Photodienol

Hofmann degradation of the nonnatural protoberberine 454 afforded the 10-membered ring base 455 (65%) in addition to the styrene-type compound (13%) (Scheme 92). Dihydroxylation of the former with N-bromosuccinimide in the presence of a large excess of hydrochloric acid and subsequent oxidation of the product diol 456 with periodic acid afforded the dialdehyde 457. On irradiation in tert-butyl alcohol 457 provided ( )-cis-alpinigenine (445) along with ( )-alpinigenine (441) as a result of endo and exo intramolecular cycloaddition, respectively, of the intermediate photodienol (221,222). 

It was shown previously that photodienols derived from a-substituted conjug) aliphatic esters could be protonated enantioselectively in aprotic solvents an<... 

To be very enantioselective, this reaction has to meet several important requirements. First, photoenols have to be produced as either pure Z or E stereoisomers to allow enantioselective photodeconjugation. Even so, protonation of the Z or stereoisomers from the same, rear side, for example, would produce opposite enantiomers and a low enantiomeric excess (ee) would result (Scheme 3). Fortunately, photoenolization of aliphatic enones is only possible from the Z isomer excited in its singlet state, and the excited molecule has to adopt an s-cis conformation to place the excited carbonyl and the y-H close enough to allow y-H abstraction. Consequently, the enol is formed in a unique configuration. All these observations have led several groups to propose a concerted process involving a 1,5 antarafacial sigmatropic shift for the formation of photodienols [16]. 

Figure 1. Transition state involved in the protonation of a photodienol in the presence of a /3-aminoalcohol.

Enantioselective photodeconjugation occurs with lactones, esters, and conjugated enones [33]. In principle, as soon as a prochiral photodienol can be produced, an enantioselective protonation is expected in the presence of a chiral -aminoalcohol. However, the corresponding acids and amides are unsuitable starting materials for enantioselective photodeconjugation. 

Figure 3. Transition states involved in the asymmetric protonation of a photodienol induced by ( —)-ephedrine.

The enantioselectivity observed for the deconjugation of ester and lactones is very sensitive to temperatures. Concentrations of R and S isomers formed are directly proportional to the rates /cr and of protonation of the intermediate photodienol. 

Scheme 5. Enantioselective protonation of photodienols by chiral -aminoalcohols.

When lactate is used as a chiral auxiliary, the proximity of the enolic hydroxyl group and the carboxyl of the lactate induces an interaction between the functional groups in the photodienol. Therefore, a surprising solvent effect, and even a reversal of the diastereoselectivity with the content of 2-propanol in water, was reported [53]. Except for lactate 8f in methanol and 2-propanol/water mixtures, it was possible to correlate the chirality of the new asymmetric center with the configuration of the lactyl chiral auxiliary. When (S)-lactyl derivatives were examined, models indicated that the S-configuration of the new chiral center can be deduced from a sterically easier approach of the carboxylate group at the re face of the a-carbon of the dienol. 

When irradiated in solution, cis-acetylcyclooctene (c-24) undergoes a very efficient Z photoisomerization and a photostationary state, where the cis isomer is predominant, is rapidly obtained [60]. For longer irradiation periods, the t-24 isomer leads to a mixture of photodienols in a much slower process. These photodienols can be characterized by either spectroscopy or chemical trapping [61]. As observed for other strained cyclenones [62], it is not possible to isolate the trans isomer from its Z E mixture in solution [63]. 

The formation of P,y-unsaturated isomers from photodienols is also strongly dependent on the nature of the solvent and/or the presence of additives, which could catalyze the phototropic step. By using nonpolar solvents, such as methylene chloride or hexane, irradiation is usually unsuccessful. By contrast, introduction to the medium of a small amount of an acid or a base such as imidazole and dimethyfimidazole or diethylamine greatly enhances the rate of the reaction and also the yields... 

When the starting ester is substituted by a group different from a hydrogen atom, the photodienol produced can be considered as a prochiral species. The selective protonation of one of the two Si or Re faces can then be expected under appropriate conditions to furnish a mixture enriched in one of the two stereoisomers. Two approaches toward this goal have been considered for esters, as depicted on Scheme 16 ... 

Enantioselective protonation of the prochiral photodienol performed by use of an external chiral source of protons (pathway a)... 

Awandi, D., Henin, E, Muzart, J., and Pete, J. R, Reversal of diastereoselectivity in protonation of chiral photodienols. Tetrahedron Asymm., 2,1101,1991. 

Piva, O. and CarameUe, D., Asymmetric protonation of photodienols enantioselective synthesis of (R)-2-methylalkanols, Tetrahedron Asymm., 6, 831, 1995. 

Scheme 3.35 Enantioselective protonation of photodienols oiganocatalyzed by p-amino alcohols...

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