Nozaki-Kishi macrocyclization

Danishefsky has developed a mild oxidative procedure for the conversion of highly functionalized alkenyl boronates (obtained by alkenyl boronate cross-metathesis) to the corresponding aldehydes with trimethylamine N-oxide that was found to be compatible with hydroxyl, ketone and acid functionalities present in alkenyl boronates without protection [109]. For example, by using this methodology, it was possible to oxidize the iodoalkenyl boronate intermediate 133 to the aldehyde 134 that was subjected to intramolecular Nozaki-Kishi macrocyclization yielding 11-hy-droxy deoxyepothilone precursor 135 in 40% yield (Scheme 3.71). 

The first total synthesis of pinnatoxin A (104) was completed by Kishi s group in 1998 [67,68]. Their synthetic strategy is shown in Scheme 13. They planned to make the seven-membered iminium ring at the last stage, and the key macrocyclization was carried out by an intramolecular Diels-Alder reaction. Fragments 138-141 were coupled using the Nozaki-Hiyama-Kishi reaction, Juba coupling reaction etc. 

Mohapatra et al. reported on the macrocyclization of intermediate 31 under Nozaki-Hiyama-Kishi conditions (CrCl2, NiCl2, dimethylsulfoxide [DMSO], 85% over two steps). Subsequent deprotection afforded Amphidinolactone A (Scheme 12.30)." ... 

Berkessel et al. have used an asymmetric Nozaki-Hiyama-Kishi reaction for the synthesis of several laulilamide analogs. (/ ,/ )-DlANANE ligand 14 was used for the key NHK coupling of the macrocyclic aldehyde 61 and iodide 62. Ten mol% of the chromium(ll) complex of 14 overcame the substrate selectivity and afforded the desired configuration in a dr of 78 22 and yield of 43% (Scheme 12.40). 

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