Cyclobutanones epoxides

Cyclobutanones. Epoxidation < Lewis acid-catalyzed rearrangement utanones are valuable for the synthesi... 

Cyclobutanones. Epoxidation of an allylic methylene cyclopropane is followed by Lewis acid-catalyzed rearrangement of the strained oxaspiranes in situ. Such cyclobutanones are valuable for the synthesis of certain natural products (e.g., aplysin). 

A series of 2-vinyl-3-silyloxybicyclo[3.2.0]heptan-6-ones has also been converted to prostanoid lactones in excellent yield but variable regioselectivity. Some of the best regioselectivity was obtained using H202 in trifluoroethanol (see p. 1097).241 The strained cyclobutanone ring and the relatively unreactive terminal vinyl group favor the desired reaction in preference to alkene epoxidation. 

This chapter begins by classifying the combinations of oxidation/reduction processes with subsequent cationic transformations, though to date the details of only two examples have been published. The first example comprises an asymmetric epoxidation/ring expansion domino process of aryl-substituted cyclopropyl-idenes (e. g., 7-1) to provide chiral cyclobutanones 7-3 via 7-2, which was first described by Fukumoto and coworkers (Scheme 7.1) [2]. 

This procedure was used for the asymmetric total synthesis of the steroid (+)-equilenin (7-7) [3]. Cyclopropylidene derivates 7-4 could be converted into the cyclobutanones 7-5 in good yields by applying an asymmetric epoxidation using the chiral (salen)Mnm complex 7-6 (Scheme 7.2) [4]. It is of interest that the demethoxy-lated substrate 7-4b led to 7-5b with a very high enantiomeric excess of 93%, whereas 7-4a gave 7-5a with only 78% ee. 

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]. 

Reports have appeared claiming that triperoxo vanadates behave as nucleophilic oxidants. In particular, triperoxo vanadium complexes, A[V(02)3]3H20 (A=Na or K), are proposed as efficient oxidants of a,-unsaturated ketones to the corresponding epoxide, benzonitrile to benzamide and benzil to benzoic acid, reactions which are usually carried out with alkaline hydrogen peroxide. Subsequent studies concerning the oxidation of cyclobutanone to 4-hydroxybutanoic acid, carried out with the above-cited triperoxo vanadium compound, in alcohol/water mixtures, clearly indicated that such a complex does not act as nucleophilic oxidant, but only as a source of HOO anion. 

The use of a chiral hydroperoxide as oxidant in the asymmetric Baeyer-Villiger reaction was also described by Aoki and Seebach, who tested the asymmetric induction of their TADOOH hydroperoxide in this kind of reaction98. Besides epoxidation and sulfoxidation, for which they found high enantioselectivities with TADOOH (60), this oxidant is also able to induce high asymmetry in Baeyer-Villiger oxidations of racemic cyclobutanone derivatives in the presence of DBU as a base and LiCl as additive (Scheme 174). The yields and ee values (in parentheses) of ketones and lactones are given in Scheme 174 as... 

For example, 1-donor-substituted cyclopropancmethanols may be efficiently produced by cyclopropanation of suitably substituted enol ethers, by reaction of 1-donor-substituted 1-lithio-cyclopropanes with carbonyl compounds, or by addition of carbon nucleophiles to 1-donor-substituted cyclopropanecarbaldehydes. Oxaspiropentanes, important precursors of cyclobutanones, may as easily be obtained by epoxidation of methylenecyclopropanes, or by reaction of carbonyl compounds with diphenylsulfonium cyclopropanide and l-bromo-1-lithiocyclopropanes, respectively. Moreover, as the stereochemistry of most rearrangements may be efficiently controlled, asymmetric syntheses begin to appear. 

The required oxaspiropentanes are obtained by epoxidation of alkylidenecyelopropanes (A Section 3.2.2.1.), by reacting aldehydes and/or ketones with diphenylsulfonium cyclopropanide (B Section 3.2.2.2.), and by reacting ketones with 1-bromo-l-lithiocyclopropanes (C Section 3.2.2.3.) or diazocyclopropane (D Section 3.2.2.4.). Most widely used is diphenylsulfoni-um cyclopropanide, but for higher than 2,2-disubstituted cyclobutanones the use of alkylidene-cyclopropanes or 1-bromo-l-lithiocyclopropanes may be advantageous. Once formed, oxaspiropentanes rearrange with extreme ease. 

