4-Amino-2-ynamides

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>. 

The ynamide-Kinugasa reaction has been used for the highly stereoselective synthesis of chiral cz-amino- (3-1 actams. The application of this reaction consists in the preparation of chiral a-amino-2-azetidinones starting from chiral ynamide (Scheme 64), [158]. 

Scheme 64 Synthesis of a-amino-(3-lactams via ynamide-Kinugasa reaction...

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. ... 

Amidine synthesis. Alkynes, amines, and suUbnylazides (or phosphoryl azides) are combined to generate amidines. The alkynes and/or the amines can he functionahzed, and their use leads to amidines containing an a-amino group or a phosphoranylalkyl group, when starting from ynamides and imidophosphoranes, respectively. 

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]. 

Kim, J.Y., Kim, S.H. and Chang, S. (2008) Highly efficient synthesis of (a-amino amidines from ynamides hy the Cu-catalysed three-component coupling reactions. Tetrahedron Letters, 49, 1745-1749. 

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. 

The synthesis of 1,3-dienes via a ruthenacyclopentene intermediate is also a possible pathway. It results from intracyclic p-hydride ehmination, and this process takes place only when an exocychc p-elimination is not possible or not favored. Thus, the Cp RuCl(cod)-catalyzed hydrovinylation of ynamides proceeded in the presence of ethylene to selectively afford 2-amino-l,3-dienes [66] [Eq. (28)]. 

An experimental and theoretical investigation of electronic effects in ruthenium catalyzed cycloadditions with internal diarylalkynes has shown that 5-electron-donating group substituted triazoles should be favored [155]. This effect was further observed in the synthesis of 5-amino-triazoles from ynamides (Scheme 65) [156]. 

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