Bisaryl ethers

Many other reactions have been used to construct macrocycles, and many are related to specific bond formations and therefore not very widely applicable. Since bisaryl ethers and biphenyl units are relatively common in naturally occurring macrocycles [4] (both units can be found in the important antibiotic vancomycin, 20, Fig. 7), some approaches to their synthesis will... 

Scheme 5. Methods of synthesizing cyclic bisaryl ethers.

While each of these three methods for bisaryl ether synthesis (among several others) could potentially be applied in the macrocy-clization step needed to construct the D-O-E system, the Nicolaou group decided instead to develop their own means to form such systems using a triazene moiety on the aromatic acceptor to drive the... 

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... 

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