Alkynes propargyl amines

Functionalization of alkynes. Propargylic amine derivatives are converted to... 

Similar to the CuOTf/PyBox system, the CuBr/QUINAP system also gave high enantioselectivities of the three component reactions to construct propargyl amines from aldehydes, amines, and alkynes (Scheme 5.6). In this system various aldehydes including aromatic aldehydes and aliphatic aldehydes could be used and a wide range of chiral propargyl amines were prepared in good yields and enantioselectivities. Mechanistic studies showed that the dimeric Cu/QUINAP complex is the catalytically active species that differs from the previous reaction. 

The ability of allylzinc bromide to add to terminal alkynes was first observed with acetylenic amines as substrates. Thus, the propargylic amine 290 underwent addition of allylzinc bromide in refluxing THF and afforded after hydrolysis the allylic amine 291. This reaction occurred much more easily compared to the case of ethylenic amines (see Section III.A) and the regioselectivity was also noteworthy as a branched product was obtained predominantly82,105. It was suggested that metallation of the terminal alkyne was responsible for the observed regioselectivity. Indeed, the formation of an alkenyl... 

Nevertheless, chiral propargylic amines remain interesting substrates for achieving the diastereoselective addition of substituted allylic organozinc compounds to metallated alkynes. Besides crotylzincation, one example of diastereoselective addition of zincated allyl ethyl ether to 328 has also been reported183. 

Reaction of dichlorothiophosphoryl units with allylamines gave corresponding phosphodendrimers with terminal allyl functions while reaction with propargyl-amine afforded molecules with terminal alkyne groups. Peripheral tri- and tetra-functionality could thus be attained [108]. 

An enantioselective version of this reaction has been reported by Rueping et al.102 Treatment of an a-iminoester and an alkyne with silver acetate and a binol phosphate derivative gave propargylic amines with the highest enantiomeric ratio (er) reported as 96 4. Although the proposed catalytic cycle invoked the in situ formation of the... 

Li and coworkers have reported a novel silver-catalyzed, three-component coupling of an aldehyde, an amine, and an alkyne, and the first example of a direct addition of a silver acetylide to an aldehyde to produce propargylic alcohols (Scheme 1.41).103-105 Treatment of an aldehyde with a silver halide and secondary amine gave propargylic amines in good yields in organic solvent, water, or ionic liquids. The proposed mechanism suggests addition of a silver acetylide to the iminium ion formed in situ. 

TABLE 10.6. Propargylic Amine Formation from Aldehydes and Alkynes... 

The coupling of the three components -aldehyde, alkyne and amine- has been called A3 coupling. 7 It delivers propargyl amines, which are important synthetic intermediates and, in contrast to previously used routes, avoids the use of strong-base reagents such as BuLi, ethylmagnesium bromide or LDA, and the need for the kinds of solvents necessary for these reagents. 

Li and co-workers374,374a reported the three-component coupling reaction of an aldehyde, an amine, and a terminal alkyne catalyzed by a silver salt in water. Of various precatalysts examined, water-insoluble silver iodide gave the highest yields of the propargyl amines 452 (Scheme 137). The reaction probably proceeds via attack of a silver acetylide, generated in situ from the silver salt and the alkyne, to the iminium ion derived from the aldehyde and the... 

Propargyl amines are versatile intermediates in organic synthesis and an important structural motif in drug molecules. In addition, these p-amino-alkynes are also of importance as its two potential sites can be modified further to fit particular applications. 

Indeed, Li found that DEAD mediates the addition of terminal alkynes 27 to aliphatic tertiary methylamines 30 to provide the desired propargyl amine 31 in... 

Chiral propargylic amines are formed by mixing aldehydes, oanisidine, 1-alkynes with Mc2Zn and amino alcohol 95. ° AUcynylation of pyridinium salts is guided by Cul which is complexed to the BOX ligand 96 ... 

WMethylamines are oxidatively activated by CuBr and NBS. They are transformed into propargylic amines on reaction with 1-alkynes that are placed in the reaction media. ... 

Propargylic amines. To assemble 1-alkynes, aldehydes, and amines into propargylic amines the heating with a AgNOs/zeohte catalyst is a convenient method. ... 

Propargylic amines are high value building blocks in organic synthesis, and the corresponding stractural motif has been found in various natural products, and in compounds of pharmaceutical or phytoprotective relevance. They can be obtained by addition of alkynes to imines, bnt since imines are easily formed from aldehydes and amines. 

Highly functionalized olefins are easily accessible via silyformylation of alkynes. When coupled to other reaction systems, silylformylation reactions become even more powerful. Eilbracht et al. demonstrated that stabilized phosphorous ylides 74 could be trapped by P-silylated a-P-unsaturated aldehydes formed via silylformylation of alkynes in a one-pot synthesis. The tandem reaction proceeds with high yields for both alipathic and aromatic terminal alkynes. Protected propargyl alcohols also showed good reactivity however, propargyl amines react with low selectivity. The reaction shown below is the best-afforded result for this process. ... 

Using late transition metals, trisubstituted pyrrole products have been assembled using a Rh-catalyzed regioselective head-to-tail alkyne dimerization of protected propargylic amine substrates (Scheme 15.98) [323]. Then, upon isolation of the resultant substituted enyne product, Au(III) intramolecular hydroamination with these protected amine substrates could be used to effectively prepare amine-functionalized pyrroles in up to 88% yield. The nature of the N-protecting group dramatically impacts the yields obtained in these reactions [323]. 

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