Kinetic Resolution of Secondary Alcohols. Enantioselective Acylation Mediated by a Chiral (Dimethylamino)pyridine Derivative

Vedejs, E.; Chen, Xinhai

doi:10.1021/ja953631f

Cited by 246 publications

(120 citation statements)

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“…to maximise the effectiveness of catalyst stereochemical information it is desirable to install chiral groups as close to the nucleophilic ring nitrogen as possible, however, bulky substituents in the vicinity of the same strongly attenuate catalyst activity. 14,17c, 29 A successful (i.e. active and selective) catalyst design must necessarily embody a compromise between these opposing constraints.…”

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confidence: 99%

Asymmetric acyl-transfer promoted by readily assembled chiral 4-N,N-dialkylaminopyridine derivatives

et al. 2006

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The development of a new class of chiral 4-N,N-dialkylaminopyridine acyl-transfer catalysts capable of exploiting both van der Waals (p) and H-bonding interactions to allow remote chiral information to stereochemically control the kinetic resolution of sec-alcohols with moderate to excellent selectivity (s = 6-30). Catalysts derived from (S)-a,a-diarylprolinol are considerably superior to analogues devoid of a tertiary hydroxyl moiety and possess high activity and selectivity across a broad range of substrates.Asymmetric organocatalysis has recently been propelled from relative obscurity to the forefront of contemporary organic chemistry research and is fast-becoming a key strategy in enantioselective synthesis. 1, 2 An important facet of this broad domain is the asymmetric nonenzymatic 3 catalysis of acyl-transfer by chiral organic nucleophiles such as tertiary amines, 4-7 phosphines, 8 N-heterocyclic carbenes 9,10 and secondary alcohols. 11 Although it has been over a century since the discovery of pyridine-promoted alcohol acylation, 12 the design of efficient and selective chiral pyridine-based catalysts for these reactions is a young field less than 10 years old. The desymmetrisation of the 'hypernucleophilic' achiral catalyst 4-N,N-dimethylaminopyridine (DMAP) 13,14 via one of three general strategies, (the introduction of 'planar chirality' either 2,3-pyridofused 15 or installed at the C-3-position of the pyridine ring, 16 the use of axially chiral substituents at C-3 17 or the installation of tetrahedral chirality at either C-4, 18-23 or C-3, 24-27 ) has proven a particularly productive approach which has given rise to a number of highly selective chiral catalysts for the kinetic resolution (KR) of sec-alcohols and other asymmetric acyl-transfer processes. 15,27, 28 The design of such systems is complicated by an activityselectivity conundrum: i.e. to maximise the effectiveness of catalyst stereochemical information it is desirable to install chiral groups as close to the nucleophilic ring nitrogen as possible, however, bulky substituents in the vicinity of the same strongly attenuate catalyst activity. 14,17c,29 A successful (i.e. active and selective) catalyst design must necessarily embody a compromise between these opposing constraints.One appealing solution to this problem (inspired by enzymatic systems) is the design of promoters capable of operating by an 'induced-fit' mechanism, in which the catalyst undergoes a a Centre for Synthesis and Chemical Biology, School of Chemistry, University of Dublin, Trinity College, Dublin 2, Ireland. E-mail: connons@tcd.ie; Fax: +353 1 6712826; Tel: +353 1 6081306 b School of Chemistry, University of Dublin, Trinity College, Dublin 2, Ireland † Electronic supplementary information (ESI) available: General experimental procedures and details, characterisation data for the synthesis of catalysts 14 and 15, 1 H and 13 C NMR spectra for 6 and 7 (and their precursors), X-ray crystal structure data for 6-Bn, atomic coordinates from the DFT calculations and CSP...

