1.1- Diamines aldehydes

Hydroxy- aldehyde Diamine Route Ligand preparation Metal introduction Structure pdy- chelates Ref. 

Polymerization of a dicarbonyl compound, a diamine, and a metal salt, is the most direct route to polymeric metal-Schiff bases (VII-12). One of the earliest uses of this reaction was as a colorimetric analytical method for metal ions (16). This reaction has been carried out in aqueous media, dimethyl-formamide (50), and mixed solvents incorporating benzene (50, 75). As with most chelate polymers, insolubility hampers obtention of high molecular weight. Molecular weights of 2000-11,000 were reported for the products obtained from some halogen-substituted bis(salicy aldehyde)-diamine-uranyl complexes (75). 

Concern for the conservation of energy and materials maintains high interest in catalytic and electrochemistry. Oxygen in the presence of metal catalysts is used in CUPROUS ION-CATALYZED OXIDATIVE CLEAVAGE OF AROMATIC o-DIAMINES BY OXYGEN (E,Z)-2,4-HEXADIENEDINITRILE and OXIDATION WITH BIS(SALI-CYLIDENE)ETHYLENEDIIMINOCOBALT(II) (SALCOMINE) 2,6-DI-important industrial method, is accomplished in a convenient lab-scale process in ALDEHYDES FROM OLEFINS CYCLOHEXANE-CARBOXALDEHYDE. An effective and useful electrochemical synthesis is illustrated in the procedure 3,3,6,6-TETRAMETHOXY-1,4-CYCLOHEX ADIENE. ... 

Several blocked diamines or amino-alcohols are commercially available. The aldimine is an aldehyde-blocked diamine. The ketimine is a ketone-blocked diamine. The oxazolidine is a five-membered ring containing oxygen and nitrogen. The oxazolidine ring shown below is an aldehyde-blocked amino alcohol. The basic synthetic concepts of an aldimine, a ketimine, and an oxazolidine are shown below ... 

Both von Hirsch 1U) and Weingarten and White 39) have reported the amination of aldehydes and ketones by tris(dimethylamino)arsine (142) to yield the corresponding gem diamine (143) or enamine (144). Von Hirsch s... 

The chiral bicyclic imidazolidine 74 is deprotonated at the 2 position by s-BuLi and the resulting anion adds to alkyl halides, acid chlorides, chlorofor-mates, phenyl isocyanate, and aldehydes. The use of this compound as a chiral formyl anion equivalent seems to be limited, however, since the diastereoselectiv-ity in the addition to aldehydes is poor and hydrolysis of the products 75 to give aldehydes also produces cyclohexane-1,2-diamine, necessitating isolation of the aldehyde as its 2,4-dinitrophenylhydrazone (96SL1109 98T14255). 

Further substitution of benzoic acid leads to a drug with antiemetic activity. Alkylation of the sodium salt of p-hydroxy-benzaldehyde (8) with 2-dimethylaminoethyl chloride affords the so-called basic ether (9). Reductive amination of the aldehyde in the presence of ammonia gives diamine, 10. Acylation of that product with 3,4,5-trimethoxybenzoyl chloride affords trimetho-benzamide (11). ... 

Step 1 of Figure 29.14 Transimination The first step in transamination is trans-imination—the reaction of the PLP—enzyme imine with an a-amino acid to give a PLP—amino acid imine plus expelled enzyme as the leaving group. The reaction occurs by nucleophilic addition of the amino acid -NH2 group to the C=N bond of the PLP imine, much as an amine adds to the C=0 bond of a ketone or aldehyde in a nucleophilic addition reaction (Section 19.8). The pro-tonated diamine intermediate undergoes a proton transfer and expels the lysine amino group in the enzyme to complete the step. 

Chlorovinyl aldehydes react with benzene-1,2-diamine in the presence of hydogen chloride to yield 1,5-benzodiazepinium salts 15. Selected examples are given.266... 

A suspension of benzene-1,2-diamine hydrochloride in MeOH saturated with hydrogen chloride was added in small portions to a stirred solution of an equimolecular amount of a /Tchlorovinyl aldehyde in the minimum amount of ice-cooled MeOH. The mixture was allowed to warm to rt, stirred for a further 30 min and the precipitated benzodiazepiniutn chloride was collected. 

