Combined Proline–Surfactant Organocatalyst for the Highly Diastereo‐ and Enantioselective Aqueous Direct Cross‐Aldol Reaction of Aldehydes

Organocatalytic Asymmetric Synthesis Using Proline and Related Molecules. Part 1

“…Interestingly, Hayashi and coworkers discovered that 4-decanoyloxyproline 4 efficiently catalyzed the cross-aldol reaction of aldehydes in aqueous media (yield up to 92%, dr up to >20 : 1, ee up to 99%) (Scheme 33). 100,103 Although the precise mechanism is unclear, it is possible that the surfactant-like nature of catalyst 4 brought the acceptor and donor molecules together on the water surface. 105 it can be expected that organocatalysts derived from L-proline can sufficiently promote aldol reactions with great reactivity and high selectivity.…”

Organocatalytic Asymmetric Synthesis Using Proline and Related Molecules. Part 2.

“…97 Interestingly, Hayashi and coworkers discovered that 4-decanoyloxyproline 4 efficiently catalyzed the cross-aldol reaction of aldehydes in aqueous media (yield up to 92%, dr up to >20 : 1, ee up to 99%) (Scheme 33). 100,103 Although the precise mechanism is unclear, it is possible that the surfactant-like nature of catalyst 4 brought the acceptor and donor molecules together on the water surface. …”

In Water or in the Presence of Water?

“…We recently published another paper concerning this topic. [13] Our first report described an aldehyde-ketone aldol reaction catalyzed by siloxyproline (Scheme 1), [12,14] and the second report concerned an aldehyde-aldehyde reaction catalyzed by a combined proline/ surfactant organocatalyst (Scheme 2). [13] Both reactions proceed in the presence of a large excess of water to afford the aldol products with excellent diastereoand enantioselectivities.…”