Photocycloaddition ketones

One limitation encountered in synthetic studies of this reaction is the lack of chemoselectivity in the addition of aldehydes to unsymmetrically substituted furans. For example, the photochemical addition of benzaldehyde to 2-methylfuran provides a 1 3 1 mixture of oxetanes resulting from the exo addition of aldehyde to the more and less substituted alkenes, respectively. Ketone photocycloadditions are more selective. For instance, irradiation of 2-butanone and furan forms a 7 1 mixture of regioisomeric oxetanes (167) and (168) (1 1 mixture of epimers). 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

Preparation of oxetanes by [2- -2]-photocycloaddition reactions of ketones and dienes 98S683. 

The [2+2] photocycloaddition of an aldehyde or a ketone to an alkene to form an oxetane (e. g. Ill + IV —> V, Scheme 1) is a process that is known as the Patemo-Biichi reaction 8 it is a reaction that was first reported by Patemo in 19094 and was confirmed approximately forty-five years later by Biichi.Sa A particularly interesting variant of the Patemo-Biichi reaction is illustrated in... 

Photocycloaddition Reactions ofEnones. Cyclic a,(3-unsaturated ketones are another class of molecules that undergo photochemical cycloadditions.188 The reactive... 

Photocycloaddition Reactions of Carbonyl Compounds and Alkenes. Photocycloaddition of ketones and aldehydes with alkenes can result in formation of four-membered cyclic ethers (oxetanes), a process often referred to as the Paterno-Buchi reaction.196... 

The thermo- and photocycloaddition of alkenes will be discussed in Chapter 12, on pericyclic reactions. On the other hand, transition-metals have effectively catalyzed some synthetically useful cycloaddition reactions in water. For example, Lubineau and co-worker reported a [4 + 3] cycloaddition by reacting a,a-dibromo ketones with furan or cyclopen-tadiene mediated by iron or copper, or a-chloro ketones in the presence of triethylamine (Eq. 3.48).185... 

The photocycloaddition of an aldehyde or ketone with an olefin to yield an oxetane was reported by Paterno and Chieffi in 1909. 58> Contemporary studies on the synthetic utility and mechanistic features were initiated nearly 50 years later by Biichi et al. 59) Two review articles summarizing synthetic aspects of Paterno-Biichi reactions have been published 6.12)) and mechanistic studies have been reviewed several times. 6,38,60-62) The reaction involves the addition to olefin of a photo-excited carbonyl moiety. This circumstance makes it advantageous to review this reaction before a discussion of olefin-olefin additions, because the solution photochemistry of carbonyl compounds is probably better understood than any other aspect of organic photochemistry. Many of the reactions of carbonyl compounds have been elucidated during studies of the important phenomena of energy transfer and photosensitization. 63-65)... 

The final type of reaction that will be discussed is the highly interesting cross photocycloaddition of cyclic a, (3- unsaturated ketones with olefins. Examples were given in Eqs. 28—31. A general mechanism 94), to which there may be exceptions to be discussed later, would involve a triplet state of the enone and the reactions steps given in Eqs. 32, 33, and 35, complex formation, biradical formation, and product formation. An earlier idea that two different excited triplet states were reacting has been discounted. 100,141,142) The inefficiency of the reaction is attributed to an alternate decay of complex 77,78,ioo,i42)( an(j the excited state has a n-n configuration. 100,142)... 

This chapter deals with [2 + 2]cycloadditions of various chromophors to an olefinic double bond with formation of a four-membered ring, with reactions proceeding as well in an intermolecular as in an intramolecular pattern. Due to the variety of the starting materials available (ketones, enones, olefins, imines, thioketones, etc.. . .), due to the diversity of products obtained, and last but not least, due to the fact that cyclobutanes and oxetanes are not accessible by such a simple one-step transformation in a non-photo-chemical reaction, the [2+2]photocycloaddition has become equivalent to the (thermal) Diels-Alder reaction in importance as for ring construction in organic synthesis. 

