Enantiomerically pure dihydropyrimidinones as reagents and auxiliaries for asymmetric synthesis

Chu, Kent S.; Negrete, George R.; Konopelski, Joseph P.; Lakner, Frederick J.; Woo, Nam Tae; Olmstead, Marilyn M.

doi:10.1021/ja00031a039

Cited by 77 publications

(28 citation statements)

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“…125,127,128 Indeed, condensation of (S)-asparagine with pivalaldehyde according to the procedure described by Konopelski and co-workers, 129,130 followed by protection of the amino group, oxidative decarboxylation, and Pd-catalyzed hydrogenation, gives in good yield the chiral perhydropyrimidin-4-one (Scheme 5).…”

Section: Enantioselective Synthesis Of ␤ 2 -Amino Acids Via Chiral ␤-mentioning

confidence: 99%

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

2004

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Although they are less abundant than their alpha-analogues, beta-amino acids occur in nature both in free form and bound to peptides. Oligomers composed exclusively of beta-amino acids (so-called beta-peptides) might be the most thoroughly investigated peptidomimetics. Beside the facts that they are stable to metabolism, exhibit slow microbial degradation, and are inherently stable to proteases and peptidases, they fold into well-ordered secondary structures consisting of helices, turns, and sheets. In this respect, the most intriguing effects have been observed when beta2-amino acids are present in the beta-peptide backbone. This review gives an overview of the occurrence and importance of beta2-amino acids in nature, placing emphasis on the metabolic pathways of beta-aminoisobutyric acid (beta-Aib) and the appearance of beta2-amino acids as secondary metabolites or as components of more complex natural products, such as peptides, depsipeptides, lactones, and alkaloids. In addition, a compilation of the syntheses of both achiral and chiral beta2-amino acids is presented. While there are numerous routes to achiral beta2-amino acids, their EPC synthesis is currently the subject of many investigations. These include the diastereoselective alkylation and Mannich-type reactions of cyclic- or acyclic beta-homoglycine derivatives containing chiral auxiliaries, the Curtius degradation, the employment of transition-metal catalyzed reactions such as enantioselective hydrogenations, reductions, C-H insertions, and Michael-type additions, and the resolution of rac. beta2-amino acids, as well as several miscellaneous methods. In the last part of the review, the importance of beta2-amino acids in the formation of beta-peptide secondary structures is discussed.

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Section: Enantioselective Synthesis Of ␤ 2 -Amino Acids Via Chiral ␤-mentioning

confidence: 99%

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

2004

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“…Proton NMR was employed to monitor the cyclocondensation of asparagine and trimethylacetaldehyde in NaOH/D 2 O over 12 h. Spectral interpretation of the sample removed at 15 min indicated that an imine formed in several minutes, followed by a much slower cyclization to 1, as indicated by the disappearance of the imine singlet (7.6 ppm) and the emergence of the diastereotopic C2 proton signals (of 1) centered at 4.1 ppm. The product was cleanly formed in 4 h and exhibited a strong prevalence of trans heterocycle 1 (93% major isomer based on integration), 8 a much smaller amounts of aldehyde (4%), an imine intermediate (2%), and no evidence of the asparagine.…”

Section: Resultsmentioning

confidence: 98%

A fully-telescoped, aqueous, auxiliary-mediated asymmetric transformation

Mahindaratne¹,

Quiñones²,

Recio³

et al. 2005

Arkivoc

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Dedicated to Professor Eusebio AbstractA fully-telescoped, aqueous, auxiliary-mediated Diels-Alder cycloaddition in moderate selectivity is reported. The auxiliary is prepared from L-asparagine and trimethylacetaldehyde, and coupled without isolation to the acryloyl substrate. Direct addition of cyclopentadiene generates the cycloadduct, which is cleaved from the heterocycle upon mild treatment with acid and heat. A significantly reduced selectivity is observed relative to the two-pot synthesis in which the acrylamide is precipitated and washed prior to the cycloaddition. Vacuum-assisted removal of the acrylic acid contaminant prior to the cycloaddition substantially remedies the reduced selectivities achieved in the one-pot transformation relative to the two-step sequence. Four chemical transformations, not including acid/base reactions, are accomplished in this onepot synthesis.

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“…-A typical reaction for studying the potential of a new chiral auxiliary is the alkylation of its propanoic-acid derivative. For almost every auxiliary, the corresponding results were published [lo] [12] [17] [24c] [25] [26]. We, therefore, decided to study this reaction first.…”

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confidence: 92%

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

Studer

Hintermann

Seebàch³

1995

Helvetica Chimica Acta

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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.

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Enantiomerically pure dihydropyrimidinones as reagents and auxiliaries for asymmetric synthesis

Cited by 77 publications

References 7 publications

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

A fully-telescoped, aqueous, auxiliary-mediated asymmetric transformation

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

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Enantiomerically pure dihydropyrimidinones as reagents and auxiliaries for asymmetric synthesis

Cited by 77 publications

References 7 publications

β2‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides1,2

β2‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides1,2

A fully-telescoped, aqueous, auxiliary-mediated asymmetric transformation

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

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β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2