Defluorinative Alkylation of Trifluoromethylbenzimidazoles Enabled by Spin-Center Shift: A Synergistic Photocatalysis/Thiol Catalysis Process with CO2•.

We describe a catalytic strategy for direct single C(sp3)-F bond alkylation of trifluoromethylbenzimidazoles under a photoinduced thiol catalysis process. The CO2 radical anion (CO2•-) proved to be the most efficient single-electron reductant to realize such a transformation. The spin-center shift of the generated radical anion intermediate is the key step in realizing C-F bond activation under mild conditions with high efficiency.

Making Chiral Salen Complexes Work with Organocatalysts.

Bisimine derivatives of salicylaldehyde with chiral diamines (salens) are privileged ligands in asymmetric organometallic catalysis, which can be used in cooperation with organocatalysts as additives. The latter can be a modifier of the metal reactivity by liganding or a true co-catalyst working in tandem or in a dual system. All scenarios encountered in the literature are reviewed and classified according to the organocatalyst. In each case, mechanistic and physical-organic chemistry considerations are discussed to better understand the gears of these complex catalytic settings.

C-H Bond Alkylation of Cyclic Amides with Maleimides via a Site-Selective-Determining Six-Membered Ruthenacycle.

The first example of a ruthenium-catalyzed C-H bond alkylation via six-membered ruthenacycles is presented. This is disclosed for the C-H bond alkylation of biologically relevant cyclic amides with maleimide derivatives. The cyclic tertiary amide core acted as a directing group (DG) enabling formation of six-membered cycloruthenated species responsible for the control of the regio- and site selectivity of the reaction as well as the excellent functional group tolerance. Unexpectedly, cyclic amides were found to be better DGs than pyridine-containing ones or cyclic imides for this type of C-H bond functionalization.

Site-Selective Ruthenium-Catalyzed C-H Bond Arylations with Boronic Acids: Exploiting Isoindolinones as a Weak Directing Group.

Biologically relevant N-arylisoindolinones efficiently underwent arylation reactions under ruthenium catalysis via C-H bond functionalization. The reactions exclusively led to monoarylated products, and only ortho selectivity was observed in the aromatic ring connected to the nitrogen atom. Interestingly, no C-H bond functionalization was observed in the other benzene ring in the ortho position with respect to the carbonyl group. This ruthenium-catalyzed reaction displayed a high functional group tolerance, and it employed readily available and benchmark stable boronic acid and potassium aryltrifluoroborate derivatives as coupling partners. An appealing late-stage functionalization of indoprofen applying this methodology is showcased.

Ruthenium(ii)-catalysed selective C(sp2)-H bond benzoxylation of biologically appealing N-arylisoindolinones.

Site- and regio-selective aromatic C-H bond benzoxylations were found to take place using biologically appealing N-arylisoindolinones under ruthenium(ii) catalysis in the presence of (hetero)aromatic carboxylic acid derivatives as coupling partners. Besides the presence of two potential C(sp2)-H sites available for functionalization in the substrates, exclusive ortho selectivity was achieved in the phenyl ring attached to the nitrogen atom. Notably, the reactions occurred in a selective manner as only mono-functionalized products were formed and they tolerated a large number of functional chemical groups. The ability of the cyclic tertiary amide within the isoindolinone skeleton to act as a weak directing group in order to accommodate six-membered ring ruthenacycle intermediates appears to be the key to reach such high levels of selectivity. In contrast, the more sterically demanding cyclic imides were unreactive under identical reaction conditions.

Ru-Catalyzed Selective C-H Bond Hydroxylation of Cyclic Imides.

We report on cyclic imides as weak directing groups for selective monohydroxylation reactions using ruthenium catalysis. Whereas acyclic amides are known to promote the hydroxylation of the C(sp2)-H bond enabling five-membered ring ruthenacycle intermediates, the cyclic imides studied herein enabled the hydroxylation of the C(sp2)-H bond via larger six-membered ruthenacycle intermediates. Furthermore, monohydroxylated products were exclusively obtained (even in the presence of overstoichiometric amounts of reagents), which was rationalized by the difficulty to accommodate coplanar intermediates once the first hydroxyl group was introduced into the substrate. The same reactivity was observed in the presence of palladium catalysts.

Unmasking Amides: Ruthenium-Catalyzed Protodecarbonylation of N-Substituted Phthalimide Derivatives.

The unprecedented transformation of a wide range of synthetically appealing phthalimides into amides in a single-step operation has been achieved in high yields and short reaction times using a ruthenium catalyst. Mechanistic studies revealed a unique, homogeneous pathway involving five-membered ring opening and CO2 release with water being the source of protons.

Visible-Light-Induced Trifluoromethylation of Isonitrile-Substituted Methylenecyclopropanes: Facile Access to 6-(Trifluoromethyl)-7,8-Dihydrobenzo[k]phenanthridine Derivatives.

A new visible-light-induced trifluoromethylation of isonitrile-substituted methylenecyclopropanes is developed. A range of substituted 6-(trifluoromethyl)-7,8-dihydrobenzo[k]phenanthridine derivatives are readily furnished by this newly developed tandem reaction with moderate to good yields. This reaction allows the direct formation of two six-membered rings and three new C-C bonds, including the C-CF3 bond, under visible light irradiation.

Unprecedented Oxycyanation of Methylenecyclopropanes for the Facile Synthesis of Benzoxazine Compounds Containing a Cyano Group.

A novel intramolecular oxycyanation of methylenecyclopropanes is reported that proceeds through oxidative cleavage of the N-CN bond and subsequent palladium transfer from N to O of the amide group. A range of substituted benzo[d][1,3]oxazines with a cyano group are readily furnished by this newly developed oxycyanation reaction. Tris(4-trifluoromethylphenyl)phosphine as a ligand has been found to be crucial to effectively promote the transformation with high chemo- and regioselectivity. Moreover, the reaction outcome can be significantly affected by the electronic effect of the acyl group attached to the nitrogen atom of methylenecyclopropanes. When R(3) is a chloromethyl group, the pyrrolo[2,3-b]quinoline derivative is obtained by thermal-induced [3+2] cycloaddition of methylenecyclopropane to the methanediimine intermediate.

Amine-catalyzed tunable reactions of allenoates with dithioesters: formal [4+2] and [2+2] cycloadditions for the synthesis of 2,3-dihydro-1,4-oxathiines and enantioenriched thietanes.

The chemoselective [4+2] vs. [2+2] cycloaddition between allenoates and dithioesters can be controlled by switching the nucleophilic amine catalyst. The two modes of cyclizations represent the first example of controllable and chemoselective annulations between allenoates and dienophiles catalyzed by amine. These cyclizations are useful in offering a divergent synthesis of sulfur-containing heterocycles. On the basis of this investigation, it can be realized that dithioesters with a vicinal electron-withdrawing group can react not only like a Michael acceptor but also as a ketone or imine.