Catalytic Enantioselective Protonation Research Articles

Catalytic Enantioselective Protonation of Gold Enolates Enabled by Cooperative Gold(I) Catalysis.

Enantioselective protonation is a versatile approach to the construction of tertiary α-stereocenters, which are common structural motifs in various natural products and biologically relevant compounds. Herein we report a mild access to these chiral centers using cooperative gold(I) catalysis. From cyclic ketone enol carbonates, this asymmetric catalysis provides highly enantioselective access to cyclic ketones featuring an α tertiary chiral center, including challenging 2-methylsuberone. In combination with the gold-catalyzed formation of cyclopentadienyl carbonates in a one-pot, two-step process, this chemistry enables expedient access to synthetically versatile α'-chiral cyclopentenones with excellent enantiomeric excesses from easily accessible enynyl carbonate substrates.

Asymmetric Olefin Isomerization via Photoredox Catalytic Hydrogen Atom Transfer and Enantioselective Protonation.

Asymmetric olefin isomerization can be appreciated as an ideal synthetic approach to access valuable enantioenriched C═C-containing molecules due to the excellent atom economy. Nonetheless, its occurrence usually requires a thermodynamic advantage, namely, a higher stability of the product to the substrate. It has thus led to rather limited examples of success. Herein, we report a photoredox catalytic hydrogen atom transfer (HAT) and enantioselective protonation strategy for the challenging asymmetric olefin isomerization. As a paradigm, by establishing a dual catalyst system involving a visible light photosensitizer DPZ and a chiral phosphoric acid, with the assistance of N-hydroxyimide to perform HAT, a wide array of allylic azaarene derivatives, featuring α-tertiary carbon stereocenters and β-C═C bonds, was synthesized with high yields, ees, and E/Z ratios starting from the conjugated α-substituted alkenylazaarene E/Z-mixtures. The good compatibility of assembling deuterium on stereocenters by using inexpensive D2O as a deuterium source further underscores the broad applicability and promising utility of this strategy. Moreover, mechanistic studies have provided clear insights into its challenges in terms of reactivity and enantioselectivity. The exploration will robustly inspire the development of thermodynamically unfavorable asymmetric olefin isomerizations.

Recent Advances on Catalytic Enantioselective Protonation for Construction of α-Tertiary Carbonyl Compounds

Recent Advances on Catalytic Enantioselective Protonation for Construction of <i>α</i>-Tertiary Carbonyl Compounds

Formal Umpolung Addition of Phosphites to 2-Azaaryl Ketones under Chiral Brønsted Base Catalysis: Enantioselective Protonation Utilizing [1,2]-Phospha-Brook Rearrangement.

The formal enantioselective umpolung addition of dialkyl phosphites to 2-azaaryl ketones was developed under Brønsted base catalysis. The reaction involves the enantioselective protonation of the transient α-oxygenated (2-azaaryl)methyl anion generated through the 1,2-addition of the anion of dialkyl phosphite to the 2-azaaryl ketone and the subsequent [1,2]-phospha-Brook rearrangement. A chiral bis(guanidino)iminophosphorane organosuperbase efficiently catalyzed the reaction to provide enantio-enriched phosphates in high yields with good to high enantioselectivities. This is a rare example of the catalytic enantioselective protonation of transient carbanions other than enolates, constructing a trisubstituted stereogenic center α to 2-azaarenes.

Catalytic Reductive Cross Coupling and Enantioselective Protonation of Olefins to Construct Remote Stereocenters for Azaarenes.

A novel enantioselective protonation protocol that is triggered by reductive cross coupling of olefins is reported. When under cooperative photoredox and chiral hydrogen-bonding catalytic conditions and using a terminal reductant, various α-branched vinylketones with diverse vinylazaarenes could provide important enantioenriched azaarene derivatives containing tertiary stereocenters at their remote δ-position with high yields and enantioselectivities. This reaction system is also suitable for α-branched vinylazaarenes, thus successfully assembling elusive 1,4-stereocenters. The convenient late-stage modifications of products, especially the formation of remote ε-tertiary and ε-heteroquaternary carbon stereocenters, further highlight the important synthetic value of this method. Control experiments and density functional theory (DFT) calculations were conducted to elucidate the plausible reaction mechanism and origins of regioselectivity and stereoselectivity.

