Photoinduced enolizations

An initial cyclization to the oxazoline (159) is involved in the photodecomposition of propyzamide (160), and the conversion of dialdehyde (161) into ( )-cw-alpinigenine (162) is the result of photoinduced enolization followed by thermal [ 4 -I- 2] cycloaddition. 

Figure 8.9 Molecular structures of the keto form (filled bonds) and the photoinduced enol form (open bonds) in the photoirradiated crystal of N-3,5-di-tert-butylsalicylidene-3-carboxyaniline (a polymorph). (Adapted from [23]. Copyright 2009 The Chemical Society of japan.)...

The research groups of Mariano and West developed a photoinduced electrocydi-zation/nucleophilic addition sequence. Thus, irradiation of N-alkylpyridinium perchlorates as 5-19 in an aqueous solution led to the aziridine cations 5-20, which react in a nucleophilic addition with OH to give the isolable azabicyclo[3.1.0]hex-2-enols 5-21. These can be further transformed by a nucleophilic ring-opening of the aziridine moiety under acidic conditions to lead to useful unsymmetrically trans,trans-trisubstituted cyclopentenes 5-22 (Scheme 5.5) [10]. 

Y. Matsumoto, T. Ebata, and N. Mikami, Structure and photoinduced excited state keto enol tauto merization of 7 hydroxyquinoline (CH30H)n clusters. J. Phys. Chem. A106,5591 5599 (2002). 

Mattay et al. examined the regioselective and stereoselective cyclization of unsaturated silyl enol ethers by photoinduced electron transfer using DCA and DCN as sensitizers. Thereby the regiochemistry (6-endo versus 5-exo) of the cyclization could be controlled because in the absence of a nucleophile, like an alcohol, the cyclization of the siloxy radical cation is dominant, whereas the presence of a nucleophile favors the reaction pathway via the corresponding a-keto radical. The resulting stereoselective cis ring juncture is due to a favored reactive chair like conformer with the substituents pseudoaxial arranged (Scheme 27) [36,37]. 

In addition to the former example, Pandey et al. achieved efficient a-aryla-tion of ketones by the reaction of silyl enol ethers with arene radical cations generated by photoinduced electron transfer from 1,4-dicyanonaphthalene. Using this strategy various five-, six-, seven-, and eight-membered benzannulated compounds are accessible in yields in the range 60-70% [39],... 

A novel approach to the synthesis of lactams has been reported56 which involves reaction of such enol ethers with TMS-azide to give (triisopropylsilyl)azidohydrins, which then undergo a photoinduced Schmidt rearrangement (equation 14). 

The synthesis of indoles by the photoinduced substitution reaction of o-haloanilines (22) with carbanions derived from aliphatic ketones in liquid ammonia is an important example of the SRN1 reaction followed by a spontaneous ring closure in the reaction media in moderate to excellent yield (53%-100%) [1]. Although the enolate anions of aromatic ketones do not react in liquid ammonia with 22, they will cyclize to indoles in DM SO under photoinitiation (Scheme 10.44) [60, 61]. 

Examples of the syntheses of fused indoles by the SRN1 mechanism are depicted in Scheme 10.45. The photoinduced reactions of 22 with the enolate anions of cyclic ketones afford the corresponding indoles from moderate to good yields [61],... 

The synthesis of 3-substituted isoquinolinones and fused isoquinolinones can be performed by the photoinduced SRN1 reactions in DMSO of o-iodobenzamide with the enolates of acyclic aromatic and aliphatic ketones and cyclic ketones, respectively. These reactions proceed from moderate to good yields (Schemes 10.47 and 10.48) [65],... 

The reductive dehalogenation predominates in the photoinduced reactions of 32 with 3-pentanone, 2-methyl-3-pentanone, and 2,4-dimethyl-3-pentanone. Although, substitution is favored over reduction in all of the reactions of 32 with cyclic ketone enolates, a competing reduction is responsible for the lower yields observed with cyclopentanone and cyclohexanone compared to cyclooctanone (Scheme 10.59) [73]. 

Hydrogen abstraction from alkyl benzenes occurs efficiently by using aromatic ketones The mechanism of the reaction has been extensively studied, with ketones having both a mi and a jiji state as the lowest triplet, and found to involve some degree of electron transfer, which grows with more easily reduced ketones [32,33]. The same reaction occurs intramolecularly, e.g., in the photoinduced hydrogen transfer in 2-methyl-benzophenone to give the (trappable) enol [34-36]. 

When the photoinduced reaction of pinacolone enolate ion with bromobenzene is carried out in DMF as solvent, it leads to the formation of benzene (28%), while in liquid ammonia this byproduct is almost precluded. The reaction in DMSO produces little benzene. On the other hand, THF... 

The photostimulated reactions of vie aminohalo pyridines with acetone or pinacolone enolate ions lead to azaindoles in high yields (75-95%) [67]. When the amino group is protected as pivaloylamino derivative, (as in 17, Sch. 20), the analogs of substitution compounds 18 obtained by the photoinduced reaction of 2-amino-3-iodo-, 3-amino-4-iodo- and 4-amino-3-iodopyridines with acetone or pinacolone enolate ions, afford 5-, 6- and 7-azaindoles in almost quantitative yields by cyclization upon deprotection of the amino group and dehydration under acidic conditions (for example, see Sch. 20) [67]. 

