Recent Progress in Free Radical Transformations of Allenamides.

Allenamides are special allenes, and the unique reactivity, selectivity (both stereoselective and regionally selective) and stability of allenamides have been widely studied. In this review, the development of the free radical transformation of allenamides over the last few years will be summarized. This review discusses in detail in three parts: intermolecular radical addition to C- X (X = N, S, O, Se) bonds, metal salt mediated cyclization of allenamides, and photocatalytic cyclization of allenamides. In addition, reasonable details of the mechanisms are provided for the vast majority of these transformations.

Synthesis of Spiro Polycyclic N-Heterocycles and Indolecarbazoles via Merging Oxidative Coupling and Cascade Palladium-Catalyzed Intramolecular Oxidative Cyclization.

We report a step-economic strategy for the direct synthesis of spiro polycyclic N-heterocycles and indolecarbazole-fused naphthoquinones by merging oxidative coupling and cascade palladium-catalyzed intramolecular oxidative cyclization. In the protocol, bi-indolylnaphthoquinones were first synthesized by oxidative coupling of indoles and naphthoquinones. Subsequent cascade palladium-catalyzed intramolecular oxidative cyclization of bi-indolylnaphthoquinones gave spiro polycyclic N-heterocycles and indolecarbazoles. The intramolecular oxidative cyclization approach could also be realized by the presence or absence of iron catalysts under standard conditions. This protocol is featured with moderate to excellent yields, a wide substrate scope, and divergent structures of products.

Stereocontrolled Construction of Spirooxindole-Containing 5,6,7,8-Tetrahydropyrrolo[1,2-a]pyridine via Michael/Friedel-Crafts Domino Reaction Promoted by Secondary Amine-Squaramide.

An asymmetric Michael/Friedel-Crafts cascade reaction with Morita-Baylis-Hillman (MBH) nitroallylic esters and 3-pyrrolyloxindoles has been developed for the stereoselective construction of spirooxindole-containing tetrahydroindolizines. A range of tetracyclic scaffolds possessing three consecutive chiral centers, including an all-carbon quaternary stereocenter, were generated in 53-85% isolated yields with high diastereoselectivities and enantiopurities (≥3:1 dr, 50-98% ee). A newly synthesized bifunctional secondary amine/squaramide organocatalyst was demonstrated to exhibit better stereochemical control than their tertiary analogues.

Diastereoselective Synthesis of Pyrroloquinolines via N-H Functionalization of Indoles with Vinyl Sulfonium Salts.

A [2 + 4]/[1 + 2] annulation approach was successfully established to construct pyrroloquinoline-fused cyclopropane in a highly diastereoselective fashion (>20:1 dr). The tetracyclic 1,7-fused indoles were efficiently obtained from readily available starting materials under mild conditions. This methodology displays impressive substrate generality with two reaction components. The products resulting from this doubly annulative strategy are useful synthetic intermediates.

'On Water'-Promoted Three-Component Tandem Michael Addition/D-A Cycloaddition Reaction to Construct Polycyclic N-Heterocycles Derivatives.

'On Water'-promoted the three-component tandem Michael addition/D-A cycloaddition reaction in 80 °C at 3 h has been developed without employing any catalyst and organic solvent. The process allows facile access to polycyclic N-heterocycles derivatives contain indole and maleimide from easily accessible starting materials in moderate to high yields (up to 91 %). Compared with conventional reaction conditions, this reaction not only improves the reaction efficiency and rate but also minimizes the side reaction.

Metal-free synthesis of C2-quaternary indolinones by (NH4)2S2O8 mediated oxidative dearomatization of indoles.

An efficient metal-free, (NH4)2S2O8 mediated oxidative dearomatization of indoles for the construction of C2-quaternary indolinones was disclosed. A series of C2-quaternary indolinones derivatives with good functional group tolerance were obtained in moderate to excellent yields. This methodology provides an alternative approach for the direct generation of all-carbon quaternary centers at the C2 position of indoles. This catalytic approach represents a step-economic and convenient strategy for the oxidative dearomatization of indoles.

Stereoselective Synthesis of Chiral Hydrophenanthridines via a One-Pot Stepwise Aza-Michael/Michael/Michael Process.

