Construction of Enantiopure Taxoid and Natural Product-like Scaffolds Using a C–C Bond Cleavage/Arylation Reaction

Abstract

An approach to construct enantiopure complex natural product-like frameworks, including the first reported synthesis of a C17 oxygenated taxoid scaffold, is presented. A palladium-catalyzed C-C activation/cross-coupling is utilized to access these structures in a short sequence from (+)-carvone; the scope of this reaction is explored.

Transition Metal‐Mediated C−C Single Bond Cleavage: Making the Cut in Total Synthesis

“…Although efficient access to the macrocyclic strap has been well-established in previous syntheses,a ccessing highly functionalized cyclohexenyl fragments such as 20 has previously been aparticularly laborious endeavor, adding greatly to overall step counts. [18,19] To address the challenge of accessing fragments of this nature more efficiently,S arpong and co-workers envisioned obtaining this cyclohexenyl fragment from the chiral pool terpene (S)-carvone by employing aC ÀCb ond-cleavage reaction, which would result in as ubstantial remodeling of the carvone core framework and enable efficient access to 20.P reviously,b uilding on work pioneered by others on the C À Ccleavage/functionalization of cyclobutanols, [20][21][22] Sarpong and co-workers had established ap owerful strategy that entailed using enantioenriched cyclobutanols 22 derived from carvone in at ransition-metalmediated CÀCbond-cleavage reaction to produce aversatile organometallic intermediate 23 primed for further function-alization, including C À Cb ond-forming processes [23] (Scheme 4). Overall, this strategy provides efficient access to avariety of stereochemically rich cyclohexenones that can be elaborated to diverse natural product-like scaffolds.…”

Pd-catalyzed reactions of cyclopropanols, cyclobutanols and cyclobutenols

“…For the construction of taxol scaffold, Sarpong and co-workers carried out the arylative ringopening of (+)-carvone derivatives 38 and 39 using the Pd(OAc) 2 /(R)-BINAP procedure (Eqs 96 and 97). 93 In some cases, changing BINAP for P(t-Bu) 3 led also to effective crosscouplings (Eq. 96).…”

“…90 After the cross-coupling of 39a and 39b with 2-methylprop-1-en-1-yl bromide under experimental conditions of Eq. 97, 93 Sarpong and co-workers used a variety of vinyl bromides or iodides. 94 Optimization of the reaction conditions led to retain Pd(PCy 3 ) 2 as the catalyst and 1,4-dioxane as the solvent (Eq.…”

Übergangsmetallvermittelte Spaltung von C‐C‐Einfachbindungen

“…[18,19] Füre inen effizienteren Zugang zu diesen Fragmenten planten Sarpong et al die Synthese des Cyclohexenylfragments aus dem chiralen Te rpen (S)-Carvon über eine C-C-Bindungsspaltung,d ie zu einem deutlichen Umbau des Carvon-Kerngerüsts und damit zur effizienten Synthese von 20 führen würde.A ufbauend auf den wegweisenden Arbeiten anderer zur C-C-Spaltung/Funktionalisierung von Cyclobutanolen [20][21][22] entwickelten Sarpong et al zuvor eine effiziente Strategie,i nd er enantiomerenangereicherte Cyclobutanole 22,a us der Umwandlung von Carvon, in einer übergangsmetallvermittelten C-C-Bindungsspaltung umgesetzt wurden, die zur Bildung einer vielseitigen metallorganischen Zwischenverbindung 23 fürw eitere Funktionalisierungen, einschließlich C-C-Bindungsbildungen, führte (Schema 4). [23] Insgesamt ermçglicht diese Strategie den effizienten Zugang zu einer Vielzahl stereochemisch anspruchsvoller Cyclohexenone,die zu Gerüsten verschiedener Naturstoffe weiterentwickelt werden kçnnen.…”