SYNTHESIS AND FIRST APPLICATIONS OF A NEW CHIRAL AUXILIARY (TERT-BUTYL YL)-5,5-DIMETHYL-4-OXOIMIDAZOLIDINE-1-CARBOXYLATE)

Both enantiomers of tert-butyl tyl)-5,5-dimethyl-4-oxoimidazolidine-1- carboxylate (11; Bbdmoic) were prepared from L-alanine (Schemes 1 and 2). The parent heterocycle, 2-tert-butyl-5,5-dimethylimidazolidin-4-on e (12; from 2-aminoisobutyramide, H-Aib-NH2, and pivalaldehyde) was al so available in both enantiomeric forms by resolution with O,O'-dibenz oyltartaric acid. The compound (R)- or (S)-11 was used as an auxiliary , but also as a chiral Aib building block in a dipeptide synthesis. Th e 3-propanoyl derivative 13 of (R)-11 was used for the preparation of enantiomerically pure 2-methyl-3-phenylpropanoic acid (enantiomer rati o (e.r.) 99.5:0.5), by benzylation of the Zn-enolate (-->14; Scheme S) . Oxidative coupling of the bis-enolate derived from heptanedioic acid and (S)-11 (-->23) and methanolysis of the auxiliary gave dimethyl tr ans-cyclopentane- 1,2-dicarboxylate (26) with an e.r. of 93:7 (Scheme 5, Fig. 5). The 3-(Boc-Gly)-Bbdmoic derivative 29 was doubly deprotona ted and, after addition of ZnBr2 alkylated with alkyl, benzyl, or ally l halides to give the higher amino-acid derivatives with excellent sel ectivities (e.r. > 99.5:0.5, Schemes 6 and 7). Michael additions of cu prates to [(E)-MeCH=CHCO]Bbdmoic 36 occurred in high yields, but high diastereoselectivities were only observed with aryl cuprates (diastere oisomer ratio (d.r.) 99:1 for R = Ph, Scheme 8). Finally, 3-(Boc-CH2)- Bbdmoic 17 was alkylated through the ester Li-enolate with primary and secondary alkyl, allyl, and benzyl halides with diastereoselectivitie s (ds) ranging from 91 to 98%, giving acetals of Boc-Aib-Xux-O(t-Bu) d ipeptides (Scheme 4). The effectiveness of Bbdmoic is compared with th at of other chiral auxiliaries previously used for the same types of t ransformations.