Alcohol Nucleophiles Research Articles

An examination of the substitution chemistry of di- n-hexyldichlorosilane

Various nucleophiles were reacted with the substrate di- n-hexyldichlorosilane as model reactions for the substitution of two geminal SiCl bonds on polymer backbone repeat units. The reactants examined were chosen on the basis of steric bulk, electronic factors, and resulting stability of the product. Linear and branched alcohol nucleophiles used in conjunction with an amine proton acceptor produced disubstituted products in moderate yields, whereas bulkier reagents substituted only one siliconchlorine bond. Due to their vastly increased nucleophilicity, alkyllithium reagents were found to have increased activity and were found to produce very high yields.

Photo amidoglycosylation of an allal azidoformate. Synthesis of beta-2-amido allopyranosides.

[figure: see text] Photolysis of an allal C-3 azidoformate provoked intramolecular nitrene insertion into the glycal C=C unit and allowed direct incorporation of alcohol nucleophiles as beta-disposed substituents at C-1. The 2-amido allopyranoside products were elaborated via N-acylation and selective oxazolidinone hydrolysis, providing N-Boc-protected 2-amino sugars and simplifying stereochemical assignments. Synthesis of the potentially labile allal azidoformate was achieved via reaction of the corresponding carbonyl imidazolide with trimethylsilyl azide, facilitated by dibutyltin oxide.

Electrochemical oxidation of aspidofractinine-type alkaloids: Formation of kopsine, kopsidine, kopsinitarine and bisindole derivatives

Anodic oxidation of kopsamine on platinum in acetonitrile results in cyanation or cyanomethylation, following ring closure, while oxidation on vitreous carbon in methanol yields a dimerization product with a C2 element of symmetry. This behaviour is reproduced in the aromatic congeners of kopsamine, kopsiflorine and 11-methoxykopsilongine. Oxidation of kopsingine on platinum in CH2Cl2–MeCN leads to a stable conjugated iminium salt which can be trapped by alcohol or water nucleophiles to give kopsidines A, B, and C. Kopsidines A and B can also be obtained directly from electrooxidation in methanol or ethanol. Oxidation of dihydrokopsingine in acetonitrile gives the 17-to-5 and 17-to-3 oxo-bridged compounds directly, while oxidation in methanol yields an additional product which is a caged kopsinitarine derivative. Oxidation of an aspidofractinine derivative without unsaturation in the piperidine ring and with a C(17)-αOH function gives a C2 symmetric dimerization product as well as a caged kopsinitarine-type product. Possible pathways leading to the various products are presented.

Enantio-reversal in Candida rugosa lipase-catalyzed esterification of 3-hydroxybutyric acid

Candida rugosa lipase (CRL)-catalyzed esterification of racemic 3-hydroxybutyric acid with different nucleophilic alcohols was studied. The alcohol chain length was found to have a profound role in the enantioselectivity of the reaction. As compared to the esterification with 1-butanol, use of longer alcohols surprisingly led to an enantio-reversal. Under optimized condition, the ( R)-ester with 95–98% enantiomeric excess (ee) was obtained when the esterification was carried out with 1-hexanol and 1-octanol in the presence of freshly activated molecular sieve 4 Å.

Laser Flash Photolysis Studies on the First Superoxide Thermal Source. First Direct Measurements of the Rates of Solvent-Assisted 1,2-Hydrogen Atom Shifts and a Proposed New Mechanism for This Unusual Rearrangement1

The thermal decomposition of bis(4-carboxybenzyl)hyponitrite (SOTS-1) in aerated water under physiological conditions has previously been shown to give the superoxide radical anion in a yield of 40 mol % (Ingold, K. U.; et al. J. Am. Chem. Soc. 1997, 119, 12364). The absolute kinetics of the elementary reactions involved in the cascade of events leading from the first-formed water-soluble benzyloxyl radical to superoxide have been determined by laser flash photolysis. On the basis of these kinetics it is concluded that SOTS-1 will be suitable for studies of superoxide-induced oxidative stress in most biological systems. A water-assisted 1,2-H shift converting benzyloxyl into the benzyl ketyl radical is an important step in the above reaction cascade. The kinetics of the 1,2-H shift assisted by H2O, D2O, and a number of nucleophilic alcohols have been measured for the first time. These data have led to a proposed new mechanism involving the initial formation of a ketyl radical anion and an oxonium cation w...

