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

Abstract

Both enantiomers of teut-butyl 2-(tert-butyl)-5,5-dimethyl-4-oxoimidazolidine-1 -carboxylate (1 1 ; Bbdmoic) were prepared from L-alanine (Schemes I and 2). The parent heterocycle, 2-fert-butyl-5,5-dimethylimidazolidin-4-one (1 2; from 2-aminoisobutyramide, H-Aib-NH,, and pivalaldehyde) was also available in both enantiomeric forms by resolution with 0.0'-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 (ex.) 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-l,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 ZnBr, 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:l 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(r-Bu) dipeptides (Scheme 4). The effectiveness of Bbdmoic is compared with that of other chiral auxiliaries previously used for the same types of transformations.1. Introduction. -Since the first reports of chiral-auxiliary-induced stereoselective reactions in the early 20th century by McKenzie [l], many 'chiral inductors' have been developed and successfully applied in asymmetric synthesis. The chemistry of auxiliarycontrolled stereoselective reactions (covalently bound) has been reviewed by several authors [2-81. Normally, these chiral auxiliaries are derived from natural sources such as amino acids [2] [3], carbohydrates [4] [5], terpenes [6], and steroids [9]. Synthetic auxiliaries that can be recovered after a reaction have also been described [7] [8] [lo-131. In Fig. I , a collection of successfully applied chiral auxiliaries is presented.During the last ten years, we have developed various chiral building blocks, based on five-membered heterocycles, oxazolidinones [28], and imidazolidinones [29], for the preparation of enantiomerically pure natural and unnatural amino acids. In the present paper, we report the synthesis and some applications of a new chiral auxiliary which is based on the imidazolidinones.

Stereoselective Lewis base catalyzed formal 1,3-dipolar cycloaddition of azomethine imines with mixed anhydrides

“…To show the value of pyrazolidinones as building blocks in synthesis, we tested a first follow-up reaction. To this end, N -benzoyl deprotection in pyrazolidinones 3aa and 3da was achieved with DBU/LiBr 23 in MeOH to give the corresponding NH-pyrazolidinones. N–N bond cleavage by reduction with Raney-Ni/H 2 eventually provided stereospecifically the tetrahydroisoquinolines 5aa and 5da in good yields ( Fig.…”

Synthesis and Characterization of a New Organocatalytic Biosourced Surfactant

“…The amine moiety of the obtained 4-imidazolidinone 9 was then Boc-protected to deactivate this group prior to the coupling between 8 and 10. This protection was performed with Boc 2 O in DCM at room temperature [42]. Only the syn diastereoisomers reacted in these conditions leading to 10 in 91% yield.…”

Stereoselective coupling of ketone and carboxylate enolates

“…Thus, the oxidative coupling of carboxylic acid dianions was inhibited when the amine arising from enolate generation with Li-amides was present in the reaction medium. 5,12 3 Stereoselective coupling of the enolates of carboxylic acid derivatives One of the key features of the oxidative dimerization reaction of carboxylic acid derivatives is the possibility of achieving a high degree of simple diastereoselectivity (syn+anti ratio). 13 This has been observed in the oxidative dimerization of the Li-dianions of carboxylic acids.…”