Novel One-Pot Synthesis of 3-Amino-1-alkenylphophonates by Addition of Imines to Alkynylphosphonate Titanium(II) Complexes

Abstract

[reaction: see text] A new method of synthesis of 3-amino-1-alkenylphosphonates is described. It involves the addition of imines to the alkynylphosphonate titanium(II) complexes 2, which are prepared in situ from 1-alkynylphosphonates and Ti(O-i-Pr)(4)/2 equiv of i-PrMgCl. Compounds 4a-i were obtained regio- and stereoselectivily in high yields.

Lithiated alkylidenebis(phosphonates): Reactive phosphorus intermediates in the synthesis of 3‐amino‐1‐alkenylphosphonates

“…These strategies cannot be applied to substituted (3-amino-1-alkenyl) phosphonates because of the difficulties relating to the preparation of the starting reagents, severe reaction conditions, and the lack of the ability to control the regioselectivity, stereoselectivity, and stereospecificity of rearrangements. Another route to these compounds involves the addition of imines to the alkynylphosphonate titanium(II) complexes [19]. A similar process to prepare unsubstituted aminoalkenylphosphonates is based on the addition of the lithiated carbanion, derived from diethyl ethynyl phosphonate, to an alanine Schiff base [20].…”

Recently Synthesized Class of Vinylphosphonates as Potent Matrix Metalloproteinase (MMP‐2) Inhibitors

“…The 3-aminovinylphosphonates, compounds 24Ϫ29, were synthesized by addition of imines to the alkynylphosphonate titanium(II) complexes (Scheme 3) [32].…”

5.34 Early Transition Metal Mediated Reductive Coupling Reactions

“…Here, C-C bond formation occurs at the site of the alkyne distal to the TMS group (minor isomers were not reported; a similar sense of regiochemical control has also been observed with alkynylphoshponates). 97 Notably, the Ti-promoted coupling reaction also proceeds with ketimines and hydrazones.…”