Generation Of Enolates Research Articles

Efficient and simple preparation of functionalized 1,1-dibromoenol phosphates

The preparation of functionalized 1,1-dibromoalkenyl phosphates is described. The protocol developed for their preparation is based on the generation of enolates from α,α-dibromoketones followed by a reaction with dialkyl chlorophosphates. The procedure tolerates various functional groups including ester, ketone, and nitrile, and the yields are generally high.

ChemInform Abstract: Recent Progress in the in situ Detrifluoroacetylative Generation of Fluoro Enolates and Their Reactions with Electrophiles

AbstractReview: [52 refs.

ChemInform Abstract: Chemoselective Boron‐Catalyzed Nucleophilic Activation of Carboxylic Acids for Mannich‐Type Reactions.

AbstractThe title reaction allows the chemoselective generation of enolates from carboxylic acids using BH3·SMe2 as catalyst.

ChemInform Abstract: Palladium‐Catalyzed α,β‐Dehydrogenation of Esters and Nitriles.

A highly practical and general palladium-catalyzed methodology for the α,β-dehydrogenation of esters and nitriles is reported. Generation of a zinc enolate or (cyanoalkyl)zinc species followed by the addition of an allyl oxidant and a palladium catalyst results in synthetically useful yields of α,β-unsaturated esters, lactones, and nitriles. Preliminary mechanistic investigations are consistent with reversible β-hydride elimination and turnover-limiting, propene-forming reductive elimination.

Synthesis of phenanthrene derivatives by intramolecular cyclization utilizing the [1,2]-phospha-Brook rearrangement catalyzed by a Brønsted base.

The synthesis of functionalized phenanthrene derivatives was achieved by intramolecular cyclization utilizing the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis. Treatment of biaryl compounds having an α-ketoester moiety and an alkyne moiety at the 2 and 2' positions, respectively, with diisopropyl phosphite in the presence of a catalytic amount of phosphazene base P2-tBu provides 9,10-disubstituted phenanthrene derivatives in high yields. This reaction involves the generation of an ester enolate through an umpolung process, that is, addition of diisopropyl phosphite to a keto moiety followed by the [1,2]-phospha-Brook rearrangement, the intramolecular addition to an alkyne, and the [3,3] rearrangement of the allylic phosphate moiety in a consecutive fashion.

Palladium-Catalyzed α,β-Dehydrogenation of Esters and Nitriles

A highly practical and general palladium-catalyzed methodology for the α,β-dehydrogenation of esters and nitriles is reported. Generation of a zinc enolate or (cyanoalkyl)zinc species followed by the addition of an allyl oxidant and a palladium catalyst results in synthetically useful yields of α,β-unsaturated esters, lactones, and nitriles. Preliminary mechanistic investigations are consistent with reversible β-hydride elimination and turnover-limiting, propene-forming reductive elimination.

Catalytic generation of α-CF3 enolate: direct catalytic asymmetric Mannich-type reaction of α-CF3 amide.

The introduction of the CF3 unit is a common strategy for modifying pharmacokinetic properties and slowing metabolic degradation in medicinal chemistry. A catalytic and enantioselective addition of α-CF3 enolates allows for expeditious access to functionalized chiral building blocks with CF3-containing stereogenicity. To date, α-CF3 enolates have been a less explored class of nucleophiles because of rapid defluorination. The present study reveals that a designed α-CF3 amide enables a direct asymmetric Mannich-type reaction in a cooperative catalytic system.

ChemInform Abstract: Intramolecular Cyclization of Alkynyl α‐Ketoanilide Utilizing [1,2]‐Phospha‐Brook Rearrangement Catalyzed by Phosphazene Base.

A novel catalytic cyclization reaction of alkynyl α-ketoanilide was developed by utilizing the [1,2]-phospha-Brook rearrangement. This reaction involves the generation of an amide enolate via the umpolung process, that is the addition of dialkyl phosphite to a keto moiety followed by the [1,2]-phospha-Brook rearrangement, and the subsequent intramolecular addition of the enolate to an alkyne to afford 3,4-dihydro-2-quinolone derivatives. Under high-temperature reaction conditions, further rearrangement of the allylic phosphate moiety occurs to provide 2-quinolone derivatives.

