Propargyl amides

Bis(tnfluoromethyl)-subsntuted hetero-1,3-dienes and acetylenes react to give open-chain tnfluoromethyl-substituted N-propargylic amides, 4//-1.3 oxazines, and 2-oxazohnes [42,144] The formation of 2-oxazolmes is an example of pathway 2 (equabon 25), where only one carbon atom of the acetylene moiety IS incorporated into the new nng system The selectivity of this reaction can be controlled efficiently in favor of the five-membered nng system by altering the reaction conditions In the presence of 4-dimethylaminopyndine, the five-mem-... 

Furthermore, using (5)-2-phenyloxazolidinone led to the propargyl amide ([Pg.78]

Another example of the addition of terminal alkynes to C=N in water is the coupling of alkynes with in-situ-generated A-acylimines (Eq. 4.32) and A-acyliminium ions (Eq. 4.33). In 2002, Li et al. developed a coupling reaction of alkynes with A-acylimines and A-acyliminium ions mediated by Cu(I) in water to generate propargyl amide derivatives.57 Either an activated imine derivative or imininum derivative was proposed as the intermediate, respectively. 

Shortly after this work, Shibasaki and coworkers developed a useful method for the substitution of allyl and propargyl alcohols using Bi(OTf)3 [61]. Various amines such as tosylamine, carbamates, amides and cinnamylamide yielded allyl and propargyl amides 27a-h and 25g-h in excellent yields (Scheme 21). The addition of KPF6 was... 

Scheme 22 (a, b) Amination of the enantiopure alcohols 26a and 24a yields racemic cinnamyl and propargyl amides 27a and 25g. (c) Bismuth-catalyzed C-N bond cleavage makes this process reversible... 

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). 

Rh complexes are examples of the most effective catalysts for the polymerization of monosubstituted acetylenes, whose mechanism is proposed as insertion type. Since Rh catalysts and their active species for polymerization have tolerance toward polar functional groups, they can widely be applied to the polymerization of both non-polar and polar monomers such as phenylacetylenes, propiolic acid esters, A-propargyl amides, and other acetylenic compounds involving amino, hydroxy, azo, radical groups (see Table 3). It should be noted that, in the case of phenylacetylene as monomer, Rh catalysts generally achieve quantitative yield of the polymer and almost perfect stereoregularity of the polymer main chain (m-transoidal). Some of Rh catalysts can achieve living polymerization of certain acetylenic monomers. The only one defect of Rh catalysts is that they are usually inapplicable to the polymerization of disubstituted acetylenes. Only one exception has been reported which is described below. 

A new copper-catalyzed reaction involving imines, acid chlorides, and alkynes has been applied to the synthesis of propargyl amides 160 in a single operation by Arndtsen and co-workers. The same method allows the synthesis of N-carbamate-protected propargylamines [149]. a-Substituted amides 161 may also be prepared under palladium catalysis by substituting alkynes for vinyltin (Scheme 8.71) [150]. 

A 2008 publication by Harmata and Huang32 revealed that for a number of propargyl amide derivatives, 5 mol% of AgSbF6 at room temperature can achieve the same conversion to alkylidene oxazoles in 89-98% yield in minutes In the case of disubstitution at the propargylic position, the reactions proceeds in DCM without the... 

Iodo Pyrroles by a Consecutive 3CR of Acid Chlorides, Propargyl Amides, and Iodide... 

Annelated and Substituted Pyridines by a Consecutive 4CR of (Hetero)aryl Halides, Propargyl Amides, Ketene Acetals or S,N-Aminals, and Ammonium Chloride... 

A one-pot/two-reaction sequential ruthenium- and gold-catalyzed oxazole formation has been reported <2004CC2712>. The reaction of a propargylic alcohol and a primary amide in the presence of a Ru catalyst facilitates the formation of the intermediate propargyl amide which cyclizes upon treatment with AuCls (Scheme 61). 

Some multicomponent syntheses of trisubstituted oxazoles were described. a-Isocyano-a-alkyl(aryl)acetamides, as 131 <05S161>, was demonstrated to be a useful starting material for a three-component reaction involving isoquinoline 129 <05SL532>. A four-component synthesis was also published starting from an aldehyde, a silylamide, an acyl chloride and a terminal acetylene derivative. The overall process is a modification of a four-component synthesis of a propargylic amide 134 which can be eventually isolated <05T 11317>. 

Pyrrolidinyl amides undoubtedly form Z((9)-enolates, and the [2,3]-Wittig rearrangement of the -alkene (entry 5, [69] is highly selective. The Z-alkene was not tested, and propargylic amide enolates do not rearrange [70]. Entry 5 also shows the highest yield in the Table. As will be seen, amides of C2-symmetric amines can be excellent chiral auxiliaries in this process. 

Base-catalyzed cyclization of propargyl amides is an expeditious approach to a variety of substituted oxazoles. In addition, propargyl amides can serve as... 

Nilsson and Hacksell isolated 2,5-dimethyl-4-phenyloxazole 245 (Ri = CH3, R2 = CeHs) as the only product from methylation of N-(l-phenyl-2-propynyl)acet-amide 244 (Ri = CH3, R2 = CeHs). The authors found that propargyl amides could be cyclized to 2,5-disubstituted and 2,4,5-trisubstituted oxazoles (Scheme 1.67). Thus a propargyl alcohol 243 was converted to the corresponding amide 244 in... 

TABLE 1.21. 5-[(PHENYLSULFONYL)METHYL]-2-SUBSTITUTED OXAZOLES FROM PROPARGYL AMIDES VIA ( )-P-IODO(VINYL)SULFONES ... 

It is interesting to note that early work on ferrocene derivatives of nucleosides uses Sonogashira coupling of ethynylferrocene to 5-iodouridine or 8-bromoadenosine. This reaction was later used to synthesize ferrocenylated ODNs by solid-phase synthesis techniques. Depending on the conditions, a cyclization reaction occurs with uracil derivatives. Instead of ethynylferrocene, Grinstaff et al. used ferrocene carboxylic acid propargyl amide. 

---