Baldwin's rules in organic chemistry are a series of guidelines outlining the relative favorabilities of ring closure reactions in alicyclic compounds. They were first proposed by Jack Baldwin in 1976.
Baldwin's rules discuss the relative rates of ring closures of these various types. These terms are not meant to describe the absolute probability that a reaction will or will not take place, rather they are used in a relative sense. A reaction that is disfavoured (slow) does not have a rate that is able to compete effectively with an alternative reaction that is favoured (fast). However, the disfavoured product may be observed, if no alternate reactions are more favoured.
The rules classify ring closures in three ways:
Thus, a ring closure reaction could be classified as, for example, a 5-exo-trig.
There are sometimes exceptions to Baldwin's rules. For example, cations often disobey Baldwin's rules, as do reactions in which a third-row atom is included in the ring. An expanded and revised version of the rules is available:
The rules apply when the nucleophile can attack the bond in question in an ideal angle. These angles are 180° (Walden inversion) for exo-tet reactions, 109° (Bürgi–Dunitz angle) for exo-trig reaction and 120° for endo-dig reactions. Angles for nucleophilic attack on alkynes were reviewed and redefined recently. The "acute angle" of attack postulated by Baldwin was replaced with a trajectory similar to the Bürgi–Dunitz angle.
A 5-endo-dig ring closing reaction was part of a synthesis of (+)-Preussin:
Baldwin's rules also apply to aldol cyclizations involving enolates. Two new descriptors need to be defined: enolendo and enolexo, which refer to whether both carbons of the enolate C-C fragment are incorporated into the ring formed or not, respectively.
The rules are the following: