1644560-06-4

Upstream product

• 504-02-9 1,3-cylohexanedione 
• 340732-72-1 o-hydroxy-α-(p-anisyl)benzyl alcohol 

Relevant academic research and scientific papers

Phosphoric Acid Catalyzed Formation of Hydrogen-Bonded o-Quinone Methides. Enantioselective Cycloaddition with β-Dicarbonyl Compounds toward Benzannulated Oxygen Heterocycles

A full account of the Br?nsted acid catalyzed, enantioselective synthesis of 4H-chromenes and 1H-xanthen-1-ones from o-hydroxybenzyl alcohols and β-dicarbonyl compounds is provided. The central step of our strategy is the BINOL-phosphoric acid catalyzed, enantioselective cycloaddition of β-diketones, β-keto nitriles, and β-keto esters to in situ generated, hydrogen-bonded o-quinone methides. Upon acid-promoted dehydration, the desired products were obtained with generally excellent yields and enantioselectivity. Detailed mechanistic studies including online-NMR and ESI-MS measurements were conducted to identify relevant synthetic intermediates. A reversible formation of a dimer from the starting alcohol and the reactive o-quinone methide in an off-cycle equilibrium was observed, providing a reservoir from which the o-quinone methide can be regenerated and introduced into the catalytic cycle again. Reaction progress kinetic analysis was utilized to determine kinetic profiles and rate constants of the reaction uncovering o-quinone methide formation as the rate-limiting step. In combination with Hammett plots, these studies document the relationship between o-quinone methide stabilization by electronic effects provided by the substituents and the reaction rate of the described process. In addition, DFT calculations reveal a concerted yet highly asynchronous [4 + 2]-cycloaddition pathway and an attractive CH-πinteraction between the catalyst's tBu group and the o-quinone methide as an important stereochemical control element.

Enantio- and diastereoselective access to distant stereocenters embedded within tetrahydroxanthenes: Utilizing ortho-quinone methides as reactive intermediates in asymmetric bronsted acid catalysis

A protocol for the highly enantioselective synthesis of 9-substituted tetrahydroxanthenones by means of asymmetric Bronsted acid catalysis has been developed. A chiral binolbased N-triflyphosphoramide was found to promote the in situ generation of ortho-quinone methides and their subsequent reaction with 1,3-cyclohexanedione to provide the desired products with excellent enantioselectivities. In addition, a highly enantio- and diastereoselective Bronsted acid catalyzed desymmetrization of 5-monosubstituted 1,3-dicarbonyl substrates with ortho-quinone methides gives rise to valuable tetrahydroxanthenes containing two distant stereocenters.

Bronsted acid catalyzed, conjugate addition of β-dicarbonyls to in situ generated ortho-quinone methides - Enantioselective synthesis of 4-aryl-4H-chromenes

We describe herein a catalytic, enantioselective process for the synthesis of 4H-chromenes which are important structural elements of many natural products and biologically active compounds. A sequence comprising a conjugate addition of β-diketones to in situ generated ortho-quinone methides followed by a cyclodehydration reaction furnished 4-aryl-4H-chromenes in generally excellent yields and high optical purity. A BINOL-based chiral phosphoric acid was employed as a Bronsted acid catalyst which converted ortho-hydroxy benzhydryl alcohols into hydrogen-bonded ortho-quinone methides and effected the carbon-carbon bond-forming event with high enantioselectivity. Chiral phosphoric acids permit the in situ generation of hydrogen-bonded ortho-quinone methides which react with β-diketones and β-keto esters with excellent enantioselectivity and furnish valuable 4-aryl-4H-chromenes and related heterocycles upon subsequent cyclodehydration. These observations extend the substrate scope of enantioselective phosphoric acid catalysis towards an important additional class of compounds.