I. Synthesis of chiral ynamides. II. Reactions involving chiral ynamides

Alkynes are important building blocks in organic synthesis. Ynamines, an electron-rich variant of alkynes, contain a nitrogen atom that causes an electronic bias. This electronic bias allows ynamines to undergo various regioselective transformations. The high reactivity of ynamines makes them difficult to isolate and use. Ynamides, an electron-deficient version of ynamines, offer a balance of reactivity and stability, which makes them amenable to synthesis, isolation, and application in a variety of reactions including cycloadditions, rearrangements, and hydrohalogenation reactions.; A based-induced isomerization protocol for the synthesis of ynamides proved to be narrowly applicable; it was effective for the synthesis of 10-propynyl-9(10H)-acridone, which underwent [2+2] and [4+2] cycloaddition reactions with aldehydes and ketones. In addition, simple acyclic ynamide systems could be synthesized; ene- and diene-ynamides obtained in this fashion underwent successful RCM reactions. Isomerization yielded only allenamides for all lactam, oxazolidinone, and imidazolidinone systems.; A three-step bromination/elimination protocol was tedious and suffered from several problems; however, it offered practical entry to a variety of chiral auxiliary-based ynamides. Synthesis of chiral ynamides via copper-catalyzed N-alkynylation of amides proved to be rapid and efficient. This one-step methodology was quite general for many ynamide systems and offered access to parent ynamides, which could be further alkylated, or coupled with aryl iodides in a Sonagashira fashion, to yield new ynamides.; Preliminary data concerning cycloaddition reactions involving ynamides indicated that these reactions are not facile to effect; however, this is an area of great potential for ynamides. The value of ynamides was evidenced in highly stereoselective Ficini-Claisen and Saucy-Marbet rearrangements, which proceeded with high diastereoselectivity at moderate temperatures. Ynamides are also excellent substrates for stereoselective hydrohalogenation under mild conditions, yielding E-alpha-haloenamides, which may undergo subsequent coupling reactions with alkynes.; Finally, ynamides may be used as a functional groups in organic synthesis. The ynamide group is robust, surviving a series of typical organic transformations.