Keshaba Nanda Parida

Twist Does a Twist to the Reactivity: Stoichiometric and Catalytic Oxidations with Twisted Tetramethyl-IBX

The methyl groups in TetMe-IBX lower the activation energy corresponding to the rate-determining hypervalent twisting (theoretical calculations), and the steric relay between successive methyl groups twists the structure, which manifests in significant solubility in common organic solvents. Consequently, oxidations of alcohols and sulfides occur at room temperature in common organic solvents. In situ generation of the reactive TetMe-IBX from its precursor iodo-acid, i.e., 3,4,5,6-tetramethyl-2-iodobenzoic acid, in the presence of oxone as a co-oxidant facilitates the oxidation of diverse alcohols at room temperature.

6-Membered Pseudocyclic IBX Acids: Syntheses, X-ray Structural Characterizations, and Oxidation Reactivities in Common Organic Solvents

We designed and synthesized λ(5)-cyclic periodinanes 1 and 2, which are homologous to IBX (1-hydroxy-1-oxo-1H-1λ(5)-benzo[d][1,2]iodoxol-3-one) by one carbon, to thwart close packing of molecules in the crystal lattice to permit solubility in common organic solvents and to facilitate oxidations with enhanced reactivity. The X-ray crystal structures revealed that both 1 and 2 exist in the solid state as pseudocyclic (PC) acids, i.e., 1PC and 2PC, and that the molecules in the lattice are less weakly associated as compared to those in the parent IBX due to the twisting introduced via the sp(3) benzylic carbon. Both 1PC and 2PC are found to dissolve in palpable amounts in DCM and acetonitrile to allow oxidation of a variety of alcohols and sulfides to carbonyl compounds and sulfoxides in a facile manner. The subtle differences in the sterics due to methyl and ethyl substituents in 1PC and 2PC are found to manifest in contrasting reactivities in that the oxidations of alcohols occur faster with 2PC, while those of sulfides to sulfoxides occur more rapidly with 1PC.

Influence of (2,3,4,5,6-Pentamethyl/phenyl)phenyl Scaffold: Stereoelectronic Control of the Persistence of o-Quinonoid Reactive Intermediates of Photochromic Chromenes †

Regioisomeric photochromic chromenes 1Ch-6Ch substituted with the (2,3,4,5,6-pentamethyl/phenyl)phenyl scaffold were designed to delve into stereoelectronic effects on the spectrokinetic properties of photogenerated o-quinonoid reactive intermediates. While the latter derived from 1Ch, 2Ch, 4Ch, and 5Ch were found to exhibit notable persistence, those from 3Ch and 6Ch were found to revert rapidly at room temperature to preclude visible coloration. The intermediates of 1Ch and 2Ch were found to be marginally more stable than those of 4Ch and 5Ch, respectively, attesting to the possibility of toroidal conjugation via C(ipso)-π orbitals in the former. The rapid reversion of the intermediates of 3Ch and 6Ch is attributed to unfavorable electronic repulsion between the phenyl ring of the (pentamethyl/phenyl)phenyl scaffold and one of the lone-pairs of the o-quinonoid oxygen. Thus, the regioisomerically substituted photochromic chromenes are shown to permit control of the reversion, very rapidly as well as slowly, of the colored o-quinonoid intermediates through operation of stereoelectronic effects differently.

Oxidative Cleavage of Olefins by In Situ-Generated Catalytic 3,4,5,6-Tetramethyl-2-iodoxybenzoic Acid/Oxone

Oxidative cleavage of a variety of olefins to the corresponding ketones/carboxylic acids is shown to occur in a facile manner with 3,4,5,6-tetramethyl-2-iodobenzoic acid (TetMe-IA)/oxone. The simple methodology involves mere stirring of the olefin and catalytic amount (10 mol %) of TetMe-IA and oxone in acetonitrile-water mixture (1:1, v/v) at rt. The reaction mechanism involves initial dihydroxylation of the olefin with oxone, oxidative cleavage by the in situ-generated 3,4,5,6-tetramethyl-2-iodoxybenzoic acid (TetMe-IBX), and oxidation of the aldehyde functionality to the corresponding acid with oxone. Differences in the reactivities of electron-rich and electron-poor double bonds have been exploited to demonstrate chemoselective oxidative cleavage in substrates containing two double bonds.

