Photochemical Aldolization

Given the relatively rare appearance of oxetanes in natural products, the more powerful functionality of the Patemo-Biichi reaction is the ability to set the relative stereochemistry of multiple centers by cracking or otherwise derivitizing the oxetane ring. Schreiber noted that Patemo—Btlchi reactions of furans with aldehydes followed by acidic hydrolysis generated product 37, tantamount to a threo selective Aldol reaction. This process is referred to as photochemical Aldolization . Schreiber uses this selectivity to establish the absolute stereochemistry of the fused tetrahydrofuran core 44 of the natural product asteltoxin. ... 

Scheme 2. The Paterno-Buchi reaction as a photochemical aldol equivalent.

Example Ester (59) was needed for a photochemical synthesis of chrysanthemate ester (60), a component of the pyrethrin insecticides. The a,B disconnection (59a) gives synthon (61) and aldehyde (62). This 8,y-unsaturated compound could be made by dehydration of (63) as the double bond can appear in only the required position. On page T 149 we discussed the synthesis of (62) by the aldol dimerisation of (64), An alternative strategy is to work at the ester oxidation level (65) which means synthon (66) is needed to combine with (64). 

A remarkable combination of a photochemical [2+2] cycloaddition with a retro-aldol reaction and cyclization is the so-called de Mayo reaction. Biichi and coworkers have used this method for the total synthesis of loganin (5-35). Thus, reac-... 

Allylic alcohols react with aldehydes, in the presence of catalytic amounts of Fe(CO)s under photochemical activation conditions, to give mainly aldol products (Scheme 11).33 This novel tandem iosmerization-aldolization reaction is a process with a perfect atom economy, proceeding under neutral conditions. 

Photochemical cyclization of enones with olefins is followed by a retro-aldol reaction to give 1,5-diketones. 

The central bond in (photochemically) easily accesible bicyclo[n.2.0]-alkan-2-ones (n = 3,4) can be cleaved by retro-aldol reaction (cf. Sch. 2), but also by treatment with Broenstedt- and Lewis-acids. This is shown in Sch. 16 for the synthesis of (i)descarboxyquadrone (55) starting from indenone 56 via the cycloadduct 57 which reacts with HC1 to 58 [69], or by the preparation of the AB-ring core of Taxol 59 from cyclopentenone 60 via cycloadduct 61 which rearranges to 62 in the presence of TiCl4 [70]. 

The photoaddition of a furan and an aldehyde can serve as a photochemical version of a stereoselective aldol reaction, since the photoadduct can be viewed as a protected aldol, as indicated in Scheme 23 (Schreiber et al., 1983). 

The Patemo-Buchl reaction of furan and various aldehydes was shown to be a highly stereoselective photochemical version of the aldol reaction by S.L. Schreiber and co-workers in which the furan serves as an enolate equivalent. This strategy was applied to the total synthesis of the antifungal metabolite (+)-avenaciolide. The photocycloaddition of nonanal with excess furan proceeded in nearly quantitative yield, and the two out of the three required stereocenters were created in a single step. The photocycloadduct was first hydrogenated then hydrolyzed under acidic conditions. 

Thus, to mention only a few examples, oxidations, electrolytic redactions, most polymerizations, reactions utilizing organic peroxides as catalysts, reactions of aromatic diazonium salts in which, nitrogen is lost, and photochemical or hot-tube processes are probably free radical Qansformations The FriedelrCrafts reaction, the alkylation of aceto-acetic ester, aromatic substitution , dehydrations, and the aldol or Claisen condensations appear to involye transitory ionic intermediates. 

Irradiation at 254 nm of the imidate (Scheme 2) in aqueous solutions results in the formation of 4-cyanophenol and A -isopropylbenzamide. The photochemical step involved in the formation of the products has been shown to be C-O bond fission with the production of the phenoxide and the benzonitrilium ion. Mariano and co-workers have reported a detailed study of the electron-transfer photochemistry of a-anilino carboxylates, p-anilinoalcohols and a-an-ilinosilanes. This study has measured the rates of decarboxylation of aniliniumcarboxylate radicals. The base induced retro-Aldol fragmentations of the radical-cations formed from the p-anilinoalcohols and the influence of substituents on the nitrogen on the desilylation of the a-anilinosilanes was also investigated. In addition, the synthetic potential of some of the electron-transfer photochemistry of the carboxylate salts (181) and (182) has been examined. In these examples irradiation, using DCA in methanol or acetoni-... 

The traditional aldol analysis requires a 1,4-diketone 117 whose stereochemistry suggests a 2 + 2 photochemical cycloaddition29 also on 117 and oxidative cleavage of the product 118. 

Copper-catalysed Michael addition followed by an aldol reaction with formaldehyde, gives a 1 1 mixture of diastereoisomers of the aldol 86 that can be eliminated to the enone 83. The resulting efficient photochemical cycloaddition gives ketone 82 with total regioselectivity probably because it is intramolecular. 

An intramolecular counterpart of the photochemical step used in the formation of (6) has been successfully applied to the synthesis of 12-epi-lycopodine (14). Photolysis of (10) yielded the intermediate (11) which was converted into the diketone (12). The latter compound gave the aldol product (13) which, in four steps, produced 12-epi-lycopodine (14). An amazing simplification of the overall route resulted when it was found that the diketolactam corresponding to the ketal (15) underwent a stereospecific Michael reaction to give (13) directly in 30% yield. 

The influence of chiral inductors on the photochemical cyclization of the adamantane-substituted ketones (48) in zeolites has been examined. Only the endo-products (49) are formed. The best ees are obtained for both derivatives (X = H or F) with (—)-pseudoephedrine as the chiral auxiliary. The cyclobutanols undergo retro-Aldol ring opening to afford the ketones (50). The study was extended to the more heavily substituted derivatives (51). ... 

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