Enantioselective Michael Reaction of Malonates to Nitroolefins Catalyzed by Bifunctional Organocatalysts

Okino, Tomotaka; Hoashi, Yasutaka; Takemoto, Yoshiji

doi:10.1021/ja036972z

Cited by 1,365 publications

(656 citation statements)

References 31 publications

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“…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.

209

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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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mentioning

confidence: 99%

Enantioselective Diels–Alder reactions catalyzed by hydrogen bonding

Thadani

Stankovic²,

Rawal³

2004

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

209

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“…19 The types of catalysts which are able to simultaneously activate two reactants are manifold, ranging from, e.g., proline 21 to cinchona alkaloid derivatives 22,23 and bifunctional (thio)urea derivatives 24 (such as Takemoto's catalyst; Fig. 3), 25 and have proved their efficiency in a variety of reactions. 19,[21][22][23][24][25] The third type of catalysis that should be distinguished from multicatalysis is dual catalysis (Fig.…”

Section: Multicatalysis -A Surveymentioning

confidence: 99%

“…3), 25 and have proved their efficiency in a variety of reactions. 19,[21][22][23][24][25] The third type of catalysis that should be distinguished from multicatalysis is dual catalysis (Fig. 4).…”

Section: Multicatalysis -A Surveymentioning

confidence: 99%

Evolution of asymmetric organocatalysis: multi- and retrocatalysis

2012

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The evolution of organocatalysis led to various valuable approaches, such as multicomponent as well as domino and tandem reactions. Recently, organomulticatalysis, i.e., the modular combination of distinct organocatalysts enabling consecutive reactions to be performed in one pot, has become a powerful tool in organic synthesis. It allows the construction of complex molecules from simple and readily available starting materials, thereby maximizing reaction efficiency and sustainability. A logical extension of conventional multicatalysis is a multicatalyst, i.e., a catalyst backbone equipped with independent, orthogonally reactive catalytic moieties. Herein we highlight the impressive advantages of asymmetric organomulticatalysis, examine its development, and present detailed reactions based on the catalyst classes employed, ranging from the very beginnings to the latest multicatalyst systems. R. C. Wende was born inRosenberg (Olesno), Poland, in 1984. He studied chemistry at the Justus-Liebig University, Giessen, where he obtained his B. Sc. degree in 2008 and his M. Sc. degree in 2010. Currently he is working on his PhD under the supervision of P. R. Schreiner. His research focuses on the development of novel synthetic oligopeptide and thiourea organocatalysts for multicatalysis reactions.

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“…In order to allow synthetic analogues related to 4 and 8 the potential to translate a conformational change into a detectable change in chemical reactivity, we devised a range of achiral catalytic sites based on modifications of Takemoto's aminothiourea catalysts,47 and appended them to the N terminus of a right‐handed helical structure bearing a C terminal alanine residue. The resulting foldamers 9 a – f contain a catalytically active site with no local chirality, whose conformation may nonetheless be induced to be asymmetric by a remote stereogenic centre two helical turns, or 13–16 bonds, away.…”

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confidence: 99%

Refoldable Foldamers: Global Conformational Switching by Deletion or Insertion of a Single Hydrogen Bond

2016

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Small changes in the structure of a foldamer may lead to gross changes in conformational preference. We show that the simple insertion or deletion of a single hydrogen bond by changes in pH or by photochemical deprotection is sufficient to refold a helical oligomer, interconverting M and P screw‐sense preference. As a consequence of the switch, information may be transmitted to a remote catalytic site, selectively directing the formation of either of two enantiomeric products by a reaction involving 1,22‐remote intermolecular asymmetric induction.

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Enantioselective Michael Reaction of Malonates to Nitroolefins Catalyzed by Bifunctional Organocatalysts

Abstract: Michael reaction of malonates to nitroolefins with chiral bifunctional organocatalysts, bearing both a thiourea and tertiary amino group, afforded Michael adducts with high yields and enantioselectivities (up to 95%, up to 93% ee).

Cited by 1,365 publications

References 31 publications

Enantioselective Diels–Alder reactions catalyzed by hydrogen bonding

Enantioselective Diels–Alder reactions catalyzed by hydrogen bonding

Evolution of asymmetric organocatalysis: multi- and retrocatalysis

Refoldable Foldamers: Global Conformational Switching by Deletion or Insertion of a Single Hydrogen Bond

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