Photochemically Induced Ring Opening of Spirocyclopropyl Oxindoles: Evidence for a Triplet 1,3-Diradical Intermediate and Deracemization by a Chiral Sensitizer

Abstract

The photochemical deracemization of spiro[cyclopropane-1,3'-indolin]-2'-ones (spirocyclopropyl oxindoles) was studied. The corresponding 2,2-dichloro compound is configurationally labile upon direct irradiation at λ=350 nm and upon irradiation at λ=405 nm in the presence of achiral thioxanthen-9-one as the sensitizer. The triplet 1,3-diradical intermediate generated in the latter reaction was detected by transient absorption spectroscopy and its lifetime determined (τ=22 μs). Using a chiral thioxanthone or xanthone, with a lactam hydrogen bonding site as a photosensitizer, allowed the deracemization of differently substituted chiral spirocyclopropyl oxindoles with yields of 65-98 % and in 50-85 % ee (17 examples). Three mechanistic contributions were identified to co-act favorably for high enantioselectivity: the difference in binding constants to the chiral thioxanthone, the smaller molecular distance in the complex of the minor enantiomer, and the lifetime of the intermediate 1,3-diradical.

Keywords: enantioselectivity; hydrogen bonds; photochemistry; time-resolved spectroscopy; xanthones.

Scheme 1

Photochemical deracemization of a racemate by a chiral catalyst vs. racemization of an enantiopure compound by an achiral catalyst.

Figure 1

Structure of deracemization catalysts 1, 2 and of products 3–7 obtained enantioselectively by a photochemical deracemization reaction.

Scheme 2

Putative formation of 1,3‐diradical II from spirocyclopropyl oxindoles I as a possible sensitized (energy transfer) pathway for racemization/deracemization and structure of an alternative intermediate III accessible via electron transfer.

Figure 2

Racemization (▪) of compound 8 a to rac‐8 a in MeCN as the solvent: Time profile (c=1.5 mm) for λ _exc=405 nm in the absence (•) and in the presence (▪) of 0.15 mm thioxanthen‐9‐one (left); time profile for λ _exc=350 nm in the absence (▪) and in the presence of piperylene (right, 15 mm: •; 30 mm: ▴).

Figure 3

a) DADS of TA studies with TX in the absence (gray and light blue) and presence (black, dark blue, red) of rac‐8 a (12.3 mm) in MeCN, excited at λ _exc=355 nm. b) Electronic transitions (sticks) for ³ TX and 1,3‐diradical ³ 8 a convoluted with gaussians (the peak widths are taken from a fit of the corresponding experimental absorption bands) calculated at the RHF‐CPCM(MeCN)‐TD‐DFT‐B3LYP//DEF2‐TZVP level of theory (Supporting Information). The inset shows geometrically optimized structures.

Scheme 3

Deracemization of 2,2‐dichlorospiro[cyclopropane‐1,3′‐indoline]‐2′‐ones (rac‐8) catalyzed by chiral thioxanthone 1. [a] The reaction was performed at −25 °C.

Scheme 4

Deracemization of 2,2‐dialkyl‐substituted spiro[cyclopropane‐1,3′‐indoline]‐2′‐ones (rac‐9) catalyzed by chiral xanthone 2. [a] The reaction was performed at −25 °C.

Scheme 5

Binding constants (K _a) of complexes 1⋅ent‐8 a and 1⋅8 a as determined by ¹H NMR titration at 25 °C in [D₆]benzene. Distances between the marked carbon atoms were calculated by DFT methods (Supporting Information).

Scheme 6

Dissociation of triplet 1,3‐diradical ³ 8 a from sensitizer 1 and its decay to spirocyclopropyl oxindoles 8 a and ent‐8 a.

Scheme 7

General scheme for the deracemization of spirocyclopropyl oxindoles (Ι) catalyzed by a chiral sensitizer (Sens) via a 1,3‐diradical ΙΙ.