[4 + 2] Cycloadditions of 1-phosphono-1,3-butadienes with nitroso heterodienophiles: a versatile synthetic route for polyfunctionalized aminophosphonic derivatives.
The hetero-Diels-Alder (HDA) reaction of 1-(diethoxyphosphonyl)-1,3-butadiene, 1-(dibenzyloxyphosphonyl)-1,3-butadiene, and 1-(diethoxyphosphonyl)-3-tert-butyldimethylsilyloxy-1,3-butadiene with various nitroso heterodienophiles has been investigated as a new synthetic route for aminophosphonic derivatives. The HDA cycloadditions regioselectively led to the proximal isomers, i.e., presenting the NR(3) group in the meta position regarding the phosphonate substituent. From the resulting 6-phosphono-3,6-dihydro-1,2-oxazine cycloadducts, a limited number of chemical steps were allowed to obtain a significant variety of aminophosphonic compounds of potential interest in medicinal chemistry. This has been illustrated through the synthesis of (Z)-4-(o-tolylamino)-1-hydroxybut-2-enylphosphonic acid, diethyl 3,4-dihydroxy-1-o-tolylpyrrolidin-2-yl-2-phosphonate, 4-(o-tolylamino)-1,2,3-trihydroxybutylphosphonic acid, diethyl 3-(2-(o-tolylamino)-1-hydroxyethyl)oxiran-2-yl-2-phosphonate, and diethyl 4,5-dihydroxymorpholin-6-yl-6-phosphonate.
Monbaliu
Jean-Christophe
JC
Unité de Chimie organique et médicinale, Institut de la matière condensée et des nanosciences, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
Tinant
Bernard
B
Marchand-Brynaert
Jacqueline
J
D002070:Butadienes / Q000737:chemistry*; D003500:Cyclization; D015394:Molecular Structure; D009603:Nitroso Compounds / Q000737:chemistry*; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D002070:Butadienes; D009603:Nitroso Compounds; D063065:Organophosphonates