There is one report of a chiral reagent based on allylaluminum chemistry1 2 3 4 5 10. Bis(2-methyl-propyl)-2-propenylaluminum is treated with tin(II) triflate and chiral diamine ligand 4 to give a reagent, presumably a chiral allyltin species, that reacts with aldehydes at — 78 "C. Good enantioselectivity (80 -84% ee) is obtained with aromatic aldehydes, but with aliphatic aldehydes the selectivity is somewhat lower (53-64%)10. 

The C j-symnietric A, A"-bis(4-tnethylphenylsulfonyl)-l,2-diphcnyl-l,2-cthanediamine (see Sections 1.3.4.2.2.1. and 1.3.4.2.2.2.) also provides remarkable induced stereoselectivity in thioac-etatc aldol additions51. For example, (5)-phenyl thioacetate reacts with the bromoborolane available from the reaction of the diamine with tribromoborane to give the enolate. Subsequent addition to aldehydes affords the /5-hydroxy thioestcrs in good yield and enantiomeric excess51. 

The proline derived diamines 2 and 4 (vide supra) are also suitable chiral additives in enantiose-lective additions of a-unsubstituted enolates. Best results are obtained with the naphthyl derivative, as demonstrated in the tin(II) triflate mediated addition of the O-silylketene thio-acetal l-toT-butylthio-l-trimethylsilyloxyethane to aldehydes which delivers 3-hydroxythio esters in optical purities of up to 95% ee and chemical yields between 50 and 90 %24... 

When a mixture of aldehydes and (Z)-l-ethylthio-l-trimethylsilyloxy-l-propene is added slowly to a solution of tin(Il) triflate and 10-20 mol% of the chiral diamine 4 in acetonitrile, /1-silyloxy thioesters 5 are obtained in high simple diastereoselection and induced stereoselectivity. Thus, the chiral auxiliary reagent can be used in substoichiometric amount. A rationale is given by the catalytic cycle shown below, whereby the chiral tin(II) catalyst 6 is liberated once the complex 7 has formed33. 

Enantiomerically pure of-dibenzylamino-/V-tosylimines 2 arc accessible from amino acids. Since they are not suitable for storage it is advantageous to prepare them in situ from the corresponding aldehydes 1 and A-sulfmyl-4-toluenesulfonamide immediately before use. Addition of Grignard reagents affords the protected 1,2-diamines 3 in good yields (57-95%) and diastereoselectivities (d.r. 85 15 >95 5)8. Deprotection is achieved without racenuzation by reductive methods, see 4-6. 

A completely different kind of macro cycle, a calix-salen type macrocycle, was obtained in good yield by microwave irradiation of various dialdehydes and diamines [165]. This was the first example of a calix-type synthesis under microwave conditions and without the presence of a metal template. An example of a [3 -1- 3] cyclocondensed macrocycle 265, obtained from a bis aldehyde and a chiral diamine is reported in Scheme 97. 

In the future, further studies should be addressed to improve the chemose-lectivity and diastereoselectivity of the reductive coupling process, especially searching for novel reagents and milder experimental conditions. As a matter of fact, a few novel reductive couphng procedures which showed improved efficiency and/or stereoselectivity have not been further apphed to optically active imines. For example, a new electrochemical procedure which makes use of the spatially addressable electrolysis platform with a stainless steel cathode and a sacrificial aluminum anode has been developed for imines derived from aromatic aldehydes, and the use of the N-benzhydryl substituent allowed 1,2-diamines to be obtained with good yields and dl-to-meso ratios... 

Moreover, a dramatic increase of the reaction rate was observed when the coupUng of aromatic imines mediated by samariiun diiodide was carried out in the presence of both water and a tertiary amine or tetramethylethylene-diamine (TMEDA) [29], causing the almost instantaneous formation of the 1,2-diamine, although with undetermined diastereoselectivity. Similarly, the samarium diiodide promoted reductive coupling of iminiiun ions formed in situ by reacting ahphatic aldehydes with secondary amines and benzotriazole occurred at temperatures as low as - 70 °C [30]. Even in this case a mixture of diastereomers with undetermined ratio was obtained nevertheless, the item of diastereoselectivity induced by a chiral amine (auxiliary) is worthy of investigation. 

