PTSA-Catalyzed Reaction of Alkyl/Aryl Methyl Ketones with Aliphatic Alcohols in the Presence of Selenium Dioxide: A Protocol for the Generation of an α-Ketoacetals Library

Abstract

A novel approach has been developed for the synthesis of a wide range of α-ketoacetals by the reaction of alkyl/aryl methyl ketones and aliphatic alcohols in the presence of selenium dioxide catalyzed by p -toluenesufonic acid. This method represents a general route to obtain a wide variety of α-ketoacetals in a simple, rapid, and practical manner. This approach is particularly attractive because of the easy availability of the starting materials, mild reaction temperature, and good yields of the products. The resulting α-ketoacetals are of much synthetic value as organic intermediates.

Synergistic Catalysis of Se and Cu for the Activation of α‐H of Methyl Ketones with Molecular Oxygen/Alcohol to Produce α‐Keto Acetals†

“…MS (EI, 70 eV) m / z (%): 234 (15) [M + ], 103 (100); Known compound. [ 15b ] (CAS No. : 29097‐26‐5).…”

Design, Synthesis and Evaluation of Novel Derivatives of Curcuminoids with Cytotoxicity

“…Three aspects had to be considered in the design and synthesis of the curcuminoid derivatives: the synthesis of curcuminoid derivatives with various aromatic rings for ring A, the synthesis of the different scaffolds (β -hydroxy-α,β-unsaturated ketone, α,βunsaturated β-diketone and α,β-unsaturated ketone) of the curcuminoid derivatives and the synthesis of curcuminoid derivatives with different numbers of methoxy or hydroxy groups on each of the phenyl rings A and B, categorized as the MD series. A solution of β'-hydroxy-α,β-unsaturated ketone in CH2Cl2 was cooled to 0 °C and treated with p-toluensulfonic acid (p-TSA) for 30 min to give the corresponding α,β-unsaturated ketones 1a-7a, 12a, 14a and MD1a-12a [21]. The α,β-unsaturated ketones with a heterocyclic ring A (2-pyridine, 3-pyridine, 4-pyridine, 3-furan, 2-methyl-2-thiophene, 2-pyrrole and 3-indole) could not be synthesized in this reaction.…”

“…Using NMR analysis, compounds 19-24 and MD13 were detected in the enol form, which is interconvertible with the keto form. The A solution of β -hydroxy-α,β-unsaturated ketone in CH 2 Cl 2 was cooled to 0 • C and treated with p-toluensulfonic acid (p-TSA) for 30 min to give the corresponding α,βunsaturated ketones 1a-7a, 12a, 14a and MD1a-12a [21]. The α,β-unsaturated ketones with a heterocyclic ring A (2-pyridine, 3-pyridine, 4-pyridine, 3-furan, 2-methyl-2-thiophene, 2-pyrrole and 3-indole) could not be synthesized in this reaction.…”

Rapid, One-Step Synthesis of α-Ketoacetals via Electrophilic Etherification

“…The chemistry of α-ketoacetal compounds is incredibly versatile. − Specifically, α-ketoacetals, and their derivatives, are frequently employed in the synthesis of pharmaceutically important heterocycles, − natural products, porphyrins, antiviral or antitumor agents, , and bioactive molecules . As a “protected glyoxal”, α-ketoacetals strategically direct nucleophiles to the less reactive carbonyl while protecting the more reactive aldehyde as an acetal; ,, furthermore, the acetal-protecting group, at the α-position, has even been reported to increase the reactivity of the adjacent carbonyl .…”

“…As a “protected glyoxal”, α-ketoacetals strategically direct nucleophiles to the less reactive carbonyl while protecting the more reactive aldehyde as an acetal; ,, furthermore, the acetal-protecting group, at the α-position, has even been reported to increase the reactivity of the adjacent carbonyl . This moiety is far more stable in ambient conditions than its deprotected counterpart, which makes α-ketoacetal compounds a satisfactory, practical, and advantageous substitute for the highly important dicarbonyl structural motif. ,,− Unfortunately, despite the auspicious potential of this functional group, to our knowledge, a programmable, yet inexpensive, method of α-ketoacetal synthesis has not been widely adopted in the literature. , Traditionally, α-ketoacetals are produced via diverse variations of selenium-catalyzed oxidations (Scheme a) − , or reactions of Grignard reagents and functionalized carbonyl compounds (Scheme b). , However, both of the foregoing reactions are limited by the necessity of harsh conditions, ,, extended reaction times, or sensitive synthetic setups and reagents. , …”