A practical one-pot radical-ionic sequence for the preparation of epoxides: application to the synthesis of unnatural polyhydroxylated alkaloids

A Formal Intermolecular Iodolactonization Reaction Based on a Radical‐Ionic Sequence

“…However, when 8a was treated under a variety of acidic conditions [trifluoroacetic acid (TFA), para ‐toluenesulfonic acid (PTSA), HCl, or heating], 10 was not observed, but a complex mixture of degradation products was formed instead. Basic conditions were not evaluated because similar ATRA adducts were previously converted into their corresponding epoxides upon treatment with base 6…”

“…However, atom transfer radical additions5 (ATRAs or Kharash reactions) are powerful tools for the simultaneous construction of carbon–carbon and carbon–heteroatom bonds and produce valuable synthetic intermediates that are embedded with various functional groups for further synthetic manipulation. Recently, our group reported some new radical‐ionic sequences for the synthesis of epoxides6 and 1,4‐dicarbonyl compounds7 by employing an initial ATRA reaction, in which the adduct is not isolated but treated under ionic conditions (basic media or silica gel) to afford the desired molecular skeleton. On the basis of the above results, we propose that the application of an ATRA reaction between α‐iodo acid or α‐iodo ester 6 and allylic alcohol 7 would yield adduct 8 , which could be transformed into lactone 9 under standard conditions.…”

Model Studies Toward the Enantioselective Synthesis of Perhydrohistrionicotoxin: A Free-Radical Approach to the Azaspirocycle Core

“…Initially, we assumed that the ATRA reaction on either 13 or 15 would furnish a radical adduct bearing an iodine atom (see Scheme 1), which would have to be reduced, for example, with Bu 3 SnH. However, when we reacted carbamate 15 using the previously employed conditions (Et 3 B, O 2 , CH 2 Cl 2 , r.t.), 15 we observed a complex mixture of products where the only isolated product was not the expected ATRA adduct 16, but debenzylated carbamate 17 in 20% yield, along with a series of decomposition products (Table 1). Even though at this point we are not sure of the exact mechanism for this reductive ATRA reaction, a plausible mechanism might involve an intramolecular radical 1,5-hydrogen transfer, followed by oxidation of the resulting benzylic radical into an iminium salt and hydrolysis of the latter to produce the corresponding de- 19 17.…”

“…In recent years, our group has reported on the synthetic applications of atom transfer free radical reactions (ATRA or Kharasch reactions), in which the ATRA adduct is transformed in situ into a different functional group, such as an epoxide 15 or a lactone, 16 depending on the reaction conditions (Scheme 1). In the above-mentioned work, we employed a radical-ionic sequence with an unprotected allylic alcohol, allowing the ionic cyclization to be performed in one pot.…”

A Formal Synthesis of (±)-Tylophorine Based on an Atom Transfer Radical Addition Reaction

“…A few years ago, our group reported a new sequence for the preparation of epoxides, 14 based on the use of unprotected allylic alcohols as radical acceptors for an atom transfer radical addition (ATRA). The treatment of the ATRA adduct with DBU allowed the one-pot formation of an epoxide (4, Scheme 1).…”