- Synthesis of epoxides from aldehydes and tosylhydrazone salts catalysed by triphenylarsine: Complete trans selectivity for all combinations of coupling partners
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Triphenylarsine catalyses the formation of epoxides from carbonyl compounds and tosylhydrazone salts. This convergent synthesis gives complete trans selectivity for all aldehyde and tosylhydrazone salt coupling partners.
- Aggarwal, Varinder K.,Patel, Mamta,Studley, John
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- Simple preparation of trans-epoxides via ylide intermediates
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A practical route to epoxides with control of the relative and absolute stereochemistry has been developed, allowing epoxides to be readily prepared on a 20 mmol scale by generating the reactive intermediate (the diazo compound) in situ from benzaldehyde tosylhydrazone sodium salt. In this paper, we describe the optimum conditions for three procedures to obtain the desired racemic and enantiomerically enriched epoxides (Scheme 1). High diastereoselectivities (98-100%) and very high yields of epoxide were obtained. Asymmetric epoxidation was carried out using the chiral camphor-derived [2.2.1] bicyclic sulfide 4 and the desired epoxide was obtained with excellent enantioselectivity (94%). Georg Thieme Verlag Stuttgart.
- Aggarwal, Varinder K.,Aragoncillo, Cristina,Winn, Caroline L.
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- Benzylic Ammonium Ylide Mediated Epoxidations
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A high yielding synthesis of stilbene oxides using ammonium ylides has been developed. It turned out that the amine leaving group plays a crucial role as trimethylamine gives higher yields than DABCO or quinuclidine. The amine group also influences the diastereoselectivity, and detailed DFT calculations to understand the key parameters of these reactions have been carried out.
- Roiser, Lukas,Robiette, Rapha?l,Waser, Mario
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- An effective dual copper-and sulfide-catalytic system for the epoxidation of aldehydes with phenyldiazomethane
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Epoxides have been obtained from alde-hydes and phenyldiazomethane using catalytic amounts of both the copper homoscorpionate com-plexes Tp xCuL (Tpx = homoscorpionate ligand; L = acetonitrile or tetrahydrofuran, THF) and dimethyl sulfide (SMe2) in high yields and diasteroselectivities, and with activities higher (TOF = 46 h-1) than those already known with rhodium-or copper-based cata-lysts. Among the copper(I) homoscorpionate com-plexes tested, TpBr3Cu(NCCH 3) showed the highest catalytic activity under mild conditions. The catalytic activity is controlled by electronic effects induced by the Tp x ligand as well as by the stability of the TpxCu(SR 2) adducts. Indeed, in the case of TpMs as ligand, the TpMsCu(THT) (THT = tetrahydrothio-phene) and Tp MsCu(SMe2) species could be isolated as very stable crystalline solids, the molecular struc-ture of the former being confirmed by single-crystal X-ray diffraction analysis. The in situ generation of PhCHN 2 from benzaldehyde tosylhydrazone sodium salt at 60 °C in methyl tert-butyl ether as solvent and TpMsCu(THF) as the catalyst also showed high cata-lytic activities, improving those already reported with copper-based catalysts.
- Pereira, Ana,Martín, Carmen,Maya, Celia,Belderrain, Tomás R.,Pérez, Pedro J.
