Ynamides, reactions with

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. ... 

The reaction has been exemplified with a variety of aryl-substituted alkynes, but it is interesting to note that a similar reaction with an epoxide-ynamide derivative 81 (Scheme 5.37), catalyzed with AgBF4, yielded the tricyclic central core 82 of gibberic acid. 

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. ... 

A-Sulfonylamidines can be prepared by three-component coupling [31] of alkynes (R = alkyl, aryl or silyl), sulfonyl azide and amine, which is known as click chemistry. [32] The use of alkyl azides in place of sulfonyl azide without a copper catalyst results in the formation of 1,2,3-triazoles (Scheme 3.18). This reaction shows substrate tolerance to each component. Reaction with an optically active amino ester is performed without racemiza-tion. A-Boc-ynamide (R = NPhBoc) can act as the alkyne component in the synthesis of N-Boc-aminoamidines [33]. 

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. 

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. ... 

N,iV-Disulfonyl ynamides react with salicylaldehydes through a keteni-mine intermediate in the presence of triethylamine giving access to 3-substituted iminosulfonylcoumarins (140BC3986). Biscoumarins fused at the pyrone ring arise from the indium(III) trifluoromethanesulfonate-catalyzed reaction of methyl coumarin-3-carboxylate with phenols, in good yields (14JOC8723). A library of 3,3 -biscoumarin-based protein kinase inhibitors is achieved from the condensation of 2 -hydroxyacetophenones... 

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). 

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. 

The tandem Cu(i)-catalyzed reaction of the ynamide 24 with Phi and NaNj affords the cycloadduct 25 in 75 % yield... 

Yes, many functionalized alkynes such as ynamides and ynol ethers are well tolerated in several metal-catalyzed vinyl ester syntheses [139, 140] Decarboxylation is a common side reaction with this chemistry however, a copper-catalyzed approach has minimized this secondary process and generated good to excellent yields of the vinyl esters with electron-rich aryl carboxylic acids [130]... 

However, in this case the electron-rich 1-methoxypropyne was used as the monoalkyne. First, 108 was converted into yne-ynamide 109 by three steps, including a Sonogashira reaction with trimethylsilylacetylene and the ynamide formation based on the alkynyliodonium salt 105. Yne-ynamide 109 was then alkylated with iodopen-tane, and subsequent desilylation with TBAF provided the diyne 110 (44% yield over two steps). The key cyclotrimerization of diyne 110 with 1-methoxypropyne was carried out in toluene at room temperature in the presence of 10 mol % of Wilkinson s catalyst and afforded chemo- and regioselectively carbazole 111 (82% yield, isomer... 

The intramolecular [2+2+1] cycloaddition promoted by pentacarbonyliron can also be extended to silyl protected yne-ynamides (Scheme 4-7) and yne-ynol ethers (Scheme 4—8) ° to give after demetalation cyclopentadienones with fused N- or 0-heterocycles of different ring size. Subsequent Diels-Alder reaction with dimethyl acetylenedicarboxylate (DMAD) or ethyl propiolate transforms the cyclopentadienone moiety into the corresponding benzene derivative. 

Cossy and coworkers described a precise combination of a Heck and a Suzuki-Miyama reaction using ynamides and boronic acids to give indole and 7-azaindole derivatives [46]. Thus, reaction of 6/1-73 with 6/1-74 using Pd(OAc)2 as catalyst led to 6/1-75 in 68% yield (Scheme 6/1.18). 

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). 

DFT calculations on the intramolecular Diels-Alder reaction of penta-l,3-dienyl acrylates predict stereoselectivities that are in good agreement with the experimen- (g) tal results.85 Another DFT study at the B3LYP/6-31G(d) level of the intramolecular Diels-Alder cycloaddition of 5-vinylcyclohexa-1,3-dienes has been reported. Reaction rates are influenced by dienophile twisting and substituent effects.86 The intramolecular dehydro-Diels-Alder reactions of ynamides (79) provides a new synthesis of benzo[fc]-, tetrahydrobenzo[fc]-, naphtho[l,2-/j -, and dibenzo[a,c]carbazoles... 

Ruthenium catalysts were used as alternatives to the usual copper catalysts. Ynamides 102 reacted with various azides 103 in the ruthenium-catalyzed Huisgen [3+2] cycloaddition reaction to yield l-protected-5-amido 1,2,3-triazoles 104 <07T8094>. The formation of 1,5-... 

Albeit no examples of a stable bicyclo[3.2.0]hept-5-ene obtained by a metal-catalyzed reaction from a 1,6-enyne have been observed, interestingly, following earlier work done with PtCl2 as catalyst,it was found that the gold-catalyzed reaction of 1,6-ene-ynamides gives cyclobutanones (equation 42), in a process that probably proceeds through unstable bicyclic enamines. 

An indium-mediated radical cyclization sequence has been used to synthesize stereoselectively 3-alkylideneoxindoles [65, 66]. The generation of predominantly the i -isomer, such as seen with 96 below, is attributed to the strong coordination of the indium to the carbonyl of the oxindole intermediate, and the transformation of various iodo-ynamides to the cyclized oxindoles occurred in good yield. Selective approaches to the E- and disubstituted 3-alkylideneoxindoles involving a tandem palladium-catalyzed cross coupling reaction were also highlighted in this report. 

A direct metal-free amination of arylethynes by the reaction of terminal alkynes 513 with hypervalent iodine imide allows a simple, one-step synthesis of an important class of ynamides 514 (Scheme 3.203) [582]. 

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