Stereoselective Synthesis of the Monomeric Unit of Actin Binding Macrolide Rhizopodin

An efficient, scalable, and stereocontrolled synthesis of the entire carbon framework of an actin binding dimeric macrolide rhizopodin has been accomplished in its protected form. The key features of our synthesis include a titanium catalyzed <i>anti</i> acetal aldol reaction, a substrate controlled diastereoslelective prenyl stannylation, a Mukaiyama aldol reaction, an indium mediated diastereoselective propargylation, and an advanced stage Stille coupling reaction

Formal Synthesis of Actin Binding Macrolide Rhizopodin

Formal synthesis of an actin binding macrolide rhizopodin was achieved in 19 longest linear steps. The key features of the synthesis include a stereoselective Mukaiyama aldol reaction, dual role of a Nagao auxiliary (first, as a chiral auxiliary of choice for installing hydroxy centers and, later, as an acylating agent to form an amide bond with an amino alcohol), late stage oxazole formation, and Stille coupling reactions

Diversity-Oriented Approach to <i>N-</i>Heterocyclic Compounds from α‑Phenyl-β-enamino Ester via a Mitsunobu-Michael Reaction Sequence

Herein we delineate a novel route for the diastereoselective construction of diversely substituted <i>N</i>-heterocyclic ring systems as valuable scaffolds for natural products and pharmaceuticals, starting from an easily accessible prochiral α-phenyl-β-enamino ester. The reaction sequence relies on the unexplored reactivity of α-phenyl-β-enamino ester as a nucleophilic partner in the Mitsunobu reaction to forge the <i>N</i>-tethered alkene–alcohol/thiol/amine intermediate, which was subjected to an intramolecular hetero-Michael addition reaction under mild conditions to furnish the respective <i>N</i>-heterocyclic compounds embedded with an exocyclic chiral center in high yields and excellent diastereoselectivities. The methodology is amenable for a broad range of substrates based on a metal-free approach

Diversity-Oriented Approach to <i>N-</i>Heterocyclic Compounds from α‑Phenyl-β-enamino Ester via a Mitsunobu-Michael Reaction Sequence

Herein we delineate a novel route for the diastereoselective construction of diversely substituted <i>N</i>-heterocyclic ring systems as valuable scaffolds for natural products and pharmaceuticals, starting from an easily accessible prochiral α-phenyl-β-enamino ester. The reaction sequence relies on the unexplored reactivity of α-phenyl-β-enamino ester as a nucleophilic partner in the Mitsunobu reaction to forge the <i>N</i>-tethered alkene–alcohol/thiol/amine intermediate, which was subjected to an intramolecular hetero-Michael addition reaction under mild conditions to furnish the respective <i>N</i>-heterocyclic compounds embedded with an exocyclic chiral center in high yields and excellent diastereoselectivities. The methodology is amenable for a broad range of substrates based on a metal-free approach

Diversity-Oriented Approach to <i>N-</i>Heterocyclic Compounds from α‑Phenyl-β-enamino Ester via a Mitsunobu-Michael Reaction Sequence

Herein we delineate a novel route for the diastereoselective construction of diversely substituted <i>N</i>-heterocyclic ring systems as valuable scaffolds for natural products and pharmaceuticals, starting from an easily accessible prochiral α-phenyl-β-enamino ester. The reaction sequence relies on the unexplored reactivity of α-phenyl-β-enamino ester as a nucleophilic partner in the Mitsunobu reaction to forge the <i>N</i>-tethered alkene–alcohol/thiol/amine intermediate, which was subjected to an intramolecular hetero-Michael addition reaction under mild conditions to furnish the respective <i>N</i>-heterocyclic compounds embedded with an exocyclic chiral center in high yields and excellent diastereoselectivities. The methodology is amenable for a broad range of substrates based on a metal-free approach

Diversity-Oriented Approach to <i>N-</i>Heterocyclic Compounds from α‑Phenyl-β-enamino Ester via a Mitsunobu-Michael Reaction Sequence

