Curtius rearrangement stereoselectivity

Alternative routes to -amino acids have also been explored and involve, stereoselective alkylation of chiral derivatives of y9-alanine [136-140], Curtius rearrangement of enantiomerically pure and regioselectively protected substituted-succinic acids [134, 141, 142] (the approach is also suitable for the synthesis of y9 -amino acids [143]), or the formation of chiral isoxazolidinone intermediates [144]. 

Interestingly, this substitution reaction can be applied to the stereoselective assembly of chiral quaternary centers and has been extended to the preparation of chiral tertiary alcohols via a stereoselective Baeyer-Villiger rearrangement, and chiral tertiary amines via a stereoselective Curtius rearrangement (Scheme 15)130>130a... 

The two functional groups of (6g) could also be transformed i,e the acid chloride into the isocyanate (6j) (84 %) via a Curtius rearrangement and then into the carbamate (6k) (78%) which oxidation led to the amino alcohol (61) (65 %). All these transformations are stereoselective (Figure 5). 

It has also been reported that 4-substituted-5,5-dimethyloxazoIidin-2-ones can be prepared as illustrated in eq 3. Initially, stereoselective condensation of an N-acyloxazolidinone enolate with acetone affords a functionalized acyl fragment, which is then hydrolyzed to the carboxylic acid. Reaction of the hydroxy acid with DPPA at elevated temperatures yields the target via formation of the acyl azide, Curtius rearrangement and trapping of the isocyanate intermediate by the hydroxyl group (eq 3). 

The enantioselective total synthesis of the cytokine modulator (-)-cytoxazone using a syn-stereoselective aldol addition and a Curtius rearrangement as key steps was described by J.A. Marco et al. The key intermediate acid was treated with DPPA and triethylamine in toluene at reflux. This step furnished the oxazolidinone directly and in good yield through an in situ capture of the isocyanate group by the free secondary alcohol functionality. Removal of the protecting group led to the formation of the natural product. 

Table 3. Stereoselective Synthesis of Polycyclic Aminocyclopropane Derivatives by the Curtius Rearrangement of Cyclopropanecarboxylic Acids...

Reactions of imines derived from valine tert-butyl ester with Brassard s diene proceed highly stereoselective in the presence of Lewis acids, such as EtAlCl2, at low temperature. Removal of the chiral auxiliary is achieved via a Curtius rearrangement. 

Oxabicyclo[3.2.1]oct-6-en-2-ones are also available from this chemistry, as illustrated in Scheme 30. Treatment of 84 with sodium methoxide and then lithium hydroxide, followed by subjecting the resulting acid to the standard Curtius rearrangement conditions, results in the formation of 8-oxabicyclo[3.2.1]oct-6-en-2-one (85) in 52% yield. Racemic 85 has been used by Vogel in a stereoselective synthesis of the P-C-hexopyranoside 86. ... 

And last, but not least, Fu et al. [21] reported that the planar-chiral heterocycle 45d catalyzed the enantioselective addition of hydrazoic acid to ketenes. This result in the formation of an acyl azide intermediate, which then can be subjected to Curtius rearrangement to supply a straightforward stereoselective access to chiral amines. As can be seen from Scheme 3.26, amine derivatives 56 were obtained in... 

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