Phenol cyclobutenone

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)... 

Disubstituted 4-chloro-2-cyclobutenones 75 undergo the palladium-catalyzed cross-coupling reaction with vinyl- and arylstannanes 76 or vinylzir-conium reagents to give the 4-R sa,-2-cyclobutenones 77. Without isolation, these cyclobutenones 77 are rearranged to the substituted phenols 78 on thermolysis [38], Application of this method to the stannylated heteroaromatics 79 provides a synthetic route to the aromatic benzoheterocycles 80 [39]. (Scheme 27 and 28)... 

Depending on the types of substituents and the precise reaction conditions (l,3-butadien-l-yl)carbene complexes can undergo direct cyclization to yield cyclo-pentadienes [337,350]. As mentioned in Section 2.2.5.1, cyclopentadiene formation occurs particularly easily with aminocarbene complexes [351]. Alternatively, in particular at higher reaction temperatures, CO-insertion can lead to the formation of a vinylketene complex, which, again depending on the electronic properties of the substituents and the reaction conditions, can cyclize to yield cyclobutenones, furans [91,352], cyclopentenones, furanones [91], or phenols (Dotz benzannulation) [207,251,353]. 

Substituted phenols are synthesized by the nickel(0)-catalyzed ring opening of cyclobutenones and subsequent [4+2]cycloaddition with alkynes [106]. 

Andriamiadanarivo, R., Pujol, B., Chantegrel, B., Deshayes, C., and Doutheau, A., Preparation of functionalized cyclobutenones and phenolic compounds from a-diazo P-ketophosphonates, Tetrahedron Lett., 34, 7923, 1993. 

Cobalt complexes of vinylketene by reaction with alkynes in the presence of 2 moles of cyclooctadiene 100°C during 20 hours resulted in moderate yields of phenols (ref. 17). This procedure represents the first synthesis of alkylphenols by the insertion of (fi -indenyl)cobalt(l) into a cyclobutenone, the latter being prepared by analogy with a method for cpCo(PPh3)2. With symmetrical alkynes (R = = Et) the yield was 65%, although with unsymmetrical compounds the... 

The intramolecular ketene-alkene cycloaddition has also been used to prepare highly substituted phenols. As originally formulated, a cyclobutenone such as 342 was converted to a phenol derivative (346). When 342 was heated in benzene, ketene 343 was formed. When done in the presence of an alkyne,281 an in situ [2+21-cycloaddition led to a new cyclobutenone (344) but under the reaction conditions, a four-electron electro-cyclic cleavage reaction occurred to give 345. This compound also reacted, via a six-electron electrocyclic... 

The tungsten carbene complex 408 reacts with phenylacetylene to give the phenol 409, accompanied by the methanol trapping product 410 and the cyclobutenone 41 Cycloaddition of 1,1-dimethylallene to ethyl propiolate affords the cyclobutene 412. ... 

Complexes formed from tantalum(V) chloride or niobium(V) chloride, alkynes and zinc undergo analogous reactions. Mixtures of phenols are obtained from cyclobutenones and alkynes in the presence of nickel(cyclooctadiene)2 at 0°C. Thus 4-methyl-3-phenylcyclobut-2-enone and 4-methylpent-2-yne yield 593 and 594 ". ... 

Reactions between cyclobutenones and alkynes in order to synthesize phenols have also been studied by Danheiser and coworkers [equation 8]. In particular, R = CH3O, CH3S, (CH3)2N and (CH3)3SiO are favourable substituents . The trimethylsilyloxy-substi-tuted alkyne furnishes a trimethylsilylresorcinol from which the trimethylsilyl group is easily removed. A nickel(0)-catalysed version of this synthesis of phenols from cyclobutenones and alkynes was published by Huffman and Liebeskind. ... 

Phenol synthesis. In the presence of this Ni(0) catalyst cyclobutenones can couple with internal alkynes to form phenols in 50-80% yield. Two phenols are obtained from unsymmetrical alkynes with only slight regioselectivity based on the size of the alkyl substituents. Modest selectivity obtains with oxygen-substituted alkynes. 

