Catalytic Enantioselective and Divergent Total Synthesis of (+)-10-Oxocylindrocarpidine, (+)-Cylindrocarpidine, (−)-N-Acetylcylindrocarpinol, and (+)-Aspidospermine

Abstract

The catalytic enantioselective and divergent total syntheses of Aspidosperma alkaloids (+)-10-oxocylindrocarpidine 7, (+)-cylindrocarpidine 1, (-)-N-acetylcylindrocarpinol 6, and (+)-aspidospermine 8 have been accomplished in 11 steps from a common precursor (15) on the basis of a highly concise route. The route features three metal-catalyzed reactions, including the key Pd-catalyzed decarboxylative asymmetric allylation of carbazolones developed in our laboratory. Our syntheses, using a combination of C-H activation, enantioselective catalysis, and collective synthesis, represent the first total synthesis of 10-oxocylindrocarpidine and the first asymmetric total synthesis of cylindrocarpidine and N-acetylcylindrocarpinol.

Diastereoselective synthesis of 3,4-dihydro-2H-pyran-4-carboxamides through an unusual regiospecific quasi-hydrolysis of a cyano group

“…The carbonyl group, through the formation of hemiketal ( A ), became a source of a hydroxy group that cyclized regiospecifically to the spatially proximate cyano group and caused the carboxamide formation. CACHE processes are essential for the chemistry of oxonitriles and sometimes can be the reason for unusual quasi-hydrolysis of the cyano group under mild conditions [15,19,23], but it was not mentioned by many authors [28–31]. …”

Enantioselective palladium-catalyzed allylic alkylation reactions in the synthesis of Aspidosperma and structurally related monoterpene indole alkaloids

“…In a subsequent report, the Shao group expanded their investigations to access alkaloids bearing oxygenation on the arene fragment (Scheme 12). 61 Allylic alkylation precursor 85 was synthesized in five steps and 41% overall yield from commercially available materials. Using their previously optimized conditions, α-quaternary carbazolone 86 was obtained in 90% yield and 91% ee.…”

Cascade One‐Pot Synthesis of Indanone‐Fused Cyclopentanes from the Reaction of Donor‐Acceptor Cyclopropanes and Enynals via a Sequential Hydrolysis/Knoevenagel Condensation/[3+2] Cycloaddition

“…(1)]. In addition to the cross‐coupling reaction, the vinyl group of 3k could be reduced to an ethyl group by Pd‐C/H 2 , giving the desired product 4 in 72% yield [Eq. (2)].…”