Allylic Acetates Research Articles

Nickel-Catalyzed Cross-Electrophile Coupling Reactions between Allylic Acetates and gem-Difluorovinyl Tosylate.

A nickel-catalyzed cross-electrophile coupling of allylic acetates and gem-difluorovinyl tosylate is presented, which first achieves allylic gem-difluoroolefins via C(sp3)-C(sp2) cross-electrophile coupling. In addition, this protocol was performed under mild reaction conditions, affording a variety of allylic gem-difluorovinyl arenes in moderate to good yields. Moreover, both linear and branched allylic acetate could produce a linear cross-coupling product exclusively. Mechanistic studies reveal that the reaction involves two different Ni(0)/Ni(II) catalytic cycles.

Recent Advances in the Catalytic Umpolung Carboxylation of Allylic Alcohol Derivatives with Carbon Dioxide

AbstractAllylic alcohols and their derivatives (e. g. halides, acetates, and pivalates) are readily available organic compounds that are frequently employed in organic synthesis, and especially in Tsuji‐Trost‐type allylic substitution reactions. These allylic substrates add oxidatively to transition metals such as Pd to form π‐allyl metal species, which can act as suitable electrophiles for several nucleophilic counterparts. However, under reductive conditions, the π‐allyl metal species instantly become nucleophilic and react with various electrophiles including the rather stable CO2, which is an abundant, inexpensive, non‐toxic, and renewable carbon source in organic synthesis. When CO2 is incorporated in allylic compounds, synthetically useful β,γ‐unsaturated carboxylic acid derivatives are obtained exclusively. In this review, we focus on the recent advances in such catalytic umpolung carboxylations of allyl alcohols, acetates, pivalates, and halides with CO2 under thermal, photochemical, and electrochemical conditions.

Front Cover: Recent Advances in the Catalytic Umpolung Carboxylation of Allylic Alcohol Derivatives with Carbon Dioxide (Asian J. Org. Chem. 5/2022)

Allylic alcohols and their derivatives are readily available organic compounds that are frequently employed in organic synthesis. These allylic substrates add oxidatively to transition metals to form π-allyl metal species, which instantly become nucleophilic under reductive conditions and react with various electrophiles including the rather stable CO2 to afford synthetically useful β,γ-unsaturated carboxylic acid derivatives. In this review, we focus on the recent advances in such catalytic umpolung carboxylations of allyl alcohols, acetates, pivalates, and halides with CO2 under thermal, photochemical, and electrochemical conditions. More information can be found in the Review by Tsuyoshi Mita et al.

Processes for the synthesis of γ-acetopropyl alcohol

The literature on the existing processes for the synthesis of γ-acetopropyl alcohol (acetopropanol, 5-hydroxypentan-2-one, APA) is reviewed. This substance is used to produce vitamin B1, antimalarial drugs and polymers. The promising methods for APA production are the hydrogenation-hydration of sylvan (2-methylfuran), hydrogenation of furfural, and syntheses based on allyl acetate, sodium acetoacetic ether, and γ-butyrolactone.

Cationic-palladium catalyzed regio- and stereoselective syn-1,2-dicarbofunctionalization of unsymmetrical internal alkynes

π-Extended tetrasubstituted olefins are widely found motifs in natural products, leading drugs, and agrochemicals. Thus, development of modular strategies for the synthesis of complex all-carbon-substituted olefins always draws attention. The difunctionalization of unsymmetrical alkynes is an attractive approach but it has remained faced with regioselectivity issues. Here we report the discovery of a regio- and stereoselective syn-1,2-dicarbofunctionalization of unsymmetrical internal alkynes. A cationic Pd-catalyzed three-component coupling of aryl diazonium salts, aryl boronic acids (or olefins) and yne-acetates enables access to all-carbon substituted unsymmetrical olefins. The transformation features broad scope with labile functional group tolerance, building broad chemical space of structural diversity (94 molecules). The value of this synthetic method is demonstrated by the direct transformation of natural products and drug candidates containing yne-acetates, to enable highly substituted structurally complex allyl acetate analogues of biologically important compounds. Synthetic versatility of the carboxylate bearing highly substituted olefins is also presented. The reaction outcome is attributed to the in situ formation of stabilized cationic aryl-Pd species, which regulates regioselective aryl-palladation of unsymmetrical yne-acetates. Control experiments reveal the synergy between the carboxylate protecting group and the cationic Pd-intermediate in the regioselectivity and reaction productivity; density functional theory (DFT) studies rationalize the selectivity of the reaction.

