Synthesis and conformational analysis of fructose-derived scaffolds: molecular diversity from a single molecule

Bi- and tricyclic compounds were synthesized starting from fructose. The different hydroxyl groups present in fructose were exploited in the formation of a number of conformationally constrained sugar-based scaffolds, including azido acids. Introduction of an azido group and carboxy terminus into different bicyclic iodo ethers, allowed the synthesis of different conformationally constrained azido acids. Conformational analysis of compounds 10, 11, 17, and 20 by NMR experiments assisted by molecular mechanics, allowed the determination of the distances between the relevant functional groups, that is the azido and carboxy functionalities.     

Safe radical azidonation using polystyrene supported diazidoiodate(I)

Aldehydes are converted to acyl azides and benzyl ethers to azido ethers by treatment with polymer supported iodine azide in MeCN at 83 °C. The reaction provides a safe and convenient alternative to the use of iodine azide in radical azidonations.     

Direct Catalytic Asymmetric Aldol Reaction of an α‐Azido Amide

A direct aldol reaction of an α‐azido 7‐azaindolinylamide, promoted by a Cu‐based cooperative catalyst, is documented. Aromatic aldehydes bearing an ortho substituent exhibited diastereodivergency depending on the nature of the chiral ligands used. Smooth reactions with ynals highlighted the broad substrate scope. A vicinal azido alcohol unit in the product allowed direct access to the corresponding aziridine and facile hydrolysis of the 7‐azaindolinylamide moiety furnished enantioenriched β‐hydroxy‐α‐azido carboxylic acid derivatives.     

Conversions of Allyl Ethers in a Superbasic Medium

Conversions of alkyl allyl and terpenoid allyl ethers in a superbasic medium (dimethyl sulfoxidepotassium hydroxide) are studied. The ethers with an unbranched alkyl substituent isomerize into propenyl ethers, the ethers with a branched unsaturated substituent decompose to give a hydrocarbon, and diallyl ethers isomerize into allyl vinyl ethers whose Claisen rearrangement gives rise to aldehydes.     

Organocatalytic Conjugate Addition of Azide Ion to α,β‐Unsaturated Aldehydes

An efficient and simple amine‐catatalyzed azide conjugate addition to α,β‐unsaturated aldehydes has been developed. In the presence of a catalytic amount of tertiary amine with a 1:1 mixture of NaN₃ and 37% HCl in CH₂Cl₂, α,β‐unsaturated aldehydes provided β‐azido aldehydes, which could be transformed into 1,3‐amino alcohols.     

TiCl3/PhN2-mediated radical addition of ethers to aldimines generated in situ under aqueous conditions

Ti(III)-mediated one-electron reduction of phenyldiazonium cation, followed by phenyl radical α-H atom abstraction from ethers, leads to one-pot radical addition of ethers to the C-atom of imines generated in situ from the corresponding aldehydes and imines under aqueous conditions. The reaction is not limited to aromatic aldehydes and may be applied to imines generated in situ from formaldehyde and enolizable aldehydes.     

Enantioselective organocatalytic Mukaiyama-Michael addition of silyl enol ethers to alpha,beta-unsaturated aldehydes

[reaction: see text] A highly enantioselective, organocatalytic Mukaiyama-Michael addition reaction of silyl ethers and alpha,beta-unsaturated aldehydes has been developed. The process, catalyzed by MacMillan's chiral imidazolidinone, affords delta-keto aldehydes in high yields (56-87%) and high enantioselectivities (85-97% ee). Moreover, the reaction is applicable to a wide range of silyl ethers and alpha,beta-unsaturated aldehydes and, as such, provides access to a range of important synthetic building blocks.     

Lanthanides as lewis-acid catalysts in aldol addition,cyanohydrin-forming and oxirane ring opening reactions

Lanthanide trichlorides (Ln = La,Ce,Sm) and Eu(fod)₃ catalyze the aldol addition of silyl enol ethers to aldehydes, the addition of trimethylsilyl cyanide to aldehydes and ketones as well as thesynthesis of β-cyanosilyl ethers.     

