Cyclobutanone, preparation

Cyclobutanones Prepared Using Diphenylsulfonium Cyclopropanide Generated with Potassium Hydroxide in Dimethyl Sulfoxide General Procedure 62... 

Cyclobutanone [1191-95-3] M 70.1, b 96-97 , d 0.931, n 1.4189. Treated with dilute aqueous KMn04, dried with molecular sieves and fractionally distd. Purified via the semicarbazone, then regenerated, dried with CaS04, and distd in a spinning-band column. Alternatively, purified by preparative gas chromatography using a Carbowax 20-M column at 80°. (This treatment removes acetone). 

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). 

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. ... 

An attractive synthesis of cyclobutanone (253) has been recently described using 1-isocyano-l-tosylcyclobutane(252)(equation 151)144. l-Isocyano-l-tosylcyclobutanes252 can be prepared from (tosylmethyl)isocyanide and alkyl-substituted 1,3-dibromobutanes. This method appears to be superior to previously reported methods for the preparation of cyclobutanone because of high purity and high yields. 

Cyclopropanes 13 have been prepared from a NHC-rhodium catalysed decarbonylation of cyclobutanones 11 (Scheme 5.4) [6]. The isolated complex 12... 

Cycloadditions of ketenes and alkenes have synthetic utility for the preparation of cyclobutanones.163 The stereoselectivity of ketene-alkene cycloaddition can be analyzed in terms of the Woodward-Hoffmann rules.164 To be an allowed process, the [2ir + 2-tt] cycloaddition must be suprafacial in one component and antarafacial in the other. An alternative description of the TS is a 2irs + (2tts + 2tts) addition.165 Figure 6.13 illustrates these combinations. Note that both representations predict formation of the d.v-substituted cyclobutanone. 

Table 5. Preparation of Cyclopropylcarbinols and Cyclobutanones Using Lithiated Heteratom Substituted Cyclopropanes... 

The ring expansion of cyclobutane derivatives to other carbocycles remains to be one of the most powerful tool in synthetic organic chemistry. Cyclobutanones are exceptionally facile starting materials for the preparations of y-lactones as well as cyclopentanones. 

The preparation of cyclobutanones can easily be realized by using the thermal-[2 + 2]cycloaddition of haloketenes to olefinic compounds (Eq. (2))49). 

Consequently, haloketenes can be readily generated in situ by two most widely used methods (a) the triethylamine dehydrohalogenation of an acyl halide (Eq. (3))50) (b) the dehalogenation of an a-haloacyl halide with activated zin (Eq. (4))51). Since the halogen substituents on the cyclobutanone can be reductively removed by usual procedures, the synthesis of a halocyclobutanone constitutes a formal preparation of the cyclobutanone, the synthetic utility of which is convincingly demonstrated by the following examples. 

The ring opening of certain fused ring cyclobutanones led to the preparation of larger ring system. It was reported 801 that the electrophilic addition of trimethyl-silyl iodide in the presence of catalyst promoted the ring opening of (238) (240) and (242) to afford (239), (241) and (243) respectivly 80). 

Enantioselective [2 + 2 cycloaddition.2 The chiral allylic ether (1), prepared from (lS,2R)-( + )-2-phenylcyclohexanol, undergoes enantioselective cycloaddition with dichloroketene to furnish, after one crystallization, optically pure (-)-2. This cyclobutanone after ring expansion and exposure to chromium(II) perchlorate gives... 

Cyclobutanones (11, 560-561). Ketenimium salts are more reactive than ke-tenes in [2 + 2] cycloadditions with alkenes to prepare cyclobutanones. The salts are readily available by in situ reaction of tertiary amides with triflic anhydride and a base, generally 2,4,6-collidine. The cycloaddition proceeds satisfactorily with alkyl-substituted alkenes and alkynes, but not with enol ethers or enamines.1... 

Several comparative procedures are included. The formation of 1-BENZYLINDOLE and GERANYL CHLORIDE by two different procedures are representative. An interesting comparison of three of the recent adaptations of the Claisen rearrangement on the same substrate is presented in the preparations of N.N-DIMETHYL-5/ -CHOLEST-3-ENE-5-ACETAMIDE, ETHYL-5/S-CHOLEST-3-ENE-5-ACETATE, and 5/9-CHOLEST-3-ENE-5-ACETALDEHYDE. For the utility of the procedure itself as well as for comparison with previously presented syntheses, the preparation and use of triflates in the synthesis of CYCLOBUTANONE is included. 

The best large-scale preparation of cyclobutanone is the reaction of diazomethane with ketene.2 It requires a ketene generator and implies handling of large quantities of the potentially hazardous diazo compound. A more frequently used method for the preparation of cyclobutanone starts from pentaerythritol, the final step being the oxidative degradation of methylenecyclobutane,3,4 which can also be prepared from other precursors.5 A general survey of all methods used to obtain cyclobutanone has been published.6,7... 

