Organocatalytic Reductive Amination of the Chiral Formylcyclopropanes: Scope and Applications

Abstract

We developed a sustainable three-component reductive amination protocol for the chemoselective coupling of optically active functionally rich donor− acceptor carbonyl-cyclopropanes with various amines under 10 mol % of diphenyl phosphate in the presence of Hantzsch ester as a hydride source. The catalytic selective reductive C−N coupling has wide advantages like no epimerization, no ring opening, large substrate scope, generating only mono N-alkylation products and simultaneously resulting in chiral cyclopropane-containing amines possessing many applications in the medicinal chemistry. In this article, we have shown the synthetic applications of reductive C−N coupling reaction to make chiral α-carbonyl-cyclopropane containing amines 8, double C−N coupled cyclopropane-amines 10, unusual C−N/C−C coupled cyclopropane-amines 12, chiral tert-butylsulfinamide containing cyclopropanes 14/15, and functionally rich chiral cyclopropane-fused N-heterocycles 16/18/19. Many of these chiral cyclopropane-amines 5−19 can serve as building blocks for the synthesis of drug-like small molecules, natural products, pharmaceuticals, and their analogues.

Two-step, high-yielding total synthesis of antibiotic pyrones

“…Hence, our investigation of the three-component Ramachary reductive C -alkylation commenced, 15 after synthesizing a library of C -7 alkylated products 3 from the commercially available triacetate lactone 1 with various aliphatic alkyl iodides or bromides 2 as starting materials using modified Hsung's protocol in very good to excellent yields (Scheme 2). 16 First, C -7 alkylation was performed by addition of n BuLi at −78 °C to 1 in THF and HMPA (6 : 1) followed by addition of ethyl iodide 2a , and stirring at 25 °C for 15 h gave the desired selective C -7 alkylated pyrone 3a in a very good yield of 85% (Scheme 2).…”