Study of the reactions between vinylmagnesium bromide and imines derived from (R)-glyceraldehyde -: The key step in the stereodivergent synthesis of conveniently protected, enantiopure syn- and anti-2-amino-1,3,4-butanetriol derivatives

A total stereodivergent method for the synthesis of enantiopure syn- and anti-2-amino-1,3,4-butanetriol (ABT) derivatives from inexpensive and readily available D-mannitol has been developed. Key steps include: (a) the diastereoselective addition of vinylmagnesium bromide to conveniently protected N-benzylimines derived from (R)-glyceraldehyde, and (b) the oxidative degradation of the C-C double bond of the resultant syn- and anti-vinylaminodiol derivatives. The addition of vinylmagnesium bromide in diethyl ether to the N-benzylimine derived from (R)-2,3-O-isopropylideneglyceraldehyde affords the anti-vinylaminodiol derivative, while the reaction with the N-benzylimine derived from (R)-2,3-di-O-benzylglyceraldehyde affords the syn-vinylaminodiol derivative, both with excellent diastereoselectivities (de > 98/2). Moreover, a reversal of the stereochemical course of the reaction is produced when (R)-2,3-O-isopropylideneglyceraldehyde N-benzylimine is precomplexed with ZnI2, in this case yielding the syn addition adduct as the major compound. Different reaction conditions (reagent molar ratio, reaction temperature) have been tested in order to determine their influences on the observed yields and diastereoselectivities. From the results of this study and a subsequent crossover experiment, some interesting mechanistic considerations can be inferred. Enantiopure anti- and syn-vinylaminodiol adducts have been successfully converted into conveniently protected anti- and syn-2-amino-1,3,4-butanetriol (ABT) derivatives, key building blocks in the asymmetric synthesis of biologically active compounds. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).