Aldol reaction enantioselective

Typical starting materials, catalysts, and products of the enamine-catalyzed aldol reaction are summarized in Scheme 17. In proline-catalyzed aldol reactions, enantioselectivities are good to excellent with selected cyclic ketones, such as cyclohexanone and 4-thianone, but generally lower with acetone. Hindered aldehyde acceptors, such as isobutyraldehyde and pivalaldehyde, afford high enantioselectivities even with acetone. In general, the reactions are anti selective, but there are aheady a number of examples of syn selective enamine aldol processes [200, 201] (Schemes 17 and 18, see below). However, syn selective aldol reactions are still rare, especially with cychc ketones. 

A range of chiral pre-organized diols have been studied to assess their potential to catalyse vinylogous Mukaiyama aldol reactions enantioselectively via hydrogen bonds.141... 

Figure 3.3 The 3D structures of TS3 and TS4. (From Yamanaka, M. et al. Kinetic Resolution in Chiral Phosphoric Acid Catalyzed Aldol Reactions Enantioselective Robinson-Type Annulation Reactions. Eur. J. Org. Ghent. 2012. 24, 4508-4514. Copyright Wiley-VCH Verlag GmbH Co. KGaA. Adapted with permission.)...

Although several groups found that simple proUne is not a useful catalyst under aqueous conditions, under specific, wet, conditions simple proline is able to catalyze aldehyde-aldehyde and aldehyde-ketone aldol reactions enantioselectively (aldols 17-20, Figure 24.7). Wet conditions required the use of 30mol% of proline and 3-3.8 equivalents of water [41]. 

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