A Bicyclo[3.2.0]hept-3-en-6-one Approach to Prostaglandin Intermediates

The substituted cyclopentanic structures, 6-benzyloxymethyl-7-hydroxy-2-oxabicyclo[3.3.0]octan-3-one (1), a Corey lactone derivative, and 6-exo-benzyloxymethyl-2-oxabicyclo[3.3.0]oct-7-en-3-one (2), have been obtained stereoselectively through the bicyclo[3.2.0]hept-3-en-6-one approach via 5-benzyloxymethyl-3-hydroxy-6-heptenoic acid, easily accessible from the inexpensive monoprotected cis-2-butene-1,4-diol

Reaction of Allylzinc Reagents and Zinc Enolates of Ketones with α-Amidoalkylphenyl Sulfones

α-Amidoalkylphenyl sulfones behave as N-acylimino equivalents in the reaction with functionalized allylzinc reagents. The addition products obtained using the zinc derivative of ethyl 2-(bromomethyl)acrylate can be readily transformed into α-methylene-γ-lactams using different cyclization procedures. The allylzinc reagent obtained from 3-bromo-1-acetoxy-1-propene directly affords protected 1,2-amino alcohols with a preference for the anti stereoisomer, regardless of the structure of the α-amidoalkylphenyl sulfone employed. This procedure can be extended to the use of zinc enolates obtained from α-bromo ketones and leads to the synthesis of N-protected β-amino ketones

Silicon-Tethered 1,3-Dipolar Cycloaddition of 4-Hydroxy-2-isoxazoline 2-Oxides

Silicon-Tethered 1,3-Dipolar Cycloaddition of 4-Hydroxy-2-isoxazoline 2-Oxide

Photochemical Organocatalytic Synthesis of Thioethers from Aryl Chlorides and Alcohols

Thioethers, often found in pharmaceuticals and natural compounds, typically involve metal cross-coupling reactions, high temperatures, and the use of disagreeable thiols for their synthesis. Here we present a straightforward, thiol-free organocatalytic protocol that uses mild conditions to stitch together inexpensive alcohols and aryl chlorides, yielding a diverse array of aryl alkyl thioethers. Central to this approach was the discovery that tetramethylthiourea can serve as a simple sulfur source upon intercepting photochemically generated aryl radicals. To form radicals, we used a readily available indole thiolate organocatalyst that, when excited with 405 nm light, gained a strongly reducing power, enabling the activation of typically unreactive aryl chlorides via single-electron transfer. Radical trapping by the thiourea, followed by an alcohol attack via a polar path, resulted in the formation of thioether products

Deracemization and Transacetalization of Aldehydes with Enantiomers of Betti's Base Derivatives

<div><p></p><p>Improved procedure for the deracemization of α-methyl dihydrocinnamic aldehydes (2-methyl-3-phenylpropanals) with L-(+)-tartaric acid salt of (<i>S</i>)-enantiomer of Betti's base, is presented. The method enabled the transacetalization of N,O-ketal (<i>R</i>)-enantiomer of Betti's base with various aldehydes.</p> </div

Domino Processes as a Tool for Recovering Substandard Reactions. Synthesis and Use of Nitroacetic Acid Esters and Amides

Elusive nitroacetic acid esters and amides were obtained through a halogen exchange reaction of the corresponding bromoacetic acid derivatives with polymer-supported nitrite anion. The process is flawed by a side product catalyzed degradation of the products. Domino processes turned out to be a powerful tool for overcoming such drawbacks, converting a substandard reaction into an efficient multicomponent preparation of 4-hydroxy-4,5-dihydroisoxazoles

One-Pot Direct Conversion of 2,3-Epoxy Alcohols into Enantiomerically Pure 4-Hydroxy-4,5-dihydroisoxazole 2-Oxides

A new methodology for the one-pot direct conversion of 2,3-epoxy alcohols into enantiomerically pure 4-hydroxy-4,5-dihydroisoxazole 2-oxides 1 has been found. The reaction works at room temperature and can be run at the 5−10 g scale. The mixture of 4,5-cis and 4,5-trans isomers obtained can be separated as such or as the bis-TDS ethers. A preliminary example of reductive cleavage of 1 to the corresponding amino polyol is also reported

d-Mannitol as the Chiral Source for the EPC Synthesis of Both Enantiomers of 3-Ethoxycarbonyl-4-hydroxy-2-isoxazolines and Highly Functionalized Tricyclic Systems

The EPC preparation of both enantiomers of cis- and trans 5-substituted 4-hydroxy-2-isoxazoline 2-oxides has been achieved in an enantiodivergent fashion starting from d-mannitol through the application of the tandem nitroaldol-cyclization reaction to enantiomerically pure α-mesyloxyaldehydes. These stereochemically labile aldehydes have been generated in situ and reacted under very mild domino conditions. Enantiomeric purity of the products has been assessed by 1H NMR and HPLC analyses of the corresponding Mosher's esters. The enantiomerically pure 4-hydroxy-2-isoxazoline 2-oxides have been employed as pivotal intermediates for the EPC preparation of the corresponding deoxygenated derivatives and highly functionalized tricyclic systems (HFTS) 1, useful for the preparation of 2-aminopolyols and α,α-disubstituted polyhydroxy amino acids

Enantioselective α-Benzoyloxylation of Ketones Promoted by Primary Amine Catalyst

A mixture of 9-amino-(9-deoxy)<i>epi</i>-dihydroquinidine and salicylic acid was able to promote the direct reaction of various cyclohexanones with dibenzoyl peroxide, thus affording the corresponding protected α-hydroxy carbonyl compounds in high yield and enantioselectivity. Interestingly the same catalytic salt was found to be active when 1-indanones derivatives were directly employed in the reaction with dibenzoyl peroxide furnishing chiral 1-oxo-2,3-dihydro-1<i>H</i>-inden-2-yl benzoates in high yields and enantioselectivity. Furthermore their treatment with NaBH₄ gives easy access to the corresponding enantioenriched 1,2-diols in high yields and without any loss of stereoselectivity

Solution- and Solid-Phase Synthesis of 4-Hydroxy-4,5-dihydroisoxazole Derivatives from Enantiomerically Pure <i>N</i>-Tosyl-2,3-aziridine Alcohols

Enantiomerically pure N-tosyl-2,3-aziridine alcohols are directly converted into 4-hydroxy-4,5-dihydroisoxazole 2-oxides through oxidation to the corresponding aldehydes followed by in situ tandem nitroaldol-intramolecular cyclization. This study was concerned with (i) the selection of a suitable aziridine activation, (ii) the preparation of the target 4-hydroxy-4,5-dihydroisoxazole derivatives in solution, and (iii) the elaboration of a solid-phase process using hydroxy Merrifield-supported nitroacetic acid ester