Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride.

A novel reactivity of 1,1,1-trifluoroalkanones is reported, where the reaction with AlCl results in the formation of 1,1-dichloro-1-alkenones. The reaction scope was found to be broad, with various chain lengths and aryl substituents tolerated. For substrates containing an electron-rich aromatic ring, further reactions take place, resulting in bicyclic and/or rearrangement products.

Decahydrobenzoquinolin-5-one sigma receptor ligands: Divergent development of both sigma 1 and sigma 2 receptor selective examples.

Analogues of the decahydrobenzoquinolin-5-one class of sigma (σ) receptor ligands were used to probe the structure-activity relationship trends for this recently discovered series of σ ligands. In all, 29 representatives were tested for σ and opioid receptor affinity, leading to the identification of compounds possessing improved σ selectivity and, for the first time in this series, examples possessing preferential σ affinity. Several structural features associated with these selectivity trends have been identified.

Efficient access to sp-rich tricyclic amine scaffolds through Diels-Alder reactions of azide-containing silyloxydienes.

The preparation of sp-rich scaffolds to obtain more natural product-like libraries for incorporation into screening decks is challenging. Here, we describe the use of a Diels-Alder reaction between an enone and an azide-containing silyloxydiene to gain efficient access to complex tricyclic amine scaffolds. Derivatization of these scaffolds provided a library of 80 amines, amides, sulfonamides, quinolines and indolenines, all in >20 mg quantities and >90% purities.

Probing chemical space with alkaloid-inspired libraries.

Screening of small-molecule libraries is an important aspect of probe and drug discovery science. Numerous authors have suggested that bioactive natural products are attractive starting points for such libraries because of their structural complexity and sp(3)-rich character. Here, we describe the construction of a screening library based on representative members of four families of biologically active alkaloids (Stemonaceae, the structurally related cyclindricine and lepadiformine families, lupin and Amaryllidaceae).

An enantioselective formal synthesis of berkelic acid.

An enantioselective formal synthesis of berkelic acid is described. The key step involves a late-stage silyl enol ether addition to a benzannulated oxonium ion with subsequent spiroketalization leading to construction of the tetracyclic core. Thermodynamically controlled equilibration under acidic conditions affords the desired spiroketal configuration as a single diastereoisomer.

Diastereo- and enantioselective synthesis of alpha,beta-epoxyketones using aqueous NaOCl in conjunction with dihydrocinchonidine derived phase-transfer catalysis at room temperature. Scope and limitations.

In this paper we present studies into the scope and limitations of asymmetric PTC epoxidation of enones and the oxidation-epoxidation of allylic alcohols using aqueous NaOCl in conjunction with a dihydrocinchonidine derived quaternary ammonium salt catalyst.