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Asymmetric acyl-transfer promoted by readily assembled chiral 4-N,N-dialkylaminopyridine derivatives

et al. 2006

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“…[2,5] Miller has devised several new functional peptides that catalyze the kinetic resolution of selected secondary alcohols [6] as well as a variety of other transformations. [7] Other noteworthy examples of organic catalysts include those of Fuji, [8] Spivey, [9] Oriyama, [10] Vedejs, [11] Breslow, [12] Enders, [13] and Rovis [14] as well as extensive studies of biocatalysts.[15]We were recently challenged to develop effective organic polymerization reactions in an effort to develop new materials for microelectronics, where residual metals must be avoided. During our initial survey of a variety of organic catalysts for the ring-opening polymerization (ROP) of cyclic esters we showed that nucleophilic catalysts such as tertiary amines, [16] phosphines [17] and stabilized singlet carbenes were effective polymerization catalysts for strained cyclic esters.…”

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confidence: 99%

Bredereck's Reagent Revisited: Latent Anionic Ring‐Opening Polymerization and Transesterification Reactions

Csihony¹,

Beaudette²,

Sentman³

et al. 2004

Adv Synth Catal

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The ring-opening polymerization of lactide with commercially available Bredereck-type reagents in the presence or absence of alcohol initiators was carried out affording polylactide with controlled molecular weight and narrow polydispersities. An anionic mechanism involving heterolytic cleavage to alkoxides is proposed, where these reagents function as latent anionic initiators for the ring-opening polymerization of lactide.Keywords: anionic polymerization; Brederecks reagent; carbene; organic catalysis; polylactide There has been a recent resurgence of interest in the development of organocatalytic reactions. Catalysis with simple organic molecules can provide an attractive alternative to organometallic catalysis, particularly in situations where residual metals or ligands compromise the purity or end-use of the product. Representative recent examples include MacMillans elegant studies of highly enantioselective organocatalytic inter-and intramolecular Diels-Alders reactions, 1,3-dipolar cycloadditions, 1,4-conjugate Friedel-Crafts additions as well as the alkylation of indoles. [1,2,3] Proline has proven to be an efficient organic catalyst for a variety of reactions such as the Mannich reaction to generate precursors to b-lactams, [3] and several groups have reported effective nonenzymatic catalysts for the kinetic resolution of secondary alcohols using both "planar-chiral" phosphines [4] and amine catalyst frameworks. [2,5] Miller has devised several new functional peptides that catalyze the kinetic resolution of selected secondary alcohols [6] as well as a variety of other transformations. [7] Other noteworthy examples of organic catalysts include those of Fuji, [8] Spivey, [9] Oriyama, [10] Vedejs, [11] Breslow, [12] Enders, [13] and Rovis [14] as well as extensive studies of biocatalysts.[15]We were recently challenged to develop effective organic polymerization reactions in an effort to develop new materials for microelectronics, where residual metals must be avoided. During our initial survey of a variety of organic catalysts for the ring-opening polymerization (ROP) of cyclic esters we showed that nucleophilic catalysts such as tertiary amines, [16] phosphines [17] and stabilized singlet carbenes were effective polymerization catalysts for strained cyclic esters.[18] Of these, the N-heterocyclic carbenes (NHCs) were by far the most active. Extensions of this work demonstrated that NHCs are also potent transesterification catalysts [19] for a variety of esters and alcohols. Nevertheless, while NHCs are excellent transesterification catalysts, the convenience of these species as catalysts is compromised by their sensitivity to air and moisture, necessitating airsensitive techniques. To this end, we have focused on strategies for generating the reactive N-heterocyclic carbenes in situ, [20] including the deprotonation of imidazolium salts (1), [21] or the thermolysis of adducts (2). [22] Inspired by some of the original work of Arduengo, Wanzlick, Lappert and Bredereck, [23,24,25] we reasoned that...

