Vinyl Allenes Research Articles

On the rearrangements of biologically-relevant vinyl allene oxides to cis-cyclopentenones, ketols, and Favorskii-type carboxylic acids.

In addition to stereodefined cis-cyclopentenones, the rearrangement of naturally-occurring vinyl allene oxides can provide ketols, cyclopropylcarbinols, and Favorskii-type bis-(Z)-but-2-en-1-yl acetic acids. These processes have been studied by DFT computations using (Z)-but-1-en-1-yl allene oxides as model systems. Prior studies on the stepwise cascade process starting from (Z)-but-1-en-1-yl allene oxides established as key steps the ring opening of the oxirane to give oxidopentadienyl biradicals, and their isomerization through formation of alkenylcyclopropanone intermediates prior to the conrotatory electrocyclic ring closure to cis-configured cyclopentenones. Under neutral or under acidic conditions, the corresponding ketols and cyclopropylcarbinols have been computationally characterized as resulting from SN2, SN1 and SN1'-type processes, showing that the rearrangement of vinyl allene oxides is pH-dependent. Moreover, stereoconvergent base-induced Favorskii-type rearrangements to provide bis-(Z)-but-1-en-1-yl substituted acetic acids have also been justified. Since the model system captures the structural features of the vinyl allene oxides of biological relevance, our computations provide the most comprehensive overview of the complex reactivity of these natural species.

Correction and removal of expression of concern: A unifying mechanism for the rearrangement of vinyl allene oxide geometric isomers to cyclopentenones.

Correction and removal of expression of concern for 'A unifying mechanism for the rearrangement of vinyl allene oxide geometric isomers to cyclopentenones' by Adán B. González-Pérez et al., Org. Biomol. Chem., 2014, 12, 7694-7701.

Rearrangement of vinyl allene oxide geometric isomers to cyclopentenones. Further computational insights with biologically relevant model systems.

Pathways for the rearrangement of the E and Z isomers of allyl- and methyl-substituted vinyl allene oxides to stereodefined cyclopentenones have been studied by DFT computations. Regardless of the reactant geometry, cis-configured cyclopentenones are found to be formed in a stepwise cascade comprising as key steps the ring opening of the oxirane to give an oxidopentadienyl diradical, its isomerization, and electrocyclization. An allyl substituent at the Csp3 atom of the starting vinyl allene oxide induces opposite effects on the activation energies for ring opening: a decrease owing to assistance by homoconjugation for the out motion and an increase due to the stereoelectronic stabilization of the reactant. As a result, allyl- and methyl-substituted vinyl allene oxides exhibit comparable activation energies. Only model systems with crotyl substituents afford lower activation energies than the methyl counterparts due to the additional stabilization of the forming charge deficiency at a secondary carbon by homoconjugation. Moreover, upon homoconjugative interaction reactants of Z geometry are predicted to undergo cyclization more readily than the E isomers. The results with Z-crotyl substituent are congruent with the spontaneous rearrangement of natural vinyl allene oxide derived from α-linolenic acid to a racemic cis-cyclopentenone (12-oxo-PDA).

Accounting for Diradical Character through DFT. The Case of Vinyl Allene Oxide Rearrangement.

The transformation of vinyl allene oxides into cyclopentenones is key to the biosynthesis of a number of hormone-like molecules in plants. Two competitive paths are generally accepted for this transformation: a concerted SN2-like mechanism and a stepwise path with a diradical oxyallyl intermediate. Recently, a new stepwise closed-shell path has been proposed that circumvents the key oxyallyl intermediate. In this work, we conduct a thorough computational investigation, including dynamic effects, to identify the most likely mechanism for this transformation.

Expression of concern: A unifying mechanism for the rearrangement of vinyl allene oxide geometric isomers to cyclopentenones.

Expression of concern for 'A unifying mechanism for the rearrangement of vinyl allene oxide geometric isomers to cyclopentenones' by Adán B. González-Pérez et al., Org. Biomol. Chem., 2014, 12, 7694-7701.

Energetics of the biosynthesis of cyclopentenones from unsaturated fatty acids

Polyunsaturated fatty acids like linolenic acid or arachidonic acid upon enzymatic hydroxylation (lipoxygenases) can lead to corresponding hydroperoxides. Their dehydration gave rise to vinyl allene oxides, which cyclized into cyclopentenones, precursors of jasmonic acid or prostanoids.We have studied the energetics of these cascade reactions to determine their thermodynamic parameters and reveal the key steps. The formation of hydroperoxydes from polyunsaturated fatty acids and triplet dioxygen appeared as a surprisingly slightly exergonic reaction (∼6–15 kcal mol−1). In contrast, the cumulated following reactions were highly exergonic (∼95–100 kcal mol−1). Cyclization of the (E)-vinyl allene oxides occurred with an activation barrier of ∼23 kcal mol−1, while cyclization of the (Z)-isomer required two steps: first isomerization into vinylcyclopropanone (TS: ∼20 kcal mol−1), and then isomerization of the latter into cyclopentenone (TS: ∼18 kcal mol−1).

