2-Norbornyldimethylsilyl Ethers (NDMS): A New Protecting Group for Alcohols and Carboxylic Acids

Abstract

The use of the readily available 2-norbornyldimethylsilyl group (NDMS) in the protection of alcohols and carboxylic acids is described. Stabilities of the corresponding silyl compounds towards various reagents and deprotection conditions are compared with tert-butyldimethylsilyl-, iso-propyldimethyl and trimethylsilyl groups.

silicon - protecting groups - ethers - esters - hydrosilylation

References

1a Greene TW. Wuts PGM. Protective Groups in Organic Synthesis   3rd ed.:  J. Wiley & Sons; New York: 1999. 

1b KocieŇ ski PJ. Protecting Groups   Thieme; Stuttgart: 1994. 

2 Lalonde M. Chan TH. Synthesis  1985,  817 

3 van Look G. Simchen G. Heberle J. Silylating Agents   Fluka Chemie AG; Buchs: 1995. 

4a Corey EJ. Venkateswarlu A. J. Am. Chem. Soc.  1972,  94:  6190 

4b Morrison RJ, Hall RW, Dover BT, Kamienski CW, and Engel JF. inventors; Eur. Pat. EP  525 880.  ; Chem. Abstr. 1993, 118, 192001

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4d Winterfeld J, Abele BC, and Stenzel O. inventors; PCT-WO  2000/64909.  ; Chem. Abstr. 2000, 132, 279350

5 An exemption is the AlCl₃-catalyzed hydrosilylation of 2,3-dimethyl-2-butene with dimethylchlorosilane leading to thexyldimethylchlorosilane: Oertle K. Wetter H. Tetrahedron Lett.  1985,  26:  5511 

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7

Depending on the catalyst batch, ratios of 93:7 up to 95:5 were obtained. Major isomer is 3a(exo) according to citation 6.

8

All silylethers are exo/endo-mixtures with the same ratio as the silylating agent used. The isomers can be distinguished by the different chemical shifts of the methyl groups on the silyl atom in the¹H NMR spectra. However, the more preferable method of analysis is ²⁹Si NMR spectroscopy providing only two well-distinguished signals, e.g. Dimethyl-(2-norbornyl)-phenoxy silane: ¹H NMR (300 MHz, CDCl₃), major isomer: δ = 0.12 (2s, 6 H), 0.70 (t, 1 H), 1.10-1.5 (m, 8 H), 2.12-2.30 (m, 2 H), 6.70-6.80, 6.82-6.90, 7.09-7.20 (Phenyl, 5 H); minor isomer: δ = 0.20 [Si(CH₃)₂, 6 H]. ²⁹Si NMR (99 MHz, CDCl₃), major isomer: δ = +17.6; minor isomer: δ = + 19.6 ppm. Analysis by GC providing the same ratio is also possible.