Amides ynamide

Tandem azidination- and hydroazidination-Hiiisgen [3 +2] cycloadditions of ynamides are regioselective and chemoselective, leading to the synthesis of chiral amide-substituted 1,2,3-triazoles <06OBC2679>. A series of diversely l-substituted-4-amino-l,2,3-triazoles 132 were synthesized by the copper-catalyzed [3+2] cycloaddition between azides 130 and ynamides 131 <06T3837>. 

Base-induced isomerization of propargyl amide 29a gives chiral ynamide 30a, which is subjected to ring-closure metathesis to afford cyclic enamide 31a. Diels-Alder reaction of 31a with dimethyl acetylene dicarboxylate (DMAD) gives quinoline derivative 32. In a similar manner, propargyl amide 29b is converted into ynamide 30b, RCM of which gives bicyclic compounds 31b and 31b in a ratio of 1 to 1 (Scheme 10). 

The aminocarbonylation of alkynes has been less explored as compared to that of alkenyl and (hetero)aryl halides. Nevertheless, several noteworthy applications of this reaction have been reported, including the syntheses of 2-ynamides, chiral 2-carbamoyl-7r-allylic tungsten complexes, angular triquinanes, 2-(carbamoylmethylene)tetrahydrofurans, alle-nyl amides, and others. ... 

Copper(n)-catalyzed intramolecular amidation of alkynyl bromide 217 led to macrocyclic ynamide 218 in 76% yield (Equation 21) <2006JOC4170>. 

Ynamides also participate in radical cascade reactions. The Bu3SnH-mediated cyclization of 489 afforded tricylic amide 491 in 70% yield via the intermediacy of radical 490 (Scheme 85) (030L5095). Similarly, subjection of ynamide 492, in which the carbonyl group is no longer part of the radical acceptor, to the same... 

Under the catalysis of CuCN/DMEDA (Lll), ynamides could be conveniently synthesized via N-alkynylation of amides, including oxazolidinones, lactams and... 

Alkynyl(phenyl)iodonium salts have found synthetic application for the preparation of various substituted alkynes by the reaction with appropriate nucleophiles, such as enolate anions [980,981], selenide and telluride anions [982-984], dialkylphosphonate anions [985], benzotriazolate anion [986], imidazolate anion [987], N-functionalized amide anions [988-990] and transition metal complexes [991-993]. Scheme 3.291 shows several representative reactions the preparation of Ai-alkynyl carbamates 733 by alkynylation of carbamates 732 using alkynyliodonium triflates 731 [989], synthesis of ynamides 735 by the alkyny-lation/desilylation of tosylanilides 734 using trimethylsilylethynyl(phenyl)iodonium triflate [990] and the preparation of Ir(III) a-acetylide complex 737 by the alkynylation of Vaska s complex 736 [991]. 

Reactions.—Mono-A -alkylation of simple amides can be achieved by treatment of the corresponding amide methylols with trialkylaluminium reagents. Dipole-stabilized carbanions (166) can be formed from AW-dimethylbenzamides by treatment with s-butyl-lithium these react normally with a range of electrophiles leading to analogues of the N-methyl group. ° The little-studied A -ynamides (167) are accessible from secondary amides by sequential reaction with phosgene, a nucleophile, and potassium t-butoxide. ... 

The CUSO4-1,10-phenanthroline complex efficiently catalyzes amidation of alkynyl bromides to furnish ynamides, in both intermolecular and intramolecular manners (eq 25). This C-N bond forming reaction can be used for easy construction of macrocyclic ynamides (eq 26). ... 

In 2014, Ohno and co-workers reported the synthesis of the more complex ynamides 68 based on the copper-catalyzed alkynylation of tosyl amide 66 using aryl EBX reagent 67 (Scheme 34) [158]. Interestingly, this constituted the first example of a copper-catalyzed reaction with an EBX reagent in which the alkyne group is kept in the product. Although alkynyl bromides have traditionally been used in copper catalysis for the synthesis of ynamides, they were not successful in this case. 

Copper-promoted aminations have recently been reported as a general strategy for the A-alkynylation of carbamates, sulfonates, and chiral oxazolidinones and imidazolidinones (eq 7). A variety of substituted ynamides can be synthesized via deprotonation of amides with KHMDS followed by reaction with copper(I) iodide and an alkynylbromide or iodide. 

Synthesis of Ynamides Amidative Cross-Coupling of Terminal Alkynes... 

Ynamides can be easily synthesized by metal-catalyzed amidative cross-coupling of alkynes (Scheme 4.50). Other alternatives employ lithiated amides with al-kynyliodonium salts [196], or metal-catalyzed coupling of amides with alkynyl bromides [196], potassium alkynyltrifluoroborates [197], 1,1-dihalo-1-alkenes [198], or propylic acids [199]. 

Ynamide preparation via oxidative coupling of amides and alkynes represents an efihcient alternative to known multi-step methods, such as alkyne halogenation or the synthesis of alkynyliodonium salts followed by C-N formation. The only shortcoming of this system is that 5 equiv of the amide are necessary to achieve satisfactory yields. 

The flow of this reaction has been reversed, and the coupUng of terminal alkynes with amide-functionalized iodonium reagents was developed (Scheme 3.146) [163]. This metal-Ifee reaction was attractive since nnfnnctionalized alkynes could be used to generate the ynamides. The chemistry does reqnire the preparation of the iodine(III) reagent, but once it was prepared, it could be used to functionalize an assortment of terminal acetylenes. 

A metal-free coupling of terminal acetylenes with a functionalized iodine(III) reagent generated high yields of the ynamides [163], An aerobic copper coupling reaction between terminal alkynes and secondary amides has also been successful [165]... 

This is perhaps the most popular starting point for the preparation of ynamides. This copper-catalyzed process typically uses a bromoalkyne and a secondary amide as substrates and mineral bases sueh as Cs COj. The process was attractive since it does not require the use of strong bases [166, 170-175]... 

A dehydrohalogenative coupling of alkynyl bromides with amides affords ynamides (Scheme 4-267). As substrates mostly cyclic carbamates or sulfonamides are applied. The reaction is performed employing catalytic amounts of iron(III) chloride in the presence of AA -dimethylethylenediamine as ligand. ... 

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. 

Scheme 2.34 Rhodium(I)-catalyzed [2+2+2] cycloadditions of ynamides 2.96 in the synthesis of amide-substituted chiral biaryls 2.98 and 2.99.

Interestingly, a related copper catalyst system was recently utilized by Evano and co-workers for the synthesis of N,N-acetals when coupling 1,1-dibromoalkenes with certain amides [107]. Unexpectedly, this particular transformation did not proceed through two consecutive copper-catalyzed C-N bond formations and experiments conducted on ynamides under the same experimental conditions supported the plausible role of the latter species as active intermediates in the amidation process (Scheme 28). The mechanism pathway proposed by the authors consists of a first C-N cross-coupling of the alkene with the amide, followed by dehydrobromination of the coupling product and subsequent hydroamidation of the... 

Through a sequential metal-catalyzed C-N bond formation, 2-amidoindoles 40 were conveniently constructed from o-haloaryl acetylenic bromides 38, carbamate 39 and primary amines (Scheme 13) [41]. It is believed that Cu-catalyzed intermo-lecular amidation occurred first, and the resultant o-haloaryl substituted ynamides were coupled with primary amines, affording indoles 40 after intramolecular nucleophilic attack. 

The first synthesis of A-phosphoryl ynamides (80) featuring C- and P-chirality via the copper(I)-catalysed amidative cross-couplings between... 

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