Atom Economy and Protecting-Group-Free Chemistry

3 ATOM ECONOMY AND PROTECTING-GROUP-FREE CHEMISTRY 

Metal-catalyzed amine/alcohol coupling to form amide 

SCHEME 13.9 Atom uneconomical peptide bond formation and alternative catalytic method. 

SCHEME 13.10 Proposed atom-economical dimerization of hymenidin to produce sceptrin and photochemical union of 68 and 69 to yield dictazole B. 

The aldol reaction is another class of reactions used to highlight AE, as all the atoms in the reactants end up in the product. One should note though that this transformation comes with a number of caveats. Typically, a stoichiometric base is required to form the reactive enolate, and for many asymmetric aldols, a chiral auxiliary is utilized. Although this auxiliary is present in the product after the reaction, it is usually cleaved in a subsequent step and discarded to waste. An example of innovation to address both of these issues is the asymmetric aldol reaction using a zinc-Pro-Phenol 

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Confronted with the need to develop a sustainable chemistry, we have witnessed an amazing increase in the efficiency and selectivity of synthetic methods in the last fifty years. In order to solve the problems associated with the traditional step-by-step procedures, such as the cumbersome, time-consuming, and expensive isolation of intermediates, several new criteria have been introduced atom, redox, step and pot economy or protecting-group-free synthesis. It is obvious that all variants of one-pot domino and cascade reactions or multicomponent consecutive reactions sequences may allow fulfilling these criteria. 

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