An Asymmetric Total Synthesis of Tupichilignan A using Donor–Acceptor Cyclopropanes: A Structural Revision of Tupichilignan A

Abstract

An asymmetric total synthesis of tupichilignan A was achieved using enantioenriched donor–acceptor (D–A) cyclopropanes. The key steps include an asymmetric cyclopropanation using the Hayashi–Jørgensen catalyst, an oxy‐homo‐Michael reaction of a bicyclic D–A cyclopropane, an α‐benzylation of a γ‐lactone, a decarboxylation furnishing a trans‐α,β‐dibenzyl‐γ‐lactone, a configurational inversion of a hydroxy chiral center via oxidation, and a final reduction, all of which occur with high stereoselectivity. The spectral data of the diastereomer previously identified in the literature as tupichilignan A were found to be inconsistent with the reported data for the natural product. On the basis of the spectral data of both of the synthesized diastereomers, the structure of tupichilignan A was revised, and the absolute configuration of the 7 position of tupichilignan A was changed from R to S.

Creating Stereocenters within Acyclic Systems by C–C Bond Cleavage of Cyclopropanes

“…176,177 This strategy was used for the diastereoselective copper-catalyzed addition of benzyl alcohol to activated cyclopropane 96, resulting in the formation of the key intermediate 97 en route to the total synthesis of tupichilignan A (Scheme 31). 178 A similar outcome was observed for the Sc(OTf) 3 -catalyzed kinetic resolution of racemic cyclopropane 98 (Scheme 32). Enantioenriched linear scaffolds 99 were obtained by the addition of several different nucleophiles such as alcohols, sulfides, amines, and carboxylic acids.…”

Lewis acid-catalyzed one-pot thioalkenylation of donor–acceptor cyclopropanes using in situ generated dithiocarbamates and propiolates

“…3 These transformations have already been utilized in several total syntheses, incorporating D–A cyclopropane-derived motifs at intermediate stages. 4 However, there have been limited investigations into the methods of 1,3-bisfunctionalization of D–A cyclopropanes. 5 The primary hurdle involves the controlled delivery of a nucleophile and an electrophile in a manner that directs their preference for reacting with the donor–acceptor cyclopropanes, rather than spontaneously with each other.…”