Corey s rules

It is apparent that Corey s rule requires modification when strong steric opposition to axial attack exists. In an attempt to unify the conflicting views, Valls has suggested that Corey s principle of preferred axial attack, which ensures maximum overlap, be extended. 

Finally, bridged polycyclic systems containing heteroatoms should be menctioned and they are treated in the next chapter, as an appendix to Corey s rules for the selection of "strategic bonds" (see 7.2.2). 

Application of Corey s rules to polycyclic fused ring structures. The dual graph procedure... 

Another alternative approach to the Corey s rules for the selection of "strategic bonds" are the "complexity indices" based on the mathematical model proposed by Bertz [23] which allow the "quantification" of the molecular complexity and to determine whether a given disconnection is indeed simplifying and how much so. The indices predict "strategic bonds" quite well, with the exception of those which are "core bonds" since the limitations imposed by Corey s rule number 4 do not apply here. 

Notice that "stereoselectivity" means "order" and order means "negative entropy" which, in turn, means "rigidity", "lack of flexibility" or "absence of degrees of freedom". It is always easier to exert stereochemical control in rigid monocyclic or polycyclic systems than in the more flexible open-chain compounds (remember the limitations imposed by Corey s rule number 6 see 7.2.1). 

Corey s rules number 2 and 3. Nevertheless, the synthesis is highly efficient and proceeds in only five steps. 

The synthesis of twistane involving an intermediate of type D was reported in 1976 by Hamon and Young [2]. This synthetic approach constitutes a violation of Corey s rule number 4 (which refers to "perimeter" and "core bonds") and involves a bicyclo[3.3.1]nonane precursor in which the relative configuration of the C(6) side-chain is crucial if cyclisation is to occur. The cost of such a "violation" was relatively high and a great number of drawbacks are found in the original article. 

When the first picrotoxane syntheses were published Corey s rules for S3mthesis planning and the Woodward-Hojfmann rules had just become common knowledge as well as the necessity to prepare physiologically active products in an enan-tiomerically pure form. 

The same "heuristic principles" which are applied to carbocyclic compounds also hold true for simple heterocyclic compounds containing one heteroatom. However, in the case of bridged heterocyclic molecules a modified strategic bond selection must be applied. Besides the strategic bonds which meet Corey s six rules, the bonds directly attached to nucleophilic heteroatoms -such as O, S and N-are also strategic Cf. heuristic principle HP-7), provided that they satisfy rules 2B, 4, 5 and 6. For instance, in compound 31a besides the five strategic bonds determined by rules 1-6 (cf. compound 26), the sixth darkened C-N bond in 31b is also a strategic bond. 

Corey-Winter olefin synthesis (I. I23.3-I234). Chong and Wiseman were able to demonstrate the transient existence of bicyclo[3.2.l]octenc-l (2, a bridgehead alkene which violates Bredt s rule) by application of the Corey-Winter olefin synthesis. Thus treatment of the thionocarbonatc (I) with triethyl phosphite at reflux (165°) fur 24 hr. in the presence of I,3-diphenyli obenzofurane (1, 342-343 2, 178-179) leads to the formation of two Diels-Alder adducts (3) and (4) derived from (2). 

Corey s analysis to) of polycyclic systems and strategic bond disconnections directed by maximizing simplification of intermediates is an example of the definition of new heuristics for skeletal dissection ( 6). This analysis directs the selection of particular bonds for construction. His rules also derive in part from stereochemical considerations ( 7). A further treatment of rules for bond selection via stereochemistry would be valuable. 

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