3-Tetralone pyrrolidine enamine

The pyrrolidine enamine of 2-tetralone (177) was converted to l-cyano-2-tetralone, which exists almost entirely in the enolic form (178), by reaction with cyanogen chloride (J23). Reaction of 177 with cyanogen bromide gave N-naphthylpyrrolidine (179), presumably via the unstable bromoenamine (180). The latter observation is in accord with the mode of reaction of the heterocyclic enamine (126) with cyanogen bromide, which resulted in the... 

The regioselectivity of reaction of 2-tetralone enamines depends on the amine moiety as well as the electrophilic reagent. For example, / -nitrostyrene reacts with the morpholine enamine mainly at Cl9 whereas the pyrrolidine enamine reacts exclusively at C3, in contrast to phenyl isocyanate which reacts with both enamines at (V11. / -Nitrostyrene reacts with the morpholine enamine of fraw.s-decalin-2-one at C3 from an axial direction,... 

Application of the dimethyl acetylenedicarboxylate reaction to enamines of cyclic ketones gave similar results the pyrrolidine enamines of cyclopentanone and a-tetralone gave the ring-expanded products (60 and 62, respectively) in toluene, and pyrrolizidines (61 and 63, respectively) in methanol (equation 32)53. 

The monomethylation of the pyrrolidine enamine of -tetralone shown in Scheme 41 provides a highly successful example of the reaction. Attempted alkylation of the ketone with 1 equiv. of methyl iodide in the presence of a strong base gave almost exclusively the recovered ketone and its dimethylated derivative. 

Regioselective aza-annulation reactions have been achieved through the use of aryl substituted keto enamine substrates. Aryl substitution at the a-position of the enamine provides for regioselective imine-enamine tautomerization at the non aryl (i carbon. Early studies in this area compared the utility of pyrrolidine enamine versus benzyl imine derivatives of a-tetralone.8 In the absence of solvent, aza-annulation of 75 with acrylamide led to the formation of 76, but use of imine derivative 77 resulted in significantly higher yield of 76 (eq. 19).8 Similar reactions were observed between an aryl ethyl ketone and acrylamide (72% yield, dioxane, 70 °C) or acrylonitrile when catalyzed by AICI3 at 25 °C.33... 

The iV-aminopyrrole - benzene ring methodology has been applied to a synthesis of the 9,10-dihydrophenanthrene juncusol (218) (81TL1775). Condensation of the tetralone (213) with pyrrolidine and reaction of the enamine with ethyl 3-methoxycarbonylazo-2-butenoate gave pyrrole (214). Diels-Alder reaction of (214) with methyl propiolate produced a 3 1 mixture of (215) and its isomer in 70% yield. Pure (215) was reduced selectively with DIBAL to the alcohol, reoxidized to aldehyde, and then treated with MCPBA to generate formate (216). Saponification to the phenol followed by O-methylation and lithium aluminum hydride reduction of the hindered ester afforded (217), an intermediate which had been converted previously to juncusol (Scheme 46). 

Enamines derived from relatively reactive amines, such as pyrrolidine and sterically unhindered cyclic ketones, are formed rapidly either with or without acid catalysis35,42. In the case of 2-substituted cyclic ketones (2-methylcyclohexanone,l-tetralone), cyclo-heptanone and higher cyclic ketones on the one hand, and with weakly basic (e.g. morpholine) or hindered amines on the other, the use of toluene solvent and a catalytic amount of p-toluenesulphonic acid affords good yields and shortens the reaction time. 

It was shown that the rate of formation of the enamine of 3,3-dimethylaziridine is 5 to 10 times faster than that of pyrrolidine with 2-methylcyclohexanone and 1-tetralone, probably due to decreased steric hindrance. However, the yields of monomethylated products are significantly lower with the azetidine enamine92. 

A third procedure for building aza-steroidal systems proceeds by intramolecular cyclization of enamine esters derived from jS-tetralones and appropriately substituted pyrrolidines. This reaction is illustrated in the synthesis of the 14-aza-steroid (162) by reaction of the j -tetralone (160) with a 3-substituted pyrrolidine ester. 

---