Preferred Route to Non-aromatic Cyclic Molecules the Baldwin Rules

3 Preferred Route to Non-aromatic Cyclic Molecules the Baldwin Rules 

So often synthetic or medicinal chemists experience that a certain reaction anticipated in analogy to a known example either does not work at all or affords miserable yields, or even unexpected products. The reason for such failures should be investigated concerning the unexpected mechanism of the reaction, usually due to improper reaction conditions. The failure of a certain cyclization reaction, although the disconnection of the selected bond leads to the available acyclic precursor or reagent, is also an often-encountered situation. A systematic analysis and explanation of this issue are offered by J. E. Baldwin, who proposes a series of empiric rules that we wiU discuss in this section. 

The B aldwin rules indicate which cyclizations of acyclic precursors are favored and which are not [6-8]. It is important to note the substantial difference to the Woodward-Hoffimann mles [9-11], based on the theoretical concept staling which reactions are allowed and which are forbidden by the orbital symmetry. The Baldwin rules are based on experimental observations and indicate the relative prrf-erence of the acyclic precursor to form cyclic compounds. Therefore, the expressions favored and disfavored indicate enCTgetically convenient and inconvenient cyclization. These rules refer predominantly to nucleophilic intramolecular reactions where the nucleophile approaches the C atom, which can be tetrahedral (tet, sp ), trigonal (trig, sp ) or diagonal (dig, sp). Based on experimental experience, they provide a particularly important guide for synthetic organic chemists. 

According to the concept of this book, we introduce the Baldwin mles analyzing cyclizations to five- or six-membered heterocyclic rings with the O or N atom, or their failure  

On the other hand, cyclization to TM 7.8 requires the approach of the nucleophile under a small angle, approximately 90°, and the endb-position of the double bond, both stereoelectronically unfavorable. Generally, the Baldwin rules state that cyclization to a five-membered ring is favored when the reacting double bond on the trigonal C-atom is exo and disfavored when it is endo. In Table 7.1, the Baldwin 

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