An important protecting group developed specifically for polyhydroxy compounds like nucleosides is the tetraisopropyldisiloxanyl group, abbreviated TIPDS, that can protect two alcohol groups in a molecule.
(a) The TIPDS group is somewhat hindered around the Si atoms by the isopropyl groups. Which OH is more likely to react first with TIPDS chloride? Show the product with the TIPDS group on one oxygen. (b) Once the TIPDS group is attached at the first oxygen, it reaches around to the next closest oxygen. Show the final product with two oxygens protected. (c) The unprotected hydroxy group can now undergo reactions without affecting the protected oxygens. Show the product after the protected nucleoside from (b) is treated with tosyl chloride and pyridine, followed by NaBr, ending with deprotection with Bu4NF.

Verified step by step guidance

1. Identify the hydroxyl groups in the polyhydroxy compound that can react with TIPDS chloride.
2. Determine which hydroxyl group is less sterically hindered and more likely to react first with TIPDS chloride.
3. Show the intermediate product with the TIPDS group attached to the first oxygen.
4. Illustrate how the TIPDS group reaches around to protect the next closest oxygen, forming a cyclic structure.
5. Depict the final product after the protected nucleoside is treated with tosyl chloride and pyridine, followed by NaBr, and then deprotected with Bu4NF.

Key Concepts

Protecting Groups in Organic Chemistry

Protecting groups are temporary modifications used to shield reactive functional groups during chemical reactions. In the context of polyhydroxy compounds, such as nucleosides, protecting groups like TIPDS allow selective reactions to occur on unprotected hydroxyl groups without interference from others. This strategy is crucial for multi-step synthesis where specific functional groups need to be preserved while others are modified.

Reactivity of Alcohols

Alcohols are characterized by their hydroxyl (-OH) groups, which can act as nucleophiles in chemical reactions. The reactivity of alcohols can vary based on steric hindrance and electronic effects. In the case of TIPDS protection, the steric hindrance introduced by the isopropyl groups around the silicon atoms influences which hydroxyl group will react first with TIPDS chloride, typically favoring the less hindered alcohol.

Deprotection Strategies

Deprotection is the process of removing a protecting group to restore the original functional group after the desired reactions have been completed. In this scenario, after the nucleoside is modified with tosyl chloride and pyridine, the final step involves deprotecting the TIPDS group using tetrabutylammonium fluoride (Bu4NF). This step is essential to regenerate the active hydroxyl groups for further reactions or biological activity.