The Direct Asymmetric Vinylogous Aldol Reaction of Furanones with α‐Ketoesters: Access to Chiral γ‐Butenolides and Glycerol Derivatives

Luo, Jie; Wang, Haifei; Xiao, Han; Xu, Li‐Wen; Kwiatkowski, Józef S.; Huang, Kuo‐Wei; Lü, Yixin

doi:10.1002/ange.201006316

Cited by 38 publications

(4 citation statements)

References 73 publications

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“…The fruitful versatility of 3,4-dihalofuranones of type 426a and 426b was also exploited in 2011 by Lu and co-workers, 304 who reported a diastereo- and enantioselective, direct VAR toward α-ketoesters catalyzed by the tertiary amine-thiourea bifunctional organocatalyst C16 , accessing enantioenriched γ-substituted butenolides with the creation of a quaternary stereocenter ( Scheme 118 ). Indeed, after an extensive catalyst screening, the authors found that l -tryptophan-derived catalyst C16 efficiently catalyzed the reaction between 3,4-dichlorofuran-2(5 H )-one ( 426b ) and a set of differently substituted tert -butyl glyoxylates of type 432 ( Scheme 118 , eq 1).…”

Section: Vinylogous Esters and Lactonesmentioning

confidence: 99%

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

et al. 2020

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The principle of vinylogy states that the electronic effects of a functional group in a molecule are possibly transmitted to a distal position through interposed conjugated multiple bonds. As an emblematic case, the nucleophilic character of a π-extended enolate-type chain system may be relayed from the legitimate α-site to the vinylogous γ, ε, ..., ω remote carbon sites along the chain, provided that suitable HOMO-raising strategies are adopted to transform the unsaturated pronucleophilic precursors into the reactive polyenolate species. On the other hand, when “unnatural” carbonyl ipso -sites are activated as nucleophiles (umpolung), vinylogation extends the nucleophilic character to “unnatural” β, δ, ... remote sites. Merging the principle of vinylogy with activation modalities and concepts such as iminium ion/enamine organocatalysis, NHC-organocatalysis, cooperative organo/metal catalysis, bifunctional organocatalysis, dicyanoalkylidene activation, and organocascade reactions represents an impressive step forward for all vinylogous transformations. This review article celebrates this evolutionary progress, by collecting, comparing, and critically describing the achievements made over the nine year period 2010–2018, in the generation of vinylogous enolate-type donor substrates and their use in chemical synthesis.

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Section: Vinylogous Esters and Lactonesmentioning

confidence: 99%

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

et al. 2020

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“…In this context, a direct asymmetric approach for these reactions would be highly valuable. In recent years, cyclic 2‐furanone derivatives have been used as versatile nucleophiles in direct vinylogous aldol reactions, as shown by the research groups of Zhang,8a Terada,8b Feng,8c and Lu 8d. However, because of the low electron density at the γ position of the generated dienolate,9 the direct vinylogous aldol reaction of a simple acyclic nucleophile is not favored, and the use of a bulky modifier at the α position is necessary to discriminate the reactive enolate site 10.…”

Section: Methodsmentioning

confidence: 99%

“…Encouraged by our preliminary results, we examined the enantioselective variant in the presence of various bifunctional tertiary amine/thiourea catalysts (CAT‐ 1 –CAT‐ 5 ), which can be conveniently prepared from l‐amino acids and are effective in a variety of asymmetric reactions, as reported by us and other groups 6c. 8d, 13 Our screening of reaction conditions revealed that all reactions proceeded well within 3–5 h in toluene at 25 °C in the presence of 10 mol % of catalyst, and afforded the chiral vinylogous aldol E ‐adduct 10 a in high yields with moderate to good enantioselectivities (Table 1, entries 2–6). The best selectivity was achieved with catalyst CAT‐ 3 , which was derived from L ‐valine (Table 1, entry 4, 88 % ee ).…”

