General and Chemoselective Bisphosphonylation of Secondary and Tertiary Amides

Abstract

With Tf2O as the activation reagent, a mild and general method has been developed for the bisphosphonylation of both secondary and tertiary amides. The protocol is highly efficient and chemoselective, and it tolerates a number of sensitive functional groups such as cyano, ester, and aldehyde groups.

Microwave-assisted synthesis of (aminomethylene)bisphosphine oxides and (aminomethylene)bisphosphonates by a three-component condensation

“…There are other possibilities to synthesize (aminomethylene)bisphosphonates, such as by the reaction of dimethylformamide diethyl acetal with diethyl phosphite ( Scheme 2 ) [ 33 ], by the condensation of formamides and diethyl phosphite using 2,6-di- tert -butyl-4-methylpyridine (DTBMP) as the base, and trifluoromethanesulfonic anhydride (Tf 2 O) as the catalyst ( Scheme 2 ) [ 34 ], or by the reaction of isonitriles with triethyl phosphite ( Scheme 2 ) [ 35 – 36 ]. (Aminomethylene)bisphosphonates can also be obtained starting from amides, triethyl phosphite and phosphorus oxychloride ( Scheme 3 ) [ 37 ], or in the reaction of amines with diazophosphonate in the presence of a rhodium catalyst ( Scheme 3 ) [ 38 ].…”

Reactions of Piperazin-2-one, Morpholin-3-one, and Thiomorpholin-3-one with Triethyl Phosphite Prompted by Phosphoryl Chloride: Scope and Limitations

“…Tetraethyl N -benzyl-2,3-morpholyl-3,3-bisphosphonate (compound 9 ) was obtained with a good yield in a separate reaction according to the procedure proposed recently by Wang (Scheme 5). 6 Unfortunately, attempts to use this procedure for other substrates gave unsatisfactory results yielding mixtures of the inseparable products.…”

Triflic Anhydride (Tf2O)-Activated Transformations of Amides, Sulfoxides and Phosphorus Oxides via Nucleophilic Trapping

“…For the functionalization of amides with different nucleophiles, the Huang group reported the bisphosphonylation of amides 33a for the synthesis of -amino bisphosphonates 33b, in which a phosphorus reagent served as the nucleophile partner (Scheme 33, eq 1). 65 This transformation demonstrated high chemoselectivity and tolerated various functional groups such as cyano, ester, and aldehyde. Later, the same group described a tandem cyanation/phosphonylation of secondary amides 33c in the presence of TMSCN and a phosphonate, introducing a C-C bond and a C-P bond at the carbonyl carbon.…”