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Biomedical subjects

Chris H Senanayake

Publications and source records attributed to Chris H Senanayake.

At least 19 recordsLinked to original sources
PubMed2007

Practical stereoselective synthesis of an alpha-trifluoromethyl-alpha-alkyl epoxide via a diastereoselective trifluoromethylation reaction.

A practical stereoselective synthesis is reported for an alpha-trifluoromethyl-alpha-alkyl epoxide (1), which is an important pharmaceutical intermediate. The key step involves a chiral auxiliary-controlled asymmetric trifluoromethylation reaction for the introduction of the unique trifluoromethyl-substituted tertiary alcohol stereogenic center in the target molecule. The fluoride-initiated CF3 addition to chiral keto ester 6a proceeded with a diastereoselectivity up to 86:14. The major diastereomer was readily obtained with a >99.5:0.5 dr through a simple crystallization of the crude product mixture.

Alkylation↗
PubMed2006

Epimerization reaction of a substituted vinylcyclopropane catalyzed by ruthenium carbenes: mechanistic analysis.

A novel ruthenium carbene-catalyzed epimerization of vinylcyclopropanes is reported. The reaction rate strongly depends on the presence of ruthenium ligands in solution. When the first-generation Grubbs catalyst is employed, a 5.3:1 equilibrium ratio of epimers is established quickly, but when a first-generation Hoveyda catalyst is employed, epimerization is observed only if an additional phosphine or nitrogen ligand is added. NMR and kinetic studies suggest that the isomerization reaction occurs through the intermediacy of a ruthenacyclopentene. The observation suggests that cyclopropylmethylidene ruthenium carbenes of synthetic utility may be accessible via ruthenacyclopentenes obtained via other routes.

Catalysis↗
PubMed2006

Mild iodine-magnesium exchange of iodoaromatics bearing a pyrimidine ring with isopropylmagnesium chloride.

[reaction: see text] Iodoaromatics bearing a reactive pyrimidine ring underwent a clean iodine-magnesium exchange with isopropylmagnesium chloride in the presence of bis[2-(N,N-dimethylamino)ethyl] ether to provide the corresponding Grignard reagents. The presence of bis[2-(N,N-dimethylamino)ethyl] ether prevented reduction of the pyrimidine ring and addition by isopropylmagnesium chloride. As a result, the newly formed reactive Grignard reagents were allowed to react with electrophiles in a highly selective manner to afford adducts in excellent yields.

Journal Article↗
PubMed2006

Activation of TMSCN by N-heterocyclic carbenes for facile cyanosilylation of carbonyl compounds.

N-Heterocyclic carbenes were found to be highly effective organocatalysts in activating TMSCN for facile cyanosilylation of carbonyl compounds. Cyano transfer from TMSCN to aldehydes and ketones proceeds at room temperature in the presence of only 0.01-0.5 mol % of N-heterocyclic carbene (1), leading to a range of trimethylsilylated cyanohydrins in very good to excellent yields. These conditions are extremely mild and simple and tolerate various functional groups.

Acetophenones↗
PubMed2006

Noncryogenic I/Br-Mg exchange of aromatic halides bearing sensitive functional groups using i-PrMgCl-bis[2-(N,N-dimethylamino)ethyl] ether complexes.

[reaction: see text] Iodo- and bromoaromatics bearing sensitive carboxylic ester and cyano groups underwent a selective halide-magnesium exchange with isopropylmagnesium chloride at ambient temperature in the presence of bis[2-(N,N-dimethylamino)ethyl] ether to afford the corresponding Grignard reagents. The newly formed reactive Grignard reagents were allowed to react with electrophiles such as trimethylborate to afford arylboronic acids in good to excellent yields.

Journal Article↗
PubMed2005

Addition of grignard reagents to aryl acid chlorides: an efficient synthesis of aryl ketones.

[chemical reaction: see text]. Direct addition of Grignard reagents to acid chlorides in the presence of bis[2-(N,N-dimethylamino)ethyl] ether proceeds selectively to provide aryl ketones in high yields. A possible tridentate interaction between Grignard reagents and bis[2-(N,N-dimethylamino)ethyl] ether moderates the reactivity of Grignard reagents, preventing the newly formed ketones from nucleophilic addition by Grignard reagents.

Journal Article↗
PubMed2005

A superior method for the reduction of secondary phosphine oxides.

[reaction: see text] Diisobutylaluminum hydride (DIBAL-H) and triisobutylaluminum have been found to be outstanding reductants for secondary phosphine oxides (SPOs). All classes of SPOs can be readily reduced, including diaryl, arylalkyl, and dialkyl members. Many SPOs can now be reduced at cryogenic temperatures, and conditions for preservation of reducible functional groups have been found. Even the most electron-rich and sterically hindered phosphine oxides can be reduced in a few hours at 50-70 degrees C. This new reduction has distinct advantages over existing technologies.

Aluminum↗
PubMed2005

N-heterocyclic carbene catalyzed trifluoromethylation of carbonyl compounds.

[reaction: see text]. A novel N-heterocyclic carbene (NHC) catalyzed trifluoromethylation reaction of carbonyl compounds was discovered. Both enolizable and nonenolizable aldehydes and alpha-keto esters undergo facile trifluoromethylation with TMSCF3 at room temperature in the presence of only 0.5-1 mol % of the commercially available NHC (1), providing CF3-substituted alcohols in good yields. Selective trifluoromethylation of aldehydes over ketones can be achieved under NHC catalysis. These conditions are mild and simple and tolerate a variety of functional groups.

Journal Article↗
PubMed2005

Structure elucidation and total synthesis of a unique group of trace impurities in Tipranavir drug product.

Four unknown trace impurities (7-10) were observed in the capsule formulation of the HIV drug Tipranavir after prolonged storage at 30 degrees C/70% RH. Extensive NMR and LC/MS analyses revealed the compounds to be covalent adducts between TRIS, an excipient of the formulation, and diastereomeric Tipranavir alcohols formed via slow air oxidation of the drug substance. The structures were ultimately confirmed by total synthesis with final purification by chiral, preparative supercritical fluid chromatography. A novel Favorskii rearrangement to furnish butyrolactones was also uncovered during the synthesis.

Alcohols↗
PubMed2004

Synthesis of 5-bromopyridyl-2-magnesium chloride and its application in the synthesis of functionalized pyridines.

[reaction: see text] The 5-bromopyridyl-2-magnesium chloride (2), which was not accessible previously, was efficiently synthesized for the first time via an iodo-magnesium exchange reaction with 5-bromo-2-iodopyridine (1). This reactive intermediate was allowed to react with a variety of electrophiles to afford a range of useful functionalized pyridine derivatives. Application of this methodology to 5-bromo-2-iodo-3-picoline provided a simple and economical synthesis of a key intermediate for the preparation of Lonafarnib, a potent anticancer agent.

Magnesium Chloride↗