Propargyl imines

Propargylated tosylamides also isomerize efficiently [221, 281]. On the other hand, rare examples are propargylated hydrazines [251], N-propargylated imines [282], isonitriles (must be N-propargylated) [283], ammonium salts [284] and azides [285],... 

In related reactions, Snapper and Hoveyda et al. reported an asymmetric version of Mannich-type reactions catalyzed by silver acetate.38,39 Propargyl imines proved to be susceptible to nucleophilic addition of sily lenol ethers derived from acetate esters in the... 

It is noted that terminal alkynes add to the carbon of an isonitrile in the presence of a uranium complex, giving a propargylic imine. ... 

Over the past 5 years Cu(I)-catalyzed addition of terminal acetylenes to imines has been an intense area of research for the synthesis of chiral propargyl amines. Two mechanistic proposals have been put forth which utilize Cu(I) complexes as Lewis acids in these additions. Benaglia and coworkers reported a mechanism for reactions utilizing preformed imines (Scheme 17.37). The chiral Cu(I) salt (171) initially coordinates imine (172) to generate complex (173). Subsequent coordination of the terminal acetylene (174) affords complex (175). Formation of requisite copper acetylide results in the formation of complex (176), which facilitates intramolecular addition of the acetylide to the imine. Decomplexation of the resulting propargyl imine from (177) regenerates the catalytic Cu(I) species. 

Another efficient method to prepare chiral propargylamines 42 using a multicomponent process is by alkylation of in situ formed propargyl imines from alkynals 40 and o-phenoxy aniline (11c) by dialkylzinc derivatives 41 in the presence of a chiral ligand, for instance a dipeptide, and a Lewis acid salt, as depicted in Scheme 11.16 [48], Furthermore, the synthesis of A-aryl propargyl amines can be also performed by the alkynylation using dimethylzinc and terminal acetylenes of several aldehydes and o-methoxyaniline catalyzed by (l/ ,25)-A-bis(p-methoxybenzyl)norephedrine and phenylacetylene (52-93%, 79-97% ee) [49],... 

In another route employing alkynes, it was found that heating propargyl azadienes 7 in toluene at 25-60 °C produces pyrrolic imines 8 which hydrolyze upon work-up to afford 3-acylpyrroles 9 <96JOC2185>. This exo-dig cyclization occurs with complete chemoselectivity wherein the more substituted nitrogen is involved in the cyclization. 

An unusual [4+1] cycloaddition gold-catalysed reaction between propargyl tosylates 102 and imines 103 led to the formation of eyclopent-2-enimines 104 (Scheme 5.27) [27], A possible mechanism for this reaction involves a 1,2-migration of the tosylate that generates the 1,3-diene 105 followed by a Nazarov-hke cyclisation. 

Fischer, C. 8c Carreira, E.M. (2004) Mgl2 an Additive in Ir(I)-Catalyzed Addition ofSUylacetylenes to Imines Expeditions Synthesis of Propargylic Amines. Synthesis, 9, 1497-1503. 

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. 

Reaction with Propargyl Halides. The indium-mediated coupling of propargyl bromide with a variety of imines and imine oxides afforded homo-propargylamine derivatives in aqueous media under mild conditions.78 Propargylation of glyoxylic oxime ether in the presence of a catalytic amount of palladium(O) complex and indium(I) iodide in aqueous media was also studied (Eq.11.47).79... 

The acyclic version of Larock s heteroannulation was successfully applied to the synthesis of highly substituted pyridines [166]. The annulation of rert-butylimine 210 with phenyl propargyl alcohol produced pyridine 211 regioselectively in excellent yield. The regiochemistry obtained was governed by steric effects. Furthermore, the choice of imines was crucial to the success of the heteroannulations. terr-Butylimine was the substrate of choice, since all other imines including methyl, isopropyl, allyl and benzyl imines failed completely to produce the desired heterocyclic products. 

This system was described in one report and has been synthesized by a copper-assisted cycloisomerization of alkynyl imines. The authors proposed the following mechanism at first, 372 could undergo a base-induced propargyl-allenyl isomerization to form 373 next, coordination of copper to the terminal double bond of the allene (intermediate 374) would make it subjected to intramolecular nucleophilic attack to produce a zwitterion 375. The latter would isomerize into the more stable zwitterionic intermediate 376, which would be transformed to the thiazole 377 (Scheme 55) <2001JA2074>. 

Terminal trimethylsilylacetylenes are deprotonated at the propargylic position by using sBuLi to yield a lithiated species which undergoes transmetallation with ZnBr2 to afford the allenylzinc reagent (Eq. 9.125) [99]. Additions to a-alkoxyalde-hydes are relatively unselective (Table 9.48), whereas additions to a-alkoxy imines are highly anti selective (Eq. 9.126). 

Propargylic aziridines were obtained in one step on reaction of this allenylzinc reagent with imines (Eq. 9.130) [108, 109]. 

Secondary propargylic amines 284 (R = Pr, t-Bu, C5H11, C6H13 or C7H15) rearrange to the enamines 285 and thence to the imines 286 in the presence of potassium r-butoxide313. 

The reaction of alkynyllithium compounds with alkoxycarbene tungsten complexes leads to anionic propargyl tungsten complexes (Figure 2.33 see also Figure 3.9). These intermediates are stable at low temperatures and react upon Lewis acid catalysis with aldehydes or A -sulfonyl imines to yield five-membered heterocycles [280]. Oxidative methoxycarbonylation [375] of the intermediate vinyl tungsten complex, followed by elimination of methanol leads to pyrroles or furanes (Figure 2.33 Entry 6, Table 2.22). 

Imidates, rearrangement of, 14, 1 Imines, additions of allyl, allenyl, propargyl stannanes, 64, 1 additions of cyanide, 70, 1 as dienophiles, 65, 2 synthesis, 70, 1 Iminium ions, 39, 2 65, 2 Imino Diels-Alder reactions, 65, 2 Indoles, by Nenitzescu reaction, 20, 3 by reaction with TosMIC, 57, 3 Ionic hydrogenation, 71, 1 Isocyanides, in the Passerini reaction, 65, 1... 

Common reactions of the ylide include (i) [2,3]-sigmatropic rearrangement of allylic, propargylic, and allenic ylides (ii) [l,2]-shift (Stevens rearrangement) (iii) 1,3-dipolar cycloaddition of the ylide generated from carbonyl compounds or imines with dipolarophiles, usually G=G or C=C bonds and (iv) nucleophilic addition/elimination, leading to the formation of epoxides or cyclopropanes (Figure 2). 

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