An early report by Crandall,42 that epoxidation of 2,3-diisopropylidene-l-l-dimethylcyclo-propane followed by lithium iodide catalyzed rearrangement of the resulting oxaspiropentane yields 4-isopropylidene-2,2,3,3-tetramethylcyclobutanone (1), marks the beginning of an intense use of alkylidenecyclopropanes for the construction of cyclobutanones. 

However, the low facial selectivity in epoxidations of unsymmetrical alkylidene- and cy-cloalkylidenecyclopropanes can be a serious drawback. Thus, both 2-cyclopropylidenebicy-clo[2.2.1]heptane (10)48 and 10,15-dicyclopropylidenetrispiro[3.1.3.1.3.1.]pentadecan-5-one (U)4<). so produced mixtures of stereoisomeric cyclobutanones on epoxidation and rearrangement of the resulting oxaspiropentanes. 

Tabic 5. Enantioselective Synthesis of 2-Alkyl- and 2-Aryl-2-(hydroxy-methyl)cyclobutanones by Asymmetric Epoxidation and 1,2-Rearrangement of Cyclopropylidene Alcohols55... 

Alternatively, the cyclobutanones can be made by two-step procedures, i.e. osmium(VIII) oxide oxidation to the diol followed by further oxidation either by lead(IV) acetate 85 or sodium periodate,86,87 or epoxidation followed by oxidation with periodic acid,15,63 are reported to yield the ketones. 

Reaction of cyclobutanones with trimethylsulfonium bromide in the presence of a base gave epoxides.65,332 The opposite configuration with respect to the epoxide is achieved65 when using this strategy vs. the epoxidation of the corresponding methylenecyclobutane with a peracid (see Section 5.1.2.2.). 

Irradiation of carbene complexes in CO atmosphere generates the ketene 305 and its [2+2] cycloaddition to alkene gives the cyclobutanone 306 [93], Total synthesis of (+)-cerulenin (310) has been carried out by the formation of cyclobutanone 309 by cycloaddition of 307 to the double bond of 308 as the key reaction without attacking the triple bond. Then cyclobutanone 309 was converted to (+)-cerulenin (310) via regioselective Bayer-Villiger reaction of 309, and side-chain elongation using n-methallylnickel bromide, epoxidation and hydrolysis [94],... 

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). 

Cyciopropanones and cyclobutanones are very reactive, rather like epoxides, because, while the 60 or 90 angle in the ring Is nowhere near the tetrahedral angle [108°), it is nearer 108° than the 120° preferred by the sp2 C of the C=0 group. Conversely, the small ring ketones are resistant to enolization, because that would place two sp2 carbon atoms in the ring. 

The efficiency of this method was demonstrated in a total synthesis of the antibiotic (-r)-tetrahy-drocerulenin 28 (Scheme 8) and (-h)-cerulenin [11]. Irradiation of complex 22 in the presence of the chiral iV-vinyl-oxazolidinone 24, which is easily prepared from the amino carbene complex 23 [12], leads to the cyclobutanone 25 with high diastereoselectivity. Regioselective Baeyer-Villiger oxidation followed by base-induced elimination of the chiral carbamate yields the butenolide 26 in high enantiomeric purity. This is finally converted, using Nozoe s protocol [13], to the target molecule 28 by diastereo-selective epoxidation (- 27) and subsequent aminolysis. 

Cyclobutanones are susceptible to Baeyer-Villiger oxidation. The epoxide (186) cannot be prepared by reacting the ketoalkene (185 equation 67) with MCFBA. Moderate, chemoselective epoxidation has been observed in the reaction of (185 equation 68) with ( -trichloroethylperoxycaib(Miic acid (190) prepared in situ from the triazole (189) and H2O2. ... 

The most famous asymmetric oxidation catalyst, Sharpless-Katsuki complex [Ti(0-iPr)4, t-BuOOH and ester of tartaric acid], used for the asymmetric epoxidation of allylic alcohols can also oxidize prochiral and racemic cyclobutanones 7.25 and 7.27 to enan-tiomerically enriched lactones 7.26 and 7.28, respectively. 

Cyclobutanone. Salaiin and Conia have recently published a convenient synthesis of cyclobutanone, in which the key step involves isomerization of an epoxide with... 

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