A Concise Synthesis of Presilphiperfolane Core through a Tandem TMTU–Co‐Catalyzed Pauson–Khand Reaction and a 6π Electrocyclization Reaction (TMTU=Tetramethyl Thiourea)

Abstract

The synthesis of strained polycyclic systems from readily available precursors with a minimum number of steps and with regio- and stereochemical control constitutes an important synthetic challenge. Herein, we report a tandem reaction comprising Co-TMTU (tetramethyl thiourea)-catalyzed Pauson-Khand (PK) and 6π-electrocyclization reactions for the formation of the highly strained core of presilphiperfolanols. The developed chemistry has been applied to the total syntheses of 4-epi-presilphiperfolan-8-ol and 7-epi-presilphiperfolan-1-ol.

Enantiospecific Total Synthesis of the Highly Strained (−)-Presilphiperfolan-8-ol via a Pd-Catalyzed Tandem Cyclization

“…While 6 itself is the progenitor of a number of other frame­works (such as 8 – 10 ), , natural product 5 could also potentially serve a similar role in Nature, as its separate exposure to different acid sources leads to many of these same structures, presumably via a strain-relieving ionization of its tertiary alcohol, eliminating its 1,2- trans ring fusion. To date, however, 5 has remained an unsolved synthetic challenge despite several attempts; those efforts have been able to generate its full carbon framework, but not with the proper functionalization and/or stereo­chemical arrangement of substituents at the C-4 and C-8 positions in its most strained form. By contrast, both of its cousins ( 11 and 12 ), molecules that possess a 1,2- trans ring fusion element within a slightly larger [4.3.0]­nonane framework, have been the subject of successful and creative synthetic campaigns by the groups of Stoltz and Weyerstahl .…”

Total Synthesis of Natural Terpenoids Enabled by Cobalt Catalysis

“…As shown in Figure 2E-IV , Yang and Gong ( Zhang et al, 2017 ) explored an approach of tandem Pauson–Khand and 6π-electrocyclization toward the total syntheses of 4- epi -presilphiperfolan-8β-ol (119) and 7- epi -presilphiperfolan-1β-ol (120). The preparation of cyclization precursor (117) was achieved from commercially available ketone (116) in a two-step.…”

The Total Synthesis of Diquinane‐Containing Natural Products

“…Notably,w hen compound 127 was directly subjected to the Diels-Alder reaction, the undesired C7 configuration was formed exclusively.T he major 7b isomer was further elevated to the re-porteds tructures of two natural products,w hich provided NMR evidencef or reassignment of the natural-occurring structures (Scheme 23). Comparably,Y ang and Gong group [65] developed an efficient thiourea-promoted Pauson-Khand reaction/ 6p-electrocyclization cascade of enyne substrate 131 to construct the diquinane-containing tricyclic presilphiperfolane core 133 in one pot. Unfortunately,i nt he followinge laboration to the natural product, the C7 and C4 stereochemistry problem arose and could not be solved,w hich ultimately led to two natural product analogues (Scheme 24).…”