Allylic Acetates Research Articles

Alkene Isomerization Revitalizes the Coates-Claisen Rearrangement.

The [3,3]‐sigmatropic rearrangement of allylic vinyl acetals, first investigated by Coates nearly four decades ago, is set apart from other variants of the Claisen rearrangement owing to the versatile monoprotected 1,5‐dicarbonyl motif featured in the products. Unfortunately, the synthetically elusive nature of the substrates has thus far precluded the widespread application of this attractive transformation. Herein, we show that the key allylic vinyl acetals can be efficiently generated through alkene isomerization of their readily available regioisomeric counterparts (derived from allylic alcohols and α,β‐unsaturated aldehydes), thus enabling the first systematic study of the substrate scope of this rearrangement, as well as the discovery of exceptionally mild conditions for its mediation by Lewis and Brønsted acids.

Extraction of allyl alcohol from its aqueous solution using two different ionic liquids: Intermolecular interaction and liquid-liquid phase equilibrium explorations

Allyl alcohol is a remarkable chemical intermediate. During its preparation by allyl acetate hydrolysis, an aqueous mixture is usually obtained. Because allyl alcohol can form a minimum boiling point azeotropic mixture with water, it is impossible to separate such a mixture by conventional distillation. In this work, for recovering allyl alcohol by extraction, the ionic liquid extractants (ILs) were adopted by the model of COSMO-SAC and two ILs 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ([BMP][Tf2N]) and 1-octyl-3-methylimidazolium trifluoromethanesulfonate ([OMIM][OTf]) were selected. The length of the hydrogen bond and the energy of the interaction between the ILs and (allyl alcohol/water) were calculated by quantum chemical calculations. The experimental liquid–liquid phase equilibrium (LLE) data for the ternary systems (water + allyl alcohol + [OMIM][OTf]/[BMP][Tf2N]) were explored at 298.15 K. The [OMIM][OTf] and [BMP][Tf2N] extraction capability was assessed with selectivity and partition ratio. In addition, the NRTL model was used to fit the measured tie-line values.

Enantioselective Iridium-Catalyzed Allylation of Nitroalkanes: Entry to β-Stereogenic α-Quaternary Primary Amines.

The first systematic study of simple nitronate nucleophiles in iridium-catalyzed allylic alkylation is described. Using a tol-BINAP-modified π-allyliridium C,O-benzoate catalyst, α,α-disubstituted nitronates substitute racemic branched alkyl-substituted allylic acetates, thus providing entry to β-stereogenic α-quaternary primary amines. DFT calculations reveal early transition states that render the reaction less sensitive to steric effects and distinct trans-effects of diastereomeric chiral-at-iridium π-allyl complexes that facilitate formation of congested tertiary-quaternary C-C bonds.

Deconjugative α-Alkylation of Cyclohexenecarboxaldehydes: An Access to Diverse Terpenoids.

A general and efficient method for the deconjugative α-alkylation of α,β-unsaturated aldehydes promoted by a synergistic effect between tBuOK and NaH, which considerably increases the reaction rate under mild conditions, is reported. The β,γ-unsaturated aldehyde, resulting from the α-alkylation, is transformed in high yield into the corresponding allyl acetate via a lead(IV) acetate-mediated oxidative fragmentation. This strategy could be used for the construction of the carbon skeleton of a wide variety of alkyl or arylterpenoids.

Synthesis and Modeling of Ezetimibe Analogues.

Ezetimibe is a well-known drug that lowers blood cholesterol levels by reducing its absorption in the small intestine when joining to Niemann-Pick C1-like protein (NPC1L1). A ligand-based study on ezetimibe analogues is reported, together with one-hit synthesis, highlighted in the study. A convenient asymmetric synthesis of (2S,3S)-N-α-(R)-methylbenzyl-3-methoxycarbonylethyl-4-methoxyphenyl β-lactam is described starting from Baylis–Hillman adducts. The route involves a domino process: allylic acetate rearrangement, stereoselective Ireland–Claisen rearrangement and asymmetric Michael addition, which provides a δ-amino acid derivative with full stereochemical control. A subsequent inversion of ester and acid functionality paves the way to the lactam core after monodebenzylation and lactam formation. It also shows interesting results when it comes to a pharmacophore study based on ezetimibe as the main ligand in lowering blood cholesterol levels, revealing which substituents on the azetidine-2-one ring are more similar to the ezetimibe skeleton and will more likely bind to NPC1L1 than ezetimibe.

Iridium-Catalyzed Enantioselective C–C Coupling of Ethanol with Allylic Acetates

Iridium-Catalyzed Enantioselective C–C Coupling of Ethanol with Allylic Acetates

Palladium-Catalyzed Isoquinoline Synthesis by Tandem C-H Allylation and Oxidative Cyclization of Benzylamines with Allyl Acetate.

A novel approach to synthesize 3-methylisoquinolines via a one-pot, two-step, palladium(II)-catalyzed tandem C-H allylation/intermolecular amination and aromatization is reported. A wide series of 3-methylisoquinoline derivatives were obtained directly using this method in moderate to good yields, and we highlight the synthetic importance of this new transformation.

