A-Hydroxycarboxylic acid derivatives

Dochnahl M, Fu GC (2009) Catalytic asymmetric cycloaddition of ketenes and nitroso compounds enantioselective synthesis of a-hydroxycarboxylic acid derivatives. Angew Chem Int Ed 48 2391-2393... 

Mur 207), has received renewed interest in recent years. A fine review covering the intermolecular asymmetric Diels-Alder reaction was compiled by Mori 208>. In this article the use of terpenes and carbohydrates as chiral auxiliaries is discussed no amino acid derivatives are mentioned in this context. A chiral a-hydroxycarboxylic acid derivative was also used to achieve an asymmetric Diels-Alder reaction 209). High asymmetric induction could be detected in the intramolecular Diels-Alder reaction of chiral molecules. 

The regioselective process is suitable for the synthesis of protected (3-amino-a-hydroxycarboxylic acid derivatives (racemic, no chiral ligand added) from the corresponding acrylic acid substrates. On the other hand, 1,4-bis(dihydroquininoxy)-anthraquinone mediates enantioselective formation of A-benzyloxycarbonylphenylserine. ... 

O-SuIfonyl-a-hydroxycarboxylic acids a-Hydroxycarboxylic acid derivatives... 

When /V-arenesulfonyl-a-amino acid derived boranes 13 and 14 are used in substoichiometric amounts in order to mediate enantioselective aldol additions of a,a-dimethyl substituted ketcnc acetal 15, /J-hydroxycarboxylic esters 16 are obtained in enantiomeric excess of 84 to > 99 %3fi. 

Oxazol-4-ones 132 have been prepared by Trost and co-workers via a microwave-assisted cyclocondensation of bromo imides in the presence of NaF [86]. These products where then employed for a Mo-catalyzed asymmetric synthesis of Q -hydroxycarboxylic acid derivatives 134 (Scheme 47). 

The application of RCM to dihydropyran synthesis includes a route to 2,2-disubstituted derivatives from a-hydroxycarboxylic acids. In a one-pot reaction, the hydroxy esters undergo sequential O-allylation, a Wittig rearrangement and a second O-allylation to form allyl homoallyl ethers 8. A single RCM then yields the 3,6-dihydro-2//-pyran 9. The process is readily adapted not only to variably substituted dihydropyrans but also to 2-dihydrofuranyl and 2-tetrahydrooxepinyl derivatives and to spirocycles e.g. 10 through a double RCM (Scheme 4) <00JCS(P1)2916>. 

Azotobactin is a highly fluorescent hexadentate mixed siderophore containing a pyoverdin-like bidentate ligating chromophore, derived from 2,3-diamino-6,7-dihydroxyquinoline, a hydroxamate and a a-hydroxycarboxylic acid for Fe(in) coordination. ... 

During the interval between Vongerichten s and Schmidt s investigations, there were discovered several empirical rules through which the configuration of the a-carbon atom of many a-hydroxycarboxylic acids may be inferred. Schmidt applied three of these generalizations, the salt-acid rule and the phenylhydrazide and amide rules, to the appropriate derivatives of apionic acid Table I shows the comparisons which he published. 

Masked chiral a-hetero substituted carboxylic acid enolates have also shown utility in dia-stereoselective additions to nitroalkenes. For example, derivatives of a-hydroxycarboxylic acids, e.g. l,3-dioxolan-4-ones (187) a-amino acids, e.g. 1,3-imidazolidin-4-ones (188) and a-amino-fi-hydroxy-carboxylic acids, e.g. methyl 1,3-oxazolidin-4-carboxylates (189) and methyl l,3-oxazolin-4-carboxy-lates (190), have been employed.1S0a Further, diastereoselective additions of chiral (3-hydroxyesters (191), via the enediolates, to nitroalkenes (40) afford predominant anr/ -P-hydroxyesters (192 Scheme... 

Lewis acid-promoted asymmetric addition of dialkylzincs to aldehydes is also an acceptable procedure for the preparation of chiral secondary alcohol. Various chiral titanium complexes are highly enantioselective catalysts [4]. C2-Symmet-ric disulfonamide, chiral diol (TADDOL) derived from tartaric acid, and chiral thiophosphoramidate are efficient chiral ligands. C2-Symmetric chiral diol 10, readily prepared from 1-indene by Brown s asymmetric hydroboration, is also a good chiral source (Scheme 2) [17], Even a simple a-hydroxycarboxylic acid 11 can achieve a good enantioselectivity [18]. 

For enhancement of fluorescence, molecules with intramolecular fluorescence quenching of photoinduced electron transfer (PET) of lone pairs are used. When interacting with the target molecule, this quenching will be inhibited and therefore the fluorescence can be turned on. The l,T-binaphthyl macrocycles are most extensively applied for this method they provide multiple chiral functional groups as binding sites for analytes such as a-hydroxycarboxylic acids, amines and even amino acid derivatives [5] (Fig. 3, left). 

Unlike ethylene glycol, a-hydroxycarboxylic acids, and p-mercaptoethanol, ligands such as ethanolamine, ethylenediamine, amino acids, and 2-aminoethanethiol do not form V2L2 complexes with vanadate [46], However, weakly formed products of VL stoichiometry (—546 ppm, —556 ppm) are observed with a number of a-amino acids [47], Because the amine functionality in amino acids is not suitable for formation of the cyclic [VN]2 core expected for a dimer, then one or the other of these VL compounds may correspond to the monomeric precursor to such a dimeric product. Certainly, with the a-hydroxycarboxylic acids, the monomeric complex can be a major component in solution. Similar VL complexes have not been reported for the amino alcohols. Perusal of the available reports suggests that the amine derivatives were studied under conditions where the nitrogen functionality was protonated, so the results may be somewhat misleading. 

