Cycloaddition photochemical, stereoselectivity

Thermal and photochemical electrocyclic reactions are particularly useful in the synthesis of alkaloids (W. Oppolzer, 1973,1978 B K. Wiesner, 1968). A high degree of regio- and stereoselectivity can be reached, if cyclic olefin or enamine components are used in ene reactions or photochemical [2 + 2]cycloadditions. 

Another interesting example of a photochemi-cally induced domino process is the combination of the photocyclization of aryl vinyl sulfides with an intramolecular addition as described by Dittami et al. [901 as intermediate a thiocarbonyl ylide can be assumed. The domino-Norrish I-Knoevenagel-allyl-silane cyclization developed by us allows the efficient stereoselective formation of 1,2-trans-subsituted five- and six-membered carbocycles.1911 A photochemical cycloaddition of enamino-aldehydes and enamino-ketones with the intermediate formation of an iminium salt followed by addition to allylsilanes gives access to novel bicyclic heterocy-des. New examples of photochemically induced... 

Recent research deals with stereoselective 1,3-dipolar cycloadditions of nitrones for the syntheses of alkaloids and aza heterocycles asymmetric synthesis of biologically active compounds such as glycosidase inhibitors, sugar mimetics, /3-lactams, and amino acids synthesis of peptido-mimetics and peptides chemistry of spirocyclopropane heterocycles synthesis of organic materials for molecular recognition and photochemical applications. 

It should be noted, however, that the 1,3-dipolar cycloaddition chemistry of diazo compounds has been used much less frequently for the synthesis of natural products than that of other 1,3-dipoles. On the other hand, several recent syntheses of complex molecules using diazo substrates have utilized asymmetric induction in the cycloaddition step coupled with some known diazo transformation, such as the photochemical ring contraction of A -pyrazolines into cyclopropanes. This latter process often occurs with high retention of stereochemistry. Another useful transformation involves the conversion of A -pyrazolines into 1,3-diamines by reductive ring-opening. These and other results show that the 1,3-dipolar cycloaddition chemistry of diazo compounds can be extremely useful for stereoselective target-oriented syntheses and presumably we will see more applications of this type in the near future. 

Unlike thermal [2 + 2] cycloadditions which normally do not proceed readily unless certain structural features are present (see Section 1.3.1.1.), metal-catalyzed [2 + 2] cycloadditions should be allowed according to orbital symmetry conservation rules. There is now evidence that most metal-catalyzed [2 + 2] cycloadditions proceed stepwise via metallacycloalkanes as intermediates and both their formation and transformation are believed to occur by concerted processes. In many instances such reactions occur with high regioselectivity. Another mode for [2 + 2] cyclodimerization and cycloadditions involves radical cation intermediates (hole-catalyzed) obtained from oxidation of alkcnes by strong electron acceptors such as triarylammini-um radical cation salts.1 These reactions are similar to photochemical electron transfer (PET) initiated [2 + 2] cyclodimerization and cycloadditions in which an electron acceptor is used in the irradiation process.2 Because of the reversibility of these processes there is very little stereoselectivity observed in the cyclobutanes formed. 

Cyano-substituted ethylenes react in a different way with aliphatic ketones. The orientation of photochemical cycloaddition (4.661 is the opposite of that found for electron-rich alkenes, and the reaction is highly stereoselective (4.69) in the early stages. These processes involve the formation and subsequent decay of an excited complex (exciplex) from the (n,n ) singlet state of the ketone and the alkene. Aryl ketones undergo intersystem crossing so efficiently that such a singlet-state reaction is rarely observed, but the reaction of a benzoate ester with an electron-rich alkene 14.70 rnay well be of this type, with the ester acting as electron-acceptor rather than electron-donor. 

The diverse chemistry of carbenes is beyond the scope of this account, but a few typical reactions are shown here to illustrate the usefulness of the photochemical generation of these reactive species. A carbene can insert into a C—H bond, and this finds application in the reaction of an a-diazoamide to produce a P-lactam (5.29). Carbenes derived from o-diazoketones can rearrange to ketenes, and thus a route is opened up to ring-contraction for making more highly strained systems <5.301. Carbenes also react with alkenes, often by cycloaddition to yield cyclopropanes in a process that can be very efficient (5.31) and highly stereoselective (5.321. 

