O-Allylated Pudovik and Passerini Adducts as Versatile Scaffolds for Product Diversification

Abstract

The palladium-catalyzed O-allylation of α-hydroxyphosphonates and α-hydroxyamides obtained from Pudovik and Passerini multicomponent reactions has allowed an interesting and highly straightforward access to a variety of building blocks for product diversification. These post-functionalizations include a selective base-or ruthenium hydride-mediated isomerization/Claisen rearrangement cascade and a ring-closing metathesis that allows access to a variety of diversely functionalized phosphono-oxaheterocycles.

Green and Effective Preparation of α-Hydroxyphosphonates by Ecocatalysis

“…They are especially useful as biologically active compounds such as antibiotics (e.g., Valinophos I [ 13 ], and Fosfazinomycin A III [ 14 ]); enzyme inhibitors (e.g., renin inhibitors II [ 15 ], for potential treatment of hypertension and congestive heart failure or neuraminidase inhibitor [ 16 ], for treatment of influenza infection, commonly called “the flu”); antiparasitics (e.g., inhibitors of Plasmodium falciparum growth IV [ 17 ], useful in treatment of malaria that is caused by this parasite); and insecticides (e.g., trichlorfon V ) ( Figure 1 ). Additionally, α-hydroxyphosphonic acids and their esters are very useful scaffolds in organic synthesis often used to prepare more complex molecules [ 18 ], e.g., after O -allylation and subsequent RCM or isomerization/Claisen rearrangement [ 19 ], reaction with primary amines leading to α-aminophosphonates and phosphonic acids [ 20 ], phospha-Brook rearrangement [ 21 ], reduction [ 22 ], halogenation [ 23 ], and oxidation leading to ketophosphonates ( Figure 1 ) [ 24 ].…”