Direct alkylation of N,N-dialkyl benzamides with methyl sulfides under transition metal-free conditions

Amides are a fundamental and widespread functional group, and are usually considered as poor electrophiles owing to resonance stabilization of the amide bond. Various approaches have been developed to address challenges in amide transformations. Nonetheless, most methods use activated amides, organometallic reagents or transition metal catalysts. Here, we report the direct alkylation of N,N-dialkyl benzamides with methyl sulfides promoted by the readily available base LDA (lithium diisopropylamide). This approach successfully achieves an efficient and selective synthesis of α-sulfenylated ketones without using transition-metal catalysts or organometallic reagents. Preliminary mechanism studies reveal that the deprotonative aroylation of methyl sulfides is promoted by the directed ortho-lithiation of the tertiary benzamide with LDA.

Crystal structure of 2-(2,6-diisopropylphenyl)-N,N-diethyl-3,3-dimethyl-2-azaspiro[4.5]decan-1-amine: a diethylamine adduct of a cyclic(alkyl)(amino)carbene (CAAC)

The structure of the title compound, C27H46N2, at 93 K has monoclinic (P21/n) symmetry. The title compound was prepared by treatment of 2-(2,6-diisopropylbenzene)-3,3-dimethyl-2-azaspiro[4.5]dec-1-en-2-ium hydrogen dichloride with two equivalents of lithium diethylamide. Characterization of the title compound by single-crystal X-ray diffraction and 1H and 13C NMR spectroscopy is presented. Formation of the diethylamine adduct of the cyclic(alkyl)(amino)carbene (CAAC) was unexpected, as deprotonation using lithium diisopropylamide results in free CAAC formation.

Reactivity of Poly(alkoxycarbonylmethylene)s under Basic Conditions: Alkylation of Main Chain Carbon Atoms via Ketene Silyl Acetal-type Intermediate and Cleavage of Carbon–carbon Main Chain

The reactivities of poly(alkoxycarbonylmethylene)s under basic conditions are described. The reactions of poly(ethoxycarbonylmethylene) (polyEDA’) and poly(benzyloxycarbonylmethylene) (polyBDA’) with a mixture of lithium diisopropylamide and trimethylsilyl chloride transformed a part of...

Stereoselective Synthesis of Multisubstituted Cyclohexanes by Reaction of Conjugated Enynones with Malononitrile in the Presence of LDA

Reaction of linear conjugated enynones, 1,5-diarylpent-2-en-4-yn-1-ones, with malononitrile in the presence of lithium diisopropylamide LDA, as a base, in THF at room temperature for 3–7 h resulted in the formation of the product of dimerization, multisubstituted polyfunctional cyclohexanes, 4-aryl-2,6-bis(arylethynyl)-3-(aryloxomethyl)-4-hydroxycyclohexane-1,1-dicarbonitriles, in yields up to 60%. Varying the reaction conditions by decreasing time and temperature and changing the ratio of starting compounds (enynone and malononitrile) allowed isolating some intermediate compounds, which confirmed a plausible reaction mechanism. The relative stability of possible stereoisomers of such cyclohexanes was estimated by quantum chemical calculations (DFT method). The obtained cyclohexanes were found to possess photoluminescent properties.

Trapping of Transient Thienyllithiums Generated by Deprotonation of 2,3- or 2,5-Dibromothiophene in a Flow Microreactor

Selective trapping of (4,5-dibromo-2-thienyl)lithium, known to undergo halogen dance, was achieved in a flow microreactor. This transient thienyllithium, generated by mixing 2,3-dibromothiophene and lithium diisopropylamide at –78 °C for 1.6 seconds, reacted with benzaldehyde. The reaction system is also applicable to other carbonyl compounds to afford the corresponding adducts in good yields. Moreover, the established conditions permit the conversion of 2,5-dibromothiophene into a mixture of the two constitutional isomers. The contrasting results are discussed on the basis of the reaction pathway.

An Approach to 1,1-Disubstituted Pyrazolylcyclopropane Building Blocks

An approach to isomeric 1,1-disubstituted pyrazolylcyclopropanes that relies on lithium diisopropylamide (LDA) mediated bis-alkylation­ of the corresponding pyrazolylacetonitriles is developed. The building blocks obtained can be considered as lead-like bioisosteres of arylpyrazole and pyrazolecarboxamide moieties and are thus useful for early drug discovery projects.