Effect of NOx on secondary organic aerosol formation from the photochemical transformation of allyl acetate

Smog chamber experiments were conducted to explore the photochemical degradation of allyl acetate (AA) in the presence of SO2 and to assess the role of NOx on the secondary organic aerosol (SOA) formation potential. A one-product gas-particle partitioning absorption model was used to express the formed organic aerosol. The experimental results showed a clear dependence of SOA formation potential on the NOx level. The particle mass concentrations at low NOx conditions (AA/NOx > 3) were commonly higher than those at high NOx conditions (AA/NOx < 3). The SOA yields increased with the increasing NOx concentration under low NOx conditions and decreased with the increasing NOx concentration under high NOx conditions due to the different reaction pathways of RO2 radicals. Gas chromatography-mass spectrometry (GC-MS) and Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) analysis suggested that organic nitrates and organic sulfates were formed during photochemistry experiments. Based on detected products, the mechanisms of AA photooxidation were proposed. The results of this study show the different effects of NOx concentrations on promoting and inhibiting aerosol formation, and highlight the pronounced formation of SOA from the photooxidation of AA in polluted environment.

Ethanol: Unlocking an Abundant Renewable C2 -Feedstock for Catalytic Enantioselective C-C Coupling.

With annual production at >85 million tons/year, ethanol is the world's largest-volume renewable small molecule carbon source, yet its use as a C2 -feedstock in enantioselective C-C coupling is unknown. Here, the first catalytic enantioselective C-C couplings of ethanol are demonstrated in reactions with structurally complex, nitrogen-rich allylic acetates incorporating the top 10 N-heterocycles found in FDA-approved drugs.

Ethanol: Unlocking an Abundant Renewable C2‐Feedstock for Catalytic Enantioselective C−C Coupling

AbstractWith annual production at &gt;85 million tons/year, ethanol is the world's largest‐volume renewable small molecule carbon source, yet its use as a C2‐feedstock in enantioselective C−C coupling is unknown. Here, the first catalytic enantioselective C−C couplings of ethanol are demonstrated in reactions with structurally complex, nitrogen‐rich allylic acetates incorporating the top 10 N‐heterocycles found in FDA‐approved drugs.

Palladium catalyzed oxidation of biorenewable β-citronellol and geraniol for the synthesis of polyfunctionalized fragrances

Abstract β-Citronellol and geraniol are bio-renewable compounds found in essential oils of various plants. Allylic oxidation of trisubstituted sterically highly encumbered carbon-carbon double bonds in their molecules with dioxygen can be efficiently catalyzed by the palladium acetate/p-benzoquinone combination under 5−10 atm of dioxygen pressure without the need for conventionally used metal co-catalysts. Both substrates gave allyl acetates in ca. 90% combined yield. The oxidation of geraniol proceeded with excellent site-selectivity involving only one of its two C C bonds. Geraniol gave both linear and branched allyl acetates in comparable yields, whereas the reaction of β-citronellol showed high regioselectivity for the corresponding branched product. Polyfunctionalized oxygenated terpenes produced from β-citronellol and geraniol are of a potential importance as ingredients for fragrance compositions.

Chiral phosphine-catalyzed asymmetric [4 + 1] annulation of polar dienes with allylic derivatives: Enantioselective synthesis of substituted cyclopentenes

A chiral phosphine-catalyzed asymmetric [4 + 1] annulation reaction of polar 1,3-dienes and allylic derivatives is reported. Under the catalysis of P-chiral bicyclic phosphine (15 mol%), a series of 1,1-dicyano-2,4-diaryl-1,3-dienes (21 examples) readily undergo stereoselective [4 + 1] annulation reactions with allylic acetate under mild conditions, delivering enantio-enriched polysubstituted cyclopentenes in 49–89% yields and 51–98% ee. A plausible mechanism for the reaction is also discussed.

Enantioselective Iridium-Catalyzed Allylic Alkylation of Racemic Branched Alkyl-Substituted Allylic Acetates with Malonates.

The regio- and enantioselective allylic substitution of branched alkyl-substituted allylic acetates employing malonates has been achieved through a process that calls for Krische's π-allyliridium C,O-benzoate catalyst. The protocol reported herein can be applied to a diverse set of branched alkyl substrates that are generally not well tolerated in the other two types of Ir-catalyzed allylation.

Stereodivergent Pd/Cu catalysis: asymmetric alkylation of racemic symmetrical 1,3-diphenyl allyl acetates.

We report a stereodivergent Pd/Cu catalyst system that was successfully applied to the asymmetric allylic alkylation of symmetrical 1,3-disubstituted allyl acetates with prochiral imino esters, providing efficient access to enantiopure products bearing vicinal stereocenters in a fully stereodivergent manner. The protocol proceeds smoothly under mild reaction conditions and can accommodate a range of imino esters, delivering the substituted products in high yields and with excellent diastereoselectivities (up to >20 : 1 dr) and enantioselectivities (up to >99% ee).

