- Prins reaction
are formed.
History
The original reactants employed by Dutch chemist
Hendrik Jacobus Prins in his 1919 publication werestyrene ("scheme 2"),pinene ,camphene ,eugenol ,isosafrole andanethole .In 1937 the reaction was investigated as part of a quest for di-olefins to be used in
synthetic rubber .Reaction mechanism
The
reaction mechanism for this reaction is depicted in scheme 5. Thecarbonyl reactant (2) is protonated by a protic acid and for the resultingoxonium ion 3 tworesonance structure s can be drawn. Thiselectrophile engages in anelectrophilic addition with thealkene to thecarbocation ic intermediate 4. Exactly how much positive charge is present on thesecondary carbon atom in this intermediate should be determined for each reaction set. Evidence exists forNGP of the hydroxyl oxygen or its neighboring carbon atom. When the overall reaction has a high degree of concertedness, the charge built-up will be modest.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 anelimination 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 anene reaction in "scheme 6".* 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 ofstyrene to 4-phenyl-m-dioxane ["4-Phenyl-m-dioxane" R. L. Shriner and Philip R. RubyOrganic Syntheses , Coll. Vol. 4, p.786 (1963); Vol. 33, p.72 (1953). [http://www.orgsynth.org/orgsyn/prep.asp?prep=cv4p0786 Article] ] .
* in gray: only in specific reactions and when the carbocation is very stable the reaction takes a shortcut to theoxetane 12. The photochemicalPaterno-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 asstannic chloride andboron tribromide . Thehalogen is now thenucleophile recombining with the carbocation. The cyclization of certain "allyl pulegones" in "scheme 7" withtitanium tetrachloride indichloromethane at -78°C gives access to thedecalin skeleton with the hydroxyl group and chlorine group predominantly incis configuration (91% cis) ["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. CoatesJ. Org. Chem. ; 2006; 71(4) pp 1493 - 1501; [http://dx.doi.org/10.1021/jo052142n Abstract] ] . This observed cisdiastereoselectivity 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 atin tetrachloride reaction atroom temperature .The Prins-pinacol reaction is a
cascade reaction of a Prins reaction and apinacol rearrangement . The carbonyl group in the reactant in "scheme 8" ["Scope and Facial Selectivity of the Prins-Pinacol Synthesis of Attached Rings"Larry E. Overman and Emile J. VelthuisenJ. Org. Chem. ; 2006; 71(4) pp 1581 - 1587; [http://dx.doi.org/10.1021/jo0522862 Abstract] ] is masked as a dimethylacetal and thehydroxyl group is masked as a triisopropylsilyl ether (TIPS). With lewis acidstannic chloride theoxonium 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 analdehyde group in the final product as a mixture of cis and trans isomers with modest diastereoselectivity.Uses
The Prins reaction is used in
total synthesis for example in that of "Exiguolide" ["Total Synthesis of (+)-Exiguolide" Min Sang Kwon, Sang Kook Woo, Seong Wook Na, and Eun LeeAngew. Chem. Int. Ed. 2008, 47, 1733 –1735 DOI|10.1002/anie.200705018] :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
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