Diarylmethyl amine and Tritylamine Linkers

One of the oldest linkers for amides is the (4-methylbenzhydryl)amine linker (MBHA Entry 1, Table 3.11). In contrast to the corresponding benzhydrol linker (which is cleavable by 5% TFA in DCM, 5 min [45]), acidolysis of the benzylic C-N bond of the MBHA linker requires treatment with hydrogen fluoride or a similar acid. As for A-benzylamides, the acid-lability of Al-(diarylmethyl)amides increases with the number of electron-donating substituents on the aryl groups. 

The attachment of amides to supports as A-(diarylmethyl)amides can be achieved either by acylation of resin-bound (diarylmethyl)amines, or by acid-catalyzed N-alky-lation of amides with resin-bound benzhydryl alcohols [46]. The former strategy is by far the more general. For the preparation of secondary amides RNHCOR by backbone amide linking, benzylamine linkers (Table 3.9) are more appropriate than (diary lmethyl) amine linkers, because V-al ky I - N- (di ary 1 met hy 1) amines are often difficult to acylate because of steric hindrance [242,243]. A few examples of the preparation of secondary amides by backbone amide linking to (diarylmethyl)amine linkers have been reported (Table 3.11). 

Tritylamine linkers have not been extensively used for the attachment of amides, probably because A -tritylamides are difficult to prepare. This is not the case for strongly acidic amides and cyclic imides, which are readily N-tritylated with trityl chlo- 

Entry Loaded resin Cleavage conditions Product, yield (purity) Ref. 

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