The photocycloaddition of aliphatic and aromatic aldehydes with 2,4,5-trimethyloxazole (131) gave bicyclic oxetanes 132 in almost quantitative yields hydrolitic cleavage led selectively to erytro a-amino-P-hydroxy methyl ketones 133 <00CC589>. The oxazolium salt 134 was converted to the azomethine ylide 136 via electrocyclic ring opening of the oxazoline 135. Intramolecular cycloaddition afforded 137 in 66% overall yield which was transformed into the aziridinomitosene derivative 138 . 

In Bettolo and co-workers approach to (+)-methyl trachyloban-18-oate (16), enone 13 was subjected to a photocycloaddition with 1,2-propadiene (1) to afford the [2 + 2]-cycloadduct 14 as a single product in 67% yield (Scheme 19.3) [5]. The addition proceeded exclusively from the /3-face. The resulting exocyclic olefin was eventually converted to a ketone using osmium tetroxide and NaI04 and taken on to 15, constituting a formal total synthesis of 16. 

In contrast to the preceding syntheses of kelsoene. Piers and Orellana used ethylene 8 in the [2-1-2]-photocycloaddition key step to furnish tricyclic ketone rac-lO diastereoselectively (Scheme 2) [11]. In accordance with the report by Srinivas and Mehta, attempts to homologate the sterically encumbered ketone rac-lO using the Wittig, Magnus [18, 19] or Taguchi [20] pro-... 

The Dauben-Walker approach has yielded the smallest and most strained fenestrane known to date Following the intramolecular Wadsworth-Enunons cyclization of 443 which also epimerizes the butenyl sidechain to the more stable exo configuration, intramolecular photocycloaddition was smoothly accomplished to provide 444. Wolff-ELishner reduction of this ketone afforded the Cj-symmetric hydrocarbon 445. Application of the photochemical Wolff rearrangement to a-diazo ketone 446 p,ve 447. 

The Pirrung synthesis is notable for its brevity and clever amalgamation of [2 + 2] photocycloaddition and Wagner-Meerwein rearrangement chemistry Enol ether 757 was reacted with the Grignard rea nt from 5-bromo-2-methyl-l-pentene, subjected to acid hydrolysis, and irradiated to generate the tricycle 738. Wittig olefination of this ketone and treatment with p-toluenesulfonic acid provided racemic isocomene. 

Wender and Dreyer have demonstrate that meta-areiw photocycloaddition chemistry can lead expediently to modhephene A( tate 7S>5, a photoproduct derived from indane and vinyl acetate was converted to tetracyclic ketone 797 (Scheme XCVI). Because the enolate of 797 partakes of the dynamic behavior of semibuUvalenes, it proved possible to trimethylate the substance to produce 798. A fourth methyl group was introduced by conjugate addition and the carbonyl was simultaneously converted to an olefinic center. Selective hydrogenation of799 provided modhephene in seven steps. 

Dialkyl ketones can undergo radiative deactivation (fluorescence) from the singlet in solution. For example, the quantum yield of fluorescence of acetone at 25°C is 0.01.30 However, the addition of maleic anhydride quenches this fluorescence, and the photocycloaddition product is obtained. Thus, it appears that, in this case, the photocycloaddition reaction can compete with fluorescence for the n,n singlet.32 Such is not the case with ordinary olefins. For example, the fluorescence of acetone was completely unaffected by the addition of 2-pentene,30 and the photocycloaddition reaction is inefficient.32... 

Some carbonyl compounds are unreactive in the photocycloaddition reaction because their excited states undergo molecular rearrangement. Illustrative of this point is the isomerization process involved upon irradiation of 2-methylbenzophenone. This ketone is known to be stable to irradiation in isopropanol,45 and irradiation in the presence of isobutylene yields a complex mixture which contains little, if any,... 

There are several other photochemical reactions which ketones can undergo in the absence of olefins. Here again, the products obtained depend upon the relative rates of the competing reactions. Some of these reactions are shown in Table XI. Since it is beyond the scope of this review to discuss these reactions in detail, only a few interesting examples germane to the competition with photocycloaddition will be mentioned. 

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