Captodative Olefins Research Articles

Cycloaddition reactions of o-quinone methides with polarized olefins

The review summarizes and systematizes the [4+2]-cycloaddition reactions of o-quinone methides with electron-rich and electron-deficient olefins. The electron-rich substrates include vinyl ethers, vinyl sulfides, enamines, enamides, enols, furans, benzofurans and indoles, while the electron-deficient substrates are esters of unsaturated carboxylic acids, vinyl azides and quinones. Reactions with push-pull and captodative olefins are also considered. The mechanisms of some reactions are presented. A separate part of the review addresses reactions of p-quinone methides containing an o-hydroxyphenyl substituent at the exocyclic carbon atom, which can isomerize to o-quinone methides. Much attention is paid to oligomerization of o-quinone methides, which proceeds in the absence of active dienophiles or nucleophiles.The bibliography includes 217 references.

Conjugate addition between syringol and a captodative olefin catalyzed by BF3

AbstractThe regioselectivity of the conjugate addition between syringol (1) and the captodative olefin 3‐(p‐nitrobenzoyloxy)‐but‐3‐en‐2‐one (2) is evaluated under diverse solvent and Lewis acid catalyst conditions, providing a mixture of the para/meta phenol adducts. Experimental results revealed for most of the trials that the para regioisomer is the major one. However, there is not a clear correlation between the regioselectivity of products and the polarity of the tested solvents. In this work, the reactivity descriptors and the reaction mechanism are studied in the framework of the density functional theory (DFT) to give insights about the reactivity and regioselectivity of this reaction. The Parr functions difference is used as the reactivity descriptor in each stage of the reaction explaining quite well the involved transition states. Overall, it is found that the reactivity of 1 is strongly influenced by the presence of the catalyst, while the regioselectivity of the products depends on both the catalyst and the polarity of the solvent, finding that, the meta adduct is highly dependent of the presence of nonpolar solvents.

Palladium-Catalyzed Multicomponent Reaction of Alkynes, Carboxylic Acids, and Isocyanides: A Direct Approach to Captodative Olefins.

A palladium-catalyzed multicomponent reaction of alkynes, carboxylic acids, and isocyanides has been developed with the assistance of silver salt under mild conditions. Highly functionalized captodative olefins are synthesized efficiently by this method, which can find many applications as versatile synthons in organic synthesis.

Stereoselectivity of the captodative alkenes 1-acetylvinyl arenecarboxylates in Diels-Alder reactions with cyclic dienes and stereospecific rearrangement of their bicyclo[2.2.n] α-ketol adducts

Captodative alkene 1-acetylvinyl p-nitrobenzenecarboxylate 1a was evaluated for its reactivity and stereoselectivity with cyclohexadiene (10) in Diels-Alder reactions, showing exclusive endo preference. The two hydrolyzed products of the endo and the exo adducts obtained from the Diels-Alder cycloaddition between 1a and cyclopentadiene (7) were 8b and 9b. When treated with mCPBA, a ring expansion took place to stereospecifically yield the novel 3-oxatricyclo[3.3.1.02,4]nonanone acyloins 15 and 16, respectively. In the case of the α-ketol bicyclo[2.2.2]octanes 11b and 12b, the epoxidation/Baeyer-Villiger cascade process was preferred, resulting in the syn ketoepoxide 19b from each isomer. A synthetic application of this kind of transformation was carried out by reacting ketols 8b and 9b with an excess of mCPBA through a five-step cascade process to yield the bicyclic lactone 27 asa potential precursor of racemic β-carbaxylose.

ChemInform Abstract: Synthesis of α‐Ketols by Functionalization of Captodative Alkenes and Divergent Preparation of Heterocycles and Natural Products.

AbstractThe presented method is used in the synthesis of naturally occurring alkaloid actinopolymorphol B (XVa) which is further transformed into the alkaloid tanakine (XVII).

Synthesis of α-ketols by functionalization of captodative alkenes and divergent preparation of heterocycles and natural products

Captodative alkene 1-acetylvinyl p-nitrobenzenecarboxylate 1a was evaluated for its reactivity in Lewis acid-catalyzed Michael additions with functionalized benzene rings and heterocycles, leading to diverse conjugated addition adducts. The hydrolysis of the latter resulted in the desired functionalized α-ketols, including natural alkaloid actinopolymorphol B (24a). The α-ketol core structure of these compounds was used as the building block for the synthesis of the natural alkaloid tanakine (25) and for the divergent construction of highly substituted heterocycles, such as 4-oxazolin-2-ones and butenolides, and their respective fused polycyclic derivatives.

