Amine-Catalyzed Direct Aldol Addition

Link: JACS ASAP

Morris Markert, Michael Mulzer, Bernd Schetter, and Rainer Mahrwald*

Institut für Chemie der Humboldt-Universität zu Berlin, Brook-Taylor Strasse 2, 12 489 Berlin, Germany

A new method emerged for tertiary amine-catalyzed cross aldol reaction between aldehydes and hydroxyl acetone. This method is different from previous method where tertiary amine was used in conjunction with LiClO4. The initial results are as seen in Scheme 1 of the reactions catalyzed by DBU.In the subsequent scheme, further utilities of the reaction is illustrated, using Hunig's base as catalyst. In some of these reactions, cyclic acetal was obtained along with the expected aldol adduct.As is readily seen, the reaction predominantly afforded syn-aldol product. The selectivity was probably stemed from the effect of hydrogen-bonding - a welcome complement to the previously known anti-selectivity.

The method is applicable to enolizable aldehyde. The reaction is also regioselective with regards to enolate counterpart, namely only alpha-carbon bearing OH group was observed to add to the aldehyde. In the scheme below, the method was used effectively in the synthesis of furanose 8 and sorbose 9.In addition to DBU and Hunig's base, alkaloid such as cinchonine was also found to be an effective catalyst as demonstrated in the example below.