Solvent directed chemically divergent synthesis of β-lactams and α-amino acid derivatives with chiral isothiourea

Ji, Dongsheng; Liang, Hui; Yang, Kaixuan; Feng, Zhitao; Luo, Yong‐Chun; Xu, Guo‐Qiang; Gu, Yu‐Cheng; Xu, Peng‐Fei

doi:10.1039/d1sc06127e

Cited by 17 publications

(10 citation statements)

References 71 publications

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“…Extending the reaction time to 16 h gave the β-lactone 5 in 70:30 dr and reduced yield (70%) due to the observation of ( E )/( Z ) alkenes 4 from decarboxylation in the reaction mixture. These results are consistent with an initial highly stereoselective catalytic process giving β-lactone 5 in high diastereo- and enantioselectivity, with in situ epimerization giving a mixture of diastereoisomers . To further probe this process, variation of the reaction time before addition of benzylamine, plus the use of alternative amine nucleophiles for derivatization, was investigated (Scheme c).…”

supporting

confidence: 78%

“…These results are consistent with an initial highly stereoselective catalytic process giving β-lactone 5 in high diastereo- and enantioselectivity, with in situ epimerization giving a mixture of diastereoisomers. 12 To further probe this process, variation of the reaction time before addition of benzylamine, plus the use of alternative amine nucleophiles for derivatization, was investigated ( Scheme 2 c). At 0 °C, addition of benzylamine after a 30-min reaction time gave product 6 in an improved 95:5 dr and >99:1 er but with reduced yield (36%) compared to the standard 3 h reaction time (81%, 76:24 dr, >99:1 er).…”

mentioning

confidence: 99%

“…10 As an alternative, the crude reaction mixture was treated in situ with excess benzylamine (3.0 equiv) to give the isolable βhydroxyamide derivative 6 (76:24 dr). 11 Chromatographic purification gave the separable diastereoisomers in 81% combined yield and >99:1 er for each diastereomer (Scheme 2a). In situ formation of a mixed anhydride, using phenylacetic acid and pivaloyl chloride, and subsequent HyperBTMcatalyzed cycloaddition followed by ring opening led to slightly decreased levels of diastereoselectivity (69:31 dr, >99:1 er) and product yield (57%).…”

mentioning

confidence: 99%

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Isothiourea-Catalyzed [2 + 2] Cycloaddition of C(1)-Ammonium Enolates and N-Alkyl Isatins

et al. 2022

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Enantioselective [2 + 2] cycloaddition of C(1)ammonium enolates generated catalytically using the isothiourea HyperBTM with N-alkyl isatins gives spirocyclic β-lactones. In situ ring opening with an amine nucleophile generates isolable highly enantioenriched products in up to 92:8 dr and in >99:1 er.β-Lactones are versatile synthetic building blocks and significant components of many bioactive natural products. 1,2 As a consequence, a range of enantioselective synthetic methods for their preparation has been developed, with both Lewis acid and Lewis base catalyzed approaches common. 3 In terms of Lewis base catalysis using tertiary amines, the use of cinchona alkaloids and chiral DMAP derivatives has been extensively used to promote β-lactone formation through the generation of an intermediate C(1)-ammonium enolate. 4 Although versatile, these methods typically rely on the generation of reactive monosubstituted ketenes (formed in situ from acyl chlorides) or isolable but sensitive disubstituted ketenes as starting materials. 5 In an alternative approach, Romo introduced the NCAL (nucleophile-catalyzed aldollactonization) process to prepare β-lactones from keto-acids (Scheme 1a). 6 Key to this protocol was the development of carboxylic acids as the C(1)-ammonium enolate precursor, with a modified Mukaiyama reagent used for in situ generation of a reactive ester. Addition of either a cinchona alkaloid or isothiourea catalyst was used to generate the desired C(1)ammonium enolate, with subsequent intramolecular formal [2 + 2]-cycloaddition onto the pendant carbonyl giving highly enantioenriched β-lactones. Building on this work, we previously demonstrated the use of symmetric arylacetic anhydrides as alternative C(1)-ammonium enolate precursors. 7 These anhydrides are generally readily prepared from the parent carboxylic acid, are easy to handle, and can be used in conjunction with isothiourea catalysts without requiring the excess base that is a recognized limitation of alternative protocols using carboxylic acids as starting materials. This approach was applied to the HyperBTM-catalyzed enantioselective intermolecular formation of β-lactones with perfluoroalkyl ketones and arylacetic anhydrides (Scheme 1b). Mechanistic studies using natural abundance 13 C kinetic isotope effect experiments, together with computational analyses, indicated the operation of a concerted asynchronous

