Amination reactions amino alcohol-derived chiral

In the first preparations of 128 and 129, 191 reacted with TMSNCO to give adducts 192, which were transformed to cyclic imines 193 upon dehydratation. Reaction of 193 with lithium cyclopropylacetylenide gave racemic 128 and 129, which were subjected to chiral stationary phase HPLC to isolate 128 and 129 as pure enantiomers [136, 137]. Several improvements were reported for this synthetic scheme. In particular, diastereoselective additions of lithium cyclopropyl acetylenide to the derivatives of 193 containing residues of a-phenylethyl amine or campheic acid were developed [154,155]. Moreover, an enantioselective modification of this method employing amino alcohol 194 as an asymmetric catalyst was discovered [156, 157]. Another enantioselective method involved reaction of the derivatives of 193 and cyclopropyl acetylene itself, catalysed by amino alcohol derivatives (e.g. 195) and Zn(OTf)2 [158]. 

The configuration of the amine was retained, except in the case of amino acid derivatives, which racemized at the stage of the pyridinium salt product. Control experiments showed that, while the starting amino acid was configurationally stable under the reaction conditions, the pyridinium salt readily underwent deuterium exchange at the rz-position in D2O. In another early example, optically active amino alcohol 73 and amino acetate 74 provided chiral 1,4-dihydronicotinamide precursors 75 and 76, respectively, upon reaction with Zincke salt 8 (Scheme 8.4.24). The 1,4-dihydro forms of 75 and 76 were used in studies on the asymmetric reduction of rz,>S-unsaturated iminium salts. 

Chiral fl-amino esters. The conjugate addition of primary amines to alkyl crotonates proceeds in satisfactory yield when carried out under high pressure. French chemists have recently examined this reaction using crotonates derived from chiral alcohols. Thus addition of diphenylmethylamine to 8-phenylmenthyl croton-ate proceeds in 85-90% chemical yield and in 60% de. Optical yields are increased... 

One application in liquid chromatography which does alter the separation process is the use of a specific series of derivatives to enable the separation of chiral (optical isomers) forms of alcohols, amines and amino acids using reverse-phase separation. FLEC is available in the two chiral forms (+)-l-(9-fluorenyl) ethyl chloroformate and (—)-l-(9-fluorenyl) ethyl chlorofor-mate (Figure 3.12). Reaction of two stereoisomers of a test compound (e.g. T+ and T—) with a single isomer of the derivatizing reagent (e.g. R+) will result in the formation of two types of product, T+R+ and T—R+. It is possible to separate these two compounds by reverse-phase chromatography. 

The above azomethine ylide cycloadditions have been extended to an enantioselective version involving amino alcohols both as chiral ligands and amine bases. Thus, reactions of the N-metalated azomethine yhdes derived from achiral methyl 2-(arylmethyleneamino)acetates, cobalt(II) chloride [or manganese(II) bromide], and chiral amino alcohols, 1 and 2 equiv each, with methyl acrylate as solvent have been performed to provide the enantiomer-enriched pyrrolidine-2,4-dicarboxylates with the enantioselectivities of up to 96% enantiomeric excess (ee) (128,129). However, a large excess of the metal ions and the chiral source (ligand and base) have to be employed. 

The first ionically bonded phase was presented by Pirkle it contained (/ )-3,5-dinitrobenzoyl phenylglycine [13]. The most commonly used 7t-acid moiety is the 3,5-dinitrophenyl group introduced by the reaction of 3,5-dinitrobenzoyl chloride (DNB-C1) on chiral selectors such as amino acids, amino alcohols, and amines. In addition, pentafluorobenzoyl derivatives have also been reported [14,15]. The 7r-basic phases are complimentary to the re-acidic phases. These CSPs include the presence of phenyl- or alkyl-substituted phenyl groups. Macaudiere et al. [9] designed a CSP containing both re-acidic and re-basic... 

In this chapter, recent applications of (W)-phcnylglycine amide (1) in asymmetric synthesis are presented (Figure 25.2). The first section deals with diastereoselective Strecker reactions for the preparation of a-amino acids and derivatives, whereas the second section focuses on diastereoselective allylation of imines for preparation of enantiomerically pure homoallylamines. This latter class of compounds is a well-known intermediate for the synthesis of, for example, many types of amines, amino alcohols, and P-amino acids. The final section describes reduction of imines providing enantiomerically pure amines. (S)-3,3-Dimethyl-2-butylamine and (S)-l-aminoindane will be presented as leading examples. The results described in this chapter originate from a longstanding cooperation in the field of chiral technology development between DSM Pharma Chemicals and Syncom B.V. 

The silylketene acetals derived from 10-(aminosulfonyl)-2-bomylesters were also good substrates in the electrophilic amination reactions using DTBAD. Enantiose-lective syntheses of a-amino acids were described by Oppolzer and co-workers [14]. The crystalline starting esters 33 were usually obtained in 82-96 % yield by reaction of acid chlorides with the chiral alcohol auxiliary 32 in the presence of AgCN (Scheme 13). 

In general, the chiral hydride reagent is generated in situ by reaction of a suitable metal hydride with chiral ligands such as alkaloids , sugar derivatives , amino alcohol chiral oxazolines tartaric acid derivatives chiral amines and chiral diols... 

Thiophosphorylation. Thiophosphoryl chloride will thio-phosphorylate amines, alcohols," amino alcohols, diols, and diamines. The rate of reaction decreases as each chlorine atom in replaced thus it is possible to replace each chlorine atom with a different substituent under controlled reaction conditions. Thiophosphoryl derivatives of chiral amino alcohols have been studied extensively as stereochemical probes for the stepwise hydrolyses and alcoholysis of thiophosphates (eq 2), which can lead to the... 

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