Acid and Base Cleavable Linker Units

2 CLASSICAL LINKER STRATEGIES 1.2.1 Acid and Base Cleavable Linker Units 

Note that many of the hnker units described above are available in multiple forms, aUowing a range of substrates to be attached and cleaved. A discussion of all these related linker units is outside the scope of this chapter, but Kurosu has written a comprehensive review. By way of example, multiple versions of the Rink (Table 1.1, Entries 2 and 3) and trityl hnker units (Table 1.1, Entries 5 and 6) are commercially available and can be selected according to the desired substrate. However, beyond these general hnker units, there are also examples of substrate-specific hnker units. Eor example, the benzhydrylamine (BHA, Table 1.1, Entry 8) and Sieber (Table 1.1, Entry 9) linkers find widespread use as acid labile carboxamide linker units, while the DHP (Table 1.1, Entry 10) and sUyl linker units (e.g.. Table 1.1, Entry 11) can be used to attach alcohols to polymer supports.  

A number of hnker units designed specifically for immobihzation of amines have also been developed. One noticeable example exploits the versatility of the 9-phenylfluorenyl-9-yl group (PHFI). The PHEI group has previously been used as a protecting group for amines and was adapted into a hnker unit by Bleicher (Table 1.1, Entry 12). Cleavage from this 

LINKER STRATEGIES IN MODERN SOLID-PHASE ORGANIC SYNTHESIS 

Apart from the common heteroatom-derived nucleophiles described, cleavage with other nucleophiles is also possible. For example, reductive cleavage with hydride sources is possible. For ester-linked substrates, Kurth et al. reported an example in which substituted propane-1,3-diols were prepared (Table 1.2, Entry 11). In related work, Chandrasekhar et al. prepared tertiary alcohols by treating an ester-linked substrate with excess Grignard reagent (Table 1.2, Entry 12). If, however, it is desirable to prepare the carbonyl derivative (and not reduce all the way to the corresponding alcohol), then Weinreb-type linker units can be used (Table 1.2, Entries 13 and 14). Treatment of substrates attached via such linkers 

---