197704-07-7Relevant academic research and scientific papers
Synthesis of N-Cbz-fluoropyrruvaldehyde N,S-ketals: Construction of highly stereoselective and high yielding synthetic reactions using multivariate modelling and design
Bjorsvik, Hans-Rene,Bravo, Pierfrancesco,Crucianelli, Marcello,Volonterio, Alessandro,Zanda, Matteo
, p. 2817 - 2826 (1997)
The synthesis of (R)-fluoropyruvaldehyde-N,S-ketals via a tandem self-immolative Pummerer-type rearrangement of enantiopure (R)-α-fluoroalkyl-β-sulfinylenamines has been studied using statistical experimental design and multivariate modelling. By this study a procedure has been established which simultaneously gives excellent enantioselectivity and synthetically useful yields. The improvement of the ee of the trifluoro derivative was from 69% to 82%. The optimised procedure has been scaled up (10 fold) and extended to the corresponding difluoro and chlorodifluoro derivatives, with similarly good results. The chemometric analysis, along with a crossover experiment, strongly supports the hypothesis of a strictly intramolecular process, according to the previously proposed mechanism.
Highly stereoselective tandem Pummerer reaction/α-hydroxy imine rearrangement of e.P. β-sulfinylenamines
Bravo, Pierfrancesco,Crucianelli, Marcello,Volonterio, Alessandro,Zanda, Matteo
, p. 353 - 354 (2007/10/03)
The highly stereoselective tandem Pummerer reaction/α-hydroxy imine rearrangement of E.P. α-fluoroalkyl-β-sulfinylenamines affording chiral non-racemic fluoropyruvaldehydes N,S-ketals is described.
Preparation of (R)-Fluoropyruvaldehyde N,S-Ketals by Highly Stereospecific Tandem Pummerer Rearrangement/1,2-p-Tolylthio Group Migration of (R)-α-(Fluoroalkyl)-β-sulfinylenamines
Volonterio, Alessandro,Zanda, Matteo,Bravo, Pierfrancesco,Fronza, Giovanni,Cavicchio, Giancarlo,Crucianelli, Marcello
, p. 8031 - 8040 (2007/10/03)
Fluoropyruvaldehyde N,S-ketals (R)-2 have been prepared in good yields (up to 88%) and ee (up to 79%) from α-(fluoroalkyl)-β-sulfinylenamines (R)-(Z)-1, through a new self-immolative tandem sequential process, consisting of a Pummerer reaction, promoted by trifluoroacetic anhydride, followed by a 1,2-migration of the p-tolylthio group, triggered by addition of silica gel or aqueous base. Each transfer of stereogenic center, from sulfur to the α-carbon and then to the β-carbon, occurs with an average degree of enantioselectivity up to 94:6. Cis geometry between the sulfinyl and the amino groups of the starting enamine (R)-1 is necessary for achieving high level of stereocontrol, since neighboring group participation by the N-Cbz amino group prevents the sulfinyl center from racemization promoted by trifluoroacetic anhydride. NMR studies have shown that imines 3 are intermediate products of the Pummerer rearrangement, which are stable in the reaction environment.
