Generation of quaternary centers by reductive cross-coupling: shifting of regioselectivity in a subset of allylic alcohol-based coupling reactions.

Regioselective titanium alkoxide-mediated reductive cross-coupling reactions of allylic alcohols with vinylsilanes and imines have previously been demonstrated to proceed with allylic transposition by formal metallo-[3,3]-rearrangement [thought to proceed by a sequence of: 1) directed carbometalation, and 2) syn-elimination]. While many examples have been described that support this reaction path, a collection of substrates have recently been identified that react by way of an alternative pathway, delivering a concise convergent route to coupled products bearing a quaternary center.

Conversion of allylic alcohols to stereodefined trisubstituted alkenes: a complementary process to the Claisen rearrangement.

A stereoselective method for the conversion of allylic alcohols to (Z)-trisubstituted alkenes is presented. Overall, the reaction sequence described is stereochemically complementary to related Claisen rearrangement reactions--processes that typically deliver the stereoisomeric trisubstituted alkene containing products.

Structure-activity relationships of the cycloalkanol ethylamine scaffold: discovery of selective norepinephrine reuptake inhibitors.

Further exploration of the cycloalkanol ethylamine scaffold, of which venlafaxine ( 1) is a member, was undertaken to develop novel and selective norepinephrine reuptake inhibitors (NRIs) for evaluation in a variety of predictive animal models. These efforts led to the discovery of a piperazine-containing analogue, 17g (WY-46824), that exhibited potent norepinephrine reuptake inhibition, excellent selectivity over the serotonin transporter, but no selectivity over the dopamine transporter. Synthesis and testing of a series of cyclohexanol ethylpiperazines identified ( S)-(-)- 17i (WAY-256805), a potent norepinephrine reuptake inhibitor (IC 50 = 82 nM, K i = 50 nM) that exhibited excellent selectivity over both the serotonin and dopamine transporters and was efficacious in animal models of depression, pain, and thermoregulatory dysfunction.

Studies on the syntheses of benzoquinone ansamycin antibiotics. Syntheses of the C5-C15 subunits of macbecin I, geldanamycin, and herbimycin A.

[reaction: see text] A general and convergent route to the C(5)-C(15) subunits of the benzoquinone ansamycin antibiotics macbecin I, geldanamycin, and herbimycin A is described. Each subunit is prepared by the stepwise coupling of differentially functionalized aldehydes with a pentenyl dianion equivalent derived from diastereoselective pentynylation and regioselective reductive coupling.