This phenol synthesis differs from the thermal reaction of cyclobutenones with alkynes (15, 160) in that activated alkynes are not required and the ultimate positions of the alkyne substituents in the phenol are different. 

The keto-enol equilibrium has often been used as a measure of the resonance stabilization for example, no enolization occurs in 3-cyclobutenones (17) and no ketone can be detected in phenol (18). Fluoroglucinol (19) behaves chemically more like a triketone than a triol thus, it readily forms the trioxime (20) with hydroxylamine (Figure 3.10). 

The currently accepted mechanism of the DBR is shown above. The rate-determining step is thought to be loss of a carbon monoxide ligand to form a coordinatively unsaturated intermediate II. This process can be facilitated thermally or photolytically. An alkyne can then coordinate to form 12. The alkyne inserts into the carbene heteroatom bond to give a new chromium carbene 13. At this point there are at least two possible pathways. In the first pathway, carbon monoxide can insert to provide chromium complexed ketene 14, which undergoes electrocyclization to give the hexadienone 15. Tautomerization completes the reaction to provide the phenol 2. Alternatively, metallacycle 16 can form prior to carbon monoxide insertion. Reductive elimination before carbon monoxide insertion leads to pentadiene 5, a commonly observed by-products of the DBR. Cyclopentanones 6, cyclobutenones 7, and indenes have also been observed as by-products in the... 

MOORE Cyclobutenone Rearrangement Thermal rearrangement of alkyl or alkenylcyclobutanones to benzofurans, quinones, phenols. 

Huffman MA, Liebeskind LS (1990) Insertion of (.eta.5-indeny)cobalt(I) into cyclobutenones the first synthesis of phenols from isolated vinylketene complexes. J Am Chem Soc 112... 

Huffman MA, Liebeskind LS (1991) Nickel(0)-catalyzed synthesis of substituted phenols from cyclobutenones and alkynes. J Am Chem Soc 113(7) 2771-2772. doi 10.1021/... 

Huffman MA, Liebeskind LS, Pennington WT (1992) Reaction of cyclobutenones with low-valent metal reagents to form.eta.4- and.eta.2-vinylketene complexes. Reaction ofeta.4-vinylketene complexes with alkynes to form phenols. Organometallics ll(l) 255-266. doi 10.1021/om00037a047... 

Kondo T, Niimi M, Nomura M, Wada K, Mitsudo TA (2007) Rhodium-catalyzed rapid synthesis of substituted phenols from cyclobutenones and alkynes or alkenes via C-C bond cleavage. Tetrahedron Lett 48(16) 2837-2839, http //dx.doi.Org/10.1016/j.tetlet.2007.02.091... 

The thermolysis of phenyl substituted cyclobutenones affords a dienyl ketene 445, which undergoes cyclization and taitomerization to give the phenol derivative 446. ... 

Alkyne insertion was achieved using a nickel(0) catalyst [59]. The cyclobutenone-alkyne coupling reaction provided substituted phenols (Scheme 3.50). Unhke the thermal reaction, unactivated alkynes readily participated in aimulation. Regioselectivity of alkyne insertion was low. 

The rhodium-catalyzed reaction of 2,3-disubstituted cyclobutenone 89 with electron-deficient alkenes dehvered 2,3,6-substituted phenols 90 (Scheme 3.51) [60]. 

Pd(PhCN)2Cl2-catalyzed reaction of 4-chloro-2,3-disubstituted-2-cyclobutenones with aryl or 1-alkenylstannane reagents afforded substituted benzannulated heteroaromatics (eq 19). This process was designed to provide 4-vinylic- (or arylic- or heteroarylic-) cyclobutenones via a palladium catalyzed cross-coupling reaction. The cross-coupled products, in turn, would be transformed to substituted phenols upon thermolysis. 

Highly functionalized phenols 131 starting materials for an indium tri-flate-induced ring closure are available from cyclobutenones 130 which with activated methylene ketones give the acridines 132 (2012JOC5173), Scheme 48. 

---