Toward a Green Atom Economy: Development of a Sustainable Multicomponent Reaction

The recently discovered photoinduced three-component reaction of diazo ketones, carboxylic acids, and isocyanides can be efficiently performed under continuous-flow conditions with consequential advantages in terms of selectivity and productivity. The investigation of the flow process and the determination of its sustainability are discussed in detail. This multicomponent reaction affords stereodefined captodative olefins, useful as synthons in organic chemistry.

Thermochemical study of 1-acetyl vinyl p-nitrobenzoate: vinyl bond enthalpy in captodative olefins.

Captodative olefins are highly reactive and selective substrates in Diels-Alder and 1,3-dipolar cycloadditions. Seeking an explanation of this fact based on molecular energetics, the thermochemical analysis of 1-acetyl vinyl p-nitrobenzoate, a captodative olefin, has been performed using semi-micro-combustion calorimetry, effusion measurements through a quartz crystal microbalance, and differential scanning calorimetry. The molar standard combustion energy and enthalpy as well as the molar standard formation enthalpy are reported along with sublimation and melting enthalpies. From these data, experimental formation enthalpy of the gas-phase is derived and compared with the theoretical value calculated through the density functional theory procedure. The olefinic bond enthalpy is also computed from experimental data, and the relevance of the results is discussed.

Three in the Spotlight: Photoinduced Stereoselective Synthesis of (Z)-Acyloxyacrylamides through a Multicomponent Approach

We report a straightforward approach to synthesize 2-acyloxyacrylamides, which are useful synthons in organic synthesis. This involves a photoactivated multicomponent reaction, performed both in batch and under continuous flow conditions. This process affords the desired compounds in a stereoselective fashion from readily available starting materials in one step, without the aid of metal catalysis. This paper illustrates the preliminary work, the extensive experiments carried out to understand the limitations of the approach, and the optimization of the conditions for the synthesis of these particular captodative olefins.

Ketene Three‐Component Reaction: A Metal‐Free Multicomponent Approach to Stereodefined Captodative Olefins

Three in the spotlight: Irradiation promotes a general, three-component reaction between diazoketones, carboxylic acids, and isocyanides. The highly functionalized captodative olefin products of this reaction are versatile synthons for organic synthesis.

On the reaction of carboxylic acids and isonitriles with conventional heating

Control over the formation of N-formylamides versus the formation of captodative alkenes from the reaction of arylacetic acids with isonitriles has been achieved. Low temperatures and high concentrations favor alkenes, and high temperatures and low concentrations favor N-formylamides.

Verdazyl Radicals as Substrates for Organic Synthesis: Unique Access to Tetrahydropyrazolotriazinones, Pyrazolotriazinones and Dihydrotetrazinylacrylonitriles

Abstract1,5‐Dimethyl‐3‐phenyl‐6‐oxoverdazyl radical was recently shown to undergo a disproportionation reaction to form an azomethine imine, which reacted with a series of dipolarophiles, to form novel tetrahydropyrazolotetrazinone heterocyclic structures, demonstrating for the first time the use of verdazyl radicals as substrates for organic synthesis. Herein, we report on the chemistry of this verdazyl radical with captodative olefins and show that the reactions that occur, either an addition reaction or a hydrogen abstraction reaction followed by a cycloaddition reaction, are defined by the captodative olefin. Also highlighted is an intramolecular rearrangement of initially formed tetrahydropyrazolotetrazinone cycloadducts to either pyrazolotriazinone or tetrahydropyrazolotriazinone structures. While the rearrangement falls under the very general definition of the Dimroth rearrangement, the mechanism that is proposed is distinct and provides the opportunity to go from one particular structural motif to another under mild conditions, expanding the usefulness of this chemistry.

