Direct Synthesis of Benzo[c]carbazoles by Pd-Catalyzed C-H [4 + 2] Annulation of 3-Arylindoles with External 1,3-Dienes.

Herein, we present a regioselective Pd-catalyzed C-H [4 + 2] benzannulation of N-unprotected 3-arylindoles with external readily available 1,3-dienes via an original sequence involving a Pd-catalyzed domino carbopalladation of 1,3-dienes/direct C2-H allylation of an indole ring followed by an oxidation or reduction step. Depending on the nature of the solvent, DCE or CH3CN, two consecutive approaches, oxidative or reductive, have been validated and applied to the design of a novel library of C6-alkyl or (E)-C6-styryl-benzo[c]carbazoles in moderate to good yields.

Enantioselective Total Synthesis of (+)-Eucophylline.

The total enantioselective synthesis of (+)-eucophylline 1 was achieved using as a key-structural motif a chiral piperidinone bearing the natural product all-carbon quaternary stereocenter. The elaboration of the latter is based on two strategies relying on the free-radical carbo-cyanation and sulfonyl-cyanation respectively of enantiopure substituted cyclopropenes and cyclobutenes. Co- or Ni-boride reduction of the nitrile functional group along with the cyclopropane and cyclobutane ring-opening then led to the formation of the chiral piperidinone ring. Further elaboration of the latter into the key 1-azabicyclo[3.3.1]nonane motif followed by its coupling with a 2-cyanoaniline allowed the formation of the tetrahydrobenzo[b][1,8]-naphthyridine skeleton of 1, which was finally accessible in 17 steps and 5.9 % overall yield from 1,1-dibromobutene.

p-Anisaldehyde-Photosensitized Sulfonylcyanation of Chiral Cyclobutenes: Enantioselective Access to Cyclic and Acyclic Systems Bearing All-Carbon Quaternary Stereocenters.

The photosensitized p-anisaldehyde-mediated addition of sulfonylcyanides onto the π-system of cyclobutenes is shown to afford highly functionalized cyclobutanes in high yields and diastereocontrol. The homochiral cyclobutene precursors are accessible on multigram scale in two steps through an asymmetric [2 + 2] cycloaddition/vinyl thioether reduction sequence. The enantiopure cyclobutylnitriles can be elaborated further through SmI2-mediated ring opening or converted into new enantiopure cyclobutenes through base-mediated sulfone elimination.