Short Scalable Route to Apiaceae Sesquiterpene Scaffolds: Total Synthesis of 4-epi-Epiguaidiol A

Abstract

The oxy-Cope/ene reaction cascade to form a locked elemane conformer allows the short scalable synthesis of versatile Apiaceae scaffolds. The divergent fate of the obtained macrocyclic germacrane is surveyed under cationic and dioxygeninduced Prins-type reaction conditions to allow the diastereoselective synthesis of oxidized Apiaceae guaiane congeners and the total synthesis of 4-epi-epiguaidiol A. Additionally, the unprecedented reduction of a hydrogen-bond-biased guaiane substrate permits the chemoselective synthesis of desoxo-jungiaguaiane.

Vinyltriarylbismuthonium Salts: Powerful Vehicles for α-Vinylation of Carbonyl Compounds

“…The broad substrate scope observed for the direct vinylation of ketone lithium enolates using Vinyl-Bis reagents opened up the possibility of developing reaction sequences in which enolates generated via conjugate addition reactions to α,β-unsaturated ketones are intercepted with the vinylation reagent. Thus, the 1,4-reduction of ( S )-carvone with l -selectride followed by capturing the intermediate enolate with 3c produced the vinyl product 9a in 92% yield, as a 8.7:1 mixture of diastereomers . When this reaction was performed at the 5.0 mmol scale, the product was isolated in 95% yield, with 8:1 diastereoselectivity.…”

Selective preparative ‘oxidase phase’ in sesquiterpenoids: the radical approach

“…Recently, Zografos’ group reported an interesting dioxygen-induced C–H oxidation for the synthesis of epi -epiguaianol ( 246 ). 65 Based on earlier findings of the group, non-natural elemane-type sesquiterpenoids can serve as ideal precursors to access germacranolides and guaianolides through an oxy–Cope-(ene) reaction (cascades). 17 Applying an oxy–Cope/ene sequence to a diasteroisomeric mixture of 241 ( anti : syn = 4 : 1), readily accessible from ( R )-carvone ( 33 ) in 7 steps, led to germacrane 242 and guaiane 243 as a 50 : 50 mixture in 70% yield (Scheme 24).…”

Phosphine-promoted intramolecular Rauhut–Currier/Wittig reaction cascade to access (hetero)arene-fused diquinanes

“…We transformed 8g to 12g via PMB deprotection followed by dehydration of the primary alcohol, Scheme 4. To undertake an oxy-Cope rearrangement, we converted 12g to the allyl vinyl carbinol 13g by the addition of the vinyl Grignard reagent, which, upon exposure to potassium hydride, prompted a cascade oxy-Cope rearrangement and intramolecular ene-type cyclization 8 to generate an unexpected octahydrobenzo[ e ]- as -indacene 14g in 54% yield. Further, 14g was converted to the tetrahydrobenzo[ e ]- as -indacene 15g under acidic conditions.…”