ChemInform Abstract: The Captodative Effect

Publisher Summary The concept of captodative substitution implies the simultaneous action of a captor (acceptor) and a donor substituent on a molecule. The chapter analyzes whether the claim of the proponents of the captodative effect has found experimental or theoretical support. The postulate of a synergetic action of a captor and a donor substituent at a radical centre and its chemical consequences has been discussed. Captodative substitution is that chemical consequences should be connected with this substitution pattern. For synthetic purposes, a captodative effect of a few kcal mol- might be helpful for the selection of a lower energy pathway in cases where a radical can react by several reaction paths, discriminated by activation barriers of closely similar energy. Synthetic applications have shown that captodative-substituted radicals generally behave like other stabilized, short-lived radicals. Left alone these radicals usually give dimers in high yield, as, for instance, allylic or benzylic radicals also do. As captodative substitution provides stability to a radical centre it is no surprise that captodative olefins are goodpartners in (2 + 2)-cycloadditions.

ChemInform Abstract: Synthesis of Trifluoromethylalkenes and Alkynes. Trifluoromethyl Captodative Olefins.

ChemInform 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.

ChemInform Abstract: Captodative Olefin 3-p-Nitrobenzoyloxy-3-buten-2-one as a Diels-Alder Ketene Equivalent for the Synthesis of γ-Hydroxycyclohexenones.

ChemInform 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.

Gold-Catalyzed Homogeneous Oxidative C−O Bond Formation: Efficient Synthesis of 1-Benzoxyvinyl Ketones

A novel Au-catalyzed homogeneous oxidative C-O bond-forming reaction involving a Au(I)/Au(III) catalytic cycle is developed. Mechanistic studies reveal the involvement of a unique intramolecular carboxy migration. From readily available propargylic benzoates, this chemistry allows efficient access to captodative alkenes and dienones, demonstrating the synthetic potential of incorporating Au(I)/Au(III) catalytic cycles into contemporary Au chemistry. The unique reactivity and the mechanistic insights would help open a new research area in gold catalysis.

ChemInform Abstract: Reactivity and Selectivity of Captodative Olefins as Dienes in Hetero‐Diels—Alder Reactions.

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.

Reactivity and Selectivity of Captodative Olefins as Dienes in Hetero‐Diels–Alder Reactions

AbstractThe reactivity and selectivity of the the captodative olefins 1‐acylvinyl benzoates 1a–1f and 3a as heterodienes in hetero‐Diels–Alder reactions in the presence of electron‐rich dienophiles is described. Heterodienes 1 undergo regioselective cycloaddition with the alkyl vinyl etherdienophiles 6a,b and 9 to give the corresponding dihydro‐2H‐pyrans 7, 8, and 10 under thermal conditions. The reactivity of these cycloadditions depends, to a large extent, on the electronic demand of the substituent in the aroyloxy group of the heterodiene. Frontier‐molecular‐orbital (FMO; ab initio) and density‐functional‐theory (DFT) calculations of the ground and transition states account for the reactivity and regioselectivity observed in these processes.

Efficient regioselective synthesis of 4‐ and 5‐substituted isoxazoles under thermal and microwave conditions

Abstractmagnified imageThe [2+3] cycloaddition reaction between nitrile oxides 2 and the captodative olefins 1 or the methyl crotonate derivatives 4 is regioselective and leads to the formation of the 5‐substituted amino‐isoxazole 3 or the 4‐substituted methoxycarbonyl‐isoxazole 5 derivatives, respectively. All these reactions are greatly accelerated by microwave irradiation without changing their regioselectivity with respect to the thermal conditions.

New Captodative Olefins: 3-(2-Furoyloxy)-3-buten-2-one and Alkyl 2-(2-Furoyloxy)-2-propenoates, and their Reactivity in Addition Reactions

A new series de captodative olefins 3-(2-furoyloxy)-3- buten-2-one and alkyl 2-(2-furoyloxy)-2-propenoates, 3a-3c, has been prepared with the aim of evaluating the effect of a heterocycle in the electron-donating moiety on the reactivity of these compounds in Diels-Alder and conjugate additions. In the former reactions, their behavior has been evaluated by reacting under thermal and catalyzed conditions with cyclopentadiene (9) and cyclohexadiene (12) as the dienes, showing a comparable reactivity, but a lower stereoselectiv- ity, with respect to the reference captodative olefins 1a and 2a. In the case of conjugate additions, the Friedel-Crafts reaction of the highly activated benzene ring of 1,2,4-trimethoxybenzene (7) led to the corresponding adduct 8 only for olefin 3a. Ab initio calculations (HF/6-31G*) of the energies and coefficients of the FMOs were car- ried out to explain the experimental reactivity in both processes. The results suggest that both the electron-withdrawing and the 2-furoy- loxy groups are involved in controlling the reactivity and selectivity