Operation of the Sequencer

Since the low-yielding nature of this reaction seemed to have its deliterious origins in the epoxide-forming step, and not the later operations of the sequence, the Nicolaou group reasoned that perhaps a better approach would be to create the epoxide ring from a diol such as 48 (see Scheme 7b). Moreover, if the ester within 42 was exchanged for a cyanide, perhaps the entire anhydride (47) could be formed in a single pot, since the same p-elimination of 49 to 50 and subsequent 5-exo-dig cyclization onto this alternate C-12 substituent would afford a carbocyclic iminobutenolide (51). 

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