Prins reaction
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[[Image:ThePrinsReaction.png|400px|right|Scheme 1. The Prins reaction]]The '''Prins reaction''' is an [[organic reaction]] consisting of an [[electrophilic addition]] of an [[aldehyde]] or [[ketone]] to an [[alkene]] or [[alkyne]] followed by capture of a [[nucleophile]] <ref>''Condensation of formaldehyde with some unsaturated compounds'' H. J. Prins, Chemisch Weekblad, 16, 64, 1072, 1510 '''1919'''</ref> <ref>[[Chemical Abstracts]] 13, 3155 '''1919'''</ref> <ref>''The Olefin-Aldehyde Condensation. The Prins Reaction''. E. Arundale, L. A. Mikeska [[Chem. Rev.]]; '''1952'''; 51(3); 505-555. [http://pubs.acs.org/cgi-bin/abstract.cgi/chreay/1952/51/i03/f-pdf/f_cr60160a004.pdf Link]</ref>. The outcome of the reaction depends on reaction conditions (''scheme 1''). With water and a protic acid such as [[sulfuric acid]] as the reaction medium and [[formaldehyde]] the reaction product is a [[diol|1,3-diol]]. When water is absent [[Dehydration reaction|dehydration]] takes place to an [[allyl alcohol]]. With an excess of [[formaldehyde]] and a low reaction temperature the reaction product is a [[dioxane]]. When water is replaced by [[acetic acid]] the corresponding [[esters]] are formed.
==History==
The original reactants employed by [[The Netherlands|Dutch]] chemist [[Hendrik Jacobus Prins]] in his 1919 publication were [[styrene]] (''scheme 2''), [[pinene]], [[camphene]], [[eugenol]], [[isosafrole]] and [[anethole]].
[[Image:Styrene Prins reaction.png|300px|center|Scheme 2. The Prins reaction with styrene]]
In 1937 the reaction was investigated as part of a quest for di-olefins to be used in [[synthetic rubber]].
[[Image:Isoprene Prins reaction.png|400px|center|Scheme 3. Isoprene Prins reaction]]
==Reaction mechanism==
The [[reaction mechanism]] for this reaction is depicted in '''scheme 5'''. The [[carbonyl]] reactant ('''2''') is [[protonation|protonated]] by a protic acid and for the resulting [[oxonium ion]] '''3''' two [[resonance structure]]s can be drawn. This [[electrophile]] engages in an [[electrophilic addition]] with the [[alkene]] to the [[carbocation]]ic intermediate '''4'''. Exactly how much positive charge is present on the [[secondary carbon]] atom in this intermediate should be determined for each reaction set. Evidence exists for [[NGP]] of the hydroxyl oxygen or its neighboring carbon atom. When the overall reaction has a high degree of [[concerted reaction|concertedness]], the charge built-up will be modest.[[Image:Prins reaction mechanism.png|600px|center|Scheme 5. Prins reaction mechanism]]
The three reaction modes open to this oxo-[[carbenium]] intermediate are:
* in blue: capture of the carbocation by water or any suitable nucleophile through '''5''' to the 1,3-adduct '''6'''.
* in black: proton abstraction in an [[elimination reaction]] to unsaturated compound '''7'''. When the olefin carries a methylene group, elimination and addition can be concerted with transfer of an allyl proton to the carbonyl group which in effect is an [[ene reaction]] in ''scheme 6''.
[[Image:Carbonyl ene vs Prins reaction.png|center|400px|Scheme 6. Carbonyl-ene reaction versus Prins reaction]]
* in green: capture of the carbocation by additional carbonyl reactant. In this mode the positive charge is dispersed over oxygen and carbon in the resonance structures '''8a''' and '''8b'''. Ring closure leads through intermediate '''9''' to the [[dioxane]] '''10'''. An example is the conversion of [[styrene]] to 4-phenyl-m-dioxane <ref>''4-Phenyl-m-dioxane'' R. L. Shriner and Philip R. Ruby [[Organic Syntheses]], Coll. Vol. 4, p.786 ('''1963'''); Vol. 33, p.72 ('''1953'''). [http://www.orgsynth.org/orgsyn/prep.asp?prep=cv4p0786 Article]</ref>.
