Science of Synthesis

Riva, R.; Banfi, L.; Basso, A., Science of Synthesis: Multicomponent Reactions, (2014) 1, 327.

General Introduction

The multicomponent reaction of a carbonyl compound, an isocyanide, and a carboxylic acid to give α-acyloxy amides was discovered in 1921 in Florence (Italy) by Mario Passerini[‌1‌] and as such it is the oldest isocyanide-based multicomponent reaction. For many years, this reaction attracted very little interest until, at the end of the last century, the great usefulness of isocyanide-based multicomponent reactions in combinatorial synthesis was eventually recognized. The classical Passerini reaction allows the synthesis of α-acyloxy amides, including depsipeptides, with the simultaneous introduction of three diversity inputs, under mild conditions and with a high degree of atom economy. However, the scope of this old reaction has been recently expanded, bringing about access to many different scaffolds (including heterocyclic) by using alternatives to carboxylic acids, through intramolecular modifications, or by exploiting post-condensation transformations. The Passerini reaction, or its “truncated” variant, is one of the easiest ways to convert carbonyl compounds into α-acyloxy or α-hydroxy amides, realizing a typical “umpolung” process, with the isocyanide acting as an acyl anion equivalent.

Me 8888, e eeeeeeee eeeeee ee eeee eeeeeeeeeee eee eee eeeeeeee eee eeeeeeeee ee Meeeeee Meeeeeeee.[‌8‌] Meeeeee, eeeee eeee eeeee 888 eeeeee ee eeee eeeeeee eeee eeeeeeee, eeeeeeeeeeeee eee eeeeeee eeeeeeee ee eee Meeeeeeee eeeeeeee. Mee eeee eeeeee, ee eeee eeeeeee, eeeeeeee eeee eee eeee eeeeee eeeeeeeeee eee eeeeeeeee eeeeeeee. Me eeeeeeeeeee eeeeee ee eeee eeeeeee eee eeeeeeee eeeeeeee.[‌8‌]

Meeeeeee eeeeeee eeeeeeeee eeeeeeeeee eeee eeee eeeeeeee eeeeee eee eeeee,[‌8‌,‌8‌] eee eeee eeeeeeeee eeeeeeee eee ee eeeee ee ‌Meeeee 8‌.[‌8‌] Meeeeeeee ee eeee eeeeeeeeee, eee eeeeeeee-eeeeee eeeeeee eeeeee ee eeeeeeeeeee ee eee eeeeeeeeee eeee eeee eee eeeeeeee eeeeeeee eeeeee eeee eee eeeeeeeeee ee e eeeeeeeee eee ee eeee eee eeeeeee α-eeeeeeee eeeeeeeeeeee ‌8‌ eeeeeee e eeeeeeeeee eeeeeeee eeeeee eeeeeeeeee eeeee ‌8‌. Meee eeeeeeeee ee ee eeeeeeeee eeee eee eeee eeee eee eeeeeeee (eeeeeeee ee eeee eeeeeee eee eee eeeeeee Mee eeeeeeee) ee eeeeee ee eeeeee eeeeeeee. Meee, eee α-eeeeeeee eeeeee ‌8‌ eeeeeeeeee ee eee eeeee eeeeeee ‌8‌. Me ee eee eeeee ee eee eeee-eeeeeeee eeee ee eee α-eeeeeeee ee eee eeeee eeeeeeeeeeeee; e eeeeee eeeeeeeeeee eeeee eeeeeeee eeee ee eee ee eee eeeeee.[‌8‌] Meee eeee eeee eeeeeeee eee eeeeeeeeeeee ee ee eeeeeeeeee eeeeeeee ee eee eeeeeeeeee eeee ee eee eeeeeeeeee eeeee. Meee eeeeeee eeeeeeeee eeee ee eeeeeee eeeeeeeeeeee eeee eeeeeeeee eeee eee Meeeeeeee eeeeeeee ee eeeee eeeee ee eeee ee eee eeeee eeeeeeeee.[‌8‌] Meeeeee, eeee eeeeeeeeee eee eeeeeee eee eeeee e eeeeee, eeeeeee eee eeeeeeeeeee eeeee eee eeeeeee eee ee eeeeeeeeeeee eee eee eeee-eeeeeeee eeee eee ee eeeeeeeee ee eee eee eeeee.

‌Meeeee 8‌ Meeeeeeee ee eee Meeeeeeee Meeeeeee[‌8‌]

References