Nitrogen-tethered phenol derivative

The other key step in the synthetic approaches to FR901483 is the elaboration of the quaternary spirocenter at C(l) (Scheme 4). Sorensen, Ciufolini, and Wardrop all use an oxidative spirocyclization of nitrogen tethered phenol derivatives, employing hypervalent iodine reagents, to generate the spirocenter at C(l). In contrast, in the other approaches the formation of the quaternary stereocenter does not coincide with the... 

The other two enantioselective syntheses of FR901483 reported by Sorensen and Ciufolini (sections 3.2.2 and 3.2.3) as well as an approach to the demethylamino derivative by Wardrop (section 4.1) have in common the elaboration of the l-azaspiro[4.5]decan-8-one intermediates by means of an oxidative azacyclization from a nitrogen-tethered phenol derivatives. In the following section an overview of this process is given. 

The hypervalent iodine oxidation of nitrogen-tethered phenol derivatives, a straightforward entry to l-azaspiro[4.5Jdecanediones... 

The more challenging task of direct C-N bond formation has recently been accomplished by utilization of the oxazoline ring as the nitrogen donor [76 - 78]. This approach was demonstrated by the preparation of spirolactams such as 17 from oxazoline derivatives of tyrosine and related phenolic acids by oxidation with BAIB in trifluoroethanol (Scheme 25), and similar conversions of indole-tethered oxazalones to tetracyclic products through spirolactam intermediates. It is noteworthy that phenolic amides, amines, and iminoethers were not useful for this purpose [78]. 

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