Photoinduced [2+2] cycloaddition (the Paterno-Buchi reaction) of 1-acetylisatin with acyclic enol ethers afford the spiro(3f/-indole-3,2 -oxetane)s 43 with moderate regio- and diastereoselectivity via the mi triplet state of the isatin derivative without involvement of single electron transfer <02JCS(P1)345>. 

However, in recent years, it has become apparent that several photoinduced oxidation reactions do not involve singlet oxygen as the reactive intermediate, and, consequently, the reaction products cannot be accounted for the mechanisms shortly reported above. Moreover, since the first report on the photochemical stereospecific synthesis of the most fascinating peroxide derivatives, i.e., 1,2-dioxetanes [32], it clearly appeared, with a few notable exceptions [33,38], that only electron-rich olefins, such as enamines, enol ethers, and thio-substituted... 

Figure 9-10. Examples of photoinduced reactions in drug molecules. (I) Photoinduced isomerization (Ib), cyclization and enol-keto isomerization (Ic) of stilboestrol (la). (II) Photoinduced reactions of ketoprofen (Ila) and its degradation product (Ilb) decarboxylation (Ilb), reduction (lie), and dimerization (IIc) products of the drug. (Ill) A -dealkylation of methotrexate followed by oxidation. (IV) Dehalogenation (IVb) and photohydrolysis (IVc) of frusemide (IVa) [44].

Similar to the deprotonation of enol radical cations, silyl enol ether radical cations can undergo loss of trialkylsilyl cations (most likely not as ionic silicenium ions [190]). Based on photoinduced electron transfer (PET), Gass-man devised a strategy for the selective deprotection of trimethylsilyl enol ethers in the presence of trimethylsilyl ethers [191]. Using 1-cyanonapthalene (1-CN) ( = 1.84 V) in acetonitrile/methanol or acetonitrile/water trimethylsilyl enol ether 93 ( j = 1.29 V) readily afforded cyclohexanone 64 in 60%. Mechanistically it was proposed that the silyl enol ether radical cation 93 undergoes O-Si bond cleavage, most likely induced by added methanol [192-194], and that radical 66 abstracts a hydrogen from methanol. Alternatively, back electron transfer from 1-CN - to 66 would yield the enolate of cyclohexanone which should be readily protonated by the solvent. 

Oxidative coupling of silyl enol ethers as a useful synthetic method for carbon-carbon bond formation has been known for a long time. Several oxidants have been successfully applied to synthesize 1,4-diketones from silyl enol ethers, e.g. AgjO [201], Cu(OTf)2 [202], Pb(OAc)4 [203] and iodosobenzene/BFj EtjO [204]. Although some of these reagents above are known to react as one-electron oxidants, the potential involvement of silyl enol ether radical cations in the above reactions has not been studied. Some recent papers, however, have now established the presence of silyl enol ether radical cations in similar C-C bond formation reactions under well-defined one-electron oxidative conditions. For example, C-C bond formation was reported in the photoinduced electron transfer reaction of 2,3-dichIoro-1,4-naphthoquinone (98) with various silyl enol ethers 99 [205], From similar reactions with methoxy alkenes [206,207] it was assumed that, after photoexcitation, an ion radical pair is formed. 

A similar electron transfer mechanism has been proposed for photosensitized electron transfer catalysis of the Mukaiyama-aldol reaction of aldehydes and ketones with enol silanes [301], Photoinduced electron transfer from enol silanes to a monocationic -bridged porphyrin [302, 303] leads to the production of a... 

The enol silyl ether (56) undergoes a photoinduced reaction in the presence of chloranil to give cyclohexenone and the adduct (57) and the currently available evidence suggests that the reaction proceeds by electron transfer to the photo-activated chloranil to give (56) A photophysical study has appeared of the chromophore-quencher compounds [Au(CCPh)(L )] (L = 10-[(diphenylphosphi-no)methyl]anthracene) and [Au(CCPh)(L )]BPh4 (L = l-[2-(diphenylphosphin-oxy)ethyl]pyridinium], 1 -[2-(diphenylphosphinoxy)ethyl]-4-methyl pyridinium, 1 -[2-(diphenylphosphinoxy)ethyl]-4-tert-butylpyridinium, and 1 -[2-(diphenylpho-sphinoxy)ethyl]triethylammonium in which the Au(CCPh) chromophore is linked by a flexible tether to the acceptors. 

One way of carrying out nucleophilic aromatic substitution reactions under mild conditions is the Ar RNl process, which is initiated by (usually, but not necessarily, photoinduced) electron transfer to an aryl halide, e.g., from an enolate Cleavage of the resulting aryl radical anion with loss of a halide anion gives an aryl radical that combines with the enolate, thus forming the desired aryl-carbon bond. 

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