Fragmentation of β-hydroxy hydroperoxides

A β-hydroxy hydroperoxide was obtained through base-catalyzed disproportionation of a hydroperoxy endoperoxide available by singlet oxygenation of cyclohepta-1,4-diene. Vitamins E and C induce fragmentation of this β-hydroxy hydroperoxide generating aldehydes, especially in the presence of redox active metal ions such as those present in vivo, e.g., under conditions of "iron overload". This chemistry may contribute to the oxidative cleavage of polyunsaturated fatty acyls that produces similar aldehydes, which damage proteins and DNA through covalent adduction resulting in "oxidative injury".     

The asymmetric synthesis of chiral cyclic α-hydroxy phosphonates and quaternary cyclic α-hydroxy phosphonates

A highly practical, catalytic enantioselective cyclic phosphite addition to aldehydes and ketones was developed. The reaction rate of the asymmetric hydrophosphonylation was significantly enhanced by the addition of silver carbonate. Particularly, significant improvement has been achieved on the asymmetric hydrophosphonylation of unactivated ketones, giving quaternary α-hydroxy phosphonates with excellent enantioselectivity (up to 99% ee).     

Fluoroalkanosulfonyl fluorides-mediated cyclodehydration of β-hydroxy sulfonamides and β-hydroxy thioamides to the corresponding aziridines and thiazolines

An efficient method for the fluoroalkanosulfonyl fluoride-induced cyclodehydration of β-hydroxy sulfonamides and β-hydroxy thioamides to the corresponding aziridines and thiazolines is reported. Mild reaction conditions, operational simplicity, and high yields are the major advantages of this method.     

Humicola lanuginosa lipase-catalyzed enantioselective resolution of β-hydroxy sulfides: versatile synthons for enantiopure β-hydroxy sulfoxides

Humicola lanuginosa lipase-catalyzed acylation of β-hydroxy sulfides provides both the (R)- and (S)-enantiomers in high enantiomeric purity. In two cases the resolved hydroxy sulfides were oxidized to give β-hydroxy sulfoxides in >99% e.e. The effect of substituents on enantioselectivity is discussed.     

AlEt3-promoted eliminative ring-opening of β-hydroxy epoxides: highly stereoselective synthesis of terminal α-hydroxy olefins

AlEt₃-promoted eliminative ring-opening of β-epoxy alcohols leading to α-hydroxy olefins is reported. This eliminative ring-opening reaction is shown to be highly stereoselective, thus providing an alternative asymmetric synthesis for α-hydroxy olefins.     

Absolute configurational assignment of α-hydroxy acids and α-hydroxy esters from their Cupra A circular dichroism spectra

The in situ formed complexes of cuprammonium solution (Cupra A) with optically active α-hydroxy acids and α-hydroxy esters show circular dichroism spectra suitable for determination of the absolute configuration of both groups of compounds. In the long wavelength spectral region, compounds of R configuration at the α carbon atom display a positive Cotton effect of around 600 nm and a negative one at ca. 720 nm, whereas (S)-α-hydroxy acids and esters exhibit negative and positive Cotton effects, respectively, in the same spectral range.     

Organocatalytic synthesis of α-hydroxy and α-aminophosphonates

A new and highly flexible procedure is described for the synthesis of α-amino- and α-hydroxy phosphonates. In the presence of a catalytic amount of oxalic acid (10 mol %), trimethyl phosphite reacts with aldehydes or imines (generated in situ from an aldehyde and an amine) to yield the corresponding coupled products in good yield.     

Synthesis of α-hydroxy(polyprenyl) bisphosphonates

Bisphosphonates derived from natural terpenes were synthesized by phosphonylation of corresponding aldehydes. The general strategy of introduction of the phosphonate groups into the polyprenol molecule involves successive treatment of a hydroxyl compound by Swern reagent to oxidize the C-OH group into C=O and a (EtO)₃P/[PyH]⁺ClO _? ⁴ mixture to phosphylate the resulting carbonyl compound.     

Zink-bis-(2-hydroxy?thyl)dithiocarbamidat

Ohne Zusammenfassung     

Electrophilic asymmetric syntheses of α-hydroxy carboxylic acids

Asymmetric electrophilic synthesis of α-hydroxy carboxylic acids from chiral amide derivatives of tert-butyl- and trialkylsilyl- protected glycolic and lactic acids are described which lead to chiral α-hydroxy carboxylic acids in 60–95% diastereomic excess.     

