Synthetic Studies toward the Haouamines

A concise synthetic approach toward the haouamines based on Stork−Danheiser alkylation and Friedel−Crafts chemistry is described. A novel electrophilic aromatic substitution with concomitant formation of an enol triflate is reported

Synthetic Studies toward the Haouamines

A concise synthetic approach toward the haouamines based on Stork−Danheiser alkylation and Friedel−Crafts chemistry is described. A novel electrophilic aromatic substitution with concomitant formation of an enol triflate is reported

Diastereoselective Formation of a New Palladacycle and Organic Compounds Derived from Vinylcarbenoids as Side Products in the Synthesis of 5-Pallada-<i>trans</i>-tricyclo[4.1.0.0^2,4]heptanes from Acceptor-Substituted Cyclopropenes

When a large excess of dimethyl 3,3-dimethylcyclopropene-1,2-dicarboxylate was used in a reaction with Pd2(dba)3·CHCl3, only reduced yields of tetramethyl 3,3,7,7-tetramethyl-5-pallada-trans-tricyclo[4.1.0.02,4]heptane-1,2,4,6-tetracarboxylate were obtained. One side product was the new palladacyle dimethyl 3-(3,4-bis(methoxycarbonyl)-5,5-dimethyl-5H-furan-2-ylidene)-1,1,4,4-tetramethyl-6-oxodihydro-5-oxa-2-palladacyclopropa[c]pentalene 1a,3a-dicarboxylate; its structure was proven by a crystal structure analysis of the bpy complex. The other side products are the 1,3,5-triene methyl (Z)-2-isopropylidene-3,4,5-tris(methoxycarbonyl)-6-methylhepta-3,5-dienecarboxylate (14), the allyl alcohol dimethyl (Z)-2-(1-hydroxy-1-methylethyl)but-2-enedicarboxylate (15), the 1,3-diene dimethyl (Z)-2-isopropenylbut-2-enedicarboxylate (16), and the allyl ether dimethyl 2-isopropylidene-3-methoxysuccinate (17). The formation of most of these side products is interpreted as the reaction of a vinyl carbenoid species with O-nucleophiles

Rational Design of a Chiral Palladium(0) Olefin Complex of Unprecedented Stability

A chiral bidentate olefin ligand L with a 1,4a,5,8a-tetrahydro-naphthalene-2,6-dione framework has been designed, which forms a homoleptic palladium(0) complex L2Pd of unprecedented stability

Rational Design of a Chiral Palladium(0) Olefin Complex of Unprecedented Stability

A chiral bidentate olefin ligand L with a 1,4a,5,8a-tetrahydro-naphthalene-2,6-dione framework has been designed, which forms a homoleptic palladium(0) complex L2Pd of unprecedented stability

Development of a Friedel−Crafts Triflation

The development of a new variant of the Friedel−Crafts reaction that yields 3-aryl enol triflates is described. The reaction is practical, is atom-economical, and works well with electron-rich arene substrates

A Fast Ab Initio Predictor Tool for Covalent Reactivity Estimation of Acrylamides

Thanks to their unique mode of action, covalent drugs represent an exceptional opportunity for drug design. After binding to a biologically relevant target system, covalent compounds form a reversible or irreversible covalent bond with a nucleophilic amino acid. Due to the inherently large binding energy of a covalent bond, covalent binders exhibit higher potencies and thus allow potentially lower drug dosages. However, a proper balancing of compound reactivity is key for the design of covalent binders, to achieve high levels of target inhibition while minimizing promiscuous covalent binding to nontarget proteins. In this work, we demonstrated the possibility to apply the electrophilicity index concept to estimate covalent compound reactivity. We tested this approach on acrylamides, one of the most prominent classes of covalent warheads. Our study clearly demonstrated that, for compounds with molecular weight (MW) below 250 Da, the electrophilicity index can be directly used to estimate compound reactivity. On the other hand, for leadlike molecules (MW > 250 Da) we implemented a new truncation algorithm that has to be applied before reactivity calculations. This algorithm can ensure the localization of HOMO/LUMO orbitals on the compound warhead and thus a correct estimation of its reactivity. Our results also indicate that caution should be used when employing the electrophilicity index to estimate the reactivity of nonterminal acrylamides. The nonparametric nature of this method and its reasonable computational cost make it a suitable tool to support covalent drug design

A Highly Diastereoselective Recognition Process as the Basis for the Resolution of Palladatricyclo[4.1.0.0^2,4]heptanes

The synthesis of palladatricyclo­[4.1.0.0^2,4]­heptane diastereomers by positional selective transesterification with (1<i>R</i>,2<i>S</i>,5<i>R</i>)-(−)-menthol is used for the resolution of these chiral organometallic compounds. The separation process of the two diastereomers is simplified by an unprecedented aggregation phenomenon. In a molecular recognition process the highly diastereoselective formation of dimers of strongly differing stability allows an efficient separation by normal column chromatography. The stereoselective dimerization was proven by IR and mass spectroscopic studies as well as ¹H NMR techniques and X-ray crystal structure analysis

A Highly Diastereoselective Recognition Process as the Basis for the Resolution of Palladatricyclo[4.1.0.0^2,4]heptanes

The synthesis of palladatricyclo­[4.1.0.0^2,4]­heptane diastereomers by positional selective transesterification with (1<i>R</i>,2<i>S</i>,5<i>R</i>)-(−)-menthol is used for the resolution of these chiral organometallic compounds. The separation process of the two diastereomers is simplified by an unprecedented aggregation phenomenon. In a molecular recognition process the highly diastereoselective formation of dimers of strongly differing stability allows an efficient separation by normal column chromatography. The stereoselective dimerization was proven by IR and mass spectroscopic studies as well as ¹H NMR techniques and X-ray crystal structure analysis