Corey-Seebach Reaction

The Corey-Seebach reaction, also known as Seebach Umpolung, is a named reaction in organic chemistry that allows for acylation by converting aldehydes into lithiated 1,3-dithianes, which serve as acyl anion equivalents. This reaction was named after its discoverers, Elias J. Corey and Dieter Seebach[1].

The Corey-Seebach reagent is formed by the reaction of an aldehyde or a ketone with 1,3-propane-dithiol under acidic conditions, followed by deprotonation with n-butyllithium[2][3]. The lithiated 1,3-dithiane can be alkylated with various electrophiles, including alkyl halides, epoxides, ketones, acyl halides, and iminium salts. After hydrolysis of dithioacetals, this can yield a variety of products such as ketones, β-hydroxyketones, α-hydroxyketones, 1,2-diketones, and α-aminoketones[1].

The Corey-Seebach reaction is of particular interest as it allows for the conversion of aldehydes to ketones, a transformation that is not typically possible through standard reactions of aldehydes. However, the reaction is not widely used due to its cumbersome nature, particularly because the deprotection of dithianes is inefficient[1].

Despite its limitations, the Corey-Seebach reaction has found applications in the synthesis of a variety of natural products, including alkaloids, terpenoids, and polyketides[3]. It is also a classic example of polarity inversion or "umpolung", a concept in organic chemistry where the typical reactivity of a functional group is reversed[7].

Citations:

[1] https://en.wikipedia.org/wiki/Corey%E2%80%93Seebach_reaction

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254450/

[3] https://pubmed.ncbi.nlm.nih.gov/37298842/

[4] https://www.researchgate.net/figure/The-Corey-Seebach-reaction-Note-Treatment-of-aldehyde-8-with-1-3-propanedithiol-yields_fig3_338018783

[5] https://www.wikiwand.com/en/Corey%E2%80%93Seebach_reaction

[6] https://www.researchgate.net/publication/371112143_The_Corey-Seebach_Reagent_in_the_21st_Century_A_Review

[7] https://en.wikipedia.org/wiki/Umpolung

[8] https://www.youtube.com/watch?v=-G2X1O43YSI

[9] https://www.mdpi.com/1420-3049/28/11/4367/review_report

[10] https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/chem.202003000

[11] https://www.princeton.edu/~orggroup/supergroup_pdf/Umpolung2.pdf

[12] https://www.youtube.com/watch?v=pwPIxl1eSn0

[13] https://ethz.ch/content/dam/ethz/special-interest/chab/chab-dept/department/images/Emeriti/Seebach/PDFs/156-PULI_Ump-E.pdf

[14] https://link.springer.com/chapter/10.1007/978-3-319-03979-4_74

[15] https://www.wikidata.org/wiki/Q1132609