Enamine hydroxyalkylation

The enamine-imine tautomerism of the indolenine system gives rise to rearrangement reactions of interest in indole alkaloid chemistry. Thus the synthesis of dihydroburnamicine (625) utilized the rearrangement of an acetoxyindolenine to an a-hydroxyalkyl indole, presumably through an intermediate enamine. Similarly 2,3-dialkyl indoles undergo oxidations to 2-acyl indoles (626-631). 

The reaction of tnfluoromethyl-substituted N-acyl umnes toward nucleophiles in many aspects parallels that of the parent polyfluoro ketones Heteronucleophiles and carbon nucleophiles, such as enamines [37, 38], enol ethers [38, 39, 40], hydrogen cyanide [34], tnmethylsilylcarbomtnle [2,41], alkynes [42], electron-nch heterocycles [43], 1,3-dicarbonyl compounds [44], organolithium compounds [45, 46, 47, 48], and Gngnard compounds [49,50], readily undergo hydroxyalkylation with hexafluoroace-tone and amidoalkylation with acyl imines derived from hexafluoroacetone... 

Fig. 12.18. Hydroxyalkylation of an enamine (—> hydroxy-enamine C), followed by in-situ-dehydration (—> dienamine F) and acidic workup (—> ft,/i-unsatu rated ketone E). Since the enamine A is produced from cyclopentanone, the figure shows the second part of a two-step reaction, which is an alternative to the base-mediated crossed aldol condensation (see Section 13.4.1).

Tertiary amines form complexes with mercury(II) ion, which then give iminium ions by loss of a piotoa Addition of perchloric acid permits isolation of the iminium ion as the perchlorate salt and generally the more-substituted ion is favored (equation 14). Intramolecular trapping by a hydroxyalkyl group is also possible to form aminals (equation 15). The lactam products result from over-oxidation, which is promoted by heat. Basification on the other hand usually allows the isolation of enamines although hydroxyenamines have been obtained by reaction of enamines with mercury(II) acetate (equation 16), while dihydroaromatic systems undergo aromatization (equation 17). ... 

There is appreciable interest in naphtho[2,3-c]pyran-5,10-diones because of their biological activity. A one-pot synthesis of the system involves the conjugate addition of enamines to 2-(l-hydroxyalkyl)-1,4-benzoquinones and the subsequent cyclisation (Scheme 24). The amine function may be lost or retained. Several natural products have been synthesised using this protocol <01JCS(P1)2977>. 

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