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Baldwin's rules
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<h2 id="applications">Applications</h2> <p>In one study, seven-membered rings were constructed in a <a href="/facts/Tandem_reaction/lWpMYkLM">tandem</a> 5-<i>exo-dig</i> <a href="/facts/Addition_reaction/LvIngK0g">addition reaction</a> / <a href="/facts/Claisen_rearrangement/GJvfAk6h">Claisen rearrangement</a>:<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> </p> <p>A 6-<i>endo-dig</i> pattern was observed in an <a href="/facts/Allene/54hMEu5N">allene</a> - <a href="/facts/Alkyne/VHI4N5Wo">alkyne</a> 1,2-addition / <a href="/facts/Nazarov_cyclization/VC19yzbs">Nazarov cyclization</a> tandem catalysed by a <a href="/facts/Gold/1znknojp">gold</a> compound:<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> </p><p>A 5-<i>endo-dig</i> ring closing reaction was part of a synthesis of (+)-Preussin:<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> </p> <h2 id="rules-for-enolates">Rules for enolates</h2> <p>Baldwin's rules also apply to aldol cyclizations involving <a href="/facts/Enolate/D13WdFNR">enolates</a>.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a><a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> Two new descriptors need to be defined: <i>enolendo</i> and <i>enolexo</i>, which refer to whether both carbons of the enolate C-C fragment are incorporated into the ring formed or not, respectively. </p> <p>The rules are the following:<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> </p> Dis/favored ring closures for enolates<table><tbody><tr><td></td><td colspan="5"><i>enolendo</i></td><td colspan="5"><i>enolexo</i></td></tr><tr><td>type</td><td>3</td><td>4</td><td>5</td><td>6</td><td>7</td><td>3</td><td>4</td><td>5</td><td>6</td><td>7</td></tr><tr><td><i>exo-tet</i></td><td>✗</td><td>✗</td><td>✗</td><td>✓</td><td>✓</td><td>✓</td><td>✓</td><td>✓</td><td>✓</td><td>✓</td></tr><tr><td><i>exo-trig</i></td><td>✗</td><td>✗</td><td>✗</td><td>✓</td><td>✓</td><td>✓</td><td>✓</td><td>✓</td><td>✓</td><td>✓</td></tr></tbody></table> <h2 id="exceptions">Exceptions</h2> <p>These rules are based on empirical evidence and numerous "exceptions" are known.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a><a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> Examples include: </p> <ul><li>cyclisations of <a href="/facts/Cation/wrbwhF3z">cations</a></li> <li>reactions involving third-row atoms, such as <a href="/facts/Sulfur/IK0amTfM">sulfur</a></li> <li>Transition metal catalysis</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Jack E. Baldwin (1976). "Rules for Ring Closure". J. Chem. Soc., Chem. Commun. (18): 734–736. doi:10.1039/C39760000734.(Open access) <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Baldwin, J. E.; et al. (1977). "Rules for Ring Closure: Ring Formation by Conjugate Addition of Oxygen Nucleophiles". J. Org. Chem. 42 (24): 3846. doi:10.1021/jo00444a011. <a href="/wiki/J._Org._Chem." target="_blank">/wiki/J._Org._Chem.</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>The Baldwin Rules: Revised and Extended. Gilmore, K; Mohamed, R. K.; Alabugin, I. V. WIREs: Comput. Mol. Sci. 2016, 6, 487–514. http://wires.wiley.com/WileyCDA/WiresArticle/wisId-WCMS1261.html doi:10.1002/wcms.1261 <a href="http://wires.wiley.com/WileyCDA/WiresArticle/wisId-WCMS1261.html" target="_blank">http://wires.wiley.com/WileyCDA/WiresArticle/wisId-WCMS1261.html</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>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 <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Alabugin, I. Gilmore, K.; Manoharan, M. Rules for Anionic and Radical Ring Closure of Alkynes. J. Am. Chem.Soc. 2011, 133, 12608-12623, doi:10.1021/ja203191f <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>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 <a href="/wiki/J._Org._Chem." target="_blank">/wiki/J._Org._Chem.</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>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 <a href="/wiki/J._Org._Chem." target="_blank">/wiki/J._Org._Chem.</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Overhand, Mark; Hecht, Sidney M. (1994). "A Concise Synthesis of the Antifungal Agent (+)-Preussin". Journal of Organic Chemistry. 59 (17): 4721–4722. doi:10.1021/jo00096a007. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Baldwin, J (1982). "Rules for ring closure: application to intramolecular aldol condensations in polyketonic substrates". Tetrahedron. 38 (19): 2939–2947. doi:10.1016/0040-4020(82)85023-0. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>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 <a href="/wiki/ISBN_(identifier)" target="_blank">/wiki/ISBN_(identifier)</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>J. Clayden, N. Greeves, S. Warren, Organic Chemistry, 2nd ed., OUP Oxford, 2012, ISBN 978-0199270293 <a href="/wiki/ISBN_(identifier)" target="_blank">/wiki/ISBN_(identifier)</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>J. E. Baldwin, J. Cutting, W. Dupont, L. Kruse, L. Silberman, R. C. Thomas. J. Chem. Soc., Chem. Commun., 1976, 736-738. doi:10.1039/C39760000736 <a href="/wiki/J._Chem._Soc.,_Chem._Commun." target="_blank">/wiki/J._Chem._Soc.,_Chem._Commun.</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>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 <a href="http://pubs.rsc.org/en/content/articlehtml/2013/cc/c3cc43872d" target="_blank">http://pubs.rsc.org/en/content/articlehtml/2013/cc/c3cc43872d</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> </ol>