* in gray: only in specific reactions and when the carbocation is very stable the reaction takes a shortcut to the [[oxetane]] '''12'''. The photochemical [[Paterno-Büchi reaction]] between alkenes and aldehydes to oxetanes is more straightforward.
==Variations==
Many variations of the Prins reaction exist because it lends itself easily to cyclization reactions and because it is possible to capture the oxo-carbenium ion with a large array of nucleophiles.
The '''halo-Prins reaction''' is one such modification with replacement of protic acids and water by [[lewis acid]]s such as [[stannic chloride]] and [[boron tribromide]]. The [[halogen]] is now the [[nucleophile]] recombining with the carbocation. The cyclization of certain ''allyl pulegones'' in ''scheme 7'' with [[titanium tetrachloride]] in [[dichloromethane]] at -78°C gives access to the [[decalin]] skeleton with the hydroxyl group and chlorine group predominantly in [[cis configuration]] (91% cis) <ref>''Syn- and Anti-Selective Prins Cyclizations of ,-Unsaturated Ketones to 1,3-Halohydrins with Lewis Acids'' R. Brandon Miles, Chad E. Davis, and Robert M. Coates [[J. Org. Chem.]]; '''2006'''; 71(4) pp 1493 - 1501; [http://dx.doi.org/10.1021/jo052142n Abstract]</ref>. This observed cis [[diastereoselectivity]] is due to the intermediate formation of a trichlorotitanium alkoxide making possible an easy delivery of chlorine to the carbocation ion from the same face. The trans isomer is preferred (98% cis) when the switch is made to a [[tin tetrachloride]] reaction at [[room temperature]].
[[Image:Halo-Prins reaction.png|center|500px|Scheme 7. Halo-Prins reaction]]
The '''Prins-pinacol reaction''' is a [[cascade reaction]] of a Prins reaction and a [[pinacol rearrangement]]. The carbonyl group in the reactant in ''scheme 8'' <ref>''Scope and Facial Selectivity of the Prins-Pinacol Synthesis of Attached Rings'' [[Larry E. Overman]] and Emile J. Velthuisen [[J. Org. Chem.]]; '''2006'''; 71(4) pp 1581 - 1587; [http://dx.doi.org/10.1021/jo0522862 Abstract]</ref> is masked as a dimethyl [[acetal]] and the [[hydroxyl]] group is masked as a [[trimethylsilyl|triisopropylsilyl ether]] (TIPS). With lewis acid [[stannic chloride]] the [[oxonium ion]] is activated and the pinacol rearrangement of the resulting Prins intermediate results in ring contraction and referral of the positive charge to the TIPS ether which eventually forms an [[aldehyde]] group in the final product as a mixture of cis and trans isomers with modest diastereoselectivity.
[[Image:Prins pinacol reaction.png|center|400px|Scheme 8. Halo-Prins reaction]]
==Uses==
The Prins reaction is used in [[total synthesis]] for example in that of ''Exiguolide'' <ref>''Total Synthesis of (+)-Exiguolide'' Min Sang Kwon, Sang Kook Woo, Seong Wook Na, and Eun Lee [[Angew. Chem. Int. Ed.]] '''2008''', 47, 1733 –1735 {{DOI|10.1002/anie.200705018}}</ref>:
[[Image:PrinsreactionApplication.svg|center|400px|Prins reaction Kwon 2008]]
==External links==
* Prins reaction in Alkaloid total synthesis [http://www.chemistry.msu.edu/courses/cem852/classics/Chapter26a.pdf Link]
* Prins reaction @ [http://www.organic-chemistry.org/namedreactions/prins-reaction.shtm organic-chemistry.org]
==References==
<div class="references-small"><references /></div>
[[Category:Addition reactions]]
[[Category:Carbon-carbon bond forming reactions]]
[[de:Prins-Reaktion]]
[[Category:Name reactions]]