Propargylamines, synthesis

SCHEME 340 Propargylamine synthesis by metal-catalyzed A -coupling reactions. 

Gonzalez-Bejar M, Peters K, Hallett-Tapley GL, Grenier M, Scaiano JC (2013) Rapid one-pot propargylamine synthesis by plasmon mediated catalysis with gold nanoparticles on ZnO under ambient conditions. Chem Commun 49(17) 1732-1734... 

Several new methods for the synthesis of the oxazole nucleus were published. A new consecutive three-component oxazole synthesis by an amidation-coupling-cycloisomerisation sequence was developed. The synthesis started from propargylamine 92 and acyl chlorides. To extend this process, a four component sequence involving a carbonylative arylation by substitution of one acyl chloride with an aryl iodide and a CO atmosphere was also performed <06CC4817>. 

A copper-catalyzed one-pot three-component atom-economical C-H functionalization process was used to form enantioenriched propargylamines. This protocol was also employed for the synthesis of the alkaloid (A)-(+)-coniine (Equation (196)).159 159a... 

A versatile synthesis of triazolopyrazines has been elaborated by Akritopoulou-Zanze et al. <2004TL8439>. The method involves two steps a multicomponent Ugi reaction and a subsequent ring closure. Thus, arylaldehydes, propargylamine, cyclohexylisocyanide, and azidoacetic acid yielded the intermediate 406 which easily underwent cyclization to give the partially saturated derivative 407 in excellent yields. 

Similarly, an efficient procedure of general applicability was described for the synthesis of propargylamines by copper(I)-catalyzed amination of bromoal-lenes [75], It should be mentioned that by use of an enantioenriched allene 142 (R1 = nPr, R2 = Me), the optical purity was completely transferred to alkyne 143 (R3 = nBu) [73],... 

Dyatkin, A. B. Rivero, R. A. The Solid Phase Synthesis of Complex Propargylamines Using the Combination of Sonogashira and Mannich Reactions, Tetrahedron Lett. 1998,39, 3647-3650. 

This method has been used for a general asymmetric synthesis of amines by a similar mono- or dialkylalion of propargylamine using the same ehiral adjunct... 

SYNTHESIS A solution of 10.5 g propargylamine hydrochloride in 40 mLMeOH was treated with 2.0 g 3,4-methylenedioxyphenylacetone (see under MDMA for its preparation) followed by 0.55 g sodium cyanoborohydride. Concentrated HC1 was added as needed, to keep the pH constant at about 6. The reaction seemed to progress very slowly. After about five days, the reaction mixture was added to 400 of H20,... 

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]. 

Scheme 9.27. Enantioselective three-component reaction for the synthesis of propargylamines.

Dealkylation of tertiary amines with dibenzoyl peroxide, 44, 74 Decarboxylation, intermolecular, of isocyanates to carbodiimides, 43,32 Decker synthesis of amines, 44, 7t, 75 Dehalogenation of l,l,2-trichloro-2,3,3-trifluorocydobutane, 42,45 Dehydration, of formamides with phosphorus oxychloride to isocy-anides, 41, 13, 101 of 4- 2-hydroxyethyl)piperidine to quinuclidine, 44, 90 Dehydrohalogenation of 2-chloroallyl-amines to propargylamines, 44,55 Delepine reaction, to prepare 2-bromo-allylamine, 43, 6 Deoxyanisoin, 40,16 Deoxybenzoin, 40, IT Deoxypiperoin, 40, IT Deaylamine, 41, 8T... 

A practical gold-catalyzed route to 4-substituted oxazolidin-2-ones 160 has been described. This synthesis starts from JV-Boc propargylamines 158. This route was applied to both terminal and internal triple bonds although the latter react much more slowly <07EJ03503>. 

In an exploration of multi-component reactions for the synthesis of a diverse array of heterocyclic scaffolds Martin et al. demonstrated a cascade reaction involving the imine, formed from the condensation of 2-azidobenzaldehyde 97 with propargylamine, acetyl chloride and ketene acetal 98 to furnish the triazolo-fused benzodiazepine 99 via an intramolecular [3+2] cycloaddition <07OL4223>. 

Heterocyclic-2-propyne-l-amine derivatives have been prepared from propargylamine using the Gabriel synthesis (2,3) as illustrated in Eq. 2 ... 

An effective MCR has been developed by Organ and Li and co-workers [178] for the synthesis of tertiary propargylamines 125 by reacting an aldehyde, an amine... 

Yet the first examples of cyclization of 1,5-enynes with gold were disclosed by the group of Arcadi in the context of a new synthesis of pyridines (equation 48). The cyclization of propargyl enamines catalyzed by sodium tetrachloroaurate gives substituted pyridines in a general way. The enamines were formed in situ from propargylamine and the corresponding ketone. 

Other nucleophiles that have been used in this context are acetylides (alkynes). The addition of those to iminium cations generated in situ from aldehydes and secondary amines accomplishes a gold(III)-catalyzed three-component coupling for the synthesis of propargylamines, as can be observed in equation (124). The reactions are performed in water or in tetrahydrofuran (THF) when supported catalysts are employed.Chiral prolinol derivatives as... 

A novel imidazole synthesis utilizes the salt IV-isopropylacetonitrilium tetra-chloroferrate (8) in condensation with an amino acid ester. The salt is readily made from acetonitrile, ferric chloride and isopropyl chloride. For example, with norvaUne methyl ester a 40% yield of 5-hydroxy-l-isopropyl-2-methyl-4-propylimidazole results. The reaction is believed to proceed via an intermediate amidine. Similarly, 1-isopropyl-2,5-dimethylimidazole is formed when (8) reacts with propargylamine (Scheme 4.1.5) [43, 44). 

One-pot synthesis of 2-imino-5-methylene-l,3-selenazolidines was achieved by reactions of alkyl isoselenocyanates with propargylamines in high yields (Equation 24) <2006H(68)1607>. 

In the presence of copper acetylide complexes, the reaction of aldehydes with acetylene and secondary amines (eq. (2)) leads to propargylamines [6]. In contrast to the synthesis of butynediol, this reaction is catalyzed homogeneously. 

---