Silver-Catalyzed Long-Distance Aryl Migration from Carbon Center to Nitrogen Center

Abstract

Selective cleavage of an inert C-C bond followed by C-O/N bond formation through a long-distance aryl migration from a carbon to a nitrogen center via Ag catalysis is reported. The migration products were easily converted into γ-hydroxy amines and tetrahydroquinoline derivatives in quantitative yields. Preliminary mechanistic studies indicated a radical pathway.

γ‐Functionalizations of Amines through Visible‐Light‐Mediated, Redox‐Neutral C−C Bond Cleavage

“…[1] a-a nd b-Functionalizations of aliphatic amines via C(sp 3 )ÀHb ond activation are well established, [2,3] while derivatizations at the g-position have been much less explored. [5] Aryl migration via radical ipso substitution represents ah ighly enabling strategy for remote functionalizations, [6] although the need of stoichiometric and toxic radical initiators (such as Bu 3 SnH, AIBN) [6,7] or oxidants (Ag salts, hypervalent iodine reagents) [5,8] combined with harsh reaction conditions (typically T > 100 8 8C) limits the broad applicability of these transformations. [4] CÀCb ond cleavage has also been used in this context as demonstrated by Shi and co-workers,w ho recently reported an elegant synthesis of g-hydroxyamines through an oxidative aryl migration process (Scheme 1B).…”

“…Para-substituted arenes proved to be efficient migration partners delivering compounds 3-6 (R = Me, tBu, F, Ph) in moderate to excellent yields whereas more electronically biased substrates (e.g. Significant selectivities in favour of the migration of the more electron-rich aromatic ring [5] were observed even in the case of electronically similar arenes as demonstrated by the productive reactions yielding compounds 13-15.I nt he case of highly electronically differentiated substrates,only products stemming the migration of the electron rich aromatic could be identified and isolated in moderate yield from the reaction media (16)(17)(18). Meta-substituted derivatives were also well tolerated as demonstrated by the reactions to form 7 and 8.…”

“…[4] CÀCb ond cleavage has also been used in this context as demonstrated by Shi and co-workers,w ho recently reported an elegant synthesis of g-hydroxyamines through an oxidative aryl migration process (Scheme 1B). [5] Aryl migration via radical ipso substitution represents ah ighly enabling strategy for remote functionalizations, [6] although the need of stoichiometric and toxic radical initiators (such as Bu 3 SnH, AIBN) [6,7] or oxidants (Ag salts, hypervalent iodine reagents) [5,8] combined with harsh reaction conditions (typically T > 100 8 8C) limits the broad applicability of these transformations. [9] Moreover,harvesting the resulting C-centered radical/cations generated upon migration in as ubsequent intermolecular C(sp 3 )ÀC(sp 3 )b ond formation is virtually unprecedented under the highly oxidative or reductive conditions.Asaresult, the remote functionalization of amines involving the formation of an ew C(sp 3 ) À C(sp 3 ) bond remains af ormidable challenge.…”

Copper‐Catalyzed Arylation of Remote C(sp3)−H Bonds in Carboxamides and Sulfonamides

“…Therelatively harsh reaction conditions and the instability of the N-haloamines have nevertheless limited to some extent its synthetic applications.Amajor breakthrough addressing this issue came in 1980 when Suµrez and co-workers reported adirect conversion of 1b into the corresponding pyrrolidines 2 using as toichiometric amount of iodine and phenyliodine diacetate as oxidants. [2,3] Subsequently,s ilver salt catalyzed, iodine-catalyzed, and triiodide-mediated versions of the HLF reaction were developed by the groups of Li, [4] Shi, [5] MuÇiz, [6] and Nagib, [7] respectively.M ore recently,t he groups of Knowles [8] and Rovis [9] independently developed ap hotoredox-catalyzed remote functionalization of simple carboxamides and sulfonamides.I nt hese latter examples,t he Ccentered radical B was trapped by aMichael acceptor leading to 3.C losely related to the HLF reaction, the group of Yu reported metal-catalyzed g-halogenation of imides to give 4, [10] while Shi [11] and Nevado [12] described aneophyl-type 1,4-Ct oNaryl migration for the generation of the carbon radicals.…”

Radical aryl migration enables diversity-oriented synthesis of structurally diverse medium/macro- or bridged-rings

“…The selective addition of diverse radicals to unactivated alkenes represents an efficient way for the functionalization of such alkenes2021. In addition, great advances have been achieved in the field of aryl migration following radical ipso substitution at an aromatic ring for constructing new organic compounds1622232425262728293031. Despite these advances, no radical-based protocol has been available for the conversion of unactivated alkenes into medium- to large-sized and related bridged ring libraries via aryl migration, especially for access to such chiral skeletons.…”