Rhodium Catalyzed Tandem Conjugate Addition‐Protonation: An Enantioselective Synthesis of 2‐Substituted Succinic Esters.

Moss, Rebecca J.; Wadsworth, Kelly J.; Chapman, C. J.; Frost, Christopher G.

doi:10.1002/chin.200505080

Cited by 3 publications

(4 citation statements)

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“…Frost and coworkers55 explored Rh-catalyzed additions of organotrifluoroborate salts to itaconate substrates with water as the stoichiometric proton donor (e.g., 78 → 79 → 80 , Figure 6a). The metal-to-ligand ratio was found to be important in the selectivity of the reaction.…”

Section: Enantioselective Protonation By Means Of Chiral Brønsted Basementioning

confidence: 99%

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Enantioselective protonation

2009

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Enantioselective protonation is a common process in biosynthetic sequences. The decarboxylase and esterase enzymes that effect this valuable transformation are able to control both the steric environment around the proton acceptor (typically an enolate) and the proton donor (typically a thiol). Recently, several chemical methods to achieve enantioselective protonation have been developed by exploiting various means of enantiocontrol in different mechanisms. These laboratory transformations have proven useful for the preparation of a number of valuable organic compounds.A fundamental method to generate a tertiary carbon stereocenter is to deliver a proton to a carbanion intermediate. However, enantioselective transfer of a proton presents unusual challenges, specifically, manipulating a very small atom and avoiding product racemization at a particularly labile stereocenter. As a result, the conditions for a successful enantioselective protonation protocol may be very specific to a certain substrate class. Tertiary carbon stereocenters are extremely common in valuable biologically active natural products, and thus the need for synthetically useful enantioselective methods to form these stereocenters is vital. 1In this review, we discuss several strategic approaches to enantioselective protonation. Emphasis has been placed on recently developed methods and their accompanying mechanisms in order to update the most recent prior reviews on this topic. 2,3,4,5,6,7,8 Each method relies on particular stereochemical control elements based on the mechanism of the protonation transformation. Appreciation of these controlling elements may lead to improved methods for preparing valuable chiral materials for a variety of synthetic applications. Important Factors in Achieving Enantioselective ProtonationSeveral of the most important practical features of enantioselective protonation were enumerated in Fehr's 1996 review. 2 Principal among these is the fact that enantioselective protonations are necessarily kinetic processes since under thermodynamic control racemate would be formed. Accordingly, it is often necessary to match the pK a of the proton donor and the product to prevent racemization before product isolation. It is unfortunate that the same anion stabilizing groups (e.g., ketones) that make protonations relatively easy to achieve also impart a degree of instability in the product. This has led some researchers to explore hydrogen atom transfer reactions in lieu of Brønsted acid-mediated protonations (see the subsection Enantioselective Hydrogen Atom Transfer below).Correspondence should be addressed to B.M.S. stoltz@caltech.edu. The authors declare no competing financial interests. NIH Public Access Author ManuscriptNat Chem. Author manuscript; available in PMC 2010 April 27. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptIn addition to the obvious challenges of product stability under the reaction conditions, the rapid rate of proton exchange in solution often leads to significant l...

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Section: Enantioselective Protonation By Means Of Chiral Brønsted Basementioning

confidence: 99%

“…a) Several other research groups57,55,58,59 have explored Rh-catalyzed conjugate addition/protonation sequences with various activated electrophiles and carbon-based nucleophiles. b) Sodeoka and coworkers60 found that nitrogen nucleophiles could undergo enantioselective conjugate addition/protonation in the presence of a cationic Pd catalyst.…”

Section: Figuresmentioning

confidence: 99%

Enantioselective protonation

2009

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“…The rhodium-catalysed conjugate addition of organometallic donors has evolved into a versatile tool for the assembly of complex molecules and intermediates in natural product synthesis [ 1 , 2 , 3 , 4 , 5 , 6 ]. The mechanistic and stereochemical aspects of the reaction have been thoroughly investigated for additions to prochiral substrates [ 7 ] and processes involving enantioselective protonation [ 8 , 9 , 10 ]. When the addition occurs to a chiral acceptor, the diastereoselectivity can be controlled by substrate [ 11 ], ligand [ 12 ] or organometallic donor [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Trans-Selective Rhodium Catalysed Conjugate Addition of Organoboron Reagents to Dihydropyranones

2015

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The selective synthesis of 2,6-trans-tetrahydropyran derivatives employing the rhodium catalysed addition of organoboron reagents to dihydropyranone templates, derived from a zinc-catalysed hetero-Diels-Alder reaction, is reported. The addition of both arylboronic acids and potassium alkenyltrifluoroborates have been accomplished in high yields using commercially-available [Rh(cod)(OH)]2 catalyst. The selective formation of the 2,6-trans-tetrahydropyran stereoisomer is consistent with a mechanism involving alkene association and carbometalation on the less hindered face of the dihydropyranone.

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“…Although Rh(I)-catalyzed conjugate addition/asymmetric protonation with organometallic reagents has been proven to be a powerful strategy for the construction of chiral tertiary carbon, achieving high enantiocontrol remains an unmet challenge. , The major obstacle is that unlike in conventional asymmetric conjugate additions, the stereochemical outcome is determined not at the insertion step (Figure a) but at the protonation step of the resulting oxa-π-allylrhodium intermediate (Figure b). As illustrated, the insertion intermediate oxa-π-allylrhodium I could be in equilibrium with C-bound species II and O-bound species III .…”

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Water as a Direct Proton Source for Asymmetric Hydroarylation Catalyzed by a Rh(I)–Diene: Access to Nonproteinogenic β²/γ²/δ²-Amino Acid Derivatives

Chen

Liu

et al. 2020

Org. Lett.

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A highly enantioselective rhodium-catalyzed intermolecular hydroarylation of α-aminoalkyl acrylates using water as a direct proton source has been realized by employing a chiral bicyclo[3.3.0] diene ligand, allowing efficient access to a broad range of α-aryl-methyl-substituted β2-, γ2-, and δ2-amino esters with excellent enantioselectivities (up to 98% ee) under exceptionally mild conditions. By utilizing this method, a series of structurally interesting benzo-fused heterocyclic molecules and the corresponding β2-, γ2-, and δ2-amino acids are facilely constructed.

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Rhodium Catalyzed Tandem Conjugate Addition‐Protonation: An Enantioselective Synthesis of 2‐Substituted Succinic Esters.

Cited by 3 publications

References 1 publication

Enantioselective protonation

Enantioselective protonation

Trans-Selective Rhodium Catalysed Conjugate Addition of Organoboron Reagents to Dihydropyranones

Water as a Direct Proton Source for Asymmetric Hydroarylation Catalyzed by a Rh(I)–Diene: Access to Nonproteinogenic β²/γ²/δ²-Amino Acid Derivatives

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Rhodium Catalyzed Tandem Conjugate Addition‐Protonation: An Enantioselective Synthesis of 2‐Substituted Succinic Esters.

Cited by 3 publications

References 1 publication

Enantioselective protonation

Enantioselective protonation

Trans-Selective Rhodium Catalysed Conjugate Addition of Organoboron Reagents to Dihydropyranones

Water as a Direct Proton Source for Asymmetric Hydroarylation Catalyzed by a Rh(I)–Diene: Access to Nonproteinogenic β2/γ2/δ2-Amino Acid Derivatives

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Water as a Direct Proton Source for Asymmetric Hydroarylation Catalyzed by a Rh(I)–Diene: Access to Nonproteinogenic β²/γ²/δ²-Amino Acid Derivatives