Bio-inspired Water-Driven Catalytic Enantioselective Protonation.

Catalytic enantioselective protonation of a prochiral carbanion in water is a common transformation in biological systems, but has been beyond the capability of synthetic chemists since unusually rapid movement of a proton in water leads to uncontrolled racemic protonation. Herein we show a crucial role of water, which enables a highly enantioselective glyoxalase I-mimic catalytic isomerization of hemithioacetals which proceeds via enantioselective protonation of an ene-diol intermediate. The use of on-water condition turns on this otherwise extremely unreactive catalytic reaction as a result of the strengthened hydrogen bonds of water molecules near the hydrophobic reaction mixture. Furthermore, under on-water conditions, especially under biphasic microfluidic on-water conditions, access of bulk water into the enantio-determining transition state is efficiently blocked, consequently enabling the enantioselective introduction of a highly ungovernable proton to a transient enediol intermediate, which mimics the action of enzymes.

Cover Picture: Catalytic Enantioselective Protonation of Monofluorinated Silyl Enol Ethers towards Chiral α‐Fluoroketones (Chin. J. Chem. 8/2019)

The cover picture shows a highly enantioselective organocatalytic protonation of monofluorinated silyl enol ethers to α‐secondary α‐fluoroketones using water as proton source. Notably, in the presence of D2O and MeOD, the facile access of chiral α‐deuterated α‐fluoroketones in excellent enantioselectivity is achieved. More details are discussed by Zhou et al. on page 799–806. image

Catalytic Enantioselective Protonation of Monofluorinated Silyl Enol Ethers towards Chiral α‐Fluoroketones

Summary of main observation and conclusionDescribed herein is an organocatalytic enantioselective protonation of monofluorinated silyl enol ethers, affording an array of optically active α‐secondary α‐fluoroketones in good to high yields and enantioselectivities, under the catalysis of bifunctional cinchonidine derived squaramide C4. It represents a rare example of facile synthesis of enantioenriched α‐secondary α‐fluoroketones. With D2O as the deuterium source and MeOD as the solvent, the first highly enantioselective preparation of chiral α‐deuterated α‐fluoroketones in &gt;92% deuteration is developed.

ChemInform Abstract: Progress in Catalytic Asymmetric Protonation

AbstractReview: [66 refs.

Progress in Catalytic Asymmetric Protonation

AbstractEnantioselective protonation represents an appealing approach for the construction of nonracemic chiral tertiary carbon centres, frequently found in a large range of bio‐relevant organic compounds. The development of efficient catalytic processes has hitherto been regarded as a challenging goal for the synthetic chemist. Significant developments in catalytic enantioselective protonation (EP) that have been emerging over the last few years (2009–2013) are presented in this microreview. These include not only catalytic EP processes from preformed enol derivatives and useful tandem Michael addition/protonation sequences, but also unprecedented catalytic cascade reactions involving enantioselective protonation as a crucial stereo‐determining step. Here, special attention is paid to the scope and limitations of these new catalytic EP processes, while valuable mechanistic insights into the catalytic cycles and into the key enantioselective protonation steps are provided.

ChemInform Abstract: Enantioselective Protonation of Alkenyl Trifluoroacetates Catalyzed by Chiral Tin Methoxide.

AbstractOptically active ketones containing a tertiary stereogenic center at the α‐position are obtained by catalytic enantioselective protonation of alkenyl trifluoroacetates.

Enantioselective Protonation of Alkenyl Trifluoroacetates Catalyzed by Chiral Tin Methoxide

Go catalytic! A catalytic enantioselective protonation of alkenyl trifluoroacetates was achieved by using an in situ generated chiral tin bromide methoxide as the chiral catalyst in the presence of methanol. Optically active ketones containing a tertiary stereogenic center at the α-position were obtained with enantioselectivities of up to 94 % ee.

