Enantioselective protonations: fundamental insights and new concepts

Duhamel, Lucette; Duhamel, Pierre; Plaquevent, Jean‐Christophe

doi:10.1016/j.tetasy.2004.09.035

Cited by 210 publications

(43 citation statements)

References 158 publications

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“…This procedure represents a 'one-pot, two-step' methodology and has been widely used employing a stoichiometric or catalytic amount of the chiral protonating/deprotonating agent. Since this technique has been recently reviewed, [106] we refer to this publication for further information.…”

Section: Enantioselective Protonationmentioning

confidence: 99%

From a Racemate to a Single Enantiomer: Deracemization by Stereoinversion

et al. 2006

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Abstract:The stereoinversion of one enantiomer into its mirror-image counterpart within a racemate furnishes a single stereoisomeric product in 100 % theoretical yield. This extremely efficient type of deracemization, whereby substrate and product possess an identical chemical structure, can be achieved by using bio-or chemo-catalysts or combinations thereof and is applicable to secondary alcohols, amines and a-substituted carboxylic acids. Special emphasis is devoted to the theoretical background of the onepot, single-step deracemization of sec-alcohols.

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Section: Enantioselective Protonationmentioning

confidence: 99%

From a Racemate to a Single Enantiomer: Deracemization by Stereoinversion

et al. 2006

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“…To achieve a homogeneous enantioselective protonation, the racemic allyl β-ketoester (±)-2 was exposed to Pd 2 (dba) 3 , (S)-t-Bu-PHOX (1), and a variety of achiral organic proton donors (Table 1). Gratifyingly, the use of dimethyl malonate did indeed lead to protonated product 3, although the ee was moderate (entry 1).…”

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confidence: 99%

“…It was found that, in general, large substituents between the carbonyls of the proton source decrease the enantiopurity of 3, although smaller groups (e.g., CH 3 ) are tolerated (entries [1][2][3][4][5]. In contrast to the acyclic case, addition of a third resonance withdrawing group (e.g., acetyl) severely decreased reactivity and product ee (cf.…”

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confidence: 99%

Homogeneous Pd-Catalyzed Enantioselective Decarboxylative Protonation

et al. 2008

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General homogeneous conditions for the palladium-catalyzed synthesis of carbonyl compounds with tertiary carbon stereocenters at the α-position are reported. The highly reactive catalyst tolerates a variety of substrate substitution and functionality, and generates enantioenriched cyclic ketones from racemic allyl β-ketoester starting materials.Enantioselective protonation of achiral enolates or enol equivalents is an efficient route to access carbonyl compounds with tertiary carbon stereocenters at the α-position. Several distinct methods involving chiral proton sources or chiral catalysts have been developed for the enantioselective protonation of metal enolates. 1,2 However, most of the reported methods are limited in substrate scope, few are catalytic, and together they do not provide a general solution for the enantioselective protonation of enolates. 1dPreviously, we reported a series of catalytic enantioselective allylation reactions that deliver carbonyl compounds with adjacent quaternary stereocenters from various enolate precursors (Scheme 1). 3,4 Crucial to the success of these transformations was the use of catalysts derived from Pd(0) and chiral phosphinooxazoline (PHOX) ligand 1. 5,6 Based on kinetic and mechanistic studies carried out in our laboratories as well as computational studies performed in collaboration with the W. A. Goddard group at Caltech, 7 we believe that in the course of the reaction a chiral Pd-enolate is generated in solution. We chose to explore a proton electrophile to take further advantage of this valuable intermediate for the preparation of tertiary stereocenters. 8 As a result of these studies, we reported a highly enantioselective catalytic system for the decarboxylative protonation of racemic allyl β-ketoesters in the presence of Pd(OAc) 2 , (S)-t-Bu-PHOX (1), 4 Å molecular sieves (MS), and HCO 2 H (Scheme 1). 9 Although this protocol is capable of generating cycloalkanones with excellent ee, each substrate required optimization of the amounts of 4 Å MS and HCO 2 H in order to suppress competitive allylation and maximize product ee. Moreover, the heterogeneous nature of the reaction hinders investigation of the mechanism of protonation. In response, we have sought substantially different protonation conditions to allow further development of a practical synthetic process. Herein, we report a highly enantioselective, general homogeneous catalytic system for the facile synthesis of tertiary stereocenters by protonation of ketone enolates.To achieve a homogeneous enantioselective protonation, the racemic allyl β-ketoester (±)-2 was exposed to Pd 2 (dba) 3 , (S)-t-Bu-PHOX (1), and a variety of achiral organic proton donors (Table 1). Gratifyingly, the use of dimethyl malonate did indeed lead to protonated product 3, although the ee was moderate (entry 1). Acetoacetic esters (entries 2 and 3) provided 3 in significantly higher ee than the malonate case, but at the expense of conversion. Acetylacetone derivatives (entries 4-6) were very reactive, with the more acidic a...

