Quinolones photocycloadditions

The tetrahydro-2-quinolone (212) affords a very small yield of 1,2-cycloadduct on irradiation with diphenylacetylene in methanol.189 The two major products are the 1,4-dimer and the pentacyclic derivative (213), arising presumably by intramolecular photocycloaddition... 

Due to a very efficient singlet- to triplet-state intersystem crossing, the [2 + 2]-photocycloaddition chemistry of 2-quinolones can be initiated easily by direct excitation at 300-350 nm [102], The addition of a sensitizer is not required. The parent compound has been first employed in a [2 + 2]-photocycloaddition as early as 1968 [103]. With regard to regio- and stereoselectivity, 2-quinolone (107) behaves as expected, exhibiting a preference for HTproduct formation with electron-rich olefins, such as 1,1-dimethoxyethene (Scheme 6.39, DMA = N,N-dimethylacetamide). The highly efficient reaction delivers product 108 quantitatively [104], The preference for... 

Recent interest in the use of N-unsubstituted 2-quinolones stems from the fact, that they coordinate effectively to chiral lactam-based templates via two hydrogen bonds. The prototypical template to be used in photochemical reactions is compound 115, which can be readily prepared from Kemp s triacid [108]. The template is transparent at a wavelength X > 290 nm, and can be nicely used in stoichiometric amounts for enantioselective photochemical and radical reactions [109]. Conditions which favor hydrogen bonding (nonpolar solvent, low temperature) are required to achieve an efficient association of a given substrate. The intramolecular [2 + 2]-photocycloaddition of 4-alkylquinolone 114 proceeded in the presence of 115 with excellent enantioselectivity, and delivered product 116 as the exclusive stereoisomer (Scheme 6.41) [110]. Application of the enantiomer ent-115 ofcomplexing agent 115 to the reaction 111 —> 112 depicted in Scheme 6.40 enabled enantioselective access to (+ )-meloscine [111]. 

Bach, T., Bergmann, H., Grosch, B., and Harms, K. (2002) Highly enantioselective intra- and intermolecular [2 + 2] photocycloaddition reactions of 2-quinolones mediated by a chiral lactam host host-guest interactions, product configuration, and the origin of the stereoselectivity in solution. Journal of the American Chemical Society, 124, 7982-7990. 

Enantioselectivity in intermolecular enone+ alkene photocycloadditions is quite difficult to accomplish, due to the fact that stereochemical information inherent in the starting materials can easily be lost on the stage of the triplet 1,4-biradical intermediate. Nevertheless highly enantioselective photocycloadditions of quinolones to alkenes mediated by a chiral lactam... 

The intermolecular [2 + 2] photocycloaddition reactions of 2-quinolones such as 59 mediated by a chiral lactam host 60 or ent-60 were reported with enantioselectivities of 93%. The intermolecular version of this reaction was also shown to be highly enantioselective. One example shown in Scheme 9 afforded cycloadduct 63 in 92% ee with a diastereoselectivity of >95 5 <02JA7982>. 

The efficiency of these chiral host compounds has been shown in highly enantioselective photocyclization and photocycloaddition reactions of prochiral lactams. These substrates, for example 2-quinolone derivatives, are expected to coordinate to lactam 44 with its NH-group as the hydrogen donor and the carbonyl group as the hydrogen acceptor, as depicted in Scheme 15. In this complex, any... 

Even higher enantioselectivities were accomplished in the case of intra-and intermolecular [2 + 2]-photocycloadditions of 2-quinolone derivatives. Upon... 

The scope of this approach was widened by the observation of excellent enantioselectivities in intermolecular [2+ 2]-photocycloaddition reactions with various alkenes [62,71]. In the presence of an excess amount of alkene, 4-me thoxy-2-quinolone (57) was converted with high chemo- and regioselectivity to the exo and endo cyclobutanes 59 and 60. With 4-penten-1-ol (58a), allyl acetate (58b), methyl acrylate (58c), and vinyl acetate (58d), the exo diastereomers 59a-d were formed with high simple diastereoselectivity and in high yields (80-89%), Under optimized irradiation conditions (2.4 eq. of host 44 or ent-44, — 60°C), high enantiomeric excesses were achieved in all instances, as depicted in Scheme 22. These enantiomeric excesses are unprecedented for an intermolecular photochemical reaction. 

In the host-guest complex of template 60 with substrate 61, the two enantio-faces of quinolone 61 are distinctly discriminated. As one of the enantiofaces of 61 is blocked by the benzotriazole moiety of 60, photochemical attack to the substrate is expected to occur from the open face. Indeed, in the presence of 60 and its enantiomer (ent-60), highly enantioselective intramolecular [2 + 2] photocycloaddition of allyl quinolonyl ether 62 [134] and intermolecular [2 + 2] photocycloaddition of quinolone 61 to alkenes 63 [135] were reported to occur in solution (Scheme 23). The intermolecular photocyeloaddition of 63 to 61, as well as the intramolecular photocyeloaddition of 62 proceeded with excellent enantioselectivities (81-98% ee) and in high yields (61-89%). 

While the chiral complexing agents (+)-12 and (-)-12 proved to be generally suitable for a wide range of enantioselective [2+2]-photocycloaddition reactions on the c-bond of 2(l//)-quinolones, their applicabil-... 