Enantioselective Protonation Catalyzed by Chiral Br^|^oslash;nsted Bases

The proton is the smallest group in synthetic organic chemistry. Moving a proton within a catalytic cycle in an enantioselective manner is a formidable task that has attracted the attention of many chemists. Furthermore, catalytic enantioselective protonation is an atom economical method of generating chiral carbon centers. Variations of this kind of reaction catalyzed by transition metals catalysts have been well investigated. On the other hand, a complementary approach to this reaction, the use of chiral Brønsted base catalysts is relatively less explored. We have developed several protonation reactions using chiral bicyclic guanidine as the Brønsted base catalyst. In this review, we will report these reactions and other related examples recently described by other groups.

Deracemization of &amp;alpha;-Substituted Carbonyl Compounds via Catalytic Enantioselective Protonation of their Corresponding Enolates

Deracemization of &amp;alpha;-Substituted Carbonyl Compounds via Catalytic Enantioselective Protonation of their Corresponding Enolates

Correction to Catalytic Enantioselective Protonation of Nitronates Utilizing an Organocatalyst Chiral Only at Sulfur

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionORIGINAL ARTICLEThis notice is a correctionCorrection to Catalytic Enantioselective Protonation of Nitronates Utilizing an Organocatalyst Chiral Only at SulfurKyle L. Kimmel, Jimmie D. Weaver, Melissa Lee, and Jonathan A. Ellman*Cite this: J. Am. Chem. Soc. 2012, 134, 28, 11828Publication Date (Web):July 3, 2012Publication History Published online3 July 2012Published inissue 18 July 2012https://doi.org/10.1021/ja306016bCopyright © 2012 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views1477Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (156 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Catalytic Enantioselective Protonation of Nitronates Utilizing an Organocatalyst Chiral Only at Sulfur

The highly enantioselective protonation of nitronates formed upon the addition of α-substituted Meldrum's acids to terminally unsubstituted nitroalkenes is described. This work represents the first enantioselective catalytic addition of any type of nucleophile to this class of nitroalkenes. Moreover, for the successful implementation of this method, a new type of N-sulfinyl urea catalyst with chirality residing only at the sulfinyl group was developed, thereby enabling the incorporation of a diverse range of achiral diamine motifs. Finally, the Meldrum's acid addition products were readily converted to pharmaceutically relevant 3,5-disubstituted pyrrolidinones in high yield.

ChemInform Abstract: Chiral Broensted Acid from a Cationic Gold(I) Complex: Catalytic Enantioselective Protonation of Silyl Enol Ethers of Ketones.

AbstractOptically active cyclohexanones as well as a cycloheptanone are formed from the corresponding silyl enol ethers.

ChemInform Abstract: Catalytic Enantioselective Protonation of Enol Trifluoroacetates by Means of Hydrogenocarbonates and Cinchona Alkaloids.

AbstractCyclic enol trifluoroacetates undergo efficient asymmetric protonation yielding the corresponding ketones in up to 93% e.e.

Gold-Catalyzed Enantioselective Protonation

The catalytic enantioselective protonation of silyl enol ethers was realized via a cationic gold-activated Brønsted acid. While enantio­selective protonations of cyclic silyl enol ethers of ketones are known (see Review below), no prior precedents on Brønsted acid catalyzed protonation existed for the acyclic variants.

Chiral Brønsted acid from a cationic gold(I) complex: catalytic enantioselective protonation of silyl enol ethers of ketones.

A chiral Brønsted acid has been developed from a cationic gold(I) disphosphine complex in the presence of alcoholic solvent and applied to the enantioselective protonation reaction of silyl enol ethers of ketones. Various optically active cyclic ketones were obtained in excellent yields and high enantioselectivities, including cyclic ketones bearing aliphatic substrates at the α-position. Furthermore, the application of this Brønsted acid was extended to the first Brønsted acid-catalyzed enantioselective protonation reaction of silyl enol ethers of acyclic substrates, regardless of their E/Z ratio.