Ynamides, addition

The reaction can be done intramolecularly. N-Benzyl pent-4-ynamide reacted with tetrabutylammonium fluoride to an alkylidene lactam. Similar addition of a tosylamide-alkene, with a palladium catalyst, led to a vinyl Al-tosyl pyrrolidine. Similar cyclization reactions occur with tosylamide-alkynes. ... 

This kind of reactivity turned out to be particularly attractive when applied to suitably functionalized terminal alkynes. Oxidative monoaminocarbonylation of 4-yn-l-ols led to the formation of tetrahydrofuran derivatives through intramolecular conjugate addition of -OH group to the triple bond of the initially formed 6-hydroxy-2-ynamide intermediates (Scheme 38) [310]. 

A highly regio- and stereo-selective Brpnsted acid-catalysed addition of aromatic heterocycles, such as pyrroles, furans, and indoles, to ynamides RC=CN(R)(EWG), catalysed by Tf2NH at —35 °C, has been developed as an equivalent of hydroarylation of ynamides.41... 

Propargyl alcohol was first monoaminocarbonylated leading to 4-hydroxy-2-ynamide 111. This first stage is followed in situ by conjugate addition of dialkylamine to the triple bond of the ynamide to yield 112 which gives spontaneously an intramolecular lactonization to afford the furanone 113. Similarly, lactams have been prepared using propargyl amines [99]. 

It is now usual to promote these cycloadditions by catalysts for example, reaction with A -tosyl-ynamides, using ruthenium or copper catalysts, giving 1-substituted 5- and 4-amino triazoles, respectively the formation of the 1,4-substitution pattern with copper catalysis and 1,5-pattem with ruthenium catalysis seems to be general. The latter metal will also promote addition to internal alkynes. ... 

In an effort to expand the click chemistry concept, Ijsselstijn et al. [43] have reported the use of two N-protected ynamides (60) as dienophiles in the Cu(I)-catalyzed cycloaddition reaction with a variety of azides, including glycosyl azides (Scheme 12). The ynamides were successfully clicked under the standard conditions for these reactions [Cu(OAc)2/Na-ascorbate] giving rise to 1-substituted 4-amino 1,2,3-triazole-Iinked sugars (61). These results are noteworthy as they allow direct access to amino triazole rings, which are found in some bio active molecules. However, additional studies are required in order to evaluate the scope and appUcability to more complex ynamides. 

Addition of Alcohols to Ynamines and Ynamides (Ficini-Claisen Rearrangement)... 

Scheme 10.129 Diastereoselective formation of aldol surrogates by sequential carbocupra-tion of chiral ynamides/zinc carbenoid homologation/aldol-type addition [110].

This Rh-catalyzed reaction was logically extended to the regioselective carbomet-aUation of the same ynamide substrates with organoboron reagents [112]. In the presence of a substoichiometric amount of the [Rh(cod)(MeCN)2]BF4 complex, ynamides in aqueous THF under microwave irradiation underwent highly regioselective addition of organoboronic acids to the carbon-carbon triple bond (Scheme 10.133). 

Hashmi et al. reported that 7V-alkynyl carbamates underwent 1-catalyzed 5-endo-digcyclizdXion, yielding oxazolinones. In this case, the nitrogen was substituted with another EWG in addition to the Boc moiety due to the need in substrate preparation and perhaps attenuating the reactivity of the ynamide moiety (eq 12). ... 

In addition, cyclobutanones are synthesized via platinum(II)-catalyzed cycli-zation of 1,7-ene-ynamides II-6 (Scheme 3.5). The cyclobutanones are fanned after hydrolysis of the corresponding bicycle[4.2.0] compounds II-7. 

Other important molecules that are useful intermediates in the synthesis of natural products are chiral diols. anli-l,2-Diols of type 30 were obtained in good yields (75-85%) and moderate to good diastereoselectivity (76-96% de) by a nickel-catalyzed three-component addition of a-silyloxy aldehydes 27, alkynyl silanes 28a, and reduction with triisopropyl silane (29a) (Scheme 11.11) [31]. The diastereoselectivity of this process could be explained by the Felkin model. Alternatively, a chiral alkynyl derivative can control the outcome of the reaction. Thus, the coupling of optically active, oxazolidinone-derived ynamides, aldehydes, and silane as reducing agent led to the formation of y-siloxyenamide derivatives with diastereoselectivities up to 99% [32]. 

SCHEME 2.94 Palladium-catalyzed addition of carboxylic acids to ynamides [139]. 

Sato A, Yorimitsu H, Oshima K. Radical additions of arene-thiols to ynamides for the selective synthesis of A-[(Z)-(aryl-sulfanyl)-l-alkenyl]amides. Bull. Korean Chem. Soc. 2010 31 570-576. 

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