FeSO 4 ·7H 2 O-Catalyzed Four-Component Synthesis of Protected Homoallylic Amines

et al. 2008

Chemistry A European J

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The acid-catalyzed benzylic and allylic alkylation of protic nucleophiles is fundamentally important for the formation of carbon-carbon and carbon-heteroatom bonds, and it is a formidable challenge for benzylic and allylic amine derivatives to be used as the alkylating agents. Herein we report a highly efficient benzylic and allylic alkylation of protic carbon and sulfur nucleophiles with sulfonamides through double Lewis acid catalyzed cleavage of sp(3) carbon-nitrogen bonds at room temperature. In the presence of a catalytic amount of inexpensive ZnCl(2)-TMSCl (TMSCl: chlorotrimethylsilane), 1,3-diketones, beta-keto esters, beta-keto amides, malononitrile, aromatic compounds, thiols, and thioacetic acid can couple with a broad range of tosyl-activated benzylic and allylic amines to give diversely functionalized products in good to excellent yields and with high regioselectivity. Furthermore, the cross-coupling reaction of 1,3-dicarbonyl compounds with benzylic propargylic amine derivatives has been successfully applied to the one-step synthesis of polysubstituted furans and benzofurans.

Section: Resultsmentioning

confidence: 99%

Selective Benzylic and Allylic Alkylation of Protic Nucleophiles with Sulfonamides through Double Lewis Acid Catalyzed Cleavage of sp³ Carbon–Nitrogen Bonds

Liu

et al. 2008

Chemistry A European J

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“…Very recently, a new four-component aza-Sakurai reaction catalyzed by substoichiometric amounts of FeSO 4 and using aldehyde derivatives has been published, the results being in general moderate. [11] With this study we would like to show the first example in which the unmodified commercial nanopowder magnetite can be used (and re-used) as a typical heterogeneous Lewis acid catalyst in usual and mild organic synthetic protocols.…”

mentioning

confidence: 99%

“…This step was previously described as the only Fe(II)-catalyzed step under homogeneous conditions. [11] However, under higher temperature conditions the catalyst seems to be unnecessary. Finally, the isolated carbamate 10 was submitted to reaction under different catalyst conditions.…”

mentioning

confidence: 99%

Unmodified Nano‐Powder Magnetite Catalyzes a Four‐ Component Aza‐Sakurai Reaction

2008

A new catalyst for an old material: magnetite is an excellent Lewis acid catalyst for the four-component aza-Sakurai reaction. The process could be repeated up to 15-times without losing effectiveness, with the catalyst recycling being as easy as the use of a simple magnet. The catalyst is selective and could discriminate between aldehyde and ketone functionalities, catalyzing first the reaction with the higher electrophilic aldehyde.

“…(1)], [2] which was found later by Ramón and Yus to proceed smoothly in the presence of unmodified nanopowder magnetite at 110 8C. [3] The products resulting from these multicomponent reactions are alkoxycarbonyl-protected primary amines (carbamates), which are widely used as synthetic intermediates for biologically important molecules.…”

Section: Introductionmentioning

confidence: 99%

Byproduct‐Catalyzed Four‐Component Reactions of Aldehydes with Hexamethyldisilazane, Chloroformates, and Nucleophiles in Acetonitrile Leading to Protected Primary Amines, β‐Amino Esters, and β‐Amino Ketones

Weng

et al. 2009

Chemistry A European J

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Multicomponent reactions are a very powerful tool for the construction of complex organic molecules by using readily available starting materials. While most of the multicomponent reactions discovered so far consist of three components, the reactions with four or more components remain sparse. We have successfully developed several four-component reactions using a catalytic amount of water as a hydrolyzing agent to decompose byproduct chlorotrimethylsilane (TMSCl) to yield secondary byproduct HCl that serves as a catalyst. In the presence of 40 mol % of water, the four-component reaction of aldehydes with hexamethyldisilazane (HMDS), chloroformates, and silylated nucleophiles proceeds smoothly at room temperature to give a range of protected primary amines in moderate to excellent yields. Importantly, a wide variety of protic carbon nucleophiles, such as beta-keto esters, beta-diketones, and ketones, have further been explored as suitable substrates for the synthesis of protected beta-amino esters and beta-amino ketones that are useful building blocks for various pharmaceuticals and natural products. These four-component reactions proceed through a pathway of tandem nitrogen protection/imine formation/imine addition, and the decomposition of byproduct TMSCl, generated in the first step of nitrogen protection, with water results in the formation of secondary byproduct HCl, a strong Brønsted acid that catalyzes the following imine formation/imine addition. Taking advantage of the fact that alcohols or phenols are also able to decompose byproduct TMSCl to yield secondary byproduct HCl, no catalyst is needed at all for the four-component reactions with aldehydes bearing hydroxy groups.