Oxetanes bicyclic

The photocycloaddition of aliphatic and aromatic aldehydes with 2,4,5-trimethyloxazole (131) gave bicyclic oxetanes 132 in almost quantitative yields hydrolitic cleavage led selectively to erytro a-amino-P-hydroxy methyl ketones 133 <00CC589>. The oxazolium salt 134 was converted to the azomethine ylide 136 via electrocyclic ring opening of the oxazoline 135. Intramolecular cycloaddition afforded 137 in 66% overall yield which was transformed into the aziridinomitosene derivative 138 . 

An intramolecular substitution of trimethylamine fix>m 17 gave a bicyclic oxetane 18 in a diastereoselective process <98MI2185>. A [2+2]cycloaddition of 2,2,4,5-tetrasubstituted 2,3-dihydrofuran to aryl aldehydes gave the bicyclic oxetane 19 <98JCS(P1)3261>. 2,2-Disubstituted-3-bromooxetane was obtained by a 4-endo-tcig cyclization process of 3,3 -disubstituted allyl alcohol in the presence of bis(collidine)bromine hexafluorophosphate <99JOC81>. 

The preferred elimination of a molecule of carboxylic acid instead of water in this case may be explained by the intermediate formation of a bicyclic oxetane 289. Along with conversions described here, which have some analogy with what is known from a-1 dimerizations and reactions of monomeric C-adducts, a new transformation has been found in the case of 4-1 dimerization, namely disproportionation, as shown in the following paragraphs. 

Sakamoto et al. also demonstrated an absolute oxetane synthesis in the solid-state photolysis of Y-( ,(3-unsaturatcd carbonyl)benzoylformamides 43. [28] The X-ray analysis of Y-isopropyl substituted imide 43a revealed that the crystal system was monoclinic and the space group P2. Crystals of 43a were powdered and photolyzed at 0°C. The imide undergoes the [2+2] cycloaddition to afford the bicyclic oxetane 44a, which is a mixture of diastereomers, namely, syn- and anh-isomers at the C-7 position. In this reaction optically active. syn-oxctanc 44a with 37% ee (84% chemical yield) and racemic anti-44a were obtained. The solid-state photoreaction proceeded even at -78°C, and optically active syn-44n which showed ee value as high as >95% ee, (conv 100%, chemical yield 89%) was formed in a higher diastereomeric ratio (syn/anti = 6.5). Under identical conditions A-bcnzyl substituted 43b was irradiated in the solid state. 

The exo-selective formation of bicyclic oxetanes of furan derivatives is reported as being successful when applied to the synthesis of natural products (Scheme 7.19) [15e,37]. For example, the total synthesis of asteltoxin and avenaciolide was achieved from 3,4-dimethylfuran and furan, with the PB reaction being used as an initial step of the synthesis. 

Scheme 7.21 The exo-selective formation of bicyclic oxetanes during the PB reactions of oxazoles and vinylene carbonate.

Scheme 7.22 Stereoselective formation of bicyclic oxetanes in the PB reaction of 1,3-dioxol derivatives.

A completely different product class, a-amido, (3-hydroxy carboxylic acids, can be obtained from the [2+2]-photocycloaddition of aldehydes to 5-methoxyoxazoles and subsequent hydrolysis of the bicyclic oxetanes [3]. Compound 3 is available from the triplet benzaldehyde addition to dimethyl 5-methoxyoxazole in diastereomerically pure (erythro-selective) form. 

Griesbeck and Mattay described photocycloaddition of methyl and ethyl trimethyl pyruvates (25) with di-isopropyl-1,3-dioxol. In contrast to the reaction with ethyl pyruvate, the bicyclic oxetane 26 was formed with very high (>98%) diastereoisomeric excess (Sch. 7) [29]. An X-ray analysis revealed the unusual endo-tert-butyl configuration. Semiempirical calculation indicated that this clearly is the kinetic product formed by a biradical... 

In contrast to the diastereoselectivity of the 2,3-dihydrofuran photocycloaddition, the photocycloaddition of furan with aromatic as well as aliphatic aldehydes proceeded with unusually high exo-diastereo-selectivity to give the bicyclic oxetanes 119 in good yield (Sch. 39) [123]. The diastereoselectivity of reaction of furan with acetaldehyde and benzaldehyde (iexo/endo) were 19 1 and 212 1, respectively. 

