2021 Publications

Kuiyong Dong, Haifeng Zheng, Yongliang Su, Ahmad. Humeidi, Hadi Arman, Xinfang Xu,* and Michael P. Doyle* Catalyst-Directed Divergent Catalytic Approaches to Expand Structural and Functional Scaffold Diversity via Metallo-Enolcarbene Intermediates. ACS Catal2021, accepted. 

1

An efficient and novel Ag(I)-catalyzed methodology for the synthesis of multisubstituted 4-silyloxypyrrole-3-carboxylates with broad variability for the placement of substituents at the 2, 5-, and N-positions. Convenient conversion of imino ethers that include oxazolines, benzoxazoles and benzimidates with silyl-protected enoldiazoacetates to fully substituted pyrroles with uniformly high chemo- and regioselectivity. Mechanistic studies confirm a [3+2]-cycloaddition/C-O band cleavage/[1,5]-proton transfer cascade process.

Kuiyong Dong, Ahmad Humeidi, Wendell Griffith, Hadi Arman, Xinfang Xu,* Michael P. Doyle* A General Methodology to Highly Functionalized Pyrroles by Ag(I)-Catalyzed Transformations of Imino Ethers. Angew. Chem. Int. Ed. 2021, accepted.

 

2

 

Catalyst-directed access to divergent products involving three different metals that exclusively form three different products from the same reactants is reported. Each catalyst directs an individual metallo-enolcarbene pathway from enoldiazoacetates and alkenes to a specific product. These include highly selective intermolecular cyclopropanation catalyzed exclusively by dirhodium(II) carboxylates, providing spiro-substituted dihydrooxazoles with greater than 20:1 diastereoselectivity and up to 99% ee; vinylogous addition with subsequent 1,6-proton transfer occurring independently with either Au(I) or Cu(I) catalysis or [3+2]-cycloaddition with a Cu(II) catalyst; and direct cycloaddition with the C=N bond of methylenedihydrooxazoles followed by rearrangement forming multiply substituted pyrroles in the presence of a silver catalyst. Allylic aromatization via vinylogous addition selectively delivers aromatic oxazole derivatives from methylenedihydrooxazoles, and when aromatization does not occur by 1,6-proton transfer, [3+2]-cycloaddition is the outcome. The conversion of methylenedihydrooxazoles to polyfunctionalized pyrroles is unprecedented. This catalyst-dependent formation of metallo-enolcarbene intermediates with alkenes demonstrates the tremendous potential of this approach to diversity-oriented-synthesis.

 

Zheng, H.; Wang, R.; Wang, K.; Wherritt, D.; Arman, H.; Doyle, M. P. “Formal [4+4]-, [4+3]-, and [4+2]-Cycloaddition Reactions of Donor-Acceptor Cyclobutenes, Cyclopropenes and Siloxyalkynes Induced by Brønsted Acid Catalysis” Chem. Sci. 2021, 12, DOI: 10.1039/D1SC00158B

 

3

Brønsted acid catalyzed formal [4+4]-, [4+3]-, and [4+2]-cycloadditions of donor-acceptor cyclobutenes, cyclopropenes, and siloxyalkynes with benzopyrylium ions are reported. [4+2]-cyclization/deMayo-type ring-extension cascade processes produce highly functionalized benzocyclooctatrienes, benzocycloheptatrienes, and 2-naphthols in good to excellent yields and selectivities. Moreover, the optical purity of reactant donor-acceptor cyclobutenes is fully retained during the cascade. The 1,3-dicarbonyl product framework of the reaction products provides opportunities for salen-type ligand syntheses and the construction of fused pyrazoles and isoxazoles that reveal a novel rotamer-diastereoisomerism.

De Angelis, L.; Crawford, A. M.; Su, Y.-L.; Wherritt, D.; Arman, H.; Doyle, M. P. “Catalyst-Free Formation of Nitrile Oxides and Their Further Transformations to Diverse Heterocycles” Org. Lett. 2021, 23, 925-929. DOI: 10.1021/acs.orglett.0c04130

 

4

 

The formation of nitrile oxides with diazocarbonyl compounds by nitrosyl transfer from tert-butyl nitrite under mild conditions and without the use of a catalyst or an additive is reported. This transformation is broadly applicable to the synthesis of furoxans by dimerization, isoxazoles and isoxazolines by cycloaddition. This methodology is also applied for the mmol-scale synthesis of two biologically active compounds. The formation of the nitrile oxide from a diazoacetamide is stable and confirmed experimentally.

 

Marichev, K. O.; Wang, K.; Greco, N.; Dong, K.; Chen, J.; Lei, J.; Doyle, M. P. “Strain-Induced Nucleophilic Ring Opening of Donor-Acceptor Cyclopropenes for Synthesis of Monosubstituted Succinic Acid Derivatives” Chem. Eur. J. 2021, 27, 340-347. DOI: 10.1002/chem.202003427

 

2

 

Silyl protected γ-substituted enoldiazo compounds under Rh(II) catalysis generate 1,2,3-trisubstituted donor-acceptor cyclopropenes that undergo
catalyst free or DMAP-catalyzed nucleophilic Favorskii-type ring opening with aliphatic amines, hydrazines, anilines,
alcohols and thiols to afford a series of amido-esters, mixed diesters and diamides, including α-substituted tetrahydropyridazine-3,6-diones and pyrrolidine-2,5-diones, in high yields.