Radical annulation using a radical reagent as a two-carbon unit.

Radical annulation has emerged as one of the most efficient and straightforward methods for synthesizing cyclic/polycyclic compounds as the core structures can be constructed through a single procedure comprising multiple bond-forming steps. Particularly, radical annulation using a radical reagent as a cyclization partner and two-carbon unit greatly expands the diversity of cyclic skeletons and the functionality of radical reagents. We herein have highlighted the representative processes reported in the past decade for radical annulation using a radical reagent as a two-carbon unit, including [2 + 2 + 2], [3 + 2], [4 + 2], and [5 + 2] modes, with an emphasis on their reaction mechanisms. These studies not only pave the way toward annulation but also provide insight into the exploration of a new reaction mode for radical chemistry.

Synthesis of spirocyclic Δ4-isoxazolines via [3 + 2] cycloaddition of indanone-derived ketonitrones with alkynes.

A [3 + 2] cycloaddition of indanone-derived nitrones and alkynes under mild conditions is developed, allowing facile synthesis of spirocyclicindenyl isoxazolines with structural diversity. The sequential protocol of generated in situ ketonitrone from unsaturated ketones and N-alkylhydroxylamines is also achieved successfully, affording the desired products in considerable yield with moderate to good diastereoselectivity. Moreover, the spirocyclic product can be conveniently transformed into indenyl-based allylic alcohol and enamide.

Intramolecular ipso-halocyclization of 4-(p-unsubstituted-aryl)-1-alkynes leading to spiro[4,5]trienones: scope, application, and mechanistic investigations.

A new, general method for the synthesis of spiro[4,5]trienones is described by the intramolecular ipso-halocyclization of 4-(p-unsubstituted-aryl)-1-alkynes. In the presence of halide electrophiles, a variety of 4-(p-unsubstituted-aryl)-1-alkynes underwent the intramolecular ipso-halocyclization with water smoothly, affording the corresponding halo-substituted spiro[4,5]trienones in moderate to good yields. The obtained spiro[4,5]trienones can be applied in constructing the azaquaternary tricyclic skeleton via Pd-catalyzed Heck reaction. Notably, the prepared spiro[4,5]trienones and azaquaternary tricycles are of importance in the areas of pharmaceuticals and agrochemicals. The mechanism of the intramolecular ipso-halocyclization reaction is also discussed according to the (18)O-labeling experiments and DFT calculations.

Ruthenium-catalyzed annulation of alkynes with amides via formyl translocation.

The first example of Ru-catalyzed intramolecular annulation of alkynes with amides via formyl translocation has been developed, which provides an efficient approach for the synthesis of 1H-indole-3-carbaldehydes.

Copper-catalyzed intramolecular C-H oxidation/acylation of formyl-N-arylformamides leading to indoline-2,3-diones.

A new, efficient Cu-catalyzed intramolecular C-H oxidation/acylation method has been developed for the synthesis of substituted indoline-2,3-diones (isatins). In the presence of CuCl(2) and O(2), a variety of formyl-N-arylformamides underwent the tandem reaction to afford the corresponding indoline-2,3-diones in moderate to good yields. It is noteworthy that the reaction serves as the first example of transition-metal-catalyzed transformation for the preparation of indoline-2,3-diones.

Selective synthesis of 3-aryl quinolin-2(1H)-ones and 3-(1-arylmethylene)oxindoles involving a 2-fold arene C-H activation process.

A novel and selective palladium-catalyzed C-H activation protocol has been developed for the synthesis of 3-aryl quinolin-2(1H)-ones and 3-(1-arylmethylene)oxindoles with use of PivOH as the switch. In the presence of Pd(OAc)(2), AgOAc, and PivOH, a variety of N-methyl anilides reacted with arenes to afford the corresponding 3-aryl quinolin-2(1H)-ones in moderate yields, whereas the selectivity was shifted toward 3-(1-arylmethylene)oxindoles in the absence of PivOH.

Palladium-catalyzed decarboxylative coupling of allylic alkynoates with arynes.

A novel and selective protocol for the synthesis of 1-allyl-2-ethynylbenzenes has been developed by palladium-catalyzed decarboxylative coupling of allylic alkynoates with arynes. This new route allows for both sp-sp(2) and sp(2)-sp(3) couplings of allylic alkynoates with arynes in one pot involving a decarboxylation process.

Synthesis of (E)-3-(isobenzofuran-3(1H)-ylidene)indolin-2-ones by the palladium-catalyzed intramolecular C-H functionalization process.

