A highly stereoselective and flexible strategy for the convergent synthesis of long-chain polydeoxypropionates: application towards the synthesis of the glycolipid membrane components hydroxyphthioceranic and phthioceranic acid.

A highly stereocontrolled and flexible access to biologically relevant polydeoxypropionates in optically pure form has been developed. Taking advantage of our previously established strategy for the asymmetric and stereodivergent synthesis of trideoxypropionate building blocks, we have now been able to assemble large polydeoxypropionate chains with defined configuration in a highly convergent manner. Central steps of this approach include two Suzuki-Miyaura cross-coupling reactions with subsequent highly diastereoselective hydrogenations to join three advanced synthetic intermediates in excellent yield and with full stereochemical control. We have applied this strategy successfully towards the asymmetric synthesis of glycolipid membrane components phthioceranic acid and hydroxyphthioceranic acid, the latter of which was synthesized on a half-gram scale.

Organocatalytic access to enantioenriched dihydropyran phosphonates via an inverse-electron-demand hetero-Diels-Alder reaction.

The enantioselective inverse-electron-demand hetero-Diels-Alder reaction of the remote olefin functionality in dienamines has been developed by the simultaneous activation of α,ß-unsaturated aldehydes and acyl phosphonates. The dual activation is based on an organocatalyst that activates both the α,ß-unsaturated aldehyde, through dienamine formation, and the acyl phosphonate by hydrogen-bonding. The enantioselective reaction results in the formation of dihydropyran frameworks with three contiguous stereogenic centers. Different substitution patterns are possible for both the heterodiene and the dienophile, and the target products are obtained in good yields and up to 92% ee. The potential of the reaction is demonstrated by transformation of the products into valuable and complex synthons.

Dienamine-mediated inverse-electron-demand hetero-diels-alder reaction by using an enantioselective H-bond-directing strategy.

Giving directions: optically active dihydropyrans bearing three contiguous stereogenic centers can be efficiently prepared by the title reaction. High stereo- and regiocontrol can be achieved by employing a bifunctional H-bond-directing aminocatalyst.

Selective access to both diastereoisomers in an enantioselective intramolecular Michael reaction by using a single chiral organocatalyst and application in the formal total synthesis of (-)-epibatidine.

Two in one: Both diastereoisomers of 4-nitro-3-substituted cyclohexanones are accessed selectively by an intramolecular Michael reaction using a single chiral aminocatalyst (see scheme). Mechanistic studies show that the reaction is selective for the cis-diastereoisomer and that the trans-diastereoisomer arises over time. DFT calculations suggest that the cis-selectivity is due to a favorable electrostatic interaction between the iminium ion and the nucleophile.

Optically active thiophenes via an organocatalytic one-pot methodology.

A general methodology for the synthesis of trisubstituted, optically active thiophenes by an organocatalytic one-pot reaction cascade is presented. The target products are synthesized in good yields (up to 92%) and with excellent enantioselectivities (up to 98% ee). Importantly, based on practical and easily available starting materials, the presented methodology can be conducted under mild reaction conditions. To further elucidate the generality, the synthesis of optically active thienoindoles, as well as selenophenes, is also demonstrated.

A general, asymmetric, and noniterative synthesis of trideoxypropionates. Straightforward syntheses of the pheromones (+)-vittatalactone and (+)-norvittatalactone.

A novel, highly stereocontrolled, and very flexible synthetic access to biologically relevant trideoxypropionate building blocks in optically pure form has been developed. On the basis of a three-step sequence comprising a thermal oxy-Cope rearrangement, an iridium-catalyzed hydrogenation, and an auxiliary-controlled enolate methylation, trideoxypropionates with easily adjustable relative configuration were synthesized in excellent yields. In addition, the functionalized end groups allow for chemoselective manipulations and further elongation of the chain. The underlying strategy constitutes the first noniterative process for the assembly of polydeoxypropionates and has further been applied in total syntheses of the pheromones (+)-vittatalactone and (+)-norvittatalactone, which had been isolated from the striped cucumber beetle Acalymma vittatum.

A non-iterative, flexible, and highly stereoselective synthesis of polydeoxypropionates--synthesis of (+)-vittatalactone.

A short sequence comprising an oxy-Cope rearrangement, iridium-catalyzed hydrogenation, and enolate methylation provides trideoxypropionates with excellent diastereocontrol. A straightforward synthesis of the cucumber beetle pheromone (+)-vittatalactone illustrates this new strategy.