A formal synthesis of 6-deoxyerythronolide B: Exploiting the thiazolidinethione chiral auxiliary

A highly versatile asymmetric aldol addition methodology has been previously described by the Crimmins group. Titanium enolates of N-acylthiazolidinethiones are used in aldol additions to provide either non-Evans or Evans syn aldol adducts with high selectivity by changing the amount or nature of the amine base. The chiral auxiliary is easily cleavable to a variety of products including the aldehyde in a single step. The practicality and efficiency of this methodology is highlighted by completion of a formal synthesis of 6-deoxyerythronolide B via a linear, iterative approach. This dissertation describes a convergent approach to 6-deoxyerythronolide B utilizing a ring closing olefin metathesis reaction, as well as the linear approach, culminating in a formal synthesis of the natural product in 23 steps.