A novel and selective protocol has been developed for the synthesis of (E)-3-(isobenzofuran-3(1H)-ylidene)indolin-2-ones by Pd-catalyzed oxidative intramolecular C-H functionalization reactions of various 3-(2-(hydroxymethyl)aryl)-N-methyl-N-arylpropiolamides in moderate yields. Mechanisms involving a C-H activation process were proposed for this transformation on the basis of the observed values of kinetic isotope effects.

Electrophilic ipso-cyclization of N-(p-methoxyaryl)propiolamides involving an electrophile-exchange process.

A novel electrophilic ipso-cyclization involving an electrophile-exchange process has been developed. In the presence of CuX (X = I, Br, SCN) and electrophilic fluoride reagents, a variety of N-(p-methoxyaryl)propiolamides and 4-methoxyphenyl 3-phenylpropiolate were cyclized to selectively afford the corresponding spiro[4.5]decenones in moderate to good yields. It is noteworthy that two azaquaternary tricyclic products were synthesized through a two-step pathway involving an electrophilic ipso-cyclization and then an intramolecular Heck reaction.

Electrophilic ipso-iodocyclization of N-(4-methylphenyl)propiolamides: selective synthesis of 8-methyleneazaspiro[4,5]trienes.

A novel and selective method for the synthesis of 8-methylenespiro[4,5]trienes via intramolecular electrophilic ipso-iodocyclization of N-(4-methylphenyl)propiolamides has been developed. In the presence of ICl or I 2, 8-methylene-1-azaspiro[4,5]trienes were selectively prepared from the electrophilic ipso-iodocyclization of N-(4-methylphenyl)propiolamides in moderate to good yields.

Synthesis of (2-oxoindolin-3-ylidene)methyl acetates involving a C-H functionalization process.

A novel palladium-catalyzed oxidative C-H functionalization protocol for the synthesis of (2-oxoindolin-3-ylidene)methyl acetates has been developed. In the presence of Pd(OAc)2 and PhI(OAc)2, a variety of N-arylpropiolamides underwent the C-H functionalization reaction with acids to afford the corresponding (E)-(2-oxoindolin-3-ylidene)methyl acetates selectively in moderate to excellent yields.

Selective synthesis of spiro[4,5]trienyl acetates via an intramolecular electrophilic ipso-iodocyclization process.

A general and efficient intramolecular electrophilic ipso-iodocyclization of para-unactivated arylalkynes has been developed for the synthesis of spiro[4,5]trienyl acetates. In the presence of NIS (N-iodosuccimide) and HOAc, para-unactivated arylalkynes, including N-arylpropiolamides and phenyl 3-phenylpropiolate, underwent the intramolecular electrophilic ipso-iodocyclization smoothly in moderate to good yields.

Reusable Cu2O/PPh3/TBAB system for the cross-couplings of aryl halides and heteroaryl halides with terminal alkynes.

An efficient and reusable Cu2O/PPh3/TBAB (n-Bu4NBr) system for the cross-coupling reactions of aryl and heteroaryl halides with terminal alkynes has been developed. Four types of Cu2O, including bulky Cu2O, cubic Cu2O nanoparticles, octahedral Cu2O nanoparticles, and spherical Cu2O nanoparticles, were examined, and the octahedral Cu2O nanoparticles were found to be the most effective catalyst for the reaction. In the presence of the octahedral Cu2O nanoparticles, PPh3, and TBAB, a variety of aryl and heteroaryl halides were reacted with alkynes including alkynols smoothly in moderate to good yields. Noteworthy is that the Cu2O/PPh3/TBAB system can be recovered and reused several times without loss of any activities.

Reusable copper-catalyzed cross-coupling reactions of aryl halides with organotins in inexpensive ionic liquids.

A combination of Cu2O nanoparticles with P(o-tol)3 shows highly catalytic activity for the Stille cross-coupling reaction. A series of copper catalysts and ligands were evaluated, and Cu2O nanoparticles combined with P(o-tol)3 provided the best results. In the presence of Cu2O nanoparticles and P(o-tol)3, a variety of aryl halides including aryl chlorides underwent the Stille reaction with organotins smoothly in moderate to excellent yields using inexpensive TBAB (n-Bu4NBr) as the medium. It is noteworthy that the Cu2O/P(o-tol)3/TBAB system can be recovered and reused at least three times without any loss of catalytic activity among the reactions of aryl iodides and activated aryl bromides.