Total Synthesis of Farnesin through an Excited‐State Nazarov Reaction

Abstract

The asymmetric total synthesis of farnesin, a rearranged ent‐kaurenoid, was achieved through a convergent approach involving photo‐Nazarov and intramolecular aldol cyclizations to build the syn‐syn‐syn hydrofluorenol ABC ring system and bicyclo[3.2.1]octane CD ring system in the first application of a UV‐light‐induced excited‐state Nazarov cyclization of a non‐aromatic dicyclic divinyl ketone in a total synthesis. Unlike the conventional acid‐promoted ground‐state Nazarov reaction, the excited‐state Nazarov reaction enables stereospecific formation of the highly strained syn‐syn‐syn‐fused hydrofluorenone scaffold through a disrotatory cyclization.

Total Synthesis of (−)-Lamellodysidine A via an Intramolecular Diels–Alder Reaction

“…Experimental procedure, single-crystal X-ray analysis of 1, and 1 H and 13 C NMR spectroscopic data (PDF)…”

“…Intermediate compounds 12, 13, and 4 were obtained when the reaction was conducted at room temperature. 12 Finally, the opening of the γ-lactone ring of 3 by hydrolysis and subsequent oxidation with IBX 13 furnished lamellodysidine A as a single isomer in a 77% yield. All the analytical data ( 1 H NMR, 13 C NMR, HRMS, IR, and [α] D ) of synthetic 1 matched those reported for the natural product.…”

“…12 Finally, the opening of the γ-lactone ring of 3 by hydrolysis and subsequent oxidation with IBX 13 furnished lamellodysidine A as a single isomer in a 77% yield. All the analytical data ( 1 H NMR, 13 C NMR, HRMS, IR, and [α] D ) of synthetic 1 matched those reported for the natural product. In addition, the stereochemistry and absolute configuration of synthetic 1 were clearly confirmed by X-ray crystallographic analysis (CCDC 2113718).…”

Recent Applications of Asymmetric Organocatalytic Methods in Total Synthesis

“…[20] In 2020, Gao and co-workers reported a convergent approach for the total synthesis of farnesin (514, Scheme 54). [101] One of the key intermediates of this synthesis, intermediate 506, was obtained from an NHC-catalyzed reac-tion. As shown in Scheme 54, they first synthesized the aldehyde 504, which was allowed to react with formaldehyde under the catalysis of the NHC catalyst generated in-situ from the thiazolium salt 505.…”

“…Further elaborations of this molecule afforded farnesin (514) via a multistep sequence that included photo-Nazarov reaction, intramolecular aldol reaction, and oxidation (Scheme 54). [101] In 2020, Scheidt and co-workers reported total synthesis of rauwolscine (525, Scheme 55). [102] The key intermediate for this synthesis, an enantioenriched enol lactone 517, was obtained by an NHC-catalyzed annulation reaction of the commercially available aldehyde 515, using 516 as the catalyst.…”