Skeletal rearrangements in the 2,3-diazanorbornene series. A fast access to highly functionalized cyclopentanes.

[reaction: see text] Acid-catalyzed nucleophilic substitution of bicyclic hydrazine-epoxide involves nitrogen participation, leading to a skeletal rearrangement. This transformation enables the fast preparation of disubstituted bicyclic hydrazines in a regio- and stereoselective manner, leading to several polyfunctional diaminocyclopentanes after hydrogenolysis.

A straightforward synthesis of ynones by reaction of dimethylalkynylaluminum reagents with acid chlorides.

Alkynyldimethylaluminum reagents react with various aromatic and aliphatic acid chlorides in a fast and efficient way. This reaction provides a simple entry to numerous ynones, using readily available, inexpensive, and nontoxic metalating agent, and does not require any transition metal as a catalyst.

Synthesis of novel polycyclic indolyldiamines.

A rapid and stereoselective access to novel polycyclic indolyldiamines is described. The key step involves simple chemoselective transformations of a common bicyclic aminal intermediate, easily available on a large scale from an enantiomerically pure cyano oxazolopiperidine precursor.

Palladium-catalyzed cross-coupling of aryl electrophiles with dimethylalkynylaluminum reagents.

[reaction: see text] Alkynyldimethylaluminum reagents are easily available from terminal alkynes and trimethylaluminum via a triethylamine-catalyzed metalation. These compounds can react with various aromatic and heterocyclic halides in the presence of palladium in a fast and efficient way. This catalyzed cross-coupling reaction provides a simple entry to numerous internal alkynes, using a readily available, inexpensive, and nontoxic metalating agent.

Synthesis and reactivity of mixed alkynylalanes by direct triethylamine-catalyzed alumination of terminal alkynes.

[reaction: see text] Terminal alumination of alkynes by DIBALH or trimethylaluminum can be performed in a simple manner in the presence of a small amount of triethylamine. This new Lewis-base-catalyzed process delivers mixed alkynyldialkylalanes of great interest, without the need of an initial deprotonation step with lithium or sodium derivatives followed by a transmetalation.

Stereoselective ring opening of meso bicyclic hydrazines: a straightforward approach to hydrazino cyclopentenic cores.

The diastereoselective synthesis of hydrazinocyclopentenes 6 or 7 can be achieved in a straightforward manner from Diels-Alder adduct 4 using an acid-catalyzed rearrangement or a palladium-catalyzed allylic substitution reaction. In the latter case, enantioenriched compounds with ee values up to 58% can be obtained when an appropriate chiral ligand is used. [reaction: see text]

Total enantioselective synthesis and in vivo biological evaluation of a novel fluorescent BODIPY alpha-galactosylceramide.

Natural killer T (NKT) cells are a distinct subset of mature lymphocytes endowed with features of activated and regulatory T cells. alpha-Galactosylceramides (alpha-GalCers), the synthetic prototype of which is KRN7000, are the only natural reagents recognised by the T-cell receptor of NKT cells. The alpha-GalCer-activated NKT cells promptly release IFN gamma and IL-4 (IFN=interferon; IL=interleukin) and undergo apoptotic death within hours. In mice, activated NKT cells are responsible for antitumour activity and protection against autoimmune diseases. KRN7000 can thus be considered as the root of a family of novel immunoregulatory drugs. To get insights into the in vivo behaviour of alpha-galactosylceramides, an original fluorescent derivative has been prepared by following a convergent synthetic scheme. This strategy allows the introduction of different acyl chains, carbohydrate residues and various labels in the final steps of the synthesis. The fluorescent BODIPY probe derived from a versatile glycolipid precursor is as active as KRN7000 for inducing apoptosis of liver NKT cells. Fluorescence was detected in peritoneal macrophages and splenic antigen-presenting cells, in Kupffer-like cells in the liver, but not in lymphocytes.

Reversal of enantioselectivity in the asymmetric rhodium- versus iridium-catalyzed hydroboration of meso substrates.

The Ir-catalyzed asymmetric hydroboration of bicyclic hydrazines with ee and chemical yields up to 64% is reported. The switch from rhodium to iridium leads systematically to opposite enantiomers in this desymmetrization reaction.

Asymmetric Synthesis. 39.(1) Synthesis of 2-(1-Aminoalkyl)piperidines via 2-Cyano-6-phenyl Oxazolopiperidine.

The asymmetric synthesis of a series of 2-(1-aminoalkyl) piperidines using (-)-2-cyano-6-phenyloxazolopiperidine 1 is described. LiAlH(4) reduction of 1 followed by hydrogenolysis led to the diamine 3. The same strategy applied to C-2-methylated compound 7 afforded [(2S)-2-methylpiperidin-2-yl]methanamine (9). Addition of lithium derivatives to the cyano group of 1 resulted in the formation of an intermediate imino bicyclic system (11a-c) which could be diastereoselectively reduced to substituted diamino alcohols 13a-c. The addition of an excess of PhLi to 1 in the presence of LiBr furnished disubstituted amine 19, the precursor of diphenyl[(2S)-piperidin-2-yl]methanamine (22).