Azido‐Substituted BODIPY Dyes for the Production of Fluorescent Carbon Nanotubes

A series of azido‐dyes were synthesized through Knoevenagel reactions of an azido‐BODIPY with aromatic aldehydes. The nature of the substituents allowed the fine tuning of their spectroscopic properties. The dyes were used to decorate oxidized multiwalled carbon nanotubes (ox‐MWCNTs), bearing terminal triple bond groups, by CuAAC reactions, affording fluorescent materials. This decoration allowed the efficient determination of the internalization of the ox‐MWCNT derivatives by different model cancer cells, such as MCF7.     

Catalytic asymmetric synthesis of hydroxy enol ethers: approach to a two-carbon homologation of aldehydes

[reaction: see text] Hydroboration of ethoxy acetylene, transmetalation to zinc, and addition to aldehydes in the presence of a chiral amino alcohol ligand (MIB) affords hydroxy enol ethers with high ee. The resultant enantiomerically enriched hydroxy enol ethers were converted to protected hydroxy aldehydes, a useful synthetic building block for the construction of a variety of polyoxygenated natural products. In addition, diastereoselective formation of syn- and anti-1,3-diols was studied.     

Catalytic Enantioselective Oxidative Cross‐Coupling of Benzylic Ethers with Aldehydes

The first one‐pot enantioselective oxidative coupling of cyclic benzylic ethers with aldehydes has been developed. A variety of benzylic ethers were transformed into the corresponding oxygen heterocycles with high enantioselectivity. Mechanistic experiments were conducted to determine the nature of the reaction intermediates. The application of this strategy to coupling reactions with other nucleophiles besides aldehydes was also explored.     

Scope and limitations of chiral B-

A new chiral oxazaborolidine catalyst was prepared in situ from 3, 5-bis(trifluoromethyl)phenylboron dichloride and N-(p-toluenesulfonyl)-(S)-tryptophan. This catalyst is much more active than Corey's original catalyst for the Mukaiyama aldol reaction of aldehydes with silyl enol ethers. The observed syn selectivities and re-face attack of silyl enol ethers on carbonyl carbon of aldehydes imply that the extended-transition state model is applicable.     

Tandem carbocupration/oxygenation of terminal alkynes

[chemical reaction: see text]. A direct and general synthesis of alpha-branched aldehydes and their enol derivatives is described. Carbocupration of terminal alkynes and subsequent oxygenation with lithium tert-butyl peroxide generates a metallo-enolate. Trapping with various electrophiles provides alpha-branched aldehydes or stereo-defined trisubstituted enol esters or silyl ethers. The tandem carbocupration/oxygenation tolerates alkyl and silyl ethers, esters, and tertiary amines. The reaction is effective with organocopper complexes derived from primary, secondary, and tertiary Grignard reagents and from n-butyllithium.     

A synthesis of optically active α-quaternary α-amino acids and esters by assembling three components, ketones, (R)-chloromethyl p-tolyl sulfoxide, and sodium azide, via sulfinyloxiranes

Treatment of lithium α-sulfinyl carbanion of chloromethyl p-tolyl sulfoxides with ketones at low temperature afforded adducts in almost quantitative yields, which were exposed to t-BuOK to give sulfinyloxiranes in high yields. The sulfinyloxirane was reacted with benzylamine to give α-amino aldehyde, which was oxidized with iodine in methanol to afford α-amino carboxylic ester in moderate yield. The sulfinyloxiranes were treated with sodium azide to afford α-azido aldehydes in good yields. Oxidation with NaClO₂ followed by catalytic hydrogenation of the azido group of the α-azido aldehydes gave α-quaternary α-amino acids in good overall yields. The oxidation of the azido aldehydes with iodine in methanol in the presence of KOH followed by the catalytic hydrogenation resulted in α-quaternary α-amino acid methyl esters in good yields. When these reactions were carried out starting from unsymmetrical ketones and optically pure (R)-chloromethyl p-tolyl sulfoxide, a new method for a synthesis of optically active α-quaternary α-amino acids and esters in good overall yields was realized.     

