Asymmetric Enamine Catalysis

Mukherjee, Santanu; Yang, Jung Woon; Hoffmann, Steffen; List, Benjamin

doi:10.1021/cr0684016

Cited by 2,606 publications

(907 citation statements)

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“…In particular, two modes of carbonyl activation by chiral secondary amines have led to the discovery of a large number of previously undescribed reactions (Scheme 2): (i) Iminium catalysis (23), wherein lowest unoccupied molecular orbital (LUMO) lowering activation is accomplished via the transient condensation of an α,β-unsaturated aldehyde and an amine catalyst, has enabled the enantioselective conjugate addition or cycloaddition of enals with a wide range of external π-nucleophiles or cycloaddition partners and (ii) enamine catalysis (24), a reaction mode wherein a catalytic amount of a chiral enamine exhibits increased propensity to react with a broad selection of electrophiles by raising the highest occupied molecular orbital (HOMO).…”

Section: Enantioselective Somo Catalysismentioning

confidence: 99%

Direct and enantioselective α-allylation of ketones via singly occupied molecular orbital (SOMO) catalysis

Mastracchio

Warkentin

Walji

et al. 2010

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

110

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The first enantioselective organocatalytic α-allylation of cyclic ketones has been accomplished via singly occupied molecular orbital catalysis. Geometrically constrained radical cations, forged from the one-electron oxidation of transiently generated enamines, readily undergo allylic alkylation with a variety of commercially available allyl silanes. A reasonable latitude in both the ketone and allyl silane components is readily accommodated in this new transformation. Moreover, three new oxidatively stable imidazolidinone catalysts have been developed that allow cyclic ketones to successfully participate in this transformation. The new catalyst platform has also been exploited in the first catalytic enantioselective α-enolation and α-carbooxidation of ketones.asymmetric synthesis | organocatalysis T he enantioselective catalytic α-alkylation of simple ketones remains a fundamental goal in chemical synthesis (1-4). Seminal work from Doyle and Jacobsen (5), Trost and co-workers (6-8), Stoltz and co-workers (9, 10), Braun and co-workers (11,12), and Hartwig and co-workers (13, 14) has introduced valuable previously undescribed technologies for (i) the enantioselective alkylation of preformed or in situ generated metal enolates (5,6,(11)(12)(13)(14)(15)(16)(17) and (ii) the asymmetric and decarboxylative conversion of allyl keto carbonates to α-allylated ketones (7-10). With these key advances in place, a goal now for asymmetric catalysis has become the direct α-allylation of simple ketone substrates (18,19), an elusive yet potentially powerful bond construction (Scheme 1).Recently, we questioned whether the catalytic principles of singly occupied molecular orbital (SOMO) activation (20) might be translated to ketonic systems, thereby providing an unreported mechanism for direct and enantioselective α-carbonyl alkylation. Despite the superficial similarities between aldehydes and ketones, these carbonyl families exhibit largely different steric and electronic properties with respect to catalyst interactions. As a consequence, the translation of enantioselective activation modes between these carbonyl subclasses is often difficult (if not unattainable in many cases) (21,22). Herein, we describe the invention of a previously undisclosed family of organocatalysts that enable cyclic ketones to successfully function within the SOMO-activation platform while being chemically robust to oxidative reagents. Moreover, we document the introduction of a previously undescribed catalytic α-ketone alkylation reaction that is immediately amenable to asymmetric induction. Enantioselective SOMO CatalysisOver the last decade, the field of enantioselective synthesis has witnessed tremendous progress in the successful implementation of small organic molecules as asymmetric catalysts. In particular, two modes of carbonyl activation by chiral secondary amines have led to the discovery of a large number of previously undescribed reactions (Scheme 2): (i) Iminium catalysis (23), wherein lowest unoccupied molecular orbital (LUMO) lowering a...

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Section: Enantioselective Somo Catalysismentioning

confidence: 99%

Direct and enantioselective α-allylation of ketones via singly occupied molecular orbital (SOMO) catalysis

Mastracchio

Warkentin

Walji

et al. 2010

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

110

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“…enamine catalysis | mechanism | organocatalysis W ithin the last 10 y, enamine catalysis, the catalytic activation of carbonyl compounds via enamine intermediates, has grown into a powerful approach to organic synthesis (1)(2)(3)(4). Among the many different primary and secondary amine catalysts that have been developed in this field, the amino acid proline remains a privileged motif and there are literally dozens of reaction types that are catalyzed with this wonderful natural product (5).…”

mentioning

confidence: 99%

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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“…The asymmetric catalytic Mannich reaction represents a powerful methodology to prepare a number of pharmaceutically and agrochemically relevant products [63]. Although recently various chiral organocatalysts have been successfully applied to promote these reactions, the number of approaches involving chiral metal complexes remains limited.…”

Section: Enantioselective Lanthanide-catalyzed Mannich-type Reactionsmentioning

confidence: 99%

Recent developments in enantioselective lanthanide-catalyzed transformations

Pellissier

2017

Coordination Chemistry Reviews

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Asymmetric Enamine Catalysis

Cited by 2,606 publications

References 465 publications

Direct and enantioselective α-allylation of ketones via singly occupied molecular orbital (SOMO) catalysis

Direct and enantioselective α-allylation of ketones via singly occupied molecular orbital (SOMO) catalysis

Crystal structures of proline-derived enamines

Recent developments in enantioselective lanthanide-catalyzed transformations

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