Spirolactamization, oxidative

Cu2+ and Hg2+ are perhaps the most obvious targets for reaction-based signaling systems. However, this approach has also been realized for monovalent Ag+. Here, again a rhodamine derivative (rhodamine B spirolactam 48, Fig. 18) allows the highly selective detection of Ag+ with a detection limit of 14 ppb in water containing 20% ethanol. Silver nanoparticles, a topical analyte today, can also be detected, after oxidation of the particles with H2O2/H3PO4 [141]. The selectivity was tested with Ca2+, Ba2+, Mg2+, Cr2+, Mn2+, Fe3+, Co2+, Ni2+, Cu+, Cu2+, Zn2+, Pd2+, Cd2+, Hg+, and Hg2+ and no interference was found. 

For this purpose, the chiral acid (R)-(-)-22 was chosen as the starting material and converted to the spirolactam 25. Condensation with benzylamine followed by catalytic dihydroxylation and oxidation gave aldehyde 23. 

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]. 

Lactams.2 N,N-Dialkenyl-P-oxoamides are oxidized by Mn(OAc)3 to lactams and spirolactams via a radical cyclization. Ethanol is a better solvent than acetic acid or acetonitrile. 

This reaction type was also reported by Cossy who applied an intramolecular reaction for preparing azaspiranic systems (Scheme 6). A-Diallylaminocarbonyl enamine 10 was oxidized by Mn(III) acetate to generate cation radical CRIO, which cyclized to give spirolactam 11. 

A route to spirolactams involves oxidation of oxazolines derived from t)rosine. Simple amides give the corresponding spirolactones. ... 

In summary, the total synthesis of (-)-FR901483 was accomplished by an oxidative cyclization of a phenolic oxazoline to a spirolactam in the key step. The longest linear sequence leading to FR901483 through a Snider-type inversion encompasses 20 steps from commercial L-tyrosine and it proceeds with an overall yield of 1%. The alternative synthesis involving a Sorensen-type Mitsunobu inversion is shorter (17 steps), and it affords identical overall yield (1.3%). 

The oxidative spirocyclization of phenolic substrates containing an internal nitrogen nucleophile provides a useful tool for the construction of nitrogen heterocycles [287, 315-318], For example, the hypervalent iodine-induced cyclization of phenolic oxazolines 251 affords the synthetically useful spirolactam products... 

In a similar procedure, the amide derivatives of phenolic substrates 62 can be catalytically oxidized to the respective N-fused spirolactams 63 using catalytic amounts of /7-iodotoluene and mCPBA as the terminal oxidant (Scheme 4.32) [61]. 

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