Synergistic formal ring contraction for the enantioselective synthesis of spiropyrazolones

Abstract

We report the first ring contraction/formal [6 + 2] cycloaddition using synergistic Pd(0)/secondary amine catalysis, obtaining [5,5]-spiropyrazolone derivatives in excellent yields and stereoselectivities. We detected the key palladium activated intermediate in its protonated form by mass spectrometry and characterized its structure by infrared spectroscopy and DFT calculations, allowing us to propose a conceivable mechanistic pathway for this reaction.

A New Insight into the Stereoelectronic Control of the Pd0‐Catalyzed Allylic Substitution: Application for the Synthesis of Multisubstituted Pyran‐2‐ones via an Unusual 1,3‐Transposition

“…Indeed, in the h 2 -intermediates 4d and 4j (4/4_rot)t he alignmento ft he Pd-C(5) and C(6)ÀOb onds deviates from collinearity by mere + 188 and + 168 (E), respectively,w hich is well within the 308 tolerance [20][21][22] proposed for the Wagner-Meerwein rearrangements (vide supra). [28] On the contrary,t he same deviation for 4u is as large as + 498 whichp rovides an elegant and intuitive stereoelectronic explanation for the lack of reactivity of the compound.…”

“…Computational resources were provided by the IT4Innovations National Supercomputing Center,p roject LM2015070 of the Czech Ministry of Education. We also thank Prof. Jana Roithovµ for discussing the computational detailsm entioned in reference [28],a nd Mr.T omµš Belloň for designingt he cover image.…”

Identifying reactive intermediates by mass spectrometry

“…These reactions are typically catalysed by palladium complexes that are oen neutral in solution. They can be detected as protonated ions or as anions, 14,15 but it is by far not a general rule. Therefore, these intermediates are oen studied using charge-tagging approach.…”

Enamine/Transition Metal Combined Catalysis: Catalytic Transformations Involving Organometallic Electrophilic Intermediates

“…Furthermore, the group of Rios also successfully disclosed various strategies for the preparation of carbocycles type molecules. For instance, through the enantioselective ring expansion of vinyl cyclopropanes, providing highly substituted [86], formal ring contraction for the generation of spiropyrazolones 106 [87], the asymmetric synthesis of cyclopentanes with four stereogenic centers 108 [88], the enantioselective acetyl aza-arene addition to α,β-unsaturated aldehydes affording chiral 2-acyl pyridines and pyrazines 110 [89], or, very recently disclosed, the highly enantioselective cascade reaction for the synthesis of dihydroacridines 112 (Scheme 23) [90]. Topics in Current Chemistry (2019) 377:38…”