Polycyclic Indoline-Benzodiazepines through Electrophilic Additions of α-Imino Carbenes to Tröger Bases.

Polycyclic indoline-benzodiazepines can be accessed through the intermolecular reaction of Tröger bases with N-sulfonyl-1,2,3-triazoles. Under RhII catalysis, α-imino carbenes are generated and a subsequent cascade of [1,2]-Stevens, Friedel-Crafts, Grob, and aminal formation reactions yield the polycyclic heterocycles as single isomers (d.r.>49:1, four stereocenters including two bridgehead N atoms). Further ring expansion by insertion of a second α-imino carbene leads to elaborated polycyclic 9-membered-ring triazonanes.

Synthesis of Pyrrolidines and Pyrrolizidines with α-Pseudoquaternary Centers by Copper-Catalyzed Condensation of α-Diazodicarbonyl Compounds and Aryl γ-Lactams.

N-aryl γ-lactams react intermolecularly with acceptor-acceptor diazo reagents, usually dicarbonyl compounds, in a copper-catalyzed process to yield functionalized pyrrolidines with α-pseudoquaternary centers. As 1,2-acyl or -phosphoryl migration is preferred, single regioisomers are obtained. Furthermore, in the presence of a Lewis acid, subsequent Friedel-Crafts reactions yield tricyclic pyrrolizidines in excellent yields (90-96 %) and diastereoselectivities (up to >20:1).

A temporary-bridge strategy for enantioselective organocatalyzed synthesis of aza-seven-membered rings.

We report the first enantioselective organocatalyzed domino synthesis of azepane moieties. This temporary-bridge strategy is based on a conceptually original annulation of ambident electrophilic and 1,4-bis-nucleophilic α-ketoamides with 1,3-bis-electrophilic enals. The obtained oxygen-bridged azepanes can be selectively transformed into optically active azepanone, azepanol or azepanedione derivatives of high synthetic value.

α,ß-Unsaturated acyl cyanides as new bis-electrophiles for enantioselective organocatalyzed formal [3+3]spiroannulation.

α,ß-Unsaturated acyl cyanides are key bis-electrophile substrates for successful domino enantioselective organocatalyzed Michael-intramolecular acylation domino sequences. This new reactivity has been applied to the synthesis of enantioenriched azaspiro[4,5]decanone ring systems by a formal [3+3]spiroannulation, constituting a rare example of synthesis of glutarimides in an optically active form.

Access to polyfunctionalized diquinanes, hydrindanes, and decalines via TiCl4 promoted Michael-aldol and Baylis-Hillman reactions.

The addition of 0.5 equiv of TiCl(4) to (cyclo)alkanones tethered to α,ß-unsaturated ketones afforded polyfunctionalized diquinanes, hydrindanes, and decalines. These products, resulting from a Michael-aldol or a Baylis-Hillman reaction, can be obtained with high or total diastereoselectivity in moderate to high yields. These scaffolds represent interesting building blocks for the synthesis of complex natural products.

The shortest synthetic route to puromycin analogues using a modified Robins approach.

We are reporting on the utility of commercial vinyl isocyanate for a practical synthetic route from adenosine to N(6)-bis-demethylpuromycin in seven steps and 65% overall yield. A clean one-pot conversion of 3'-bromo-2'-carbamoyl derivative 8 to 3'-amino-3'-deoxyadenosine derivative 10 is the main feature of this synthetic pathway. This synthesis is the shortest synthetic route toward 3'-(aminoacylamido)deoxyadenosines to date.