DFT and Experimental Exploration of Intramolecular [2 + 2 + 2] Cycloaddition of Oxanorbornadienedicarboxylates and Analogues

The facile intramolecular [2 + 2 + 2] homo-Diels–Alder cycloadditions of oxanorbornadienedicarboxylates and analogues have been investigated by theoretical calculations using B3LYP and M06-2X density functional methods and experimental confirmation. The oxanorbornadienedicarboxylates formed from furans and but-2-ynedioates undergo the resulting intramolecular [2 + 2 + 2] cycloaddition in a concerted but asynchronous fashion, requiring energy barriers of about 30 kcal/mol to construct five- and three-membered rings simultaneously. Bridgehead substitutents have little influence on the regioselectivity, whereas 5-substitutents involving steric hindrance or electron-acceptor groups are predicted to attenuate the cycloaddition at the substituted side. Furthermore, the linker length, unsaturated bonds, and bridge-ring size are very sensitive to the cyclization rate. Additionally, aza- and norbornadienedicarboxylates demonstrate less reactivity, while thionorbornadienedicarboxylates show more reactivity with the challenge of their synthesis. The intermolecular version was also evaluated in comparison with the intramolecular version. Finally, our experimental tests verified the calculational prediction of the regioselectivity and reactivity

Annuloselectivity in Cycloadditions of Ketenes with Imines: A DFT Study

The annuloselectivity defined as the annulation selectivity between [2 + 2] cycloaddition and two kinds of novel cascade [2 + 2 + 2] cycloadditions (2 ketenes + imine and ketene + 2 imines) in a Staudinger reaction to afford three classes of annulation products has been studied in depth with the density functional theory (DFT) calculations. The computed results indicate that the cascade [2 + 2 + 2] reaction of ketene <b>4</b> and ketimine <b>5</b> initiates the dimerization of the ketene as the rate-determining step, affording a lactone that further converts to α-acetylketene, followed by the [4 + 2] cycloaddition with imine <b>5</b> to furnish a 2,3-dihydro-1,3-oxazin-4-one derivative. That is very competitive to the normal Staudinger reaction. The alternative [2 + 2 + 2] cycloaddition undergoes the hetero-Diels–Alder (HDA) cycloaddition of the zwitterionic intermediates generated from ketenes and conjugated imine <b>11</b> with less steric hindrance as a good dienophile to afford 2,3,4,5-tetrahydropyrimidin-6­(1<i>H</i>)-ones, which is the most favorable pathway in the case of the Staudinger reaction system. The HDA process is supported and confirmed experimentally by X-ray crystallography via analysis of the stereochemistry of the cycloadducts. The further investigation into the nature of the frontier molecular orbitals accounts well for the origin of the annuloselectivity. The extensive studies on ketenes containing various representative substituents reveal that ketenes with electron-donor and conjugated monosubstituents are inclined to dimerization, preferring the [2 + 2 + 2] cycloaddition of two molecules of ketenes and one molecule of imines, while less steric bulky imines with ketenes are apt to the [2 + 2 + 2] cycloaddition of one molecule of ketenes and two molecules of imines

Annuloselectivity in Cycloadditions of Ketenes with Imines: A DFT Study

The annuloselectivity defined as the annulation selectivity between [2 + 2] cycloaddition and two kinds of novel cascade [2 + 2 + 2] cycloadditions (2 ketenes + imine and ketene + 2 imines) in a Staudinger reaction to afford three classes of annulation products has been studied in depth with the density functional theory (DFT) calculations. The computed results indicate that the cascade [2 + 2 + 2] reaction of ketene <b>4</b> and ketimine <b>5</b> initiates the dimerization of the ketene as the rate-determining step, affording a lactone that further converts to α-acetylketene, followed by the [4 + 2] cycloaddition with imine <b>5</b> to furnish a 2,3-dihydro-1,3-oxazin-4-one derivative. That is very competitive to the normal Staudinger reaction. The alternative [2 + 2 + 2] cycloaddition undergoes the hetero-Diels–Alder (HDA) cycloaddition of the zwitterionic intermediates generated from ketenes and conjugated imine <b>11</b> with less steric hindrance as a good dienophile to afford 2,3,4,5-tetrahydropyrimidin-6­(1<i>H</i>)-ones, which is the most favorable pathway in the case of the Staudinger reaction system. The HDA process is supported and confirmed experimentally by X-ray crystallography via analysis of the stereochemistry of the cycloadducts. The further investigation into the nature of the frontier molecular orbitals accounts well for the origin of the annuloselectivity. The extensive studies on ketenes containing various representative substituents reveal that ketenes with electron-donor and conjugated monosubstituents are inclined to dimerization, preferring the [2 + 2 + 2] cycloaddition of two molecules of ketenes and one molecule of imines, while less steric bulky imines with ketenes are apt to the [2 + 2 + 2] cycloaddition of one molecule of ketenes and two molecules of imines

Synthesis of β‑Phosphinolactams from Phosphenes and Imines

Various cis-β-phosphinolactams are synthesized stereoselectively for the first time from imines and diazo­(aryl)­methyl­(diaryl)­phosphine oxides under microwave irradiation. Diazo­(aryl)­methyl­(diaryl)­phosphine oxides first undergo the Wolf rearrangement to generate phosphenes. Imines nucleophilically attack the phosphenes followed by an intramolecular nucleophilic addition via less steric transition states to give final cis-β-phosphinolactams. C-Styrylimines generally give rise to β-phosphinolactams in higher yields than C-arylimines. The stereoselectivity and proposed mechanism are rationalized by DFT theoretical calculation