Asymmetric dehydration of β-hydroxy esters via kinetic resolution

Catalytic asymmetric dehydration of β-hydroxy esters via kinetic resolution has been investigated. The kinetic resolution of rac-β-hydroxy esters in the presence of prolinol chiral ligand 2a and BrZnCH₂CO₂t-Bu can provide highly enantioenriched β-hydroxy esters 3 and 5-11 with selectivity factors ranging from 15 to 42.     

Stereoselective synthesis of syn-α-methyl-β-hydroxy esters

Boron enolates of an ethyl ketone structurally related to erythrulose react with achiral aldehydes in a highly stereoselective fashion to yield 1,2-syn/1,3-syn stereoisomers. Oxidative cleavage of the aldol adducts yields enantiopure O-formylated syn-α-methyl-β-hydroxy esters, easily cleaved to the corresponding hydroxyl-free compounds. The aforementioned ketone behaves therefore as a chiral propionate enolate equivalent.     

Rate constants for cyclizations of α-hydroxy radical clocks

The 1-hydroxy-1-methyl-6,6-diphenyl-5-hexenyl radical (4a) and the 1-hydroxy-1-methyl-7,7-diphenyl-6-heptenyl radical (4b) were prepared from the corresponding PTOC esters (anhydrides of a carboxylic acid and N-hydroxypyridine-2-thione). The key step in the synthetic method for the precursors was a coupling reaction of the respective carboxylic acids with the thiohydroxamic acid, which was conducted for ca. 5 min and followed rapidly by chromatography. Rate constants for cyclizations of radicals 4a and 4b in acetonitrile and in THF were measured directly between -30 and 60 °C by laser flash photolysis methods. The Arrhenius functions in acetonitrile are log k = 9.9-2.6/2.303RT and log k = 8.9-4.4/2.303RT (kcal mol(-1)) for 4a and 4b, respectively. Rate constants for cyclizations at room temperature of 9 × 10(7) s(-1) and 4 × 10(5) s(-1) are somewhat larger than the rate constants for cyclizations of analogous alkyl radicals. Crude rate constants at room temperature for H-atom trapping of 4a by thiophenol and 4b by t-butylthiol were k(T) = 1.2 × 10(9) M(-1) s(-1) and k(T) = 2 × 10(7) M(-1) s(-1), respectively, which are modestly larger than rate constants for reactions of alkyl radicals with the same trapping agents.     

Synthesis of fused tetrahydropyrans by hydroalkoxylation of δ-hydroxy allenes

Fused tetrahydropyrans were synthesized by silver(I)- and mercury(II)-mediated intramolecular hydroalkoxylations of δ-hydroxy allenes installed on a tetrahydropyran template. Cyclization of simple allenes was promoted by silver perchlorate to afford vinyl-substituted trans-fused bis-tetrahydropyrans, whereas cyclization of methyl-substituted allenes at the internal allenic carbon atom was achieved more effectively with a catalytic amount of mercuric triflate rather than with silver salts.     

Efficient preparation of β-hydroxy aspartic acid and its derivatives

We reported an efficient and practical synthetic route to various properly-protected erythreo-β-OH-Asp compounds, which are key β-branched a-amino acid units in coralmycin A and other peptide natural products.     

Enantioselective synthesis of β-hydroxy carboxylic acids: direct conversion of β-oxocarboxylic acids to enantiomerically enriched β-hydroxy carboxylic acids via neighboring group control

β-Oxocarboxylic acids can be reduced to the corresponding β-hydroxy carboxylic acids employing DIP-Cl^™ as a reducing agent. The β-carboxylic substituent exerts a remarkable neighboring group effect on the reduction. The reaction presumably proceeds in an intramolecular fashion through a `rigid' bicyclic transition state assembly, which produces enantioselectivities approaching 99%.     

Trifluoromethyl group induced highly stereoselective synthesis of α-hydroxy carbonyl compounds

The reaction of enolate prepared from ethyl 3-methyl-4,4,4-tri-fluorobutyrate with MoO₅-Py-HMPA complex provides ethyl (2S,3S)-2-hydroxy-3-methyl-4,4,4-trifluorobutyrate predominantly. In contrast, NaBH₄ reduction of the corresponding 2-oxobutyrate affords (2R, 3S)-hydroxyester preferentially.     

Stereocontrolled synthesis of D-α-hydroxy carboxylic acid from L-amino acids

Optically active D-α-hydroxy carboxylic acids are obtained from L-amino acids via L-α-halocarboxylic acids and their stereoselective reaction with cesium p-nitrobenzoate.