A one-pot, two-step aza-Michael/Michael/Michael process was developed to diastereospecifically construct C6a,C10a-cis-hydrophenanthridines in a highly enantioselective manner (83-99% ee). The tricyclic products were provided in 50-99% isolated yields, sequentially promoted by bifunctional squaramide and diamine in a one-pot operation. This doubly annulative protocol indicated that the complicated polycyclic structures could be easily constructed via full employment of the available reaction sites of readily prepared precursors.

Iron catalyzed C-C dehydrogenative coupling reaction: synthesis of arylquinones from quinones/hydroquinones.

An atom-economical approach for the synthesis of arylquinones was achieved successfully via direct oxidative C-C dehydrogenative coupling reaction of quinones/hydroquinones with electron-rich arenes using an inexpensive Fe-I2-(NH4)2S2O8 system. The efficiency of this catalytic approach was established with a broad scope of substrates involving quinones and hydroquinones to give high yields (60-89%) of several arylated quinones. The present protocol is simple, practical, and shows good functional group tolerance.

Diastereoselective construction of tetracyclic chromanes via a triply annulative strategy.

A triple Michael/aldol cascade reaction has been established to construct tetracyclic chromanes in a diastereoselective fashion (≥5 : 1 dr). The polycyclic products were generated in 50-78% isolated yields under mild and metal-free conditions. Five reactive sites of enolate-tethered divinyl ketones were sequentially utilized to form four C-C bonds in a one-pot operation, leading to a construction of three new rings. Up to six consecutive stereocenters, including two quarternary stereogenic centers, were created in this domino process.

Assembly of polycyclic N-heterocycles via copper-catalyzed cycloamination of indolylquinones and aromatic amines.

The copper-catalyzed cycloamination of indolylquinones and various (hetero)aromatic amines under ligand-free conditions for the synthesis of polycyclic N-heterocycles has been developed. This method allows facile access to polycyclic N-heterocycles with the tolerance of chloride, bromide, amino, thio, etc. groups in moderate to high yields (60-89%).

Construction of Chiral Isotetronic Acid-Fused Thiochromane via Doubly Annulative Strategy.

A sulfa-Michael/aldol/lactonization cascade reaction has been established to construct isotetronic acid-fused thiochromanes in a highly stereoselective fashion (≥11:1 dr, 35-98% ee). The tricyclic products were obtained in 35-99% isolated yields in the presence of a bifunctional squaramide. Three reactive sites of ß,γ-unsaturated α-ketoester, including the less-explored ester carbonyl group, were sequentially utilized to construct two fused heterocycles in a one-pot operation.

Copper-catalyzed one-pot amine-alkylation of quinones with amines and alkanes.

A copper-catalyzed one-pot amine-alkylation of quinones with amines and alkanes in the presence of di-tert-butyl peroxide (DTBP) was developed via a radical reaction process. Various alkanes and aromatic or aliphatic amines with diverse structures and electronic properties are suitable substrates, and the chirality of amines can be maintained for the transformation. This method has high step and atom economy for straightforward access to aminated and alkylated quinones from readily available starting materials.

t-BuOK mediated oxidative coupling amination of 1,4-naphthoquinone and related 3-indolylnaphthoquinones with amines.

The transition-metal free amination of 1,4-naphthoquinone and related 3-indolylnaphthoquinones with amines, such as various (hetero)aromatic amine and aliphatic amine via t-BuOK-mediated oxidative coupling at room temperature has been developed. This reaction provides efficient access to the biologically important and synthetically useful 2-amino-1,4-naphthoquinones and 2-amino-3-indolylnaphthoquinones with good yields under mild conditions. The present protocol is simple, practical and shows good functional group tolerance. In addition, the obtained 2-amino-3-indolylnaphthoquinones were further transformed to synthesize polycyclic N-heterocycles.

A Construction of α-Alkenyl Lactones via Reduction Radical Cascade Reaction of Allyl Alcohols and Acetylenic Acids.

An iron-catalyzed cascade reaction of radical reduction of allyl alcohols and acetylenic acids to construct polysubstituted α-alkenyl lactones has been developed. In this paper, various allyl alcohols can form allyl ester intermediates and are further transformed into alkyl radicals, which form products through intramolecular reflex-Michael addition. In addition, this method can be used to prepare spirocycloalkenyl lactones. Interestingly, this protocol can be used to synthesize the skeleton structure of natural products. Moreover, the product can be further transformed into a ß-methylene tetrahydrofuran and tetrahydrofuran diene.