The fact that molecules in L-B films keep fairly rigid relative orientations (at least within a microdomain) is potentially useful for regio- and stereoselective addition reactions (Figure 8.23). Here a derivative of cirfnamic acid forms the head-to-head dimer in the photochemical cycloaddition reaction. 

In an another mechanistic study, Foote and co-workers reported a possible charge-transfer mechanism for the photochemical [2+2] cycloadditions of electron-rich ynamines [56-58]. Further studies on the regio- and stereoselectivity upon addition of less electron-rich substrates such as alkyl-substituted 1,3-bu-tadienes [59], acyclic enones [60], and aryl alkenes [61] to C60 were performed in more recent years. 

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). 

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. 

Photochemical [2 + 2]cycloaddition to enones. This reaction has been shown to occur mainly from the less-hindered a-side of steroidal enones.2 Cycloaddition to the cyclopentenone (1) is also stereoselective, but the stereoselectivity and the yields are dependent upon the solvent. The highest yields are generally obtained in an apolar solvent (such as hexane). 

Thiocarbonyl compounds participate in a wide variety of reactions leading to cyclic compounds. In the majority of cases such cycloaddition reactions are thermally or photochemically induced and occur with a full or high degree of stereoselectivity. 

Photochemically induced [2 + 2] cycloaddition is of extraordinary importance in organic synthesis,as this is a method ideally suited for the preparation of sterically congested compounds. The reaction may occur by a concerted mechanism allowed by rules of orbital symmetry, or, more often, via a biradical pathway. For preparative purposes, the most widely exploited is the enone-alkene photochemical [2 + 2] cycloaddition. This reaction proceeds with high regioselectivity, although its stereoselectivity might be low. The first example of the utilization of this reaction for the synthesis of a natural compound, a-cariophyllene 385, was described by Corey (Scheme 2.129). Adduct 386, formed as a mixture of stereoisomers in high yield from simple precursors, was further transformed via the tricyclic intermediate 387 into the... 

Intramolecular meta photocycloaddition of 2-MeC6H4CH2CMe2CH2CH CH2 provides appropriate tetracyclic precursors from which the key tricyclic framework required for the synthesis of ( )-ceratopicanol can be obtained.This constitutes an example of a typical holosynthon. N-Benzoyl-N-benzylcinnama-mides and related compounds will photocycloadd in the presence of benzil to give 3-azatricyclo[5.2.2.0 ]undeca-8,10-dien-4-ones with high stereoselectivity, and this constitutes the first example of a photochemical [4+2] cycloaddition of an enone to a benzene ring. For example, irradiation of (60 R = H, alkyl, phenyl = H, Me X = H, OMe, Cl, etc.) gives (61 same R, R, X). 

A stereoselective synthesis of aminoalkyl-substituted P-lactams (41) has been developed, the key step of which is [2+2] cycloaddition of imines to ketenes generated photochemically from diazoketones (42), which are derived from protected a-amino acids. A number of steroidal diazoketones related to progesterone have been synthesized as potential photoaffinity labelling reagents for the mineralocorticoid receptor. ... 

Tetrahydrophthalic anhydride and the corresponding imide were found to be efficient partners in intermolecular [2 -I- 2] photochemical cycloaddition reactions with alkenols (e.g., e ,s-bulcn-2-cne-l,4-diol) and alkynols (Scheme 2.20). The corresponding cyclobutane adducts have been synthesized in high yields with levels of stereoselection (as high as 10 1) almost unprecedented in classical intermolecular cycloadditions. ... 

Only a few intramolecular thioaldehyde [4 + 2] cycloadditions have been executed to date. Vedejs et al. have looked at systems such as that shown in equation (88).Their photochemical method is useful in effecting intramolecular reactions but stereoselectivity in the process was only moderate. Baldwin and Lopez have described the single intramolecular cycloaddition shown in equation (89) which involves a new thermal method for generating thioaldehydes from alkyl thiosulfinates. ... 

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