The Role of Homoaromaticity in the Tropylium-Catalyzed Carboxylic Acid O-H Insertion with Diazoesters

The tropylium catalyzed carboxylic acid O-H insertion with diazoesters providing α-hydroxy esters was reported recently through an activated carbene as the key intermediate. We report a revised mechanism involving a unique homoaromatic intermediate with the tropylium ion and the diazoester based on the DFT calculations. Our computational model provides a clear insight into the binding of the tropylium ion with the diazoester providing the homoaromatic intermediate. The reaction profiles of four different pathways were compared. The energies of the intermediates and the transition states are reported at B97-D3(SMD)/def2TZVP//B97-D3/def2TZVP (in dichloromethane). The energy profiles were compared across a few computational methods to study the sensitivity of our model across methods.

Copper-Catalyzed Cross-Dehydrogenative Coupling of α-Hydroxy Esters with Nitromethane

An efficient copper-catalyzed tandem oxidation/nitro-aldol reaction of hydroxyl compounds with nucleophiles is developed. In this work, β-nitro-α-hydroxy esters were prepared via cross-dehydrogenative coupling reaction using α-hydroxy esters as hydroxyl compounds and nitromethane as a nucleophile. The reaction is believed to undergo an oxidation of hydroxyl group and then an addition of the generated carbonyl group. It’s an example of CDC reactions related to hydroxyl compounds via carbonyl intermediates.

Synthetic strategies of phosphonodepsipeptides

Phosphonodepsipeptides are phosphorus analogues of depsipeptides and phosphonate-linked analogues of naturally occurring peptides. They are more stable than phosphonopeptides and have been widely applied as enzyme inhibitors, haptens for the production of antibodies, biological agents, and prodrugs. The synthetic strategies towards phosphonodepsipeptides are reviewed, including the phosphonylation of hydroxy esters with phosphonochloridates, the condensation of phosphonic monoesters and hydroxy esters, the alkylation of phosphonic monoesters with 1-(alkoxycarbonyl)alkyl halides or sulfonates, multicomponent condensation of amides, aldehydes, and dichlorophosphites followed by alcoholysis with hydroxy esters, the phosphinylation of hydroxy esters with phosphonochloridites followed by oxidation, and the carbene insertion of N-protected amino acids with 1-diazoalkylphosphonates. This review includes the synthesis of α-, β-, and γ-phosphonodepsipeptides and phosphonodepsipeptides with C-1-hydroxyalkylphosphonic acids.

Diastereoselective Reduction of Selected α-substituted β-keto Esters and the Assignment of the Relative Configuration by 1H-NMR Spectroscopy

Background:: Chiral β-hydroxy esters and α-substituted β-hydroxy esters represent versatile building blocks for pheromones, β-lactam antibiotics and 1,2- or 1,3-aminoalcohols. Objective:: Synthesis of versatile α-substituted β-keto esters and their diastereoselective reduction to the corresponding syn- or anti-α-substituted β-hydroxy esters. Assignment of the relative configuration by NMR-spectroscopy after a CURTIUS rearrangement of α-substituted β-keto esters to 4-substituted 5-methyloxazolidin-2-ones. Method:: Diastereoselective reduction was achieved by using different LEWIS acids (zinc, titanium and cerium) in combination with complex borohydrides as reducing agents. Assignment of the relative configuration was verified by 1H-NMR spectroscopy after CURTIUS-rearrangement of α-substituted β-hydroxy esters to 4-substituted 5-methyloxazolidin-2-ones. Results:: For the syn-selective reduction, titanium tetrachloride (TiCl4) in combination with a pyridine-borane complex (py BH3) led to diastereoselectivities up to 99% dr. High anti-selective reduction was achieved by using cerium trichloride (CeCl3) and steric hindered reducing agents such as lithium triethylborohydride (LiEt3BH). After CURTIUS-rearrangement of each α-substituted β-hydroxy ester to the corresponding 4-substituted 5-methyloxazolidin-2-one, the relative configuration was confirmed by 1H NMR-spectroscopy. Conclusion:: We have expanded the procedure of LEWIS acid-mediated diastereoselective reduction to bulky α-substituents such as the isopropyl group and the electron withdrawing phenyl ring.