Guillaume Vincent

Studies toward spiroetherone A uncovered an unexpectedly rich reactivity landscape within the avarane skeleton. An intramolecular Michael addition onto a quinone enabled access to the characteristic spiroenedione core of the natural product. Alongside this transformation, diverse and unanticipated reaction pathways emerged, generating structurally complex molecular architectures. These included an unusual S _N Ar on an electron‐rich arene, a McMurry‐type ketone–ester coupling with concomitant reductive deoxygenation, or Wagner–Meerwein rearrangements furnishing oxaspiro[4.5]dienone and dihydrochromane scaffolds. As other divergent transformations developed, a (3 + 2) quinone monoacetal dimerization produced a dibenzofuran motif close to popolohuanone E, whereas a PIDA‐mediated alkene–phenol nitrile cyclization/Ritter reaction sequence delivered an unprecedented pentacyclic bridged imidate. This work demonstrates how synthetic exploration toward complex natural products can reveal unforeseen modes of reactivity and skeletal diversification.

We report our quest toward the total synthesis of the reported structure of the sesquiterpene pestalustaine A and its unprecedented tricyclic skeleton. Our retrosynthesis involved a transannular Michael addition of a 1,3‐keto‐ester and enal‐containing bicyclo[4.4.1]undec‐3‐ene obtained from the ring expansion of a chiral γ,γ−disubstituted cyclohexanone and stereoselective Hosomi‐Sakurai reaction. Serendipity allowed us to uncover powerful divergent and unexpected cyclizations of this bicycle in ionic or oxidative conditions, giving access to complex tricyclic architectures such as tricyclo[5.2.1.1 ^2,5 ]undecane, octahydro‐1,5‐methanonaphthalene, octahydro‐12,6‐methanonaphthalene frameworks, and the octahydro‐1,5‐methanoazulene reported skeleton of pestalustaine A. The present synthetic study also led us to note a discrepancy between the reported structure of pestalustaine A and the 2D NMR data, which led us to propose a revised structure of the natural product to a caryophyllene‐type framework, a reassignment supported by computational prediction of NMR chemical shifts.

We report our quest toward the total synthesis of the reported structure of the sesquiterpene pestalustaine A and its unprecedented tricyclic skeleton. Our retrosynthesis involved a transannular Michael addition of a 1,3‐keto‐ester and enal‐containing bicyclo[4.4.1]undec‐3‐ene obtained from the ring expansion of a chiral γ,γ−disubstituted cyclohexanone and stereoselective Hosomi‐Sakurai reaction. Serendipity allowed us to uncover powerful divergent and unexpected cyclizations of this bicycle in ionic or oxidative conditions, giving access to complex tricyclic architectures such as tricyclo[5.2.1.1 ^2,5 ]undecane, octahydro‐1,5‐methanonaphthalene, octahydro‐12,6‐methanonaphthalene frameworks, and the octahydro‐1,5‐methanoazulene reported skeleton of pestalustaine A. The present synthetic study also led us to note a discrepancy between the reported structure of pestalustaine A and the 2D NMR data, which led us to propose a revised structure of the natural product to a caryophyllene‐type framework, a reassignment supported by computational prediction of NMR chemical shifts.

We report the total synthesis of (−)‐owerreine, a bis‐indole alkaloid biosynthetically assembled from two deoxoapodine units. This aspidosperma monomeric template was synthesized via a domino Michael/Mannich/ N ‐allylation sequence from a chiral indolyl‐ N ‐sulfinylimine and a DIAD‐oxidation‐promoted cycloetherification. It was further divergently transformed into an enamine precursor and an α,β−unsaturated indolenine, which were diastereoselectively assembled in the presence of the Eschenmoser salt through a [4+2] annulation. DFT calculations were deployed to gain insight into the mechanism and diastereoselectivity of this key step.

We report our quest toward the total synthesis of the reported structure of the sesquiterpene pestalustaine A and its unprecedented tricyclic skeleton. Our retrosynthesis involved an transannular Michael addition of a 1,3-keto-ester and enal-containing bridged-7,7-bicycle obtained from the ring expansion of a chiral disubstituted cyclohexanone and stereoselective Hosomi-Sakurai reaction. Serendipity, allowed us to uncover powerful divergent and unexpexpected cyclizations of this bicycle in ionic or oxidative conditions giving access to complex tricyclic architectures such as tricyclo[5.2.1.12,5]undecane, octahydro-1,5-methanonaphthalene, octahydro-12,6-methanonaphthalene frameworks and the octahydro-1,5-methanoazulene reported skeleton of pestalustaine A. The present synthetic study also led to note a discrepancy between the reported structure of pestalustaine A and the 2D NMR data which led to propose a revised structure of the natural product to a caryophyllene-type framework.

We report the total synthesis of owerreine, a bis-indole alkaloid biosynthetically assembled from two deoxoapo-dine units. This aspidosperma monomeric template was synthesized via an Andrade’s domino Michael/Mannich/N-allylation sequence from a chiral indolyl-N-sulfinylimine and a DIAD-oxidation-promoted cycloetherification and further divergently transformed into an enamine precursor and an alpha,beta-unsaturated indolenine which were diastereoselectively assembled in presence of the Eschenmoser salt through a [4+2] annulation.

We report the total synthesis of dactyloquinone A and spiroetherone A from a meroterpenoid scaffold obtained by the deconjugative alkylation of a Wieland–Miescher type ketone. For dactyloquinone A, we employed an intramolecular hydrofunctionalisation of the internal trisubstituted alkene with a quinone monoacetal via a metal‐hydride hydrogen atom transfer (MHAT) process to form the key C─O bond. For spiroetherone A, we relied on a stereospecific quinol–spiroenedione rearrangement. The initially postulated structure of spiroetherone A was first synthesized, but was found to be different from the natural product. Finally, spiroetherone A was shown to be epimeric at the spirocyclic carbon. This finding was confirmed by total synthesis involving epimerization of the spirocycle via a late‐stage singlet oxygen [4+2] cycloaddition to a cyclohexadiene derived from the initial enedione.

We report a ferrocene-mediated electrochemical intermolecular oxidative annulation between malonates and styrenes that avoids the use of excess oxidants such as Mn(OAc)₃. The reaction proceeds via presumably the generation of a malonyl radical that adds to the styrene. After further anodic oxidation, the resulting benzylic carbocation is intercepted by one of the esters to deliver the desired γ-lactones.

We report the total synthesis of dactyloquinone A and spiroetherone A from a meroterpenoid scaffold obtained by the deconjugative alkylation of a Wieland–Miescher type ketone. For dactyloquinone A, we employed an intramolecular hydrofunction-alisation of the internal trisubstituted alkene with a quinone monoacetal via a metal-hydride hydrogen atom transfer (MHAT) process to form the key C–O bond. For spiroetherone A, we relied on a stereospecific quinol-spiroenedione rearrangement. The initially postulated structure of spiroetherone A was first synthesized, but was found to be different from the natural product. Finally, spi-roetherone A was shown to be epimeric at the spirocyclic carbon. This finding was confirmed by total synthesis involving epimeri-zation of the spirocycle via a late-stage singlet oxygen [4+2] cycloaddition to a cyclohexadiene derived from the initial ene-dione.

We report access to the core of biologically relevant aromatic abietane diterpenoids and to the formal synthesis of podocarpic and lambertic acids or γ-lactones via an electrochemical bicyclization process initiated by the ferrocene-mediated anodic oxidation of a malonate via single electron-transfer. This approach permits escaping the use of excess of oxidants such as Mn(OAc)₃ and the associated complicated purification.