2018 Publications

Cheng, Q.-Q.; Yu, Y.; Yedoyan, J.; Doyle, M.P. “Vinyldiazo Reagents and Metal Catalysts: A Versatile Toolkit for Heterocycle and Carbocycle Construction” ChemCatChem 2018, 488-496. (DOI: 10.1002/cctc.201701346)

Vinyldiazo reagents and metal catalysts employed with selected reactants for heterocycle or carbocycle formation.The toolkit on the left contains the substituted vinyldiazo compound (substituents colored red) and the transition metal of the catalyst used.

Yu, Y.; Sha, Q.; Cui, H.; Chandler, K. S.; Doyle, M.P. “Displacement of Dinitrogen by Oxygen. A Methodology for the Catalytic Conversion of Diazocarbonyl Compounds to Ketocarbonyl Compounds by 2,6-Dichloropyridine-N-oxide” Org. Lett. 2018, 20. (DOI:  10.1021/acs.orglett.7b03912)

Dirhodium(II) catalyzed dinitrogen extrusion from diazocarbonyl compounds by 2,6-dichloropyridine-N-oxide forms ketocarbonyl compounds in near quantitative yields. Reactions occur at room temperature, and the pyridine product does not coordinate with dirhodium(II) to inhibit catalysis. Anhydrous tricarbonyl compounds, as well as dicarbonyl compounds, are conveniently prepared by this methodology, and they have been used in situ for catalytic ene and aldol transformations.

Mazzola, E. P.; Gutierrez, O.; Fraenkel, G. A.; Chow, A.; Doyle, M. P.; Mandler, M. D.; Dykstra, R.; Garg, D.; Ridge, C. D. “Unusually large scalar coupling between geminal protons in a saturated pyrimidine” Concepts Magn. Reson. Part A. 2018; 45A: e21424. https://doi.org/10.1002/cmr.a.21424

An unusually large geminal coupling has been observed in a stereochemically rigid system that permits a favorable coupling alignment between the methylene protons and an adjacent carbon‐carbon double bond. Such couplings have been found to depend on both the alignment of a line connecting the geminal hydrogens and the nodal plane of the adjacent double bond, and the orientation of lone‐pair electrons on adjacent heteroatoms. Electron withdrawal from symmetrical bonding orbitals results in more slightly positive geminal coupling constants while that from antisymmetrical bonding orbitals produces more negative coupling constants, which has been found to be very large in certain rigid systems.

Cheng, Q.-Q.; Massey, L. A.; Willett, B. S.; Deng, Y.; Arman, H.; Doyle, M. P. “Copper-Catalyzed Formal [4+2]-Cycloaddition of Enoldiazoimides with Sulfur Ylides” Angew. Chem. Int. Ed. 2018, 57, 10343-10346. doi.org/10.1002/anie.201805323

Enoldiazoimides, a new subclass of enoldiazo compounds, generate enol‐substituted carbonyl ylides whose reactions with sulfur ylides enable an unprecedented formal [4+2] cycloaddition. The resulting multifunctionalized indolizidinones, which incorporate sulfur, are formed in good yields under mild reaction conditions. The uniqueness of this transformation stems from the role of the silyl‐protected enol, since the corresponding acetyldiazoimide failed to provide any cross‐products in metal‐catalyzed reactions with sulfur ylides. This copper‐catalyzed cycloaddition is initiated with the generation of enol‐substituted carbonyl ylides and sulfur ylides from enoldiazoimides and sulfonium salts, respectively, and proceeds through stepwise six‐membered ring formation, C−O and C−S bond cleavage, and silyl and acetyl group migration.

Marichev, K. O.; Wang, Y.; Carranco, A. M.; Garcia, E. C.; Yu, Z.-X.; Doyle, M. P. “Rhodium(II)-catalysed generation of cycloprop-1-en-1-yl ketones and their rearrangement to 5-aryl-2-siloxyfurans” Chem. Commun. 2018, 54, 9513-9516. DOI: 10.1039/C8CC05623D

Donor–acceptor cyclopropenes formed from enoldiazoketones undergo catalytic rearrangement to 5-aryl-2-siloxyfurans via a novel mechanism that involves a nucleophilic addition of the carbonyl oxygen to the rhodium-activated cyclopropene.

