ESI-MS study on the aldol reaction catalyzed by l-proline

Márquez, César; Metzger, Jürgen O.

doi:10.1039/b518288c

Cited by 99 publications

(75 citation statements)

References 25 publications

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“…5) reveals the following facts: the oxazolidinones derived from aldehydes are more stable with the substituent at C(2) in the exo-position, in nonsymmetrical ketone derivatives the larger substituent will prefer to reside in the exoposition, and in oxazolidinones derived from symmetrical ketones the substituent in the exo-position is less sterically hindered (Fig. 5, a and b) 42 ). Furthermore, in the spirocyclic cyclohexanone-derived oxazolidinone 8, the conformer with axial O-atom and equatorial N-atom has to be assumed to be more stable than the conformer with the two heteroatoms reversed 43 ) (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…For a dissociative ring-opening of an oxazolidinone to a zwitterionic iminium carboxylate (Fig. 5, d), a process that formally does not follow a 42 ) All pivalaldehyde derivatives have exclusively exo-configuration [16 -19] [55], so has the chloral derivative of proline [7]. In oxazolidinones derived from aldehydes RCHO with smaller R groups, NMR-detectable amounts of a minor diastereoisomer have been reported ([8] and hitherto unpublished results by W. Prikoszovich, B. Linder, Novartis Pharma AG, Basel).…”

Section: Methodsmentioning

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

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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: 99%

Section: Methodsmentioning

confidence: 99%

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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“…Although aldehyde-derived "Seebach oxazolidinones" (15)(16)(17) have long been known, their ketone analogues have only recently been detected and characterized by us (14) and later isolated also by Seebach et al (18). Interestingly, the condensation product of acetone and proline has also been detected by Marquez and Metzger using mass spectrometry (19). In light of our previous careful NMR-spectroscopic characterization of this adduct as an oxazolidinone (14), their assignment as an enamine appears to be questionable.…”

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confidence: 97%

Crystal structures of proline-derived enamines

Bock

Lehmann

List

2010

Proc. Natl. Acad. Sci. U.S.A.

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The isolation and structural characterization of both aldehyde-and ketone-derived proline enaminones are reported and discussed. Crystal structures of 10 proline enamines provide information on stereochemical aspects, i.e., double bond configuration and synvs. anti-positioning of the carboxylate relative to the enamine double bond. Furthermore, the obtained crystal structures are compared with the density functional theory-calculated structures of the ground and transition state and the postulated SeebachEschenmoser transition state.enamine catalysis | mechanism | organocatalysis

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“…Furthermore, based on List's studies [46] we have also observed the presence of a linear relationship between the enantioselectivity of the catalyst and the observed enantioselectivity of the aldol product, thus supporting the involvement of only one molecule of the prolinethioamide in the transition state [18]. For the L-proline catalyzed aldol reaction all assumed intermediates involved were characterized by ESI-MS study [47]. While using the 1 H NMR technique, the formation of assumed iminium ion was observed in the thioamide catalyzed reaction [30].…”

Section: Mechanism Of the Aldol Reaction Catalyzed By Prolinamide Dermentioning

confidence: 99%

Prolinethioamides versus Prolinamides in Organocatalyzed Aldol Reactions—A Comparative Study

2011

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Various organocatalysts have been developed for the aldol reaction but particular attention has been paid to prolinamide derivatives. They are easy to prepare and their catalytic activity can be readily tuned through structural modification. In this review, the comparison of catalytic activities between prolinethioamides and their respective amides in direct asymmetric aldol reactions is presented.

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ESI-MS study on the aldol reaction catalyzed by l-proline

Abstract: The aldol reaction catalyzed by L-proline has been monitored and the accepted mechanism confirmed by intercepting and characterizing, for the first time, all the proposed intermediates by ESI-MS/MS.

Cited by 99 publications

References 25 publications

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

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

Crystal structures of proline-derived enamines

Prolinethioamides versus Prolinamides in Organocatalyzed Aldol Reactions—A Comparative Study

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