Erythrinan acyliminium ions

The greater electrophilicity of the A -acyliminium ion as compared with an ordinary iminium ion was nicely illustrated as early as 1957. In experiments directed at the total synthesis of erythrina alkaloids, cyclization of iminium ion (60) to the erythrinane skeleton (61) fails (equation 34). However, A(-acylim-inium ions (62) and (63) can both be converted into the desired skeleton in good yields. A recent il-... 

Besides this widespread pathway based on the intermediate N-acyliminium ion, several other established methods have been applied to construct the C5/C13 bond of the erythrinane skeleton. Thus, the Heck reaction has proved to be an attractive approach to the target compounds. The synthesis reported by Rigby (Scheme 10) starts with a smooth [1 -I- 4] cycloaddition of certain isocyanides to the vinyl isocyanate 79 affording the required hydroindolone 80. Then the iodoarene moiety has been installed by AT-alkylation with the phenethylmesylat 81 giving the N-alkylated precursor 82. Cyclization of 82 under Heck conditions yields the expected 7,8-dioxoerythrinane 83 as a single diastereomer, which then has been converted to ( )-2-cpi-erythrinitol (84) in twelve additional steps (64). 

In a new attractive B/C(a) route the required N-disubstituted amine derivatives, e.g. the metalated carboxamides 169, have been generated in situ, reacting at first the primary phenethylamins 52 or 167 with trimethylaluminum followed by the enolacetates of cyclohexanoyl carboxylic acids 168. The intermediates 169 eliminate acetic acid affording the Ai-acyliminium ions (170), which cyclize to the desired erythrinanes 68 and 96. Due to the typical H NMR shift of 14-H given (5 = 6.93 ppm (31)) the products should possess the B/C cw-configura-... 

Furthermore, sulfur containing compounds, especially a-S-function-alized acetamide derivatives are suitable precursors to assemble the erythrinane framework via a combined radical/acyliminium ion cyclization. Thus, treatment of the xanthate 178 (Scheme 31) with lauroyl peroxide causes B ring generation via the radicals 179 and 180. After further oxidation of the latter forming the acyliminium ion 181, cat-alytical amounts of p-toluenesulfonic acid induces the ring closure to the aromatic unit furnishing 15,16-dimethoxy-2,8-dioxoeiythrinane (175) in 82% yield (96). 

Finally, there is also only a single report descrihing the sequential formation of the rings A, B, and C of the erythrinane framework in one step. Starting from the complex homoveratrylimide derivative 191 this triple cascade process involves - apart from the initial Pummerer reaction 191 —1192 - the Diels-Alder reaction 192 —> 193 as well as the final acyliminium ion cyclization 194 —1195 providing the erythrinane 195 in 83% yield. This in turn could be converted to ( )-erysotramidine (73) by a sequence already reported (76) (Scheme 34). The requisite educt 191 has been smoothly prepared through six steps in 45% overall yield (80). 

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