Masters of Mediation: MN(SiMe3)2 in Functionalization of C(sp3)-H Latent Nucleophiles.

Organoalkali compounds have undergone a far-reaching transformation being a coupling partner to a mediator in unusual organic conversions which finds its spot in the field of sustainable synthesis. Transition-metal catalysis has always been the priority in C(sp3)-H bond functionalization, however alternatively, in recent times this has been seriously challenged by earth-abundant alkali metals and their complexes arriving at new sustainable organometallic reagents. In this line, the importance of MN(SiMe3)2 (M=Li, Na, K & Cs) reagent revived in C(sp3)-H bond functionalization over recent years in organic synthesis is showcased in this minireview. MN(SiMe3)2 reagent with higher reactivity, enhanced stability, and bespoke cation-π interaction have shown eye-opening mediated processes such as C(sp3)-C(sp3) cross-coupling, radical-radical cross-coupling, aminobenzylation, annulation, aroylation, and other transformations to utilize readily available petrochemical feedstocks. This article also emphasizes the unusual reactivity of MN(SiMe3)2 reagent in unreactive and robust C-X (X=O, N, F, C) bond cleavage reactions that occurred alongside the C(sp3)-H bond functionalization. Overall, this review encourages the community to exploit the untapped potential of MN(SiMe3)2 reagent and also inspires them to take up this subject to even greater heights.

Brønsted Base Prompted sp3 C-H Latent Nucleophiles to Access α-Branched Amines Bearing ß-Carbonyl by Cleaving Amide and Ester Bonds.

α-Branched amines are key motifs that exist in a plethora of natural products and pharmaceuticals. Herein we disclose the first convergent synthesis of α-branched amines bearing ß-carbonyl in isoindolinones by employing unactivated tertiary amides and unactivated alkyl esters as benign electrophile sources. The reaction proceeds by the direct aroylation of a C(sp3)-H carbon adjacent to the nitrogen atom in core isoindolinones. Several amides and esters were screened to choose the potential acyl source for the substrate scope. The reaction is carried out with a repertoire of substrates under mild conditions and shows high functional group compatibility. Remarkably the reaction is amenable to organometallic ferrocenyl ester and indole methyl esters bearing an acidic NH moiety. Strikingly no trace of amidation product 8 is observed. In particular α-branched amines bearing ß-carbonyl synthesized from indole methyl esters are considered important targets, as both motifs are prevalent in many drugs. This protocol is scalable, and products obtained from indole methyl esters show strong solid-state emission properties which are complementary with DFT calculations.

Ruthenium(II)-catalyzed oxidative dehydrogenation and hydroarylation of maleimides with phthalazinones - insights into additive-controlled product selectivity.

Herein, we developed ruthenium(II)-catalyzed oxidative dehydrogenation and hydroarylation of maleimides with phthalazinones. The product selectivity is controlled by the additives, and the hydroarylated product was obtained in water, which is an important highlight of this study. Control experiments were conducted to elucidate a plausible mechanism. These experiments suggest the occurrence of an oxidative dehydrogenation pathway over E2-type elimination - the key step in producing Heck-type products.

Ene-Reductase: A Multifaceted Biocatalyst in Organic Synthesis.

Biocatalysis integrate microbiologists, enzymologists, and organic chemists to access the repertoire of pharmaceutical and agrochemicals with high chemoselectivity, regioselectivity, and enantioselectivity. The saturation of carbon-carbon double bonds by biocatalysts challenges the conventional chemical methodology as it bypasses the use of precious metals (in combination with chiral ligands and molecular hydrogen) or organocatalysts. In this line, Ene-reductases (ERs) from the Old Yellow Enzymes (OYEs) family are found to be a prominent asymmetric biocatalyst that is increasingly used in academia and industries towards unparalleled stereoselective trans-hydrogenations of activated C=C bonds. ERs gained prominence as they were used as individual catalysts, multi-enzyme cascades, and in conjugation with chemical reagents (chemoenzymatic approach). Besides, ERs' participation in the photoelectrochemical and radical-mediated process helps to unlock many scopes outside traditional biocatalysis. These up-and-coming methodologies entice the enzymologists and chemists to explore, expand and harness the chemistries displayed by ERs for industrial settings. Herein, we reviewed the last five year's exploration of organic transformations using ERs.

Acylation of oxindoles using methyl/phenyl esters via the mixed Claisen condensation - an access to 3-alkylideneoxindoles.

Predominantly, aggressive acid chlorides and stoichiometric coupling reagents are employed in the acylating process for synthesizing carbonyl tethered heterocycles. Herein, we report simple acyl sources, viz. methyl and phenyl esters, which acylate oxindoles via the mixed Claisen condensation. This straightforward protocol is mediated by LiHMDS and KOtBu and successfully applied to a wide range of substrates. It is a noteworthy transformation that skips the stepwise generation of enolates and acylation, and the reaction is performed at a moderate temperature with no side reactions. This protocol produces the first examples of ortho-substituents in an aryl ring flanked with electron-donating and electron-withdrawing substrates. Interestingly, robust organometallic ferrocenyl methyl ester cleaved under these conditions with ease. Furthermore, biologically important Tenidap's analog was synthesized by this protocol.

Synthesis of topologically constrained naphthalimide appended palladium(ii)-N-heterocyclic carbene complexes - insights into additive controlled product selectivity.

Topologically constrained naphthalimide appended Pd-NHCs were synthesized and characterized. These structurally related complexes were catalytically compared with previously synthesized Pd-NHCs in the regioselective heteroannulation of o-haloanilines and arylethynyl-trimethylsilane. The unique effect of an additive on product selectivity has been clearly demonstrated. The scope of the reaction with respect to different TMS protected alkynes and o-haloanilines is presented. Importantly, the step-economical regioselective synthesis of N-alkyl-3-aryl-indoles from o-haloanilines and arylethynyl-trimethylsilane assisted by Pd(ii)-NHCs has been clearly demonstrated via one-pot heteroannulation, TMS deprotection and N-alkylation. In addition, synthetic utility was demonstrated with several derivatizations.