Allenyl Acetates Research Articles

DFT Study on the Mechanisms and Selectivities in Rh (III)-Catalyzed [5 + 1] Annulation of 2-Alkenylanilides and 2-Alkylphenols with Allenyl Acetates.

The mechanisms and regio-, chemo-, and stereoselectivity were theoretically investigated in the Rh(III)-catalyzed [5 + 1] annulation of 2-alkenylanilides and 2-alkylphenols with allenyl acetates. Two different reactants, 2-alkenylanilides and 2-alkylphenols, were selected as model systems in the density functional theory calculations. The obtained theoretical results show that both these reactants exhibit similar steps, namely, (1) N-H/O-H deprotonation and C-H activation, (2) allenyl acetate migratory insertion, (3) β-oxygen elimination, (4) intramolecular nucleophilic addition of the nitrogen/oxygen-rhodium bond resulting in [5 + 1]-annulation, and (5) protonation with the formation of the desired product and regeneration of the Rh(III) catalyst. The theoretical evidence suggests that the selectivity is determined at the step of allenyl acetate's migratory insertion. Moreover, the regioselectivity is driven by electronic effects, while the interaction energies (C-H···π and C-H···O interactions) play a more imperative role in controlling the stereoselectivity. The obtained theoretical results not only well rationalize the experimental observations but also provide important mechanistic insights for related types of [5 + 1]-annulation reactions.

Dithiophosphinylation of Allenyl Acetates: Access to 1,2-Bis(diphenylphosphino)ethane-Type Bidentate Ligands.

1,2-Bis(diphenylphosphino)ethanes (DPPEs) are versatile and immensely important ligands in transition metal catalysts. Here we report the dithiophosphinylation of readily available allenyl acetates to give DPPEs in high yields and regioselectivity. This protocol features a broad substrate scope and mild conditions, avoiding the use of transition metals and air-sensitive sources of phosphorus. Mechanism studies indicate that the reaction was accomplished via an SN2'-type addition-elimination followed by a 1,4-addition step.

Synthesis of structurally diverse pyrazolo[1,2-a]pyrazolones based on the selective C–H bond alkenylation–annulation of 1-arylpyrazolidinones with allenyl acetates

Presented herein is a concise synthesis of diverse pyrazolo[1,2-a]pyrazolones based on condition-controlled divergent reactions of 1-arylpyrazolidinones with allenyl acetates.

Unsymmetrical relay C–H alkenylation and [2 + 2] cycloaddition ofN-arylsydnones with allenyl acetates leading to quinoline-fused cyclobutanes

In this paper, we present a direct, effective and atom-economical access toward quinoline-fused cyclobutane derivatives through Rh(iii)-catalyzed cascade reactions ofN-arylsydnones with allenyl acetates.

Pd(ii)-catalyzed β- and γ-C-(sp3)-H dienylation with allenyl acetates.

Recent years have seen the emergence of transition metal catalyzed C-H activation as a powerful synthetic tool in organic chemistry. Allenes have fascinated synthetic chemists due to their unique reactivity. While directing group assisted functionalization of C(sp2)-H bonds with allenes is well documented in the literature, their coupling with more challenging aliphatic C(sp3)-H bonds remains elusive. In this regard, we hereby report a Pd(ii) catalyzed 8-aminoquinoline directed aliphatic C(sp3)-H dienylation protocol using allenyl acetates. A variety of carboxylic acids including fatty acids and amino acids were efficiently functionalized at β and γ-positions to afford diversely functionalized 1,3-dienes. Preliminary mechanistic studies revealed the crucial role of the base in the success of the transformation. The reaction proceeds via regioselective 2,3-migratory insertion of the allene with the alkylpalladium(ii) species followed by β-acetoxy elimination.

Ru(II)-Catalyzed Regioselective Annulation of 2-Hydroxystyrenes with Allenyl Acetates via Vinylic C-H Activation.

Herein, we disclose an unprecedented and robust Ru(II)-catalyzed non-oxidative [5+1] annulation of 2-hydroxystyrenes with allenyl acetates to access biologically relevant chromene skeletons. The heteroatom on allene plays a pivotal role in controlling the regioselectivity of migratory insertion, and the reaction proceeds through a Ru-σ-allyl pathway, which has been elusive so far in C-H activation reactions with allenes. The protocol is sustainable in nature as it proceeds at room temperature and avoids the use of any toxic metal oxidants. In addition, the synthetic utility of the protocol was also demonstrated by late stage functionalization and modular synthesis of various natural product conjugates.

