Enantioselective rhodium-catalyzed allylic alkylation of acyclic α-alkoxy substituted ketones using a chiral monodentate phosphite ligand

Evans, P. Andrew; Clizbe, Elizabeth A.; Oliver, Samuel J.

doi:10.1039/c2sc20141k

Cited by 38 publications

(25 citation statements)

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“…Ac ombination of Wilkinsonsc atalyst and ac hiral monodentate phosphite was reported by Evans for the allylic alkylation of acyclic a-alkoxy aryl ketones (Scheme 13). [32] As tudy with ap reformed configurationally defined enolate provided insight into the origin of asymmetric induction. Tr eatment of the silyl enol ether with methyllithium gave the a-alkylated ketone with the same yield and enantioselectivity as the corresponding aryl ketone,p roving that the enolate geometry is not responsible for the formation of the minor enantiomer.The alkylation process is believed to proceed through as aturated 18-electron rhodium allyl complex, which suppresses the direct coordination of the enolate through an outer-sphere process.T he p-facial selectivity of the nucleophilic addition determines the enantioselectivity ( Figure 5).…”

Section: Methodsmentioning

confidence: 99%

Direct Asymmetric Alkylation of Ketones: Still Unconquered

2017

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The alkylation of ketones is taught at basic undergraduate level. In many cases this transformation leads to the formation of a new stereogenic center. However, the apparent simplicity of the transformation is belied by a number of problems. So much so, that a general method for the direct asymmetric alkylation of ketones remains an unmet target. Despite the advancement of organocatalysis and transition-metal catalysis, neither field has provided an adequate solution. Indeed, even use of an efficient and general stoichiometric chiral reagent has yet to be reported. Herein we describe the state-of-the-art in terms of direct alkylation reactions of some carbonyl groups. We outline the limited progress that has been made with ketones, and potential routes towards ultimately achieving a widely applicable methodology for the asymmetric alkylation of ketones.

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Section: Methodsmentioning

confidence: 99%

Direct Asymmetric Alkylation of Ketones: Still Unconquered

2017

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“…[32] Eine Untersuchung mit einem zuvor hergestellten, konfigurativ definierten Enolat lieferte Erkenntnisse zum Ur- [33] Dabei entstanden neue quartäre Zentren mit hoher Enantioselektivität. [32] Eine Untersuchung mit einem zuvor hergestellten, konfigurativ definierten Enolat lieferte Erkenntnisse zum Ur- [33] Dabei entstanden neue quartäre Zentren mit hoher Enantioselektivität.…”

Section: Metallkatalytische Methodenunclassified

“…Evans et al beschrieben eine Kombination des Wilkinson-Katalysators mit einem chiralen einzähnigen Phosphit für die allylische Alkylierung von acyclischen a-Alkoxyarylketonen (Schema 13). [32] Eine Untersuchung mit einem zuvor hergestellten, konfigurativ definierten Enolat lieferte Erkenntnisse zum Ur- [35] Mit der a-Allylierung cyclischer Ketone gelang List et al ein wichtiger Fortschritt (Schema 15). [36] Diese hervorragende atomçkonomische Methode kombiniert die Palladiumkata- [37] So gelang die a-Allylierung von nicht geschützten a-Hydroxyketonen durch die kombinierte Wirkung eines chiralen Ir-Phosphoramiditkomplexes und eines chiralen Zn-ProPhenol-Komplexes (Schema 16).…”

Section: Metallkatalytische Methodenunclassified

Direkte asymmetrische Alkylierung von Ketonen: noch immer ein unerreichtes Ziel

2017

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Die Alkylierung von Ketonen ist Teil des Grundstudiums der Chemie. In vielen Fällen führt diese Umwandlung zu einem neuen stereogenen Zentrum. Allerdings täuscht die scheinbare Einfachheit der Umwandlung über eine Reihe von Schwierigkeiten hinweg, die so groß sind, dass eine allgemeine Methode für die direkte asymmetrische Alkylierung von Ketonen bisher unerreicht ist. Trotz der Weiterentwicklung der Organo‐ und Übergangsmetallkatalyse liefert bisher keine von beiden eine adäquate Lösung. Sogar die Anwendung eines effizienten und allgemein verwendbaren stöchiometrischen Reagens muss erst noch beschrieben werden. Dieser Kurzaufsatz beschreibt den aktuellen Stand in Bezug auf direkte Alkylierungsreaktionen einiger Carbonylgruppen und bespricht den begrenzten Fortschritt bei Ketonen sowie mögliche Wege, die letztlich zu einer breit anwendbaren Methode für die asymmetrische Alkylierung von Ketonen führen können.

