A Simple Organocatalytic Enantioselective Cyclopropanation of α,β‐Unsaturated Aldehydes

A highly chemo‐ and enantioselective organocatalytic cyclopropanation of α,β‐unsaturated aldehydes with bromomalonate and 2‐bromoacetoacetate esters is presented. The reaction is catalyzed by chiral amines and gives access to 2‐formylcyclopropanes in high yields and up to 99 % ee.     

Organocatalytic Enantioselective Aziridination of α‐Substituted α,β‐Unsaturated Aldehydes: Asymmetric Synthesis of Terminal Aziridines

The first example of a highly enantioselective organocatalytic aziridination of α‐substituted α,β‐unsaturated aldehydes is presented. The reaction is catalyzed by simple chiral amines and gives access to highly functional terminal azirdines containing an α‐tertiary amine stereocenter in high yields and enantiomeric ratios (95.5:4.5–98:2).     

Enantioselective Organocatalytic Conjugate Addition of Aldehydes to α,β‐Unsaturated Thiol Esters

The first example of an organocatalytic asymmetric Michael addition of aldehydes to α,β‐unsaturated thiol esters promoted by chiral diphenylprolinol silyl ether is presented. The reaction occurs with good yields, diastereoselectivity and excellent enantioselectivity.     

A Triazole Organocatalyst with Spiropyrrolidine Framework and its Application to the Catalytic Asymmetric Addition of Nitromethane to α,β‐Unsaturated Aldehydes

A series of new water‐compatible “spiropyrrolidine triazole” catalysts was designed and synthesized. The asymmetric Michael addition of nitromethane and α,β‐unsaturated aldehydes in an aqueous system was investigated to evaluate these new catalysts, and the resulting adducts were obtained with excellent enantioselectivity (up to 95.5% ee) and moderate to good yield (63–88%).

     

Ruthenium(II)‐Catalyzed Protocol for Preparation of Diverse α,β‐ and β,β‐Dihaloenones from Diazodicarbonyls

Efficient one‐step syntheses of α,β‐ and β,β‐dihaloenones were achieved by ruthenium(II)‐catalyzed reactions between cyclic or acyclic diazodicarbonyl compounds and oxalyl chloride or oxalyl bromide in moderate to good yields. This methodology offers several significant advantages, which include ease of handling, mild reaction conditions, one‐step reaction, and the use of an effective and non‐toxic catalyst. The synthesized compounds were further transformed into highly functionalized novel molecules bearing aromatic rings on the enone moiety using the Suzuki reaction.

     

Highly Enantioselective Michael Addition of Cyclic 1,3‐Dicarbonyl Compounds to β,γ‐Unsaturated α‐Keto Esters

A highly enantioselective Michael addition of cyclic 1,3‐dicarbonyl compounds to β,γ‐unsaturated α‐keto esters catalyzed by amino acid‐derived thiourea‐tertiary‐amine catalysts is presented. Using 5 mol% of a novel tyrosine‐derived thiourea catalyst, a series of chiral coumarin derivatives were obtained in excellent yields (up to 99%) and with up to 96% ee under very mild conditions within a short reaction time.     

The One‐Pot Wittig Reaction: A Facile Synthesis of α,β‐Unsaturated Esters and Nitriles by Using Nanocrystalline Magnesium Oxide

Nanocrystalline magnesium oxide was found to be an effective heterogeneous, solid base catalyst for the one‐pot Wittig reaction to afford α,β‐unsaturated esters and nitriles in excellent yields with high E‐stereoselectivity in the presence of triphenylphosphine under mild conditions.     

Regio‐ and Enantioselective Copper‐Catalyzed 1,4‐Conjugate Addition of Trimethylaluminium to Linear α,β,γ,δ‐Unsaturated Alkyl Ketones

A regio‐ and enantioselective copper‐catalyzed 1,4‐conjugate addition of trimethylaluminium to linear δ‐aryl‐substituted α,β,γ,δ‐unsaturated alkyl ketones was developed. A series of γ,δ‐unsaturated alkyl ketones were obtained in good yields with high regio‐ and enantioselectivity (up to 88% ee and 96:4 dr). Expansion of the reaction scope to substrates containing aromatic heterocycles also afforded good yields and enantioselectivities (up to 91% ee) with very high regioselectivities, exclusively providing the single 1,4‐products.

