Ley-Griffith Oxidation

The Ley-Griffith oxidation, also known as the Ley-Griffith reaction, is a chemical process used for the selective oxidation of primary and secondary alcohols to aldehydes and ketones, respectively. The central catalyst in this reaction is tetrapropylammonium perruthenate (TPAP), which is often used in combination with a co-oxidant, N-methylmorpholine N-oxide (NMO). TPAP is a solid, air-stable compound that is soluble in a variety of organic solvents[1].

General Features:

• TPAP is used in small amounts (typically 5 mol%) and is known for its high turnover number (TON), which is approximately 250[1].
• The reaction is fast but can be explosive on a multigram scale, so cooling may be necessary[1].
• The presence of molecular sieves can enhance the reaction rate and efficiency[1].
• The work-up typically involves purification through silica-gel column chromatography[1].

General Conditions:

• The reaction is usually carried out in dichloromethane (DCM) at room temperature for 1–16 hours, yielding 80–95% of the product[1].
• The typical reagent ratio is 5 mol% TPAP, 1 equivalent of the alcohol, and 1.5 equivalents of NMO[1].

Mechanism Insights:

• TPAP oxidizes the alcohol to form a TPAP-alcohol complex (ruthenate ester), which then rearranges to deliver the ketone[1].
• NMO acts to reactivate the catalyst by reoxidizing the reduced ruthenium species[1][10].

Mechanistic Study:

• A comprehensive study has shown that the oxidation of diphenylmethanol by TPAP is initially slow but accelerates due to the formation of insoluble RuO2, which catalyzes the reaction via a heterogeneous process[2].
• Water produced by the alcohol oxidation leads to the formation of RuO2, which is necessary for the catalysis to proceed efficiently[2].

Applications and Variants:

• TPAP is also used to cleave vicinal diols to form aldehydes or ketones[8].
• There are several modifications and alternative applications of the Ley-Griffith reaction that have been reported, which utilize TPAP as a catalyst for various synthetic transformations[4].

Safety and Handling:

• Due to the potential for explosive reactions on a larger scale, TPAP and NMO should be added carefully to the reaction mixture[10].

The Ley-Griffith oxidation is a valuable tool in organic synthesis due to its mild conditions and compatibility with sensitive functional groups, making it suitable for the synthesis of complex molecules[12].

Citations:

[1] https://nrochemistry.com/ley-griffith-oxidation/

[2] https://pubs.rsc.org/en/content/articlelanding/2017/sc/c7sc04260d

[3] https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/cctc.202000413

[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863698/

[5] https://www.researchgate.net/publication/340898048_Two_Simple_and_Highly_Efficient_Variants_of_the_Griffith-Ley_Oxidation_of_Alcohols

[6] https://youtube.com/watch?v=s7IbM-mI_n0

[7] https://pubmed.ncbi.nlm.nih.gov/29508453/

[8] https://en.wikipedia.org/wiki/Tetrapropylammonium_perruthenate

[9] https://www.organic-chemistry.org/chemicals/oxidations/tetrapropylammonium-perruthenate-tpap.shtm

[10] https://en.chem-station.com/reactions-2/2014/04/tpap-ley-griffith-oxidation.html

[11] https://chemistry-europe.onlinelibrary.wiley.com/doi/am-pdf/10.1002/ejoc.201800860

[12] https://www.sciencedirect.com/topics/chemistry/tetrapropylammonium-perruthenate

[13] https://www.degruyter.com/document/doi/10.1515/9783110608373-054/html