Methylene substituted cyclic compounds

However, it may also reflect the greater ease with which the larger ring systems can accommodate the slereoelectronic requirements for ( 5-scission (Section 

Substituents (e.g. CH , Ph) which lend stabilization to the new radical center, or increase strain in the breaking bond, also favor ring-opening (Table 4.5). 

Bailey et al observ ed that ring-opening polymerization of the monomers 

The extent of the second P-scission step depends on the nature of substituents at the 2-position and the reaction conditions (Table 4.6). 

The 2-phenyl-2-alkyl derivatives give 100% ring-opening but still give 100% elimination of the ring-opened product at 120 The 2-phenyl derivative is 

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Stansbury and Bailey. A review by Colombam on addition-fragmentation processes is also relevant. Monomers used in ring-opening are typically vinyl (e.g. vinylcyclopropane - Scheme 4.20 Section 4.4.2.1) or methylene substituted cyclic compounds (e.g. ketene acetals - Section 4.4.2.2) where addition to the double bond is followed by p-scission. 

The desUylation strategy has been used for the cycloaddition of the parent thiocarbonyl yhde la with aldehydes and reactive ketones. The product obtained using A-methyl-3-oxoindolinone as the trapping agent corresponds to the spiro-cyclic compound 125 (168). Thioketene (5)-methylide (127) was reported to react with aromatic aldehydes and some ketones to furnish 2-methylene-substituted 1,3-oxathiolanes (128) (51) (Scheme 5.42). 

Alkylidene-phosphapyrazolines 98-101 are much more thermally stable than their relatives 88, which do not possess the exo-methylene substitution. Dediazo-niation of 98 required heating in toluene at 110°C and gave one or more of the following products, probably via intermediate diphenylmethylene(vinylidene)phos-phoranes methylenephosphiranes, (2-siloxyvinyl)phosphanes, 2//-l,3-oxaphos-pholes, and l-alkylidene-2,3-dihydro-l//-benzo[c]phospholes (169). Thermolysis of 100 ( R = t-Bu, 1-adamantyl) afforded isolable 2-phosphabutadienes (169). The photochemical elimination of N2 from 98 generated cyclic azomethine imine dipoles 104 (Scheme 8.24), which rearrange to compounds 105 and 106 that could be further trapped with DMAD to form 107 (170). 

Several indium-mediated intramolecular carbonyl allylation reactions have been investigated, and it has been found that these reactions provide an easy access to a variety of cyclic compounds. The intramolecular cyclization of 49a-c mediated by indium in aqueous media proceeds smoothly to afford carbocyclic systems containing y-hydroxy-Q -methylene esters 50a-c, which either spontaneously or readily cyclize to give fused o -methylene-y-butyrolactones 51a-c (Scheme 52). The same cyclization of 49d is too slow to compete with the side-reaction, in which the bromide is substituted by a hydroxy group. The ring junction stereochemistry of fused lactones 51 has been found to be cis in all cases. Of the two possible transition states, the one leading to the m-fused compounds is preferred, because the chair-chair conformation is favored over the chair-boat conformation.209... 

Dicyano-substituted triafulvenes react with enamines to produce exclusively the cross-conjugated dicyanomethylene compounds 519, whose formation can be rationalized by a methylene bicyclo(2,l,0)pentane intermediate 51879 296 Since cyclanone enamines 520 and other cyclic enamines 522 react analogously, this C-C-insertion 237) of the triafulvene ring skeleton into the enamine C=C bond represents a versatile ring expansion mode (C + C3), which makes accessible a series of unsaturated medium-ring compounds (521/523) that are otherwise difficult to synthesize. 

The discovery of the ethylidenecarbapenems, the asparenomycins, as naturally occurring /J-lactamase inactivators in the early 1980s was another striking point in /J-lactamase inhibitor research. The substituted exomethylene function in asparenomycins is a distinctive feature of this class of compounds, which many scientists recognized could be a key factor for /J-lactamase inhibition. The exo cyclic methylene is expected to increase the acylation ability, and form an a,/J-unsaturated ester of the active site serine residue as an acyl-enzyme complex. This ester will be similar in structure to the acyl-enzymes formed from clavulanate and sulfone fragmentation, and will be quite resistant to hydrolytic deacylation. Thus, the exocyclic methylene promotes acylation by the enzyme and subsequently represses deacylation. Based on... 

Reaction of 31d-f or 154 with a cyclic active methylene compound such as 5,5-dimethylcyclohexane-l,3-dione (dimedone) gave 299a-d (47-85%), which by subsequent cyclization led to the substituted 1,2,3,4,5,6,7,8-octahy-droxanthenes 300a-d (72-90%) <1999CCC1135>. 

Using this principle, Kibayashi and coworkers [147] have introduced a sequential cyclic carbopalladation-Stille vinylation of enyne compounds. Upon treating the enyne 196 and vinyl tributylstannane with catalytic amounts of Pd2(dba)3 CHCI3 in the presence of AcOH the allyl-substituted methylene cyclopentane 197 was formed in 53% yield (Scheme 80). The subsequent cross-coupling occurs with complete suppression of /M I-climinalion and the Alder-ene product 198 was not detected. Likewise, this sequence was extended to heteroatom-linked enynes and further vinyl tin compounds to provide the heterocyclic analogs 199 in moderate to excellent yields (Scheme 81). 

Preformed iminium salts have been used extensively in organic synthesis. The facility of the condensation is a function of iminium salt substitution. Treatment of formaldehyde-derived methyl(methylene)ammonium halides (or trifluoroacetates) (46) with Grignard and lithium reagents results in the high yield formation of dimethylaminomethyl-containing compounds (47). Subsequent oxidation or alkylation of these products has been employed to generate terminal alkenes (48 Scheme 7). As expected, addition yields are modest for the mote-hindered iminium salts derived frrom other aldehydes and are somewhat lower for those derived from cyclic ketones. ... 

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