This modification of the Curtius reaction has been used extensively in many laboratories and has been found to be generally applicable. Some examples from the literature include the stereoselective synthesis of a wide variety of cyclopropylamine derivatives from the corresponding acids,11-13 the stereoselective preparation of some substituted norbornylamines from easily isomerized acids,14 the preparation of some 1-aminocyelobutancearboxylic acids from the corresponding acid esters,18 the preparation of a substituted cyclobutanone from... 

The Cj - and 54-symmetric tetraesters of tricyclo[3.3.0.0 ]octane (430 and 431) have been prepared by oxidation of diene 429 To access the parent hydrocarbon (435), acid chloride 432 was transformed to the derived ketene which undergoes intramolecular [2+2] cycloaddition The resulting cyclobutanone (433) serves as precursor to perester 434 whose thermal decomposition proceeds with chain transfer in competition with cleavage The unique arrangement of the carbon atoms in 435 is such that the smallest rings are all five-membered. The highly symmetric structure may be viewed as a constrained cisoid bicyclo[3.3.0]octane (as well as the symbol of NATO). 

Isocyano-l-tosylcyclobutane (20) can be prepared in 71 % yield by intermolecular cyclodialkylation of tosylmethyl isocyanide with 1,3-dibromopropane in the presence of sodium hydride.12 Cyclobutane 20 can also serve as an appropriate precursor of cyclobutanone indeed, smooth acid-catalyzed hydrolysis provides cyclobutanone in 84-88% yield.29... 

Ketene thioacetals can also be used as ketene equivalents in the preparation of cyclobutanones and cyclobutanes. Boron trifluoride catalyzes the [2 + 2] cycloaddition of 2-[(l-pyrro-lidinyl)mcthylene]-1,3-dithiane (39) with dimethyl maleate (40).17 Although the cycloadduct is obtained in good yield, stereochemical integrity is not maintained and the thermodynamically most stable isomer predominates. 

Spirocyclic 2-alkylidenecyclobutanones can be prepared from vinylidenecycloalkane additions with dimethylketene (see Tabic 1). Alternatively, cycloaddition of cycloalkylidenemethanone to allenes permits synthesis of spirocyclic cyclobutanones. This latter route is more attractive because of the greater availability of simple allcnes as compared with the alkylidenecycloalka-nes. The in situ generation of cyclohexylidenemethanone in the presence of excess tetramethyl-allcnc produced the spirocyclic ketone 9 in reasonable yield.5... 

Steroids represent rigid chiral systems which are convenient substrates for mechanistic studies of geometric details. Early studies on the difacial selectivity of ketene to steroidal alkene cycloadditions led to the preparation of optically pure cyclobutanones. The addition of dichloroketene to 2- or 3-methyl-5a-cholcst-2-ene (1) generates the cyclobutanones 2 and 3 with regio- and stereoselectivity. The cycloadditions proceed to give the adducts resulting from ketene approach to the a-face.4... 

Ketene itself and simple alkylketenes are inert towards nonactivated alkenes. F or the preparation of cyclobutanones formally derived from ketene or an alkylketene and nonactivated alkenes, the more reactive dichloroketene or alkylchloroketenes can be used. The corresponding a,a-dichloro- or oc-chlorocyclobutanones can readily be dechlorinated by treatment with zinc in acetic acid, or tributyltin hydride in near quantitative yields. F or example cycloaddition of substituted cyclohexene to dichloroketene gave dichlorocyclobutanone 1 which was dechlorinated to 2 with zinc.13,18 Likewise cycloaddition of cycloalkcnes to chloro(methyl)ketene gave 3 which was dechlorinated to 4.14... 

Although this method is commonly used for preparation of the parent cyclobutanone (ketene,/ diazomethane see Houben-Weyl, Yol. 4/4, pp406), the reaction of substituted ketenes with diazomethane gives mixtures of 2- and 3-substituted cyclobutanones with the 3-substituted derivative being formed preferentially. 

Although limited by formation of isomeric mixtures, this method represents the only method for the preparation of simple 2- and 3-silyl- and gcrmyl-substituted cyclobutanones. The [2 + 2] cycloadditions of silyl- and germylketenes with alkenes do not take place readily. 

The homopropargyl rearrangement is of preparative interest for the synthesis of cyclobu-tanone and substituted cyclobutanones (Table 3). For example, the rearrangement of 4-(triflu-oromethanesulfonyloxy)but-l-yne (4) takes place almost quantitatively (76% conversion) in the presence of trifluoroacetic acid and sodium trifluoroacetate to produce cyclobutanone.6... 

---