Seven-membered ring compounds, synthesis

An important application of the potential for bis-alkylation is the use of a dihalide 7 as alkylating agent. This variant allows for the synthesis of cyclic compounds 8 by this route, mainly five- to seven-membered ring compounds have been prepared ... 

Synthesis of simple seven-membered ring compounds labelled with tritium... 

Due to the plethora of bicyclo[5.3.0]ring systems in natural products and the limited number of efficient methods that facilitate the construction of seven-membered rings the synthesis of bicyclo[5.3.0]compounds based on a PK reaction has recently been a subject of intense interest. Generally, the preparation of larger ring systems [n.3.0] (n>4) has proven challenging with traditional PK reaction catalysts. One of the few examples reported is the Co2(CO)g catalyzed formation of the azabicyclo[5.3.0j-decenonone derivative 15 (X = OTBS) from the conformationally restricted substrate 14... 

The intramolecular cyclization of a nitro group with a triple bond has been extended to the synthesis of six- and seven-membered ring compounds analogous to isatogens. Thus, the reaction of the acetylene group with the nitro group in 39 yields 2-phenyl-3-oxobenzo[prepared from the corresponding biphenyl derivative.19... 

Another example is compound 214, which imitates the trombin-bound structure of the fibrin peptide A, and is an inhibitor of this protease. The first step of this synthesis, Scheme 63, involves opening of 208 to the seven-membered ring compound 209. Subsequent acylation with 210 to form 211 is followed by an intramolecular oxidative cycloaddition to provide tricyclic lactam 212. Nucleophilic ring opening proceeds readily with glycine methyl ester to afford lactam 213 in 88% yield, which was transformed into 214 using solid-phase protocols [161]. 

Irradiation of tetramethylcyclobutanedione (16) in furan gives an 8-oxabicyclo[3.2.1]oct-6-en-3-one derivative via oxyallyl cation (17). This reaction is the first example of the cycloaddition of cyclopropanones. Although the syntheses of a few seven-membered ring compounds have been subsequently carried out by means of this photoreaction, interest in cyclopropanone chemistry has been directed to structure and reactivity relationships, but not to organic synthesis. ... 

Syntheses and uses of isotopically labelled dienes and polyenes 821 2. Synthesis of simple seven-membered ring compounds labelled with tritium... 

In the presence ofnickel(O) catalysts, ethyl cyclopropylideneacetate participated in [3+2+2], [4+3], and [4+3+2] annulation to furnish medium-sized carbocy-cles (Table 2.5) [116]. Synthesis of seven-membered ring compounds by formal o-bond metathesis between the MCP and four-membered ring compounds was also achieved [117]. 

Monocyclic carbasugars. The 1,3-dipolar cycloaddition was used in the synthesis of polyhydroxylated compound with the seven-membered ring (Fig. 16).29... 

The Mannich reaction consists on the condensation of a CH-activated compound with a primary or a secondary amine and a non-enolizable aldehyde or ketone to afford p-aminocarbonyl derivatives known as Mannich bases (Scheme 20). This sequence is of great use for the constmction of heterocyclic targets, as illustrated for example by the Robinson-Schopf synthesis of tropinone in 1937 or by the preparation of some azabicyclo[3.3.1]nonanones or pyranocoumarine derivatives (Fig. 1) [100]. In the following, representative recent examples of the formation of five- to seven-membered ring heterocycles will be presented. 

The enthalpy of fomation of two such species has been measured, namely the cyclopropane and cycloheptane derivatives. The difference between the values for these two species, both as solids, is 238.1 kJmol . Is this difference plausible Consider the difference between the enthalpies of formation of the parent cycloalkanes as solids, 194 kJ mol . The ca 44 kJ mol discrepancy between these two differences seems rather large. However, there are idiosyncracies associated with the enthalpies of formation of compounds with three-membered rings and almost nothing is known at all about the thermochemistry of compounds with seven-membered rings. Rather, we merely note that a seemingly well-defined synthesis of cycloheptyl methyl ketone was shown later to result in a mixture of methyl methylcyclohexyl ketones, and superelectrophilic carbonylation of cycloheptane resulted in the same products as methylcyclohexane, namely esters of 1-methylcyclohexanecarboxylic acid. The difference between the enthalpies of formation of the unsubstituted alicyclic hydrocarbons cycloheptane and methylcyclohexane as solids is 33 kJmol . This alternative structural assignment hereby corrects for most of the above 44 kJ mol discrepancy in the enthalpies of formation of the two oximes. More thermochemical measurements are needed, of oximes and cycloheptanes alike. 

Quite recently, we have described the seven-membered ring y-turn mimetic 25f45l (Scheme 16) designed to mimic a proposed bioactive conformation in the cyclic pentapeptide mal-formin family. The synthesis is depicted in Scheme 17. The compounds were tested in a relevant bioassay, but were devoid of activity. 

The chemistry of seven-membered rings with three heteroatoms 1,2,4 has improved since CHEC(1984) was published. In the first volume, these compounds were included in Chapter 6.08 devoted to seven-membered rings with two or more heteroatoms and only few references on synthesis were reported. In CHEC-II(1996), a single chapter for these compounds mainly covered new synthetic methods, spectroscopy, and reactivity, but still there was a lack of activity reports. 

---