Rh-Catalyzed Construction of Quinolin-2(1<i>H</i>)‑ones via C–H Bond Activation of Simple Anilines with CO and Alkynes

A novel and efficient Rh-catalyzed carbonylation and annulation of simple anilines with CO and alkynes through N–H and C–H bond activation for the direct synthesis of quinolin-2­(1<i>H</i>)-ones has been developed. Simple anilines without preactivation, broad substrate scope with hetero/polycycles, and high-value products make this protocol very practical and attractive. A key rhodacycle complex was isolated and well-characterized

Rh-Catalyzed Construction of Quinolin-2(1<i>H</i>)‑ones via C–H Bond Activation of Simple Anilines with CO and Alkynes

A novel and efficient Rh-catalyzed carbonylation and annulation of simple anilines with CO and alkynes through N–H and C–H bond activation for the direct synthesis of quinolin-2­(1<i>H</i>)-ones has been developed. Simple anilines without preactivation, broad substrate scope with hetero/polycycles, and high-value products make this protocol very practical and attractive. A key rhodacycle complex was isolated and well-characterized

Visible-Light-Mediated Enantioselective Photoreactions of 3‑Alkylquinolones with 4‑<i>O</i>‑Tethered Alkenes and Allenes

The title compounds undergo intramolecular [2 + 2] photocycloaddition reactions when irradiated with visible light in the presence of a chiral sensitizer. Up to four defined stereogenic centers are formed in a single step (14 examples with a tethered alkene, 6 examples with an allene, 72–99% yield, 81–99% ee) at catalyst loadings as low as 0.5 mol %. The alkyl group in the 3-position is crucial for the success of the reaction as it leads to a significant decrease of the triplet energy

Mechanistic Insight into the Formal [1,3]-Migration in the Thermal Claisen Rearrangement

The thermal formal [1,3]-sigmatropic shift of allyl aryl ethers has been studied in depth experimentally with the aid of the density functional theory (DFT) calculations of the B3LYP function. Three mechanistic possibilities, referred to as the radical, ionic, and concerted mechanisms, have previously been put forth to explain the thermal [1,3]-rearrangement process. However, the intercrossing and radical trapping experiments indicate the rearrangement is an intramolecular process. The computational studies reveal that the concerted C­[1,3]-sigmatropic shift suffered from a higher energetic barrier to allow the rearrangement to proceed under the conditions used. However, a tandem O­[1,3]-sigmatropic shift with a configuration inversion of the oxygen atom and [3,3]-sigmatropic shift (the Claisen rearrangement) is the most likely pathway for the formal [1,3] rearrangement. Furthermore, the rearrangement experiments with a designed optically active substrate and O­[1,3]-sigmatropic shift examples verify the new cascade rearrangement. In addition, computational and experimental studies indicate that water molecule assists the proton shift during the isomerization. The combined methods provide the new insight into the mechanism of the thermal formal [1,3]-migration in the Claisen rearrangement and the novel O­[1,3]-sigmatropic shift as well

Annuloselectivity in Reactions of Diacyl Dichlorides and Imines: Combined Experimental and Theoretical Studies

The annuloselectivity defined as the annulation selectivity between [2 + 2] and cascade annulations of diacyl dichlorides and imines in the presence of organic bases to afford bis-β-lactams and 2,3-dihydro-1,3-oxazin-4-ones has been studied extensively with a combination of experiments and density functional theory (DFT) calculations. The present results indicate that it is the preference of diacyl dichlorides in the formation of cyclic α-oxoketenes in the presence of organic bases that controls the annuloselectivity. The cascade annulations of hexanedioyl and heptanedioyl dichlorides undergo the chloride-assisted cyclization of the corresponding ω-chlorocarbonylalkylketenes as the rate-determining step in the presence of triethylamine, rather than the generation of bisketenes followed by dimerization, affording five- and six-membered cyclic α-oxoketenes followed by the [4 + 2] annulations with imines to furnish 2,3-dihydro-1,3-oxazin-4-ones. This is an energetically competitive pathway to the normal Staudinger cycloaddition. Further decreasing (pentanedioyl dichloride) or increasing the linker length (octanedioyl and nonanedioyl dichlorides) results in the enhanced energetic barriers for the cyclization, which is less competitive to the direct Staudinger cycloaddition to afford bis-<i>trans</i>-β-lactams as the sole products. The current results provide an insight into the annuloselective control in the reactions of diacyl dichlorides and imines

Copper-Catalyzed Oxygenation Approach to Oxazoles from Amines, Alkynes, and Molecular Oxygen

A novel and efficient oxygenation approach to trisubstituted oxazoles via a copper-catalyzed aerobic oxidative dehydrogenative annulation of amines, alkynes, and O2 has been developed. This transformation combines dioxygen activation and oxidative C–H bond functionalization and provides a practical protocol for the preparation of oxazole derivatives, which are privileged units found in various bioactive compounds or other natural products. 18O-labeling experiments were conducted to reveal that oxygenation was involved in this chemistry