The asymmetric synthesis of unsymmetrical vicinal diamines by samarium diiodide induced reductive coupling of nitrones derived from aUphatic aldehydes with optically pure N-tert-butanesulfinyl aromatic imines has been recently reported [41]. For example, the reaction between nitrone 55 and... 

Double asymmetric induction operates when the azomethine compound is derived from a chiral a-amino aldehyde and a chiral amine, e.g., the sulfin-imine 144 [70]. In this case, the R configuration at the sulfur of the chiral auxihary, N-tert-butanesulfinamide, matched with the S configuration of the starting a-amino aldehyde, allowing complete stereocontrol to be achieved in the preparation of the diamine derivatives 145 by the addition of trifluo-romethyl anion, which was formed from trifluoromethyltrimethylsilane in the presence of tetramethylammonium fluoride (Scheme 23). The substituents at both nitrogen atoms were easily removed by routine procedures see, for example, the preparation of the free diamine 146. On the other hand, a lower diastereoselectivity (dr 80 20) was observed in one reaction carried out on the imine derived from (it)-aldehyde and (it)-sulfinamide. 

Similarly, the oxazoHdine (it,S)-147, obtained as a mixture of epimers at C2 from N,N-dibenzyl (it)-phenylalaninal and hl-benzyl (S)-valinol, reacted with Grignard reagents to form in situ the iminium ion 148, from which the diamino alcohols 149 were produced as a single diastereomer [71 ] (Scheme 23). On the other hand, when the oxazoHdine derived from the (S)-aldehyde was used, the diamino alcohol was obtained as a 70 30 mixture of diastereomers. Alhough the preparation of the primary 1,2-diamines was not explored in that paper, compoimds 149 would be the precursors of the syn 1,2-diamine... 

The Strecker reaction has been performed on the aldehyde 182 prepared from L-cysteine [86] (Scheme 28). The imine was formed in situ by treatment with benzylamine, then TMS cyanide was added to afford prevalently in almost quantitative yield the syn-diamine 183, which is the precursor of (-l-)-biotin 184. The syn selectivity was largely affected by the solvent, toluene being the solvent of choice. Since the aldehyde 182 is chemically and configurationally unstable, a preferred protocol for the synthesis of 183 involved the prehminary formation of the water-soluble bisulfite adduct 185 and the subsequent treatment with sodium cyanide. Although in this case the syn selectivity was lower, both diastereomers could be transformed to (-l-)-biotin. 

In 1999, Shi el al. showed that a diphenylthiophosphoramide derived from (li ,2i )-l,2-diaminocyclohexane could be used as a ligand in the catalytic asymmetric addition of ZnEt2 to aldehydes in the presence of Ti(Oi-Pr)4, providing the corresponding alcohols in enantioselectivities of 40-50% ee (Scheme 3.20). Another class of new ligands such as the phenylthio-phosphoramide of (7 )-1,1 -binaphthyl-2,2 -diamine was developed by the same group, and further tested as a ligand in the same conditions (Scheme 3.20). ... 

The use of chiral C2-symmetric trifluoromethanesulfonamides derived from (i )-1,1 -binaphthyl-2,2 -diamine in similar reactions to those described above has led to the formation of the expected alcohols with enantioselectivities of 43-54% ees. Better enantioselectivities were observed by Paquette et al, resulting from the use of chiral C2-symmetric VERDI (verbenone dimers) disulfonamides derived from the dimerisation of (+ )-verbenone. Stereoselectivity levels ranging from 72 to 98% ee were observed, depending on the structural characteristics of the aldehyde (Scheme 3.45). ... 

In 1991, Kobayashi el al. prepared novel chiral S/N ligands for the tin-mediated aldol reaction of silyl enol ethers with aldehydes. As an example, the reaction of benzaldehyde afforded the expected syn aldol product as the major product with a good yield and an enantioselectivity of up to 92% ee (Scheme 10.26). Moreover, other aldehydes such as substituted benzaldehydes or aliphatic unsaturated aldehydes were converted into their corresponding aldol products with enantioselectivities of more than 90% ee. It was checked that the corresponding diamine ligands provided less active complexes for the same reactions. 

High boiling polar compounds, diols, phenols, methyl esters of. dicarboxylic acids, amines, diamines, ethanolamines, amides, aldehydes and ketones. 

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