Larger Bicyclic Compounds

The first example of a cycloaddition reaction of a multiple bond to a diene was reported in 1917 Surprisingly, it was found that benzal azine adds to 2 equivalents of several unsaturated systems, when offered in excess, to yield bicyclic compounds. This reaction was named "criss-cross" cycloaddition [190], Exploitation of the preparative potential of criss-cross cycloaddition began only in the early 1970s, when hexafluoroacetone azine became available on a larger scale [191,192] The study of this reaction proved to be an impetus tor the development of azine chemistry [183, 193]... 

First of all, the stereochemistry about the cyclobutane in the photoadducts is cis in almost all cases (equations 64-68). There are rare exceptions, but these usually result from systems where the cy-cloalkenone is larger than six members or when the tethering chain can easily accommodate the trans cyclobutane (equations 6 72). " The most noteworthy exception is the recent example reported by Winkler in which dioxolenone (35) produced exclusively the trans cycloadduct (36) which was readily converted to the smallest known inside-outside bicycloalkanone (37). This photoproduct presumably arises from initial cyclization in the chair-like conformation (38) (equation 73). Similarly, (39) has been converted to the carbon skeleton of the naturally occurring inside-outside bicyclic compound ingenol (equation 74). ... 

Similarly, cyclopropane reacts readily with electrophiles such as bromine, whereas cyclobutane and the larger carbocycles are inert. This carries over to the corresponding bicyclic compounds. Bicyclobutane is extraordinarily reactive towards electrophiles, bicyclo[2.1.0]pentane has high reactivity, but bicyclo[2.2.0]hexane is almost inert". This does not correspond to differences in driving force for the reactions, in fact a reverse correlation is found ... 

The intramolecular cyclopropanations of a-diazocarbonyl compounds have been extensively studied and recently reviewed . The reaction is satisfactorily accomplished when the diazo carbon atom is proximal to the double bond in the substrate. Thus, the construction of bicyclo[3.1.0]hexane and bicyclo[4.1.0]heptane skeletons has been achieved by this method, whereas the synthesis of bicyclo[5.1.0]octane or the larger bicyclic systems has usually been difficult (equation 73). Bicyclo[2.1.0]pentan-2-ones expected in the reaction of j8,y-unsaturated diazoketones are generally labile and readily undergo the ring cleavage to give jS,y-unsaturated ketenes. ... 

Ring strain in the smaller bicyclic compounds leads to adducts from the addition of Hg to the carbon atom holding fewer hydrogens " ". For the larger bicyclo[3.1.0]-heptane exclusive attack of Hg at the carbon holding more hydrogen, results in the... 

Turning to bicyclic systems, and a study of reaction with ethoxide, a small increase in the rate of reaction relative to pyridines is found for chloroquinolines at comparable positions. In the bicyclic compounds, quatemisation again greatly increases the rate of nncleophilic substitution, having a larger effect (-10 ) at C-2 than at C-4 (-10 ). °... 

Streitwieser and Holtz have discussed the reactivity patterns of the acyclic and the bicyclic molecules (4,28). They proposed largely on the basis of Bredt s rule that the rate constant for tris(trifluoromethyl)methane should be much larger than the rate constant for the bicyclic compound, X, if carbon-fluorine hyperconjugation were important. The observation that these compounds ex-... 

The Prins reaction of a tenfold or larger excess of formaldehyde with 1-substituted 4-phenyl-l,2,3,6-tetrahydropyridines gives the bicyclic compound (42), 2 which exists in the 0-inside conformation as previous work had suggested should be the case. 

FIGURE 7.30 The tied-back bicyclic compound reacts faster with ethyl iodide than does triethylamine, which is effectively the larger compound. The larger nucleophile has a more diifrcult time in attacking the rear of the carbon-iodine bond in ethyl iodide. 

Bridgehead double bonds can be accommodated in larger ring-bridged bicyclic compounds such as bicyclo[3.2.2]non-l-ene, B. Although this compound has been prepared in the laboratory, it is an extremely reactive alkene. 

The increased basicity of pyrrolizidine (pATa = 11.68) compared with indolizidine (p/sTa = 10.15) and quinolizidine (pAa = 10.19) has been attributed to ring fusion, the basicity of the ra-fused N-bridgehead aza bicycles being larger than that of the frans-fused bases. The basicity of hydroxyindolizidines has been helpful in assigning the conformation of these compounds. 

These recommendations and extension of nomenclature practices to apply to points of attachment outside the ring are basic to the rules for forming the names of the bicyclic radicals. Since the enumeration of the four parent compounds larger than the ring carbon skeletons is fixed, the position number of a point of attachment on radicals derived from them is predetermined and will not always be numbered as 1. For radicals derived from the nor- structures numbered according to the bicyclo plan, preference in assigning low numbers according to accepted practice is in the order point or points of attachment, double bonds, substituents. In the nor- names the position number of a point of attachment also will not always be numbered as 1. 

---