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Baldwin's rulesFrom Wikipedia, the free encyclopedia

Baldwin's rules in organic chemistry are a series ofguidelines outlining the relative favourabilities of ringclosure reactions in alicyclic compounds. They were firstproposed by Jack Baldwin in 1976.[1][2]

Baldwin's rules discuss the relative rates of ring closuresof these various types. These terms are not meant todescribe 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 alternativereaction that is favoured (fast). However, the disfavoured product may beobserved, if no alternate reactions are more favoured.

The rules classify ring closures in three ways:

the number of atoms in the newly formed ringinto exo and endo ring closures, depending whether the bond broken during the ring closure is inside(endo) or outside (exo) the ring that is being formedinto tet, trig and dig geometry of the atom being attacked, depending on whether this electrophilic

carbon is tetrahedral (sp3 hybridised), trigonal (sp2 hybridised) or digonal (sp hybridised).

Thus, a ring closure reaction could be classified as, for example, a 5­exo­trig.

Baldwin discovered that orbital overlap requirements for the formation of bonds favour only certaincombinations of ring size and the exo/endo/dig/trig/tet parameters. Interactive 3D models of several of thesetransition states can be seen here (http://www.chemtube3d.com/Baldwin'sRule­Classes.html) (javarequired).

There are sometimes exceptions to Baldwin's rules. For example, cations often disobey Baldwin's rules, asdo reactions in which a third­row atom is included in the ring.

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Baldwin dis/favoured ring closures3 4 5 6 7

type exo end exo end exo end exo end exo endtet trig dig

The rules apply when the nucleophile can attack the bond in question in an ideal angle. These angles are180° (Walden inversion) for exo­tet reactions, 109° (Bürgi–Dunitz angle) for exo­trig reaction and 120° forendo­dig reactions. Angles for nucleophilic attack on alkynes were reviewed and redefined recently.[3] The"acute angle" of attack postulated by Baldwin was replaced with a trajectory similar to the Bürgi–Dunitzangle.[4]

Contents

1 Applications2 Rules for enolates3 Exceptions4 References

Applications

In one study, seven­membered rings were constructed in a tandem 5­exo­dig addition reaction / Claisenrearrangement:[5]

A 6­endo­dig pattern was observed in an allene ­ alkyne 1,2­addition / Nazarov cyclization tandemcatalysed by a gold compound:[6]

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A 5­endo­dig ring closing reaction was part of a synthesis of (+)­Preussin:[7]

Rules for enolates

Baldwin's rules also apply to aldol cyclizations involving enolates:[8][9]

The rules are the following:[10]

Dis/favored ring closures for enolatesenolendo enolexo

type 3 4 5 6 7 3 4 5 6 7exo­tet exo­trig

Exceptions

These rules are based on empirical evidence and numerous "exceptions" are known.[11][12] [13] Examplesinclude:

cyclisations of cationsreactions involving third­row atoms, such as sulfur

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References

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Categories: Physical organic chemistry Stereochemistry

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1. Baldwin, J. E., Rules for Ring Closure, J. Chem. Soc., Chem. Commun. 1976, 734. doi:10.1039/C39760000734

(https://dx.doi.org/10.1039%2FC39760000734)(Open access)

2. Baldwin, J. E. et al. (1977). "Rules for Ring Closure: Ring Formation by Conjugate Addition of OxygenNucleophiles". J. Org. Chem. 42 (24): 3846. doi:10.1021/jo00444a011(https://dx.doi.org/10.1021%2Fjo00444a011).

3. Gilmore, K.; Alabugin,I. V. Cyclizations of Alkynes: Revisiting Baldwin's Rules for Ring Closure. Chem. Rev.2011. 111, 6513–6556. doi:10.1021/cr200164y (https://dx.doi.org/10.1021%2Fcr200164y)

4. Alabugin, I. Gilmore, K.;Manoharan, M. Rules for Anionic and Radical Ring Closure of Alkynes. J. Am.Chem.Soc. 2011, 133, 12608­12623, doi:10.1021/ja203191f (https://dx.doi.org/10.1021%2Fja203191f)

5. Li, X.; Kyne, R. E.; Ovaska, T. V. Synthesis of Seven­Membered Carbocyclic Rings via a Microwave­AssistedTandem Oxyanionic 5­exo dig Cyclization−Claisen Rearrangement Process, J. Org. Chem., 2007, 72, 6624doi:10.1021/jo0710432 (https://dx.doi.org/10.1021%2Fjo0710432)

6. Guan­You Lin, Chun­Yao Yang, and Rai­Shung Liu. Gold­Catalyzed Synthesis of Bicyclo[4.3.0]nonadieneDerivatives via Tandem 6­endo­dig/Nazarov Cyclization of 1,6­Allenynes J. Org. Chem. 2007, 72, 6753­6757doi:10.1021/jo0707939 (https://dx.doi.org/10.1021%2Fjo0707939)

7. Overhand, Mark; Hecht, Sidney M. (1994). "A Concise Synthesis of the Antifungal Agent (+)­Preussin". TheJournal of Organic Chemistry 59 (17): 4721. doi:10.1021/jo00096a007(https://dx.doi.org/10.1021%2Fjo00096a007).

8. Baldwin, Jack E.; Kruse, Lawrence I. (1977). "Rules for ring closure. Stereoelectronic control in the endocyclicalkylation of ketone enolates". Journal of the Chemical Society, Chemical Communications (7): 233.doi:10.1039/C39770000233 (https://dx.doi.org/10.1039%2FC39770000233).

9. Baldwin, J (1982). "Rules for ring closure: application to intramolecular aldol condensations in polyketonicsubstrates". Tetrahedron 38 (19): 2939. doi:10.1016/0040­4020(82)85023­0(https://dx.doi.org/10.1016%2F0040­4020%2882%2985023­0).

10. M. B. Smith, J. March, March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6th ed.,Wiley­Interscience, 2007, ISBN 978­0­471­72091­1

11. J. Clayden, N. Greeves, S. Warren, Organic Chemistry, 2nd ed., OUP Oxford, 2012, ISBN 978­019927029312. J. E. Baldwin, J. Cutting, W. Dupont, L. Kruse, L. Silberman, R. C. Thomas. J. Chem. Soc., Chem. Commun.,

1976, 736­738. doi:10.1039/C39760000736 (https://dx.doi.org/10.1039%2FC39760000736)13. Finding the right path: Baldwin "Rules for Ring Closure" and stereoelectronic control of cyclizations. Alabugin,

I. V.; Gilmore, K. Chem. Commun., 2013, 49, 11246 – 11250.http://pubs.rsc.org/en/content/articlehtml/2013/cc/c3cc43872d

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