Baldwin's Rules for Ring Closure

The general observation that certain ring sizes are easier to make via a cyclization reflects both the enthalpic stability of the transition state and the entropic probability that the nucleophilic and electrophilic sites will encounter each other with the proper geometric orientation.  A molecular orbital argument is that there must be sufficient spatial interaction between the HOMO (or the specific MO containing the nucleophilic electrons) and the LUMO (or some other low-energy acceptor orbital arising from the breaking bond).  These arguments have been systematized and summarized by Baldwin and coworkers (J. Chem. Soc., Chem. Commun., 1976, 734).

Compare two 5-member ring closures.

The first is a 5-endo-trig closure:

Examining the interaction between oxygen and carbon, we see that the overlap between the electrons on oxygen and the LUMO of the enone is minimal; oxygen lies along the node of the MO.
5endo_trig.pdb	Show the oxygen lone pair Show the LUMO Clear orbitals This ring closure is unsuccessful.

A successful ring closure is a 5-exo-tet closure:

Malonate5.pdb		Show the interacting atomic orbitals Show the actual HOMO Show the C-Br antibonding MO Clear orbitals This ring closure works.

The ease with which the HOMO can overlap the LUMO assists the development of a new C-C bond and speeds the reaction.

The summary of the rules is listed below (X = unfavorable, ! = favorable).

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Last updated: 09/29/2003