Photocycloaddition reactions regioselectivity

Photocycloaddition reactions have been used as key transformations in many organic syntheses to construct organic compounds having unique structures that are hardly accessible by other methods. However, their stereoselectivity is not necessarily high, and many efforts have been done to attain the highly regioselective and stereoselective photocycloadditions. They are discussed in terms of the electronic nature of substrates, the steric repulsions between substituents, and the conformational restrictions of intramolecular reactions. 

Intermolecular and intramolecular photocycloaddition and photoaddition to aromatic rings in the electron-donor and electron-acceptor systems were discussed in this chapter. The highly stereoselective and regioselective photocycloaddition is a synthetically useful method for the construction of polycyclic carbon-skeleton compounds, including natural products. New aspects for the stereoselective intermolecular and intramolecular photocycloaddition reactions via exciplexes in less... 

Control over the absolute configuration in cyclohexenone photocycloadditions has been achieved by auxiliary-induced diastereoselectivity. In particular, esters related to compound 26, which are derived from a chiral alcohol but not from methanol, lend themselves as potential precursors, from which the chiral auxiliary can be effectively cleaved [42, 43]. In a recent study, the use of additives was advertised to increase the diastereomeric excess in these reactions [44], An intriguing auxiliary-induced approach was presented by Piva et al., who employed chiral 13-hydroxy-carboxylic adds as tethers to control both the regioselectivity and the diastereoselectivity of intramolecular [2 + 2]-photocycloaddition reactions [45]. In Scheme 6.14 the reaction of the (S)-mandelic acid derived substrate 38 is depicted, which led with very good stereocontrol almost exclusively to product 39a, with the other diastereoisomer 39b being formed only in minor quantities (39a/39b = 96/4). Other acids, such as (S)-lactic acid, performed equally well. The chiral tether could be cleaved under basic conditions to afford enantiomerically pure cydobutane lactones in good yields. 

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. 

The synthesis of oxetanes from alkenic precursors has been demonstrated and the range and scope of Patemo-Biichi photocycloadditions are broad. In general, both the reaction regioselectivity and stereoselectivity can often be predicted by considering the reaction mechanism (Section 2.4.2) for example, the directing effects of alkene substituents are readily imderstood. Synthetic applications are numerous owing to the rtq>id stereocontrolled assembly of multifimctional targets. 

This reaction pathway is usually favoured when an aromatic moiety and an alkene bear electron-withdrawing and electron-donating substituents, respectively (or vice versa). This addition involves a charge transfer and the course of the reaction is sensitive to the solvent polarity. Such a mechanism may resemble that of [2 + 2] photocycloaddition of alkenes to aji-unsaturated carbonyl compounds (Section 6.3.2). Scheme 6.81 shows examples of two intermolecular processes and one intramolecular [2 + 2] photocycloaddition reaction (a) crotononitrile (196) is added to anisole (197) to yield several stereoisomers of 198 in 38% chemical yield and with high regioselectivity, which is linked to bond polarization in the exciplex 818 (b) hexafluorobenzene (199) reacts with 1-ethynylbenzene (200) to form the bicyclo[4.2.0]octa-2,4,7-triene 201 in 86% yield 819 and (c) irradiation of 202 in methanol leads to the single photoproduct 203. 820... 

The Patemo-Buchi reaction is one of the more predictable photocycloaddition reactions. Regiocontrol of the photoproduced oxetane is a function of the stepwise addition of the carbonyl chromophore to the alkene [30]. In the case of electron-rich alkenes, excitation of the carbonyl group produces a triplet species that adds to the alkene. The product regioselectivity is a result of addition that generates the most stable biradical, and the triplet lifetime of the intermediate biradical allows for substantial stereoselectivity prior to closing (see Scheme 2). Electron poor alkenes are more likely to undergo cycloaddition with carbonyl groups directly from an exciplex [31]. 

Owing to the interest in cycloadducts of dioxinones in the synthesis of natural products, the intermolecular 2 -i- 2 photocycloaddition reaction of numerous dioxinones has been generalized [159]. In an attempt to control the regioselectivity of the cycloaddition and the configuration of the asym-... 

The intermediate 37 can be viewed as arising from interaction of the triplet excited state of the indole with the alkene partner so as to form the most stable triplet 1,4-biradical intermediate possible. Alternatively, 37 may arise from attack of the 2-position of the triplet-excited indole on the less-substituted, and hence less sterically hindered terminus of the alkene. Either way, the preferential formation of 37 means that with monosubstituted alkenes, the photocycloaddition reaction with AT-acylin-doles is regioselective, while with unsymmetrically 1,2-disubstituted alkenes the reaction will be nonregioselective, as was seen for the reaction between N-benzoylindole and methyl 3-methyl-2-butenoate shown in Scheme 19. Should it be desired, the opposite regiochemistry to that normally obtained with monosubstituted alkenes can be induced by tethering the alkene to the indole [52] the reaction of 1,2-disubstituted alkenes can be made regioselective in the same way [53]. Examples of this are shown in Schemes 20 and 21. 

A series of (2+2) photocycloaddition reactions have been carried out using (5R)-5-menthyloxy-2(5H)-furanone (32) as the substrate. Photoaddition of cyclopentenone to this substrate gives the four products (33)-(36) with some level of regioselectivity but no facial selectivity. Interestingly, cyclohexenone, cyclohepten-one and cyclooctenone fail to undergo the mixed addition. High facial selectivity is observed when more complex enones such as the 3,5,5-trimethylcyclohexenone and isophorone, (37) are used. The reaction affords adducts of the type illustrated... 

A comparable approach was used by some of the same authors in the study of the regioselectivity of the photochemical [2 -I- 2] cycloaddition of triplet carbonyl compounds with a series of ground state electron-rich and electron-poor alkenes, the Paterno-Buchi reaction,yielding oxetanes. Very recently, the regioselectivity of the [2 -I- 2] photocycloaddition reaction between triplet (n-n ) acrolein and substituted olens in their... 

Exceptions due to steric and electronic reasons are known see (a) Carless, H. A. J. and Halfhide, A. F. E., Highly regioselective [2-i-2]-photocycloaddition of aromatic aldehydes to acylfurans, /. Chem. Soc., Perkin Trans. 1, 1081,1992 (b) Schreiber, S. L., Desmaele, D., and Porco, Jr., J. A., On the use of unsymmetrically substituted furans in the furan-carbonyl photocycloaddition reaction synthesis of a kadsurenone-ginkgoKde hybrid. Tetrahedron Lett., 29, 6689,1988. 

The photocycloaddition of triplet benzophenone to norbornene was originally reported by Scharf and Korte. The photoproduct 101 that is formed in high exo-selectivity could be thermally cleaved to the 5,e-unsaturated ketone 102, an appHcation of the carbonyl-olefin metathesis (COM) concept. The 1,4-biradical formed in the interaction of norbornene with o-dibenzoyl-benzene was trapped in an intramolecular fashion by the second carbonyl moiety. A highly regioselective reaction of triplet benzophenone was reported with 5-methylenenorborn-2-ene, with preferential attack toward the exo CC double bond. A number of publications have discussed the photocycloaddition reactions of triplet carbonyl compounds to norbornadiene and quadricyclane, as weU as the competition between the Paterno-Biichi reaction and the sensitized norbornadiene/quadricyclane interconversion. Oxetane formation has also been reported for the photoreaction of biacetyl and para-quinones with benzvalene. ... 

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