Photochemical Deracemization of Chiral Sulfoxides Catalyzed by a Hydrogen-Bonding Xanthone Sensitizer

Abstract

Several chiral sulfoxides with a lactam hydrogen-bonding site were prepared and their photochemical behavior was studied in the presence of xanthone and thioxanthone sensitizers. While acyclic sulfoxides showed only decomposition, chiral benzothiazinone-1-oxides with a stereogenic sulfur atom underwent a stereomutation upon irradiation at λ = 366 nm in the presence of catalytic quantities of a xanthone sensitizer. A chiral xanthone with a 1,5,7-trimethyl-3-azabicyclo-[3.3.1]nonan-2-one backbone was employed in catalytic quantities (5 mol%) to achieve a deracemization reaction of racemic benzothiazinone-1-oxides in acetonitrile solution. Five substrates could be successfully deracemized in good yields and with up to 55% ee.

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

“…Thehigh yield of the photochemical deracemization is notable given the high triplet energy of the sensitizer and its notorious tendency for C À Habstraction in the excited state. [11,28] Xanthone 2 was shown to be compatible with chloro,a lkoxy and protected amino groups.F rom prior work, [13] the compatibility of the catalyst with bromo,sulfoxy, and cyano groups had been established.…”

“…Mechanistic Analysis and Discussion. Among the critical parameters that have been identified for the deracemization to be successful, [10,[12][13][14] the most obvious parameter is the association of the two oxindole enantiomers I and ent-I to the sensitizer.I na ni deal scenario,t he major enantiomer I does not bind to the sensitizer while enantiomer ent-I shows efficient binding.W ed etermined the specific binding constants for the two enantiomers ent-8aand 8ato sensitizer 1 by NMR titration [29] and identified abetter binding of the former enantiomer (Scheme 5). However,the values were unexpectedly low and indicated only am inor binding preference for ent-8a.Based on these data alone the degree of deracemization and the observed enantioselectivity cannot be accounted for.…”

“…forms (1 and ent-1)a sw as the related compound 2 [11] and its enantiomer ent-2.W ork with cyclopropanes 4 [12] was performed employing mainly catalyst ent-1 and chiral sulfoxides 5 [13] were deracemized with catalyst ent-2.A llenes have remained so far the best suited substrate class and 3-(1'-alkenylidene)-pyrrolidin-2-ones (6)h ave recently been employed in the context of synthetic work which aimed at asubsequent conversion of axial into point chirality. [14] In the same study,c atalyst 1 was also found to successfully deracemize azepan-2-one 7 albeit in lower ee.…”

Recent developments in enantioselective photocatalysis

“…A similar mechanism is proposed for the deracemisation of sulfoxides rac - 197 ; however, the enantioselectivities are lower (5 examples, up to 78:22 er), which the authors attribute to the catalyst differentiating between the sterics of an oxygen atom and a lone pair of electrons ( Scheme 30 ) [ 87 ]. Bach et al also found that alkenes 198 can undergo a light-induced rearrangement to cyclopropane 199 in the presence of 185 ( Scheme 30 ) [ 88 ].…”

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

“…In subsequent studies, the thioxanthone was used in both enantiomeric forms ( 1 and ent ‐ 1 ) as was the related compound 2 [11] and its enantiomer ent ‐ 2 . Work with cyclopropanes 4 [12] was performed employing mainly catalyst ent ‐ 1 and chiral sulfoxides 5 [13] were deracemized with catalyst ent ‐ 2 . Allenes have remained so far the best suited substrate class and 3‐(1′‐alkenylidene)‐pyrrolidin‐2‐ones ( 6 ) have recently been employed in the context of synthetic work which aimed at a subsequent conversion of axial into point chirality [14] .…”