categories, oxidation and reduction of starting materials. For example, photoirradiation onto an aqueous suspension of platinum-loaded Ti02 converts primary alkylamines into secondary amines and ammonia, both of which are not redox products.34) ln.a similar manner, cyclic secondary amines, e.g., piperidine, are produced from a,co-diamines.34) Along this line, trials of synthesis of cyclic imino acids such as proline or pipecolinic acid (PCA) from a-amino acids, ornithine or lysine (Lys), have beer. successfuL35) Since optically pure L-isomer of a-amino acids are available in low cost, their conversion into optically active products is one of the most important and practical chemical routes for the synthesis of chiral compounds. It should be noted that l- and racemic PCA s are obtained from L-Lys by Ti02 and CdS photocatalyst, respectively. This will be discussed later in relation to the reaction mechanism. 

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],... 

A water-soluble, recyclable ruthenium(II) complex including a chiral diamine ligand has been used for asymmetric transfer hydrogenation of cyclic imines and iminiums in water, with yields and ee up to 99%.49... 

Chiral amino alcohols and diamines. The chiral vtc-diols available by catalytic asymmetric dihydroxylation of alkenes (14, 237-239) can be converted via a derived cyclic sulfite into chiral 1,2-amino alcohols and diamines as shown in equation I. The same transformations are useful in conversion of 1-alkyl- or arylethane-1,2-diols into the corresponding amino alcohols and diamines. 

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... 

Scheme 5.17).40 A three-step reduction-deprotection protocol liberated the aratz -vicinal diamine 21. A six-membered cyclic transition-state structure was proposed to account for the anti selectivity after a two-electron reduction of the nitrone. The chiral A-tert-butylsulfinyl group directs the attack of the carban-ion to the Sz-face of the C=N double bond of the imine. 

Diamination of alkenes can also be achieved intramolecularly through the nickel-catalyzed oxidation reaction, affording a wide-range of different cyclic sulfamides <07AG(E)7125>. The cyclization of sulfamide 223 proceeds in the presence of NiCU or Ni(acac)2 (10 mol%) and PhI(OAc)2 with complete selectivity, and no products other than cyclic sulfamides are observed. An initial involvement of aminometalation generates a cyclic intermediate 224. The subsequent oxidative C-N bond formation, presumably via a Ni(III) intermediate from oxidation with PhI(OAc)2, yields the bicyclic sulfamide 225. The reaction scope is well extended to the formation of spiro-cyclic sulfamides, tricyclic sulfamides and chiral substrates... 

Dimeric sapphyrins 5.138 and 5.139, containing chiral bridging units have also been synthesized. These were obtained by treating the activated form of the sapphyrin mono-acid 5.109 with a chiral diamine (i.e., 5.135 or 5.136 Figure 5.6.3). This afforded the corresponding sapphyrin dimers 5.138 and 5.139 in yields as high as 60% (Schemes 5.6.8 and 5.6.9). The cyclic sapphyrin dimer 5.140 was also prepared from the chiral diamine 5.137 and bis-acid sapphyrin 5.109. However, in this latter instance a stepwise synthetic approach was required. It involved reacting two equiva-... 

The Michael addition of malonates to cyclic enones, catalyzed by chiral Ru(77 -arene)(p-toluenesulfonyl-l,2-diamine), has been performed to afford the adduct with excellent enantiomeric excess [91,92]. A related catalyst was designed to perform sequentially the Michael addition to cyclic enone and the enantioselective hydrogenation of the ketone. Thus, the chiral ruthenium catalyst B containing trans hydride and borohydride ligands was able to enan-tioselectively (96% ee) promote the Michael addition of malonate to cyclo-hexenone. Further in situ catalytic hydrogenation (400 psi H2) was performed and led to excellent diastereoselectivity transicis 30/1 [93] (Scheme 43). 

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