Iron-Catalyzed Borrowing Hydrogen C-Alkylation of Oxindoles with Alcohols.
ABSTRACT: A general and efficient iron-catalyzed C-alkylation of oxindoles has been developed. This borrowing hydrogen approach employing a (cyclopentadienone)iron carbonyl complex (2?mol?%) exhibited a broad reaction scope, allowing benzylic and simple primary and secondary aliphatic alcohols to be employed as alkylating agents. A variety of oxindoles underwent selective mono-C3-alkylation in good-to-excellent isolated yields (28?examples, 50-92?% yield, 79?% average yield).
Project description:Herein we report the iron-catalyzed ?-C(sp3)-methylation of primary alcohols using methanol as a C1 building block. This borrowing hydrogen approach employs a well-defined bench-stable (cyclopentadienone)iron(0) carbonyl complex as precatalyst (5 mol %) and enables a diverse selection of substituted 2-arylethanols to undergo ?-C(sp3)-methylation in good isolated yields (24 examples, 65% average yield).
Project description:In this paper, we established highly efficient Cu-catalyzed tandem tert-alkylation C-H cyclization of ?-bromocarbonyls and methacrylamides to produce substituted oxindoles. The maximum turnover number was up to 48?000 with reasonable yield. Although the catalyst loadings were very low, the reaction was not involving radical chain reaction. The resulting oxindoles were able to transform into aza-multicyclic compound via a reduction.
Project description:The direct C3 alkylation of indoles and oxindoles is a challenging transformation, and only a few direct methods exist. Utilizing the underexplored ability of triaryl boranes to mediate the heterolytic cleavage of ?-nitrogen C-H bonds in amines, we have developed a catalytic approach for the direct C3 alkylation of a wide range of indoles and oxindoles using amine-based alkylating agents. We also employed this borane-catalyzed strategy in an alkylation-ring opening cascade.
Project description:This paper develops a methodology for cyclometalated iridium complex-catalyzed N-alkylation of amines with alcohols via borrowing hydrogen in the aqueous phase. The cyclometalated iridium catalyst-mediated N-alkylation of amines with alcohols displays high activity (S/C up to 10,000 and yield up to 96%) and ratio of amine/imine (up to >99:1) in a broad range of substrates (up to 46 examples) using water as the green and eco-friendly solvent. Most importantly, this transformation is simple, efficient, and can be performed at a gram scale, showcasing its potential for industrially synthesizing N-alkylamine compounds.
Project description:A highly regio-, diastereo-, and enantioselective allylic alkylation reaction of 3-monosubstituted oxindoles catalyzed by molybdenum is described. The reaction is affected by the electronic and steric variations of the nucleophile. The use of appropriate N-protecting group is particularly important for achieving high regio- and diastereoselectivity. Products from this reaction, containing vicinal quaternary-tertiary stereogenic centers, are valuable synthetic intermediates and should find utility in alkaloid synthesis.
Project description:The synthesis of a variety of 2-oxindoles bearing an all-carbon quaternary center at the pseudo benzylic position has been achieved via a 'transition-metal-free' intramolecular dehydrogenative coupling (IDC). The construction of 2-oxindole moieties was carried out through formation of carbon-carbon bonds using KOt-Bu-catalyzed one pot C-alkylation of ?-N-arylamido esters with alkyl halides followed by a dehydrogenative coupling. Experimental evidences indicated toward a radical-mediated path for this reaction.
Project description:Synthetically versatile 3,3-disubstituted fluorooxindoles exhibiting vicinal chirality centers were obtained in high yields and with excellent enantio-, diastereo-, and regioselectivity through catalytic asymmetric fluoroenolate alkylation with allylic acetates. The reaction proceeds under mild conditions and can be scaled up without compromising the asymmetric induction. The unique synthetic usefulness of the products is highlighted by the incorporation of additional functionalities and the formation of 3-fluorinated oxindoles exhibiting an array of four adjacent centers of chirality. A new C-F bond functionalization path that provides unprecedented possibilities for the stereoselective generation of a chiral quaternary carbon center in the alkaloid scaffold is introduced.
Project description:A diastereodivergent asymmetric Michael-alkylation reaction between 3-chloro-oxindoles and ?,?-unsaturated-?-ketoesters has been achieved using L-RaPr2 /Sc(OTf)3 and L-PrPr2 /Mg(OTf)2 metal complexes as catalysts. Both rel-(1R,2S,3R) and rel-(1S,2S,3R) chiral spiro cyclopropane oxindoles were constructed in good yields, diastereoselectivities and ee values. The diastereodivergent control may originate from different alkylation pathways after the Michael addition, with either intramolecular trapping of the aza-ortho-xylylene intermediate or direct SN2 substitution.
Project description:Hydrogen borrowing catalysis serves as a powerful alternative to enolate alkylation, enabling the direct coupling of ketones with unactivated alcohols. However, to date, methods that enable control over the absolute stereochemical outcome of such a process have remained elusive. Here we report a catalytic asymmetric method for the synthesis of enantioenriched cyclohexanes from 1,5-diols via hydrogen borrowing catalysis. This reaction is mediated by the addition of a chiral iridium(I) complex, which is able to impart high levels of enantioselectivity upon the process. A series of enantioenriched cyclohexanes have been prepared and the mode of enantioinduction has been probed by a combination of experimental and DFT studies.
Project description:The gram-scale synthesis of important flavoring ketones via alkylation of acetoacetic ester on substituted benzylic carbon followed by decarboxylation using a heterogeneous, commercial, solid acid catalyst is reported. The flavoring ketones were synthesized by the alkylation of acetoacetic ester, which proceeds through an SN1-type reaction to generate an alkylated (?-ketoester) intermediate at the benzylic carbon, which is decarboxylated under the acidic condition. Among the solid acid catalysts used, Amberlyst-15 was found to be the best catalyst under the solvent-free condition. This protocol was successfully employed for the synthesis of various flavoring ketones such as raspberry ketone and ginger ketone with almost complete conversion and 82% isolated yield. The para-donating groups on the benzylic alcohol showed a high rate of reaction. The catalyst was easily recovered and reused 6 times without losing its activity and selectivity. Moreover, this reaction was demonstrated at a 10 g scale, which implicated the potential applicability of the protocol in the industry.