Catalytic Photoredox Allylation of Aldehydes Promoted by a Cobalt Complex

AbstractThe preparation of homoallylic alcohols by addition of organometallic allyl compounds to carbonyls is an important strategy in organic chemistry. Allylating organometallic cobalt species can be generated employing stoichiometric quantities of Zn acting as reductant. To avoid the employment of stoichiometric amount of Zn, we have developed an allylation reaction of aromatic and aliphatic aldehydes promoted by photoredox catalysis in the presence of a cobalt complex, and we present herein a full account of our research. In the presence of the abundant CoBr2 (10 mol %), 4,4′‐di‐tert‐butyl‐2,2′‐dipyridyl (dtbbpy, 10 mol %), allyl acetate (3 equiv.), [Ir(dtbbpy)(ppy)2]PF6 (ppy=2‐phenylpyridine, 2 mol %), and N,N‐diisopropylethylamine (4 equiv.), an allylation of aldehydes is taking place, in moderate to good yields. Substrates scope, limitations, and photophysical investigations of this new process are reported.magnified image

Nickel-Catalyzed Reductive Allylation of Aldehydes with Allyl Acetates

AbstractCarbonyl allylation reactions constitute an important step in the formation of carbon–carbon reactions, and involve various related reactions that chiefly use allylmetal reagents. This report presents a nickel-catalyzed carbonyl allylation reaction using allyl acetate, which produces homoallyl alcohols in moderate to good yields, as an efficient methodology under reductive coupling conditions.

Naphthalenes and Quinolines by Domino Reactions of Morita-Baylis-Hillman Acetates.

An efficient synthetic route to highly functionalized naphthalenes and quinolines has been developed using domino reactions between Morita–Baylis–Hillman (MBH) acetates and active methylene compounds (AMCs) promoted by anhydrous K2CO3 in dry N,N-dimethylformamide (DMF) at 23 °C. The substrates incorporate allylic acetates positioned adjacent to a Michael acceptor as well as an aromatic ring activated toward a SNAr ring closure. A control experiment indicated that the initial reaction was an SN2’-type displacement of a side chain acetoxy by the AMC anion to afford the alkene product bearing the added nucleophile trans to the SNAr aromatic ring acceptor. Thus, equilibration of the alkene geometry of the initial product was required prior to cyclization. Products were isolated in good to excellent yields. Numerous cases (24) are reported, and several mechanistic possibilities are discussed.

Ultrasound Study of Binary Liquid Mixtures Allyl Acetate with Di-Oxane at 300c

Ultrasound Study of Binary Liquid Mixtures Allyl Acetate with Di-Oxane at 300c

Regio- and Enantioselective Palladium-Catalyzed Asymmetric Allylation of N-Fluorenyl Trifluoromethyl Imine.

A palladium-catalyzed asymmetric allylation of N-fluorenyl trifluoromethyl imine with allylic acetates is disclosed. This method provides scalable and efficient access to polysubstituted chiral α-trifluoromethyl amines bearing two adjacent stereocenters and one allyl group in high yields with excellent regio-, diastereo-, and enantioselectivity. Importantly, this method also provides a powerful strategy for the synthesis of both regioisomeric products and the regioselectivity is controlled by the chiral catalysts and optically active substrates.

Exploring the Mechanism of Catalysis with the Unified Reaction Valley Approach (URVA)—A Review

The unified reaction valley approach (URVA) differs from mainstream mechanistic studies, as it describes a chemical reaction via the reaction path and the surrounding reaction valley on the potential energy surface from the van der Waals region to the transition state and far out into the exit channel, where the products are located. The key feature of URVA is the focus on the curving of the reaction path. Moving along the reaction path, any electronic structure change of the reacting molecules is registered by a change in their normal vibrational modes and their coupling with the path, which recovers the curvature of the reaction path. This leads to a unique curvature profile for each chemical reaction with curvature minima reflecting minimal change and curvature maxima, the location of important chemical events such as bond breaking/forming, charge polarization and transfer, rehybridization, etc. A unique decomposition of the path curvature into internal coordinate components provides comprehensive insights into the origins of the chemical changes taking place. After presenting the theoretical background of URVA, we discuss its application to four diverse catalytic processes: (i) the Rh catalyzed methanol carbonylation—the Monsanto process; (ii) the Sharpless epoxidation of allylic alcohols—transition to heterogenous catalysis; (iii) Au(I) assisted [3,3]-sigmatropic rearrangement of allyl acetate; and (iv) the Bacillus subtilis chorismate mutase catalyzed Claisen rearrangement—and show how URVA leads to a new protocol for fine-tuning of existing catalysts and the design of new efficient and eco-friendly catalysts. At the end of this article the pURVA software is introduced. The overall goal of this article is to introduce to the chemical community a new protocol for fine-tuning existing catalytic reactions while aiding in the design of modern and environmentally friendly catalysts.