Diastereoselective multicomponent phosphoramidate-aldehyde-dienophile (PAD) process for the synthesis of polysubstituted cyclohex-2-enyl-amine derivatives

Opening up the Toolbox: Synthesis and Mechanisms of Phosphoramidates

“…The observed product conversions were in the range 56-99%. Aromatic and aliphatic aldehydes such as 2-naphthaldehyde, benzo[d] [1,3]dioxole-5-carbaldehyde, 5,6-dihydro-2H-pyran-3-carbaldehyde and 3-methylbut-2-enal were used in the reaction along with aromatic and aliphatic phosphoryl azide such as 3-nitrophenyl (4-nitrophenyl) phosphorazidate, bis(2,2,2-trichloroethyl) phosphorazidate, and diethyl phosphorazidate. However, lower yields were obtained from aliphatic aldehydes when compared with the aromatic aldehydes, suggesting that the synthetic procedure favors electron-rich aromatic aldehydes.…”

“…Chabour et al reported a diastereoselective P-N synthesis via the PAD process using a TsOH acid catalyst and a dienophile, maleimide (Scheme 17) [1]. Flash chromatography was used to isolate the desired product in 40-88% yield.…”

“…Chabour et al proposed a mechanism of the reaction in which (EtO) 2 P(O)NH 2 reacts with (or is activated by) acetic anhydride to form diethyl acetylphosphoramidate and acetic acid (Scheme 39) [1]. Meanwhile, the aldehyde protonated in the presence of an acid catalyst, TsOH, reacts with the diethyl acetylphosphoramidate complex to give the cationic diethyl (alkene-acetamido)phosphonate complex intermediate.…”

“…Phosphoramidates (P-N) are a class of organophosphorus compounds known for the presence of a single covalent bond between the tetracoordinate P(V) atom and N(III) atom. There are generally three types of phosphoroamidates, which are distinguished according to the substitution on the P and N atoms ( Figure 1) [1]. Another feature of these organophosphorous compounds, defined as (RO)2P(O)NR'2 (R, R' = H, alkyl, aryl, heteroaryl), is a stable phosphoryl bond (P=O).…”

“…Phosphoramidates (P-N) are a class of organophosphorus compounds known for the presence of a single covalent bond between the tetracoordinate P(V) atom and N(III) atom. There are generally three types of phosphoroamidates, which are distinguished according to the substitution on the P and N atoms ( Figure 1 ) [ 1 ].…”