Prolines 3-hydroxy ketone donor

S)-Proline also catalyzed Mannich reactions of ketone donors in a three-component (donor ketone, 4-methoxyaniline, aryaldehyde) protocol, as shown in Table 2.16 [84b, 90, 91]. In these three component reactions, the C-C bond formation occurred at both a-positions of unsymmetrical alkyl ketones (entry 3), and the ratio of the regioisomers depended on the reactant ketones and aldehydes. When the reaction was performed using a ketone donor possessing an a-hydroxy or methoxy group, C-C bond formation occurred exclusively at the oxy-substituted a-carbon (entries 5-7) the major diastereomer was again the syn-product. The enantioselectivities of (S)-proline-catalyzed three-component... 

Important extensions of proline catalysis in direct aldol reactions were also reported. Pioneering work by List and co-workers demonstrated that hydroxy-acetone (24) effectively serves as a donor substrate to afford anfi-l,2-diol 25 with excellent enantioselectivity (Scheme 11) [24]. The method represents the first catalytic asymmetric synthesis of anf/-l,2-diols and complements the asymmetric dihydroxylation developed by Sharpless and other researchers (described in Chap. 20). Barbas utilized proline to catalyze asymmetric self-aldoli-zation of acetaldehyde [25]. Jorgensen reported the cross aldol reaction of aldehydes and activated ketones like diethyl ketomalonate, in which the aldehyde... 

An important feature of this reaction is that in contrast to most other catalytic asymmetric Mannich reactions, a-unbranched aldehydes are efficient electrophiles in the proline-catalyzed reaction. In addition, with hydroxy acetone as a donor, the corresponding syn-l, 2-aminoalcohols are furnished with high chemo-, regio-, diastereo-, and enantioselectivities. The produced ketones 14 can be further converted to 4-substituted 2-oxazolidinones 17 and /i-aminoalcohol derivatives 18 in a straightforward manner via Baeyer-Villiger oxidation (Scheme 9.4) [5]. 

It is interesting to note that anri-selectivity of aldolization (with L-proline promotion) involving hydroxyacetone as the donor is switched in the Mannich reaction. Thus syn-2-hydroxy-3-arnino ketones are obtained as major products. 

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