Editing Diels–Alder reaction (section)

===Stereospecificity and stereoselectivity===

Diels–Alder reactions, as concerted cycloadditions, are [[stereospecific]]. Stereochemical information of the diene and the dienophile are retained in the product, as a ''syn'' addition with respect to each component. For example, substituents in a ''cis'' (''trans'', resp.) relationship on the double bond of the dienophile give rise to substituents that are ''cis'' (''trans'', resp.) on those same carbons with respect to the cyclohexene ring. Likewise, ''cis'',''cis''- and ''trans'',''trans''-disubstituted dienes give ''cis'' substituents at these carbons of the product whereas ''cis'',''trans''-disubstituted dienes give ''trans'' substituents:<ref name="KirmseMönch1991">{{cite journal |last1=Kirmse |first1=W. |last2=Mönch |first2=D. |year=1991 |title=Umlagerungen von 1,4,4- und 2,2,5-Trimethylbicyclo[3.2.1]oct-6-yl-Kationen |journal=Chemische Berichte |volume=124 |issue=1 |pages=237–240 |doi=10.1002/cber.19911240136}}</ref><ref>{{cite journal |last1=Bérubé |first1=G. |last2=DesLongchamps |first2=P. |year=1987 |title=Stéréosélection acyclique-1,5: Synthèse de la chaîne latérale optiquement active de la vitamine E |journal=Bulletin de la Société Chimique de France |volume=1 |pages=103–115}}</ref>
[[File:Diels-alder-stereospecificity.png|center|frameless|500x500px]] [[File:Secondary orbitals.png|300x300px|''Endo'' and ''exo'' transition states for cyclopentadiene adding to [[acrolein]]; ''endo''/''exo'' product ratio for this and various other dienophiles|alt=|thumb]]

Diels–Alder reactions in which adjacent stereocenters are generated at the two ends of the newly formed single bonds imply two different possible stereochemical outcomes. This is a [[stereoselective]] situation based on the relative orientation of the two separate components when they react with each other. In the context of the Diels–Alder reaction, the transition state in which the most significant substituent (an electron-withdrawing and/or conjugating group) on the dienophile is oriented towards the diene π system and slips under it as the reaction takes place is known as the ''endo'' transition state.  In the alternative ''exo'' transition state, it is oriented away from it. (There is a more general usage of the terms [[Endo-exo isomerism|''endo'' and ''exo'']] in stereochemical nomenclature.)

In cases where the dienophile has a single electron-withdrawing / conjugating substituent, or two electron-withdrawing / conjugating substituents ''cis'' to each other, the outcome can often be predicted. In these "normal demand" Diels–Alder scenarios, the ''endo'' transition state is typically preferred, despite often being more sterically congested. This preference is known as the '''Alder endo rule'''.  As originally stated by Alder, the transition state that is preferred is the one with a "maximum accumulation of double bonds."  ''Endo'' selectivity is typically higher for rigid dienophiles such as [[maleic anhydride]] and [[benzoquinone]]; for others, such as [[acrylate]]s and [[crotonate]]s, selectivity is not very pronounced.<ref>{{cite journal |last1=Houk |first1=K. N. |last2=Luskus |first2=L. J. |year=1971 |title=Influence of steric interactions on endo stereoselectivity |journal=Journal of the American Chemical Society |volume=93 |issue=18 |pages=4606–4607 |doi=10.1021/ja00747a052}}</ref>
[[File:Endo-TS.png|center|frameless|400x400px|The ''endo'' rule applies when there the electron-withdrawing groups on the dienophile are all on one side.]]The most widely accepted explanation for the origin of this effect is a favorable interaction between the π systems of the dienophile and the diene, an interaction described as a ''secondary orbital effect'', though [[electric dipole|dipolar]] and [[Van der Waals force|van der Waals]] attractions may play a part as well, and solvent can sometimes make a substantial difference in selectivity.<ref name="cb474" /><ref>{{cite journal |last1=Kobuke |first1=Y. |last2=Sugimoto |first2=T. |last3=Furukawa |first3=J. |last4=Fueno |first4=T. |year=1972 |title=Role of attractive interactions in endo–exo stereoselectivities of Diels–Alder reactions |journal=Journal of the American Chemical Society |volume=94 |issue=10 |pages=3633–3635 |doi=10.1021/ja00765a066}}</ref><ref>{{cite journal |last1=Williamson |first1=K. L. |last2=Hsu |first2=Y.-F. L. |year=1970 |title=Stereochemistry of the Diels–Alder reaction. II. Lewis acid catalysis of syn-anti isomerism |journal=Journal of the American Chemical Society |volume=92 |issue=25 |pages=7385–7389 |doi=10.1021/ja00728a022}}</ref> The secondary orbital overlap explanation was first proposed by Woodward and Hoffmann.<ref>{{Cite book|title=The conservation of orbital symmetry|last1=Woodward|first1=R. B.|last2=Hoffmann|first2=R.|isbn=9781483282046|location=Weinheim|oclc=915343522|date = 2013-10-22}}</ref> In this explanation, the orbitals associated with the group in conjugation with the dienophile double-bond overlap with the interior orbitals of the diene, a situation that is possible only for the ''endo'' transition state.  Although the original explanation only invoked the orbital on the atom α to the dienophile double bond, Salem and Houk have subsequently proposed that orbitals on the α and β carbons both participate when molecular geometry allows.<ref>{{Cite journal|last1=Wannere|first1=Chaitanya S.|last2=Paul|first2=Ankan|last3=Herges|first3=Rainer|last4=Houk|first4=K. N.|last5=Schaefer|first5=Henry F.|last6=Schleyer|first6=Paul Von Ragué|date=2007|title=The existence of secondary orbital interactions|journal=Journal of Computational Chemistry|language=en|volume=28|issue=1|pages=344–361|doi=10.1002/jcc.20532|pmid=17109435|s2cid=26096085|issn=1096-987X|doi-access=}}</ref>
[[File:Cyclopentadiene dimerization endo ts.jpg|center|frameless|400x400px]]
Often, as with highly substituted dienes, very bulky dienophiles, or [[reversible reaction]]s (as in the case of [[furan]] as diene), steric effects can override the normal ''endo'' selectivity in favor of the ''exo'' isomer.