Preparation of (R)-Fluoropyruvaldehyde N,S-Ketals by Highly Stereospecific Tandem Pummerer Rearrangement/1,2-p-Tolylthio Group Migration of (R)-alpha-(Fluoroalkyl)-beta-sulfinylenamines.
Fluoropyruvaldehyde N,S-ketals (R)-2 have been prepared in good yields (up to 88%) and ee (up to 79%) from alpha-(fluoroalkyl)-beta-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 alpha-carbon and then to the beta-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.
Volonterio
Alessandro
A
Dipartimento di Chimica, Ingegneria Chimica e Materiali, Università di L'Aquila, Via Vetoio, I-67010 Coppito, Italy.
Zanda
Matteo
M
Bravo
Pierfrancesco
P
Fronza
Giovanni
G
Cavicchio
Giancarlo
G
Crucianelli
Marcello
M