Prins reaction

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History

The original reactants employed by Dutch chemist Prins in his 1919 publication were styrene (scheme 2), pinene, camphene, eugenol, isosafrole and anethole.

In 1937 the reaction was investigated as part of a quest for di-olefins to be used in synthetic rubber.

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.

• 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 ^[4].
• 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 acids 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) ^[5]. 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.

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 ^[6] is masked as a dimethyl acetal and the hydroxyl group is masked as a 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.

References

1. ^  Condensation of formaldehyde with some unsaturated compounds H. J. Prins, Chemisch Weekblad, 16, 64, 1072, 1510 1919
2. ^  Chemical Abstracts 13, 3155 1919
3. ^  The Olefin-Aldehyde Condensation. The Prins Reaction. E. Arundale, L. A. Mikeska Chem. Rev.; 1952; 51(3); 505-555. Link
4. ^  4-Phenyl-m-dioxane R. L. Shriner and Philip R. Ruby Organic Syntheses, Coll. Vol. 4, p.786 (1963); Vol. 33, p.72 (1953). Article
5. ^  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; Abstract
6. ^  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; Abstract