Herein we delineate a novel route for the diastereoselective construction of diversely substituted <i>N</i>-heterocyclic ring systems as valuable scaffolds for natural products and pharmaceuticals, starting from an easily accessible prochiral α-phenyl-β-enamino ester. The reaction sequence relies on the unexplored reactivity of α-phenyl-β-enamino ester as a nucleophilic partner in the Mitsunobu reaction to forge the <i>N</i>-tethered alkene–alcohol/thiol/amine intermediate, which was subjected to an intramolecular hetero-Michael addition reaction under mild conditions to furnish the respective <i>N</i>-heterocyclic compounds embedded with an exocyclic chiral center in high yields and excellent diastereoselectivities. The methodology is amenable for a broad range of substrates based on a metal-free approach

Diversity-Oriented Approach to <i>N-</i>Heterocyclic Compounds from α‑Phenyl-β-enamino Ester via a Mitsunobu-Michael Reaction Sequence

Herein we delineate a novel route for the diastereoselective construction of diversely substituted <i>N</i>-heterocyclic ring systems as valuable scaffolds for natural products and pharmaceuticals, starting from an easily accessible prochiral α-phenyl-β-enamino ester. The reaction sequence relies on the unexplored reactivity of α-phenyl-β-enamino ester as a nucleophilic partner in the Mitsunobu reaction to forge the <i>N</i>-tethered alkene–alcohol/thiol/amine intermediate, which was subjected to an intramolecular hetero-Michael addition reaction under mild conditions to furnish the respective <i>N</i>-heterocyclic compounds embedded with an exocyclic chiral center in high yields and excellent diastereoselectivities. The methodology is amenable for a broad range of substrates based on a metal-free approach

An Approach to a Bislactone Skeleton: A Scalable Total Synthesis of (±)-Penifulvin A

An efficient and scalable total synthesis of the architecturally challenging sesquiterpenoid (±)-penifulvin A has been accomplished via a 12-step sequence with an overall yield of 16%. For the construction of this structurally complex tetracyclic molecule, the key steps used included 1,4-conjugate addition, a Pd(0) catalyzed cross-coupling reaction between an enol phosphate and trimethyl aluminum, Claisen rearrangement using the Johnson orthoester protocol, Ti­(III)-mediated reductive epoxide opening–cyclization, Lewis acid catalyzed epoxy-aldehyde rearrangement, and finally a substrate controlled oxidative cascade lactonization process

Application of Cp₂TiCl-Promoted Radical Cyclization: A Unified Strategy for the Syntheses of Iridoid Monoterpenes

An expedient approach toward the unified total syntheses of (+)-iridomyrmecin, (−)-isoiridomyrmecin, (+)-7-<i>epi</i>-boschnialactone, (+)-teucriumlactone, and (−)-dolichodial in chirally pure forms starting from readily available (+)-β-citronellene is delineated combining step economy and simplicity. Highlights include a Ti­(III)-mediated reductive epoxide opening-cyclization for the construction of the core cyclopenta­[<i>c</i>]­pyran skeleton of the iridoid lactones with complete diastereoselectivity for the newly created bridgehead stereogenic centers. Subsequent transformations facilitate a short access to (+)-teucriumlactone and (−)-dolichodial and formal access to potentially other iridoids

Application of Cp₂TiCl-Promoted Radical Cyclization: A Unified Strategy for the Syntheses of Iridoid Monoterpenes

An expedient approach toward the unified total syntheses of (+)-iridomyrmecin, (−)-isoiridomyrmecin, (+)-7-<i>epi</i>-boschnialactone, (+)-teucriumlactone, and (−)-dolichodial in chirally pure forms starting from readily available (+)-β-citronellene is delineated combining step economy and simplicity. Highlights include a Ti­(III)-mediated reductive epoxide opening-cyclization for the construction of the core cyclopenta­[<i>c</i>]­pyran skeleton of the iridoid lactones with complete diastereoselectivity for the newly created bridgehead stereogenic centers. Subsequent transformations facilitate a short access to (+)-teucriumlactone and (−)-dolichodial and formal access to potentially other iridoids