A unifying mechanism for the rearrangement of vinyl allene oxide geometric isomers to cyclopentenones.

A new mechanism for the rearrangement of vinyl allene oxide geometric isomers to stereodefined cyclopentenones is proposed based on DFT computations. This mechanism comprises two steps, first the ring opening of the oxirane to give a vinylcyclopropanone, and then a [1,3]-C sigmatropic rearrangement. Depending primarily on the allene oxide double bond geometry the stepwise pathway is either competitive (for E allene oxides) or favored (for Z allene oxides) relative to the already described SN2-like concerted pathway. All bond-forming reactions take place through helically chiral transition states, which allows the stereochemical information of the substrates to be transferred to that of the products, in particular in the case of (enantiopure) Z allene oxides. In addition to revealing one more of the fascinating mechanisms with memory of chirality, the results deepen our understanding of the important jasmonate and clavulone biosynthetic pathways that occur in plants and corals.

Synthesis of Biotinylated Galiellalactone Analogues

Two biotinylated derivatives of the fungal metabolite galiellalactone (1) were synthesized in order to facilitate the investigation of the molecular mechanism of action of the galiellalactonoids. Galiellalactone is a STAT3-signaling inhibitor that inhibits growth in vitro as well as in vivo of prostate cancer cells expressing activated STAT3. To provide a suitable point of attachment for biotin, the 8-hydroxymethyl derivative (3) and its 7-phenyl analogue 4 were synthesized by a modified tandem Pd-catalysed carbonylation and intramolecular vinyl allene Diels-Alder procedure previously developed. The two primary alcohols obtained, 3 and 4, were coupled to biotin as the 6-aminohexanoic acid amide, activated as the acid chloride, yielding the derivatives 5 and 6.

ChemInform Abstract: Pyridines and Pyridine Derivatives from Vinyl Allenes and Imines.

AbstractLewis acid mediated reaction of acyclic vinyl allenes and imines gives tetrahydropyridines with complete diastereoselectivity.

Pyridines and pyridine derivatives from vinyl allenes and imines

The Lewis acid mediated reaction of acyclic vinyl allenes and imines, yielding tetrahydropyridines has been carried out. Only one cycloadduct was observed in each case, and thus, the reaction progressed in all cases with total regio-, face- and endo/exo selectivities. The cycloadducts were transformed into polysubstituted pyridines, including bipyridines, by catalytic transfer hydrogenation using cyclohexene as hydrogen donor in good yield. The reaction was extended to the aromatization of the bicyclic cycloadducts prepared in previous works from the reaction of semicyclic vinyl allenes and imines, yielding tetrahydropyridines.

A density functional theory study on the Diels-Alder reactions with vinylallenes as dienes

The Diels-Alder (DA) reactions of vinylallenes (VA) with ethylenes were investigated using the global electrophilicity and nucleophilicity of the corresponding reactants as global reactivity indexes defined within the conceptual density functional theory. The reactivity and regioselectivity of these reactions were predicted by analysis of the energies, geometries, and electronic nature of the transition-state structures. In general, substitution by the electron-accepting acetyl group favors the reaction, whereas substitution by the electron-releasing methoxy group provides the opposite effect, regardless of being on VA or ethylene. However, the substitution effect in ethylene is apparently greater than that in VA. It has also been disclosed that substitution by electron-accepting group on both reactants accelerates the reaction, and the reaction may give different regioselectivity from that between VA and acetyl-substituted ethylene. This has also been verified by our experiments. It seems that the DA reactions with VAs as the diene components can generally be classified as nonpolar asynchronous with the endo product formation (wherever possible) being more pronounced. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011

Generation and Trapping of Cyclopentenylidene Gold Species: Four Pathways to Polycyclic Compounds

Cyclopentenylidene gold complexes can easily be formed from vinyl allenes through a Nazarov-like mechanism. Such carbenes may transform in four different ways into polycyclic frameworks: electrophilic cyclopropanation, C-H insertion, C-C migration, or proton shift. We have studied the selectivity of these different pathways and used our findings for the expedient preparation of valuable complex molecules. An application to the total synthesis of a natural product, Delta(9(12))-capnellene, is presented. DFT computations were carried out to shed light on the mechanisms.

ChemInform Abstract: An Unexpected Rearrangement of the α‐Phenyl Pyrane Derivatives Prepared via Hetero‐Diels—Alder Reaction of Acyclic Vinyl Allenes and Aldehydes.

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.

Study of an Unexpected Rearrangement of the α-Phenyl Pyrane Derivatives Prepared via Hetero-Diels−Alder Reaction of Acyclic Vinyl Allenes and Aldehydes

The Lewis acid catalyzed hetero-Diels-Alder reaction between acyclic vinyl allenes and aldehydes as heterodienophiles was studied. This reaction allows for the preparation of pyrane derivatives in good yields, high facial and regioselectivity and moderate endo/exo ratio. When benzaldehyde was used as the heterodienophile, rearranged products were obtained depending on the reaction conditions. DFT calculations were used to study the rearrangement, concluding that it is a highly selective ionic process, driven by the stability of the rearranged products.

