Acetylene derivs enamines

Other interesting synthetic applications of the ketone-derived enamine alkylation are found in the monomethylation of steroid enamines (249), extension of the benzylation reaction (250) to a ferrocene derivative (251), the use of a-bromoesters (252) and ketones (252) or their vinylogues (25J), in the syntheses of alantolactone (254-256), isoalantolactone (257), and with a bridged bis-enamine (258). The use of bifunctional alkylating agents is also seen in the introduction of an acetylenic substituent in the synthesis of the characteristic fragrant constituent of jasmine (259), the synthesis of macrocyclic ketolactones (260), the use of butyrolactone (261), and the intermolecular or intramolecular double alkylations of enamines with dihalides (262). 

Pyridine-Derived Enamines and Related Ylids with Acetylenic Esters... 

Additions to 1-acetylene-l-pbosphonium salts Ketones and enamines from acetylene derivatives... 

Acetylene derivatives from enamines via quaternary enammonium salts... 

H-l,4-Benzodiazepine-3,5(lH,4H)-diones from anthranilamides Enamines from acetylene derivs. 

A 50-60%-soln. of N,N-diethylprop-2-ynylamine in hexane passed al 65° during ca. 40 min. through a KNHa-on-alumina catalyst N,N-diethylprop-l-ynyl-amine. Y 65%. F. e. s. A. J. Hubert and H. G. Viehe, Soc. (G) 1968, 228 enamines from 2-ethyleneamines s. Soc. (G) 1968, 2048 1,3-dienes from acetylene derivatives, also conjugated tetraenes from a,co-diynes, s. Ghem. Ind. 1968, 975. 

Nonactivated terminal acetylenes have been added to enamines derived from aldehydes. A long reaction time or catalysis by copper(I) chloride is necessary. Thus the enamine (16) formed the adduct (72) on heating with phenylacetylene (64). 

A two-carbon ring expansion of cyclic ketones was achieved by the addition of acetylenic esters and diesters to the enamine derivatives of the ketones, and reported almost simultaneously from several laboratories (337-343). The intermediate bicyclic adduct could be isolated in some cases. 

Dicarbomethoxyacetylene has also been added to the pyrrolidine enamine derivative of acetylacetone, demonstrating a new synthesis of phthalic esters (345). A 3-acylpyridine synthesis was achieved by the addition of an acetylenic aldehyde to the vinylogous amide derived from ammonia and dihydroresorcinol (346). 

These reactions are related to the formation of pyrroles and quinolines from aminocarbonyl compounds and acetylenes (582,583) and may be contrasted with the formation of pyran derivatives by electrophilic attack on an enamine, followed by addition of an oxygen function to the imonium carbon (584-590). 

Alternatively, the enamine portion may be located in the Aralkyl chain. For instance, piperidines bearing a 7-chloro substituent yielded quinolizidines 263 through a conjugate addition of the nitrogen atom to acetylenic sulfones followed by an intramolecular alkylation (Scheme 55) <2000JOC4543>. Other cyclizations that are summarized below used as starting materials piperidine derivatives obtained by similar conjugate additions to vinyl sulfones (see Section 12.01.9.3.6). 

Hendrickson and co-workers have used the reaction of a-amino-ketones with acetylenic esters for synthesizing pyrrole derivatives. Thus, in the reaction of a-aminopropiophenone with DMAD, an intermediate enamine adduct (56) is formed, which ultimately gives rise to the pyrrole 57 in presence of methanolic HCl [Eq. (16)]. Pandit and Huisman have shown the generality of this scheme in the synthesis of polycyclic pyrrole derivatives. 

Several cycloaddition reactions of 2,5-dihydrothiophene derivatives have been reported. Compounds possessing an enamine system undergo [2 + 2] cycloaddition with acetylene-dicarboxylic ester (Scheme 215) (77AHC(2l)253). Diels-Alder addition of the 2,5-di-hydrothiophene-3-carboxylic ester (557) with butadiene, followed by desulfurization, leads to the trisubstituted cyclohexane (558) (B-74MI31404). 

Condensation of cyclic enaminoamides (246) with dimethyl acetylene-dicarboxylate gives 2-azepinone derivatives (247) (85AJC1847). Similarly, immonium salts (248) when treated with bases give enamines, which subsequently react with dimethyl acetylenedicarboxylate or unsaturated ketones and give azepines (81AP787). The reaction of primary enaminonitriles with dimethyl acetylenedicarboxylate proceeds in a similar fashion (84CPB2596). Another route to azepines has been described (95JHC57) (Scheme 51). 

The reaction of enamines with acetylenic compounds has been the subject of intensive studies. In general, alkyl acetylenedicarboxylates and propiolates undergo initial cycloaddition (Chapter 18) to form cyclobutene derivatives. These cyclobutenes rearrange, in most cases spontaneously, to form products whose structures depend on the starting enamine and on the reaction conditions126-128 (Scheme 45). 

The adduct 65 of aziridine to the acetylenic phosphonium salt 64 readily rearranges to the enamine 66, which in refluxing acetonitrile is converted into the pyrroline derivative 68 by opening of the aziridine ring and recyclization of the resulting zwitterion 67 (equation 33)54. 

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