Contemporaneous Dual Catalysis: Aldol Products from Non‐Carbonyl Substrates

Trost, Barry M.; Tracy, Jacob S.

doi:10.1002/chem.201502973

Cited by 18 publications

(4 citation statements)

References 40 publications

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“…Thus, reaction of vanadium enolate 228 with vinyl epoxides 229 as masked aldehydes in the presence of a Lewis acid, provided aldol products 230 ( Scheme 41 , right). 206 Vanadium enolates in the presence of diazocompounds 231 as electrophiles provided ketones 232 from a direct sigmatropic amination reaction ( Scheme 41 , bottom). 207 Noteworthy, reaction of allenes with diazocompounds are well-known to yield vinyl diazines through Alder-ene mechanisms.…”

Section: Synthetic Utilitymentioning

confidence: 99%

“…Instead of delivering the corresponding enones from demetalation/isomerization of species 228 , intermediates 228 were envisioned as coupling reagents with both electrophiles and nucleophiles, providing a wide and diverse family of functionalized ketones. Thus, reaction of vanadium enolate 228 with vinyl epoxides 229 as masked aldehydes in the presence of a Lewis acid, provided aldol products 230 (Scheme , right) . Vanadium enolates in the presence of diazocompounds 231 as electrophiles provided ketones 232 from a direct sigmatropic amination reaction (Scheme , bottom) .…”

Section: Synthetic Utilitymentioning

confidence: 99%

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Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality

2021

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The allene functionality has participated in one of the most exciting voyages in organic chemistry, from chemical curiosities to a recurring building block in modern organic chemistry. In the last decades, a special kind of allene, namely, allenol, has emerged. Allenols, formed by an allene moiety and a hydroxyl functional group with diverse connectivity, have become common building blocks for the synthesis of a wide range of structures and frequent motif in naturally occurring systems. The synergistic effect of the allene and hydroxyl functional groups enables allenols to be considered as a unique and sole functionality exhibiting a special reactivity. This Review summarizes the most significant contributions to the chemistry of allenols that appeared during the past decade, with emphasis on their synthesis, reactivity, and occurrence in natural products.

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Section: Synthetic Utilitymentioning

confidence: 99%

Section: Synthetic Utilitymentioning

confidence: 99%

Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality

2021

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“…Notably, such a process would allow for the generation of aldol products from starting materials that lack carbonyl groups. 22 Additionally, by utilizing activated aryl and vinyl epoxides, we could in situ generate β,γ-unsaturated aldehydes, which are highly susceptible to enolization and consequently present issues in traditional enolate chemistry. Indeed, by utilizing 5 mol % tris(triphenysilyl)vanadate to promote the 1,3-transposition and 16 mol % lanthanum triflate as the Meinwald catalyst, modest to high yields of the aldol products could be obtained (Figure 19).…”

Section: Vanadium/lanthanum Dual Catalysis Aldol Reactionmentioning

confidence: 99%

“…Building upon our previous work on dual catalysis, we sought to determine whether we could combine the vanadium-catalyzed formation of enolates with the Meinwald rearrangement of epoxides to form aldehydes. Notably, such a process would allow for the generation of aldol products from starting materials that lack carbonyl groups . Additionally, by utilizing activated aryl and vinyl epoxides, we could in situ generate β,γ-unsaturated aldehydes, which are highly susceptible to enolization and consequently present issues in traditional enolate chemistry.…”

Section: Allenyl Alcohols As Enolate Precursorsmentioning

confidence: 99%

Catalytically Generated Vanadium Enolates Formed via Interruption of the Meyer–Schuster Rearrangement as Useful Reactive Intermediates

Trost

Tracy

2020

Acc. Chem. Res.

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Conspectus Enolate chemistry is one of the most fundamental strategies for the formation of carbon–carbon and carbon–heteroatom bonds. Classically, this has been accomplished through the use of stoichiometric quantities of strong base and cryogenic reaction temperatures. However, these techniques present issues related to enolate regioselectivity and functional group tolerance. While more modern methods utilizing stoichiometric activating agents have overcome some of these limitations, these processes add additional steps and suffer from poor atom economy. While certain classes of highly acidic nucleophiles have enabled the development of elegant and general catalytic solutions to address all of these limitations, functionalizing less acidic nucleophiles remains difficult. To overcome these challenges, we developed an alternative general approach for the formation and subsequent functionalization of metal enolates that leverages catalytic amounts of Lewis acid and entirely avoids the need for exogenous base or stoichiometric additives. To do so, we re-engineered the classical Meyer–Schuster rearrangement, which normally converts propargylic alcohols into α,β-unsaturated carbonyl compounds. By careful control of reaction conditions and by selection of an appropriate vanadium-oxo catalyst, the transient metal enolates formed via the 1,3-transposition of propargylic or allenylic alcohols can be guided away from simple protonation reaction pathways and toward more synthetically productive carbon–carbon, carbon–halogen, and carbon–nitrogen bond-forming processes. By utilizing readily available propargylic and allenylic alcohols as our starting materials and relying on a catalytic 1,3-transposition to generate metal enolates in situ, all issues related to the regioselectivity of enolate formation are resolved. Likewise, utilization of a simple isomerization for enolate formation results in a highly efficient process that can be 100% atom economical. The mild reaction conditions employed also allow for remarkable chemoselectivity. Functional groups not typically conducive to enolate chemistry, such as alkynyl ketones, methyl ketones, free alcohols, and primary alkyl halides, are all well tolerated. Finally, by varying the substitution patterns of the alcohol starting materials, enolates of ketones, esters, and even amides are all accessible. Utilizing this strategy starting from propargylic alcohols, we have developed functionalization reactions that produce highly substituted and geometrically defined α-functionalized α,β-unsaturated carbonyl compounds. Such processes include aldol, Mannich, and electrophilic halogenation reactions, as well as dual catalytic reactions wherein catalytically generated vanadium enolates are trapped with catalytically generated palladium π-allyl electrophiles. In the case of allenylic alcohols, we have developed complementary aldol, Mannich, halogenation, and dual catalytic processes to generate α′-functionalized α,β-unsaturated carbonyl products. The results described in this work showcas...

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Asymmetric Catalytic Vinylogous Addition Reactions Initiated by Meinwald Rearrangement of Vinyl Epoxides

Song

et al. 2021

Angewandte Chemie

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The first catalytic asymmetric multiple vinylogous addition reactions initiated by Meinwald rearrangement of vinyl epoxides were realized by employing chiral N,N′‐dioxide/ScIII complex catalysts. The vinyl epoxides, as masked β,γ‐unsaturated aldehydes, via direct vinylogous additions with isatins, 2‐alkenoylpyridines or methyleneindolinones, provided a facile and efficient way for the synthesis of chiral 3‐hydroxy‐3‐substituted oxindoles, α,β‐unsaturated aldehydes and spiro‐cyclohexene indolinones, respectively with high efficiency and stereoselectivity. The control experiments and kinetic studies revealed that the Lewis acid acted as dual‐tasking catalyst, controlling the initial rearrangement to match subsequent enantioselective vinylogous addition reactions. A catalytic cycle with a possible transition model was proposed to illustrate the reaction mechanism.

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Contemporaneous Dual Catalysis: Aldol Products from Non‐Carbonyl Substrates

Cited by 18 publications

References 40 publications

Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality

Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality

Catalytically Generated Vanadium Enolates Formed via Interruption of the Meyer–Schuster Rearrangement as Useful Reactive Intermediates

Asymmetric Catalytic Vinylogous Addition Reactions Initiated by Meinwald Rearrangement of Vinyl Epoxides

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