Other Ring Contractions

Other Ring-contractions.—Sodium methoxide converts the epoxy-steroid analogue (201) into (202).  

5- trimethylcyclohex-3-enone, 2,5,5-trimethylcycIohex-2-enone, and 3,3-dimethyl-2-( 1 -propeny l)cyclobutanone.  

Treatment of the tribenzocyclo-octane (205) with n-butyl-lithium in HMPA at 80—120°C gives 9-(2-tolyl)fIuorene after aqueous quench. Similarly the bicyclic analogue (206) gave (207).  

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Into Other Ring-Contracted Systems To Furan and Pyrrole Derivatives... 

The other ring contraction involves cleavage of the pjo idine ring under very mild conditions. Diazotization of 3-aminopyridinium salts (R = alkyl, allyl, aryl) gives lH-triazole-4-acraldehyde derivatives. A possible mechanism for the reaction is shown in Scheme 27. 

Other ring contractions that give azapentalene derivatives include the rearrangement of a fused oxazine to a pyrazolo[l,5-a]indol-4-one with acetic anhydride,165 and an interesting photochemical contraction of a cyclic lactone, which produces an isomeric fused indolone by a mechanism thought to involve the first meta photo-Fries rearrangement [Eq. (19)].166 The product was used as an intermediate for the synthesis of mitomycin antibiotics (Section VI,A). 

Several other ring contractions which lead to pyrroles are summarized in the reviews of Patterson (76S281) and Jones and Bean (B-77M130602), but none appear to have the generality or efficiency that would be required to be of broad synthetic applicability. 

Despite the presence of a 4-phenyl group in the 6-methyl derivatives (34d,e,g), they were only converted into the 3,3-dimethyl-2,3-dihydrotriazines (43) no other ring-contracted products were obtained (Equation (1)). 

Hydroxy-6-methyl-2-phenylpyridazin-3(2Fr)-one and 4-hydroxy-5-nitropyridazin-3(2FT)-one rearrange in acidic medium to 3-methyl-l-phenylpyrazole-5-carboxylic acid and 4-nitropyrazole-5-carboxylic acid. 4-Hydroxypyridazin-3(2FT)-ones with a hydroxy group or other group at positions 5 or 6, which is easily replaced in alkaline medium, are transformed into 5-(or 3-)pyrazolones with hot alkali. An interesting example is ring contraction of 5-chloro-4-(methylthio)-l-phenylpyridazin-6(lFT)-one which gives, besides pyrazole derivative (127), 4-hydroxy-5-methylthio-l-phenylpyridazin-6(lFf)-one (128 Scheme 41). 

There are several examples of the formation of pyridazines from other heterocycles, such as azirines, furans, pyrroles, isoxazoles, pyrazoles or pyrans and by ring contraction of 1,2-diazepines. Their formation is mentioned in Section 2.12.6.3.2. 

Ring contraction and intramolecular cyclization constitute a convenient route to ring-fused systems that would be difficult to synthesize in other ways. H- 1,2-Diazepines (538) undergo electrocyclic ring closure to the fused pyrazole system (539) (71CC1022). Azepines also undergo similar valence bond isomerizations. 

Such reductive ring contractions of sulfones are formally similar to two other methods capable of supplanting a sulfur atom by a carbon-carbon double bond the Ramberg-Backlundand Stevens rearrangements. The distinguishing feature of this novel approach to cyclobutenes consists in the resultant higher level of alkyl substitution at the sp -hybridized centers. 

Ring contraction to 3 6 fused, e.g. 17, rather than 4 5 fused ring systems, accompanied by phenylation, occurs on treating l//-azepine-l-carboxylates, e.g. 16. with pailadium(II) acetate in benzene solution.242 In solvents other than benzene, ring-scission products result (see Section... 

If, however, the 7-position is blocked by a methyl group, then a more complex reaction ensues involving ring contraction, methyl migration and loss of the nitrogen function to give 4,6.6-trimethyl-2,3,5-triphenylcyclohexa-2,4-dienone (12% mp 198 C) and other unidentified... 

Into Other Ring Systems Into Heterocycles with Ring Contraction... 

As these results show, 1,2-shift only occurs if there is a substituent on the double bond. In such a case, rearrangement can lead from a bent secondary vinyl cation, 199, to a more stable linear secondary vinyl cation, 200, whereas in the absence of a double-bond substituent, a similar 1,2-alkyl shift would lead to an unstable primary vinyl cation. Interestingly, triflate 205 reacts only by methyl shift and shows no ring-contraction. On the other hand, triflate 206 reacts via... 

More recently, several similar thermal rearrangements of other cyclic sulfoxides involving reversible intramolecular cycloelimination of sulfenic acid have also been reported . A detailed study of this rearrangement which, in certain cases, is accompanied by ring expansion or ring contraction has been performed by Jones and coworkers. These authors found that at 140 °C in xylene, conditions under which acyclic sulfoxides readily decompose , thian 1-oxide (180a) was inert after 6 days. 

Scheme 10.14 gives some other examples of Wolff rearrangement reactions. Entries 1 and 2 are reactions carried out under the classical silver ion catalysis conditions. Entry 3 is an example of a thermolysis. Entries 4 to 7 are ring contractions done under photolytic conditions. Entry 8, done using a silver catalyst, was a step in the synthesis of macbecin, an antitumor antibiotic. Entry 9, a step in the synthesis of a drug candidate, illustrates direct formation of an amide by trapping the ketene intermediate with an amine. 

Formation and characterization of zirconacyclopropanes and zirconacyclopropenes In addition to / -H abstraction of dialkylzirconocenes discussed earlier (Schemes 5 and 6), several other methods are also available for the preparation of three-membered zirconacycles as summarized in Scheme 35. From the viewpoint of cyclic carbozirconation reactions, especially those under Zr-catalyzed conditions, /3-H abstraction, 7t-ligand substitution, and decarbometallative ring contraction are particularly important. As such, these three-membered zirconacycles are generally unstable, but they can be stabilized with phosphines, for example, PMe3, and other bases, and are fully identified. Some of the well-identified examples are shown in Scheme 36.206-209... 

The zeolite structure also plays a large role in RC product distribution. Weitkamp et al.62 conducted experiments with Pt/HZSM-5 catalysts, which have very narrow pore sizes when compared with other zeolites, such as USY or SAPO. They found that c is I trans-1,3-dime thylcyclopentane was formed, while 1,1 and 1,2-DMCP were not. This indicates that the more oval shaped 1,3-DMCP was able to diffuse through the pores, while the more bulky and spherical isomers were not, and thus not seen in the product distribution. In short, when compared with dealkylation to cyclohexane, ring contraction of MCH is a more effective pathway to yield higher ON products. However, in order to further improve the ON, ring-opening of the RC isomers may be necessary, as shown below. 

Triazolotriazepinones 475, obtained by reaction of 4,5-diamino-3-aryloxymethyl-l,2,4-triazoles 474, on heating with acetic anhydride undergo ring contraction reaction to yield l-acetyl-3-aryloxymethyl-6-methyl-pyrazolo[5,l-f][ 1,2,4]triazoles 476 (Scheme 54) <2003IJC(B)2054>. This type of transformation has been previously documented by other authors <1974JHC751>. 

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