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supporting information
p. 2942 - 2951
(2014/03/21)
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- A new protocol for the in situ generation of aromatic, heteroaromatic, and unsaturated diazo compounds and its application in catalytic and asymmetric epoxidation of carbonyl compounds. Extensive studies to map out scope and limitations, and rationalization of diastereo- and enantioselectivities
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A variety of metalated tosylhydrazone salts derived from benzaldehyde have been prepared and were reacted with benzaldehyde in the presence of tetrahydrothiophene (THT) (20 mol %) and Rh2(OAc)4 (1 mol %) to give stilbene oxide. Of the lithium, sodium, and potassium salts tested, the sodium salt was found to give the highest yield and selectivity. This study was extended to a wide variety of aromatic, heteroaromatic, aliphatic, α,β-unsaturated, and acetylenic aldehydes and to ketones. On the whole, high yields of epoxides with moderate to very high diastereoselectivities were observed. A broad range of tosylhydrazone salts derived from aromatic, heteroaromatic, and α,β-unsaturated rated aldehydes was also examined using the same protocol in reactions with benzaldehyde, and again, good yields and high diastereoselectivities were observed in most cases. Thus, a general process for the in situ generation of diazo compounds from tosylhydrazone sodium salts has been established and applied in sulfur-ylide mediated epoxidation reactions. The chiral, camphor-derived, [2.2.1] bicyclic sulfide 7 was employed (at 5-20 mol % loading) to render the above processes asymmetric with a range of carbonyl compounds and tosylhydrazone sodium salts. Benzaldehyde tosylhydrazone sodium salt gave enantioselectivities of 91 ± 3% ee and high levels of diastereoselectivity with a range of aldehydes. However, tosylhydrazone salts derived from a range of carbonyl compounds gave more variable selectivities. Although those salts derived from electron-rich or neutral aldehydes gave high enantioselectivities, those derived from electron-deficient or hindered aromatic aldehydes gave somewhat reduced enantioselectivities. Using α,β-unsaturated hydrazones, chiral sulfide 7 gave epoxides with high diastereoselectivities, but only moderate yields were achieved (12-56%) with varying degrees of enantioselectivity. A study of solvent effects showed that, while the impact on enantioselectivity was small, the efficiency of diazo compound generation was influenced, and CH3CN and 1,4-dioxane emerged as the optimum solvents. A general rationalization of the factors that influence both relative and absolute stereochemistry for all of the different substrates is provided. Reversibility in formation of the betaine intermediate is an important issue in the control of diastereoselectivity. Hence, where low diastereocontrol was observed, the results have been rationalized in terms of the factors that contribute to the reduced reversion of the syn betaine back to the original starting materials. The enantioselectivity is governed by ylide conformation, facial selectivity in the ylide reaction, and, again, the degree of reversibility in betaine formation. From experimental evidence and calculations, it has been shown that sulfide 7 gives almost complete control of facial selectivity, and, hence, it is the ylide conformation and degree of reversibility that are responsible for the enantioselectivity observed. A simple test has been developed to ascertain whether the reduced enantioselectivity observed in particular cases is due to poor control in ylide conformation or due to partial reversibility in the formation of the betaine.
- Aggarwal, Varinder K.,Alonso, Emma,Bae, Imhyuck,Hynd, George,Lydon, Kevin M.,Palmer, Matthew J.,Patel, Mamta,Porcelloni, Marina,Richardson, Jeffery,Stenson, Rachel A.,Studley, John R.,Vasse, Jean-Luc,Winn, Caroline L.
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p. 10926 - 10940
(2007/10/03)
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- First Epoxidation Reaction of Carbonyl Compounds via Ferrocenyl Sulfur Ylides
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Epoxidation reactions of carbonyl compounds (aldehydes and a ketone) mediated by sulfanyl ferrocenes have been successfully achieved in a one-pot reaction, under mild conditions. This reaction implies intermediary formation of a sulfonium salt (a ferrocenyl one was observed for the first time by 1H NMR) and then an ylide. The diastereoselectivity of the formation of stilbene oxide was unusual: the effect of steric hindrance and aromatic nature of the sulfide substituents have been evidenced. A catalytic asymmetric example with a planar chiral ferrocene is described.
- Miniere, Stephanie,Reboul, Vincent,Arrayas, Ramon Gomez,Metzner, Patrick,Carretero, Juan Carlos
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p. 2249 - 2254
(2007/10/03)
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- Additions of benzylsulfonium ylides to aldehydes and ketones: Are they under kinetic or thermodynamic control?
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The reaction of benzylsulfonium ylides with aromatic aldehydes gives predominantly trans epoxides whilst aliphatic aldehydes give mixtures of cis and trans epoxides. In order to probe the origin of the diastereoselectivity, single diastereoisomers of betaine intermediates were prepared by independent methods and subjected to ring closure and cross-over experiments. It was found that anti betaines derived from aliphatic and aromatic aldehydes gave exclusively trans epoxides. syn Betaines derived from aromatic aldehydes also gave exclusively trans epoxides whilst syn betaines derived from aliphatic aldehydes gave mixtures of cis and trans epoxides. From ring closure experiments in the presence of a more reactive aldehyde (cross-over experiments) it was found that anti betaines derived from aliphatic and aromatic aldehydes gave epoxides without incorporation of the more reactive aldehyde. In contrast, syn betaines derived from aromatic aldehydes gave exclusively epoxides derived from the more reactive aldehyde whilst syn betaines derived from aliphatic aldehydes gave mixtures of epoxides. These experiments indicated that the high trans selectivity observed in epoxidation with aromatic aldehydes is a result of irreversible formation of the anti betaine and reversible formation of the syn betaine. With aliphatic aldehydes the lower selectivity results from only partial reversibility in formation of the syn betaine.
