Baldwin's rules
Baldwin's Rules in organic chemistry are a series of guidelines outlining the relative favourabilities of ring closure reactions in alicyclic compounds. They were first proposed by Jack Baldwin in 1976. [1][2]
The rules classify ring closures in three ways:
- the number of atoms in new ring formed
- into exo and endo ring closures, depending whether the bond broken during the ring closure is inside (endo) or outside (exo) the ring which is formed
- into tet, trig and dig, depending whether the electrophilic carbon is tetrahedral/sp3 (tet), trigonal/sp2, (trig) or digonal/sp, (dig)
Thus, a ring closure reaction could be classified as, for example, a 5-exo-trig.
Baldwin discovered that orbital overlap requirements for the formation of bonds favour only certain combinations of ring size and the exo/endo/dig/trig/tet parameters.
There are sometimes exceptions to Baldwin's rules. For example, cations often disobey Baldwin's rules, as do reactions in which a second-row atom is included in the ring.
| Baldwin dis/favoured ring closures |
|
3 |
4 |
5 |
6 |
7 |
| type |
exo |
end |
exo |
end |
exo |
end |
exo |
end |
exo |
end |
| tet |
√ |
|
√ |
|
√ |
X |
√ |
X |
√ |
|
| trig |
00 |
X |
√ |
X |
√ |
X |
√ |
√ |
√ |
√ |
| dig |
X |
√ |
X |
√ |
√ |
√ |
√ |
√ |
√ |
√ |
The rules apply when the nucleophile can attack the bond in question in an ideal angle. These angles are 180° for exo-tet reactions, 109° for exo-trig reaction and 120° for endo-dig reactions.
Applications
In one study seven-membered rings were constructed in a tandem 5-exo-dig addition reaction / Claisen rearrangement:[3]
A 6-endo-dig pattern was observed in a allene - alkyne 1,2-addition / Nazarov cyclization tandem catalysed by a gold compound [4]:
A 5-endo-dig ring closing reaction was part of a synthesis of (+)-Preussin [5]
The Baldwin rules also apply to aldol cyclizations involving enolates [6] [7]:
The rules are the following:[8]
| Dis/favored ring closures for enolates |
|
enolendo |
enolexo |
| type |
3 |
4 |
5 |
6 |
7 |
3 |
4 |
5 |
6 |
7 |
| exo-tet |
X |
X |
X |
√ |
√ |
√ |
√ |
√ |
√ |
√ |
| exo-trig |
X |
X |
X |
√ |
√ |
√ |
√ |
√ |
√ |
√ |
References
- ^ Baldwin, J. E., Rules for Ring Closure, J. Chem. Soc., Chem. Commun. 1976, 734. doi:10.1039/C39760000734(Open access)
- ^ Baldwin, J. E., et al., Rules for Ring Closure: Ring Formation by Conjugate Addition of Oxygen Nucleophiles, J. Org. Chem., 1977, 42 (24), 3846. doi:10.1021/jo00444a011
- ^ Li, X.; Kyne, R. E.; Ovaska, T. V. Synthesis of Seven-Membered Carbocyclic Rings via a Microwave-Assisted Tandem Oxyanionic 5-exo dig Cyclization−Claisen Rearrangement Process, J. Org. Chem., 2007, 72, 6624 doi:10.1021/jo0710432
- ^ Guan-You Lin, Chun-Yao Yang, and Rai-Shung Liu. Gold-Catalyzed Synthesis of Bicyclo[4.3.0]nonadiene Derivatives via Tandem 6-endo-dig/Nazarov Cyclization of 1,6-Allenynes J. Org. Chem. 2007, 72, 6753-6757 doi:10.1021/jo0707939
- ^ Overhand, Mark; Hecht, Sidney M. (1994). "A Concise Synthesis of the Antifungal Agent (+)-Preussin". The Journal of Organic Chemistry 59 (17): 4721. doi:10.1021/jo00096a007.
- ^ Baldwin, Jack E.; Kruse, Lawrence I. (1977). "Rules for ring closure. Stereoelectronic control in the endocyclic alkylation of ketone enolates". Journal of the Chemical Society, Chemical Communications (7): 233. doi:10.1039/C39770000233.
- ^ Baldwin, J (1982). "Rules for ring closure: application to intramolecular aldol condensations in polyketonic substrates". Tetrahedron 38 (19): 2939. doi:10.1016/0040-4020(82)85023-0.
- ^ M. B. Smith, J. March, March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6th ed., Wiley-Interscience, 2007, ISBN 978-0-471-72091-1