Editorial (Thematic Issue: An Overview on the Recent Achievements in Nonmetal Asymmetric Catalysis)

It is our great pleasure as Guest Editors of the journal ‘Mini-Reviews in Organic Chemistry’ to present you with a ‘mini-hot topic issue’ on nonmetal asymmetric catalysis. Asymmetric catalysis entails the catalytic, selective, and reproducible generation of a given enantiomer of a chiral product from achiral reactants. Leading the quest of asymmetric catalysis is the need of the pharmaceutical, flavors and fragrances, and agrochemical industries for enantiopure molecules because the different enantiomers or diastereomers of a molecule often have different biological activity. Nearly 85% of new drugs in the market are chiral. Organocatalysis can be used as environmentally-friendly alternatives to transition-metal catalysts as no toxic metals are required. The principle interactions of organocatalyst are non-covalent, such as hydrophobic, hydrogen bonding, van der Waals and electrostatic as in enzymes. These catalysts are often inexpensive to prepare and reaction can be performed under aerobic environments and in wet solvents. The beneficial impact of organocatalytic reactions on a large scale production of chiral intermediates has been demonstrated. Therefore, this special issue aims to review the advances in nonmetal asymmetric catalysis during the last decade, specified in organocatalysis. The first review related to the above mentioned topic is written by Drs. Leow, Shen and their colleagues, who explore organocatalytic enantioselective protonation of enol derivatives. As they mentioned, the proton is the smallest functional group in organic synthesis and it is extremely challenging to control it in terms of enantioselectivity. Traditional methods are using pre-formed enolates obtained from the direct deprotonation of carbonyl compounds by strong bases. The newer strategies involve the usage of silyl enol ethers, tautomerization of enols or in situ generation of transient enolates. They can be generated through either additions to ketenes, conjugate additions to Michael acceptors, rearrangements, or isomerization of double/triple bonds. In the following article, as an alternative of the most popular asymmetric sulfur-Michael addition, Dr. Zhiyong Jiang and his colleagues summarized the advance on asymmetric α-sulfenylation. Two asymmetric protocols were discussed respectively, including transition-metal catalysis and organocatalysis. It was noted that the unprecedented substrate scopes still exist which represents developing rooms, although asymmetric α-sulfenylation has obtained remarkable progress in recent years; and novel and easily prepared sulfenylated reagents are still highly desirable. In the last article in this issue, Dr. Hansen and his colleagues gave an overview over the major advances in asymmetric enamine catalysis since, and including, 2008 with focus on strategic transformations and catalyst development. As they noted, enamine-catalysis has become a powerful enabling technology for enantioselective chemical synthesis, which could be attributed to a rapid evolution of novel catalyst architectures and strategies, combined with the design and discovery of strategically important, asymmetric transformations. This exciting field will continue to expand, fuelled by its unique ability to generate novel and stereodefined structural complexity in the synthesis of organic molecules. We would like to sincerely thank all the reviewers for their valuable contributions that ensured the quality of articles to be published in this special issue. It was a great opportunity for us to cooperate with researchers from all over the world including United States, Norway, Taiwan and Mainland China. We hope that readers will enjoy this issue, obtain useful information, and be inspired with new ideas for future research on nonmetal asymmetric catalysis.

Enantioselective annulations for dihydroquinolones by in situ generation of azolium enolates.

A convergent, catalytic asymmetric formal [4 + 2] annulation for the synthesis of dihydroquinolones has been developed. Carboxylic acids can be employed as precursors to NHC enolates through an in situ activation strategy. Simultaneous generation of a reactive aza-o-quinone methide under the basic conditions employed for NHC generation leads to a dual activation approach.

Intramolecular cyclization of alkynyl α-ketoanilide utilizing [1,2]-phospha-Brook rearrangement catalyzed by phosphazene base.

A novel catalytic cyclization reaction of alkynyl α-ketoanilide was developed by utilizing the [1,2]-phospha-Brook rearrangement. This reaction involves the generation of an amide enolate via the umpolung process, that is the addition of dialkyl phosphite to a keto moiety followed by the [1,2]-phospha-Brook rearrangement, and the subsequent intramolecular addition of the enolate to an alkyne to afford 3,4-dihydro-2-quinolone derivatives. Under high-temperature reaction conditions, further rearrangement of the allylic phosphate moiety occurs to provide 2-quinolone derivatives.

Rh‐Catalyzed AldehydeAldehyde Cross‐Aldol Reaction under Base‐Free Conditions: In Situ Aldehyde‐Derived Enolate Formation through Orthogonal Activation

The chemoselective generation of aldehyde-derived enolates to realize an aldehyde-aldehyde cross-aldol reaction is described. A combined Rh/dippf system efficiently promoted the isomerization/aldol sequence by using primary allylic, homoallylic, and bishomoallylic alcohols; secondary allylic and homoallylic alcohols; and trialkoxyboranes that were derived from primary allylic and homoallylic alcohols. The reaction proceeded at ambient temperature under base-free conditions, thus giving cross-aldol products with high chemoselectivity. Mechanistic studies, as well as its application to double-aldol processes under protecting-group-free conditions, are also described.

