Organocatalytic Enantioselective Cross‐Vinylogous Rauhut–Currier Reaction of Methyl Coumalate with Enals

Abstract

The organocatalytic enantioselective intermolecular cross‐vinylogous Rauhut–Currier (RC) reaction of methyl coumalate with α,β‐unsaturated aldehydes is reported, and the enals are activated by iminium catalysis to serve as the Michael acceptors and methyl coumalate is used as an activated diene to generate a latent enolate. The excellent selectivity is driven by the aromaticity of methyl coumalate, and the post transformation of this heterocyclic structure into other electron‐deficient arenes and heterocycles have addressed, in part, the challenging selectivity issues of the intermolecular cross‐RC reactions and the limited scope of iminium catalysis.

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

“…Finally, it is worth mentioning the direct, organocatalytic, enantioselective intermolecular cross- vinylogous Rauhut–Currier reaction of methyl coumalate 717 and α,β-unsaturated aldehydes 718 recently developed by Liu and Zu, in which the enals were activated via iminium ion catalysis to serve as the Michael acceptors and methyl coumalate was used as an activated diene to generate the latent enolate ( Scheme 184 ). 484 Indeed, prolinol silylether A13 in the presence of 2-trifluoromethylbenzoic acid ( 720 ) as cocatalyst promoted the conjugate addition of pronucleophilic ester 717 to a varied repertoire of aromatic and aliphatic enals 718 to provide enantioenriched products 719 in high yields (up to 99%) and enantioselectivity (up to 99%). Several alternative pathways were proposed with a common pattern: a first nucleophilic, conjugate addition of EtOH or the prolinol to the C6 of methyl coumalate 717 would generate a transient dienolate 717′ , which could trigger the subsequent intermolecular 1,4-addition to the chiral, α,β-unsaturated iminium ion 718′ .…”

2‐Pyrone – A Privileged Heterocycle and Widespread Motif in Nature

“…[125] et al reported an organocatalyzed enantioselective Rauhut-Currier reaction of methyl coumalate (191) with α,β-unsaturated aldehydes 313. [128] The enals 313 were activated by iminium catalysis to serve as Michael-acceptors, while 1,6-addition of a nucleophile to pyrone 191 generated the latent enolate. The latter is also facilitated by the activation of pyrone 191 by the organocatalyst 314.…”

“…Enantioselective Rauhut-Currier reaction of methyl coumalate (191). [128] Scheme 64. Morita-Baylis-Hillman reaction of methyl coumalate (191).…”

Efficient Preparation of Methyl 2‐Oxo‐3‐aryl (heteroaryl)‐2H‐pyran‐5‐carboxylate via Pd‐Catalyzed Negishi Coupling

“…In addition, reactions with soft nucleophiles such as β‐ketoesters, 1,3‐diketones, or amines allow access to 2H ‐pyrans, [28] aromatic compounds, [29] and pyridines, [30–31] respectively. To the best of our knowledge, the involvement of methyl coumalate in a cross‐vinylogous Rauhut‐Currier reaction [32] and in a Morita‐Baylis‐Hillman reaction [33] are the scarce examples of processes giving access to coumalate adducts. Surprisingly, there is no report of carbon‐carbon bond formation from methyl 3‐bromo coumalate (3‐BrMC) and an organometallic species under transition metal catalysis, whereas brominated, triflyloxy‐ or tosyloxy‐pyran‐2‐ones readily react under Sonogashira, [34] Negishi, [5] Suzuki, [35–38] Stille [39–42]− type couplings or with Me 3 Al−dimethylaminoethanol complex as coupling reagent [43] .…”