Synthesis of 2,3-Disubstituted Pyrrolidines and Piperidines via One-Pot Oxidative Decarboxylation−β-Iodination of Amino Acids

Abstract

A new synthesis of 2,3-disubstituted pyrrolidines and piperidines is described. This mild procedure is based on the one-pot oxidative decarboxylation-beta-iodination of alpha-amino acid carbamates or amides. The iodine is introduced at the previously unfunctionalized 3-position. Different substituents can be introduced at C-2, e.g., hydroxy, alkoxy, allyl, alkyl, etc. A trans relationship between the C-2 and C-3 substituents is exclusively obtained. The influence of the solvent and the ring size of the starting amino acid are studied, as well as the nature of the protecting group on the nitrogen. The stereoselectivity of the reaction was also studied using chiral methyl (2S,4S)-4-acetyloxyproline-1-carboxylate (8). The products obtained can be manipulated to give bicyclic systems present in many natural products. By using the tandem decarboxylation-iodination-alkylation reaction, 2-substituted-3-iodopyrrolidines are formed, which are precursors of 2-substituted-2,5-dihydropyrrols.

Bis(trimethylsilyl)ketene Acetals as C,O‐Dinucleophiles: One‐Pot Formation of Polycyclic γ‐ and δ‐Lactones from Pyridines and Pyrazines

“…These multiple introduction of halides and halide exchange reactions can be attributed to reversible opening and closure of the lactone ring. [54] …”

One‐Pot Conversion of Amino Acids into 2,5‐Disubstituted Oxazoles: No Metals Needed

“…The first steps of the process (conversion 1 → 5 ) were previously reported by our group 21a. Thus, the decarboxylation of amino acids (such as compound 1 ) using (diacetoxyiodo)benzene (DIB) and iodine under the irradiation of visible light, generated an iminium ion such as intermediate 3 .…”

One‐Pot Conversion of Proline Derivatives into Iodinated Iminosugar‐Based Nucleosides, Useful Precursors of Highly Functionalized Nucleoside Analogues

“…The process also worked with the purine bases trimethylsilyl‐chloropurine and trimethylsilyl‐benzyloxypurine (Scheme ). In these cases, the best results were obtained when the intermediate acyliminium ion was trapped with methanol to give (±)‐ 18 ,7b followed by solvent removal and replacement with acetonitrile. After addition of the silylated base and the Lewis acid at 0 °C, separable mixtures of non‐halogenated and iodinated products were obtained.…”