Catalytic activity of sorbents containing metals, and nucleophilicity of alcohols activated with fluoride anion in reaction of nucleophilic substitution in 2,3-dichloronaphthazarines

In reaction of 5, 8-dihydroxy-2, 3-dichloro-6-ethyl-7-ethoxy-1,4-naphthoquinone and 6-tert-butyl-5,8-dihydroxy-2,3-dichloro-l,4-naphthoquinone proceeding on the surface of molecular sieves, calcium phosphate and carbonate, neutral alumina, or magnesium silicate with nucleophilic reagents (methanol, 2-methoxyethanol, monomethyl ethers of di- and triethylene glycols) activated with fluoride anion the yield of products decreased in this nucleophiles series. The most active catalysts among sorbents are alumina and magnesium silicate. All the sorbents are also efficient catalysts of alkoxy groups interchange.

Direct transacylation of 2,2,2-trihaloethyl esters with amines and alcohols using phosphorus (III) reagents for reductive fragmentation and in situ activation.

Amides and esters have been synthesized from 2,2,2-trihaloethyl esters in one pot using phosphorus-(III) reagents as reductants, with resultant carboxylate activation as an acyloxyphosphonium intermediate, and in situ trapping by amine or alcohol nucleophiles. Secondary and tertiary amides were synthesized, including a dipeptide, in good yields using hexamethylphosphorous triamide (Me2N)3P, as reducing agent. Optimal yields of esters derived from primary and secondary alcohols were obtained using tributylphosphine and DMAP. Tribromoethyl esters provided yields superior to those obtained with trichloroethyl esters.

Synthesis of spiro-cyclopropane derivatives containing multiple chiral centers

Tandem asymmetric double Michael addition/internal nucleophilic substitution of the novel chiral source, 5-(l-menthyloxy)-3-bromo-2 (5H)-furanone with nucleophilic alcohol compounds has been investigated. The tandem asymmetric reaction can afford four new stereogenic centers with one reaction and give optically pure spiro-cyclopropane derivatives 5a–5d which are difficult to obtain by routine methods. The synthetic method for 5a–5d was studied in de-tail and the new compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]20, IR,1H NMR,13C NMR, MS and elementary analysis. The absolute configuration of the sprio [5-l-menthyloxy-3-bromobutyrolactocyclopropane-3”, 3’ (4’-methyloxy-5’-menthyloxybutyrolactone) ] (5a) was established by X-ray crystallography. The work can provide important synthetic strategy in synthesis of some new optically active spiro-cyclopropane analogues and some biologically active molecules with complex structure.

Exploring the Mechanism of Neighboring Group Assisted Glycosylation Reactions

Glycosyl donors based on the 2,6-di-O-acyl-3,4-O-isopropylidene-d-galactopyranosyl-(leaving group) structure have been shown experimentally to have a high propensity for giving acyl transfer to the alcohol nucleophile as major side products in the glycosylation reaction. The corresponding cations of these relatively rigid glycosyl donors were investigated by density functional methods. The precursor cations resulting from neighboring group assistance from the 2-O-acyl group were found to be the most stable. The nucleophile methanol most favorably approaches the LUMO of such cations on the former carbonyl carbon. The resulting stable intermediate has a long C−O bond of 2.79 Å. It is suggested that such intermediates can lead to both acyl transfer and β-glycoside after passing through at least one further transition state.

Synthesis of enantiomerically pure spiro-cyclopropane derivatives containing multichiral centers

A novel chiral source, 5-( R)-[(1 R,2 S,5 R)-(−)-menthyloxy]-3-bromo-2(5H)-furanone ( 5a), was obtained in 46% yield with d.e.≥98% from the epimeric mixture of 5-( l-menthyloxy)-3-bromo-2(5H)-furanone ( 5a+ 5b) obtained via the bromination of an epimeric mixture of 5-( l-menthyloxy)-2(5H)-furanone ( 3a+ 3b) followed by the elimination of hydrogen bromide. The asymmetric reaction of 5a with a nucleophilic alcohol afforded enantiomerically pure spiro-cyclopropane derivatives containing four stereogenic centers, 9a– 9e, in 50–68% yield with d.e.≥98%. The enantiomerically pure compounds 9a– 9e were identified on the basis of their analytical data and spectroscopic data, such as [α] D 20, UV, IR, 1H NMR, 13C NMR, MS and elementary analysis. The absolute configuration of the chiral spiro-cyclopropane compound 9a was established by X-ray crystallography.

