Caio C. Oliveira

Intermolecular Enantioselective Heck-matsuda Arylations Of Acyclic Olefins: Application To The Synthesis Of β-aryl-γ-lactones And β-aryl Aldehydes

We describe herein a synthetically useful method for the enantioselective intermolecular Heck-Matsuda arylation of acyclic allylic alcohols. Aryldiazonium tetrafluoroborates were applied as arylating agents in the presence of Pd(TFA)2 and a chiral, commercially available, bisoxazoline ligand. The methodology is straightforward, robust, scalable up to a few grams, and of broad scope allowing the synthesis of a range of β-aryl-carbonyl compounds in good to high enantioselectivities and yields. This new enantioselective Heck-Matsuda arylation allowed the synthesis of β-aryl-γ-lactones and β-aryl aldehydes, which play a vital role as key intermediates in the synthesis of the biologically active compounds, such as (R)-baclofen, (R)-rolipram, (S)-curcumene, (S)-dehydrocurcumene, and (S)-tumerone.

Stereoselective Synthesis of Aryl Cyclopentene Scaffolds by Heck–Matsuda Desymmetrization of 3‐Cyclopentenol

A new enantioselective Heck-Matsuda desymmetrization reaction was accomplished by using 3-cyclopentenol to produce chiral five-membered 4-aryl cyclopentenol scaffolds in good yields and high ees, together with some 3-aryl-cyclopentanones as minor products. Mechanistically, the hydroxyl group of 3-cyclopentenol acts as a directing group and is responsible for the cis- arrangement in the formation of the 4-aryl-cyclopentenols.

Chemo-, Regio- and Stereoselective Heck Arylation of Allylated Malonates: Mechanistic Insights by ESI-MS and Synthetic Application toward 5-Arylmethyl-γ-lactones

We describe herein a general method for the controlled Heck arylation of allylated malonates. Both electron-rich and electron-poor aryldiazonium salts were readily employed as the aryl-transfer agents in good yields and in high chemo-, regio-, and stereoselectivity without formation of decarboxylated byproducts. Reaction monitoring via ESI-MS was used to support the formation of chelated Pd species through the catalytic cycle. Additionally, some Heck adducts were successfully used in the total synthesis of pharmacologically active γ-lactones.

Chapter 1 – Substrate-Directed Heck–Matsuda Arylations: From Curiosity to a Valuable Synthetic Tool

The Heck arylation of olefins by the substrate-directed Heck–Matsuda strategy using arenediazonium salts, especially the tetrafluoroborates, constitutes an effective way to synthesize functionalized olefins, thus making them more valuable intermediates in organic synthesis. The basic principle of the method relies on the complexation of a cationic δ-aryl-palladium species to a nearby functional group on the substrate in which structural and electronic arrangement governs the arylation process in a regio- and stereoselective manner. The present review highlights this strategy focusing on some selected syntheses accomplished in our laboratory. The synthetic strategy includes the directed arylation of allylic acetates, allylamine derivatives, and functionalized cyclopentene substrates. Illustrative syntheses include the kavalactones yangonine, methysticin, and dehydromethysticin, the antifungal drug naftifine, the phytohormones abamine and abamine SG, the drug cinacalcet, and the muscle relaxant alverine. Moreover, the method was also applied to the successful total synthesis of the sphingosine 1-phosphate agonist VPC01091, a promising drug for the treatment of multiple sclerosis. The examples presented herein demonstrate the substrate-directed strategy method as a general one applicable to metal-catalyzed processes other than the palladium-catalyzed Heck reaction.