Acetal,triphenyl phosphorane,enol ether,acidic hydrolysis,nitroxyl

Two acetals were synthesised with hydroxymethyl triphenylphosphonium chloride as the alcoholic component. Reaction with ketones in the Wittig synthesis yielded enol ethers which were hydrolysed to aldehydes under acid catalysis. Tetrahydropyranyloxy compounds could be hydrolysed under milder conditions whereas, methoxymethyl ethers needed slightly more drastic conditions than the methyl ethers normally used in this synthesis.     

Unexpected copper-catalyzed aerobic oxidative cleavage of C(sp3)-C(sp3) bond of glycol ethers

An unexpected Cu-catalyzed oxidative cleavage of the C(sp(3))-C(sp(3)) bond in glycol ethers by using air or molecular oxygen as the terminal stoichiometric oxidant is demonstrated. As a result, the corresponding α-acyloxy ethers and formates of 1,2-ethanediol are formed by direct coupling of carboxylic acids and aldehydes with glycol ethers under the reaction conditions. This method represents the first example of Cu-catalyzed aerobic cleavage of saturated C-C bond in ethers.     

The breakdown of vinyl ethers as a two-center synchronous reaction

The experimental data on the molecular decomposition of vinyl ethers of various structures to alkanes and the corresponding aldehydes or ketones in the gas phase were analyzed using the method of intersecting parabolas. The enthalpies and kinetic parameters of decomposition were calculated for 17 reactions. The breakdown of ethers is a two-center concerted reaction characterized by a very high classical potential barrier to the thermally neutral reaction (180–190 kJ/mol). The kinetic parameters (activation energies and rate constants) of back reactions of the formation of vinyl ethers in the addition of aldehydes or ketones to alkanes were calculated using the method of intersecting parabolas. The factors that influenced the activation energy of the decomposition and formation of ethers were discussed. Quantum-chemical calculations of several vinyl ether decomposition reactions were performed. Ether formation reactions were compared with the formation of unsaturated alcohols as competitive reactions, which can occur in the interaction of carbonyl compounds with alkenes.     

Über die Reaktion von tertiären Vinylcarbinolen mit Vinyläthern Eine neue Methode Zur Herstellung von γ,δ-ungesättigten Aldehyden

A novel acid catalysed reaction of vinyl ethers with tertiary vinyl carbinols giving γ, δ-unsaturated aliphatic and alicyclic aldehydes in high yields is described. This new procedure for the utilization of the Claisen rearrangement reaction provides a convenient and efficient route to such aldehydes.     

Catalytic enantioselective three-component hetero-[4+2] cycloaddition/allylboration approach to alpha-hydroxyalkyl pyrans: scope, limitations, and mechanistic proposal

This article describes the design and optimization of a catalytic enantioselective three-component hetero-[4+2] cycloaddition/allylboration reaction between 3-boronoacrolein, enol ethers, and aldehydes to afford alpha-hydroxyalkyl dihydropyrans. The key substrate, 3-boronoacrolein pinacolate (2) was found to be an exceptionally reactive heterodiene in the hetero-[4+2] cycloaddition catalyzed by Jacobsen's chiral Cr(III) catalyst 1. The scope and limitations of this process were thoroughly examined. The adduct of 3-boronoacrolein pinacolate and ethyl vinyl ether was obtained in high yield and with over 95 % enantioselectivity. This cyclic alpha-chiral allylboronate adds to a very wide variety of aldehyde substrates, including unsaturated aldehydes and alpha-chiral aldehydes to give diastereomerically pure products. Acyclic 2-substituted enol ethers can be employed, in which case the catalyst promotes a kinetically selective reaction that favors Z enol ethers over the E isomers. Surprisingly, 3-boronoacrolein pinacolate was found to be a superior heterodiene than ethyl (E)-4-oxobutenoate, and a mechanistic interpretation based on a possible [5+2] transition state is proposed.     

Lewis acid promoted aldol reaction of fluorinated silyl enol ethers from new fluoroacetylsilane derivatives

New fluorinated silyl enol ethers with various trialkylsilyl groups were synthesized. Various fluorinated β-hydroxy ketones were synthesized by Lewis acid promoted aldol reaction of silyl enol ethers with diverse aldehydes. Reactivity of various trialkylsilyloxy groups toward Lewis acid was also studied.