Annelation reaction effects

The reactions of fused and unfused a-pyrones with magnesium alkoxides, sodium alkoxides, and water as the nucleophile have been studied in depth, particularly with respect to the effects of chelation <1996J(P1)2715>. The annelation reactions of pyranose derivatives, with acetylacetone and ethyl acetoacetate, to give a variety of annelated fused pyrans have been reported, with the products obtained as single diastereoisomers (Scheme 13) <1997LA1019>. 

In general, the synthesis of [n]helicenes involves two key synthetic steps, i.e. connection and annelation. The most efficient approaches to [njhelicenes use multiple annelations, forming two or more rings in one synthetic step however, relatively few annelation reactions have been implemented effectively. 

Dianions of /8-keto-esters can be alkylated with a-chloro-ethers to give 5-alkoxy-jS-keto-esters in ca. 70% yield. These compounds serve as useful alternatives to y5-unsaturated-/8-keto-esters in the Robinson annelation reaction.Clean nucleophilic displacement of bromine from y-bromoacetoacetates can be effected by prior protection of the keto-ester system as the sodium enolate. ... 

Condensation Reactions.—Trost has reviewed the preparation and synthetic uses of cyclopropyldiphenylsulphonium ylides. The regioselectivity and chemospecificity of the cyclopentane and cyclopentenone annelation reactions have been examined. Whereas diphenylsulphonium methylide does not cyclopropanate simple, unactivated olefins such as tetramethylethylene, transfer of a methylene group from the ylide can be effected stereospecifically in the presence of a copper catalyst and this reaction may provide a model for biological cyclopropanations by the ylide derived from S-adenosyl-methionine. Attempts to catalyse a similar transfer to unactivated olefins using PdCl2 were not successful. ... 

The interesting aza-propellane skeleton of metaphanine, a complex hasubanan alkaloidj has been effectively constructed by Ibuka et at. using a modified Robinson annelation reaction.The synthesis is completed by stepwise oxidative introduction of oxygen functions at C-8 and C-10 which eventually furnishes the unique hemiketal ring in the molecule. 

Mechanistic evidence indicates 450,451> that the triplet enone first approaches the olefinic partner to form an exciplex. The next step consists in the formation of one of the new C—C bonds to give a 1,4-diradical, which is now the immediate precursor of the cyclobutane. Both exciplex and 1,4-diradical can decay resp. disproportionate to afford ground state enone and alkene. Eventually oxetane formation, i.e. addition of the carbonyl group of the enone to an olefin is also observed452. Although at first view the photocycloaddition of an enone to an alkene would be expected to afford a variety of structurally related products, the knowledge of the influence of substituents on the stereochemical outcome of the reaction allows the selective synthesis of the desired annelation product in inter-molecular reactions 453,454a b). As for intramolecular reactions, the substituent effects are made up by structural limitations 449). 

This reaction can be used to effect a [3 + 2] or a [3 + 2 + 2] annelation to a cyclopentenone ketal or a cycloheptadienone ketal, respectively. Thus the adduct of a vinylcuprate with 1 rearranges thermally (240-290°) to 3-cyclopentenone ketals (3) in 50-80% yield (equation I). [3 + 2 + 2]Annelation involves preparation of... 

A rather difficult double Wittig reaction (Eq. 3.24) has been effected with enhanced efficiency under sonication [123], The process constitutes a novel type of annelation of an aromatic ring when applied to o-quinones. 

Neighboring group participation effects appear to play a crucial role in the nucleophilic substitution of chlorine in Michael adducts of 1-R, 2-R, 3-X. Thus, this substitution proceeds very easily in any of the adducts formed with an electron rich nitrogen, sulfur and oxygen Michael donor. For the adducts of nitrogen nucleophiles, the facile substitution of the chlorine has been suggested to occur via formation of intermediate aziridinium ions 103 [8] (Scheme 32), and this postulate was later supported by isolation of azaspiropentane derivatives under appropriate conditions in several reactions (see Sect. 3.2.2) [11b, 53,56]. It is most likely that alkylthio substituents in adducts of type 85 participate in the same way to first form spirocyclopropane-annelated thiiranium ion intermediates which are subsequently opened by attack of the incoming nucleophile. 

Development of a predictive model for the reactivity of annelated benzenes is facilitated by the partitioning of substituent effects into their steric and electronic parameters. In order for this to be accomplished, reference reactions are needed which depend uniquely on one type of parameter. Typically conformational equilibria serve as good references of steric effects, whereas acid-base equilibria serve as good references of electronic effects. 

Proton acid-base reactions are not particularly sensitive to stoic compression, and hence provide a good measure of inductive effects. For acid-base character, three sets of reference reactions can be used. The easiest of these to perform experimentally requires an analogy be drawn between the relative pK values of a series of protonated annelated pyridines and the pK values of the analogous isoelectronic benzene. The second is a direct measure of the kinetic acidity of the a- and P-sites on a soies of annelated benzenes. The third is a related direct assessment of kinetic acidity by protodetritiation. 

Aside from NMR, general spectroscopic data have not had great impact on either the bond fixation or the reactivity question. This is probably because the magnitude of the energy necessary to cause either the reaction selectivities or bond fixation is close to the error in these methods. The NMR studies stand out from this generalization. Chemical shift data have been useful in demonstrating that the effects of strained annelations are localized to the C - and tpjo-carbons. Coupling constant... 

Nazarov-type cyclization of x,x-dienones. The cyclization of a,a -dienones of type 1 to annelated cyclopentenones (2) is effected in yields of 10-20% with the usual Lewis acid catalysts SnCl4, CF3COOH, or BF3 etherate. However, reaction of 1 with 2 equiv. of ISi(CH3)3 effects this cyclization in 48% yield. However SnCl4 is more satisfactory for cyclization to ring-fused cyclopentenoid systems such as 4. 

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