Axially Chiral Amidinium Ions as Inducers of Enantioselectivity in Diels−Alder Reactions

Schuster, Tilmann; Bauch, Markus; Dürner, Gerd; Göbel, Michael

doi:10.1021/ol991276i

Cited by 117 publications

(46 citation statements)

References 6 publications

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“…Their initial studies, employing achiral amidinium ions derived from palmitic acid, highlighted the importance of non-coordinating counterions, such as the tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (BAr Modest enantioselectivity in the Diels-Alder reaction was achieved by using catalyst 8 (Scheme 11). [52] The possibility that the phenol groups of 8 participate in additional Hbonding contacts with the diketone electrophile was suggested. High enantioselectivity in an amidinium-catalyzed reaction was reported more recently by Johnston and coworkers.…”

Section: Chiral Guanidinium and Amidinium Ionsmentioning

confidence: 99%

Asymmetric Catalysis by Chiral Hydrogen‐Bond Donors

2006

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Hydrogen bonding is responsible for the structure of much of the world around us. The unusual and complex properties of bulk water, the ability of proteins to fold into stable three-dimensional structures, the fidelity of DNA base pairing, and the binding of ligands to receptors are among the manifestations of this ubiquitous noncovalent interaction. In addition to its primacy as a structural determinant, hydrogen bonding plays a crucial functional role in catalysis. Hydrogen bonding to an electrophile serves to decrease the electron density of this species, activating it toward nucleophilic attack. This principle is employed frequently by Nature's catalysts, enzymes, for the acceleration of a wide range of chemical processes. Recently, organic chemists have begun to appreciate the tremendous potential offered by hydrogen bonding as a mechanism for electrophile activation in small-molecule, synthetic catalyst systems. In particular, chiral hydrogen-bond donors have emerged as a broadly applicable class of catalysts for enantioselective synthesis. This review documents these advances, emphasizing the structural and mechanistic features that contribute to high enantioselectivity in hydrogen-bond-mediated catalytic processes.

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Section: Chiral Guanidinium and Amidinium Ionsmentioning

confidence: 99%

Asymmetric Catalysis by Chiral Hydrogen‐Bond Donors

2006

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“…Als Katalysator fungierte hier ein chirales Amidiniumsalz, das die gewünschten Produkte in guten Selektivitäten lieferte. [16] Eine effizientere Methode wurde wenig später von Yamamoto und Nakashima am Beispiel einer Reaktion von Ethylvinylketon mit verschiedensten Dienen beschrieben. [6] In dieser Arbeit wurden erste Versuche mit dem bereits zuvor beschriebenen BP ent-15 a durchgeführt.…”

Section: Metall-liganden Oder Brønsted-säurenunclassified

Modulation der Acidität – hoch acide Brønsted‐Säuren in der asymmetrischen Katalyse

et al. 2011

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Chirale, hoch acide Brønsted‐Säuren haben sich als metallfreie Katalysatoren in der organischen Synthese etabliert und konnten mittlerweile in einer Vielzahl enantioselektiver C‐C‐ und C‐X‐Bindungsknüpfungen eingesetzt werden. Die hohe Acidität dieser neuen Katalysatoren macht sie zu nützlichen Hilfsmitteln für die Aktivierung verschiedener Imine, Carbonyle und weiterer schwach basischer Substrate. Durch die Bildung chiraler Kontaktionenpaare ergeben sich völlig neue Aktivierungsmöglichkeiten für die asymmetrische Katalyse. Dieser Kurzaufsatz gibt einen Überblick über das rationale Design dieser neuen Organokatalysatoren und beschreibt verschiedenste, kürzlich erschienene Anwendungen.

