A New Horner−Wadsworth−Emmons Type Coupling Reaction between Nonstabilized β-Hydroxy Phosphonates and Aldehydes or Ketones

Abstract

Treatment of nonstabilized beta-hydroxy phosphonic acid mono methyl esters with diisopropyl carbodiimide at ambient temperature leads to clean stereospecific elimination. The phosphonic acid mono alkyl esters are accessible by the selective partial saponification of dimethyl or diethyl alkyl phosphonates with NaOH or MgBr(2). Isolated yields over both hydrolysis and elimination steps average 55-75%.

The Importance of Hydrogen Bonding and Aromatic Stacking to the Affinity and Efficacy of Cannabinoid Receptor CB2Antagonist, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide (SR144528)

“…37 Treatment of 34 with n-butyllithium and the aldehyde 32 gave the adduct 35 , which partly eliminated to the olefin 4 . Treatment of the residual 35 with MgBr 2 and heating was expected to provide the corresponding phosphate monoester 38 but gave instead the target olefin 4 . The combined 4 containing fractions were purified chromatographically (2.7%).…”

Synthesis of a [14C]‐steroid intermediate: an application of a nonstabilized Horner–Wadsworth–Emmons olefination approach

“…As a consequence, olefination using nonstabilized HWE reagents has been viewed as a difficult transformation. However, a report by Reichwein and Pagenkopf showed that the resulting hydroxyphosphonate undergoes elimination via a saponification–dehydration sequence . To our delight, this was indeed the case when we subjected our substrate to the reported conditions using unlabeled dimethyl methylphosphonate.…”

“…However, a report by Reichwein and Pagenkopf showed that the resulting hydroxyphosphonate undergoes elimination via a saponification-dehydration sequence. 3 To our delight, this was indeed the case when we subjected our substrate to the reported conditions using unlabeled dimethyl methylphosphonate. Encouraged by this initial result, we prepared the [ 14 C]-HWE reagent via the Michaelis-Arbuzov reaction.…”

Synthesis of Chiral Tertiary Boronic Esters: Phosphonate-Directed Catalytic Asymmetric Hydroboration of Trisubstituted Alkenes

“…Direct phosphonate olefination is limited in scope since β-hydroxy phosphonates lacking electron withdrawing substituents on the α-carbon are not prone to eliminate without activation. 22 However, Corey 23 found that β-hydroxy thionophosphonates readily undergo elimination to form alkenes. Treating phosphonate 17 with Lawesson’s reagent 24 affords thionophosphonate 18 .…”