Neuartige asymmetrische Cyclisierung zu optisch aktiven Steroid‐CD‐Teilstücken

Eder, Ulrich; Sauer, Gerhard; Wiechert, Rudolf

doi:10.1002/ange.19710831307

Cited by 393 publications

(107 citation statements)

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“…Instead, its results pointed to an exceptional sensitivity to conditions of the stereochemical outcome of such a reaction. This implied that no conclusion could be drawn from the model study with regard to the mechanism of the stereoselection observed by Hajos and Parrish [11], and by Eder et al [12].…”

Section: Methodsmentioning

confidence: 92%

“…While the N-acyl derivatives of type 3 are quite stable 12 ), the bicyclic oxazolidinones 2 are difficult to purify and isolate on a preparative scale 13 ) for two reasons: i) They must be handled under exclusion of moisture; neat liquid samples or solutions in common organic solvents turn cloudy on contact with air, due to formation of the insoluble amino acids. ii) They undergo decarboxylation at elevated temperatures, with generation of azomethine ylides, which can be trapped by dipolarophiles 14 ), as shown for oxazolidinone 2a in the reaction with tetrakis(methoxycarbonyl)ethylene (!…”

Section: Methodsmentioning

confidence: 99%

“…Short Summary of the Work Performed in the 1970 s. That early work had been an attempt to respond to the challenge of a mechanistic rationalization of the (at the time) dramatic stereoselection observed in the proline-catalyzed aldolization step of the formation of the Wieland -Miescher ketone by Hajos and Parrish [11], and by Eder, Sauer, and Wiechert [12] in 1971/1974. The experimental effort was based on the conception of two hypothetical stereoselection factors, both stereoelectronic in nature: one of them referred to a possible role of the carboxylate group of the proline-substrate enamine derivative (see formulae I and II) in the sense that an intramolecular nucleophilic participation of a carboxylate Oatom in the product-determining step (presumed to be the electrophilic addition of a carbonyl C-atom to the enamine C¼C bond) would prefer the trans-antiperiplanar mode (i.e., I) as against the trans-lateral mode (i.e., II).…”

mentioning

confidence: 99%

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Are Oxazolidinones Really Unproductive, Parasitic Species in Proline Catalysis? – Thoughts and Experiments Pointing to an Alternative View

Seebàch¹,

Beck²,

Badine³

et al. 2007

Helvetica Chimica Acta

227

202

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Dedicated to Professor Yoshito Kishi on the occasion of his 70th birthdayThe N,O-acetal and N,O-ketal derivatives (oxazolidinones) formed from proline, and aldehydes or ketones are well-known today, and they are detectable in reaction mixtures involving proline catalysis, where they have been considered parasitic dead ends . We disclose results of experiments performed in the early 1970 s, and we describe more recent findings about the isolation, characterization, and reactions of the oxazolidinone derived from proline and cyclohexanone. This oxazolidinone reacts (THF, room temperature) with the electrophiles b-nitrostyrene and chloral (¼ trichloroacetaldehyde), to give the Michael and aldol adduct, respectively, after aqueous workup (Scheme 5). The reactions occur even at À 758 when catalyzed with bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or EtN(i-Pr) 2 (DIPEA) (10%; Table 1). It is shown by NMR (Figs. 1 and 3) and IR analysis (Figs. 2 and 4) that the primarily detectable product (before hydrolysis) of the reaction with the nitro-olefin is again an oxazolidinone. When dissolved in hydroxylic solvents such as MeOH, hexafluoroisopropanol ((CF 3 ) 2 CHOH; HFIP), AcOH, CF 3 COOH, or in LiBr-saturated THF, the ring of the oxazolidinone from cyclohexanone and proline opens up to the corresponding iminium ion (Tables 2 -4), and when treated with strong bases such as DBU (in (D 8 )THF) the enamino-carboxylate derived from proline and cyclohexanone is formed (Scheme 8). Thus, the two hitherto putative participants (iminium ion and enamine) of the catalytic cycle (Scheme 9) have been characterized for the first time. The commonly accepted mechanism of the stereoselective C,C-or C,X-bond-forming step (i.e., A -D) of this cycle is discussed and challenged by thoughts about an alternative model with a pivotal role of oxazolidinones in the regio-and diastereoselective formation of the intermediate enamino acid (by elimination) and in the subsequent reaction with an electrophile (by trans-addition with lactonization; Schemes 11 -14). The stereochemical bias between endo-and exo-space of the bicyclo[3.3.0]octane-type oxazolidinone structure (Figs. 5 and 6) is considered to possibly be decisive for the stereochemical course of events.Helvetica Chimica Acta -Vol. 90 (2007) Finally, the remarkable consistency, with which the diastereotopic Re-face of the double bond of pyrrolidino-enamines (derived from proline) is attacked by electrophiles (Schemes 1 and 15), and the likewise consistent reversal to the Si-face with bulky (Aryl) 2 C-substituents on the pyrrolidine ring (Scheme 16) are discussed by invoking stereoelectronic assistance from the lone pair of pyramidalized enamine N-atoms.1. Introduction. -We would hardly have considered to become engaged in the timely research area of organocatalysis , had not, in the recent literature, the name of one of the present authors (D. S.) been implied in a statement on the mechanism of the stereoselection in proline catalysis (see title) such that this author was incited to ...

