Iridium‐Catalyzed Reductive Nitro‐Mannich Cyclization

Abstract

A new chemoselective reductive nitro-Mannich cyclization reaction sequence of nitroalkyl-tethered lactams has been developed. Relying on the rapid and chemoselective iridium(I)-catalyzed reduction of lactams to the corresponding enamine, subsequent nitro-Mannich cyclization of tethered nitroalkyl functionality provides direct access to important alkaloid natural-product-like structures in yields up to 81 % and in diastereoselectivities that are typically good to excellent. An in-depth understanding of the reaction mechanism has been gained through NMR studies and characterization of reaction intermediates. The new methodology has been applied to the total synthesis of (±)-epi-epiquinamide in four steps.

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.…”

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,n eue kooperative Katalysator-Designs und neue Reaktionskaskaden. Während seiner Präsentation zeigte er seine Ergebnisse zur Total/Retro-Synthese von Manzamin A, [25] (AE)-Epi-Epichinamid, [26] (AE)-Vincadifformin, [27] (À)-Himalensin A [28] sowie die Spätfunktionalisierung von Amiden und Lactamen. [29] Er präsentierte auch Beispiele fürB IMP-katalysierte Reaktionen ("BIMP" steht fürb ifunktionelle Iminophosphoran-Katalysatoren), wie Nitro-Mannich-Reaktionen (Abbildung 5) [30] und Sulfa-Michael-Additionsreaktionen.…”

Expeditious and Divergent Total Syntheses of Aspidosperma Alkaloids Exploiting Iridium(I)‐Catalyzed Generation of Reactive Enamine Intermediates

“…Our hope was that the enamine could act as an electron‐rich nucleophile/dienophile and be readily intercepted by a strategically placed diene to afford pentacyclic natural products such as minovine and vincadifformine via a formal Diels–Alder reaction. Recent work from our group had indeed demonstrated the feasibility of generating and trapping reactive iminium ions—via enamine intermediates—from nitroalkyl‐linked lactam starting materials in a reductive nitro‐Mannich cyclization cascade using Vaska's catalyst in the presence of a silane terminal reductant …”