Diketones polycyclic

Tamariz and coworkers [42] have described a versatile, efficient methodology for preparing N-substituted-4,5-dimethylene-2-oxazolidinones 42 (Figure 2.5) from a-diketones and isocyanates and have also studied their reactivity in Diels-Alder reactions. This is a method for synthesizing polycyclic heterocyclic compounds. Some of the reactions of diene 42 are summarized in Scheme 2.18. The nitrogen atom seems to control the regiochemistry of the reaction. 

An interesting family of polycyclic pyrroles was described in 2005 using again the synthetic sequence of a Stetter reaction for the preparation of the starting 1,4 diketones followed by a microwave-assisted Paal-Knorr condensation [35]. For example, cyclopentenone 23 (obtained in a Pauson-Khand cyclization) reacted imder Stetter reaction conditions to give the amino ketone 25 (Scheme 8). The microwave-assisted Paal-Knorr cyclization of 25 with different amines gave a small collection of tricychc pyrrole 2-carbox-amides. 

The pyrrolizine diketone 281 reacted with 1,2-diaminobenzene to give the polycycle 326.136... 

Intramolecular cyclisation of a 4-arylbutanoic acid system is also an important step in a convenient synthesis of the polycyclic system, chrysene, which is formulated and described in Expt 6.12. Here, methyl cinnamate is first subjected to reductive dimerisation to give methyl meso-ft,y-diphenyladipate, which is accompanied by some of the ( + )-form. The meso isomer (16) is the most easily isolable and cyclisation occurs smoothly in sulphuric acid to yield the diketone 2,1 l-dioxo-l,2,9,10,ll,18-hexahydrochrysene, which is obtained as the trans form (17) as shown in the following formulation. Clemmensen reduction of this ketone followed by dehydrogenation (in this case using selenium) completes the synthesis of chrysene. 

The Pfitzinger reaction provides a simple and convenient method for the synthesis of condensed polycyclic compounds containing a heterocycle from readily obtainable starting materials. Cyclic ketones and, more rarely, diketones are often used as starting compounds. 

A rather more exotic 1,3-diketone has been converted into polycyclic benzodiazepines (8) by heating it with a variety of substituted o-phenyl-enediamines, usually in glacial acetic acid, but in some cases in ethanol containing mineral acid [78JCS(CC)557 82JCR(M)0834, 82JCR(S)70] (Scheme 3). 

When you need to synthesize a p-hydroxy ketone or aldehyde or an a,p-unsaturated ketone or aldehyde, use an aldol reaction. When you need to synthesize a p-diketone or p-keto ester, use a Claisen reaction. When you need to synthesize a 1,5-dicarbonyl compound, use a Michael reaction. The Robinson annulation is used to synthesize polycyclic molecules by a combination of a Michael reaction with an aldol condensation. 

As part of the synthesis of 1,6-dimethyldodecahedrane 108), an interesting case has been reported 109) of cyclization of a polycyclic diketone in which two new cyclo-pentanol rings were formed, as illustrated by the partial structures shown below. X-ray crystallographic analysis showed that conformational factors were particularly favorable for this unique result. 

Cyclohexanediones. Paquette and co-workers have applied Saegusa s method (6, 139) to the intramolecular oxidative coupling of 1. Addition of the dicnolate obtained from 1 to a solution of anhydrous CUCI2 in THF and DMF at - 78° affords the polycyclic diketone 2 in 58% yield. 

Hydroxyphenalen-l-one (5) is a polycyclic P-diketone. A large ir-delocalization in 5 causes a remarkable red shift of the absorption bands, which can be exploited to achieve NIR lanthanide luminescence by visible light excitation with wavelengths up to 475 nm. 

The classic precursors used for generating diradicals are cyclic, bicychc and polycyclic diazenes. However, diradicals have also been made by Norrish type I photochemical extrusion of CO from cychc ketones, by thermal cleavage of vinyl and divinylcyclopropanes, by pinacol reactions of diketones, by Bergman-type cyclisations of endiynes, by several types of photoelectron transfer reactions and in other ways. Most synthetic applications have started with a derivative of 2,3-diazabicyclo[2.2.1]hept-2-ene which on heat-... 

