Alkynes nitrogen nucleophiles

Cyclizations with nitrogen nucleophiles involving alkynes and allenes have received little attention until recently. The cyclizations of several a-aminoallenes to 3-pyrrolines with silver tetrafluoroborate was reported by Claesson and coworkers (equation 133).264 A similar cyclization to form A -carba-penems has been reported (equation 134).265 Diastereomeric allenes (R1 R2) were shown to cyclize with complete stereocontrol. Cyclization with palladium chloride in the presence of allyl bromide or electrophilic alkenes allowed for the intermediate vinylpalladium species to be trapped by the electrophile.2651 A related product was obtained by cyclization of an alkynic substrate (equation 13S).265 Other examples of 5-endo cyclization of p-aminoalkynes50 include the formation of indoles by cyclization of 2-alkynylanilines with mercury salts200 or palladium chloride,266a,266b,266c formation of 1-pyrrolines with catalytic palladium chloride (equation 136)198 and formation of pyrroles by cyclization of hydroxy-substituted p-aminoalkynes.198,2666... 

Cyano-derivatives can be readily obtained by a ruthenium-catalyzed addition of various hydrazines to terminal alkynes [89] in which the cyano carbon atom arises from the terminal alkyne carbon atom. The tris(pyrazolyl)borate (Tp) complex RuCl(Tp)(PPh3)2 (1 mol%) was found to be the most active catalyst, and N,N-dimethylhydrazine (5 equiv.) the best nitrogen source. The proposed mechanism involves the nucleophilic attack of the nitrogen nucleophile on the a-carbon of a vinylidene intermediate (Scheme 8.27). Proton migration in the resulting a-hydrazi-nocarbene, followed by deamination, would give the nitrile derivative and regenerate the catalytic species. 

Table 19. Additions of nitrogen nucleophiles to alkynes, RC CR, to form acyclic adducts ... 

The sp C-H bonds of terminal alkynes are well known to become activated by metal salts in the presence of bases. A variety of research groups have examined the use of terminal alkynes as nucleophiles for the oxidative addition to the C-H bond adjacent to the nitrogen atom of amines. Li and co-workers examined the oxidative coupling of /V,/V-dimethylaniline 26 with 1-alkynes 27 (Scheme 15) [31, 32]. 

Iodo-indoles can be prepared simply by using the halogen (or bis(pyridine)iodonium(I) tetrafluorobo-rate ) to activate the alkyne for nucleophilic attack by the nitrogen. Even iV,iV-dimethyl orf/fo-alkynyl-anilines take part in such closures, iodomethane being lost in the final stage, with formation of an A -methyl indole. " ... 

The aminopalladation-reductive elimination domino reaction of alkynes containing nitrogen nucleophiles close to the carbon-carbon triple bond has been shown to be a valuable methodology for the synthesis of the pharmaceutically important indole ring system and a variety of nitrogen-containing heterocycles. 

A nitrogen nucleophile (98) reacts with ethynyl(phenyl)iodonium salt to give an ylide (99), which loses iodobenzene to give vinylidine (100). The vinylidine rearranges by 1,2-hydrogen shift to the corresponding alkyne in the usual way. ... 

Compared with aUylic C-H bond, benzylic C-H bond has similar BDE. Under the oxidative conditions, it is still susceptible to undergo SET to form a benzyl radical or carbocation, which would like to be trapped by a series of C(sp )-H nucleophiles or electron-rich aromatic rings (Scheme 2.30). For example, active methylenic 1,3-dicarbonyl compounds [148-153], nitrogen nucleophiles (amines or amides or almidine), [154—158] IV-hydroxyamides [159], ketones [160, 161], aldehydes [162], electron-rich alkenes [163], aromatic rings [164, 165], and terminal alkynes [166] are good coupling partners in the oxidative benzylic C-H bond... 

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