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Section: Methodsmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Are Oxazolidinones Really Unproductive, Parasitic Species in Proline Catalysis? – Thoughts and Experiments Pointing to an Alternative View

Seebàch¹,

Beck²,

Badine³

et al. 2007

Helvetica Chimica Acta

227

202

View full text Add to dashboard Cite

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“…For the optimization of activity and selectivity, directed-evolution methodologies (combined with an efficient selection or screening tool) outperform combinatorial ligand libraries. [3][4][5][6][7][8][9][10][11][12][13] With the hope of alleviating some of the inherent limitations of both enzymatic and organometallic catalysis, two approaches have recently witnessed a revival: 1) organocatalysis [14][15][16][17][18][19] and 2) artificial metalloenzymes based on either covalent [20,21] or supramolecular anchoring [22] of a catalytic moiety in a macromolecular host. [23][24][25][26][27][28][29][30] Inspired by the early works of Whitesides and Wilson, [22] we recently reported artificial metalloenzymes based on the biotin-avidin technology.…”

mentioning

confidence: 99%

Tailoring the Active Site of Chemzymes by Using a Chemogenetic‐Optimization Procedure: Towards Substrate‐Specific Artificial Hydrogenases Based on the Biotin–Avidin Technology

et al. 2005

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Dedicated to Professor George M. WhitesidesCatalysis offers efficient means to produce enantiopure products. Traditionally, enzymatic and homogeneous catalysis have evolved independently to afford mild, robust, active, and highly selective catalysts. [1, 2] Both systems are often considered complementary in terms of substrate and reaction scope, operating conditions, enantioselectivity mechanism, reaction medium, etc. For the optimization of activity and selectivity, directed-evolution methodologies (combined with an efficient selection or screening tool) outperform combinatorial ligand libraries. [3][4][5][6][7][8][9][10][11][12][13] With the hope of alleviating some of the inherent limitations of both enzymatic and organometallic catalysis, two approaches have recently witnessed a revival: 1) organocatalysis [14][15][16][17][18][19] and 2) artificial metalloenzymes based on either covalent [20,21] or supramolecular anchoring [22] of a catalytic moiety in a macromolecular host. [23][24][25][26][27][28][29][30] Inspired by the early works of Whitesides and Wilson, [22] we recently reported artificial metalloenzymes based on the biotin-avidin technology. [31][32][33][34][35] Herein, we report our efforts to produce substrate-specific and S-selective artificial metalloenzymes based on the biotin-avidin technology for the hydrogenation of a-acetamidodehydroamino acids.The starting point for the chemogenetic-optimization procedure presented herein is the identification of [Rh(cod)-(biot-1)] + &S112G Sav (cod = 1,5-cyclooctadiene, biot =[*] Dr.

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“…1,2 Beginning from the discovery of the L-proline-catalyzed aldol reaction, [3][4][5] over the years, it evolved into a general strategy for the activation of carbonyl compounds. Ten years ago, this mode of activation was limited to the formation of enamines and iminium ions as intermediates (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%