- Aggarwal, Varinder K.,Calamai, Simone,Ford, J. Gair
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p. 593 - 599
(2007/10/03)
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- A Novel Catalytic Cycle for the Synthesis of Epoxides Using Sulfur Ylides
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A novel, neutral catalytic cycle for the synthesis of epoxides from carbonyl compounds and diazo compounds using catalytic quantities of transition metal salts and sulfides has been developed.In this catalytic cycle, the diazo compounds is decomposed by the transition metal salt to give a metallocarbene, and this is picked up to the sulfide to give a sulfur ylide, which then reacts with the aldehyde to give an epoxide and returns the sulfide back into the catalytic cycle.To obtain good yields of epoxides it is necessary to maintain a low concentration of the diazo compound (by slow addition), otherwise dimerisation of the diazo compound is the dominant reaction.Factors affecting the outcome of the reaction were studied.The reactions are relatively insensitive to solvent, but are sensitive to the structure of the sulfide, the metal salt and the concentration.Unhindered sulfides give good yields of epoxides with any metal salt, but with hindered sufides higher yields are obtained with Cu(acac)2 than with Rh2(OAc)4.The yields of epoxides are sensitive to sulfide concentration especially when using substoichiometric amounts of sulfides.Higher concentration leads to faster rates of formation and subsequent reaction of the sulfur ylides, and consequently to higher yields.This novel catalytic cycle has also been applied to base-sensitive aldehydes.We found that our new catalytic cycle for epoxidation gives much improved yields of epoxides compared to those obtained by traditional sulfur ylide chemistry and is tolerant to a wide variety of sensitive functional groups.Ketones also participate in the catalytic cycle, although they give reduced yields of epoxides compared to aldehydes and require a slightly elevated temperature. - Keywords: catalysis; diazo compounds; epoxidations; sulfur ylides; synthetic methods
- Aggarwal, Varinder K.,Abdel-Rahman, Hesham,Fan, Li,Jones, Ray V. H.,Standen, Mike C. H.
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p. 1024 - 1030
(2007/10/03)
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- Kinetic (Not Equilibrium) Factors Are Dominant in Wittig Reactions of Conjugated Ylides
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The Wittig reaction of ester-, vinyl-, or benzyl-stabilized ylides is examined in detail.Extensive control experiments have been performed to probe the oxaphosphetane intermediates, and reversal in these systems is ruled out as a significant (>5percent) process.Betaine reversal, on the other hand, can be detected in the control experiments, depending on the conditions.Maximum betaine reversal is associated with formation of the anti betaine rotamers, while syn betaines can be generated in ethanol or THF without significant reversal cases.It is emphasized that betainesare obligatory intermediates in the control experiments, but they are neither obligatory nor likely intermediates in Wittig reactions, especially the E-selective examples conducted in aprotic solvents.Only the oxaphosphetanes are required to describe the overall Wittig process from ylide to alkene.Other intermediates are not necessary, including zwitterions, specific conformers, pseudorotamers, etc.The traditional control experiments are more complex and are shown to involve anti betaines as well as syn betaines (2, 24, 25), and in certain cases, hydroxy ylides (28) derived from the betaines.The E-selective reactions of ester-stabilized ylides are described as asynchronous cycloadditions with a relatively advanced, oxaphosphetane-like transition state.Exceptionally E-selective olefination is achieved using the allylic dibenzophospole ylide 11a.The intermediate oxaphosphetanes 14a, 15a, and 15b are observed for the first time in a conjugated-ylide reaction.
- Vedejs, Edwin,Fleck, Thomas J.
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p. 5861 - 5871
(2007/10/02)
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