Isovaleric anhydride, acylation

Steric effects were evaluated by a study of the DMAP-catalysed acylation of 1 y, 2y and 3y alcohols by acetic, propionic, isobutyric, isovaleric, and pivalic anhydrides in CH2C12 at 20 °C. In all cases the reaction kinetics could be described by rate laws containing a DMAP-catalysed term and an uncatalysed (background) term. Steric effects were evident in both reactions, but were generally greater for the DMAP-catalysed reaction. For example, the uncatalysed reactions between cyclohexanol and acetic and pivalic anhydrides differed about 500-fold, but for the corresponding DMAP-catalysed reactions the factor was 8000-fold. The implications of these findings for the kinetic resolution of alcohols were discussed.32... 

An improvement resulting in a decreased amount of the second acylation product is the introduction of mixed anhydrides with a-branched carboxylic acids like isovaleric and pivalic acid, due to deactivating electronic and steric effects. 

Formation of the peptide bond via mixed or unsymmetrical anhydrides gained considerable popularity after their introduction in the early forties. These intermediates were constructed in such a way that the blocked amino acid is practically the sole acylating moiety while the acid which plays the role of activator is eliminated. Acetic acid or benzoic acid are not well suited for this role. A search for better solutions led to branched long-chain fatty acids, such as isovaleric acid (Vaughan and Osato 1951). In these mixed anhydrides (prepared via the acid chlorides) reactivity of the activating part of the anhydride... 

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