Sha, Q.; Wang, J.; Doyle, M. P. “Synthesis of 1H-Pyrrol-3(2H)-ones via Three-Component Reactions of 2,3-Diketo Esters, Amines, and Ketones” J. Org. Chem. 2018, 83 , 11288–11297. DOI:10.1021/acs.joc.8b01887

An efficient one-pot, three-component reaction of 2,3-diketo esters with amines and ketones has been developed for the synthesis of 1H-pyrrol-3(2H)-ones. By using trifluoroacetic acid (TFA) as the additive and acetonitrile (MeCN) as the solvent, this convenient method provides a library of 1H-pyrrol-3(2H)-ones in moderate to good yields. The simple protocol features readily available starting materials, a straightforward process, good functional group tolerance, and broad substrate scope.

Dong, K.; Pei, C.; Zeng,, Q.; Wei, H.; Doyle, M. P.; Xu, X. “Selective C(sp3)–H Bond Insertion in Carbene/Alkyne Metathesis Reactions. Enantioselective Construction of Dihydroindoles” ACS Catal. 2018, 8, 9543–9549. DOI: 10.1021/acscatal.8b02822

A general access to chiral dihydroindole derivatives in high yields is achieved by C–H functionalization in a highly site- and enantioselective cascade reaction of propargyl diazoacetates. Highly site-selective intramolecular C(sp3)–H bond insertions are realized by catalyst control. Sterically demanding dirhodium carboxylates, optimized with Rh2(S-BTPCP)4, favor C–H insertion into 1° C–H bonds with regioselectivities reaching >95:5 (1° > 2° benzylic) and >90% ee. With Rh2(S-TBPTTL)4, preferential 2° and 3° C–H bond insertion occurs due to the configuration of catalyst and electronic effects. The chiral dirhodium catalyst not only promotes carbene/alkyne metathesis (CAM) to generate the donor/donor carbene intermediate, but is also responsible for the observed asymmetric induction in the terminating C–H bond insertion reaction.

Marichev, K. O.; Adly, F. G.; Carranco, A. M.; Garcia, E. C.; Arman, H.; Doyle, M. P. “Catalyst Choice for Highly Enantioselective [3 + 3]-Cycloaddition of Enoldiazocarbonyl Compounds” ACS Catal. 2018, 8, 10392–10400. DOI: 10.1021/acscatal.8b03391

Chiral copper(I) catalysts are preferred over chiral dirhodium(II) catalysts for [3 + 3]-cycloaddition reactions of enoldiazocarbonyl compounds with nitrones and acyliminopyridinium ylides, forming chiral oxazines and pyrazines in very high yield and enantioselectivity. Yields and stereoselectivities from reactions of enoldiazoketones are virtually the same as those from the corresponding esters and amides, but products from enoldiazoketones are precursors to chiral 1,3-dicarbonyl derivatives that provide additional opportunities in heterocyclic synthesis through the formation of pyrazoles and isoxazoles.

Qiu, H.; Arman, H.; Hu, W.; Doyle, M. P. “Intramolecular cycloaddition/- rearrangement cascade from gold(III)-catalyzed reactions of propargyl aryldiazoesters with cinnamyl imines” Chem. Commun. 201854, 12828 – 12831. DOI: 10.1039/C8CC07885H

Conjugated cycloheptene-1,4-dione-enamines are cycloaddition products from a surprising rearrangement in a Au(III)-catalysed reaction between propargyl aryldiazoacetates and cinnamyl imines. This complex transformation occurs through an initial rapid Au(III)-catalysed [4+3]-cycloaddition to form dihydroazepinyl aryldiazoacetates followed by a subsequent uncatalyzed domino transformation that occurs by sequential [3+2]-cycloaddition-/nitrogen extrusion and acyloxy migration/retro-Michael addition/tautomerization.