The addition of an a-hydroxycarboxylic acid to a tetraethylene, propylene, diethylene, or hexylene glycol titanate gives water-soluble complexes suitable for gelling aqueous solutions of hydroxyl polymers, such as poly(vinyl alcohol) (PVA), or cellulose (qv) derivatives. These are useful as binding agents for glass fibers, clays (qv), and paper coatings (85). 

This procedure offers a convenient method for the esterification of carboxylic acids with alcohols2 and thiols2 under mild conditions. Its success depends on the high efficiency of 4-dialkylaminopyridines as nucleophilic catalysts 1n group transfer reactions. The esterification proceeds without the need of a preformed, activated carboxylic acid derivative, at room temperature, under nonacidic, mildly basic conditions. In addition to dichloromethane other aprotic solvents of comparable polarity such as diethyl ether, tetrahydrofuran, and acetonitrile can be used. The reaction can be applied to a wide variety of acids and alcohols, including polyols,2 6 a-hydroxycarboxylic acid esters,7 and even very acid labile... 

Syntheses, Structures, and Properties of Molecular >. Si-Silicates Containing Bidentate l,2-Diolato(2-) Ligands Derived from a-Hydroxycarboxylic Acids, Acetohydroximic Acid, and Oxalic Acid ... 

In this paper, we report on the synthesis and structural characterization of a series of related zwitterionic (molecular) spirocyclic X Si-silicates (mononuclear A, Si-silicon(IV) complexes) containing two bidentate l,2-diolato(2-) ligands derived from a-hydroxycarboxylic acids, such as glycolic acid, 2 methyllactic acid, benzilic acid, and citric acid. In addition, some analogous zwitterionic X Ge-germanates (mononuclear X Ge-germanium(rV) complexes) are described. Furthermore, we report on the synthesis and structural characterization of related zwitterionic x Si,X Si -disilicates (binuclear X Si-... 

Zwitterionic X Si-Silicates Containing Two Bidentate Diolato(2-) Ligands Derived from a-Hydroxycarboxylic Acids... 

The results presented here suggest that a rich complex chemistry of pentacoordinate silicon with ligands derived from a-hydroxycarboxylic acids (including tartaric acid), hydroximic acids, and oxalic acid may be developed. As most of these ligands derive from natural products and as some of these X Si-silicon(IV) complexes were shown to exist in aqueous solution, compounds of this formula type are of particular interest it has been speculated in the literature [16] that silicon transport in biological systems might be based on higher coordinate Si species, and complexes such as the title compounds could be of interest as model systems in this respect. 

With regard to asymmetric synthesis, the possibility that a stereogenic center outside the sigmatropic framework can direct the stereochemical outcome of the electrocyclic process has been intensively exploited recentlyOne method for asymmetric induction has been realized with X representing a chiral carboxylic acid derivative. From the various chiral auxiliaries studied, the C2 symmetrical amide (32) seems to be the most effective, giving via its zirconium enolate) essentially 100% diastereoselectivity and erythro selection, thus permitting ready access to optically active a-hydroxycarboxylic acids (equation 40). 

Activation of a-hydroxycarboxylic acids with TBTU leads to the formation of iV,iV-dimethylcarbamoyl derivatives [197]. The coupling of this class of carboxylic acids can be safely accomplished with phosphonium salts. 

Optically active 3-amino-2-hydroxycarboxylic acid derivatives are often key components of medicinally important compounds. The synthesis of isopropyl (2i ,35)-3-amino-4-cyclo-hexyl-2-hydroxybutyrate (126) (Scheme 28) takes advantage of a [2 + 2]-cycloaddition reaction of the chiral imines 123, prepared from 63, to assemble the important diastereomeric azetidinone 124 as the crucial precursor for completion of this novel synthesis. Protection of the hydroxy group of 63 as either the TBS ether 119 or the tert-buty ether 120, followed by a DIBAL reduction at —78 °C, produces smoothly one of the aldehydes 121 or 122. Condensation of these aldehydes with either di-p-anisylmethylamine or benzylamine in the presence of anhydrous magnesium sulfate affords the four possible chiral imines 123a—d (Scheme 26). 

Recently, we succeeded in developing syntheses of dianionic A, 5 i-silicates with SiOe skeletons containing three unsymmetric bidentate ligands. These ligands derive from (i) aceto- or benzohydroximic acid, (ii) a-hydroxycarboxylic acids (such as glycolic acid and benzilic acid), or (iii) 6-hydroxycarboxylic acids of the salicylic acid type. In the case of such unsymmetric bidentate ligands, special stereochemical features have to be considered, i.e. fac/mer-isomehsm and yl/d-enantiomerism. 

Compounds 33 and 34 are silicon(IV) complexes with three bidentate ligands derived from a-hydroxycarboxylic acids. They were synthesized according to Schemes 24.2 or 24.3 and were isolated as mer-33 and fac-34T/2C4H8O2 (C4H8O2 = l,4-dioxane).f ... 

R. Tacke, O. Dannappel, M. MUhleisen, "Syntheses, Structures, and Properties of Molecular Si-Silicates Containing Bidentate l,2-Diolato(2 ) Ligands Derived from a-Hydroxycarboxylic Acids, Acetohydroximic Acid, and Oxalic Acid New Results in the Chemistry of Pentacoordinate Silicon ", in Organosilicon Chemistry 11 From Molecules to Materials (Eds. N. Auner, J. Weis), VCH, Weinheim, 1996, pp. 427-446. 

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