In this review we investigate the use of complex ester fragment couplings within natural product total syntheses. Using examples from the literature up to 2014 we illustrate the state-of-the-art as well as the challenges within this area of organic synthesis.

The first organocatalytic asymmetric reaction between 1,4-cyclohexanedione and nitroalkenes has been studied, affording bicyclo[3.2.1]octane derivatives containing four continuous stereogenic centres. The products were obtained through a domino Michael–Henry process as a single diastereoisomer with excellent enantioselectivities.