Synthesis and photochemistry of chiral bichromophoric compounds

This thesis describes a multidisciplinary study on the combination of stereochemistry and mechanistic organic photochemistry of chiral bichromophoric compounds. In particular the photooxygcnation and photochemical rearrangements of these compounds are discussed. Furthermore, the synthesis, in high optical purity, of a molecule whose chirality js solely due to the presence of a locaUzed excited state is investigated; a phenomenon belonging prior to this research to the realm of fantasy. Some of the bichromophoric compounds possess a 2-prop-l-enol unit with the feasibility for a diastcreose1ective photochemical intramolecular rearrangement, conform the observations for gennaerol and racemic mixtures of tctnl.a.lkyl-ethylidene-naphthalenols. According to quantum chemical calculations of Dormans, Fransen and Buck on the mechanism of this photochemical rearrangement in 2-propenol, excitation of 2-propen-l-01 involves a 90(> twisted ene moiety, which is accompanied by charge separation (sudden polarization). For 2-propenol this separation of charge is dictated by the neighbouring electronegative OM functionality. As a result, the hydroxyl group then shifts to the positively charged tenninus of the allylic fragment in the plane of the double bond. This wplanar" photochemical [1,3]-OH shift involving sudden polarization was also claimed to occur for racemic 2-naphthalenols. The results of chapter 2, 3 and 4, show that the photochemical behaviour of 1,2,3,4-tetrahydro-4-ethyl-l, I ,4-uimethyl-(3Z)ethylldene- 2(lH)-naphthaJenols, synthesized in their optical pure form, and endo hydroxy· bieyclo[4.4.0]-nonadiene derivatives, is quite different with respect to the occurrence of the sigmatropic photochemical shifts, and more common reactions have been found instead. Chirality solely due to the presence of a localized singlet e)(cited state was first noted and discussed by Schippers and Dekke.rs for the irradiation of an achiral 1,7- diketone with circularly polarized light The local excitation of such achiral ketones gives rise to two enantiomeric fOnTIs, provided the excitation remains localized at the carbonyl group. However, for a locally singlet-excited 1,3-diketone, synthesized by Meijer, via thermolysis of an optically active l,2-dioxetane, racemization occurred within the excited state. Due to the close proximity of the carbonyls, energy transfer was too fast to observe optical activity of the excited state. The results in chapter 5 show, however, that one of the smallest deviations from achirality, Le. chirality solely du~ to the presence of an excited state, can be accomplished in high enantiomeric excess. Chapter 2 describes the synthesis and characterisation of optically pure (2S,4R)and (2R,4R)-1,2-3,4-tetrahydro-4-ethyl-l, 1 ,4.trimelhyJ.(3Z)·ethylidene-2(1 H)-naphthalenols. A seven-step procedure has· been developed. The optically pure R-2-methyl-2-phenylbutanoic acid, obtained by resolution of the quinine salts of the racemic butanoic acid, was employed as the key starting material. The acylation of isobutene with the optically active 2-methyl-2-phenyJ·butanoyl chloride, followed by a Friedel-Craft cycJil..ation, an oxidation and a Wittig reaction gave two isomeric 3,4-dihydro-ethyl-trimethyl-(3Z) ethyIidene-2(lH)-naphthalenones. Separation of the isomers by HPLC and reduction gave the optically pure target molecules for the purpose of photochemistry and photooxygenation described in chapter 3. All compounds were fully characterized with one- and two·dimensional NMR spectroscopy, including INADF.QUATE. In chapter 3 the reinvestigation of the photochemistry of the optically pure 2- naphthalenols is described. The results show that besides E·Z isomerization, indanes are formed by the elimination of formaldehyde. Semiempirical MNDO, AMI, and PM3 calculations revealed that in the preferential ground-state conformation the hydroxyl group (l(Xupies an orthogonal position with respect to the exocyclic double bond. Fluorescence measurements confirm, that the reactive state is the triplet state. In fact we have been unable to identify photoproducts via a planar [l,3]-OH shift as claimed for racemic 2- naphthalenols. As a matter of fact, the results in this chapter lead to a negative conclusion with respect to the feasibility and actual occurrence of the [1,3]-OH shift for the (2S,4R). and (2R,4R)-1 ,2-3,4-tetrahydro-4-ethyl-l, 1 ,4-trimcthyl-(3Z)-ethylidene-2-naphthalenols. Since photooxygenation of chiral alcohols attained increasing interest, we have investigated the photochemistry of the optically active naphthalenols in the presence of o~ygen. The results show that the double bond is rapidly ox.ygenated which leads to stereoselectivc formation of an cpoxide and an ally lie hydroperoxide. The observed regioand stereospecificity is explained by the selective coordination of the hydroxyl group in the ehiral 2.propen-l-ol unit with the attacking c1cctrophilic oxygen. In Chapter 4 the photochemistry of 9-endo-hydroxy-9-"C~o-vinyl"bicyclo[4.2.1] nona-2,4-diene analogues is described. On the basis of deuterium labelling experiments, conformational analysis and one- and twodimensionaJ NMR spectroscopy, it was established that a light-induced intramolecular formal hydrogen transfer occurred towards one of the termini of the endocyclic diene. The hydrogen transfer takes place on the endo side of the molecule and can also be considered as an oxy retro-ene reaction. Prolonged irradiation revealed an intramolecular cycloaddition of the a,/J·unsaturated ketone in a secondary photoprocess, in which strained pyrnns were fonned via a triplet bisa1lylic biradical intermediate. The results in Chapter 5 show that a compound, whose chirality is solely due to the presence of localized electronic excitation energy, can been achieved_ The optically active excited 1,6- diketone with an optical purity> 98% and a lifetime of ... 2 ns was prepared by thennolysis of an optically pure 1,2-dioxetane. The synthetic route is mainly based on the steJ"eO" and regiosclcctive enzymatic reduction with HLADHfNADH and low-temperature photooxygenation of electron rich olefins_ The optical activity was evidenced by a non-vanishing circular polarization in the chemiluminescence. In addition, the work described in this chapter, shows, that circularly polarized chemiluminescence generated from a 1,2-dioxetane precursor, provides some insight into intramolecular energy transfer in diketones since this process would provide for racemization of the chiral excited state