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“…In den vergangenen Jahren hat DMAP verschiedenen Arbeitsgruppen als Grundlage für die Entwicklung chiraler Acylierungskatalysatoren gedient. [7] Wir berichten nun über die erhöhte katalytische Aktivität von 4-(Dialkylamino)pyridinen, deren 4-Aminogruppe durch Ringschluss zum Pyridinring konformativ fixiert ist. Aus früheren Arbeiten war bekannt, dass 4-Pyrrolidinopyridin (PPY, 2) [3a, 8, 9] ein wirksamerer Acylierungskatalysator als DMAP ist.…”

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Steigerung der katalytischen Aktivität von 4‐(Dialkylamino)pyridinen durch konformative Fixierung

et al. 2003

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Professor Heinrich Nöth zum 75. Geburtstag gewidmet 4-(Dimethylamino)pyridin (DMAP, 1) wurde vor über 30 Jahren als hoch wirksamer nucleophiler Katalysator zur Gruppenübertragung in die Synthesechemie eingeführt [1,2] und hat sich seitdem als Standardreagens [3] für Acylierungen, Veresterungen, [4] Makrolactonisierungen [5] und Silylierungen, [6] um nur einige Anwendungen zu nennen, bewährt. In den vergangenen Jahren hat DMAP verschiedenen Arbeitsgruppen als Grundlage für die Entwicklung chiraler Acylierungskatalysatoren gedient. [7] Wir berichten nun über die erhöhte katalytische Aktivität von 4-(Dialkylamino)pyridinen, deren 4-Aminogruppe durch Ringschluss zum Pyridinring konformativ fixiert ist. Aus früheren Arbeiten war bekannt, dass 4-Pyrrolidinopyridin (PPY, 2) [3a, 8, 9] ein wirksamerer Acylierungskatalysator als DMAP ist. Offensichtlich hängt die katalytische Aktivität von der Stabilisierung des N-Acylpyridinium-Ions durch Wechselwirkung mit dem freien Elektronenpaar der 4-Aminogruppe ab.[10] Eine Verbesserung dieser Wechselwirkung sollte daher mit einer Erhöhung der Katalyseleistung einhergehen. Von 4,4'-Bis(dialkylamino)benzhydryl-Kationen ist bekannt, dass die Einbindung des Stickstoffatoms in ein konformativ fixiertes Ringsystem deutlich besser stabilisierte Kationen liefert.[11] Dies wird durch die Reihe der Benzhydryl-Kationen 3-5 illustriert (Schema 1), in der das Bisjulolidinyl-Derivat 5 etwa 300-mal weniger elektrophil ist als das einfache Bisdimethylamino-Derivat 3. Wir schlossen daraus, dass eine konformative Fixierung verbunden mit dem positiven induktiven Effekt der meta-Alkylgruppe sich in ähnli-cher Weise auf die entsprechenden 4-(Dialkylamino)pyridine auswirken sollte, weil die Erhöhung der Elektronendichte am Pyridinstickstoffatom eine Stabilisierung des N-Acylpyridinium-Ions bewirkt. Für unsere Studie verwendeten wir die 4-(Dialkylamino)pyridine 6 und 7.Die höhere Stabilität der von 6 und 7 abgeleiteten NAcyl-Zwischenstufen lässt sich durch Berechnung der Reaktionsenthalpie für den Acetyltransfer gemäß Gleichung (1) Schema 1. Relative Reaktivitäten von Benzhydryl-Kationen, abgeleitet aus den Geschwindigkeitskonstanten ihrer Reaktionen mit p-Nucleophilen (20 8C).

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Kinetic Resolution of Secondary Alcohols. Enantioselective Acylation Mediated by a Chiral (Dimethylamino)pyridine Derivative

Cited by 246 publications

References 14 publications

Asymmetric acyl-transfer promoted by readily assembled chiral 4-N,N-dialkylaminopyridine derivatives

Asymmetric acyl-transfer promoted by readily assembled chiral 4-N,N-dialkylaminopyridine derivatives

Bredereck's Reagent Revisited: Latent Anionic Ring‐Opening Polymerization and Transesterification Reactions

Steigerung der katalytischen Aktivität von 4‐(Dialkylamino)pyridinen durch konformative Fixierung

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