Cyclobutanones, from oxaspiropentanes

This method for the preparation of cyclobutanone via oxaspiropentane is an adaptation of that described by Salaiin and Conia. The previously known large-scale preparations of cyclobutanone consist of the reaction of the hazardous diazomethane with ketene, the oxidative degradation or the ozonization in presence of pjrridine of methylenecyclobutane prepared from pentaerythritol, or the recently reported dithiane method of Corey and Seebach, which has the disadvantage of producing an aqueous solution of the highly water-soluble cyclobutanone. A procedure involving the solvolytic cyclization of 3-butyn-l-yl trifluoro-methanesulfonate is described in Org. Syn., 54, 84 (1974). 

Table 3. Stereoreversed Cyclobutanone Formation from Oxaspiropentanes...

Strained -oxidoalkyl i enyl selenoxides, such as l-oxido-l-(r-phenylsdenoxyalkyl)cyclopropanes, derived from oxaspiropentanes with tetraalkyl-substituted oxirane rings, and l-(r-hydroxyalkyl)-l-selenoxycyclobutanes, - obtained on oxidation of the corresponding selenides or on reaction of a-li-thioalkyl selenoxides with cyclobutenones, possess a high propensity to rearrange to cyclobutanones... 

Oxaspiropentanes rapidly and efficiently rearrange to cyclobutanones when reacted with Lewis acids.The parent cyclobutanone (73) was obtained in almost quantitative yield from oxaspiropentane by treatment with a catalytic amount of lithium iodide. ... 

A stereoreversed cyclobutanone formation was realized starting from oxaspiropentanes by using the selenoxide function as a leaving group. Treating oxaspiropentanes 94 with sodium benzeneselenolate in ethanol affords j8-hydroxy selenides 95 which, on oxidation with 3-chloro-peroxybenzoic acid at — 78 to — 30 °C, led directly to the corresponding cyclobutanones 96 (Table 3). The stereochemistry in this reaction is opposite to that normally observed in the acid-catalyzed rearrangement of oxaspiropentanes. 

Evidence for the intermediacy of carbenes in these dehalogenations comes from the isolation of (851) when (850) is treated with sodium naphthalene (NaNp), from the formation of cyclobutanones via oxaspiropentanes when gfcm-dihalogenocyclo-propanes are treated with BuLi in the presence of ketones, and from the intramolecular trapping of the carbene by a double bond in an olefinic or allenic dibro-mocyclopropane. 

Seebach has described in detail the alternative preparation of cyclobutanones via oxaspiropentane intermediates/ 1-Bromo-l-lithiocyclopropanes react with ketones or aldehydes to give bromohydrins (259) which are readily converted via oxaspiro-pentanes (260) to cyclobutanones. A variety of examples are described. Overall yields vary somewhat with substitution pattern, but can be as high as 90% in the most favourable cases. A variation of the sequence is the conversion of the dibromocyclo-propane into its 1-bromo-l-thiomethyl derivative before lithiation and reaction with a carbonyl partner. As dibromocyclopropanes are readily available from the addition of dibromocarbene to olefins, this sequence affords a useful method of annelat-ing cyclobutanones to olefins, and is complementary to the Trost secoalkylation procedure. 

The procedure described here is a large-scale preparation with satisfactory yields of a still very expensive but simple compound from very cheap and readily available starting materials and with ordinary laboratory equipment. This rearrangement of oxaspiropentanes into cyclobutanones appears to be general for the preparation of substituted cyclobutanones. ... 

The facility of the rearrangement to cyclobutanones is reflected in the high chemoselectivity. The cases of oxaspiropentanes from epoxyketones offer a particularly difficult challenge. Nevertheless, no problems resulted (Table 2, entries 19, 20, 38 and 39). Oxaspiropentanes which form particularly stabilized carbonium ions frequently rearrange to cyclobutanones during their formation. For example, cyclo-propylmethyl ketone and benzophenone led only to cyclobutanones in their condensations with 9. In one case, further reaction of the ylide with the rearranged cyclobutanone was noted (Eq. 31) 58). 

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 first rearrangement of an oxaspiropentane probably occurred in terpene l39 which was isolated from Zieria smithii and later,40 but mistakenly,41 thought to be chrysanthenone (2), to which it readily rearranges. Interestingly, this rearrangement now constitutes one of the most powerful instruments for the construction of cyclobutanones. 

Formation of CK-configurated cyclobutanones has also been observed with 2-methylcyclopen-tanone and 2-methylcyclohexanone/8 However, stereoreversed eyclobutanone formation can be achieved by opening the intermediate oxaspiropentane with sodium phenyl selenide, oxidation of the resulting / -hydroxy selenide with 3-chloroperoxybenzoic acid and subsequent rearrangement in the presence of pyridine/18 Thus, from one oxaspiropentane 8, either stereoisomeric eyclobutanone cis- or lrans-9 was produced. The stereoreversed eyclobutanone formation proceeds from a stereohomogenous / -hydroxy selenoxide and is thought to be conformationally controlled. 

Bromo-l-lithiocyclopropanes, readily obtained by transmetalation of 1,1-dibromocyclo-propanes with butyllithium in tetrahydrofuran at — 100 CC, undergo addition to aldehydes and ketones forming bromohydrins. On warming, before workup, the adducts from ketones (but not from aldehydes) eliminate lithium bromide and cyclizc to oxaspiropentanes, which may be rearranged to cyclobutanones by treatment with acids (Table 6).76-78... 

Only a few examples exist where diazocyclopropane has been used for annulations via oxa-spiropentanes. 1,3-Bisdiazopropane reacted with cyclohexanone, probably by previous formation of diazocyclopropane, to give spiro[2.6]nonan-4-one (2, 27%) and spiro[3.5]nonan-l-one (1, 10%).82 83 The latter was formed from the corresponding oxaspiropentane.83 Diazocyclopropane, as generated from /V-cyclopropyl-iV-nitrosourea or /V-cyclopropyl-iV-nitrosocarba-mate, behaves similarly. It reacts with cyclobutanone to give spiro[2.4]heptan-4-one (4, 80%) and spiro[3.3]heptan-l-one (3, 7%).84... 

Oxaspiropentanes have been synthesized by the epoxidation of methylenecyclo-propanes with peracetic49), peroxybenzimidic 50), with p-nitroperbenzoic46) and m-chloroperbenzoic acid51). The parent oxaspiropentane 95, a convenient precursor of cyclobutanone 46was obtained from the peracid oxidation of a methylene chloride solution of methylenecyclopropane 94, Eq. (27)46,51). 

Meifaylenecyclopropanes undwgo oxidative ring expansion in a two-step sequence peroxy acid oxidation K> an oxaspiropentane followed by lithium i de induced rearrangement yields a cyclobutanone in moderate yield, as illustrated in equation (49). Cyclobutanone is a minor product from the reaction of... 

The cyclobutanones derived from a,p-epoxyketones present several unique opportunities for further synthetic transformations. The oxaspiropentanes are formed in over 90% yield by the cyclopropylide reaction under the same conditions utilized previously. Rearrangement of the spiroepoxide in the presence of a second epoxide can be carried out with aqueous fluoroboric... 

The oxaspiropentane — cyclobutanone rearrangement has been used to prepare the previously unknown 2-acylcyclobutanones (43) and their mono-acetal derivatives (acetal of side-chain ketone),while a related rearrangement of cyclopropylmethanols (44) provides an entry into 2-vinylcyclobutanones (45). Chiral 2-methylcyclobutanones have been obtained from 1,3-dibromo-propanes by condensation with an optically active TosMIC derivative. ... 

---