The asymmetric addition of terminal ynamides to trifluoromethyl ketones with a readily available chiral zinc catalyst gives CF3‐substituted tertiary propargylic alcohols in up to 99 % yield and 96 % ee. The exclusion of organozinc additives and base as well as the general synthetic utility of the products are key features of this reaction. The value of the β‐hydroxy‐β‐trifluoromethyl ynamides is exemplified by selective transformations to chiral Z‐ and E‐enamides, an amide, and N,O‐ketene acetals. The highly regioselective hydration, stereoselective reduction, and hydroacyloxylation reactions proceed with high yields and without erosion of the ee value of the parent β‐hydroxy ynamides.

Ynamides consist of a polarized triple bond that is directly attached to a nitrogen atom carrying a sulfonyl, an alkoxycarbonyl, an acyl or another electron withdrawing group. The triple bond polarization renders ynamides broadly useful building blocks with synthetic opportunities that go far beyond traditional alkyne chemistry. The versatile reactivity of ynamides in cycloadditions, cycloisomerizations, regioselective additions with various nucleophiles or electrophiles, ring-closing metathesis, and many other reactions has been investigated in detail during the past decades. A common feature of these methods is that the triple bond is consumed and either cleaved or transformed to a new functionality. The wealth of reports on these ynamide reactions is in stark contrast to the dearth of carbon-carbon bond formations that leave the triple bond of terminal ynamides intact. The recent introduction of effective synthetic methods for the preparation of terminal ynamides has set the stage to fully explore the synthetic potential of this intriguing class of compounds. This digest letter summarizes the most effective routes to terminal ynamides and the current state of selective nucleophilic addition, substitution and coupling reactions, including the first examples of asymmetric synthesis.

The first catalytic asymmetric addition of ynamides to aliphatic and aromatic aldehydes is described. This reaction provides unprecedented access to a diverse family of N-substituted propargylic alcohols that are obtained in high yield and ee in the presence of 10 mol% of zinc triflate and N-methylephedrine The use of apolar solvent mixtures is essential to avoid product racemization and to optimize ee’s without compromising conversion.

The addition of ynamides to acyl chlorides and N-heterocycles activated in situ with ethyl chloroformate has been accomplished at room temperature using copper iodide as catalyst. This economical and practical carbon–carbon bond formation provides convenient access to a variety of 3-aminoynones from aliphatic and aromatic acyl chlorides in up to 99% yield. The addition to pyridines and quinolines occurs under almost identical conditions and proceeds with good to high regioselectivity, producing the corresponding 1,2-dihydro-N-heterocycles in up to 95% yield.

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Die asymmetrische Addition terminaler Inamide an Trifluormethylketone mit einem leicht zugänglichem chiralen Zink-Katalysator ergibt CF 3 -substituierte tertiäre Propargylalkohole mit bis zu 99 %A usbeute und 96 %e e. Der Ausschluss von organischen Zinkadditiven und Basen sowie der Nutzen der Produkte für Synthesen sind besondere Merkmale dieser Reaktion. Der Wert der b-Hydroxy-b-trifluormethylinamide ist exemplarischmit ausgewählten Umwandlungen zu chiralen Z-und E-Enamiden, einem Amid und N,O-Ketenacetalen belegt. Die äußerst regioselektive Hydratisierung, stereoselektive Reduktionen und Hydroacyloxylierungen erfolgen mit hohen Ausbeutenu nd ohne Erosion des ee der verwendeten b-Hydroxyinamide.

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