Polymer-bound diisopropyl chlorosilane

(reagent used as a linker for solid-phase organic synthesis)

Alternate Name: (diisopropylchlorosilyl)polystyrene.

Preparative Methods: lithiated polystyrene can be prepared via direct lithiation of cross-linked polystyrene with (1:1) BuLi and TMEDA at 65 °C in cyclohexane (1).1 Subsequent addition of diisopropyl-dichlorosilane in benzene followed by washing with excess benzene and drying in vacuo provides the desired functionalized polymer. Loading can be determined by hydrolysis and acid-base titration.2

Handling, Storage, and Precautions: reagent is water sensitive and cannot be stored for prolonged periods.

Rasta-(diisopropylchlorosilyl) TEMPO Methylpolystyrene Resin

Silyl styrene monomers were prepared from p-bromostyrene via lithium-halogen exchange with BuLi followed by quenching with diisopropylchlorosilane (2).3 Addition of a large molar excess of monomer to a suspension of TEMPO-methylpolystyrene resin and heating to 130 °C for 20 h in a capped vial under nitrogen gave a solid. Washing of the solid alternately with methylene chloride and methanol and drying in vacuo gave Rasta-(diisopropylsilyl)-TEMPO methylpolystyrene resin (3).3

Subsequent treatment with 1,3-dichloro-5,5-dimethylhydantoin in THF provides the Rasta-(diisopropylchlorosilyl) TEMPO methylpolystyrene resin (4).3

Silyl Linkers for Solid-Phase Organic Synthesis

Silyl ether linkers are advantageous for solid-phase organic synthesis due to their ease of formation and cleavage, provided that the synthetic strategy does not require other silyl protecting groups or strongly acidic conditions.4 (Diisopropylchlorosilyl)polystyrene can be used as a silyl ether linker by treatment of an alcohol with the reagent resin in the presence of a base such as pyridine or diisopropylethylamine (5). Cleavage of the silyl ether linker can be effected cleanly with TBAF in methylene chloride or tetrahydrofuran.

Diisopropylsilyl linkers on polystyrene resins have been used in solid-phase synthesis of oligosaccharides and glycoconjugates via the glycal assembly method (6).1,5,6

Diisopropylsilyl linkers are more stable to glycosylation conditions than their diphenyl counterparts (see polymer-bound diphenyl chlorosilane). Rasta-(diisopropylchlorosilyl) TEMPO methyl- polystyrene resins have been demonstrated as viable polymeric supports (7),2 however, the increased complexity of their preparation from commercially available starting materials has thus far precluded broader general application.

Related Reagents.

Polymer-bound diphenyl chlorosilane, trityl chloride resin; Merrifield resin.

1. Zheng, C.; Seeberger, P. H.; Danishefsky, S. J., J. Org. Chem. 1998, 63, 1126.
2. Chan, T.-H.; Huang, W.-Q., J. Chem. Soc., Chem Commun. 1985, 909.
3. Lindsley, C. W.; Hodges, J. C.; Filzen, G. F.; Watson, B. M.; Geyer, A. G., J. Comb. Chem. 2000, 2, 550.
4. Seeberger, P. H.; Haase, W.-C., Chem. Rev. 2000, 100, 4349.
5. Seeberger, P. H.; Danishefsky, S. J., Acc. Chem. Res. 1998, 31, 685.
6. Savin, K. A.; Woo, J. C. G.; Danishefsky, S. J., J. Org. Chem. 1999, 64, 4183.

Diana K. Hunt & Peter H. Seeberger

Massachusetts Institute of Technology, Cambridge, MA, USA

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