Re₂O₇‐Mediated Dehydrative Cyclization Reactions: Total Synthesis of Herboxidiene and Its 12‐Desmethyl Analogue

Abstract

Re 2 O 7 catalysis effects efficient and stereoselective dehydrative cyclization reactions from monoallylic diols,with stereocontrol arising from thermodynamic equilibration. This method was applied to ar apid synthesis of the spliceosome inhibitor herboxidiene. The route was also utilized for the synthesis of an analogue that highlights the importance of asingle methyl group in biasing the conformation in the acyclic region of the molecule. Scheme 1. Re 2 O 7 -mediated allylic alcohol ionization. Scheme 2. Re 2 O 7 -mediated dehydrative cyclization. Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.201705924. Angewandte Chemie Communications compounds 22 and 36. Conflict of interestTheauthors declare no conflict of interest.

Syntheses and Biological Importance of Herboxidiene/GEX1A

“…In 2016 we published a total synthesis of herboxidiene by newly developed gold‐catalyzed Hosomi–Sakurai type of reaction of lactols and Stille reaction as key reactions . Recently in 2017 Floreancig and coworkers developed dehydrative cyclization reactions of monoallylic diols with Re 2 O and they implemented this method to the total synthesis of herboxidiene …”

“…[32] Recently in 2017 Floreancig and coworkers developed dehydrative cyclization reactions of monoallylic diols with Re 2 O and they implemented this method to the total synthesis of herboxidiene. [33] Here is a brief we described account on total syntheses reported up to date.Herboxidiene/GEX1A like many polyketidetype natural products, contributes well fragment convergent syntheses. Retrosynthetic analysis of herboxidiene has often followed in identifying almost similar fragments at same disconnection as highlighted in Figure 5.…”

“…Recently in 2017, Floreancig et al developed an efficient dehydrative cyclisation reaction of monoallylic diols with Re 2 O 7 producing tetrahydropyrans with good stereoselectivity. [33] this method was implemented to the total synthesis of herboxidiene. The retrosynthetic analysis reveals the key intermediate 110, which was prepared from two key subunits β-lactone 111 and alkyne 112.…”

“…Recently in 2017, Floreancig et al . developed an efficient dehydrative cyclisation reaction of monoallylic diols with Re 2 O 7 producing tetrahydropyrans with good stereoselectivity . this method was implemented to the total synthesis of herboxidiene.…”

Stereoselective Decarboxylative Alkylation of Titanium(IV) Enolates with Diacyl Peroxides

“…2 Indeed, the alkylation of alkaline enolates of chiral N-acyl oxazolidinones 3 and pseudoephedrines 4,5 hold a prominent position among the carbon-carbon bond forming reactions and usually remain the method of choice for the synthesis of natural products. 6,7 These, as well as related methods, [8][9][10] proceed through a SN2 mechanism so their scope is restricted to a set of privileged electrophiles (Scheme 1). Furthermore, Evans reported that titanium(IV) enolates of chiral N-acyl oxazolidinones may undergo stereoselective SN1-like alkylations with certain oxocarbenium intermediates (Scheme 1).…”