Synthesis and First Applications of a New Chiral Auxiliary (tert‐butyl 2‐(tert‐butyl)‐5,5‐dimethyl‐4‐oxoimidazolidine‐1‐carboxylate)

Abstract

AbstractBoth enantiomers of tert‐butyl 2‐(tert‐butyl)‐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‐one (12; from 2‐aminoisobutyramide, H‐Aib‐NH2, and pivalaldehyde) was also available in both enantiomeric forms by resolution with O,O′‐dibenzoyltartaric acid. The compound (R)‐ or (S)‐11 was used as an auxiliary, but also as a chiral Aib building block in a dipeptide synthesis. The 3‐propanoyl derivative 13 of (R)‐11 was used for the preparation of enantiomerically pure 2‐methyl‐3‐phenylpropanoic acid (enantiomer ratio (e.r.) 99.5:0.5), by benzylation of the Zn‐enolate (→ 14; Scheme 3). Oxidative coupling of the bis‐enolate derived from heptanedioic acid and (S)‐11 (→ 23) and methanolysis of the auxiliary gave dimethyl trans‐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 deprotonated and, after addition of ZnBr2 alkylated with alkyl, benzyl, or allyl halides to give the higher amino‐acid derivatives with excellent selectivities (e.r. > 99.5:0.5, Schemes 6 and 7). Michael additions of cuprates to [(E)‐MeCHCHCO]‐Bbdmoic 36 occurred in high yields, but high diastereoselectivities were only observed with aryl cuprates (diastereoisomer 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 diastereoselectivities (ds) ranging from 91 to 98%, giving acetals of Boc‐Aib‐Xxx‐O(t‐Bu) dipeptides (Scheme 4). The effectiveness of Bbdmoic is compared with that of other chiral auxiliaries previously used for the same types of transformations.