Tert-nitroaldols

Catalytic asymmetric nitroaldol (Henry) reactions of ketones lead to synthetically versatile chiral tertiary nitroaldols. Enantioselective nitroaldol reactions of a-keto esters have been achieved using chiral Cu and Mg complexes, and cinchona alkaloids [140]. However, there are no reports on the asymmetric synthesis of tertiary nitroaldols derived from simple ketones. Even for a racemic version, only a few methodologies with limited substrate scope are available. The difficulty arises from the attenuated reactivity of ketones and their strong tendency toward a retro-nitroaldol reaction under basic conditions. (S)-LLB catalyst was found suitable to promote retro-nitroaldol reaction and a kinetic resolution of racemic tert-nitroaldols was realized. (S)-LLB preferentially converted the matched (R)-enantiomer into ketone and nitromethane, whereas the mismatched (S)-enantiomer remained unchanged and was recovered in an enantiomerically... 

Table 13.37 Kinetic resolution of racemic tert-nitroaldols using (S)-LLB and (S)-Li3[La(biphenol)3] complex...

The enantioselective nitroaldol reaction of phe-nylalaninals 45 with nitromethane was also promoted with the N-anthracenylmethyl ammonium fluorides in the presence of potassium fluoride.1411 Interestingly, as shown in Scheme 16, the major product was the (2R,3S)-isomer 46a when N,N-dibenzyl-(S)-phenylalaninal and 12 (R=benzyl, X=F) were used while the (2S,3S)-isomer 46b was major when N-tert-butoxycarbonyl derivative 45b and 12 (R=allyl, X=Br) together with potassium fluoride were used. The nitroalcohols 46a and 46b were respectively converted to amprenavir 47a, a HIV protease inhibitor, and its diastereomer 47b. The... 

The butyrolactone skeleton of precursors for the sugar component of the glycoside antibiotics L-ristosamine and L-daunosamine can be readily assembled by a nitroaldol reaction of 3-nitropropionate (553) with 831, followed by lactonization [229] (Scheme 111). The initial condensation gives 832 in only moderate yield, probably due to the reversible nature of the nitroaldol reaction. If the crude product is treated with pyridinium tosylate, a mixture of lactones 833 and 834 is produced with concomitant loss of the THP group. The ratio of lactones is dependent on the base used in the nitroaldol condensation. Use of potassium tert-butoxide affords a 2 1 mixture of 833 and 834. The ratio can be increased to 5 1 with KF 2H20/tetrabutylammonium chloride, but the overall yield decreases. 

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