Selective silylation of primary hydroxy groups in the presence of secondary alcohol.
The bulky isopropyl groups (vs. ethyl) allow for more selective reductions, e.g., beta-selective reduction of anomeric C-phenyl ketals, but do not diminish their activity (e.g. in the copper triflate catalyzed reductive etherification of trimethylsilyl ethers).
Triisopropylsilane is used as a protecting group in peptide synthesis and is also used as a reducing agent for the selective reduction of anomeric C-phenyl ketals. It is used in the selective silylation of primary hydroxyl groups without affecting the secondary hydroxyl group. It is used in the preparation of anti-1,2-diols catalyzed by a Ni(O) N-heterocyclic carbine complex with high diastereoselectivity.
Very sterically-hindered silane. Used as a cation
scavenger in the deprotection of peptides.
Hindered hydrosilanes such as triisopropylsilane (TIS) are commonly used as cation scavengers in the deprotection of amino acid side-chains following solid‐phase peptide synthesis (SPPS). Protecting groups such as trityl (Trt) and tert‐butyl (But ) form stable cations upon acidolysis and are easily removed from N‐, O‐, and S‐containing amino acid side‐chains (for cysteine (Cys) But is not easily removed). In acid, TIS drives the equilibrium towards cleavage of the protecting group from the amino acid side chain by donating a hydride to the resulting cation in an irreversible manner. Although TIS and other hindered hydrosilanes are exclusively thought of as protecting group scavengers in SPPS, they are actually mild reducing agents. They can reduce a carbon‐heteroatom bond and can, therefore, directly participate in the removal of a protecting group from an amino acid side‐chain[1].
[1] Emma J. Ste.Marie, Robert J. Hondal. “Reduction of cysteine-S-protecting groups by triisopropylsilane.” Journal of Peptide Science 24 11 (2018).
