Ring expansion, acid catalyzed

Since aromatic substitutions, aliphatic substitutions, additions and conjugate additions to carbonyl compounds, cycloadditions, and ring expansion reactions catalyzed by Fe salts have recently been summarized [17], this section will focus on reactions in which iron salts produce a critical activation on unsaturated functional groups provided by the Lewis-acid character of these salts. 

From four-membered rings An acid-catalyzed transformation has been observed in the conversion of l-[l-methylsulfinyl-l-(methylthio)alkyl]cyclo-butanol to 3-methyl-2-(methylthio)cyclopentanone [9]. - Rearrangement of a /3-lactone to a y-lactone derivative in the presence of magnesiumdibromide [10]. - A borontrifluoride catalyzed cyclobutene to cyclopentene rearrangement [11]. - Ring expansion of a [2+2] photoadduct to a five-membered ring [12]-... 

Maltol. Otsuka Chemical Co. in Japan has operated several electroorganic processes on a small commercial scale. It has used plate and frame and aimular cells at currents in the range of 4500—6000 A (133). The process for the synthesis of maltol [118-71 -8], a food additive and flavor enhancer, starts from furfural [98-01-1] (see Food additives Flavors and spices). The electrochemical step is the oxidation of a-methylfurfural to give a cycHc acetal. The remaining reaction sequence is acid-catalyzed ring expansion, epoxidation with hydrogen peroxide, and then acid-catalyzed rearrangement to yield maltol, ie ... 

A number of examples of acid catalyzed ring expansion of acyl and thioacyl azetidines to sbc-membered rings have been reported (B-73MI50903). This type of rearrangement (Scheme 2) is similar to the more general vinylaziridine to pyrroline ring expansion. 

A combination of a Pd-catalyzed nucleophilic substitution by a phenol and a ring expansion was described by Ihara and coworkers [127] using cis- or trans-substituted propynylcyclobutanols 6/l-262a or 6/l-262b. The product ratio depends on the stereochemistry of the cyclobutanols and the acidity of the phenol 6/1-263. Thus, reaction of 6/l-262b with p-methoxyphenol 6/1-263 (X = pOMe) led exclu-... 

Simiraly, alkynones undergo arylative cyclization with arylboronic acids in the presence of a rhodium catalyst (Equation (49)).400 When acetylenic /3-keto esters are employed as shown in Equation (50), arylative cyclization (formation of cyclobutanols) and subsequent, facile acid-catalyzed bond cleavage take place to give <5-keto esters.401 Ring expansions of cyclic [3-keto esters are also possible according to this reaction. 

Cyelobutanone has been prepared by (1) reaction of diazomethane with ketene,4 (2) treatment of methylenecyclobutane with performic acid, followed by cleavage of the resulting glycol with lead tetraacetate,s (3) ozonolysis of methylenecyclobutane, (4) epoxidation of methylene-cyclopropane followed by acid-catalyzed ring expansion,7 and (5) oxidative cleavage of cyclobutane trimethylene thioketal, which in turn is prepared from 2-(co-chloropropyl)-l,3-dithiane.8... 

Sinfelt et al. (120) observed a twofold increase in the -heptane aromatiza-tion rate when the platinum content of their alumina-supported catalyst increased from 0.10 to 0.60%. At the same time, the rate of methylcyclo-pentane ring expansion remained constant. This result also serves as evidence for metal-catalyzed aromatization over dual-function catalysts without the participation of any Cg cyclic intermediate. The cyclization activity of platinum itself was independent of the nature of the support (109). Pure acidic cyclization prevailed with olefin feed (30, 109). 

Special attention has been paid to acid-catalyzed ring expansion. Sterba and Haensel (J19) reported that the rate of benzene formation from methyl-cyclopentane increases with increasing fluorine content of the catalyst (up to 1.0% F with 0.3% Pt on alumina). At the same time, increasing platinum content also promoted this reaction (up to 0.075% Pt with 0.77% F on alumina). This indicates the remarkable cooperative action of a dual function catalyst (119, p. 11). 

Another unusual two-step [3 + 2] cycloaddition involves the ring expansion of tert-bu-tyl-l-vinylcyclopropane-l-carboxylate 148 to the a-ethylidenebutyrolactone 149 (Scheme 14.18) [108]. When the reaction is catalyzed by boron tribromide the monocycHc product 149 is formed, but when the Lewis acidic oxidant VOCl2(OEt) is used, a very unusual dimeric product (150) is formed. 

The common motif shared by non-heme iron oxygenases contains an active site, where two histidines and one carboxylate occupy one face of the Fe(ll) coordination sphere. These enzymes catalyze a variety of oxidative modification of natural products. For example, in the biosynthesis of clavulanic acid, clavaminic acid synthase demonstrates remarkable versatility by catalyzing hydroxylation, oxidative ring formation and desaturation in the presence of a-ketoglutarate (eq. 1 in Scheme 7.22) [80]. The same theme was seen in the biosynthesis of isopenicillin, the key precursor to penicillin G and cephalosporin, from a linear tripeptide proceeded from a NRPS, where non-heme iron oxygenases catalyze radical cyclization and ring expansion (eq. 2 in Scheme 7.22) [81, 82]. 

