Organocatalytic Transfer Hydrogenation of Cyclic Enones

Tuttle, Jamison B.; Ouellet, Stéphane G.; MacMillan, David W. C.

doi:10.1021/ja0653066

Cited by 229 publications

(62 citation statements)

References 14 publications

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“…The application of our SOMO-activation platform to enantioselective ketone allylation was first evaluated with cyclohexanone, allyltrimethylsilane, ceric ammonium nitrate, and 20 mol% of imidazolidinone 2, an amine catalyst that has previously enabled Diels-Alder reactions with cyclic enones via iminium activation (21,22). As revealed in Scheme 5, we were happy to find that the critical alkylation step could be achieved in both a direct and enantioselective fashion using imidazolidinone 2; however, competitive catalyst degradation (via methyl furan oxidation) consistently led to poor levels of reaction efficiency (Scheme 5, 42% yield, 93% ee).…”

Section: Resultsmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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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.

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111

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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: Resultsmentioning

confidence: 99%

mentioning

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.

Self Cite

111

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“…14 In 2006, Rueping extended this strategy to reduce quinolines, 15 employing sterically congested chiral BINOL-phosphoric acids. This reaction was found to be highly solventdependent, in which nonpolar (e.g., benzene) gave the best enantioselectivity.…”

Section: Asymmetric Hydrogenation Of Quinoline and Isoquinoline Derivmentioning

confidence: 99%

Asymmetric Hydrogenation of Heteroaromatic Compounds

2007

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“…Actually, the enantioselective transfer hydrogenation of a wide range of β-substituted carbocycles was carried out in 2006 by MacMillan et al [14] and List et al [15] (Scheme 2). The possibility to accommodate severe steric constraints on the ketone component, and the scarce influence on the enantiocontrol with variation in its electronic nature, are among the advantages of MacMillan group's reaction.…”

Section: Transfer Hydrogenationsmentioning

confidence: 99%

Asymmetric Organocatalytic Reactions of α,β-Unsaturated Cyclic Ketones

2011

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Abstract:The 1,4-conjugate addition of nucleophiles to α,β-unsaturated carbonyl compounds represents one fundamental bond-forming reaction in organic synthesis. The development of effective organocatalysts for the enantioselective conjugate addition of malonate, nitroalkane and other carbon and heteroatom nucleophiles to cycloenones constitutes an important research field and has been explored in recent years. At the same time, asymmetric Diels-Alder reactions have been developed and often a mechanism has been demonstrated to be a double addition rather than synchronous. This review aims to cover literature up to the end of 2010, describing all the different organocatalytic asymmetric 1,4-conjugate additions even if they are listed as transfer hydrogenation, cycloadditions or desymmetrization of aromatic compounds.

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Organocatalytic Transfer Hydrogenation of Cyclic Enones

Abstract: General Information. Commercial reagents were purified prior to use following the guidelines of Perrin and Armarego. 1 Non-aqueous reagents were transferred under nitrogen via syringe or cannula and purified according to the method of Grubbs.

Cited by 229 publications

References 14 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

Asymmetric Hydrogenation of Heteroaromatic Compounds

Asymmetric Organocatalytic Reactions of α,β-Unsaturated Cyclic Ketones

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