Cyclobutanone derivatives

Some other methods to synthesize 1,4-dicarbonyI compounds via cyclopropane or cyclobutanone derivatives are given in sections 1.13.1 and 1.13.2. 

If a bromomethyl- or vinyl-substituted cyclopropane carbon atom bears a hydroxy group, the homoallyiic rearrangement leads preferentially to cyclobutanone derivatives (J. Sa-laun, 1974). Addition of amines to cydopropanone (N. J. Turro, 1966) yields S-lactams after successive treatment with tert-butyl hypochlorite and silver(I) salts (H.H. Wasserman, 1975). For intramolecular cyclopropane formation see section 1.16. 

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]. 

The ambivalent aptitude of sulfur [19] to stabilize adjacent anionic as well as cationic centers is a remarkable fact that has shown to be a reliable feature for the assembly of four-membered ring scaffolds utilizing cyclopropyl phenyl sulfides [20]. Witulski and coworkers treated the sulfide 1-69 with TsOH in wet benzene (Scheme 1.19) [21]. However, in addition to the expected cyclobutanone derivative 1-70, the bicyclo[3.2.0]heptane 1-70 was also obtained as a single diastereoisomer, but in moderate yield. Much better yields of 1-71 were obtained using ketone 1-72... 

Irradiation of as-3,4-H-9-substituted 6-oxo-3,4-dihydro-2//,6//-pyrido[l,2-/d[l,3 thia/ine-4-carboxylates in benzene afforded tricyclic condensed cyclobutanone derivatives, sometimes as a diastereomeric mixture <2000J(P1)4373>. 

Not too many examples of this process exist. Protonation of the vinyl cyclobutanones derived from a,P-unsaturated ketones creates just such a reactive intermediate. 

Diethyl A-(4-hydroxy-4-phenylpiperidin-1 -yl)methylenemalonate did not react with ketene in acetone to give a cyclobutanone derivative (64JMC68). 

New Cyclobutane, Cyclobutene and Cyclobutanone Derivatives derived from the Adduct of Phenylacetylene with l.l-Difluoro-2.2-dichloroethyle-ne. J. Amer. chem. Soc. 75, 4765 (1953)-... 

Another method for the asymmetric version of the Baeyer-Villiger reaction was presented by Lopp and coworkers in 1996 . By employing overstoichiometric quantities of Ti(OPr-t)4/DET/TBHP (1.5 eq./1.8 eq./1.5 eq.), racemic andprochiral cyclobutanones were converted to enantiomerically enriched lactones with ee values up to 75% and moderate conversions up to 40% (Scheme 171). Bolm and Beckmann used a combination of axially chiral C2-symmetric diols of the BINOL type as ligands in the zirconium-mediated Baeyer-Villiger reaction of cyclobutanone derivatives in the presence of TBHP (or CHP) as oxidant (Scheme 172) . With the in situ formed catalysts 233a-d the regioisomeric lactones were produced with moderate asymmetric inductions (6-84%). The main drawback of this method is the need of stoichiometric amounts of zirconium catalyst. 

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... 

Ketcnc equivalents, such as ketene acetals and thioacetals, can be used in cycloadditions to electron-deficient alkenes (see Sections 1.3.2.1. and 1.3.2.2.). In an example of a fumaric acid diester fitted with two chiral alcohol auxiliary groups, the aluminum(III)-catalyzed cycloaddition of 1,1-dimethoxyethene with di-(—)-menthyl fumarate (9) proceeds with > 99% diastereomeric excess. Intermediate 10 can be readily converted to cyclobutanone derivatives.17, 18... 

By virtue of their high stereoselectivity, nucleophilic additions to cyclobutanone derivatives have been utilized to prepare the five-membered rings of prostaglandins with complete control of stereochemistry. This chemistry has been reviewed.65 The conversion of 3-emio-(tert-butyldimethylsiloxy)tricyclo[3.2.0.02,7]heptan-6-one (30) to 7-am7-(3-terf-butyldimethylsiloxy-oct-l-enyl)-5- ,wdy-( rt-butyldimethylsiloxy)bicyclo[2.2.1]heptan-2-one (31) in 88% yield provides a good example.66... 

Formula 366) gives a bicyclic enol ether (Formula 367) which is hydrolyzed to Formula 368 (161,162). The sequence of Formulas 366-368 represents a potentially general synthesis of bicyclic cyclobutanone derivatives. A clever synthesis of m-3-cyclobutene-l,2-dicarboxylic acid anhydride (Formula 369) has been accomplished by irradiation of muconic anhydride (Formula 370) in ether (163). 

The second reports the addition to a cyclobutanone derivative that leads to the formation of a A -pyrazoline derivative.112... 

How can one explain the origin of these products in which one finds, aside from the former carbene ligand and the pyrrolidone, just an additional carbonyl group It seems plausible that the carbene ligand first of all reacts with carbon monoxide to form methoxy (phenyl) ketene. This, in turn, forms with the polarized olefin a cyclobutanone derivative which by ring opening goes over to the observed product (Fig. 6). 

Triple-bond participation has been mainly studied (by Hanack and his school) in reactions of homopropargyl derivatives 31 under solvolytic conditions. In all cases of Table 3, except 1 and 2, compounds 31 yield, besides (and very often instead of) the expected solvolysis products, cyclobutanone derivatives (32) and alkyl cyclopropyl ketones (33). 

The relative yields of cyclized products increase greatly with the decreasing nucleophilicity (2a-c, 3 and 4 of Table 3) and with the increasing ionizing power of the solvent. Cyclobutanone derivatives (32) are usually obtained in much greater amounts than cyclopropyl ketones (33) but, when mercuric ions are added, formation of 33 is overwhelming. The effect of R in 31 on the product distribution is illustrated in cases 3b, 4a, 5a, 6a, and 7. 

A large number of catalysts have been shown to be active in the oxidation of cycloalkanones to lactones using only hydrogen peroxide as the oxidant. Methyl-trioxorhenium (MTO) is moderately active in the oxidation of linear ketones [242] or higher cycloalkanones [243] but it is particularly active in the oxidation of cyclobutanone derivatives (Fig. 4.82), which are oxidized faster with MTO than with other existing methods [244]. 

From this state, ring strain facilitated predissociation to a "biradical-like" transition state [135] or vibrational relaxation (k ) to S may occur. It is also conceivable that transition state [135] could be produced directly from S °. Alternatively, molecules in the S ° state could intersystem cross (kST) to the triplet manifold (T ). For 2-alkylidenecyclobutanones, reactivity is manifested in isomerization about the exocyclic carbon-carbon double bond, while for the saturated cyclobutanone derivatives studied, definitive evidence for solution-phase reactivity is not available. If analogy is again made to the vapor-phase photochemistry of cyclobutanone [21], reactivity could conceivably result in decarbonylated products. Indeed, preliminary evidence has been obtained from sensitization experiments employing m-xylene as triplet sensitizer that decarbonylation of a saturated cyclobutanone is enhanced by selective population of its state (35). ... 

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