Total Synthesis of (−)-Himalensine A

Abstract

The first enantioselective synthesis of (-)-himalensine A has been achieved in 22 steps. The synthesis was enabled by a novel catalytic, enantioselective prototropic shift/furan Diels-Alder (IMDAF) cascade to construct the ACD tricyclic core. A reductive radical cyclization cascade was utilized to build the B ring, and end-game manipulations featuring a molecular oxygen mediated γ-CH oxidation, a Stetter cyclization to access the pendant cyclopentenone, and a highly chemoselective lactam reduction delivered the natural product target.

Synthesis of Azabicyclic Building Blocks for Daphniphyllum Alkaloid Intermediates Featuring N‐Trichloroacetyl Enamide 5‐endo‐trig Radical Cyclizations

“…The resulting organic extract was washed with a saturated solution of sodium thiosulfate and brine, dried, and concentrated to afford 7 (120 mg, pale yellow oil, 95 %). 1 (8). LiAlH 4 (90 mg, 4.0 equiv.)…”

Ein Fest der Wissenschaft inmitten der Natur: Die 54. Bürgenstock‐Konferenz

“…Die Hauptbeiträge seiner Forschung behandelten die Entwicklung neuer, hoch enantioselektiver Methoden, die Totalsynthese komplexer Naturstoffe, neue kooperative Katalysator‐Designs und neue Reaktionskaskaden. Während seiner Präsentation zeigte er seine Ergebnisse zur Total/Retro‐Synthese von Manzamin A, (±)‐Epi‐Epichinamid, (±)‐Vincadifformin, (−)‐Himalensin A sowie die Spätfunktionalisierung von Amiden und Lactamen . Er präsentierte auch Beispiele für BIMP‐katalysierte Reaktionen (“BIMP” steht für bifunktionelle Iminophosphoran‐Katalysatoren), wie Nitro‐Mannich‐Reaktionen (Abbildung ) und Sulfa‐Michael‐Additionsreaktionen…”

A Celebration of Science amidst Nature: The 54th Bürgenstock Conference

“…Main contributions of his research linked to new, highly enantioselective methods development, total synthesis of complex natural products, new cooperative catalyst designs, and new cascade reactions. During his presentation he showed his results on the (total/retro) synthesis of manzamine A, (±)‐epi‐epiquinamide, (±)‐vincadifformine, (−)‐himalensine A, late‐stage functionalization of amides and lactams . He also presented examples of BIMP‐catalyzed reactions (BIMP/ bifunctional iminophosphorane‐type catalysts), such as nitro‐Mannich reactions (Figure ), and sulfa‐Michael addition reactions…”

“…[24] Thesecond lecture on Tu esday was presented by Darren J. Dixon (University of Oxford). Thetopic of his lecture was the catalytic approaches for simplifying complex molecule synthesis.H is research focuses on catalytic stereoselective synthesis,a nd on the investigation of new methodologies,which are able to simplify the synthesis of structurally complex frameworks,n atural products and molecules of biological importance.Main contributions of his research linked to new, highly enantioselective methods development, total synthesis of complex natural products,n ew cooperative catalyst designs,a nd new cascade reactions.D uring his presentation he showed his results on the (total/retro) synthesis of manzamine A, [25] (AE)-epi-epiquinamide, [26] (AE)-vincadifformine, [27] (À)-himalensine A, [28] late-stage functionalization of amides and lactams. [29] He also presented examples of BIMPcatalyzed reactions (BIMP/ bifunctional iminophosphoranetype catalysts), such as nitro-Mannich reactions ( Figure 5), [30] and sulfa-Michael addition reactions.…”