In work which remains unpublished, Wenkert has succeeded in cleverly transforming 2-methylcyclopentanone into isocomene The key elements of his strategy (Scheme LXXXIII) are the acid-catalyzed ring expansion of methoxycyclopropane 747 to 748 and the regiospecific homologation of the cyclobutanone to 749. Unfortunately, the Wolff-Kishner reduction of this penultimate intermediate affords both 731 and its epimer. 

Cephalexin 7- (D-a-Aminophenylacetamido) cephalosporanic acid Aromatic alkylation, amination, imine formation, amidation (sidechain), fermentation, deamidation (penicillin nucleus), acid-catalyzed ring expansion... 

Preparation by Ring Expansion of Cyclododecanone. Radical addition of allyl alcohol to cyclododecanone, for example, with di-/cr/-butyl peroxide as a radical initiator, yields 2-(7-hydroxypropyl)cyclododecanone. This is converted into 13-oxabicyclo[10.4.0]hexadec-l(12)-ene by acid-catalyzed dehydration [202], Addition of hydrogen peroxide, in the presence of sulfuric acid, gives 12-hydroperoxy-13-oxabicyclo[10.4.0]hexadecane. Cleavage of the peroxide by heating in xylene gives 15-pentadecanolide as well as a small amount of 15-pentadec-l l(and 12)-enolide and 12-hydroxy-15-penta-decanolide [203]. 

The acid-catalyzed ring expansions of tertiary cyclohexylazides to tetrahydroazepines may be viewed as an intramolecular version of the Schmidt reaction and in general proceed in high yield. Unfortunately, the reaction is of little synthetic value as the imines formed are readily hydrolyzed to w-aminoketones in the strong acid media (B-67MI51600). However, the reaction is successful with 9-azido-9-phenylacridone, which on thermolysis or photolysis ring-expands to a mixture of 9-phenyliminoacridone (15-35%) and 6-phenyl-11//-dibenz[6,e]azepin-ll-one (65-85%) (76TL3141). 

Acid-catalyzed ring expansions of related 6-5-4 tricyclic systems are also known. For example, the acetal (257), formed by cycloaddition of keten acetal and 3-ethoxyisoindolone, in hydrochloric acid rearranges to the 2-benzazepine-l,5-dione (258) (75JA7288). 

The oxepins (7 equation 54) and (92 equation 55) resulted from the spontaneous isomerization of their valence tautomeric arene oxide forms which were produced by photorearrangement of 2,3-epoxybicyclo[2.2.0]hex-5-ene (67JA3922) and phenanthrene 9,10-oxide (91) (73CC37) respectively. A rather specific synthetic route to the relatively stable oxepins (180)-(182) was based upon the acid-catalyzed dehydration and ring expansion of 2,6-di-r-butylcyclohexadiene-l,4-diols (Scheme 34) <71AG(E)425,71TL1257). 

The acid-catalyzed ring expansion of a spiroepoxide (equation 58) also yielded only the keto tautomer of a 1-benzoxepin. The enolic form of the oxepin in this example however was stabilized by conversion to the diacetate (194) (69CB205). 

A new method for the synthesis of 2-substituted, as well as 2,4- and 2,5-disubstituted, cyclopentanones in 53-93% yield has been reported.81 For example, the Lewis acid catalyzed transformation of l-propanoyl-l-(4-tolylsulfanyl)cyclobutane gave 2-ethyl-2-(4-tolylsulf-anyl)cyclopentanone (1) in 93 % yield. The formation of the cyclopentanone is best explained by a mechanism which involves initial coordination of aluminum trichloride to the carbonyl oxygen, followed by ring expansion to form the sulfur-stabilized carbocation. Finally, migration of the ethyl group to the carbocation center regenerates concomitantly the carbonyl function.81... 

A similar acid-catalyzed ring expansion was reported for corresponding 0,0-acetals. In this case, however, acetals of eyeIohex-3-enones 2 were formed.5... 

Lewis acid catalyzed ring expansion is found for 2-azabicyclo[3.2.0]heptane-5-carboxylates with an imidate group in the five-membered ring, e.g. 978 which rearranged to give 10.79,80... 

Hydroxymethyltetrahydrofuran is converted into 5,6-dihydrcM-//-pyran and the acid catalyzed rearrangement of other 2-substituted tetrahydrofurans forms 3-hydroxytetrahydropyrans (Scheme 27). Thiepan-4-one results from ring expansion of tetrahydrothiopyran-4-one (Scheme 28). 

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