An Efficient Preparation of β-Aryl-β-ketophosphonates by the TFAA/H₃PO₄-Mediated Acylation of Arenes with Phosphonoacetic Acids

Abstract

Beta-aryl-beta-ketophosphonates can be efficiently prepared in good yield by using a TFAA/85% H 3PO 4-mediated acylation of electron-rich arenes with phosphonoacetic acids. The conditions offer advantages over existing methods of preparing these useful compounds by not requiring the use of strong base, cryogenics, or an anhydrous and inert atmosphere. Furthermore, some functional groups not tolerated with the reaction conditions used in existing methods are compatible with the herein described conditions.

Relative impact of 3- and 5-hydroxyl groups of cytosporone B on cancer cell viability

“…Introducing the n -octanoyl group at the 2-position of intermediate 8 to produce 9 (step d) employed the potent acylating agent octanoyl bis(trifluoroacetyl)phosphate, which was formed in situ from n -octanoic acid and trifluoroacetic anhydride in phosphoric acid. 18,19 Its potency may account for the debenzylation that occurred at the 5-position to give a 1: 10 mixture of the 3,5-dibenzyl ether 9 and 3-benzyl ether 10. Deprotection of 3-benzyl ether 10 using boron tribromide at −78 °C produced Csn-B (1).…”

Catalytic and Direct Oxyphosphorylation of Alkenes with Dioxygen and H‐Phosphonates Leading to β‐Ketophosphonates

“…Initially, under an oxygen atmosphere, the reaction of styrene (1 a) with (iPrO) 2 P(O)H (2 a) was performed to examine the catalytic activity of various transition-metal complexes including Au, Ag, Cu, Ru, Rh, Ni, Pd, Pt, Bi, In, Ti, and Fe salts (see Table S1 in the Supporting Information). Among the above-mentioned metal salts examined, copper salts, especially CuBr 2 , was found to be the most effective catalyst to generate the desired product 3 aa ( [11][12][13][14][15][16][17]. The addition of a base was critical to the success of this oxyphosphorylation reaction and no product was detected in the absence of a base.…”

“…[11] Generally, b-ketophosphonates are prepared by the reaction of a-haloketones with trialkylphosphites (Arbuzov reaction) [12] or acylation of alkylphosphonates with carboxylic acid derivatives by employing stoichiometric amounts of organometallic reagents (Scheme 1). [13] Alternative procedures include oxidation of b-hydroxyalkylphosphonates with stoichiometric amounts of inorganic oxidants, [14] acylation of arenes with phosphonoacetic acids, [15] and metal-mediated reactions of a-halophosphonates with esters. [16] However, almost all of these methods suffer from limitations such as low atom economy, poor substrate scope, tedious procedures, relatively harsh reaction conditions, or requiring excess amounts of organometallic reagents.…”

Friedel–Crafts acylation of ferrocene with alkynoic acids

“…A similar system (carboxylic acid/TFAA/H 3 PO 4 ) has been employed for acylation of purely organic substrates [17,18] but it failed in the case of ferrocene [17].…”