Amino-amides, preparation from

Both Siegel et al. (122) and Lawrence et al. (123) have described automated systems for the purification of small arrays of amines and amides. A 48-member array of P-amino alcohols prepared from epoxides and amines was purified using SPE by Shuker et al. (124). Blackburn et al. (125) have described the purification of a 60-member 3-aminoimidazo[l,2-fl]pyridine array obtained from a multiple-component condensation, and Bussolari et al. (126) purified a small array of phenylpropyl amines obtained from dihydrocoumarins and amines. A few applications where ion-exchange resins have been substituted with other solid phases have also recently appeared. For example, the purification of several carbohydrate arrays tagged as hydrophobic O-laurates using Ci8 silica producing up to 10-30 mg of >90% pure individuals was described by Nilsson et al. (127), and Curran et al. purified fluorous-... 

In addition to the acetate aldol problem, stereoselective aldol additions of substituted enolates to yield 1,2-anti- or f/treo-selective adducts has remained as a persistent gap in asymmetric aldol methodology. A number of innovative solutions have been documented recently that provide ready access to such products. The different successful approaches to anri-selective propionate aldol adducts stem from the design of novel auxiliaries coupled to the study of metal and base effects on the reaction stereochemistry. The newest class of auxiliaries are derived from A-arylsulfonyl amides prepared from readily available optically active vicinal amino alcohols, such as cw-l-aminoindan-2-ol and norephedrine. 

The Swem oxidation of A-Fmoc-protected -amino alcohols 8 (Scheme 4) and the reduction of Weinreb amides prepared from Fmoc-a-amino acids with LiAlH4 at — 78°C were compared [83]. Both approaches afforded comparable synthetic yields, typically between 70 and 90% of the... 

So, we were able to prepare selectively syn and anti trifluoromethyl amino alcohols. The next step was a search for a chiral approach to these compounds. Two approaches have been investigated to obtain chiral anti amino alcohols first we performed the reaction of epoxy ethers 3 with the chiral dimethylaluminum amide, prepared from the fi -phenethylamine and MeaAl (Scheme 5). From 3a, the reaction was effective leading, after reduction to the anti diastereoisomers 8a and 9a stereoselectively (Scheme 5). However, the chiral amine induced no selectivity anti amino alcohols 8a and 9a were obtained in a 50/50 mixture. Their separation was performed by crystallisation of the mandelate salts. Although this access to homochiral anti amino alcohols is somehow tedious, it is general since oxirane ring opening is efficient whatever the R substituent, and since epoxy ethers, substituted with various fluoroalkyl groups, are available. ... 

Reaction of 10a and 11a with the aluminum amide prepared from MejAl and the (R)-phenethylamine and subsequent reduction step occurred with the same excellent anti/syn diastereoselection as precedently, leading respectively to anti amino alcohols 8a and 9a. These amino alcohols were obtained in an excellent purity from 10a (8a/9a = 93/7) and from 11a (9a/8a = 90/10). The stereoisomeric excess is the same as the enantiomeric excess of starting epoxy ethers. No racemization occurred in the reaction ring opening does not involve a carbenium ion, and no enolization occurs from intermediate A or B. Both enantiommc amino alcohols 12a and 13a were obtained by debenzylation with palladium hydroxide imfortunately, we have not been able to assign the absolute configuration of the asymmetric carbons of 8a and 9a (Scheme 7). 

The following example illustrates in detail the preparation of amino benzoic acids from the hot reaction product obtained by the oxidation of a xylene and containing a mixture of salt, amide salt and diamide of a phthalic acid. 

A more general method for preparation ofa-amino acids is the amidotnalmatesynthesis, a straightforward extension of the malonic ester synthesis (Section 22.7). The reaction begins with conversion of diethyl acetamidomalonate into an eno-late ion by treatment with base, followed by S 2 alkylation with a primary alkyl halide. Hydrolysis of both the amide protecting group and the esters occurs when the alkylated product is warmed with aqueous acid, and decarboxylation then takes place to vield an a-amino acid. For example aspartic acid can be prepared from, ethyl bromoacetate, BrCh CCHEt ... 

A variety of chiral amides as well as oxazolidones388 and imidazolidones389,390 may easily be prepared from amino alcohols that are derived from amino acids391 392. The addition of the lithium enolates of these amides under kinetically controlled conditions to a,/i-unsaturated esters yields optically active pentanedioates. Both syn- and //-5-amino-5-oxopcntanoates may be obtained with good diastereomeric ratios192. 

A series of imidazolidin-4-ones 117 were prepared from a-amino amides 116 that reacted with aldehydes without solvent at 200 °C imder microwave irradi-... 

Apparently there are no mild chemical reactions that can be used to transform the amide linkages in the backbone of conventional poly-(amino acids) into nonamide linkages such as ester, urethane, or carbonate bonds. Consequently, it is usually not possible to simply replace the backbone amide bonds of conventional poly (amino acids) by nonamide linkages. Pseudopoly(amino acids) must therefore be prepared from scratch by suitably designed polymerization reactions. 

The application of / -(diphenylphosphinyl)benzenesulphonic acid (58) to the synthesis of esters of amino-acids has made the work-up much simpler, since the resultant oxide is water-soluble. Diphenylphosphinyl isocyanate (59) can be prepared from diphenylphosphinic amide. 

For the preparation of sterically crowded amides amino magnesium salts have been recommended for the reaction with imidazolides in order to increase the nucleophilicity of the amine moiety. Amino magnesium salts are prepared from the appropriate amines and ethyl magnesium bromide in tetrahydrofuran [90]... 

New examples of the preparation of stannylamines, largely by established methods, are shown in Equations (164) and (165). Sodium bis(trimethylstannyl)amine can be prepared from sodium amide and a stannylamine,499 and can act as the precursor to other bis- and tris(stannyl)amino compounds.499 500 The tristannylamines are planar about the nitrogen, with the unshared pair in a 2p orbital. Tris(chlorodimethylstannyl)amine, with five-coordinate tin, is close to centrosymmetrical, and reacts with pyridine to give a tetrastannabicyclo[3.1.1]heptane.501... 

More recently, the chiral phosphonate 85 has been used as a CDA with chiral amines to form diastereomeric phosphonic amides (86)79 which are analyzed by 31P-NMR spectroscopy for the determination of enantiomeric ratios. The reagent is readily prepared from (5)-2-butanol and phosphorous trichloride, and all a-amino acids and amines thus far examined react quantitatively in a few hours at room temperature in aqueous ethanol79. 

The 1,3-dipolar cycloaddition of equimolar amounts of enamide and aryl azide at room temperature, over a period of time (3 days to 10 months), affords the A -1,2,3-triazolines (733) as stable crystalline products (Equation (63)). In refluxing ethanol, however, the reaction yields the corresponding triazoles as the major product with loss of the amides <92JOC3075>. 5-Amino-1-aryl-1,2,3-triazolines (e.g., (734)-(735)) are readily prepared from the [3 -I- 2] cycloaddition of azides to... 

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