Rh(iii)-Catalyzed [5 + 1] annulation of 2-alkenylanilides and 2-alkenylphenols with allenyl acetates.

Herein, we report a mild and highly regioselective Rh(iii)-catalyzed non-oxidative [5 + 1] vinylic C–H annulation of 2-alkenylanilides with allenyl acetates, which has been elusive so far. The reaction proceeds via vinylic C–H activation, regioselective 2,3-migratory insertion, β-oxy elimination followed by nucleophilic cyclization to get direct access to 1,2-dihydroquinoline derivatives. The strategy was also successfully extended to C–H activation of 2-alkenylphenols for constructing chromene derivatives. In the overall [5 + 1] annulation, the allene serves as a one carbon unit. The acetate group on the allene is found to be crucial both for controlling the regio- and chemoselectivity of the reaction and also for facilitating β-oxy elimination. The methodology was scalable and also further extended towards late stage functionalization of various natural products.

Computationally Guided Catalyst Design in the Type I Dynamic Kinetic Asymmetric Pauson–Khand Reaction of Allenyl Acetates

The Rh(I)-catalyzed allenic Pauson-Khand reaction (APKR) is an efficient, redox-neutral method of synthesizing α-acyloxy cyclopentenones. An enantioselective APKR could provide access to chiral, nonracemic α-acyloxy and α-hydroxy cyclopentenones and their corresponding redox derivatives, such as thapsigargin, a cytotoxic natural product with potent antitumor activity. Rapid scrambling of axial chirality of allenyl acetates in the presence of Rh(I) catalysts enables the conversion of racemic allene to enantiopure cyclopentenone product in a dynamic kinetic asymmetric transformation (DyKAT). A combined experimental and computational approach was taken to develop an effective catalytic system to achieve the asymmetric transformation. The optimization of the denticity, and steric and electronic properties of the ancillary ligand (initially (S)-MonoPhos, 58:42 er), afforded a hemilabile bidentate (S)-MonoPhos-alkene-Rh(I) catalyst that provided α-acyloxy cyclopentenone product in up to 14:86 er. Enantioselectivity of the Rh(I)-(S)-MonoPhos-alkene catalyst was rationalized using ligand-substrate steric interactions and distortion energies in the computed transition states. This asymmetric APKR of allenyl acetates is a rare example of a Type I DyKAT reaction of an allene, the first example of DyKAT in a cyclocarbonylation reaction, and the first catalyst-controlled enantioselective APKR.

Concise Total Synthesis of Enigmazole A.

An efficient entry into the phosphorylated marine macrolide enigmazole A is described. Enigmazole A interferes with c-Kit signaling by an as yet unknown mode of action and is therefore a potential lead in the quest for novel anticancer agents. Key to success is a gold-catalyzed cascade comprising a [3,3]-sigmatropic rearrangement of a propargyl acetate along the periphery of a macrocyclic scaffold, followed by a transannular hydroalkoxylation of the resulting transient allenyl acetate. This transformation mandated the use of a chiral gold catalyst to ensure a matching double-asymmetric setting. Other noteworthy steps are the preparation of the oxazole building block by a palladium-catalyzed C-H activation, as well as the smooth ring-closing alkyne metathesis of a diyne substrate bearing a propargylic leaving group, which has only little precedent.

Concise Total Synthesis of Enigmazole A

AbstractAn efficient entry into the phosphorylated marine macrolide enigmazole A is described. Enigmazole A interferes with c‐Kit signaling by an as yet unknown mode of action and is therefore a potential lead in the quest for novel anticancer agents. Key to success is a gold‐catalyzed cascade comprising a [3,3]‐sigmatropic rearrangement of a propargyl acetate along the periphery of a macrocyclic scaffold, followed by a transannular hydroalkoxylation of the resulting transient allenyl acetate. This transformation mandated the use of a chiral gold catalyst to ensure a matching double‐asymmetric setting. Other noteworthy steps are the preparation of the oxazole building block by a palladium‐catalyzed C−H activation, as well as the smooth ring‐closing alkyne metathesis of a diyne substrate bearing a propargylic leaving group, which has only little precedent.