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“…The palladium-or nickel-catalyzed asymmetric a-arylation [3] and a-alkenylation [4] of carbonyl compounds provides an efficient method for the synthesis of chiral ketones substituted with quaternary stereogenic centers, but their application to the asymmetric synthesis of products containing hydrogen at the chiral carbon should present a problem due to the difficulty in keeping the stereogenic character of the chiral carbon center bound to an acidic hydrogen under basic conditions at a high reaction temperature. Another important method of providing a-chiral ketones is the catalytic asymmetric protonation of enolates, [5][6][7] but the asymmetric synthesis at the stage of carbon-carbon bond formation is more desirable. Our approach is to apply the rhodium-catalyzed asymmetric 1,4-addition [8,9] to the asymmetric synthesis of a-aryl ketones.…”

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confidence: 99%

Asymmetric 1,4‐Addition of Organoboron Reagents to Quinone Monoketals Catalyzed by a Chiral Diene/Rhodium Complex: A New Synthetic Route to Enantioenriched 2‐Aryltetralones

Tokunaga

Hayashi

2007

Adv Synth Catal

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A novel synthetic approach to 2-aryltetralones with high ee has been developed through asymmetric 1,4-addition of arylboronic acids to naphthoquinone monoketals catalyzed by a rhodium complex with the (R,R)-Ph-bod* ligand. The asymmetric addition proceeded in high yields with excellent enantioselectivity.Keywords: asymmetric catalysis; boron; chiral diene ligands; conjugate addition; quinone monoketals; rhodium Enantiomerically pure carbonyl compounds bearing aryl or alkenyl groups at the a position to the carbonyl moiety, which are represented by the 2-aryltetralones, constitute key intermediates to biologically important compounds.[1] Although their preparation using a stoichiometric amount of chiral reagents has been reported, [1,2] their catalytic asymmetric synthesis has not been well developed. The palladium-or nickel-catalyzed asymmetric a-arylation [3] and a-alkenylation [4] of carbonyl compounds provides an efficient method for the synthesis of chiral ketones substituted with quaternary stereogenic centers, but their application to the asymmetric synthesis of products containing hydrogen at the chiral carbon should present a problem due to the difficulty in keeping the stereogenic character of the chiral carbon center bound to an acidic hydrogen under basic conditions at a high reaction temperature. Another important method of providing a-chiral ketones is the catalytic asymmetric protonation of enolates, [5][6][7] but the asymmetric synthesis at the stage of carbon-carbon bond formation is more desirable. Our approach is to apply the rhodium-catalyzed asymmetric 1,4-addition [8,9] to the asymmetric synthesis of a-aryl ketones. Herein we report that the asymmetric 1,4-addition of aryl-and alkenylboron reagents to quinone monoketals [10] is efficiently catalyzed by a chiral diene/rhodium complex [11][12][13][14] and one of the enantioenriched addition products (96-99 % ee) is readily converted into a 2-aryltetralone without loss of enantiomeric purity.

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Enantioselective protonations: fundamental insights and new concepts

Cited by 210 publications

References 158 publications

From a Racemate to a Single Enantiomer: Deracemization by Stereoinversion

From a Racemate to a Single Enantiomer: Deracemization by Stereoinversion

Homogeneous Pd-Catalyzed Enantioselective Decarboxylative Protonation

Asymmetric 1,4‐Addition of Organoboron Reagents to Quinone Monoketals Catalyzed by a Chiral Diene/Rhodium Complex: A New Synthetic Route to Enantioenriched 2‐Aryltetralones

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