From the Archives: Crouch's 'Selective Monodeprotection of Bis-silyl Ethers'

Continuing our exploration of underappreciated gems hidden within the archives, this post highlights Crouch's invaluable work on the 'selective monodeprotection of bis-silyl ethers.'[1] This humble Tetrahedron paper stands as an indispensable reference guide for planning synthetic pathways that require the strategic use of silyl protecting groups.

In the intricate world of total synthesis, most routes call for the judicious application of orthogonal protecting group strategies. Protecting alcohols as their corresponding silyl ethers is a powerful and well-studied means of concealing these groups until the point in the synthesis where the functionality can be unveiled. However, the situation becomes more complex when the selective deprotection of one silyl ether in the presence of another silyl ether is required. In these situations, Crouch's paper becomes indispensable.

'A bible for planning silyl protecting group strategies'

The popularity of silyl ethers as alcohol protecting groups stems from their versatility. Usually introduced via their corresponding silyl chlorides, a wide array of silyl protecting groups is readily available. Silyl ethers exhibit varying degrees of chemical stability, typically following the order of TBDPS > TBDMS > TES > TMS (although many more are available). This diversity in stability arms chemists with the capability to selectively mask and unmask alcohols, offering precise control over synthetic transformations. Furthermore, their susceptibility to tetra-n-butylammonium fluoride (TBAF) allows chemoselective removal in the presence of other functional groups.

Most organic chemists are well-acquainted with common principles, such as the ability to deprotect primary silyl ethers in the presence of secondary silyl ethers, or possibility of the cleavage of TMS ethers amidst TBDMS ethers. But what happens when the challenge is to liberate a secondary TMS group in the presence of a primary TES group? Or, alternatively, when a secondary TBDMS group needs to be unmasked while a primary TBDPS group stays intact? These permutations, among numerous others, pose intricate conundrums in the field of organic synthesis.

Thankfully, Crouch's painstaking survey of the literature and meticulous tabulation of all known selective deprotections involving compounds with dual silyl groups has provided a comprehensive and indispensable resource for chemists navigating these intricate pathways.

Crouch summarizes all the known examples for the selective monodeprotection of a silyl ether in the presence of another silyl ether

In summary, organic chemists often find themselves in need of precise methods for selectively removing one silyl group from bis-silyl ethers. Crouch's 2004 paper offers an exhaustive review of successful instances where this goal has been accomplished. Over the years, countless syntheses have greatly benefited from the insights presented in this work. As the body of literature on selective silyl ether deprotections continued to expand with new examples, Crouch recognized the need for an update. Consequently, in 2013, Crouch published a revised version of the paper titled 'Selective deprotection of silyl ethers.' [2]

References

1. Crouch, R. D. Selective monodeprotection of bis-silyl ethers. Tetrahedron, 2004, 60, 5833–5871.

2. Crouch, R. D. Selective deprotection of silyl ethers. Tetrahedron, 2013, 69, 2383–2417.