Bicyclic acetals reactivity

Unsymmetrically 2,5-disubstituted furan derivatives 61 reacted with 1-Me in good to very good yields, but gave mixtures of regioisomers and diastereomers endo/exo-62y endo/exo-65,the bicyclic acetals 62c-d showed a distinct tendency to be cleaved upon chromatographic separation. Dimethylfuran 61b, surprisingly, is less reactive towards 1-Me than furan (57) which is probably due to steric reasons (Scheme 16) [46]. 

In general, bicyclic acetals are highly reactive toward acid-catalyzed hydrolysis. For example, the hydrolysis of 2,7-dioxabicyclo[2.2.1]heptane (2) in aqueous acetone containing dichloroacetic acid was 2.5 x 104 times faster than that of an acyclic reference compound, dimethyl acetal. [77] 2,6-Dioxabicyclo[Z2.1]heptane (79) is more reactive, and hydrolyzed 6.9 x 10s times faster than dimethyl acetal. [78] These rate accelerations for bicyclic acetals arise from a partial liberation of the ring strain on hydrolysis, and have been correlated to the reactivities of bicyclic acetals in the cationic ring-opening polymerization. [5]... 

Reactivity. The reactivities of the bicyclic orthoesters can be compared examining the conditions necessary to form polymer. Although the hydrolytic reactivities were not accelerated, these monomers were Indeed very reactive In polymerization. In contrast to the behavior of the bicyclic acetals, no correlation Is found between the hydrolytic reactivity and the reactivity towards cationic Initiators for the bicyclic orthoesters. The following order can be proposed [2.2.1] > [2.2.2] > [3.2.1] > [3.3.1] which Is the expected order from the ring strains (18-19). 

The cis-fiised bicyclic acetal 176 could also be afforded as a single diastereomer via this strategy with 175 as the substrate (Scheme 66) [37], Mild Lewis acid, e.g., BF3 EtaO, was inactive and only the stronger oxophiUc Lewis acid Tip4 (20 mol%) could facilitate the transformation for the reason that secondary C—H was less reactive than the tertiary C-H bond in 173. 

An example of the vinylogous reactivity is the reaction of 52 with cyclopentadiene (Tab. 14.9) [77]. Rhodium(II) acetate-catalyzed decomposition of 52 in dichloro-methane, yields a 2 1 mixture of the bicyclic system 53 derived from the [3-1-4] cycloaddition, and the bicyclo[2.2.1]heptene 54 resulting from electrophihc attack at the vinylic position followed by ring closure. When Rh2(TFA)4 is used as the catalyst, bicy-clo[2.2.1]heptene 54 becomes the dominant product, while the reactivity of the vinyl terminus is suppressed using a hydrocarbon solvent as observed in the Rh2(OOct)4-cat-alyzed reaction in pentane, which affords a 50 1 ratio of products favoring the [3-1-4] cycloadduct 53. 

Yokozawa reported that the 2-substituent strongly affects the reactivity of a 2-substituted-oxazoline 360 with dimethyl 2,2-dicyano-3-ethoxy-l,l-dicarboxylate as shown in Scheme 8.115. Thus, oxazoline itself, 360 (R = H), gave the annulated bicyclic product 361 that resulted from collapse of the zwitterionic intermediate 362, whereas simple 2-alkyloxazolines, 360 (R = Me, Et), gave an alternating (1 1) copolymer. 2-Phenyloxazoline, 360 (R = Ph), was unreactive under the reaction conditions. The zwitterionic intermediate 362 (R = Me) was trapped by acetic acid to give the open-chain adduct 363 that resulted from nucleophilic ring opening at the 5-position of the oxazolinium zwitterion. 

A second and more recent example, the photochemical rearrangement of 4,4-diphenylcyclohexadienone (VIII), was provided by the present author and co-workers (4, 5,14). This compound (VIII) when photolyzed in aqueous dioxane with light of wavelength above 310 mp. was found (4, 5) to afford the bicyclic ketone IX, 2,3-diphenylphenol (X) and an acid whose structure was shown (14) to correspond to XI. Additionally, 3,4-diphenylphenol (XII) was shown (14) to be a minor by-product. Strikingly and reminiscent of the dependence of product distribution on solvent in santonin photolysis, it was found (14) that approximately equal quantities of 3,4-diphenylphenol and 2,3-diphenylphenol (X) were formed when the photolysis was run in 50% aqueous acetic acid. [Control experiments (14) demonstrated that neither 4,4-diphenylcyclohexadienone nor bicyclic ketone IX were reactive in the dark under the aqueous dioxane or aqueous acetic acid reaction conditions, in the presence or absence of acid XI.] Furthermore, the bicyclic ketone IX has been demonstrated to afford 2,3-diphenylphenol (X) and the photoacid XI on photolysis in aqueous dioxane, and consequently this ketone may be formulated as a reaction intermediate in the formation of X and XI from 4,4-diphenylcyclohexadienone (VIII) (4, 5, 14). 

The versatile functionality pattern of bicyclic MO-acetal-y-lactams (found in conjunction with their ir-face-selective alkylation) can also be applied to Diels-Alder reactions of the corresponding alkenic methoxycarbonyl-activated derivative (427) (Scheme 102). ° Noncatalyzed addition of 2,3-dimethylbu-tadiene to dienophile (427) (60 C, 8 h) proceeded exclusively from the ir-face opposite the isopropyl substituent. The reactivities of the latent immonium and carbonyl groups in adduct (428) were exploit during transformation into [l,3,4)propellane (434). 

The photochemical reactions of the bicyclic compounds (201 a, c) in acetonitrile-methanol solution in the presence of 1,4-dicyanobenzene have been studied. The irradiation of (201a) affords the mixture of trans cis methoxy derivatives (201b) which are also photochemically reactive under the same conditions. The products from (201a) are formed by the photochemical addition of methanol to the furan (202). This furan is formed by production of the radical cation of (201a) followed by deprotonation affording a doubly benzylic radical. The study was extended to the monocyclic system (203) which on electron-transfer-induced irradiation afforded the acetal... 

Outstanding regioselectivities have been reported when rhodium(II) acetate was employed as a catalyst [6-11]. The reactivity of the hydrocarbon component decreases in the order tertiary > secondary > primary C-H [8]. While the a,5-in-sertion yields the preferred cyclopentanones, the a,y-mode has occasionally been observed, too both the four-membered spirocycle (Structure 10) and the bicyclic... 

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