ChemInform Abstract: Oxy Effects on the Platinum‐Catalyzed Carbo‐ and Oxacyclizations of 2‐Oxiranyl‐1‐(1‐oxyalk‐2‐ynyl)benzenes.

AbstractEpoxides, bearing an acyloxy group, undergo a PtCl2‐catalyzed cyclization via an initial 1,3‐acyloxy‐shift, nucleophilic attack on an allenyl acetate and 1,2‐alkyl shift to afford 2‐naphthyl ketones.

Oxy Effects on the Platinum‐Catalyzed Carbo‐ and Oxacyclizations of 2‐Oxiranyl‐1‐(1‐oxyalk‐2‐ynyl)benzenes

AbstractWe report new platinum‐catalyzed protocols for the synthesis of carbocycles and oxacycles from 2‐oxiranyl‐1‐(1‐oxyalk‐2‐ynyl)benzenes. For 1,2,2‐trisubstituted epoxides bearing an acyloxy group, their platinum‐catalyzed cyclizations proceed through an initial 1,3‐acyloxy shift, followed by an intramolecular attack of an allenyl acetate at the carbonyl group, ultimately giving 2‐naphthyl ketones through a selective 1,2‐alkyl shift. 1,1‐Disubstituted epoxides bearing a siloxy group undergo an oxacyclization to give bicyclic ketals with high diastereoselectivity.

An S N2′ displacement approach to allenyl acetates

Reaction of cuprates derived from R 3MgBr/CuI/LiBr (R 3 = n-alkyl) with R 1C CCH(O 2CR 2) 2 (R 1 = sp 2 hybridised substituent, R 2 = mainly Me, alkyl, Ph) provides access to allenyl esters R 1R 3C C CH(O 2CR 2) (51–88%). Such species are not accessible via rearrangement of precursor propargylic R 1R 3C(O 2CR 2)C CH.

Gold-Catalyzed Diastereoselective Synthesis of α-Fluoroenones from Propargyl Acetates

A diastereoselective preparation of α-fluoroenones from propargyl acetates has been developed proceeding via a gold-catalyzed rearrangement-fluorination cascade. Control reactions are consistent with a mechanism involving a gold-mediated 3,3-sigma-tropic shift followed by a direct, nongold-catalyzed electrophilic fluorination of the allenyl acetate intermediate.

ChemInform Abstract: Synthesis of (E)‐α‐Ethynyl‐α,β‐unsaturated Esters (VI) from Allenyl Acetates (V) Catalyzed by DABCO and Their Application to Sonogashira Cross‐Coupling Reactions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of (E)-α-Ethynyl-α,β-unsaturated Esters from Allenyl Acetates Catalyzed by DABCO and Their Application to Sonogashira Cross-Coupling Reactions