Kinetic, ESI-CID-MS and Computational Studies of π-Allyliridium C,O-Benzoate-Catalyzed Allylic Amination: Understanding the Effect of Cesium Ion.

The mechanism of π-allyliridium C,O-benzoate-catalyzed allylic amination was studied by (a) reaction progress kinetic analysis (RPKA), (b) tandem ESI-MS analysis, and (c) computational studies involving density functional theory (DFT) calculations. Reaction progress kinetic analysis (RPKA) reveals a zero-order dependence on allyl acetate, first-order dependence on catalyst and fractional-order dependence on amine. These data corroborate rapid ionization of the allylic acetate followed by turnover limiting C-N bond formation. To illuminate the origins of the 0.4 kinetic order dependence on amine, ESI-MS analyses of quaternary ammonium-labelled piperazine with multistage collision induced dissociation (CID) were conducted that corroborate intervention of cesium-bridged amine dimers that dissociate to form monomeric cesium amide nucleophiles. Computational data align with RPKA and ESI-CID-MS analyses and suggest early transition states mitigate the impact of steric factors, thus enabling formation of highly substituted C-N bonds with complete levels of branched regioselectivity. Specifically, trans-effects of the iridium complex facilitate nucleophilic attack at the more substituted allyl terminus trans to phosphorus with enantioselectivity governed by steric repulsions between the chiral bisphosphine ligand and the π-allyl of a dominant diastereomer of the stereogenic-at-metal complex. Beyond defining aspects of the mechanism of π-allyliridium C,O-benzoate-catalyzed allylic amination, these data reveal that a key feature of cesium carbonate not only lies in its enhanced basicity, but also its capacity for Lewis-acid enhanced Brønsted acidification of amines.

Combined Effect of Palladium Catalyst and the Alcohol to Promote the Uncommon Bis‐Alkoxycarbonylation of Allylic Substrates

AbstractA chemoselective method for the carbonylation of allylic substrates CH2=CHCH2X (X=OAc, OC(O)CH2CN, OPh, OEt, OC(O)OPh, OC(O)OiBu, N(H)C(O)Ph, N(Ph)C(O)Ph, N(H)Boc, N(Ph)Boc, Ph, CO2Bn, CN), leading to alkyl succinates with preservation of the X group, under Pd(II)‐catalyzed oxidative carbonylation conditions, has been developed. Our method shows a completely different inverse chemoselectivity with respect to the “classical” substitutive carbonylation of the allyl compounds, which is known to provide β,γ‐unsaturated carbonyl derivatives through the formation of a π‐allylpalladium intermediate. An accurate study, carried out using allyl acetate as model substrate, allowed to maximize the selectivity in the envisioned 2‐CH2X substituted succinates. The best catalyst is generated in situ by mixing Pd(TFA)2 (TFA=trifluoroacetate) and the N,N′‐di(anthracen‐9‐yl)butane‐2,3‐diimine ligand. p‐Benzoquinone was used as oxidant in presence of benzyl alcohol, which acts as a nucleophile and as a solvent, under 4 bar of CO at 20 °C. A combined effect of the ligand and the nucleophile, rationalized through DFT calculations, has been observed both in promoting the bis‐alkoxycarbonylation process and in preventing π‐allylpalladium‐mediated side reactions, allowing the attainment of succinate derivatives with moderate to good yields.

Aerobic Allylic Amination Catalyzed by a Pd(OAc)2/P(OPh)3 System with Low Catalyst Loading.

A Pd(OAc)2/P(OPh)3 combination catalyzed Tsuji-Trost-type allylic amination under aerobic conditions. Both aromatic and aliphatic secondary amines were transformed into the corresponding allylic amines with a tiny amount of the catalyst system (typically 0.02 mol % Pd), only when allylic phosphates were employed as electrophiles. Other typical electrophiles, such as allylic acetate and carbonate, were marginally reactive. A Pd(0) complex, Pd[P(OPh)3]3, formed in situ was suggested as an active species by mechanistic experiments.

Nickel‐Mediated Enantioselective Photoredox Allylation of Aldehydes with Visible Light

AbstractHere we report a practical, highly enantioselective photoredox allylation of aldehydes mediated by chiral nickel complexes with commercially available allyl acetate as the allylating agent. The methodology allows the clean stereoselective allylation of aldehydes in good to excellent yields and up to 93 % e.e. using a catalytic amount of NiCl2(glyme) in the presence of the chiral aminoindanol‐derived bis(oxazoline) as the chiral ligand. The photoredox system is constituted by the organic dye 3DPAFIPN and a Hantzsch's ester as the sacrificial reductant. The reaction proceeds under visible‐light irradiation (blue LEDs, 456 nm) at 8–12 °C. Compared to other published procedures, no metal reductants (such as Zn or Mn), additives (e.g. CuI) or air‐sensitive Ni(COD)2 are necessary for this reaction. Accurate DFT calculations and photophysical experiments have clarified the mechanistic picture of this stereoselective allylation reaction.

