Palladium-catalyzed cross-coupling reactions of amines with alkenyl bromides: a new method for the synthesis of enamines and imines

The palladium-catalyzed cross-coupling reaction of alkenyl bromides with secondary and primary amines gives rise to enamines and imines, respectively. This new transformation expands the applicability of palladium-catalyzed C-N bond forming reactions (the Buchwald-Hartwig amination), which have mostly been applied to aryl halides. After screening of different ligands, bases, and solvents, the catalytic combination [Pd(2)(dba)(3)]/BINAP in the presence of NaOtBu in toluene gave the best results in the cross-coupling of secondary amines with 1-bromostyrene (dba=dibenzylideneacetone, BINAP=2,2'-bis(diphenylphosphino)-1,1'-binaphthyl). The corresponding enamines are obtained cleanly and in nearly quantitative yields. However, steric hindrance seems to be a limitation of the reaction, as amines carrying large substituents are not well converted. The same methodology can be applied to the coupling of secondary amines with 2-bromostyrene. Moreover, the reaction with substituted 2-bromopropenes allows regioselective synthesis of isomerizable terminal enamines without isomerization of the double bond. The best catalytic conditions for the cross-coupling of 1-bromostyrene with primary amines include again the use of the Pd(0)/BINAP/NaOtBu system. The reaction gives rise to the expected imines in very short times and with low catalyst loadings. A set of structurally diverse imines can be prepared by this methodology through variations in the structure of both coupling partners. However, 2-bromostyrene failed to give good results in this coupling reaction, probably due to product inhibition of the catalytic cycle. Competition experiments of vinyl versus aryl amination reveal that the reaction occurs preferentially on vinyl bromides.     

Titanium-mediated cross-coupling reactions of imines with ketones or aldehydes: an efficient route for the synthesis of 1,2-amino alcohols

The cross-coupling reactions of imines with ketones using Ti(OⁱPr)₄/c-C₅H₉MgCl reagent lead to 1,2-amino alcohols after hydrolysis. The coupling reactions with aldehydes could also afford 1,2-amino alcohols, however, in some cases, aziridines were obtained as major products in a stereoselective manner.     

Solid-phase synthesis of aryl, heteroaryl, and sterically hindered alkyl amines using the Curtius rearrangement

An efficient method for the solid-phase synthesis of aryl amines, heteroaryl amines, and sterically hindered alkyl amines has been developed. The key step in this process was the formation of resin-bound carbamates (B) by the Curtius rearrangement of aryl carboxylic acids with Wang resin providing the trapping hydroxyl group. N-Alkylation reactions of B gave secondary amines in good yield. Some biaryl amines, which are found widely in biologically active substances, were also prepared by the Suzuki reaction of resin-bound carbamates of 2-iodoaniline (16) or 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (21). The developed methods can be applied to the preparation of libraries containing aryl, heteroaryl, and sterically hindered alkyl amine structures as the pharmacophores.     

A mild and efficient oxidation of alcohols to aldehydes and ketones with periodic acid catalyzed by chromium(III) acetylacetonate

Chromium(III) acetylacetonate was found to be an efficient catalyst (10 mol%) for the oxidation of alcohols to aldehydes and ketones with periodic acid (1.5 equiv.) in acetonitrile at room temperature.     

Facile and convenient synthesis of functionalized propargylic alcohols and amines: an InBr3-Et3N reagent system promotes the alkynylation of aldehydes and N,O- or N,S-acetals

The use of a novel InBr₃-Et₃N reagent system to promote the alkynylation of not only a variety of aromatic/heterocyclic or bulky aliphatic aldehydes but also N,O- or N,S-acetals is described. The use of N-silyl-N,O-acetals and 1-alkynes could lead to the direct production of primary propargylic amines in good yields.     

Palladium(0) nanoparticle-catalyzed sp C-H activation: a convenient route to alkyl-aryl ketones by direct acylation of aryl bromides and iodides with aldehydes

Palladium(0) nanoparticles efficiently catalyze aliphatic aldehyde C-H functionalization by aryl halides to produce alkyl-aryl ketones in good yields. A wide range of substituted aryl and hetero-aryl bromides/iodides and open-chain aldehydes of varied chain length participated in this reaction.     

Zirconocene-mediated intermolecular coupling of Si-tethered diynes with alkynes, ketones, aldehydes, and isocyanates by means of novel skeletal rearrangement of zirconacyclobutene-silacyclobutene and zirconacyclohexadiene-silacyclobutene fused-ring intermediates

Bis(alkynyl)silanes react with low valent zirconocene species to afford zirconacyclobutene intermediates. These in situ generated reactive organometallic intermediates can react with alkynes, ketones, aldehydes, and isocyanates by means of a novel skeletal rearrangement. When a zirconacyclobutene intermediate was treated with an alkyne, an alpha-alkynylsilyl zirconacyclopentadiene was formed. Addition of dimethyl acetylenedicarboxylate (DMAD) and CuCl resulted in one-pot formation of an alkynylsilyl-benzene derivative from three different alkynes. At a higher temperature, the alpha-alkynylsilylzirconacyclopentadiene was transformed by means of an intramolecular skeletal rearrangement to a zirconacyclohexadiene-silacyclobutene fused-ring compound, which reacted with DMAD in the presence of CuCl affording the same alkynylsilyl-benzene derivative. When treated with a ketone, an aldehdye, or an isocyanate, the zirconocyclobutene intermediate also underwent the above-mentioned skeletal rearrangement, generating zirconocene-mediated cross-coupling products.