Aryne Multicomponent Reactions by Directed C-H Activation.

Arylation via ortho C-H activation by the aid of directing groups has been explored recently by many researchers. Herein, a palladium-catalyzed C-H arylation using 8-aminoquinoline as a bidentate directing group has been developed. The reaction furnishes only C-H arylation, unlike previous methods where cyclization to corresponding isoquinolones is observed.

Enantiospecific total synthesis of macrolactone Sch 725674.

The enantiospecific total synthesis of 14-membered macrolactone Sch 725674 was accomplished from tartaric acid. Key reactions in the synthesis include the Ley's dithiaketalization of an alkynone derived from the bis-Weinreb amide of tartaric acid, Boord olefination, and ring-closing metathesis of an acrylate ester.

Synthesis of 7,9-diazabicyclo[4.2.2]decanes as conformationally restricted κ receptor agonists: fine tuning of the dihedral angle of the ethylenediamine pharmacophore.

In order to slightly modify the orientation of the pharmacophoric structural elements of the potent κ agonists 7 and 8, the three-membered bridge of these compounds was enlarged to four carbon atoms. Reductive amination of the bicyclic ketone 11 with pyrrolidine and NaBH(OAc)3 provided the pyrrolidine 12 with excellent diastereoselectivity (>99:1). The diastereomeric pyrrolidine 24 was established by a stepwise strategy, involving an unselective nucleophilic substitution of the triflate 20 with NaN3 as key step.

Synthesis and biological evaluation of conformationally restricted σ(1) receptor ligands with 7,9-diazabicyclo[4.2.2]decane scaffold.

The key step in the synthesis of the 7,9-diazabicyclo[4.2.2]decane system was a modified Dieckmann condensation of piperazinebutyrate 11, which makes use of trapping the first cyclized intermediate with TMS-Cl.

Bicyclic sigma receptor ligands by stereoselective Dieckmann analogous cyclization of piperazinebutyrate.

Starting from racemic 2-aminoadipic acid (6) the piperazinedione 10 with a butyrate side chain was synthesized in four reaction steps. The four-carbon bridge was established upon deprotonation of 10 with LHMDS and subsequent trapping of the lithium alcoholate with Me(3)SiCl to give diastereoselectively the mixed methyl silyl ketal 12 in 94% yield. The relative configuration of the new center of chirality was determined by X-ray crystal structure analysis of 12.