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Synthesis and First Applications of a New Chiral Auxiliary ( tert ‐butyl 2‐( tert ‐butyl)‐5,5‐dimethyl‐4‐oxoimidazolidine‐1‐carboxylate)
Author(s) -
Studer Armido,
Hintermann Tobias,
Seebach Dieter
Publication year - 1995
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19950780512
Subject(s) - chemistry , deprotonation , alkylation , enantiomer , medicinal chemistry , diastereomer , chiral auxiliary , aryl , stereochemistry , alkyl , organic chemistry , enantioselective synthesis , catalysis , ion
Abstract Both 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‐NH 2 , 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 ZnBr 2 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 )‐MeCHCHCO]‐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‐CH 2 )‐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.