ChemInform Abstract: Synthesis of Cyclic Compounds Having exo‐Methylene Groups Through the Diels—Alder Reactions of Vinyl Allenes Obtained from Propargyl Bromide and Indium.

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.

Synthesis of Cyclic Compounds Having exo-Methylene Groups through the Diels-Alder Reactions of Vinyl Allenes Obtained from Propargyl Bromide and Indium

affording effi-cient synthetic methods for complex ring compounds. How-ever, because it is not easy to effectively prepare a variety ofvinyl allenes, its application to organic reactions has beenlimited despite the potential of vinyl allenes in organicsynthesis. Although vinyl allenes were used in the Diels-Alder reactions, development of synthetic method of cycliccompounds having

Tandem Gold(I)‐Catalyzed Cyclization/Electrophilic Cyclopropanation of Vinyl Allenes.

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, please click on HTML or PDF.

Tandem Gold(I)-Catalyzed Cyclization/Electrophilic Cyclopropanation of Vinyl Allenes

We have developed an expedient method for the synthesis of polycyclic compounds from propargyl acetates or vinyl allenes involving up to three Au(I)-catalyzed elemental steps: 3,3-rearrangement, metalla-Nazarov reaction, and electrophilic cyclopropanation. The reaction proceeds under very mild conditions and in short times. The mechanism has been studied by DFT computations.

Gold(I)‐Catalyzed Synthesis of Functionalized Cyclopentadienes.

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, please click on HTML or PDF.

Gold(I)‐Catalyzed Synthesis of Functionalized Cyclopentadienes

mechanistic pathways: a concerted rearrangement (path a) involving direct addition of the olefin on the epoxide or a stepwise mechanism (path b) through a Nazarov cyclization of an oxypentadienyl cation (2, X=O ). The regioselectivity of the cyclization is dictated by donation of the oxyanion into the resulting cation leading to the formation of a ketone. Recently, stabilization of developing positive charge through back-bonding from phosphinegold(I) complexes has been implicated in a number of rearrangement reactions. Therefore, we hypothesized that coordination of cationic phosphinegold(I) complexes to a vinyl allene might mimic these reaction pathways through similar back-bonding, leading to metal–carbenoid intermediate 3 (X=R3PAu ). These intermediates would further rearrange into substituted cyclopentadienes, important building blocks in organic and organometallic chemistry. 7] In light of our recent success in using [Ph3PAuCl] with AgSbF6 in dichloromethane for carbon–carbon bond-forming reactions, we chose this system for preliminary studies of the proposed cycloisomerization (Table 1). Treatment of vinyl allene 4 with 2 mol% cationic triphenylphosphinegold(I) afforded the desired cyclopentadiene 5 as a single regioisomer in 97% yield after 1 min at 0 8C (Table 1, entry 1). Similar results were obtained when a lower temperature or lower catalyst loading were used (Table 1, entries 2 and 3). Control experiments employing either 5 mol% [Ph3PAuCl] or 5 mol% AgSbF6 as the sole catalyst did not lead to any conversion of 4 into 5 (Table 1, entries 4 and 5). Other transition-metal complexes showed no catalytic activity; however, gold(III) chloride rapidly consumed 4 to afford a small amount of 5 (Table 1, entry 6). With optimal conditions in hand, the scope of the gold(I)catalyzed cycloisomerization of vinyl allenes was examined. We were pleased to find that the reaction allowed for the regiospecific synthesis of functionalized cyclopentadienes in high yields with a variety of substitution patterns (Table 2). Substitution at the allene terminus was well tolerated, encompassing linear alkyl (Table 2, entries 8 and 9), oxygenated (entries 3–7), secondary benzyl (entry 1), and phenyl substituents (entry 2). Notably, the gold(I)-catalyzed reaction can be easily carried out on a gram scale albeit with a slightly diminished yield (Table 2, entry 1). Furthermore, the stability of acid-labile protecting groups, such as tetrahydropyranyl (Table 2, entry 9) and silyl ethers (entries 3, 4, 6, and 7), isopropylidene acetal (entry 5), and an N-Boc amine (entry 6), is a testament to the mildness of the reaction conditions. Bicyclic cyclopentadienes are readily produced from the cycloisomerization of vinyl allenes containing cyclic alkenes (Table 2, entries 1–6). Additionally, the gold(I)catalyzed reaction can be employed for the synthesis of cyclopentadienes with a quaternary carbon center (Table 2, entries 2 and 3). The use of a more electron-rich gold(I) complex, [tBu3PAuCl], as a catalyst gave improved yields for some vinyl allenes (Table 2, entries 5, 6, 8, and 9). For example, switching the gold catalyst from [Ph3PAuCl] to [tBu3PAuCl] resulted in an improved yield for the formation of cyclopentadiene 21 (Table 2, entry 8). Table 1: Catalyst optimization.