A recent synthesis of the tricyclic secoiridoid ( )-sarracenin (98) relied on the Patemo-Biichi addition of acetaldehyde and cyclopentadiene as the initial step. Irradiation of cyclopentadiene and acetaldehyde provided a 5 1 mixture of bicyclic oxetanes (97) and (96) in 5-10% yield. Treatment of the crude photolysate with CSA and methanol followed by tosylation of the cmde product gave (99), which represents the toluenesulfonate ester derived from the major oxetane (97). The tosylate was displaced by the anion prepared from dimethyl 3-styrenylmalonate to afford the substituted malonate (100) in 84% yield (Scheme 10). Attempts to effect ring opening of the oxetane mixture were unsuccessful. Decarboxylation and demethylation gave the alcohol (102) which was subjected to ozonolysis and reductive work-up to afford ( )-sarracenin in 60% yield. The oxetane-based synthesis is noteworthy due to its brevity and use of a biosynthetically postulated trialdehyde equivalent. 

In studies directed towaids the synthesis of the fungal isonitrile antibiotic isonitrin B (103), a cy-clopentanoid metabolite related to trichoviridine (104), various trialkylsilyl enol ethers were irradiated with propionaldehyde to produce equimolar amounts of stereoisomeric bicyclic oxetanes (105). The corresponding silyl dienol ethers, however, gave little oxetane product owing to preferential diene photopolymerization. The use of vinyl epoxide derivatives such as (106), however, offers a possible access to the epoxycyclopentanoid system with simultaneous control of the face selectivity of the photoaddition by the epoxide moiety. 

In addition to the functionalization protocols of Schemes 13 and 14, vinylic substitution reactions involving metalation and palladium-mediated carbon-carbon bond formation have been formulated," which further broaden the variety of stmctural types available from the Patemo-BUchi reaction. For example, deprotection and stannylation of photoaldol (133), followed by refimctionalization of the a-enol ether position of vinylstannane (134), gave the substituted oxetane (135) in good overall yield. Similar functionalization of bicyclic oxetane (136) via exo-face dihydroxylation and acid-catalyzed reorganization of the acetal to the protected 3-deoxy-( )-streptose (137) has been reported, which illustrates the synthetic utility of such processes in the synthesis of polyoxygenated materials." ... 

The stereoselective synthesis of unsaturated oxetanes has recently been achieved by Feigenbaum and coworkers.Previous studies have indicated that photochemical cis-trans isomerization of enals is rapid and results in the formation of equivalent amounts of stereoisomeric alkene adducts. " For example, irradiation of rran.r-crotonaldehyde and 2,6-dimethylfuran produced a 1 1 mixture of alkenic isomers (174) and (175) in 64% yield. Irradiation of 4-trimethylsilylbutyn-2-one and furan provided with S 1 stereoselectivity the bicyclic oxetane (176) in which the methyl group occupies the exo position, presumably because of the small steric requirement of the triple bond. Desilyation of the protected al-kyne produced an alkynic oxetane which was hydrogenated under Lindlar conditions to bicyclic vinyl-oxetane (177) attempts to use the unprotected butyn-2-one gave low isolated yields of oxetane because of extensive polymerization. The stereochemical outcome thus broadens previous alkynyloxetane syn-theses and makes possible the preparation of new oxetane structures that may be synthetically useful. 

In addition to furan, other heterocycles have been examined." Thiophene undergoes efficient photocycloaddition with benzaldehyde to afford a single exo photoproduct (183) in 60% yield. As reported by Jones and coworkers,the photolysis of IV-methylpyrrole in the presence of aldehydes or ketones yields the corresponding 3-hydroxyalkyl derivative (184), even when the reaction mixture is free from any trace of acid. In order to use the pyrrole nucleus for stereoselective alkaloid synthesis (cf. caesalpinine, 185) in the fashion developed with the furan nucleus, pyrrole substituents that stabilize the presumed intermediate bicyclic oxetane must be discovered. 

Campbell and Foldi [64] and Penczek and Vansheidt [65] have prepared and polymerized a number of bicyclic oxetanes. In these compounds the substitution on the 3-carbon of the oxetane ring was in the form of a hydrocarbon ring. Penczek and Vansheidt [65] made some kinetic measurements. Their rate data compared with earlier values are shown in Table 4. They point out that the strain in the second ring has no... 

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