Lili Zhu

Total Synthesis of (±)-Cafestol: A Late-Stage Construction of the Furan Ring Inspired by a Biosynthesis Strategy

An efficient bioinspired approach to the total synthesis of (±)-cafestol features a late-stage installation of the furan ring with a mild Au-catalyzed cycloisomerization. The Et2AlCl-promoted aldehyde-ene cyclization and subsequent Friedel-Crafts reaction deliver a requisite tricyclic system in gram scale with high stereo- and regioselectivity. Moreover, a highly stereoselective SmI2-mediated aldehyde-alkene radical cyclization furnishes the key bicyclo[3.2.1]octane skeleton to offer an advanced intermediate for the synthesis of other oxygenated ent-kaurene diterpenoids.

Synthesis of Polyketide Stereoarrays Enabled by a Traceless Oxonia-Cope Rearrangement†

Polyketide antibiotics bearing skipped polyols represent a synthetic challenge. A SiCl4-promoted oxonia-Cope rearrangement of syn,syn-2-vinyl-1,3-diols was developed to forge an array of 1,5-pentenediols, thus providing versatile motifs for the preparation of 1,2,3,5-stereoarrays in a highly stereoselective manner. Further exploration with Sn(OTf)2 realized the rearrangement of a cross-aldehyde which tactically warrants the utility of the current approach to access complex polyketides. The origin of high stereoselectivity is attributed to a chairlike anti-conformation of the oxonium ion intermediate.

A Chiral Pentenolide-Based Unified Strategy toward Dihydrocorynantheal, Dihydrocorynantheol, Protoemetine, Protoemetinol, and Yohimbane

An organocatalytic cross-aldol reaction of formaldehyde (formalin) with alkyl aldehydes, followed by the Z-selective Horner-Wadsworth-Emmons (HWE) reaction and immediate lactonization, afforded γ-alkylated pentenolides in good overall yields and excellent enantioselectivities. Based on this scalable sequence, five quinolizidine alkaloids were synthesized in a unified and concise manner. The development of an in situ activation of a tertiary amide to improve the efficiency of the Bischler-Napieraiski (B-N) reaction was also noteworthy due to the generality to sensitive substrates for a variety of target molecules.

Catalytic Aza-Wacker Annulation: Tuning Mechanism by the Activation Mode of Amide and Enantioselective Syntheses of Melinonine-E and Strychnoxanthine

An unprecedented N-substituent of the amide was found to be crucial for the successful annulation to establish 2-azabicyclo[3.3.1]nonane and other ring skeletons in good yield. The novel catalytic aza-Wacker annulation methodology was further illustrated in the concise syntheses and the absolute configuration determinations of melinonine-E and strychnoxanthine.