Dynamic Kinetic Asymmetric Domino Oxa‐Michael/Carbocyclization by Combination of Transition‐Metal and Amine Catalysis: Catalytic Enantioselective Synthesis of Dihydrofurans

Abstract

Into the pot: A one‐pot highly chemo‐ and enantioselective catalytic domino oxa‐Michael/carbocyclization between α,β‐unsaturated aldehydes and propargylic alcohols is presented. This dynamic kinetic transformation requires a combination of transition‐metal and amine catalysis to afford functionalized dihydrofurans in good to high yields and up to 99.5:0.5 e.r.

Highly Enantioselective Cascade Transformations by Merging Heterogeneous Transition Metal Catalysis with Asymmetric Aminocatalysis

“…We have recently reported on a one-pot homogeneous dynamic kinetic asymmetric transformation (DYKAT) employing chiral amines and Pd(PPh 3 ) 4 or PdCl 2 as co-catalysts for the preparation of a wide range of cyclopentenes and dihydrofurans in high yields (Figure 1)1415.…”

“…Thus, the design and discovery of novel cooperative catalytic systems to conquer this challenge are particularly pressing. In 2006, we discovered that C-C bond formation could be achieved by combining homogeneous transition-metal catalysis with aminocatalysis, and have since then developed dual catalytic systems for reactions, such as enantioselective α-allylic alkylaion of various carbonyl compounds1112, enantioselective β-alkylation of α,β-unsaturated aldehydes13, carbocyclizations of various enynes1415 and for the synthesis of homoallylboronates16. While successful, this methodology still suffers from drawbacks, the main being related to the use of homogeneous catalysts that are tedious to remove, resulting in inefficient separation, purification and recycling of the catalyst1718192021.…”

Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations

“…237 The authors reasoned that while the addition of propargyl alcohol (PrgOH) to the iminium intermediate was expected to be reversible and non-selective, the participation of palladium via its interaction with the triple bond would force the reaction forward. Irreversible asymmetric induction takes place at this stage of the reaction, as only the sterically favored diastereomeric Pd-alkyne complex 281 can entertain a nucleophilic attack to forge oxacyclopentane 282 that contains an exocyclic olefin at this stage.…”

Combined heterogeneous metal/organic catalysts for eco-friendly synthesis

“…Different Pd(0)-catalysts were used for the ARC [48,57,68]. Here the catalysts systems with Pd(0)-AmP-MCF or Pd(0)-aminopropyl-controlled pore glass (Pd(0)-AmP-CPG) as the co-catalyst exhibited a broad substrate scope and delivered various carbocycles 10, heterocycles 11 and 12 with high ers [69][70][71]. Here Pd(0)-AmP-CPG was the most efficient co-catalyst for this relay sequence.…”