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“…The second metal-free catalysis of Diels-Alder reactions is based on the activation of the dienophile by hydrogen bonding, a form of Brønsted acid catalysis, with a chiral catalyst. To date this approach has been reported to provide only modest successes [Յ50% enantiomeric excess (ee)] (13). In this article, we report the highly enantioselective carbon Diels-Alder reactions (up to 92% ee) catalyzed through hydrogen bonding to an organic catalyst (14).…”

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confidence: 99%

“…The same group has recently reported highly enantioselective Mannich reactions catalyzed by a similar thiourea catalyst (29,30). In the area of cycloadditions, Göbel and coworkers (13) showed that enantioselective catalysis of Diels-Alder reactions could be achieved through hydrogenbond-mediated association of a dienophile to an axially chiral amidinium ion. Other recent examples of the use of hydrogen bonding are enantioselective Morita-Baylis-Hilman reactions of cyclic enones catalyzed by chiral BINOL derivatives (31), and Michael additions of malonates to nitroolefins catalyzed by functionalized thioureas (32).…”

mentioning

confidence: 99%

Enantioselective Diels–Alder reactions catalyzed by hydrogen bonding

Thadani

Stankovic²,

Rawal³

2004

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

210

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Like molecules of life (e.g., proteins and DNA), many pharmaceutical drugs are also asymmetric (chiral); they are not superimposable on their mirror images. One mirror image form (enantiomer) of a drug can have desirable activity, the other not. Consequently, the development of methods for the selective synthesis of one enantiomer is of great scientific and economic importance. We report here that a simple, commercially available chiral alcohol, ␣,␣,␣ ,␣ -tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL), catalyzes the all-carbon Diels-Alder reactions of aminosiloxydienes and substituted acroleins to afford the products in good yields and high enantioselectivities (up to 92% enantiomeric excess). It is remarkable that the reactions are promoted by hydrogen bonding, the ubiquitous ''glue'' that helps to keep water molecules together and holds up the 3D structures of proteins. Hydrogen bond catalysis is little used in chemical synthesis, wherein most reactions are promoted by complexes of Lewis acidic metal salts coordinated to chiral ligands. As it does for enzymes, hydrogen bonding not only organizes TADDOL into a well defined conformation, but, functioning as a Brønsted acid catalyst, it also activates the dienophile toward reaction with the diene. The gross structure of the TADDOL has been found to have a profound influence on both the rate and the enantioselectivity of the cycloadditions. These structure-function effects are rationalized by evaluating the conformation adopted by the TADDOLs in the crystal state. It is suggested that , -stacking plays an central role in the overall catalytic cycle, in particular, the enantioselective step.M ost biomolecules are asymmetric (chiral), that is, they are not superimposable on their mirror image. Likewise, small molecules that might be used to modulate the response of the biomolecule are also frequently chiral. One mirrorimage form (enantiomer) of the small molecule may elicit a desirable response, such as stimulation or inhibition of a particular function, whereas the other image might produce no response or a completely different response. It is, in part, for this reason that a tremendous effort has been put into the development of methods for the selective synthesis of one enantiomer. In 2002, single enantiomer drugs comprised 37% ($152 billion) of the total market of Ϸ$400 billion. This number is projected to increase steadily, such that chiral drugs will constitute a market of Ͼ$200 billion by 2008. The growing economic importance of chiral compounds has spurred major research efforts from many laboratories, academic and industrial, directed at the selective preparation of chiral compounds. In this report, we describe our results on the hydrogenbonding-mediated catalysis of the all-carbon Diels-Alder reaction.The premier process for forming functionalized cyclohexenes, with up to four new stereogenic centers (1), the Diels-Alder reaction plays a pivotal strategic role in the synthesis of numerous complex natural products (2). The steady evolution of this reaction...

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Axially Chiral Amidinium Ions as Inducers of Enantioselectivity in Diels−Alder Reactions

Cited by 117 publications

References 6 publications

Asymmetric Catalysis by Chiral Hydrogen‐Bond Donors

Asymmetric Catalysis by Chiral Hydrogen‐Bond Donors

Modulation der Acidität – hoch acide Brønsted‐Säuren in der asymmetrischen Katalyse

Enantioselective Diels–Alder reactions catalyzed by hydrogen bonding

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