Photochemical reactions regioselectivity

This study demonstrates that the addition of the 2-diazopropane with the triple bond of propargyl alcohols is regioselective, and affords new antibacterial 3H-pyrazoles. The photochemical reaction of these 3H-pyrazoles selectively leads to a- and 6-hydroxy cyclopropenes. The overall transformation constitutes a simple straightforward route to substituted cyclopropenyl alcohols without initial protection of the propargyl alcohol hydroxyl group. 

Clennan, E.L. and Sram, J.P. (2000). Photochemical reactions in the interior of a zeolite. Part 5. The origin of the zeolite induced regioselectivity in the singlet oxygen ene reaction. Tetrahedron 56, 6945-6950... 

Both target compounds discussed in this review, kelsoene (1) and preussin (2), provide a fascinating playground for synthetic organic chemists. The construction of the cyclobutane in kelsoene limits the number of methods and invites the application of photochemical reactions as key steps. Indeed, three out of five completed syntheses are based on an intermolecular enone [2+2]-photocycloaddition and one—our own—is based on an intramolecular Cu-catalyzed [2+2]-photocycloaddition. A unique approach is based on a homo-Favorskii rearrangement as the key step. Contrary to that, the pyrrolidine core of preussin offers a plentitude of synthetic alternatives which is reflected by the large number of syntheses completed to date. The photochemical pathway to preussin has remained unique as it is the only route which does not retrosynthetically disconnect the five-membered heterocycle. The photochemical key step is employed for a stereo- and regioselective carbo-hydroxylation of a dihydropyrrole precursor. 

A photochemical reaction of the silyl enol ether of acetophenone and benzaldehyde provided the 2,3-diphenyl-3-trimethylsilyloxyoxetane (13) with excellent regioselectivity (> 95 5) and diaster-eoselectivity (> 95 5) (91TL7037). In this example, the diastereoselection was explained by anti-approach of the two phenyl groups during the carbon-carbon bond forming step from the diradical intermediate (Scheme 7). 

The range of alkenes that may be used as substrates in these reactions is vast Suitable catalysts may be chosen to permit use of ordinary alkenes, electron deficient alkenes such as a,(3-unsaturated carbonyl compounds, and very electron rich alkenes such as enol ethers. These reactions are generally stereospecific, and they often exhibit syn stereoselectivity, as was also mentioned for the photochemical reactions earlier. Several optically active catalysts and several types of chiral auxiliaries contained in either the al-kene substrates or the diazo compounds have been studied in asymmetric cyclopropanation reactions, but diazocarbonyl compounds, rather than simple diazoalkanes, have been used in most of these studies. When more than one possible site of cyclopropanation exists, reactions of less highly substituted alkenes are often seen, whereas the photochemical reactions often occur predominantly at more highly substituted double bonds. However, the regioselectivity of the metal-catalyzed reactions can be very dependent upon the particular catalyst chosen for the reaction. 

FMO calculations using PM3-C1 were used to investigate the regioselectivities obtained by the photochemical reactions between 2-pyridone and pcnta-2,4-dienoate.46 The hard and soft acid-base principle has been successfully used to predict product formation in Patemo-Buchi reactions.47 The 2 + 2-photo-cycloaddition of homobenz-valene with methyl phenylglyoxylate, benzyl, benzophenone, and 1,4-benzoquinone produced the corresponding Patemo-Buchi products.48 The photo-cycloaddition of acrylonitrile to 5-substituted adamantan-2-ones produces anti- and svn-oxetanes in similar ratios irrespective of the nature of the 5-substituent49... 

Vinylnorcaradiene derivatives 1175 undergo a photochemical reaction resulting in the regioselective cleavage of one of the cyclopropyl a-bonds and the formation of isochroman-3-ones (Equation 457) <1997CC1973>. 

