Skipped dienes (1,4‐dienes) are widely distributed in a variety of biologically active natural products. The synthesis of these skipped dienes is a relatively undeveloped area compared with that of conjugated dienes (1,3‐dienes) due to the sp3‐hybridized carbon between two olefins. Especially, development of methods to meet both high stereoselectivity and convergency is highly challenging. This review focuses on recent advances in the synthesis of skipped dienes in the total synthesis of complex natural products, which are classified into three classes; a) skipped dienes comprised of two disubstituted olefins, b) skipped dienes including trisubstituted olefin(s), and c) 3‐methyl skipped dienes.

The chiral synthesis of (+)-saxitoxin and its derivatives is described. Two consecutive carbon–nitrogen bonds at C-5 and C-6 in saxitoxin were effectively installed by the sequential Overman rearrangement of an allylic vicinal diol derived from d-malic acid. The bicyclic guanidine unit was constructed by the intramolecular aminal formation of an acyclic bis-guanidine derivative possessing a ketone carbonyl at C-4. From the bicyclic aminal intermediate, (+)-saxitoxin, (+)-decarbamoyl-β-saxitoxinol [(+)-dc-β-saxitoxinol], and the unnatural skeletal isomer, (−)-iso-dc-saxitoxinol, were synthesized.