The Prins-Pinacol reaction is a two-step process that begins with the Prins reaction, where an alkene attacks an aldehyde activated by a Lewis acid to form a cationic intermediate. This is followed by a pinacol rearrangement, where a methyl shift pushes the cation onto an oxygen. The reaction forms complex natural product backbones and allows stereoselective tetrahydropyran synthesis. Driving forces include increased stability of the carbocation intermediate and relief of ring strain. The Lewis acid activates the aldehyde for attack.

1. Organic Pedagogical Electronic
Network
The Prins-Pinacol Reaction
Andy Clevenger
University of Utah

2. Overview
(top) Reddy, B.V.S.; Reddy, S.G.; Reddy, M.R.; Bhadra, M.P.; Sarma, A.V.S. Org. Biomol. Chem. 2014, 12,
7257-7260
The Prins-Pinacol reaction is a two step process. It begins with
the Prins reaction, which is the attack by a nucleophilic alkene
on a Lewis acid-activated aldehyde. This forms a cationic
intermediate. The pinacol rearrangement is a methyl shift
which pushes the cation on to an oxygen, which is then
deprotonated.

3. History
Prins: https://en.wikipedia.org/wiki/Prins_reaction
Pinacol: https://en.wikipedia.org/wiki/Pinacol_rearrangement
In 1919, Dutch chemist Hendrick
Jacobus Prins found the first step of
this reaction by combining styrene and
formaldehyde in concentrated H2SO4.
The pinacol rearrangement was first
found by Wilhelm Rudolph Fittig in
1860. It is an acid-catalyzed method
for converting a 1,2-diol into a
carbonyl.

4. Prins-Pinacol Mechanism: Forming the Activated Carbonyl
Reddy, B.V.S.; Reddy, S.G.; Durgaprasad, M.; Bhadra, M.P.; Sridhar, B. Org. Biomol. Chem. 2015, 13, 8729-8733.
In this first step, the more exposed alcohol attacks the activated aldehyde. The
oxygen on the activated aldehyde is removed as the Lewis Acid complex and a
highly reactive oxocarbenium ion is formed.

5. Prins-Pinacol Mechanism: Prins Reaction
Reddy, B.V.S.; Reddy, S.G.; Durgaprasad, M.; Bhadra, M.P.; Sridhar, B. Org. Biomol. Chem. 2015, 13, 8729-
8733.
The alkene attacks the activated carbonyl and forms the six-membered ring
in the Prins reaction. The cation is now at a more stable tertiary center.

6. Prins-Pinacol Mechanism: Pinacol Rearrangement
Reddy, B.V.S.; Reddy, S.G.; Durgaprasad, M.; Bhadra, M.P.; Sridhar, B. Org. Biomol. Chem. 2015, 13, 8729-
8733.
In this pinacol rearrangement, there is an aryl methyl shift. The C-C
bond shifts to the carbocation position while one of the lone pairs on the
alcohol closes down to form a carbonyl. With deprotonation, the Prins-
Pinacol reaction is complete.

7. Driving Forces Behind the Prins-Pinacol Reaction
Reddy, B.V.S.; Reddy, S.G.; Reddy, M.R.; Bhadra, M.P.; Sarma, A.V.S. Org. Biomol. Chem. 2014, 12, 7257-
7260
• Most of the force driving this reaction to completion is the increased
stability of the cation.
• Ring strain relief can also drive this reaction to completion.
In this example, the strained four membered ring reacts and becomes a
fused pyran-cyclopentanone compound which has much less ring strain.

8. Prins-Pinacol Applications
• Complex backbones of natural products
• Stereoselective tetrahydropyran synthesis
• Many natural product syntheses
• Convienent reaction pathway to establish a carbonyl and close a ring
system

9. Questions
Why can’t the Prins-Pinacol reaction occur on a ketone instead of an
aldehyde?
A) Steric hindrance-the alkene can’t attack the oxocarbenium ion
B) The oxocarbenium ion will not be able to form
C) The carbonyl will not be activated by the Lewis acid
D) The alkene can’t attack the ketone oxocarbenium ion due to
reduced reactivity

10. Questions
What is the role of the Lewis acid in the Prins-Pinacol reaction?
A) It stabilizes the oxocarbenium ion
B) It activates the aldehyde for attack by an alcohol
C) It stabilizes the carbocation intermediate
D) It deprotonates the protonated carbonyl at the end of the reaction

11. Questions
Which of these compounds is the correct Prins-Pinacol product for the given
reaction?
A) C)
B)

12. Questions
What can be a driving force behind the Prins-Pinacol reaction?
A) Ring strain relief
B) Increased carbocation stability
C) Increased stability with the formation of a carbonyl
D) All of the above

13. Questions
What functional group can undergo the Prins-Pinacol reaction with an
aldehyde?
A) A 1,2-diol
B) A 1,2-diketone
C) An alpha, gamma-hydroxyl alkene
D) An ester

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Contributed by:
Andy Clevenger (Undergraduate)
University of Utah, 2016