Photocycloaddition retro

From a preparative point of view the heteroatom in P-position has an influence because important latent cyclobutane cleavage pathways exist in the product. The prototypical reaction of this type is the [2 + 2]-photocycloaddition/retro-aldol reaction sequence (de Mayo reaction) [55-57], the course of which is illustrated for substrate A3 (Q = O, PG = protecting group) in the reaction with ethylene as a generic olefin. 

The extension of this intramolecular photocycloaddition-retro-Mannich-Mannich sequence to -substituted secondary vinylogous amides, the photochemistry of which had been originally reported by Schell and Cook (Scheme 18), was also examined... 

An intramolecular vinylogous amide photocycloaddition, retro-Mannich fragmentation and final Mannich cyclization cascade provided a useful method for the synthesis of the complex ABCE ring system [91], The preparation of the requisite photosubstrate is outlined in Scheme 28. After cluomatographic separation, the cis alcohol was irradiated and led to the formation of aminals in a 2 1 ratio. Equilibration studies of the Swem oxidation products revealed that exposure of the minor diketone to sodium methoxide in methanol effected conversion to the manzamine-unlike... 

An Approach to the Synthesis of the Manzamine Alkloids via the Vinylogous Amide PhotocycloAddition/Retro-Mannich Fragmetation/Mannich Closure Cascade (pharM). Winkler, J. D. Stelmach, J. E. Siegel, M. G. Haddad, N. Axten, J. and Daily III, W. P. Isr. J. Chem. 1997, 37, 47. 

White JD, Ihle DC (2006) Tandem photocycloaddition-retro-mannich fragmentation of enaminones. A route to spiropyrrolines and the tetracyclic core of koumine. Org Lett 8 1081-1084... 

The appropriately substituted vinylogous amides can imdergo an intramolecular photocycloaddition-retro-Mannich-Mannich sequence. This sequence is analogous to the photocycloaddition-retro-aldol-aldol sequence shown in the formation of 19 from 15 (vide supra). Thus, irradiation of 110 leads to the formation of ketoimine 112, the product of photoaddition followed by rerra-Mannich fragmentation. Reaction of 112 with 1 equiv of trimethyloxonium tetrafluoroborate, followed by treatment of the resulting iminium ketone with aqueous hydrochloric acid, provides the photocycloaddition-re/ro-Mannich-Mannich product 113 in 50% yield from the acyclic photosubstrate 110. ... 

The photocycloaddition-retro-Mannich-Mannich methodology is featured in a concise synthesis of mesembrine. Irradiation of vinylogous amide 114 effects photocycloaddition-re/ro-Maimich sequence to give product 116 via the cyclobutane intermediate 115. Methylation with trimethyloxonium tetrafluoroborate followed by treatment with DMAP produces mesembrine in 84% yield. Other applications include construction of the bicyclic core of peduncularine and synthetic approaches to hetisine alkaloids and 8-substituted 6-azabicyclo[3.2.1]octan-3-ones. ... 

A novel intramolecular photocycloaddition involving vinylogous amides and allenes led to an interesting type lb entry to functionalized pyrroles <060L4031>. For example, photolysis of allene 11 provided fused pyrrole 12 via a [2+2] cycloaddition and retro-Mannich reaction. 

In the formation of tetraenes from bicyclo[4.2.0]octa-2,4-dienes, two bonds are broken. This may occur in one concerted reaction which can be regarded as a retro [2 + 2] cycloaddition. It is also possible that the central bond, being part of a cyclohexadiene system, is the first one to break in a thermal, concerted disrota-tory process that leads to a 1,3,5-cyclooctatriene derivative. Ring opening of the cyclooctatriene then might take place photochemically, again disrotatory, to produce a tetraene. This two-step sequence was first observed by Mirbach et al. [114] in their study of the photocycloaddition of the two parent molecules benzene and ethene. The same explanation for the formation of a tetraene was given by Nuss et al. [160] in their report on the intramolecular ortho photocycloaddition of ( )-6-(2-methoxyphenyl)-5,5-dimethyl-2-hexenenitrile (see Scheme 40). 

Upon [2 + 2]-photocycloaddition to product E and protecting group removal, the retro-aldol fragmentation can be initiated by base or acid treatment (Scheme 6.18). Under basic conditions, alkoxide F generates an enolate which is subsequently protonated to the 1,5-diketone G. 

A very useful extension of the de Mayo reaction has been recently introduced by Blechert et al. (Scheme 6.26) [78]. The retro-aldol fragmentation was combined with an intramolecular enantioselective allylation (asymmetric ring-expanding allylation) catalyzed by a chiral Pd complex. Bicycloheptane 68, for example, was accessible by intermolecular [2 + 2]-photocycloaddition of cyclopentenone 67 with allene. Further transformation in the presence of Pd2(dba)3 (dba = dibenzylideneacetone) and the chiral oxazoline ligand 69 (tBu-phox) resulted in the enantioselective formation of cycloheptadione 70. 

Figure 11 Different pathways for concerted Retro 2 + 2 Photocycloaddition (photocleavage) of a cyclobutane dimer.

A key step in the synthesis of 12-epi-lycopodine reported by Wiesner and coworkers is the intramolecular [2 + 2] photocycloaddition of a vinylogous imide and an allene. Irradiation of photosubstrate 46 produced a single cyclobutane 47, in which the allene added to the vinylogous imide anti to the methyl group (Scheme 13)31. Photoadduct 47 was converted to ketal-alcohol 48 via a three-step sequence of ketalization, epoxida-tion and reduction. Hydrolysis of the ketal unmasked the /Miydroxy ketone functionality. Retro-aldol fragmentation followed by aldol closure gave hydroxyketone 49, which was readily converted to the polycyclic alkaloid 12-epi-lycopodine. 

Winkler and coworkers have coupled the photocycloaddition and retro-Mannich fragmentation of an acyclic vinylogous amide with a subsequent Mannich closure to produce perhydroindole structures as outlined in Scheme 2445. The acyclic secondary... 

In contrast to intermolecular photoaldols, which can be manipulated with facility, intramolecular cycloadducts undergo retro-[2 + 2] cycloaddition when subjected to hydrolytic conditions. In an alternative protocol, oxymercuration of (229) afforded a-mercurio ketone (230 42%) which was acetylated under standard conditions to provide 1,4-diketone (231) quantitatively. Similarly, epoxidation of (229) provided functionalized photoaldol (232), which was hydrolyzed and acetylated to form a-acetoxy derivative (233). Finally, hydrolysis of (234) (4 1 THF/0.1 N HCl) gave lactol (235) in nearly quantitative yield, illustrating the utility of the intramolecular furan carbonyl photocycloaddition in spirocycle formation. 

An intramolecular photocycloaddition of a vinylogous amide tethered at C-3 of a 1-acylindole has also been achieved in a stereospecific reaction, in which the cyclobutane adduct (332) undergoes a retro-Mannich reaction to give the imino ketone (333), a synthetic precursor of vindorosine (Scheme 104) <90JA8971>. 

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