Cyclopropane, annulated

Treatment of 1,2-cyclopropane-annulated carbohydrate derivatives with Lewis acid (Scheme 29) is a convenient route to 2-substituted-2,3,6,7-tetrahydrooxepines <1995TL6831, 1997JOC6615>. 

In analogy to the mono-alkylated cyclopropanes annulated cyclopropanes gave methylated cyclic products 10, 11,and 12 upon catalytic hydrogenolysis. 

In a quite interesting but unfortunately also very special reaction the dienophile-directed exo/endo-selectivity was described in connection with cyclopropane annulation [124]. 

This method can be employed to the formation of acyclic and cyclic Ti -dienyl-iumiron complexes. T) -Cycloheptadienyliumiron and n -qrclooctadienyliumiron complex salts are readily available using this procedure starting from T -cycloheptatriene- or (T -cyclooctatriene)iron complexes, respectively. Protonation of tricarbonyl(cyclooctatetraene)iron by noncoordinating acids is known to afford cyclopropane annulated Ti -cycloheptadienyliumiron complexes. This procedure has been exploited for the synthesis of c -2-(2 -carboxycyclopropyl)glycines. ... 

Carson and Kerr in 2009 deployed an intramolecular imine cyclopropane annulation for the total synthesis of the immunosuppressive alkaloid (-)-FR901483 (112, Scheme 41.24), isolated from the fermentation broth of Cladobotryum sp." " The key formal [3+2] cycloaddition was performed by adding the complex cyclopropane gem-diester 108 to a 70°C preheated (to avoid eliminative ringopening of the cyclopropane) dilute solution of excess paraformaldehyde (7 equiv) with a catalytic amount of ytter-bium(lll) triflate (7.5 mol%) in dichloroethane. Pyrrobdine 110 was thus obtained in 67%. It is likely that the mechanism is stepwise opening of the cyclopropane by the nitrogen of the imine 109 followed by intramolecular addition of the formed malonate to the imminium species 111. Finally, monodecarboxylation, Curtius rearrangement, and incorporation of the phosphate moiety provided (-)-FR901483 112. 

A variety of compounds containing a P,y-enone chromophore in a complex molecular framework have been synthesized and their photochemical reactions have been examined. In the majority of the chromophoric systems, the P,y-enone group is part of a bicyclo[2.2.2] octane framework in which the oxa-di-ji-methane reaction is most general and efficient. Mehta and Srikrishna reported an oxa-di-Jt-methane reaction in the tricychc compound 131 and its halo analogue that, upon sensitized irradiation, gave 132. It is interesting to note that [jt -l-Jt ]-cycloaddition was not observed. Similarly, the P,y-enone 133 underwent the ODPM reaction to give the compound 134 with a cyclopropane annulated bicyclo [3.3.0] octane framework, in excellent yield (Scheme 25). ... 

Some years ago we began a program to explore the scope of the palladium-catalyzed annulation of alkenes, dienes and alkynes by functionally-substituted aryl and vinylic halides or triflates as a convenient approach to a wide variety of heterocycles and carbocycles. We subsequently reported annulations involving 1,2-, 1,3- and 1,4-dienes unsaturated cyclopropanes and cyclobutanes cyclic and bicyclic alkenes and alkynes, much of which was reviewed in 1999 (Scheme l).1 In recent days our work has concentrated on the annulation of alkynes. Recent developments in this area will be reviewed and some novel palladium migration processes that have been discovered during the course of this work will be discussed. 

Intramolecular cyclopropanation of [(7 H-benzocycloheptene-7-yl)diazomethyl]-diphenylphosphinoxide 172 represents the first synthesis of a benzo-annulated octavalene (173)180). Not unexpectedly, carbenic rearrangement products 174 and 175 are also formed. 

This wide range of transformations includes many reactions which are one way or another connected with cyclopropane derivatives. The cyclopropane moieties can be part of the structure of both the linear dienes or of annulated polycyclic unsaturated systems as well as being part of a spiro compound. 

The dianions of 1,2-dicarboxylates 13. prepared with LDA from the parent esters, react with dihalomethanes to form annulated cyclopropane derivatives 14101. 

The major direction taken with Fischer carbenes, however, has been annulation reactions (e.g., Eqs. 11-13) rather than cyclopropanation and insertion. Here, the dissociation of carbon monoxide initiates the sequence of events that lead to product (e.g., Eq. 42). °° Alternatively, an unsaturated unit conjugated with the carbene... 

In 1992, Trost and his co-workers investigated desymmetrization of cyclic w j-o-diesters with lithium sulfonyl-methylenenitronate as a nucleophile in the presence of Trost s ligand 118, where the corresponding cyclic compounds are obtained with an excellent enantioselectivity via intramolecular cyclization (Scheme 15),103,103a Asymmetric cyclopropanation and lactone annulation are achieved according to this protocol (Scheme Nitroalkanes can also be employed as carbon-centered nucleophiles in lieu of malonates (Scheme 17). ... 

Takaki reports that ketone enolates add to dimethylstyryl sulfonium perchlorate (155) or methyl styryl sulfone (156) in a Robinson-type annulation sequence to afford the corresponding 3-hydroxythiadecalin (157) or 5-dioxide (158), respectively subsequent reductive desulfonation of (158) affords diene (159).131 However, additions to acceptor (155) suffer from competing cyclopropanation which is dependent on the electrophilicity of the carbonyl group and the ring size of the ketone (Scheme 61). As an aside, DeLucchi reports that l,l-bis(benzenesulfonyl)ethylene (160) adds to ketones at the more substituted a-carbon under neutral conditions in refluxing acetonitrile (equation 18).132... 

In a preliminary study toward the total synthesis of the kopsane alkaloid 140, which may exhibit cholinergic activity, the formal [3 + 2] annulation reaction of 3-alkylindoles with 1,1-cyclopropane diesters was studied in the presence of Yb(OTf)3 either at elevated temperature or at high pressure. For example, N-methyltetrahydrocarbazole (141) with styryl-substituted cyclopropane 142 produced a mixture of diastereomeric adducts 143a and 143b (3 1) in 49% yield at 1.3 GPa for 7 days (Scheme 39) [89]. 

This reaction looks like [3 + 2] annulation with cyclopropane and alkyne derivatives. 

The stereoselectivity of this reaction rises when more bulky nucleophiles are employed (compare entries 7, 3,1, and 5). This is most impressively demonstrated by comparison of the y-lactol reduction with its allylation leading to 205 or 206, respectively (Scheme 10). Formation of tetrahydrofuran derivative 208, dihydrofuran 209, or unsaturated a-methylen-y-butyrolactone 207 illustrate that various modes of straightforward work-up procedures provide two different five membered heterocycles 93 b-96). A second example without the geminal dialkyl substitution at C-3 of the siloxy-cyclopropane depicted in Eq. 86 making available the annulated tetrahydrofuran-3-carboxylate 210 underlines the generality of the C-C-bond forming hydroxyalkylation reaction via ester enolates. 

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