Domino reductive fragmentation

Scheme 3.6. Samarium(ll)iodide-promoted domino reductive fragmentation/aldol reaction.

Samarium(II) iodide has been proven to be an efficient reagent to initiate radical processes that can be utilized in domino reactions. In 2001, Schwartz and coworkers [16] reported a domino reductive fragmentation and aldol reaction with 1,4-diketones promoted by Sml2 to afford the ring contracted products. The Reissig... 

Domino Reductive Fragmentation/Barbier-iype AUylation... 

This Strategy based on the zinc-promoted domino reductive fragmentation/Barbier-type allylation followed by RCM has been used to prepare several carbocyclic natural products. 

The total synthesis of alkaloid (+)-lycoricidine reported by Yadav et al. represents a further application of the sequence domino reductive fragmentation/allylation followed by ring-closing metathesis in the synthesis of bioactive natural products [42], Thus, reaction of co-iodoglycoside 29 with zinc/allyl bromide in THF/HjO afforded diene 30 (87%, dr 85 15). Ring-closing metathesis of diene 30 followed by acetylation furnished cyclohexene 31. Treatment of the acetate 31 with PhINTs in the presence of Cu(acac)2, followed by sodium naphthalenide, afforded the aziridine 32 (67%), from which (-i-)-lycoricidine (33) can be easily obtained (Scheme 3.11). 

Domino Reductive Fragmentation/Barbier-Type Propargylation... 

Another Sml2-mediated domino process was reported by the Baran group in the synthesis of (+)-Cortistatin A 51 [22]. When the bromoketone 47 was treated with Sml2 in the presence of the additive DMPU (l,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone), a cyclopropane fragmentation occurred to form an a-bromo radical 48, which underwent subsequent reduction by Smij and then bromide elimination to give 49 with a newly formed C=C double bond and a Sm(lll) enolate. After a few minutes, the addition of 2,4,4,6-tetrabromo-2,5-cyclohexadienone (TBCHD) resulted in the a-brominated product 50, which was converted into cortistatin A 51 (Scheme 5.13). 

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