Cyclobutenone

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

Recently, the ring enlargement of 4-hydroxy-2-cyclobutenones 5 was promoted by PhI(OAc)2, a popular and accessible hypervalent iodine reagent (99JOC8995). Thus, when 5a-c (R = Me, Bu, Ph) were treated with a slight excess of PhlfOAcja in dichloromethane at room temperature, the 5-acetoxy-3,4-diethoxyfuranones 13... 

The [3S+1C] cycloaddition reaction with Fischer carbene complexes is a very unusual reaction pathway. In fact, only one example has been reported. This process involves the insertion of alkyl-derived chromium carbene complexes into the carbon-carbon a-bond of diphenylcyclopropenone to generate cyclobutenone derivatives [41] (Scheme 13). The mechanism of this transformation involves a CO dissociation followed by oxidative addition into the cyclopropenone carbon-carbon a-bond, affording a metalacyclopentenone derivative which undergoes reductive elimination to produce the final cyclobutenone derivatives. 

Wittig product (57). The methylenecyclobutanes (60) were formed from the same phosphoranes and the methylenecyclopropene (59). The formation of the pyran-2-ones may involve the intermediate cyclobutenones (56) as shown. 

A-pyrrolyM-tri methyl si lyloxy)cyclobutenones and DMAD according to the following sequence (Scheme 93). The monosilylated indolizine-5,8-diols, 353, are the presumed key intermediates <1992TL7811>. 

Strained ring compounds undergo insertion of a low-valence metal complex to give metallacycles and the cycloaddition of metallacycles has a potential in synthesis, as described above. This method is useful in ring transformations of cyclobutenediones and cyclobutenones. 

The cyclobutenone 70 is transformed to the r/4-vinylketene complex 72 with (t/5-indenyl)Co(PPh3)2 71. The vinylketene complex 72 undergoes cyclization with alkynes to produce the corresponding phenols 73. FeCl3 oxidation of the (2-phenylvinyl)ketene complex, however, leads to the naphthol 74. A catalytic synthesis of phenols via the vinylketene intermediates 72 is achieved by the use of Ni(COD)2 as a catalyst [36]. (Scheme 26)... 

The rearrangement of 70 to vinylketenes is thermally possible [37]. A variety of cyclobutenones are prepared by the transition-metal-induced carbon-carbon bond formation, which elevates the synthetic utility of their ring enlargement. 

The coupling reaction of the cyelopropylcuprates 87 with the 4-chloro-cyclobutenones 75 or their ethylene acetals 86 is useful for preparing the 4-cyclopropyl-2-cyclobutenones 88. The ring fission of 88 to the cyclohep-tadienones 89 is performed by a Rh(I)-catalyst. The less substituted cyclopropane ring bond is cleaved selectively. Cyclooctadienones are obtained by using 4-cyclobutyl-2-cyclobutenones [43]. (Scheme 31)... 

There is mechanistic evidence to show that this formal (3 + 3) cycloaddition starts with attack of betaine-C at CI<2 of the three-ring (429) and leads to 2-pyrone formation either by a concerted process (429 — 428) or stepwise via cyclobutenone and 0-acyl vinylketene intermediates (430/431) depending on the leaving group ... 

Alkynyl-3-methoxy-4-hydroxycyclobutenones [31] have also been shown to cleave supercoiled DNA, and DNA damage was believed to be mediated by diradicals (Fig. 9) arising from the thermal decomposition of cyclobutenones at 49 °C. 

The cyclobutenone (359) or the a,p-unsaturated acid chloride (360) could be converted to the vinyl-ketene (361), which reacted readily with 1,3-butadiene (362)... 

Meyers and Novachek described the Stille coupling of a chiral 2-bromooxazoline with a furylstannane to produce furyloxazoline [58]. Liebeskind and Wang conducted a benzannulation of a furylstannane using a Stille coupling with 4-chloro-2-cyclobutenone 62 to elaborate benzofuranol 63 via a dienyl ketene intermediate [59]. 

The Liebeskind group cross-coupled 4-chloro-2-cyclobutenone 69 with 2-tribuylstannyl-benzothiazole to synthesize a-pyridone-based azaheteroaromatics [48], The adduct 70 underwent a thermal rearrangement to afford a transient vinylketene 71, which then intramolecularly cyclized onto the C—N double bond of benzothiazole, giving rise to thiazolo[3,2-a]pyridin-5-one 72. In another case, 2-acetyl-4-trimethylstannylthizaole (73) was coupled with an acid chloride 74 to form the desired ketone 75 [49]. 

Cycloaddition to alkynes, cyclobutenones. This ketene when formed in situ from CCI3COCI and Zn/Cu, reacts with alkynes to form 4,4-dichlorocyclobuten-ones,3 which can rearrange in part to 2,4-dichlorocyclobutenones.4 Both products are reduced to the same cyclobutenone by Zn(Cu) in HOAc/pyridine (4 1) or by zinc and acetic acid/TMEDA.5... 

The same conditions effect dechlorination of 4-alkyl-4-chlorocyclobutenones, but with considerable isomerization to the more stable cyclobutenone. 

An interesting application was described by Liebeskind and Stone, who prepared l-(methoxy-l,2-propandienyl)-2-cyclobuten-l-ols 62 by treatment of cyclobutenones 61 with lithiated methoxyallene 42 (Scheme 8.16) [59]. The authors used these primary adducts in a subsequent acid-catalyzed ring-enlargement providing 5-hydroxy -5 -vinyl- 2 -cyclopenten-1 -ol s. 

The indanols 44 and 45 can only be the products of a formal [4 + 2] cycloaddition23 of the vinylketene complex 42.a with 1-pentyne. Note that upon reaction of 42.b with diethylpropynylamine a formal [2 + 2] cycloaddition65 is seen to take place, yielding the cyclobutenone 47 along with a tricarbonylchromium complex, tentatively identified as 48.66,67 As one would expect, the vinylketene complex 42.b underwent 1,2-additions with pyrrolidine and sodium methoxide in methanol, yielding 49 and 50, respectively. The CO-insertion step leading to vinylketene formation is reversible in some systems,51,68,69 but there is no evidence of this for complex 42.a. Heating a benzene solution of complex 42.a at 80°C under an atmosphere... 

It should be noted that upon reaction with an electron-rich cyclobutenone (R1 = R3 = H, R2 = OEt), the major product formed was a cobaltacyclopen-tenone, which may also be considered to be an 772-vinylketene complex. A similar restructure was isolated after heating 114.a with a large excess of triphenylphosphine, which replaces the ligand site vacated by the central C2 unit. Interestingly, such 772-vinylketene complexes are the expected products from the analogous insertion of rhodium into cyclobutenones (e.g., 7). 

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