1 PPTS (0.2) CH2Cl2 6 0 2 AcOH (0.2) DMF 12 0 3 Pyridine (0.2) DMF 0.67 75 4 PPh3 (0.2) DMF 0.5 69 5 DABCO (0.2) DMF 0.5 75 6 DABCO (0.2) THF 4.5 50 7 DABCO (0.2) CH3CN 4.5 70 8 DABCO (0.1) DMF 2.5 81 Because synthesis of α-ethynyl-α,β-unsaturated esters is one of the challenging problems in synthetic organic chemistry, many efficient synthetic methods for the preparation of these compounds have been reported. However, the need for a highly selective synthetic method of (E)-α-ethynyl-α,β-unsaturated esters has been remained. Generally, the selective synthesis of these compounds was accomplished by the transition metalcatalyzed cross-coupling reactions of (Z)-α-halo-α,β-unsaturated esters with terminal alkynes through Sonogashira cross-coupling reaction. Nevertheless, this method is limited because the selective synthetic method of (Z)-α-halo-α,β-unsaturated esters is difficult and isomerization is somewhat occurred during the cross-coupling reactions. Although selective synthesis of (Z)α-halo-α,β-unsaturated esters via CrCl2-mediated olefinations of aldehydes with trihaloacetates was reported, the preparation of (Z)-α-halo-α,β-unsaturated esters through bromination-dehydrobromination, rearrangements, alkoxycarbonylation, deoxygenation of glycidic esters, thermal eliminations, or Wittig/Horner-Emmons/Peterson-type condensations often suffer from poor stereoselectivities, unsatisfactory yields, costly reagents, and/or lengthy procedures. Therefore, we tried to prepare selectively (E)-α-ethynyl-α,β-unsaturated esters from another precursor without the use of (Z)-α-halo-α,β-unsaturated esters. As part of our continuing studies into the utility of allene groups, we report herein the preparation of the selective synthesis of (E)-α-ethynyl-α,β-unsaturated esters from allenyl acetates catalyzed by DABCO and their application to Sonogashira cross-coupling reaction (Scheme 1). First, various allenyl acetates were prepared from the reaction of aldehydes with organoindium in situ generated from ethyl 4-bromobutynoate and indium in the presence of lithium iodide in DMF followed by acetylation (Scheme 2). Next, allenyl acetates were treated with various acids or bases (Table 1). Allenyl acetate (1d) did not react with PPTS and AcOH (entries 1 and 2). Surprisingly, treatment of 1d with pyridine (0.2 equiv) in DMF selectively produced ethyl (E)-α-ethynyl cinnamate (2d) in 75% yield (entry 3). E selectivity was determined by the chemical shift of the vinyl proton in 2d. Vinyl proton in E isomer of 2d appeared at upfield due to the shielding effect from the ester group. Encouraged by this result, triphenylphosphine and DABCO were subsequently examined. Use of triphenylphosphine (0.2 equiv) provided 2d in 69%

ChemInform Abstract: Stereoselective DABCO‐Catalyzed Synthesis of (E)‐α‐Ethynyl‐α,β‐unsaturated Esters from Allenyl Acetates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Gold‐ and Platinum‐Catalyzed Cycloisomerization of Enynyl Esters versus Allenenyl Esters: An Experimental and Theoretical Study

Ester-way to heaven: Unexpected formation of bicyclo[3.1.0]hexene 4 was the main focus of combined experimental and theoretical studies on the Au-catalyzed cycloisomerization of branched dienyne 1 (see scheme), which provided better understanding of the mechanistic details governing the cyclization of enynes bearing a propargylic ester group.Experimental and theoretical studies on Au- and Pt-catalyzed cycloisomerization of a branched dienyne with an acetate group at the propargylic position are presented. The peculiar architecture of the dienyne precursor, which has both a 1,6- and a 1,5-enyne skeleton, leads, in the presence of alkynophilic gold catalysts, to mixtures of bicyclic compounds 3, 4, and 5. Formation of unprecedented bicyclo[3.1.0]hexene 5 is the main focus of this study. The effect of the ancillary ligand on the gold center was examined and found to be crucial for formation of 5. Further mechanistic studies, involving cyclization of an enantioenriched dienyne precursor, (18)O-labeling experiments, and DFT calculations, allowed an unprecedented reaction pathway to be proposed. We show that bicyclo[3.1.0]hexene 5 is likely formed by a 1,3-OAc shift/allene-ene cyclization/1,2-OAc shift sequence, as calculated by DFT and supported by Au-catalyzed cyclization of isolated allenenyl acetate 7, which leads to improved selectivity in the formation of 5. Additionally, the possibility of OAc migration from allenyl acetates was supported by a trapping experiment with styrene that afforded the corresponding cyclopropane derivative. This unprecedented generation of a vinyl metal carbene from an allenyl ester supports a facile enynyl ester/allenenyl ester equilibrium. Further examination of the difference in reactivity between enynyl acetates and their corresponding [3,3]-rearranged allenenyl acetates toward Au- and Pt-catalyzed cycloisomerization is also presented.

Stereoselective DABCO-Catalyzed Synthesis of (E)-α-Ethynyl-α,β-Unsaturated Esters from Allenyl Acetates

(E)-alpha-ethynyl-alpha,beta-unsaturated esters were exclusively prepared in good to excellent yields from treatment of allenyl acetates with 10 mol % DABCO in DMF at room temperature.

Novozym 435‐Catalyzed Kinetic Resolution of β‐Allenols. A Facile Route for the Preparation of Optically Active β‐Allenols or Allenyl Acetates.

AbstractFor Abstract see ChemInform Abstract in Full Text.