Prins reaction

The Prins reaction is an

History

The original reactants employed by Dutch chemist Hendrik Jacobus Prins [de] in his 1919 publication were styrene (scheme 2), pinene, camphene, eugenol, isosafrole and anethole. These procedures have been optimized.^[4]

Hendrik Jacobus Prins discovered two new organic reactions during his doctoral research in the year of 1911–1912. The first one is the addition of polyhalogen compound to olefins and the second reaction is the acid catalyzed addition of aldehydes to olefin compounds. The early studies on Prins reaction are exploratory in nature and did not attract much attention until 1937. The development of petroleum cracking in 1937 increased the production of unsaturated hydrocarbons. As a consequence, commercial availability of lower olefin coupled with an aldehyde produced from oxidation of low boiling paraffin increased the curiosity to study the olefin-aldehyde condensation. Later on, Prins reaction emerged as a powerful C-O and C-C bond forming technique in the synthesis of various molecules in organic synthesis.^[5]

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

Reaction mechanism

The

resonance structures can be drawn. This electrophile engages in an electrophilic addition with the alkene to the carbocationic 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 neighbouring group participation 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.

• 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 alkene 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.^[6]
• in gray: only in specific reactions and when the carbocation is very stable the reaction takes a shortcut to the oxetane 12. The photochemical Paternò–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

The Prins-pinacol reaction is a

The key oxo-carbenium intermediate can be formed by other routes than simple protonation of a carbonyl. In a key step of the synthesis of exiguolide, it was formed by protonation of a

See also

• Heteropoly acid

References