Catalytic photochemical enantioselective α-alkylation with pyridinium salts Santhivardhana Reddy Yetra, Nathan Schmitt, Uttam K. Tambar Chemical Science, 2022 We have developed a chiral amine catalyzed enantioselective α-alkylation of aldehydes with amino acid derived pyridinium salts as alkylating reagents.
Reusable Pd@PEG Catalyst for Aerobic Dehydrogenative C−H/C−H Arylations of 1,2,3-Triazoles Francesco Ferlin, Santhivardhana Reddy Yetra, Svenja Warratz, Luigi Vaccaro, Lutz Ackermann Chemistry A European Journal, 2019 Dehydrogenative C-H arylations of 1,2,3-triazoles were accomplished with the aid of a reusable palladium catalyst in PEG. The widely applicable oxidative palladium-catalysis enabled the synthesis of fully decorated 1,2,3-triazoles with a broad functional group tolerance and ample substrate scope. The sustainability of the aerobic C-H arylation was reflected by the use of PEG as green reaction medium and demonstrated by recycling studies of the catalyst and the reaction medium.
Micellar Catalysis for Ruthenium(II)-Catalyzed C−H Arylation: Weak-Coordination-Enabled C−H Activation in H2O Santhivardhana Reddy Yetra, Torben Rogge, Svenja Warratz, Julia Struwe, Wentao Peng, Philipp Vana, Lutz Ackermann Angewandte Chemie International Edition, 2019 Chemoselective C-H arylations were accomplished through micellar catalysis by a versatile single-component ruthenium catalyst. The strategy provided expedient access to C-H-arylated ferrocenes with wide functional-group tolerance and ample scope through weak chelation assistance. The sustainability of the C-H arylation was demonstrated by outstanding atom-economy and recycling studies. Detailed computational studies provided support for a facile C-H activation through thioketone assistance.
NHC-Catalyzed Generation of α,β-Unsaturated Acylazoliums for the Enantioselective Synthesis of Heterocycles and Carbocycles Santigopal Mondal, Santhivardhana Reddy Yetra, Subrata Mukherjee, Akkattu T. Biju Accounts of Chemical Research, 2019 This Account is aimed at highlighting the recent developments in the N-heterocyclic carbene (NHC)-catalyzed generation of α,β-unsaturated acylazolium intermediates and their subsequent reactivity with (bis)nucleophiles thereby shedding light on the power of this NHC-bound intermediate in organocatalysis. This key intermediate can be generated by the addition of NHCs to α,β-unsaturated aldehyde or acid derivatives. A wide variety of bisnucleophiles can add across the α,β-unsaturated acylazoliums to form various five and six-membered heterocycles and carbocycles. Moreover, suitably substituted nucleophiles can add to this intermediate and result in valuable products following cascade processes. Employing chiral NHCs in the process can result in the enantioselective synthesis of valuable compounds. In 2013, we developed a unified strategy for the enantioselective synthesis of dihydropyranones and dihydropyridinones by the NHC-catalyzed formal [3 + 3] annulation of 2-bromoenals with readily available 1,3-dicarbonyl compounds or primary vinylogous amides. This reaction takes place under mild conditions with low catalyst loading. Interestingly, employing enolizable aldehydes as the bisnucleophiles in this annulation afforded chiral 4,5-disubstituted dihydropyranones in spite of the competing benzoin/Stetter pathways. Moreover, the use of cyclic 1,3-dicarbonyl compounds such as 4-hydroxy coumarin/pyrazolone afforded the coumarin/pyrazole-fused dihydropyranones. In addition, a [3 + 2] annulation for the synthesis of spiro γ-butyrolactones was demonstrated using 3-hydroxy oxindoles as the bisnucleophile. The interception of α,β-unsaturated acylazolium intermediates with malonic ester derivatives having a γ-benzoyl group resulted in the enantioselective synthesis of functionalized cyclopentenes via a cascade process involving a Michael-intramolecular aldol-β-lactonization-decarboxylation sequence. The use of cyclic β-ketoamides as the coupling partner for catalytically generated α,β-unsaturated acylazoliums resulted in the enantioselective synthesis of spiro-glutarimide and the reaction proceeds in a Michael addition-intramolecular amidation pathway. We have recently demonstrated the enantioselective synthesis of tricyclic δ-lactones with three contiguous stereocenters by the reaction of enals with dinitrotoluene derivatives bearing electron-withdrawing groups, under oxidative conditions. This atom-economic cascade reaction proceeds in a Michael/Michael/lactonization sequence tolerating a range of functional groups. This technique was also used for the N-H functionalization of indoles for the enantioselective synthesis of pyrroloquinolines following the aza-Michael/Michael/lactonization sequence. The use of α-arylidene pyrazolinones as the bisnucleophiles for the tandem generation of dienolate/enolates combined with the NHC-catalyzed generation of α,β-unsaturated acylazoliums resulted in the enantioselective synthesis of pyrazolone-fused spirocyclohexadienones. This formal [3 + 3] annulation proceeds via the vinylogous Michael/spiroannulation/dehydrogenation sequence to afford spirocyclic compounds with an all-carbon quaternary stereocenter. It is reasonable to believe that the chemistry of α,β-unsaturated acylazoliums, catalytically generated through NHCs, will continue to flourish and will lead to amazing results. Future challenges in this area include the applications of this key intermediate in the synthesis of biologically active natural products and drugs.
N-heterocyclic carbene-catalyzed stetter reaction and related chemistry N Heterocyclic Carbenes in Organocatalysis, 2019
Thiocarbonyl-enabled ferrocene C–H nitrogenation by cobalt(III) catalysis: Thermal and mechanochemical Santhivardhana Reddy Yetra, Zhigao Shen, Hui Wang, Lutz Ackermann Beilstein Journal of Organic Chemistry, 2018 Versatile C–H amidations of synthetically useful ferrocenes were accomplished by weakly-coordinating thiocarbonyl-assisted cobalt catalysis. Thus, carboxylates enabled ferrocene C–H nitrogenations with dioxazolones, featuring ample substrate scope and robust functional group tolerance. Mechanistic studies provided strong support for a facile organometallic C–H activation manifold.
Mild Decarboxylative C−H Alkylation: Computational Insights for Solvent-Robust Ruthenium(II) Domino Manifold N. Y. Phani Kumar, Torben Rogge, Santhivardhana Reddy Yetra, Alexander Bechtoldt, Eric Clot, Lutz Ackermann Chemistry A European Journal, 2017 Computational studies on decarboxylative C-H alkenylations provided key insights into the solvent-robust nature of C-H activation/decarboxylation domino reactions. These properties were exploited for ruthenium(II)-catalyzed C-H alkylations by a decarboxylative process with ample scope under copper-free and silver-free reaction conditions.
Organocatalytic Enantioselective Vinylogous Michael-Aldol Cascade for the Synthesis of Spirocyclic Compounds Santigopal Mondal, Subrata Mukherjee, Santhivardhana Reddy Yetra, Rajesh G. Gonnade, Akkattu T. Biju Organic Letters, 2017 Enantioselective synthesis of pyrazolone-fused spirocyclohexenols by the secondary amine-catalyzed cascade reaction of α,β-unsaturated aldehydes with α-arylidene pyrazolinones is reported. This formal [3 + 3] organocascade reaction proceeds through a vinylogous Michael-aldol sequence to furnish the spiroheterocycles with three stereocenters including an all-carbon quaternary center in good yields and selectivities. The catalytic generation of α,β-unsaturated iminium ions from enals and tandem dienolate/enolate formation from pyrazolinones are the key for the success of this spiroannulation reaction.