Stereoselective Synthesis of Dihydrofuranoindoles via the Friedel-Crafts Alkylation/Annulation Cascade Process.

A stereoselective annulation protocol was developed to construct dihydrofuranoindoles from readily available starting materials. In the presence of a bifunctional squaramide, the Friedel-Crafts alkylation/annulation cascade process occurred smoothly to provide dihydrofuranoindoles in 26-95% isolated yields exclusively as trans-diastereomers (38-99% ee). This catalytic protocol was compatible with a range of structurally distinct hydroxyindoles bearing the hydroxyl group at different positions, providing four kinds of dihydrofuranoindoles. Moreover, gram-scale synthesis and further synthetic manipulation of the product were also demonstrated.

Cobalt-Catalyzed Cycloamination: Synthesis and Photophysical Properties of Polycyclic N-Heterocycles.

The first earth-abundant cobalt-catalyzed cycloamination of indolylquinones and various (hetero)aromatic amine under ligand-free conditions for the synthesis of polycyclic N-heterocycles has been developed. The process allows facile access to polycyclic N-heterocycles with tolerance of chloride, bromide, amino, thio, etc. groups in moderate to high yields (up to 89%). In addition, The photophysical properties of the synthesized products were evaluated. These products exhibit interesting fluorescence properties, which is promising for fluorescent probes.

Chemoselective Hydrosilylation of the α,ß-Site Double Bond in α,ß- and α,ß,γ,δ-Unsaturated Ketones Catalyzed by Macrosteric Borane Promoted by Hexafluoro-2-propanol.

The B(C6F5)3-catalyzed chemoselective hydrosilylation of α,ß- and α,ß,γ,δ-unsaturated ketones into the corresponding non-symmetric ketones in mild reaction conditions is developed. Nearly 55 substrates including those bearing reducible functional groups such as alkynyl, alkenyl, cyano, and aromatic heterocycles are chemoselectively hydrosilylated in good to excellent yields. Isotope-labeling studies revealed that hexafluoro-2-propanol also served as a hydrogen source in the process.

Dehydration in water: frustrated Lewis pairs directly catalyzed allylization of electron-rich arenes and allyl alcohols.

A frustrated Lewis pair (FLP)-catalyzed allylation of allyl alcohols with electron-rich arenes has been developed. Interestingly, in this reaction, the electron-rich arenes and allyl alcohols are dehydrated in water. What's more, water was the sole byproduct of the reaction. In this protocol, various allyl alcohols can be converted into allyl cations and attacked by the electron-rich arenes to form aryl cation intermediates. Finally, the aryl cation intermediates are deprotonated to give the 1,3-diarylpropenes. In this protocol, indole allyl alcohols can undergo a bimolecular ring closure reaction, and structurally diverse tetrahydroindolo[3,2-b]carbazoles could be smoothly obtained. The reaction is not sensitive to oxygen and has been performed on a gram-scale.

B(C6F5)3-Catalyzed C-C Coupling of 1,4-Naphthoquinones with the C-3 Position of Indole Derivatives in Water.

An atom-economical and environmentally benign approach for the synthesis of indole-substituted 1,4-naphthoquinones from indoles and 1,4-naphthoquinones using readily available Lewis acidic B(C6F5)3 in water and with the recycling of water and part of the catalyst is reported. The reaction proceeded through the B(C6F5)3-catalyzed C(sp2)-H and C(sp2)-H bond coupling of 1,4-naphthoquinones with the C-3 position of indole derivatives in water. This methodology provides a facile protocol for the synthesis of some new indole-substituted 1,4-naphthoquinones in satisfactory yields and with a broad substrate scope. When compared to known methods for the synthesis of indole-substituted 1,4-naphthoquinones, this protocol is practical and efficient and does not require a transition-metal catalyst or toxic organic solvents. In addition, we utilized a simple filtration process for complete recycling of the solvent and the part of the catalyst in each reaction cycle.

Highly stereoselective synthesis of 2,3-dihydrofurans via a cascade Michael addition-alkylation process: a nitro group as the leaving group.

The Michael addition-alkylation process between gem-benzoyl-nitrostyrenes and 1,3-dicarbonyl compounds proceeded smoothly in the presence of a bifunctional squaramide, exclusively providing 2,3-dihydrofurans as trans-diastereomers in 33-92% isolated yields and excellent enantioselectivities (29->99% ee).