Evans Synthetic Approach to the Vancomycin Aglycon

Before we begin our discussion of how these two distinct strategies were reduced to practice, it is important to reiterate that both required considerable model system exploration and general strategy feasibility studies before Aey reached their full maturation as expressed here. While space constraints severely limit the degree to which we can touch upon these instructive investigations. 

Having stitched together the four aryl building blocks, all that essentially remained from 37 to complete the AB/C-O-D fragment were two macrocyclization events. The first of these closures, the formation of the C-O-D bisaryl ether system, was mildly effeeted through treatment of this compound with CuBr Me2S and K2CO3 in a mixture of pyridine and MeCN at 82 °C. Unfortunately, this macrocyclization failed to afford any atropselectivity in that both 36 and 84 were obtained in a 1 1 ratio in 67 % combined yield. 

The first critical objective in this campaign was finding a method to convert the aryl triazene into a phenol, since its mission in directing the formation of both bisaryl ether systems was now complete. Although model studies indicated its relatively facile removal, this motif unfortunately proved far more resilient within the context of 93 as direct techniques to effect its transformation into a phenol under various acidic conditions universally failed, leading only to reduced product (i. e. a hydrogen atom instead of the triazene 

Although achieving the total synthesis of the vancomycin aglycon 

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