Nickel-Mediated Enantioselective Photoredox Allylation of Aldehydes with Visible Light.

Here we report a practical, highly enantioselective photoredox allylation of aldehydes mediated by chiral nickel complexes with commercially available allyl acetate as the allylating agent. The methodology allows the clean stereoselective allylation of aldehydes in good to excellent yields and up to 93 % e.e. using a catalytic amount of NiCl2 (glyme) in the presence of the chiral aminoindanol-derived bis(oxazoline) as the chiral ligand. The photoredox system is constituted by the organic dye 3DPAFIPN and a Hantzsch's ester as the sacrificial reductant. The reaction proceeds under visible-light irradiation (blue LEDs, 456 nm) at 8-12 °C. Compared to other published procedures, no metal reductants (such as Zn or Mn), additives (e.g. CuI) or air-sensitive Ni(COD)2 are necessary for this reaction. Accurate DFT calculations and photophysical experiments have clarified the mechanistic picture of this stereoselective allylation reaction.

Nickel-catalyzed cross-electrophile allylation of vinyl bromides and the modification of anti-tumour natural medicine β-elemene.

Herein, we present a facile and efficient allylation method via Ni-catalyzed cross-electrophile coupling of readily available allylic acetates with a variety of substituted alkenyl bromides using zinc as the terminal reductant. This Ni-catalyzed modular approach displays excellent functional group tolerance and a broad substrate scope, which the creation of a series of 1,4-dienes including several structurally complex natural products and pharmaceutical motifs. Moreover, the coupling strategy has the potential to realize enantiomeric control. The practicality of this transformation is demonstrated through the potent modification of the naturally antitumor active molecule β-elemene.

Fuel-driven macromolecular coacervation in complex coacervate core micelles

Fuel-driven macromolecular coacervation is an entry into the transient formation of highly charged, responsive material phases. In this work, we used a chemical reaction network (CRN) to drive the coacervation of macromolecular species readily produced using radical polymerisation methods. The CRN enables transient quaternization of tertiary amine substrates, driven by the conversion of electron deficient allyl acetates and thiol or amine nucleophiles. By incorporating tertiary amine functionality into block copolymers, we demonstrate chemical triggered complex coacervate core micelle (C3M) assembly and disassembly. In contrast to most dynamic coacervate systems, this CRN operates at constant physiological pH without the need for complex biomolecules. By varying the allyl acetate fuel, deactivating nucleophile and reagent ratios, we achieved both sequential signal-induced C3M (dis)assembly, as well as transient non-equilibrium (dis)assembly. We expect that timed and signal-responsive control over coacervate phase formation at physiological pH will find application in nucleic acid delivery, nano reactors and protocell research.

C-Glycosylcrotylboronates for the Synthesis of Glycomimetics.

The stereoselective synthesis of E- and Z- isomers of a C- mannosyl crotylpinacolboronate via Ni-promoted reactions on an allylic acetate and a diene precursor, respectively, is described. The E- and Z- isomers reacted with 1,2-O-isopropylidene glyceraldehyde in the presence or absence of (R)- and (S)- TRIP catalysts, to give predominantly 3,4-anti and 3,4-syn crotylation products, respectively, with moderate to high facial selectivity. These products were transformed to biologically relevant C-manno-disaccharides.

Regio- and Enantioselective Iridium-Catalyzed Amination of Alkyl-Substituted Allylic Acetates with Secondary Amines.

Robust air-stable cyclometalated π-allyliridium C,O-benzoates modified by (S)-tol-BINAP catalyze the reaction of secondary aliphatic amines with racemic alkyl-substituted allylic acetates to furnish products of allylic amination with high levels of enantioselectivity. Complete branched regioselectivities were observed despite the formation of more highly substituted C-N bonds.

Ni-Catalyzed Enantioselective Allylic Alkylation of H-Phosphinates.

