Regioselectivity of Photocycloadditions

1 The Paterno-BUchi Reaction. One well-known class of photocycloadditions is the Paterno-Buchi reaction in which aldehydes or ketones combine with alkenes to give oxetanes. The excited state of the ketone is 11-71, and it is the orbitals of this state which interact with the ground-state orbitals of the alkene. The orientation usually observed for C- and X-substituted alkenes is shown for benzophenone 8.15 and 2-methylpropene 8.16. 

However, the photocycloaddition of ketones to Z-substituted alkenes does not fit the explanation based on the relative stability of the diradicals. Irradiation of a solution of acrylonitrile 8.22 in acetone 8.21 gives the adduct 8.23, together with dimers of acrylonitrile. This regioselectivity is consistent with a frontier orbital argument. 

A Z-substituted alkene has a lower-energy HOMO than C- and X-substituted alkenes, and it has a correspondingly lower-energy LUMO. Thus the interaction of the 7i orbital of the ketone 8.21 with the LUMO of the alkene 8.22 ought to be more important for a Z-substituted alkene than it was for C- or X-substituted alkene. In this interaction, the two larger lobes are on the carbonyl carbon 8.24 and on the (3 carbon 8.25, and it is these two which become bonded. Furthermore, this reaction is a singlet-state reaction, and, with /3-substituted acrylonitriles, it is stereospecific, with retention of configuration on the alkene component. 

2 Photodimerisation of Alkenes. When alkenes are irradiated, they often dimerise to give cyclobutanes. In a dimerisation reaction, the set of orbitals on the left of each pair in Fig. 8.1 and the set on the right will have identical 

23 The Photochemical Cross-Coupling of Alkenes 6 When both 

If we were to look only at the simplest examples of each kind of alkene C-,1116, X-1117 and Z-sub-stituted,1118 in the form of butadiene 8.57, phenyl vinyl ether 8.58 and acrylonitrile 8.53, we would find that this analysis seemed to be supported. 

For a singlet-state reaction, where both bonds might be being formed at the same time, we might make a further but tentative prediction. Since the orbitals which are interacting are identical on each component, the endo-HH adduct should be preferred over the exo-HH adduct, because the secondary interactions (Fig. 8.6, dashed lines) will always be bonding. 

In two cases, where the singlet- and triplet-state reactions have been carefully looked at and separated, this proves to be true. Thus coumarin 8.59, in the excited singlet state, dimerises to give only the HH dimer syn-8.60, but in the triplet state it gives both HH isomers syn-8.60 and anti-8.60, with only a trace of head-to-tail (HT) products.1119 Acenaphthylene also gives the syn dimer from the singlet-state reaction and a mixture of the syn and anti dimers from the triplet-state reaction.1120 

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We have just seen that many photochemical reactions are complementary to the corresponding ground-state reactions, and that the frontier orbitals explain this change. As with thermal pericyclic reactions, discussed in Chapter 4, the frontier orbitals can also explain many of the finer points of these reactions, most notably the regioselectivity of photocycloadditions.118... 

The effect of the alkene s substituents on the regioselectivity of the photocycloaddition could probably be best presented in the photoaddition of 74 to various alkenes62 75 (Scheme 17). 

Further experimental support for the effect of the fragmentation of the 1,4-diradical intermediates on the regioselectivity of the photocycloaddition was recently reported by Weedon and coworkers68 69, who obtained different H,H/H,T ratios between the photocycloproducts [H,H (93) and H,T (94)] and the trapped products 95-98, upon irradiation in the absence of H2Se in the former case and complete trapping of the diradical intermediates in the presence of H2Se in the latter case (Scheme 21). 

Interestingly, incorporation of an oxygen heteroatom at any allylic position in these systems strongly affects the regioselectivity of the photocycloaddition and in all cases, summarized in Scheme 25, straight products were obtained as the sole products. 

Coulombic forces will determine the regioselectivity of the ortho addition [189], In the charge-transfer complexes of monosubstituted benzenes with alkenes, the charge (positive or negative) on the arene is largely located at the carbon atoms ipso and (to a lesser extent) para to the substituent. The carbon atoms of the alkene double bond will preferentially be located in the neighborhood of either the ipso carbon or (to a lesser extent) the para carbon atom of the monosubstituted benzene. This would explain the 1,2 and 3,4 selectivity in the ortho photocycloaddition. 

The regioselectivity of the Paterno-Biichi reaction with acyclic enol ethers is substantially higher than with the corresponding unsymmetrically alkyl-substituted olefins. This effect was used for the synthesis of a variety of 3-alkoxyoxetanes and a series of derivatives [55]. The diastereoisomeric cis-and tnms-l-methoxy-l-butenes were used as substrates for the investigation of the spin state influence on reactivity, regio- and stereoselectivity [56]. The use of trimethylsilyloxyethene 62 as electron rich alkene is advantageous and several 1,3-anhydroapiitol derivatives such as 63 could be synthesized via photocycloaddition with l,3-diacetoxy-2-propanone 61 (Sch. 17) [57]. 

The Paterno-Buchi photocycloaddition of silyl 0,X-ketene acetals (with X—O, S, Se) and aromatic aldehydes was intensively investigated by Abe and coworkers in the last decade [62]. The regioselectivity of the reaction (71 vs. 72) is highly affected by the heteroatom (Sch. 19) [63,64]. The regioselectivity is rationalized by (a) the relative stability of the 1,4-biradicals and (b) the relative nucleophilicity of sp2-carbons in the respective 0,X-ketene acetal. 

A number of reviews have been published concerning the synthetic utility of photochemical 2+2 cycloadditions [1], We have previously summarized the observed regio- and stereocontrol of photocycloaddition between alkenes and excited n systems [2]. Control of solution photochemistry has been demonstrated with use of templates, tethering of reagents, and substituent stabilization to affect the regioselectivity and/or stereoselectivity. The types of photoreactions that have been investigated using these techniques are numerous. 

Fig. 20. The orientation of 3-butyl-cyclo-pen ten one (47) and the olefin in the Stern Layer of the micelle accounts for the observed regioselectivity of the photocycloaddition...

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. 

It is noted from the above reactions that the stereo- and regioselectivity of intermolecular [2+2] photocycloaddition are not completely satisfying. However, the strategy of using a tether to bring the olefin and the enone substrates together... 

A common theme in enone cycloadditions is the involvement of a triplet enone excited state. The regioselectivity of triplet photocycloadditions is typically explained by formation of the most stable intermediate biradical species (see Scheme 1). Schuster et al. [22] and Weedon et al. [23] have made significant contributions to the understanding of enone photoreactivity. Corey et al. [24] originally suggested that the [2 + 2] reaction involved a polar Jt-complex, and this justification for the observed regioselectivity continues to appear in the literature as will be described below. 

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