2-(Trimethylsilyl)ethoxymethyl chloride explained

2-(Trimethylsilyl)ethoxymethyl chloride (SEM-Cl) is an organochlorine compound with the formula C₆H₁₅ClOSi, which was developed by Bruce H. Lipshutz during his work on the synthesis of N-methylmaysenine. It is used to protect hydroxyl groups, which can be cleaved with fluoride in organic solvents selectively under mild conditions.^[1] Typically tetrabutylammonium fluoride and caesium fluoride can be used as deprotection reagents. Alternatives such as magnesium bromide,^[2] lithium tetrafluoroborate and boron trifluoride etherate were also developed to deprotect SEM group.^[3]

Further reading

• Nair . Reji N. . Bannister . Thomas D. . Tale of Two Protecting Groups—Boc vs SEM—for Directed Lithiation and C–C Bond Formation on a Pyrrolopyridazinone Core . Organic Process Research & Development . American Chemical Society (ACS) . 20 . 7 . 2016-06-21 . 1083-6160 . 10.1021/acs.oprd.6b00128 . 1370–1376.

Notes and References

1. Lipshutz . Bruce H. . Pegram . Joseph J. . β-(Trimethylsilyl)ethoxymethyl chloride. A new reagent for the protection of the hydroxyl group . Tetrahedron Letters . Elsevier BV . 21 . 35 . 1980 . 0040-4039 . 10.1016/s0040-4039(00)78684-9 . 3343–3346.
2. Vakalopoulos . Alexandros . Hoffmann . H. M. R. . Novel Deprotection of SEM Ethers: A Very Mild and Selective Method Using Magnesium Bromide . Organic Letters . American Chemical Society (ACS) . 2 . 10 . 2000-04-21 . 1523-7060 . 10.1021/ol0057784 . 1447–1450. 10814469 .
3. Book: Katritzky . A.R. . Kirby . G.W. . Meth-Cohn . O. . Rees . C.W. . Comprehensive Organic Functional Group Transformations . Elsevier Science . v. 4 . 1995 . 978-0-08-042325-8 . 2021-10-25 . 176.