Natural product synthesis organometals

Anctil, E. J. G., Snieckus, V. The directed ortho metalation-cross coupling symbiosis. Regioselective methodologies for biaryls and heterobiaryls. Deployment in aromatic and heteroaromatic natural product synthesis. J. Organomet. Chem. 2002, 653,150-160. 

Numerous organometal additions onto ene-sulfones are reported. A sulfonyl group secures powerful activation, and moreover, it can be readily removed by reduction or elimination. This makes the sulfonyl function a cherished auxiliary in natural product synthesis. A rational entry to d-(+)-carbacyclin (in 4.7% overall yield by a triply convergent synthesis) exemplifies the approach. The addition of the silyl-protected trans-(5)-3-hydroxy-l-octenyllithium onto cyclopentenyl phenyl sulfone 162 triggers a condensation with the allyl chloride tail. The carbacyclin skeleton constructed, the sequence is terminated by protodesilylation (using tetrabutylammonium fluoride hydrate), reductive removal (with lithium) of benzyl and benzenesulfinyl, and selective oxidation of the primary alcohol site (Scheme 1-117). ... 

Since the preparation of /3,/3-substituted alkenylmetals as the first-generation organometals has been achieved mostly by Zr-catalyzed carboalumination " and carbocupration, the exploitation of Protocol I has largely resorted to these two carbometallation reactions, as indicated by the results summarized in Table 13. Moreover, since it is impractical to carry out methylcupration of alkynes requiring several days at -25 the synthesis of natural products represented by 1 and 2 by the use of Protocol I has mostly been limited to those cases where Zr-catalyzed carboalumination is... 

I. SYNTHESIS OF NATURAL PRODUCTS VIA Pd-CATALYZED CROSS-COUPLING OF a-HETERO-SUBSTITUTED ORGANOMETALS... 

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