1,4-Chirality transfer via the ester enolate Claisen rearrangements in the preparation of (25R)- and (25S)-cholestenoic acids

Two variants of the Claisen rearrangement were evaluated for a stereoselective construction of a C-25 stereogenic center in cholestenoic acids based on 1,4-chirality transfer. Johnson orthoester Claisen rearrangement of (22R)- and (22S)-propargyl enol ethers proceeded in a highly stereoselective manner to give (25R)- and (25S)-isomeric allenes. The stereochemical outcome of the Ireland-Claisen rearrangement of 22-allylic alcohols was dependent on the configuration of the C-22 hydroxyl group and the geometry of the enol ether. The latter could be controlled by the solvent (THF or a mixture of THF/HMPA) chosen for the generation of silyl enolate.

Controlled β-protonation and [4+2] cycloaddition of enals and chalconesvia N-heterocyclic carbene/acid catalysis: toward substrate independent reaction control

A substrate-independent selective generation of enolates over homoenolate equivalents in NHC-catalyzed reactions of enals and chalcones is disclosed. Acid co-catalysts play vital roles in control of the reaction pathways, allowing for individual access to diverse products from identical substrates.

Direct α-Functionalization of Simple Aldehydes via Oxidative N-Heterocyclic Carbene Catalysis

A direct α-functionalization of simple aldehydes under N-Heterocyclic Carbene (NHC) catalysis and direct generation of ester enolate equivalents from nonfunctionalized aldehydes are disclosed. The catalysis involves selective enolate generation from an oxidatively generated NHC-bounded ester intermediate as a key step. The ester enolate intermediates undergo stereoselective reactions with enones and trifluoromethyl ketones.

Stereoregulations of Pyrimidinone Based Chiral Auxiliary in Aldol and Alkylation Reactions: A Convenient Route to Oxyneolignans

(S)-4-Isopropyl-1-phenyltetrahydropyrimidin-2(1H)-one was synthesized and evaluated as a chiral auxiliary for asymmetric acetate and propionate aldol reactions, by generation of titanium and lithium enolates, affording excellent yields and stereoselectivities for syn and anti aldol diastereomers, respectively. High stereoselectivities were also obtained in lithium mediated alkylation reactions. The application of the auxiliary was exemplified in the asymmetric synthesis of a natural oxyneolignan, (+)-(7S,8S)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7,9-diol-7'-oic acid.

ChemInform Abstract: NHCs in Asymmetric Organocatalysis: Recent Advances in Azolium Enolate Generation and Reactivity

AbstractReview: ca. 70 refs.

NHCs in Asymmetric Organocatalysis: Recent Advances in Azolium Enolate Generation and Reactivity

Organocatalysis represents a synthetic paradigm that has grown exponentially in popularity over the last decade, arguably becoming one of the most desired synthetic methods for the creation of enantiomerically enriched products. Within this field the use of N-heterocyclic carbenes (NHCs) has seen appreciable research activity with the realisation of many novel reaction types. This review provides a comprehensive account of recent advances in the generation and reactivity of azolium enolates with exclusive focus on those processes rendered asymmetric through the use of chiral NHCs. 1 Introduction: NHCs in Organocatalysis 1.1 Azolium Enolates 2 Azolium Enolate Generation via Ketenes 2.1 Asymmetric Formal [2+2] Cycloadditions 2.2 Asymmetric Formal [3+2] Cycloadditions 2.3 Asymmetric Formal [4+2] Cycloadditions 2.4 Asymmetric Protonation and Halogenation 3 Azolium Enolate Generation via α-Functionalised Aldehydes 4 Azolium Enolate Generation via Enals 5 Activated Esters as Azolium Enolate Precursors 6 Conclusions and Outlook

Complexity-generating hydration reactions via gold-catalyzed addition of boronic acids to alkynes

Boronic acids can serve as organic soluble substitutes for water molecules in the metal-catalyzed hydration of alkynes. The Au-catalyzed addition of boronic acids to alkynes provides an alternative method for enolate generation, which proceeds under exceptionally mild conditions. The resulting enolates can be trapped by aldehydes present in the reaction mixture, giving aldol products that can be isolated as cyclic borate esters. These compounds are versatile synthetic intermediates that can be elaborated into a variety of products by transformation of the boron moiety. The Au-catalyzed reaction of boronic acids with propargylic alcohols results in efficient Meyer–Schuster rearrangement to the corresponding enones. The rearrangement of tertiary alcohols gives (E)-enones with moderate to good selectivity, and the addition of a boronic acid to the reaction appears to enhance the level of geometrical control. The rearrangement of primary alcohols to terminal enones also occurs readily in the presence of catalytic Au(I) and a boronic acid, and the resulting terminal enones can be reacted with nucleophiles in one-pot procedures to give a variety of β-substituted ketones.

One-Step Synthesis of Highly Functionalized Monofluorinated Cyclopropanes from Electron-Deficient Alkenes

The unique combination of Zn/LiCl allowed generation of reactive zinc enolate from ethyl dibromofluoroacetate. This fluorinated enolate reacts efficiently with a wide range of functionalized electron-deficient alkenes to afford the corresponding monofluorinated cyclopropylcarboxylates in good yields.