A DIASTEREOSELECTIVE APPROACH TO ALPHA-ALLYL-BETA-AMINO ACIDS USING THE IRELAND ENOLATE CLAISEN REARRANGEMENT

Ireland enolate-Claisen rearrangements of the esters 11 derived from a range of N-alkoxycarbonyl- and related beta-alanines 9 and allylic al cohols (e.g. 10) generally lead to good yields of alpha-allyl-beta-ami no acid derivatives 13, isolated for convenience as the corresponding esters 14. The N-tert-butoxycarbonyl (BOC) derivatives 15 proved to be especially useful and led to good to excellent yields of the alpha-al lyl-beta-amino acid derivatives 16 and 17, with diastereoselectivities usually in excess of 4:1. One set of optimum conditions consists of r earrangements of the N-BOC derivatives 15 by sequential treatment with lithium diisopropylamide and trimethylsilyl chloride [3 equiv. of eac h] in tetrahydrofuran at -78 degrees C followed by similar to 4 h unde r reflux. Isolated chemical yields of the derived methyl esters 16 and 17 were generally in the range 70-88%. The stereochemical outcome of the rearrangements was deduced by conversion of the initial silyloxyme thyl derivatives 16d and 17d. derived from the esters (E)-15d and (Z)- 15d, into the corresponding cis- and trans-butyrolactones 24 and 26, r espectively. The synthetic utility was further demonstrated by convers ions of the initial hydroxyethyl derivatives 19 and 20 into the valero lactones 28 and 29 and of the syn-isomer 19 into the piperidine 30. A chair-like transition state 31 is consistent with the direct relations hip between the allylic alcohol geometry and the nature of the major d iastereoisomer of the alpha-allyl-beta-amino acid derivatives (16 and 17) obtained; the E-lithio enolates of the starting esters are presuma bly favoured due to intramolecular complexation with the enolised carb amate function.