Light - driven deracemization enabled by excited - state electron transfer

Abstract

Deracemization is an attractive strategy for asymmetric synthesis, but intrinsic energetic challenges have limited its development. Here, we report a deracemization method in which amine derivatives undergo spontaneous optical enrichment upon exposure to visible light in the presence of three distinct molecular catalysts. Initiated by an excited-state iridium chromophore, this reaction proceeds through a sequence of favorable electron, proton, and hydrogen-atom transfer steps that serve to break and reform a stereogenic C–H bond. The enantioselectivity in these reactions is jointly determined by two independent stereoselective steps that occur in sequence within the catalytic cycle, giving rise to a composite selectivity that is higher than that of either step individually. These reactions represent a distinct approach to creating out-of-equilibrium product distributions between substrate enantiomers using excited-state redox events.

Deracemization Enabled by Visible‐Light Photocatalysis

“…In addition to utilizing energy transfer as an activation mode to effect visible-light-driven deracemization, Miller, Knowles,a nd co-workers recently developed ac onceptually novel approach for the deracemization of cyclic ureas 5 via as equence of electron, proton, and hydrogen atom transfer (Scheme 4). [11] Tw ochiral catalysts,namely,1,1'-bi-2-naphthol (BINOL)-derived phosphate base 6 and peptide-based thiol 7,w ere employed to control the enantioselectivity of this process.M echanistically,t he reaction is initiated by as ingle electron transfer (SET) event between the urea and the excited state of the iridium photocatalyst. Ther esulting radical cation may undergo deprotonation with the phosphate base 6 to give ap rochiral radical Int C or simply be reduced back to the starting material by the Ir II species.A sb oth the radical cation and the phosphate base are chiral, the stereochemically matched (S)-radical cation is deprotonated much faster than the (R)-radical cation, leading to an enrichment of the slow-reacting (R)-enantiomer.Meanwhile, when using the chiral thiol 7 as ah ydrogen-atom donor, the prochiral radical Int C undergoes enantioselective HATt o favorably produce the (R)-enantiomer,t hereby further in-…”

“…[6,7] In general, three types of interaction between the photoexcited species and the reactants are involved in visible-light photocatalysis:e nergy transfer (E n T), electron transfer (ET), and hydrogen atom transfer (HAT). Gratifyingly,b yt aking full advantage of these interaction modes,r ecent studies from the groups of Bach [9,10] and Miller and Knowles [11] have achieved the selective deracemization of chiral compounds with central or axial chirality under visible-light irradiation. Herein, we highlight these works and discuss the opportunities that Scheme 1.…”

Deracemisierung durch Photokatalyse mit sichtbarem Licht

“…[6,7] Im Allgemeinen finden bei der Photokatalyse mit sichtbarem Licht drei Arten von Wechselwirkungen zwischen den photoangeregten Spezies und den Reaktanden statt:E nergietransfer (E n T), Elektronentransfer (ET) und Wasserstoffatomtransfer (HAT). Erfreulicherweise gelang es nun den Gruppen von Bach [9,10] sowie Miller und Knowles [11] in [12] Andererseits sind axial-chirale Allene konfigurativ instabil wenn sie in den Triplettzustand angeregt werden, da die beiden Enantiomere über ein achirales planares diradikalisches Intermediat ineinander umgewandelt werden kçnnen (siehe unten). [13] Diese Eigenschaft macht Allene jedoch zu geeigneten Substraten fürd ie photochemische Deracemisierung.T atsächlich wurde ein Enantiomerenüberschuss von 3.4 %( ee)b eobachtet, wenn Penta-2,3-dien in Gegenwart einer stçchiometrischen Menge eines chiralen Sensibilisators mit UV-Licht bestrahlt wurde.…”

“…Zusätzlich zur Verwendung eines Energietransfers als Aktivierungsmethode fürd ie Deracemisierung mit sichtbarem Licht entwickelten Miller, Knowles und Mitarbeiter kürzlich einen konzeptionell neuen Ansatz fürd ie Deracemisierung von cyclischen Harnstoffen 5 basierend auf einer Abfolge von Elektronen-, Protonen-und Wasserstoffatomtransfers (Schema 4). [11] Zwei chirale Katalysatoren -die von 1,1'-Bi-2-naphthol (BINOL) abgeleitete Phosphatbase 6 und das peptidbasierte Thiol 7 -w urden genutzt, um die Enantioselektivitätdieses Prozesses zu steuern. Mechanistisch wird die Reaktion durch einen Ein-Elektronen-Transfer (SET) zwischen dem Harnstoff und dem angeregten Zustand des Iridium-Photokatalysators initiiert.…”

Photochemical Deracemization of Allenes and Subsequent Chirality Transfer

“…The method was successfully applied to chiral imidazolidin-2-ones (92-99 % yield, 62-92 % ee). [8] Although more detailed mechanistic work is ongoing, a simplified scheme for the sensitized deracemization of chiral compounds is helpful to illustrate the mode of action (Scheme 1). The chiral photocatalyst distinguishes between the two enantiomeric forms of a compound by non-covalent binding.…”