Oxaspiropentanes synthesis

The same epoxide 335 was easily obtained in mild conditions (0°C, 5 min) by m-ehloroperbenzoic acid oxidation [13b]. Epoxidation of alkylidenecyclo-propanes by m-chloroperbenzoie acid has been greatly exploited as a route to the synthesis of cyclobutanones 638 via the well known ring expansion of oxaspiropentanes 637 (Scheme 98) [176,177,8]. 

The direct high yield synthesis of oxaspiropentanes from almost any type of aldehyde or ketone represents a particularly useful transformation because of the high reactivity of such compounds. This approach proves to be exceptionally simple. The DMSO reaction mixture can be directly extracted with pentane or hexane, the hydrocarbon solvent removed and the product isolated by distillation or crystallization. Since diphenyl sulfide is the only by-product extracted with the oxaspiropentane, the mixture can normally be used for most further synthetic transformations. Table 2 summarizes some of the oxaspiropentanes prepared by this method. 

An efficient synthesis of 2-[(phenylalkylmethylene)amino]cyclobutenecar-boxylates 109, 110 from primary Michael adducts 94 has been developed (Scheme 37) [8]. The key step of this dehydrochlorinative rearrangement is believed to be the lithium iodide-induced reorganization of the azaspiropentane intermediate 103, in close analogy to the well documented rearrangement of oxaspiropentanes to cyclobutanones [67]. 

The cyclobutanone ring in the ether 7, derived by ring expansion of an oxaspiropentane, intramolecularly alkylates the activated aromatic system on treatment with PTSA, leading to 2W-cyclobuta[c]chroman-4-ols 8 (X = OH). Subsequent fission of the four-membered ring yields 3,4-disubstituted 2//-chromenes <02SL796>. A variation of this approach allows the synthesis of the 4P-phenylsulfanyl derivative of 8 (X = SPh), oxidation of which affords the cyclopropa[c]chroman entity <02OL2565>. 

Oxaspiropentaaes Oxaspiropentanes (2) were suggested as intermediates in the synthesis of cyclobutanones formulated above. These have now been isolated in about 60-80 % yield by treatment of a carbonyl compound with cyclopropyidiphenylsulfonium fluoroborate (1) and soHd potassium hydroxide at 25° in DMSO followed by flash distillation of the crude extract under vacuum. 

Sulfonium ylides permit the incorporation not only of the methylene group, but of other alkyl groups. The synthesis of oxaspiropentanes has been achieved as shown in Eq. 91. 

These epoxides can be converted to vinyl siloxycyclopropanes m high yield by treatment with base and trimethylsilyl chloride. Transformations of these interesting intermediates (see Section VII) into various products are demonstrated in equation 103. Isolation of oxaspiropentanes is not required in a route to cyclobutanones which are formed by straightforward acid workup (equation 104) . These can either be expanded to y-butyrolactones by oxidation or to an enol ester by a-formylation and acid-induced fragmentation. The latter sequence has been utilized in a synthesis of acorenone... 

The reaction involving P-hydroxyalkyl selenones is by far the less attractive route to epoxides among those cited above due to the difficulties usually encountered in the oxidation step and the easy re-anangement of the p-hydroxyalkyl selenones to carbonyl compounds (Scheme 184, b and c). This meth is, however, particularly useful for the synthesis of oxaspiropentanes > (especially for those bearing a fully alkyl-substituted epoxide ring) from l-seleno-l-(l -hydroxyalkyl)cyclopropanes (Scheme 163, e Scheme 185), which carmot be obtain under other conditions. ... 

Oxaspiropentanes are classified as a unique class of cyclopropyl ethers. Two reaction courses are recognized as being associated with the reaction in the presence of lithium bases. Treatment of oxaspiropentanes with butyllithium leads to S 2-type epoxy ring opening, giving butyl-connected cyclopropanols. On the other hand, with lithium amide as base there is deprotonation at the epoxy carbon followed by epoxide ring opening. The latter reaction offers a useful synthesis of 1-vinylcyclopropanols. ... 

Cyclopropanols and their derivatives (ethers, esters) constitute the most important class of cyclopropanes which undergo this type of ring enlargement. Synthetically useful strategies to cyclobutanones have been devised based upon an efficient synthesis of appropriate cyclopropanols (see Sections 1.A.1.2.1.2. and 1.A.1.2.1.4.) or oxaspiropentanes. 

An elegant and general method for the synthesis of cyclobutanones via oxaspiropentanes 80 involves the nucleophilic addition of various 1-bromocyclopropyllithiums 79 to ketones followed by ring enlargement. In some cases rearrangement takes place spontaneously under the reaction conditions. Addition of mineral acid completes the cyclobutanone 81 formation. Some representative examples are given in Table 1. 

Table 2. Synthesis of Various Oxaspiropentanes and Cyclobutanones Utilizing Cyclopropyldiphenylsulfonium Tetrafluoroborate ...

Cyclobutauones. Trost s original cyclobutanone synthesis (4, 211-214 definitive papers ) by rearrangement of oxaspiropentanes with lithium salts results in selective formation of the cyclobutanone in which the new carbon to carbonyl bond is introduced on the more sterically hindered face of the ketone. He and Scudder have now found that the isomeric cyclobutanone becomes the predominant product if the oxaspiropentane is rearranged through a selenoxide. An example is the rearrangement of 1. When lithium perchlorate is used the cyclobutanone 2 is obtained. On treatment with sodium selenophenolate followed by oxidation, the cyclobutanone 4 becomes the major product. In some cases this new selenoxide route is stereospecific and results in essentially only one cyclobutanone. 

Cyclobutanones.—The synthesis of spirocyclic carbon compounds by various rearrangement methods has recently been reviewed,and this Report covers the recent literature on the synthesis of cyclobutanones via oxaspiropentanes. 

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