     

Chiral Bioinspired Non‐Heme Iron Complexes for Enantioselective Epoxidation of α,β‐Unsaturated Ketones

Chiral bioinspired iron complexes of N₄ ligands based on the ethylenediamine backbone display remarkable levels of enantioselectivity for the first time in the asymmetric epoxidation of α,β‐unsaturated ketones using hydrogen peroxide (up to 87% ee) or peracetic acid as oxidant, respectively. Notablely, isotopic labeling with H₂¹⁸O strongly demonstrated that there is a reversible water binding step prior to generation of the significant intermediate. Besides, the complex [L₂Fe(III)₂(μ‐O)(μ‐CH₃CO₂)]³⁺ usually derived from the decay of the LFe(IV)O species or thermodynamic sinks for a number of iron complexes was identified by HR‐MS. In addition, the possible mechanisms were proposed and LFe(V)O species may be the main active intermediate in the catalytic system.     

Organocatalytic Enantioselective Aza‐Michael Addition of Purine Bases to α,β‐Unsaturated Ketones

The first organocatalytic enantioselective aza‐Michael addition of purine bases to α,β‐unsaturated ketones has been developed, affording Michael adducts in moderate to high yields (up to 96% yield) and high to excellent enantioselectivities (up to >99% ee). A wide range of α,β‐unsaturated ketones including aliphatic and aromatic enones are tolerated in this process, generally demonstrating good reactivity, regioselectivity and enantioselectivity. The aromatic α,β‐unsaturated ketones showing quite low reactivity in the reported catalytic systems, were first successfully employed as Michael acceptors in this transformation, yielding high enantioselectivities (up to 94% ee). The utility of this method was also applied for the synthesis of enantioenriched non‐natural nucleoside analogues with potential biological activities.     

Ligand‐Free Nickel‐Catalysed 1,4‐Addition of Arylboronic Acids to α,β‐Unsaturated Carbonyl Compounds

A simple and efficient ligand‐free nickel‐based catalytic system has been developed for the 1,4‐addition of arylboronic acids to α,β‐unsaturated carbonyl compounds. With catalyst loadings of 1–2 mol%, a series of 1,4‐adducts from chalcones and cinnamates was obtained in moderate to excellent yields within 5–30 min under a nitrogen atmosphere and microwave irradiation. The 1,4‐addition of arylboronic acids to acrylates is less efficient.

     

Three‐Component Reactions of 2‐Alkynylbenzaldoximes and α,β‐Unsaturated Carbonyl Compounds with Bromine or Iodine Monochloride

The three‐component reaction of 2‐alkynylbenzaldoximes and α,β‐unsaturated carbonyl compounds with bromine or iodine monochloride is described, which generates the unexpected 2‐(4‐haloisoquinolin‐1‐yl)ethanol derivatives in good to excellent yields.     

The Tunable Functionality of α,β‐Unsaturated Carbonyl Compounds Enables Their Differential Application in Biological Systems

α,β‐Unsaturated carbonyl compounds as potential drug candidates is a controversial topic since their potential Michael acceptor activity can lead to cell damage and cytotoxicity. Nevertheless, the α,β‐unsaturated carbonyl functionality can be employed as a tool to fine tune biological activity by directly manipulating this entity. Depending on their electronic properties, α,β‐unsaturated carbonyl functionalities display different reactivities, namely Michael addition, radical scavenging, oxidation or double bond isomerization. Modifying the α‐position of the α,β‐unsaturated carbonyl system, a concept that has not been widely explored, could produce new, very interesting derivatives. Currently in drug development, irreversible binding in active sites has proven to be one answer to drug resistance in cancer treatment. Overall, natural products containing the α,β‐unsaturated carbonyl unit possess multiple biological activities that could be transferred into novel pharmaceutical agents.     