Section: Methodsmentioning

confidence: 99%

Direct Asymmetric Vinylogous Aldol Reaction of Allyl Ketones with Isatins: Divergent Synthesis of 3‐Hydroxy‐2‐Oxindole Derivatives

et al. 2013

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Hydroxy-2-oxindole derivatives, which contain a quaternary stereogenic center at the 3-position, are a family of structurally diverse natural or nonnatural products with interesting biological activities. [1] The asymmetric synthesis of 3-hydroxy-2-oxindole derivatives, such as donaxaridine (1), [1b-c] (R)chimonamidine (2), [1d] CPC-1 (3), [1e] and (À)-flustraminol B (4) [1f] (Scheme 1, series I), has recently been intensely pursued, as these compounds exhibit a broad spectrum of biological activities and are promising potential drugs. Previously established methods [2] for the preparation of these derivatives mainly focused on the asymmetric hydroxylation of 3-substituted 2-oxindoles [3] and the nucleophilic addition to isatins, [4] employing compound A as a viable synthon (Scheme 1). The synthesis of related 3-hydroxy-2oxindole derivatives (5-7) of series II has attracted considerable interest for a long time because of their fascinating architectures and potential biological activities. For example, spirolactone 5 has shown potential cytotoxic activity. [1g-i] Spiroether 6 was reported to be a CB2 agonist and is thus a potential drug candidate for reducing neuropathic and bone pains, and for treating a host of diseases, including osteoarthritis, atherosclerosis, osteoporosis, and cancers. [1g] Hexahydrozaepino[2,3-b]indole 7, which bears a unique 5,7bicyclic framework, can be used as a tranquilizer for mammals and birds. [1h-i] However, to the best of our knowledge, no asymmetric protocol that affords this class of compounds has been presented to date.Compared with the traditional "single target" approach, the design of a common intermediate is the key in the total synthesis of different products through a divergent synthesis strategy, which has enabled the formation of a variety of target molecules without compromising efficiency. [5] As part of our ongoing research efforts toward the development and utilization of synthetic tools for the formation of quaternary stereogenic centers, [3b, 6] we were interested in designing a novel organocatalytic asymmetric reaction to achieve the divergent synthesis of 3-hydroxy-2-oxindole derivatives, including those in series I and II.Retrosynthetic analyses suggested that the synthetic route to intermediates A and B was reasonable. We deduced that compound C could be assembled as the common intermediate for the divergent synthesis of 3-hydroxy-2-oxindole derivatives of series I and II. We therefore focused on the asymmetric vinylogous aldol reaction of the carbonyl-activated allyl nucleophile D with isatin (Scheme 1).The Mukaiyama-type aldol reaction of silyl dienol ethers is the favored protocol to furnish vinylogous aldol adducts, but can suffer from low atom economy and efficiency. [7] In this context, a direct asymmetric approach for these reactions would be highly valuable. In recent years, cyclic 2-furanone derivatives have been used as versatile nucleophiles in direct vinylogous aldol reactions, as shown by the research groups of Zhang, [8a] Terada, [8b]...

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“…55 In 2011, Lu and co-workers disclosed an enantioselective vinylogous aldol reaction of halogenated furanones with αketoesters catalyzed by tryptophan-derived bifunctional catalysts C12 (Scheme 11). 56 High diastereo-and enantioselectivities were observed for a wide range of substituted α-ketoesters including vinylic and alkyl substituents. Unsubstituted 2(5H)furanone 15d also afforded the corresponding aldol products, albeit a much longer reaction time was required.…”

Section: Furanone-derived Enolates As Nucleophiles 21 Asymmetric Aldo...mentioning

confidence: 99%

Catalytic Asymmetric Synthesis of Butenolides and Butyrolactones

2017

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γ-Butenolides, γ-butyrolactones, and derivatives, especially in enantiomerically pure form, constitute the structural core of numerous natural products which display an impressive range of biological activities which are important for the development of novel physiological and therapeutic agents. Furthermore, optically active γ-butenolides and γ-butyrolactones serve also as a prominent class of chiral building blocks for the synthesis of diverse biological active compounds and complex molecules. Taking into account the varying biological activity profiles and wide-ranging structural diversity of the optically active γ-butenolide or γ-butyrolactone structure, the development of asymmetric synthetic strategies for assembling such challenging scaffolds has attracted major attention from synthetic chemists in the past decade. This review offers an overview of the different enantioselective synthesis of γ-butenolides and γ-butyrolactones which employ catalytic amounts of metal complexes or organocatalysts, with emphasis focused on the mechanistic issues that account for the observed stereocontrol of the representative reactions, as well as practical applications and synthetic potentials.

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The Direct Asymmetric Vinylogous Aldol Reaction of Furanones with α‐Ketoesters: Access to Chiral γ‐Butenolides and Glycerol Derivatives

Cited by 38 publications

References 73 publications

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

Direct Asymmetric Vinylogous Aldol Reaction of Allyl Ketones with Isatins: Divergent Synthesis of 3‐Hydroxy‐2‐Oxindole Derivatives

Catalytic Asymmetric Synthesis of Butenolides and Butyrolactones

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