Brandes S, Selig P, Bach T (2004) Stereoselective intra- and intermolecular [2+2]-photocycloaddition reactions of 4-(2,-aminoethyl)quinolones. Syn-lett 2588-2590... 

Cycloaddition of but-l-yne to the quinolone (58a) gave the head-to-tail [2 + 2] adduct (59). This approach was coupled with a ring-opening reaction to provide a synthesis of quinolones bearing a substituent at C-3. For example, the cycloadduct (60), obtained from the quinolone (58b) and 2-methylbut-3-yn-2-ol, was transformed into edulinine (61). The photocycloaddition of allene to the quinolone (58b) affords the two [2 + 2] adducts (62, 59.6%) and (63, 9.7%). Diketene has also been used in cycloadditions to quinolones (58c) and (58d). The addition process is selective in that cycloaddition to (58c) yields the adduct (64) whereas (58d) affords (65). In the latter case, the cycloadduct is accompanied by the rearranged product (66). These adducts were used in further chemical transformations. 

Photocycloaddition of 1,1-dichloroethene to the quinolone (110) affords the adduct (111). The triplet excited state of the enones (112) are photoreactive and undergo addition to alkenes to afford reasonable yields of the azetidines (113). - Both electron rich and electron deficient alkenes photochemically add to the enone (114) to afford the cyclobutane adducts (115). Normally the C=N Is unreactive to (2+2)-cycloadditions but the authors believe that in this case the C=N system is activated by the trifluoromethyl group. The azetidine-2-ones (116) can be readily prepared by irradiation of the enones (114) in the presence of ketene. ... 

The regioselectivity of analogous cycloadditions in 4-(alkenyloxy)-quinolin-2-(1H)-ones is determined by the chain length irradiation of quinolone (92 n=1), for example, gave the adduct (93), whereas the related quinolone (92 n=3) was converted photochemically into the adduct (94). Intramolecular [ 2 + 2] photocycloaddition has also been employed in the preparation of photoresponsive cyclobutane-1,2-dicarbonyl-capped[2.n]diazacrown ethers. 

The intramolecular photocycloaddition of prochiral 2-quinolone 144 (Schane 1.38) was examined in the presence of chiral templates 143a,b. The amide group of chiral templates forms dual hydrogen bonds with the quinolone moiety of 144, with the bulky tetrahydronaphthalene moiety preventing the approach of olefinic double bond from the... 

A light-driven enantioselective organocatalysis intramolecular [2+2] photocycloaddition of quinolone (24) was developed by Bach et al Scheme 3.7 [13]. 

Scheme 3.7 Intramolecular organocatalytic [2+2] photocycloaddition of prochiral 4-(3 -buteny-loxy)quinolone...

Pyrrolo[2,l-a]isoquinoline derivatives (27) were synthesized using Cgo-Bodipy dyads (28) as excellent photosensitizers (Scheme 13)/ Direct irradiation of glycine methyl ester to Ceo afforded [3 - - 2] cycloadduct/ Akasaka and his coworkers found the photocycloaddition of 2-ada-mantane-2,3-[3ff]diazirine and disilyliranes to Cso-metallofullerenes/ Intra- and inter-molecular photocycloaddition of alkenes to coumarin, quinolone, and isoquinolone derivatives have been reported by several groups. Griesbeck et al. found that the intramolecular photocycloaddition of cyclohexene moiety to coumarin (29) was catalysed by molecular ojygen. [2 + 2] Photocross dimer (33) of coumarin derivative (31) and 5-fluorouracil derivative (32) was obtained by laser irradiation/ Bach reported enantioselective intramolecular photocycloaddition of coumarins (34) to alkenes catalysed by a chiral Lewis acid (36) (Scheme 14)/ ... 

He also found the enantioselective intermolecular [2 + 2] photocycloaddition of isoquinolone (37) with vinyl phosphinates (38)" and intramolecular [2 + 2] cycloaddition of quinolones (41) using chiral additives (40) and (43), assisted by strong hydrogen-bonding (Scheme 15). 

Sakamoto reported the absolute asymmetric cyclobutane formation via intramolecular [2 + 2] photocycloaddition of iV, Af-diallyl-4-methyl-l-pro-pyl-2-quinolone-3-carboxamide (50) in chiral crystalline state. He also found the two-step reaction involving hydrogenation and intermolecular photocycloaddition of (50) with alkenes (53) afforded chiral cyclobutanes (54) at a low temperature (Scheme 17). ... 

Scheme 39.23 Asymmetric intramolecular [2-l-2]-photocycloaddition reactions of 4-substituted quinolones.

Upon irradiation with X > 300 nm, the 4-alkenyloxy-2-quinolones 23 and 25 cyclized in an intramolecular [2+2]-photocycloaddition diastereoselectively to the crossed and straight cycloadducts 24 and 26, respectively. In the presence of 2.6 equivalents of host compound 21 or ent-21, high enantioselectivities were achieved in a nonpolar solvent at low temperatures." " At -60°C in toluene, 24 and 26 were obtained with >90% ee (Scheme 10). Higher temperatures (84% ee at -15°C, 39% ee at 30°C) and more polar solvents (4% ee at 30°C in acetonitrile) significantly reduced the enantioselectivity under otherwise identical conditions. 

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