Chemoselective Reduction of α,β‐Unsaturated Carbonyls over Novel Mesoporous CoHMA Molecular Sieves under Hydrogen Transfer Conditions

Chemoselective reduction of α,β‐unsaturated carbonyls to the corresponding alcohols was achieved by a catalytic transfer hydrogenation (CTH) method using cobalt(II)‐substituted hexagonal mesoporous aluminophosphate (CoHMA) molecular sieve catalyst. Further, the catalyst was found to be promising as a heterogeneous catalyst as the yield was practically unchanged after up to six cycles.     

Cascade Reactions: Sequential Homobimetallic Catalysis Leading to Benzofurans and β,γ‐Unsaturated Esters

The concatenation between a Pd(0)‐promoted deallylation catalytic cycle and a Pd(II)‐promoted heterocyclization catalytic cycle (an example of what we have named “sequential homobimetallic catalysis”) has been shown to occur starting from 1‐(2‐allyloxyphenyl)‐2‐yn‐1‐ols 1 to afford 2‐benzofuran‐2‐ylacetic esters 2 and β,γ‐unsaturated esters in high yields under carbonylative conditions. In view of the conceptual as well as the synthetic importance of the process, the mechanistic aspects and the synthetic scope of the reaction have been investigated in detail. All the experimental evidence is in agreement with the sequential homobimetallic mechanism, and the reaction has proven to be of general synthetic applicability.     

Asymmetric Aza‐Morita–Baylis–Hillman‐Type Reactions: The Highly Enantioselective Reaction between Unmodified α,β‐ Unsaturated Aldehydes and N‐Acylimines by Organo‐co‐catalysis

The highly enantioselective organo‐co‐catalytic aza‐Morita–Baylis–Hillman (MBH)‐type reaction between N‐carbamate‐protected imines and α,β‐unsaturated aldehydes has been developed. The organic co‐catalytic system of proline and 1,4‐diazabicyclo[2.2.2]octane (DABCO) enables the asymmetric synthesis of the corresponding N‐Boc‐ and N‐Cbz‐protected β‐amino‐α‐alkylidene‐aldehydes in good to high yields and up to 99% ee. In the case of aza‐MBH‐type addition of enals to phenylprop‐2‐ene‐1‐imines, the co‐catalytic reaction exhibits excellent 1,2‐selectivity. The organo‐co‐catalytic aza‐MBH‐type reaction can also be performed by the direct highly enantioselective addition of α,β‐unsaturated aldehydes to bench‐stable N‐carbamate‐protected α‐amidosulfones to give the corresponding β‐amino‐α‐alkylidene‐aldehydes with up to 99% ee. The organo‐co‐catalytic aza‐MBH‐type reaction is also an expeditious entry to nearly enantiomerically pure β‐amino‐α‐alkylidene‐amino acids and β‐amino‐α‐alkylidene‐lactams (99% ee). The mechanism and stereochemistry of the chiral amine and DABCO co‐catalyzed aza‐MBH‐type reaction are also discussed.     

A Chemoselective Hydrogenation of the Olefinic Bond of α,β‐Unsaturated Carbonyl Compounds in Aqueous Medium under Microwave Irradiation

A microwave‐assisted mild and ecofriendly catalytic transfer hydrogenation process was developed to reduce various α,β‐unsaturated carbonyl compounds into the corresponding saturated carbonyl compounds in the presence of silica‐supported palladium chloride as catalyst and a combination of MeOH/HCOOH/H₂O (1 : 2 : 3) as hydrogen source within 22–55 minutes in moderate to excellent yields with 100% chemoselectivity.     

Heterogeneous Selective Oxidation of Alkenes to α,β‐ Unsaturated Ketones over Coordination Polymer MIL‐101

The mesoporous metal‐organic framework MIL‐101 is an efficient heterogeneous catalyst for the selective allylic oxidation of alkenes with tert‐butyl hydroperoxide. The selectivity towards α,β‐unsaturated ketones reaches 86–93%. The temperature of the catalyst activation strongly affects the ketone yield. MIL‐101 is stable to chromium leaching, behaves as a true heterogeneous catalyst, can be easily recovered by filtration, and can be reused several times without loss of the catalytic performance.