A convenient and mild photochemical reaction towards the synthesis of

IGUCHI DANIELA; ERRA-BALSELLS ROSA; BONESI SERGIO M.

Mendoza

Congreso; 21st I-APS Conference; 2011

Inter-American Photochemical Society

A convenient and mild photochemical reaction towards the synthesis of substituted chroman-4-ones Daniela Iguchi, Rosa Erra-Balsells and Sergio M. Bonesi CIHIDECAR , Depto. de Química Orgánica, Fac. de Ciencias Exactas y Naturales, UBA, Pabellón II, 3er Piso, Ciudad Universitaria (1428), Buenos Aires, Argentina. The chroman-4-one (2,3-dihydro-4-oxo-4H-1-benzopyran) ring system occupies an important position among oxygen heterocycles and features in a wide variety of compounds of biological and medicinal interest. Therefore, the vast range of biological effects associated with this scaffold has resulted in the chroman-4-one ring system being considered as a privileged structure. From a synthetic viewpoint, substituted chroman-4- ones are valued both as functional intermediates and as targets in their own right. The reported methods for the synthesis of chroman-4-ones are well documented and involve i) condensation of phenols with 3,3-dimethyl acrylic acids or its derivatives (Friedel ? Craft reaction together with thermal Fries rearrangement); ii) Claisen rearrangement of propargyl ethers of phenols and, iii) Knoevenagel condensation of o-hydroxyphenones with aliphatic aldehydes and ketones (known as the Kabbe reaction). The last method perhaps is the most convenient and practical procedure involving the base ? catalyzed condensation between a 2-hydroxyphenone and an aldehyde. However, an alternative methodology scarcely considered is the photo-Fries rearrangement reaction as a key step in the synthesis of chroman-4-ones as it is illustrated in retro synthetic approach: 4H-1-benzopyran) ring system occupies an important position among oxygen heterocycles and features in a wide variety of compounds of biological and medicinal interest. Therefore, the vast range of biological effects associated with this scaffold has resulted in the chroman-4-one ring system being considered as a privileged structure. From a synthetic viewpoint, substituted chroman-4- ones are valued both as functional intermediates and as targets in their own right. The reported methods for the synthesis of chroman-4-ones are well documented and involve i) condensation of phenols with 3,3-dimethyl acrylic acids or its derivatives (Friedel ? Craft reaction together with thermal Fries rearrangement); ii) Claisen rearrangement of propargyl ethers of phenols and, iii) Knoevenagel condensation of o-hydroxyphenones with aliphatic aldehydes and ketones (known as the Kabbe reaction). The last method perhaps is the most convenient and practical procedure involving the base ? catalyzed condensation between a 2-hydroxyphenone and an aldehyde. However, an alternative methodology scarcely considered is the photo-Fries rearrangement reaction as a key step in the synthesis of chroman-4-ones as it is illustrated in retro synthetic approach: R OH R O O R OO Retro synthetic analysis R OH O Photo-Fries rearrangement step Since we are interested in the application of the photo-Fries rearrangement reaction in organic synthesis, herein we report a convenient and mild photochemical reaction of a series of para- and meta-substituted esters under a one?pot base?mediated photochemical reaction to afford a variety of substituted chroman-4-one derivatives with good yield and noticeable regioselectivity. Besides, a comparative study between the photochemical reaction under homogeneous media (organic solvents: MeOH; MeCN; cyclohexane) and heterogeneous media (biphasic system) has been carried out. The following scheme illustrates our experimental results starting from the para-substituted phenols. para- and meta-substituted esters under a one?pot base?mediated photochemical reaction to afford a variety of substituted chroman-4-one derivatives with good yield and noticeable regioselectivity. Besides, a comparative study between the photochemical reaction under homogeneous media (organic solvents: MeOH; MeCN; cyclohexane) and heterogeneous media (biphasic system) has been carried out. The following scheme illustrates our experimental results starting from the para-substituted phenols. R1 OH R1 O O O R1 O R1 = H; CH3O; CH3; Cl; NO2; CN; PhO; t-Bu; Ph. Intramolecular oxa-Michael addition Cl O Pyridine 25º C R1 O O h (254 nm) Cyclohexane KOH 10% Ar; 25ºC R1 OH R1 OH O + + O R1 O Major Photoproduct h (254 nm) Solvent Ar; 25ºC The irradiations were conducted with excitation wavelength of 254 nm, at room temperature and under inert atmosphere. The photoproducts were isolated from the photolyzed solutions and were fully characterized by means of spectroscopic methods (NMR, IR, MS). In order to characterize the photo reactive electronic excited state (singlet or triplet state) photosensitization and chemical quenching were performed. Finally, the quantum yields of the photoreactions have been also measured.