Control of aldol reaction pathways of enolizable aldehydes in an aqueous environment with a hyperbranched polymeric catalyst.

A fundamental chemoselectivity challenge that remains intrinsically unsolved in aldol-type reactions is the suppression of self-aldol reactions with enolizable aldehydes in reactions such as cross-aldol processes. Contrasting with the usual practice of using large excesses of one component to compete with the undesired self-aldehyde condensation reactions, we have developed an enzyme-like polymer catalyst consisting of a hyperbranched polyethyleneimine derivative and proline that can eliminate the self-aldol reactions by suppressing an irreversible aldol condensation pathway. Control experiments and preliminary mechanistic studies suggest that the polymer catalyst provides an optimum environment for the aldol reaction to proceed selectively in water, and the catalytic conditions provided by the polymer are difficult to duplicate with typical small molecule analogues.

One-pot multi-component asymmetric cascade reactions catalyzed by soluble star polymers with highly branched non-interpenetrating catalytic cores.

Non-interpenetrating star polymer catalysts designed to mimic the site isolation characteristics of enzymes enable the one-pot combination of multiple otherwise incompatible catalysts for asymmetric cascade reactions that involve iminium, enamine, and H-bonding catalysis. Control experiments replacing star polymer catalysts with the corresponding small molecule or linear polymer analogues lead to little or no cascade reaction. Our strategy also allows straightforward access to all possible stereoisomers of the cascade product individually by proper choice of catalyst chirality.