Radical cyclization reductive lithiation

Our strategy for the Smij-promoted synthesis of l,2-cis-C-glycosides is illustrated in Figure 3. It was assumed that one-electron transfer to the LUMO of the aryl sulfone group in A would result in concomitant cleavage of the C1 -S bond liberating an anomeric radical intermediate, as previously observed in the reductive lithiation of glycosyl phenyl sulfones." If 5-exo cyclization onto the silicon-tethered alkene/alkyne is substantially favored over a second electron transfer from Smij, then the exocyclic carbon radical B would ultimately be formed. On the other hand, reduction of the Cl-radical by... 

When there is no programmed radical cyclization reaction as discussed in the preceding section, the anomeric radical generated under reductive metallation conditions will obviously be reduced to an organometallic. This is no longer radical chemistry but the radical initiation will impose the stereoselectivity of the anionic process that follows if kinetic conditions are maintained. This situation is observed in the reductive lithiation with lithium naphthalenide (LN) of derivatives 10 where X can be Cl, SPh, or SOjPh (Fig. 13), a process first reported on cyclic a-alkoxyphenyl sulfides. ... 

The synthesis pathway started with the lithiation of ethylbenzene 121 at the benzylic position, followed by acylation of the toluate anirni intermediate at low temperature. It is noteworthy that a potentially competing orf/io-lithiati(Mi of the type championed by Snieckus 85) i.e. between the two stabilizing methoxyl radicals) was not reported under these conditions. Subsequent reduction of benzyUcetone 122 provided smooth access to the t/irco-dimethyl-substituted bicy-clic intermediate 123 via lactonization. DIBAL reduction (—> 124) and reductive debenzylation with palladium on charcoal gave the ring-opened alcohol 125, which was further demethylated to provide a 1,3-diphenol, and then carboxylated under buffered conditions to yield acid 117, also known as phenol B . This compound was formylated with trimethyl orthoformate and acid, then cyclized to give the quinone structure and natural product, 116 (Scheme 3.1). 

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