Sharpless epoxidation
The Sharpless epoxidation is a significant chemical reaction named after Karl Barry Sharpless, who was awarded the Nobel Prize in Chemistry in 2001 for his work on asymmetric oxidations, including this reaction. It is an enantioselective reaction used to synthesize 2,3-epoxyalcohols from primary and secondary allylic alcohols. The reaction employs tert-butyl hydroperoxide as the oxidizing agent and a catalyst formed from titanium tetra(isopropoxide) and diethyl tartrate. This reaction is notable for its ability to produce enantiomerically enriched products, which are valuable in the synthesis of complex organic molecules, including natural products and pharmaceuticals[1].
The catalyst used in the Sharpless epoxidation typically consists of 5–10 mol% of titanium tetra(isopropoxide) and diethyl tartrate, with the presence of 3Å molecular sieves being necessary. The structure of the catalyst is thought to be a dimer of [Ti(tartrate)(OR)2], although this is not definitively established[1].
The selectivity of the Sharpless epoxidation is a key feature, allowing for the predictable production of one enantiomer over another. This selectivity is sometimes predicted using a mnemonic involving the orientation of the double bond and substituents in relation to the diester tartrate used. The reaction's selectivity can be influenced by the size of the substituents on the olefin, with larger substituents affecting the outcome[1].
Additionally, the Sharpless epoxidation can be used for the kinetic resolution of racemic mixtures of secondary 2,3-epoxyalcohols, where the yield cannot exceed 50%, but the enantiomeric excess can approach 100% in some cases[1].
The synthetic utility of the Sharpless epoxidation is broad, applicable to a wide range of primary and secondary alkenic alcohols. It has been used in the total synthesis of various natural products, including saccharides, terpenes, leukotrienes, pheromones, and antibiotics. Despite its advantages, a limitation of this method is the necessity for the presence of an allylic alcohol in the substrate. The Jacobsen epoxidation is an alternative method that can enantioselectively oxidize alkenes and tolerates a wider array of functional groups[1].
In summary, the Sharpless epoxidation is a cornerstone of asymmetric synthesis, enabling the preparation of enantiomerically enriched epoxy alcohols with high selectivity and efficiency. Its development has had a profound impact on the field of organic chemistry, particularly in the synthesis of complex molecules and natural products.
Citations:
[1] https://en.wikipedia.org/wiki/Sharpless_epoxidation
[2] https://www.sciencedirect.com/science/article/pii/S0957416615000890
[3] https://hwpi.harvard.edu/files/myers/files/22-sharpless_asymmetric_epoxidation_reaction.pdf
[4] https://www.sciencedirect.com/topics/chemistry/sharpless-asymmetric-epoxidation
[5] https://www.researchgate.net/publication/343533342_Sharpless_Asymmetric_Epoxidation_Applications_in_the_Synthesis_of_Bioactive_Natural_Products
[6] https://www.chemistry.mcmaster.ca/silicone/SharplessEdited.pdf
[7] https://www.name-reaction.com/sharpless-epoxidation
[8] https://www.mdpi.com/1420-3049/15/2/1041
[9] https://www.youtube.com/watch?v=yxcipaAT1-0
[10] https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/sharpless-epoxidation
[11] https://pubs.acs.org/doi/10.1021/acs.jpca.3c08476
[12] https://www.organic-chemistry.org/namedreactions/sharpless-epoxidation.shtm
[13] https://www.youtube.com/watch?v=vALDSVnv6Jo
[14] https://moodle2.units.it/pluginfile.php/297501/mod_resource/content/1/Applications_SAE.pdf
[15] https://www.sciencedirect.com/topics/chemistry/sharpless-epoxidation
[16] https://www.ingentaconnect.com/content/ben/mroc/2021/00000018/00000005/art00004
[17] https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Catalytic_Asymmetric_Synthesis_%28Punniyamurthy%29/05:_Oxidation_Reactions/5.02:_Epoxidation_of_Allylic_Alcohols