The asymmetric synthesis of P-stereogenic phosphinates through allylic alkylation of H-phosphinates has been developed. With H-phosphinates and allylic acetates as the starting materials, a variety of allylic P-chiral phosphinates were accessed in high enantioselectivities of up to 92% ee and generally high yields. In addition, a further study demonstrated the applicability of this protocol, including the scale-up synthesis and facile transformation of chiral products from phosphinates to phosphine oxides with organolithium reagents under mild reaction conditions.

Nickel/Photo-Cocatalyzed C(sp2)-H Allylation of Aldehydes and Formamides.

Herein we report a nickel/photo-cocatalyzed C(sp2)-H allylation of aldehydes and formamides wherein both allyl acetates and allyl alcohols can be used as the allylating agents. In this reaction, radical-type umpolung of the formyl moiety is enabled by tetrabutylammonium decatungstate as a hydrogen-atom-transfer photocatalyst, whereas nickel serves to cleave the C-O bond of allyl acetates or allyl alcohols. The synergistic effect of these two catalysts provides new access to various β,γ-unsaturated ketones and amides with high selectivities.

Carboxylic Acid Promoted, Redox‐Neutral Ru‐Catalyzed C−H Allylation of Aromatic Ketones

AbstractA redox‐neutral, carboxylic acid promoted, [RuCl2(p‐cymene)]2 catalyzed, weakly coordinating, carbonyl assisted C−H allylation of aromatic ketones has been developed. The beneficial effect of carboxylic acid on the ruthenium catalyst towards C−H allylation of aromatic ketones has been further explored, using commercially available allyl acetate under mild reaction conditions. In addition, this method requires redox‐neutral reaction conditions, easily accessible starting materials, and shows excellent functional group compatibility.

Enantioselective Reductive Homocoupling of Allylic Acetates Enabled by Dual Photoredox/Palladium Catalysis: Access to C2-Symmetrical 1,5-Dienes

Transition-metal-catalyzed reductive coupling reactions have emerged as powerful protocols to construct C-C bonds. However, the development of enantioselective C(sp3)-C(sp3) reductive coupling remains challenging. Herein, we report a highly regio-, diastereo-, and enantioselective reductive homocoupling of allylic acetates through cooperative palladium and photoredox catalysis using diisopropylethylamine or Hantzsch ester as a homogeneous organic reductant. This straightforward protocol enables the stereoselective construction of C(sp3)-C(sp3) bonds under mild reaction conditions. A series of C2-symmetrical chiral 1,5-dienes were easily prepared with excellent enantioselectivities (up to >99% ee), diastereoselectivities (up to >95:5 dr), and regioselectivities (up to >95:5 rr). The resultant chiral 1,5-dienes can be directly used as chiral ligands in asymmetric synthesis, and they can be also transformed into other valuable chiral ligands.

Optimal modes of side-section flow in heat-pump-assisted extractive distillation systems for separating allyl alcohol–allyl acetate mixtures with butyl propionate

Objectives.To investigate the influence of side-section flow modes on the energy efficiency of apartially thermally coupled distillation sequence (PTCDS) with a vapor recompression heat pumpfor the extractive distillation of an allyl alcohol–allyl acetate mixture with n-butyl propionate andidentify modes under which the combined use of a PTCDS and heat pump are the most efficient.Methods.Mathematical modeling in the Aspen Plus V10 software package was used as the mainresearch method. The local composition equation of the non-random two-liquid model was usedas a model for describing the vapor–liquid equilibrium, while the Redlich–Kwong model was usedto consider the non-ideal vapor phase. When modeling the conventional extractive distillationscheme and PTCDS, parametric optimization was carried out according to the criterion of the totalenergy costs in the column reboilers. For the economical evaluation, Aspen Process EconomicAnalyzer V10.1 tools were used.Results.For extractive distillation of a mixture of allyl alcohol (30 wt %) and allyl acetate (70 wt %)with n-butyl propionate as an entrainer, the minimum energy consumption was achieved at thesame side-section flow mode for the variants of a PTCDS with and without a heat pump. Thereduction in energy costs relative to the conventional scheme was 20% for the sequence withouta heat pump and 38% for that with a heat pump. An economic assessment was made of thebest options in comparison with the conventional extractive distillation scheme. The PTCDS witha heat pump had an advantage over the sequence without a heat pump only for long periods ofoperation.Conclusions.For the extractive distillation of an allyl alcohol–allyl acetate mixture, the optimalmodes for the combined use of a PTCDS with a vapor recompression heat pump coincide with theoptimal modes for a PTCDS without a heat pump.

Alkene Isomerization Revitalizes the Coates–Claisen Rearrangement

AbstractThe [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.