Organocatalytic asymmetric hydroxymethylation of isoindolinones with paraformaldehyde

Scorzelli, Francesco; Mola, Antonia Di; Filosa, Rosanna; Massa, António

doi:10.1007/s00706-017-2070-1

Cited by 5 publications

(9 citation statements)

References 26 publications

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“…Contrarily, more electron-rich 1ze produced adduct 2ze using a doubled loading of A50 (20 mol %) and 48 h, which was also required for the corresponding ester derivatives ( 2zf – zh ). Remarkably, although substrate 1zf needed an even longer reaction time (96 h), product 2zf was still gathered in nearly half of the previously reported period . We hypothesized that the moderate e.r.…”

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confidence: 89%

“…Compared with aliphatic or alicyclic carbonyl compounds, the asymmetric organocatalyzed hydroxymethylation of heterocyclic substrates is generally an underdeveloped area, as illustrated in Scheme . This is evident, especially for isoindolinones (entry a), which, as difficult substrates, gained considerably less attention than their oxindole counterparts (entries b–f). , As a consequence, to our knowledge, there is only one prior procedure for the asymmetric hydroxymethylation of isoindolinones . This reaction was pioneered by Massa and co-workers in 2018 and involved the Takemoto catalyst and paraformaldehyde.…”

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confidence: 99%

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Asymmetric Organocatalyzed Transfer Hydroxymethylation of Isoindolinones Using Formaldehyde Surrogates

Svestka,

Bobal,

Waser

et al. 2024

Org. Lett.

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The piperidine-based Takemoto catalyst has been successfully employed in a novel asymmetric transfer hydroxymethylation of activated isoindolinones, allowing us to prepare the enantioenriched hydroxymethylated adducts in good to excellent yields (48−96%) and enantiopurities (81:19−97:3 e.r.). To increase the reaction rate without compromising the selectivity, carefully optimized formaldehyde surrogates were employed, providing a convenient source of anhydrous formaldehyde with a base-triggered release. The substrate scope, including 34 entries, showed the considerable generality of the asymmetric transformation, and most entries exhibited complete conversions in 24− 48 h. A scale-up experiment and multiple enantioselective downstream transformations were also carried out, suggesting the prospective synthetic utility of the products.

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confidence: 89%

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confidence: 99%

Asymmetric Organocatalyzed Transfer Hydroxymethylation of Isoindolinones Using Formaldehyde Surrogates

Svestka,

Bobal,

Waser

et al. 2024

Org. Lett.

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“…Up to now, several electrophiles such as α,β-unsaturated aldehydes, α,β-unsaturated ketones, aldehydes and sulfur reagents have been investigated in this transformation for the assembly of 3,3-disubstituted isoindolinones. In the reported examples, the installation of an electron-withdrawing group such as ester, [33][34] and CN [35] is necessary for activating the benzylic carbon at the C3-position, thus facilitating the downstream Michael addition, [33][34] aldol reaction [35][36] sulfenylation reaction [37] and fluorination. [37]…”

Section: Electrophilic α-Functionalization Of 3-substituted Isoindolinonesmentioning

confidence: 99%

“…Later in 2018, the same group further developed an asymmetric cross‐aldol hydroxymethylation reaction between 3‐substituted isoindolinones and (HCHO) n for the synthesis of derivatives with tetrasubstituted stereocenters [36] . High yields and moderate ee values were obtained for most substrates in the presence of bifunctional catalyst 118 (Scheme 38).…”

Section: Electrophilic α‐Functionalization Of 3‐substituted Isoindoli...mentioning

confidence: 99%

Recent Advances in the Direct Functionalization of Isoindolinones for the Synthesis of 3,3‐Disubstituted Isoindolinones

Chen

Zou

2021

Adv Synth Catal

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The construction of tetrasubstituted carbon centers (especially chiral ones) represents one of the most challenging and demanding topics in the synthesis of natural products and related drugs. The development of isoindolinones with this feature appears to be of great importance, because 3,3disubstituted isoindolinones, which feature all kinds of tetrasubstituted carbon centers, also including spirocyclic and all-carbon or heteroatom-containing centers, show a wide spectrum of biological and pharmaceutical activities. Therefore, the synthetic methodologies for preparing these skeletons have received significant attention during the past decade. In general, these strategies can be classified into two major categories, namely the direct functionalization of parent isoindolinones and lactam-ring-formationinvolved reactions, depending on whether there is a lactam-ring-formation process or not during the production of the final 3,3-disubstituted isoindolinone. Since the second strategy has been well reviewed, this review mainly summarizes the recent progress in the direct functionalization of parent isoindolinones to construct 3,3-disubstituted isoindolinones via three subdivided strategies.

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“…Again, in 2018, [48] activated3 -carboxyethyl isoindolinones were investigated as nucleophiles toward formaldehydei n asymmetricc ross-aldol hydroxymethylation reactions by the same group, giving tetrasubstituted stereocenter derivatives (Scheme 26). Moderate enantioselectivities with high yields were obtained in the presence of thiourea-based organocatalyst CT-3.A mongt he tested catalysts, chiral ammonium salts were less effective than the thiourea-based organocatalysts.…”

Section: Chiralthioureas Catalyzed Asymmetric Synthesiso Fisoindolinonesmentioning

confidence: 99%

Catalytic Asymmetric Synthesis of Isoindolinones

Gao

Chen

Ding

et al. 2019

Chemistry An Asian Journal

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As important reactive species, isoindolinones represent a cluster of valuable building blocks for the construction of natural‐product‐like compounds. In particular, chiral isoindolinones are the key structural feature of naturally occurring bioactive molecules. During the past decade, great advances have been made in the asymmetric synthesis of isoindolinone skeleton compounds. Hence, recent progress in catalytic asymmetric synthesis of isoindolinones is reviewed here, with emphasis on chiral organocatalysis and transition metal complexes enabled transformations. Different organocatalysts (chiral phosphoric acids, phase transfer catalysts, chiral thioureas) and chiral transition‐metal complexes (Rh, Pd, Ir, Cu, Mg, and Ni) are included in this transformation.

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Organocatalytic asymmetric hydroxymethylation of isoindolinones with paraformaldehyde

Cited by 5 publications

References 26 publications

Asymmetric Organocatalyzed Transfer Hydroxymethylation of Isoindolinones Using Formaldehyde Surrogates

Asymmetric Organocatalyzed Transfer Hydroxymethylation of Isoindolinones Using Formaldehyde Surrogates

Recent Advances in the Direct Functionalization of Isoindolinones for the Synthesis of 3,3‐Disubstituted Isoindolinones

Catalytic Asymmetric Synthesis of Isoindolinones

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