Enantioselective Hydroamination of Alkenes with Sulfonamides Enabled by Proton-Coupled Electron Transfer

Abstract

<div><p>An enantioselective, radical-based method for the intramolecular hydroamination of alkenes with sulfonamides is reported. These reactions are proposed to proceed <i>via</i> <i>N</i>-centered radicals formed by proton-coupled electron transfer (PCET) activation of sulfonamide N–H bonds. Non-covalent interactions between the neutral sulfonamidyl radical and a chiral phosphoric acid generated in the PCET event are hypothesized to serve as the basis for asymmetric induction in a subsequent C–N bond forming step, achieving selectivities of up to 98:2 er. These results offer further support for the ability of non-covalent interactions to enforce stereoselectivity in reactions of transient and highly reactive open-shell intermediates.</p></div>

Enantioselective synthesis of heterocyclic compounds using photochemical reactions

“…This interaction was used to efficiently induce chirality [83,84]. Thus the photocatalytically induced cyclization of sulfonamides 32 to the corresponding pyrrolidines 33 was carried out with high enantioselectivity (Scheme 7) [85]. The nitrogen centered radical species 34 is generated by electron transfer to the electronically excited iridium photocatalyst and a proton transfer to the chiral phosphate P1.…”

“…It must be pointed out that the chiral information that is intermediately conserved in a conformationally rigid structure is transferred by inversion of configuration. This observation is explained by the fact that the spin multiplicity changes from the triplet in the diradical intermediate 83, 85 to the singlet state in the final product 86. In such a process, intersystem crossing and radical combination concomitantly occurs when both radical carrying p orbitals are orthogonally orientated as depicted in structure 85 [158][159][160].…”

Recent developments in enantioselective photocatalysis

“…Recently, Knowles et al used a similar tricatalytic system for the enantioselective cyclisation of sulfonamides 238 (Scheme 37) [98]. In this case, the proposed mechanism involves a PCET step to give an N-centred radical that then cyclises enantioselectively to give the alkyl radical intermediate 239 • , which abstracts a hydrogen atom from TRIP-thiol to produce enantioenriched cyclic sulfonamides 239 in excellent yields and enantioselectivities (28 examples, up to 98:2 er).…”

Addition Coupled Electron Transfer (ACET) and Addition Coupled Electron Coupled Proton Transfer (ACPCET)

“…Since its first being proposed in 1981 1 , the proton coupled electron transfer (PCET) has become a well-known concept, and both its theory [2][3][4][5][6][7][8][9] and practical use [10][11][12][13][14][15][16] have been continuously explored. Under this scheme, besides the Hydrogen Atom Transfer (HAT) reaction, in which both the proton and electron being transferred involves the same orbital, during the reaction of a hydrogen donor (AH) and an acceptor (B) to give A and BH, there are three possible modes: stepwise electron transfer (ET) to form AH + and Bfollowed by a proton transfer (PT); stepwise PT affording Aand BH + followed by an ET; and, as called PCET, a concerted proton-electron transfer in one elementary step, especially when single PT or ET is thermodynamically unfavorable.…”