Ruthenium-Catalysed Additions to Alkynes: Synthesis of Activated Esters and Their Use in Acylation Reactions

Enol esters can be obtained in one step by direct addition of carboxylic acids to terminal alkynes in the presence of a ruthenium-phosphine catalyst of type RuCl₂(PR₃)(arene). The presence of a nucleophilic phosphine allows the addition of the carboxylate group to the substituted alkyne carbon with high regioselectivity. From hex-1-yne or propyne, enol esters can be obtained with a variety of carboxylic acids including N-protected α-amino acids. Alkenylacetylene derivatives are thus precursors of 2-acyloxy-1,3-dienes. Ruthenium-catalysed addition of carboxylic acids and N-protected α-amino acids to propargyl alcohol derivatives gives rise to the synthesis of β-oxopropyl esters. These enol esters and β-oxopropyl esters are shown to be efficient acylating reagents under mild conditions to produce optically active amides or dipeptides. Especially stable enol formates allow access at 25°C to a variety of formamides and α-formylamino esters and in the presence of imidazole as a catalyst, they react with functionalised alcohols to give formates. Enol oxalates are shown to give access to α-dioxo derivatives via acylation of ammonia, amines, and unsaturated alcohols. 1. Introduction 2. Catalytic Synthesis of Enol Esters 2.1. Synthesis of Hex-1-en-2-yl (1-Butylethenyl) Esters 2.2. Synthesis of Isopropenyl (1-Methylethenyl) Esters 2.3. Mechanism of the Catalytic Addition to Terminal Alkynes 2.4. Synthesis of 2-Acyloxy-1,3-Dienes 2.5. Synthesis of β-Oxoalkyl Esters 3. Use of Enol Esters as Acylating Reagents 3.1. Acylation and Dipeptides Synthesis 3.2. Enol Formates as Formylation Reagents 3.3. Enol Oxalyl Esters as Intermediates of α-Dioxo Compounds 4. Conclusion and Perspectives