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“…[6,7] Currently available routes to these structures typically give only one of the two possible diastereomers in high enantio-and diastereoselectivity. [11] In contrast to these approaches,a tt he outset of this study we sought to identify one-step,f ully stereodivergent access to a-amino b-substituted g,d-unsaturated aldehydes.F urthermore,w e expected that the lessons learned would subsequently find use with other a-heteroatom-substituted aldehydes,e nabling the stereodivergent synthesis of ad iverse set of enantioenriched building blocks.T he process would thus complement established methods for the one-step catalytic enantioselective synthesis of g,d-unsaturated carbonyls with a-N/O substituents,s uch as hydrogenation of b,b'-disubstituted dehydroamino acids, [8] nucleophilic addition to imino esters, [8] transition-metal-catalyzed allylic substitutions involving enolate nucleophiles, [12] as well as [2,3] and [3,3] sigmatropic rearrangements. [11] In contrast to these approaches,a tt he outset of this study we sought to identify one-step,f ully stereodivergent access to a-amino b-substituted g,d-unsaturated aldehydes.F urthermore,w e expected that the lessons learned would subsequently find use with other a-heteroatom-substituted aldehydes,e nabling the stereodivergent synthesis of ad iverse set of enantioenriched building blocks.T he process would thus complement established methods for the one-step catalytic enantioselective synthesis of g,d-unsaturated carbonyls with a-N/O substituents,s uch as hydrogenation of b,b'-disubstituted dehydroamino acids, [8] nucleophilic addition to imino esters, [8] transition-metal-catalyzed allylic substitutions involving enolate nucleophiles, [12] as well as [2,3] and [3,3] sigmatropic rearrangements.…”

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confidence: 99%

Stereodivergent Dual Catalytic α‐Allylation of Protected α‐Amino‐ and α‐Hydroxyacetaldehydes

et al. 2015

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Fully stereodivergent dual-catalytic a-allylation of protected a-amino-and a-hydroxyacetaldehydes is achieved through iridium-and amine-catalyzed substitution of racemic allylic alcohols with chiral enamines generated in situ. The operationally simple method furnishes useful aldehyde building blocks in good yields,m ore than 99 %e e, and with d.r.values greater than 20:1 in some cases.A dditionally,t he g,d-unsaturated products can be further functionalizedi n as tereodivergent fashion with high selectivity and with preservation of stereochemical integrity at the C a position.Formation of multiple stereogenic centers in asingle chemical transformation with complete control of absolute and relative configuration represents as ignificant challenge in asymmetric synthesis.[1] We recently described the concept of stereodivergent dual catalysis,w hereby two distinct chiral catalysts operate concurrently,yet independently,topromote bond formation with full control over the configuration of two new stereogenic centers.[2] Simultaneous use of ac hiral Ir(P,olefin) complex and achiral amine allowed implementation of this concept in the stereodivergent a-allylation of branched and linear alkanals as well as g-allylation of cyclic a,b-unsaturated aldehydes.[3] Herein, we report the enantioand diastereodivergent a-allylation of protected a-aminoand a-hydroxyacetaldehydes through dual iridium/amine catalysis (Scheme 1). Ther esulting a-N/O-substituted unsaturated aldehyde products are amenable to further elaboration under mild conditions with high selectivity.Aldehydes have been examined as substrates in amine/ transition-metal catalyzed a-allylation reactions to furnish general and useful approaches to optically active adducts. [4] Most prominently featured in these studies are a-alkylsubstituted branched and linear aldehydes.H owever,n oticeably absent is the use of protected a-amino-and a-hydroxyacetaldehydes.[5] There are merely four reactions reported to date,w hich involve Pd-catalyzed allylation to afford g,dunsaturated adducts in racemic form [5a,b] or at best 46 % ee.[5c]Theuse of asuitably protected a-aminoacetaldehyde in adual catalytic process of the type shown in Scheme 1could result in afully stereodivergent synthesis of b,b'-disubstituted a-amino acid derivatives.T he sustained interest in this class of compounds as synthetic intermediates and conformational constraints in the development of peptidomimetics continues to stimulate the development of methods for their synthesis. [6,7] Currently available routes to these structures typically give only one of the two possible diastereomers in high enantio-and diastereoselectivity. [8] In those processes that enable synthesis of the complementary diastereomer,the switch in the sense of diastereoselectivity is usually the result of ac hange in the catalyst [9] or substrate, [10] or stems from ad hoc adjustment of the reaction conditions.[11] In contrast to these approaches,a tt he outset of this study we sought to identify one-step,f ully stereodivergent a...

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Enantioselective rhodium-catalyzed allylic alkylation of acyclic α-alkoxy substituted ketones using a chiral monodentate phosphite ligand

Cited by 38 publications

References 41 publications

Direct Asymmetric Alkylation of Ketones: Still Unconquered

Direct Asymmetric Alkylation of Ketones: Still Unconquered

Direkte asymmetrische Alkylierung von Ketonen: noch immer ein unerreichtes Ziel

Stereodivergent Dual Catalytic α‐Allylation of Protected α‐Amino‐ and α‐Hydroxyacetaldehydes

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