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Isothiourea-Catalyzed [2 + 2] Cycloaddition of C(1)-Ammonium Enolates and N-Alkyl Isatins

et al. 2022

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“…A highly stereoselective convention for the solvent‐mediated coordination of chemically unrelated β‐lactams and α‐amino corrosive subordinates was successfully developed. Instead of a quaternary carbon chiral center being generated in this convention, two other types of crucial particles were also given [30] . The metal‐amino corrosive complexes demonstrated broad‐spectrum anti‐mycobacterial activity in the absence of hemolytic and cytotoxic activity suggests that these compounds provide assurance for use in treating the mycobacterial sickness [31] …”

Section: Substrate‐supported Transition Metal Chalcogenidesmentioning

confidence: 99%

Multifunctionalized Metal Chalcogenides and Their Roles in Catalysis and Biomedical Applications

et al. 2022

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Chalcogenides are more frequently used to refer sulfides, selenides, tellurides and polonides rather than oxides and all the elements in group 16 of the periodic table are chalcogens. The synthesis of transition metal chalcogenides (TMCs) and their composites involved a wide range of techniques like one pot heat up, hydrothermal, solvothermal, precipitation, co‐precipitation and biological procedures. In light of the possibility of photo‐induced charge‐transfer events leading to intra‐ensemble charge separation, the integration of TMCs onto a strong electron‐accepting material such as graphene which provides unique TMC/graphene consisted of great significance. Electrochemical water splitting is a promising technology for converting, storing and transporting hydrogen energy in a sustainable manner. Because of their unique physical and chemical properties, as well as their low cost, transition metal chalcogenides are fascinating replacements for catalysts in catalytic water splitting. Transition metal chalcogenides have worldwide attention in recent decades due to their applications in chemical sensors, biological and environmental monitoring applications from biosensors to therapeutic treatment agents.

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“…12 In 2022, Xu's group developed a protocol in which C(1)-ammonium enolate, which was generated from acetic acid ester and isothiourea, underwent intramolecular [2 + 2] cycloaddition with imine to afford β-lactam derivatives when DCM and CH 3 CN were used as solvents; however, α-amino acid derivatives were produced when EtOH was used as the solvent. 13 Moreover, naphthoquinones are readily available and stable intermediates, which are widely used for constructing diverse heterocyclic compounds. 14 In particular, the cycloaddition reactions of naphthoquinones that take place at the C3-and C2-positions have become a hot research topic in recent years.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of functionalized 3-aryl-3H-benzofuranone derivatives from aryl acetate via [3 + 2] annulation of 1,4-dihydroxy-2-naphthoic acid ester

Xie

Long

et al. 2023

Org. Biomol. Chem.

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Solvent directed chemically divergent synthesis of β-lactams and α-amino acid derivatives with chiral isothiourea

Abstract: A protocol for the chemical divergent synthesis of β-lactams and α-amino acid derivatives with isothiourea (ITU) catalysis by switching solvents was developed. The stereospecific Mannich reaction occurring between imine and...

Cited by 17 publications

References 71 publications

Isothiourea-Catalyzed [2 + 2] Cycloaddition of C(1)-Ammonium Enolates and N-Alkyl Isatins

Isothiourea-Catalyzed [2 + 2] Cycloaddition of C(1)-Ammonium Enolates and N-Alkyl Isatins

Multifunctionalized Metal Chalcogenides and Their Roles in Catalysis and Biomedical Applications

Synthesis of functionalized 3-aryl-3H-benzofuranone derivatives from aryl acetate via [3 + 2] annulation of 1,4-dihydroxy-2-naphthoic acid ester

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