Enzyme mediated polyester synthesis with the lipase from Candida rugosa

We have previously demonstrated an efficient polyester synthesis of ω-hydroxyacids catalysed by the Candida rugosa lipase in dry hexane (1,2). This method is now extended to the polymerisation of racemic 10-hydroxyundecanoic acid to explore the polymerisation of a secondary alcohol and the ability of the lipase to display stereoselectivity. The resultant polyester (∼1000 Mwt) contained monomer units with an average enantiomeric excess of 60%ee favouring the (S) enantiomer. The residual monomer was recovered with a 33%ee favouring the (R) enantiomer. The origin of this stereoselectivity has been evaluated and it has been shown to arise due to the immediate chiral environment surrounding the esterification event between the acylated enzyme and the secondary alcohol nucleophile. It is not due to recognition of the remote secondary alcohol functional group by the enzyme during initial acylation.

Libraries of N-alkylaminoheterocycles from nucleophilic aromatic substitution with purification by solid supported liquid extraction

Heterocycles containing 2 or 3 chlorine atoms have been converted to libraries of N-alkylaminoheterocycles by parallel solution phase nucleophilic aromatic substitution. The first chloride displacement was achieved with stoichiometric nucleophilic alcohols, or amines. In the final substitution, excess amine was used to ensure that all active electrophiles were consumed. The excess amine and salts were removed by automated solid s upported l iquid e xtraction (SLE). SLE is partition chromatography using buffered water immobilized on a solid support and elution by a water immiscible solvent. This is a high throughput method for liquid-liquid extraction which is easily automated using simple liquid handling robotics.

ChemInform Abstract: An Efficient Method for Catalytic and Stereoselective Synthesis of 2‐Deoxy‐α‐D‐glucopyranosides from 3,4,6‐Tri‐O‐benzyl‐2‐deoxy‐D‐glucopyranose and Several Alcoholic Nucleophiles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Facile Addition of Poorly Nucleophilic Alcohols to Unactivated Alkenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The rate of ring opening of γ‐and δ‐lactones derived from meadowfoam fatty acids

Abstractδ‐Lactones derived from meadowfoam (Limnanthes) fatty acids were reacted with amine and alcohol nucleophiles in a second‐order reaction to provide the acyclic 5‐hydroxy eicosanoic acid esters and amides. The rate of reaction for the ring opening of δ‐lactones was compared to the rate of ring opening of γ‐lactones and the rate of derivatization of meadowfoam fatty acids. δ‐Lactones showed a much larger rate for the formation of derivatives than the corresponding γ‐lactones or fatty acids. γ‐Lactone had a rate constant >7700 times larger for the formation of butyl ester than meadowfoam fatty acids. The formation of amides from δ‐lactones is even faster than the esterification reaction and requires no catalyst or solvent when conducted at the melting point of the lactone.

An Efficient Method for Catalytic and Stereoselective Synthesis of 2-Deoxy-α-d-glucopyranosides from 3,4,6,-Tri-O-benzyl-2-deoxy-d-glucopyranose and Several Alcoholic Nucleophiles

Abstract Several 2-deoxy-α-d-glucopyranosides are stereoselectively synthesized in high yields by glycosylation of various alcoholic nucleophiles with 3,4,6-tri-O-benzyl-2-deoxy-glucopyranose using a catalytic amount of trityl tetrakis(pentafluorophenyl)borate.

ChemInform Abstract: Catalytic Stereoselective Synthesis of α‐D‐Galactopyranosides from 2,3,4,6‐Tetra‐O‐benzyl‐D‐galactopyranose and Several Alcoholic Nucleophiles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Facile Addition of Poorly Nucleophilic Alcohols to Unactivated Alkenes

Electronegative substituted (polyfluorinated and polynitroaliphatic), poorly nucleophilic alcohols are efficiently added to model alkenes norbornene, cyclohexene, hex-1-ene, and hex-3-ene under mild conditions by the use of boron trifluoride-diethyl ether complex catalyst, forming the corresponding ethers.

Catalytic Stereoselective Synthesis of α-d-Galactopyranosides from 2,3,4,6-Tetra-O-benzyl-d-galactopyranose and Several Alcoholic Nucleophiles

Abstract The glycosylation reaction of several alcoholic nucleophiles with 2,3,4,6-tetra-O-benzyl-d-galactopyranose (1-hydroxy sugar) is successfully carried out by the combined use of Sn(OTf)2-Me3SiCl catalyst system and lithium perchlorate, an effective additive. Several α-d-galactopyranosides are obtained in good yields with high stereoselectivities.

Lithium Perchlorate Mediated Allylic Substitution Reaction Using a Cyclohexenyl Based Model System

A methodology was developed for the direct substitution of allylic alcohols and acetates by alcohol nucleophiles in order to synthesize allylic ethers. The reaction was mediated by highly concentrated ethereal solutions of lithium perchlorate and proceeded with high regiospecificity. Additionally, the methodology was extended to enable allyl ether exchanges to occur.