Reductive aminations, secondary amines, sulfonic acid

As illustrated by the examples in Table 3.9, resin-bound 4-alkoxybenzylamides often require higher concentrations of TFA and longer reaction times than carboxylic acids esterified to Wang resin. For this reason, the more acid-sensitive di- or (trialkoxy-benzyl)amines [208] are generally preferred as backbone amide linkers. The required resin-bound, secondary benzylamines can readily be prepared by reductive amination of resin-bound benzaldehydes (Section 10.1.4 and Figure 3.17 [209]) or by A-alkyla-tion of primary amines with resin-bound benzyl halides or sulfonates (Section 10.1.1.1). Sufficiently acidic amides can also be A-alkylated by resin-bound benzyl alcohols under Mitsunobu conditions (see, e.g., [210] attachment to Sasrin of Fmoc cycloserine, an O-alkyl hydroxamic acid). 

Similarly, it has been reported that hydrocarbons can be obtained from primary amines by treatment of the amine with aqueous sodiumhydroxide andhydroxylamine-O-sulfonic acid (Scheme 10.21) and enamines, obtained from ketones and secondary amines, can be converted to alkenes by reduction with alane (AIH3) (see Coulter, J. M. Lewis, J. W. Lynch, P. P. Tetrahedron, 1968,24,4489) (Equation 10.40). 

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