The photochemical reaction of carbonyl compounds and alkenes, which is referred to as the Paterno-Buchi (PB) reaction, was developed in 1909 [13], and is currently one of the most widely used methods for oxetane synthesis (Scheme 7.4). As exemplified in the PB reaction of benzophenone with 2-methylpropene [14], a selective formation of the oxetane is possible even when the photochemical reaction involves highly unstable molecules that is, the excited state of carbonyls. Due to its synthetic importance and mechanistic interest, the PB reaction is the most extensively studied synthetic method for oxetanes. Thus, several extensive reviews describing the PB reaction have been published since 1968, and the reader is directed towards these for further information [15]. In this chapter, methods that allow for the control of the regioselective and stereoselective formation of synthetically important oxetanes will be described. 

Before describing the regioselective, site-selective and stereo-selective preparation of oxetanes via the PB reaction, the mechanism of the photochemical reaction will be briefly summarized. The reason for this is that an understanding of the reaction... 

As mentioned in Section 7.2, when the electron transfer reaction between electron-rich alkenes and excited carbonyl compounds is energetically favorable, the RI pair becomes an important intermediate in photochemical [2 + 2] cycloaddition reactions (Scheme 7.5). The regioselectivity of these reactions may differ from that observed for the PB reaction involving 1,4-triplet biradical intermediates. Typical examples of PB reactions with very electron-rich alkenes, ketene silyl acetals (Eox = 0.9 V vs SCE), have been reported (Scheme 7.11) [27]. Thus, 2-alkoxyoxetanes were selectively formed as a result of the PB reaction with benzaldehyde or benzophenone derivatives, whereas a selective formation of 3-alkoxyoxetanes was observed in less electron-rich alkenes (see Scheme 7.9). When p-methoxybenzalde-hyde was used in the photochemical reaction, the regioselectivity was less than that observed in the case of benzaldehyde. This dramatic decrease in regioselectivity provided evidence that the selective formation of 2-alkoxyoxetanes occurred via RI pair intermediates. It should be noted that the stereoselectivity is also completely different from that associated with triplet 1,4-biradicals (vide infra). 

Bach and coworkers observed both regioselective and stereoselective oxetane formation during the PB reaction of acyclic vinyl ethers (Scheme 7.26) [15n], The stereoselectivity observed for such photochemical reactions cannot be explained using the Griesbeck Model, even though triplet, 14-biradicals were proposed as intermediates. Thus, the stereoselectivity was proposed to be largely dependent on product stability. 

In this chapter, recent developments in the regioselective, site-selective, and stereoselective preparation of oxetanes have been summarized. The relative nudeophilicity of the alkene carbons was seen to be important for regioselectivity, in addition to the well-known radical stability rule. Likewise, the three-dimensional structures of the triplet 1,4-biradicals were seen to play an important role in stereoselectivity. For photochemical reactions that proceed via radical ion pairs, the spin and charge distributions are crucial determinants of regioselectivity. It follows that the concepts used in selective oxetane synthesis should stimulate future investigations into the mechanistically and synthetically fascinating Paterno-Bitchi-type reactions. 

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. 

Shu, C., Slebodnick, C., Xu, L. etal. (2008) Highly regioselective derivatization of trimetallic nitride templated endohedral metallofullerenes via a facile photochemical reaction. Journal of the American Chemical Society, 130, 17755-17760. 

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... 

Dimerization - As reported in Part II, Chapter I the control of photochemical reactions in the constrained environment of a hydrotalcite clay as the supporting medium has been examined. This particular study examined the irradiation (X > 280 nm) of a mixture of 4-benzoylbenzoic acid and 2-phenylethe-nylbenzoic acid in this environment. While the regioselective formation of oxetanes was observed, dimerization of the phenylethenylbenzoic acid also takes... 

Mono-diene complexes of zirconocene and hafnocene have been prepared by two methods [129-131 ], viz the photochemical reaction of diphenylzirconocene in the presence of diene and the reaction of metallocene dichlorides with diene magnesium adduct. The structures and reactivity of s-cis-dicm complexes indicate that the metal-lacyclopentene (B) is the preferred canonical form. Complexes of the type Cp2Zr(j-/ra/25-1,3-diene), have been prepared they were the first examples of this mode of coordination (C). Insertion of unsaturated compounds into a diene coordinated to zirconocene results in regioselective C—C bond formation [132-136]. 

---