Total Synthesis of (–)-HM-3 and (–)-HM-4 Utilizing a Palladium-Catalyzed Addition of an Arylboronic Acid to an Allenic Alcohol Followed by Eschenmoser–Claisen Rearrangement

Abstract

The first asymmetric total synthesis of (-)-HM-3 and (-)-HM-4, aromatic sesquiterpenes isolated from the phytopathogenic fungus Helicobasidium mompa, has been achieved. Highlight of the synthesis is an enantiospecific construction of the quaternary carbon stereocenter utilizing a palladium-catalyzed addition of arylboronic acid to the allenic alcohol followed by EschenmoserClaisen rearrangement.

Asymmetric Total Syntheses of Di‐ and Sesquiterpenoids by Catalytic C−C Activation of Cyclopentanones

“…The synthesis started with preparation of the boronic acid 20 on a decagram scale by ortho lithiation of commercially available 2,3‐dimethoxytoluene followed by quenching with trimethylborate (Scheme ) . The Rh‐catalyzed asymmetric 1,4‐addition proceeded efficiently to deliver the cyclopentanone 21 in 98 % yield with 98 % ee using ( R , R )‐Ph‐bod as the chiral ligand .…”

“…Thesynthesis started with preparation of the boronic acid 20 on ad ecagram scale by ortho lithiation of commercially available 2,3-dimethoxytoluene followed by quenching with trimethylborate (Scheme 8). [29] TheRh-catalyzed asymmetric 1,4-addition proceeded efficiently to deliver the cyclopentanone 21 in 98 %yield with 98 % ee using (R,R)-Ph-bod as the chiral ligand. [30] Under the standard reaction conditions for the CÀCa ctivation of 3-arylcyclopentanones, [7a] however, only moderate conversions for the desired a-tetralone product 22 were observed (entry 1, Table 1).…”

Enantioselective palladium catalyzed conjugate additions of ortho-substituted arylboronic acids to β,β-disubstituted cyclic enones: total synthesis of herbertenediol, enokipodin A and enokipodin B

“…This observation is in line with a very recent report by Yoshida and co-workers, who also encountered reproducibility issues. 29 Alternatively, Meyers and co-workers described a reduction protocol in which 7 was converted into the corresponding thioketone and was subsequently reduced with RANEY® nickel (Ra/Ni), leading to 8 in 58% yield over the two steps. 21a This strategy proved to be reproducible in our hands, providing us with 8 in 65% yield.…”

Synthetic Study Aiming at the Tricyclic Core of 12-epi-JBIR-23/24

“…Such a failure could be attributed to the twisty boat-like conformation of ring C in 25 , which prompted us to resort to [3,3]-rearrangement. However, although an array of attempts involving Eschenmoser–Claisen rearrangement, Johnson–Claisen rearrangement, Overman rearrangement, and aliphatic Claisen rearrangement were surveyed, either recovery of 25 or the formation of undesired aromatized compounds was discovered. Alternatively, we prepared the xanthate 28 from 25 , as a precursor of [3,3]-sigmatropic rearrangement.…”