Cyclobutanone enolates

These compounds, (2) and (3), are of theoretical interest, since they have cyclic 7r-orbital systems, and ab initio MO calculations have been performed to estimate what degree of stabilization may result. This was done by calculating the AE for their formation by an isodesmic reaction with a hypothetical cyclobutanone enol ion (19a,b), which also has a four-membered ring with an allylic system conjugated to an oxygen atom. 

The adducts of 1-arylthiocyclopropyllithium 116 61) to aldehydes and ketones, upon treatment with p-toluenesulfonic acid in refluxing benzene under anhydrous conditions or with the Burgess reagent67), underwent ring expansion to 1 -phenylthiocyclobutenes, which may be hydrolyzed to cyclobutanones, desulfurized to cyclobutanes or thermo-lyzed to dienes. Thus, the cyclopropylcarbinol 233, adduct of 116a to /-butyl methyl ketone, was rearranged to the cyclobutanone enol thioether 234, Eq. (72) 139). 

Clark and coworkers have used a similar process for generation and aldol reactions of a cyclobutanone enolate one example of many is illustrated in equation (22). Direct formation of the enolate in this case gives aldols in low yield. 

Geminal alkylation (4,212-213). The definitive paper on geminal alkylation of ketones via cyclobutanones has been published. The original method involves dibromination of the cyclobutanone and consequently is not suitable for substrates containing isolated double bonds. In this case an alternative approach is available via a-trimethylenedithiocyclobutanones. Direct condensation of trimethylene dithiotosylate (4, 539-540 5, 71) with the cyclobutanone enolate fails, but can be accomplished indirectly by conversion of the cyclobutanone into an enamide by reaction with i-butoxybis(dimethylamino)-methane. The desired dithiane is then obtained by reaction of the enamide and trimethylenedithiotosylate in ethanol buffered with potassium acetate. The sequence is illustrated for 1-tetralone (1). The product (4) obtained in this way... 

NO (pyrimidine) cyclobutanone enolate trimethylenemethane 2,3 -butane dione 2-methylallyl-t/ 2-methylallyl butyraldehyde enolate 2-butanone-3-[Pg.1630]

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

Addition of alkyllithium to cyclobutanones and transmetallation with VO(OEt)Cl2 is considered to give a similar alkoxide intermediates, which are converted to either the y-chloroketones 239 or the olefinic ketone 240 depending on the substituent of cyclobutanones. Deprotonation of the cationic species, formed by further oxidation of the radical intermediate, leads to 240. The oxovanadium compound also induces tandem nucleophilic addition of silyl enol ethers and oxidative ring-opening transformation to produce 6-chloro-l,3-diketones and 2-tetrahydrofurylidene ketones. (Scheme 95)... 

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... 

Functionalised 2,3-dihydro-l,4-dioxins can be synthesised in a three step-sequence from P-keto esters. The key step is the insertion of a Rh-carbenoid derived from an a-diazo-p-keto ester into an 0-H bond of a 13-diol <99H(51)1073>. The reaction of 2-(l,4-dioxenyl)alkanols with silyl enol ethers yields 23-disubstituted 1,4-dioxanes. When 13-bis(trimethylsilyloxy)-cyclobut-l-ene is used, the expected cyclobutanone products are accompanied by a spirocyclopropane derivative <99TL863>. 1,4-Dioxane-monochloroborane 57 is a highly reactive hydroborating reagent <990L315>. 

The synthesis of chiral cyclobutanone 3 involving asymmetric induction in the a-alkylation of the chiral cyclic transition metal acyl enolate derived from 1 has been reported. The resulting aldol product 2 can be demetalated to the cyclobutanone with 100% ee.24... 

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. 

Thermal decomposition of y-lactone tosylhydrazone sodium salts are reported to yield cyclobu-tanones, which can be accounted for by rearrangement of an intermediate oxycarbene. In this manner, the sodium salts of dihydrofuran-2(37/)-one tosylhydrazones 1 were decomposed as a loose powder, at 310 C in a bulb-to-bulb distillation apparatus at an initial pressure of 0.1 Torr, to give the corresponding cyclobutanones 2 in addition to enol ethers, cyclopropanes and open-chain alkenes. Condensable products (74-76%) were collected at — 78 °C, weighed and the ratio of components was determined from their relative GC peak areas.63... 

The enolates of both cyclobutanones and acylcyclobutanes are readily formed and react smoothly with alkyl halides152,159 171,341 or carbonyl groups.92,103,, 04 172 175 However, caution is required to avoid O-alkylation in the former case. For example, dimethylation of 2,2,3,3-tetramethylcyclobutanone with potassium hydride and iodomethane gave 2,2,3,3.4,4-hexamethylcyclobutanone (2) together with l-methoxy-2,3,3,4,4-pentamethylcyclobutene (3) in a 93 6 ratio.159... 

The chemistry of cyclobutanes was remarkably exploited by Oppolzer 42), who reported that the aldol condensation of the acetal (122) with l,2-7ws(trimethylsiloxy)-cyclobutene was catalyzed by BF3 Et20 to afford the cyclobutanone (123), which was refluxed with pTsOH in benzene to give 1,3-cyclopentanedione (124). On treatment with acetylchloride in pyridine at 0 °C, the compound (124) was transformed to the enol acetate (125). Irradiation of (725) gave the intramolecular photoadduct (126). Then on successive treatments with MeMgl, KOH and MsCl in... 

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