Dihaloalkenes are oxidized to a-diketones on a variety of norbomyl derivatives, which have been serving as highly potent and inextricable templates for strained polycyclic unnatural compounds (Eq. 3.40) [76]. 

A structurally intriguing dimethyl[6]ditriaxane (84) has been synthesized from the polycyclic diketone tosylhydrazone (83) by the aprotic Bamford-Stevens reaction via a carbenic interm iate (equation 49). ... 

Reaction of 6-benzoyl-23-dihydropyran 22 with triols results in protection as polycyclic acetals as exemplified by the product 23 formed with glycerol <05CC1 3> and 2-acetyl-6-methyl-23-dihydrofuran reacts similarly with a range of 1,2-diketones to give products such as... 

The intramolecular counterpart of this reaction is a promising synthetic route to polycyclic diketones. For example, the diazo ketone (4) on treatment with triethyloxonium fluoroborate gives the diketone (3) in high yield. 

A TMSOTf-initiated cyclization of the dicarbonyl substrate was invoked to explain the reactivity pattern [79]. Selective complexation of the less hindered carbonyl group activates it toward intramolecular nucleophilic attack by the more hindered carbonyl which leads to an oxocarbenium species. Subsequent attack by the enol ether results in addition to the more hindered carbonyl group. The formation of this cyclic intermediate also explains the high stereochemical induction by existing asymmetric centers in the substrates, as demonstrated by Eq. 52, where the stereochemistry at four centers is controlled. A similar reactivity pattern was observed for the bis-silyl enol ethers of / -diketones. The method is also efficient for the synthesis of oxabicyclo[3.3.1] substrates via 1.5-dicarbonyl compounds, as shown in Eq. 53. Rapid entry into more complex polycyclic annulation products is possible starting from cyclic dicarbonyl electrophiles [80]. 

A larger number of silyl enol ethers have been studied by kinetic measurements with regard to their synthetic value as dienophiles and their reactivity the readily accessible silyl enol ethers proved to be enol equivalents <92TL8019>. Synthesis of novel heterocyclic clefts such as (153) and (154) can be achieved by (4 -I- 2) cycloaddition reactions of 1,2,4,5-tetrazines (151) with polycyclic diketones... 

Cycloaddition using an enol derivative of a cyclic 1,3-dicarbonyl compound, followed by retro-aldol reaction, results in ring expansion by two carbon atoms. Reactions of this kind have been applied to the synthesis of a number of polycyclic natural products. For example, irradiation of the enol benzoate 160 gave the tricyclic product 161 in almost quantitative yield (3.112). Dimethylation followed by hydrolysis and retro-aldol reaction gave the eight-membered ring diketone 162, used in a synthesis of the sesquiterpene ep/-precapnelladiene. 

The quasi-Favorskii rearrangement has been used often in the synthesis of unnatural, conplex, polycyclic structures. Indeed, this method is uniquely suited for such targets. However, undesired side reactions can occur. An exanple, discussed here within its mechanistic context, is based on a report by Ueda and coworkers. They treated the polycyclic dibrominated diketone 37 with potassium hydroxide in the expectation of obtaining cubane-l,3-dicarboiq lic acid 38. Given what was known about quasi-Favorskii reactions at the time (vide supra), the plan made perfect sense. However, exposure of 37 to 5% KOH for 15 min at 80 °C afforded not 38 but the cyclopropyl lactone 43 fScheme 7.12). A proposed mechanism for the process began with a Haller-Bauer cleavage, always a potential risk in quasi-Favorskii... 

The cascade rearrangements following double addition of alkenyl anions to the squarate ester was initiated by Paquette from the clue of Asensio s finding that twofold addition of organolithium (MeLi, PhLi, etc.) leads to the facile electrocyclic ring opening to 1,4-diketones [102]. This expedient method for construction of complex polycycles is achieved by a simple one-pot process... 

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