Through-space control of the persistence of photogenerated o-quinonoid intermediates in naphthalenes containing cofacially oriented chromenes and arenes.

Remarkable modulation of the persistence of the photogenerated colored o-quinonoid intermediates via a through-space interaction has been demonstrated in chromenes 1-4 based on 1,8-diarylnaphthalenes. Polar/π interaction is shown to stabilize the closed form of 4 to such an extent that photoinduced coloration is virtually invisible, while the same stabilization in the opened form of 2 permits ready coloration with a long-lived o-quinonoid intermediate.

Synthesis of o-Carboxyarylacrylic Acids by Room Temperature Oxidative Cleavage of Hydroxynaphthalenes and Higher Aromatics with Oxone

A simple procedure for the synthesis of a variety of o-carboxyarylacrylic acids has been developed with Oxone (2KHSO5·KHSO4·K2SO4); the oxidation reaction involves the stirring of methoxy/hydroxy-substituted naphthalenes, phenanthrenes, anthracenes, etc. with Oxone in an acetonitrile-water mixture (1:1, v/v) at rt. Mechanistically, the reaction proceeds via initial oxidation of naphthalene to o-quinone, which undergoes cleavage to the corresponding o-carboxyarylacrylic acid. The higher aromatics are found to yield carboxymethyl lactones derived from the initially formed o-carboxyarylacrylic acids.

Transition-Metal-Free Intermolecular α-Arylation of Ketones via Enolonium Species

Herein it is shown, for the first time, that enolonium species are powerful electrophiles capable of reacting with aromatic compounds in an intermolecular manner to afford α-arylated ketones. The reaction is compatible with a variety of functional groups, is of wide scope with respect to aromatic compounds and ketone, and even works for polymerization-prone substrates such as substituted pyrroles, thiophenes, and furans. Only 1.6 to 5 equiv of the commodity aromatic substrates is needed.

α-N-Heteroarylation and α-Azidation of Ketones via Enolonium Species

Enolonium species, resulting from the umpolung of ketone enolates by Kosers hypervalent iodine reagents activated by boron trifluoride, react with a variety of nitrogen heterocycles to form α-aminated ketones. The reactions are mild and complete in 4-5 h. Additionally, α-azidation of the enolonium species takes place using trimethylsilyl azide as a convenient source of azide nucleophile.

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

α-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. Recently, we have developed a two-step strategy for ketone enolate umpolung that has enabled the development of methods for chlorination, azidation, and amination using azoles. In addition, we have developed C-C bond-forming arylation and allylation reactions. At the heart of these methods is the preparation of the intermediate and highly reactive enolonium species prior to addition of a reactive nucleophile. This strategy is thus reminiscent of the preparation and use of metal enolates in classical synthetic chemistry. This strategy allows the use of nucleophiles that would otherwise be incompatible with the strongly oxidizing hypervalent iodine reagents. In this paper we present a detailed protocol for chlorination, azidation, N-heteroarylation, arylation, and allylation. The products include motifs prevalent in medicinally active products. This article will greatly assist others in using these methods.

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

Due to their closely matched reactivity, the coupling of two dissimilar ketone enolates to form a 1,4-diketone remains a challenge in organic synthesis. We herein report that umpolung of a ketone trimethylsilyl enol ether (1 equiv) to form a discrete enolonium species, followed by addition of as little as 1.2–1.4 equivalents of a second trimethylsilyl enol ether, provides an attractive solution to this problem. A wide array of enolates may be used to form the 1,4-diketone products in 38 to 74% yield. Due to the use of two TMS enol ethers as precursors, an optimization of the cross-coupling should include investigating the order of addition.