Prins Reaction

The Prins Reaction is the acid-catalyzed addition of aldehydes to alkenes, and gives different products depending on the reaction conditions. It can be thought of conceptually as the addition of the elements of the gem-diol carbonyl hydrate of the aldehyde across the double bond.

An excess of aldehyde and temperatures < 70 °C lead to the formation of acetals. When one equivalent of aldehyde is used and temperatures are > 70 °C diols or allylic alcohols may be isolated.

Although the mechanism is different, a Prins allylic alcohol product is equivalent to the result of an Ene Reaction.

---

Mechanism of the Prins Reaction

Recent Literature

The Catalytic Asymmetric Intermolecular Prins Reaction
C. D. Díaz-Oviedo, R. Maji, B. List, J. Am. Chem. Soc., 2021, 143, 20598-20604.

The 'Aqueous' Prins Cyclization: A Diastereoselective Synthesis of 4-Hydroxytetrahydropyran Derivatives
J. S. Yadav, B. V. S. Reddy, G. G. K. S. N. Kumar, S. Aravind, Synthesis, 2008, 395-400.

Rhenium(VII) Catalysis of Prins Cyclization Reactions
K. Tadpetch, S. D. Rychnovsky, Org. Lett., 2008, 10, 4839-4842.

Diastereoselective Synthesis of Polysubstituted Tetrahydropyrans and Thiacyclohexanes via Indium Trichloride Mediated Cyclizations
X.-F. Yang, J. T. Mague, C.-J. Li, J. Org. Chem., 2001, 66, 739-747.

Lewis Acidic Chloroaluminate Ionic Liquids: Novel Reaction Media for the Synthesis of 4-Chloropyrans
J. S. Yadav, B. V. S. Reddy, M. S. Reddy, N. Niranjan, A. R. Prasad, Eur. J. Org. Chem., 2003, 1779-1783.

Rapid and Efficient Protocol for the Synthesis of 4-Chlorotetrahydropyrans Using Niobium(V) Chloride
J. S. Yadav, B. V. Subba Reddy, M. K. Gupta, S. K. Biswas, Synthesis, 2004, 2711-2715.

Selective Prins Reaction of Styrenes and Formaldehyde Catalyzed by 2,6-Di-tert-butylphenoxy(difluoro)borane
T. Bach, J. Löbel, Synthesis, 2002, 2521-2526.

A General Catalytic Asymmetric Prins Cyclization
L. Liu, P. S. J. Kaib, A. Tap, B. List, J. Am. Chem. Soc., 2016, 138, 10822-10825.

Diastereoselective Synthesis of 2,6-Disubstituted Tetrahydropyranones via Prins Cyclization of 3-Bromobut-3-en-1-ols and Aldehydes
S. K. Bora, S. Shit, A. K. Sahu, A. K. Saikia, J. Org. Chem., 2023, 88, 3012-3021.

Preparation of trans-2-Substituted-4-halopiperidines and cis-2-Substituted-4-halotetrahydropyrans via AlCl₃-Catalyzed Prins Reaction
G.-Q. Liu, B. Cui, R. Xu, X.-M. Li, J. Org. Chem., 2016, 81, 5144-5161.

An efficient method allows the construction of 2,6-cis-4,5-dibromo-tetrasubstituted tetrahydropyran rings with well-controlled stereochemistry in good yields.
F. Liu, T.-P. Loh, Org. Lett., 2007, 9, 2063-2066.

5- and 6-Exocyclic Products, cis-2,3,5-Trisubstituted Tetrahydrofurans, and cis-2,3,6-Trisubstituted Tetrahydropyrans via Prins-Type Cyclization
S. N. Chavre, H. Choo, J. K. Lee, A. N. Pae, Y. Kim, Y. S. Cho, J. Org. Chem., 2008, 73, 7467-7471.

Tandem Bis-aldol Reaction of Ketones: A Facile One-Pot Synthesis of 1,3-Dioxanes in Aqueous Medium
V. Polshettiwar, R. S. Varma, J. Org. Chem., 2007, 72, 7420-7422.

Brønsted Acid-Mediated Stereoselective Cascade Construction of Functionalized Tetrahydropyrans from 2-(Arylmethylene)cyclopropylcarbinols and Aldehydes
G.-Q. Tian, M. Shi, Org. Lett., 2007, 9, 2405-2408.

Synthesis of Tetrahydroazepines through Silyl Aza-Prins Cyclization Mediated by Iron(III) Salts
V. Sinka, I. Fernández, J. I. Padrón, J. Org. Chem., 2022, 87, 11735-11742.

Cooperative Hydrogen-Bond-Donor Catalysis with Hydrogen Chloride Enables Highly Enantioselective Prins Cyclization Reactions
D. A. Kutateladze, E. N. Jacobsen, J. Am. Chem. Soc., 2021, 143, 20077-20083.