Synthesis of Non-racemic α-Hydroxyphosphonates via Asymmetric Phospho‐Aldol Reaction

Abstract

It has been more than 50 years since the first phospho-aldol reactions of dialkyl phosphites were reported. These efficient P-C bond-forming reactions have become the cornerstone of methods for the synthesis of α-hydroxyphosphonates and, by numerous available substitution reactions, the synthesis of other α- and γ-substituted phosphonates and phosphonic acids. Much of the interest in α- and γ-substituted phosphonates and phosphonic acids has been stimulated by reports of their biological activity, which is often dependent upon their absolute and relative stereochemistry. In this chapter, we review diastereoselective and enantioselective additions of dialkyl phosphites to aldehydes and ketones, otherwise called the phospho-aldol, Pudovik or Abramov reactions.

Enantioseparation of α‐Hydroxyallylphosphonates and Phosphonoallylic Carbonate Derivatives on Chiral Stationary Phases Using Sequential UV, Polarimetric, and Refractive Index Detection

“…All reactions were carried out in oven-dried glassware under an atmosphere of argon unless otherwise noted. Nuclear magnetic resonance (NMR) spectra were recorded in CDCl 3 7,[17][18][19] Compounds 3 were prepared by hydrophosphonylation from the appropriate aldehyde and dimethyl phosphite and were obtained from our in-house collection. 20 Enantiomerically enriched samples of allylic phosphonates 1b-f and cinnamylic phosphonates 4b-c were prepared from enriched (R)-hydroxyphosphonates 1a and 2a, respectively.…”

“…We are interested in evaluating the enantiomeric purity of α‐hydroxyallylphosphonates 1a and 1b due to their utility as valuable chiral synthetic intermediates . They have been employed for the preparation of a wide variety of biologically active compounds including both organophosphorus and, by chirality transfer, nonphosphorus‐containing target molecules . The ability to selectively prepare either enantiomer of 1b has led to the synthesis of nematocidal oxylipids and antimicrobial cyclophostins .…”

“…2 They have been employed for the preparation of a wide variety of biologically active compounds including both organophosphorus and, by chirality transfer, nonphosphorus-containing target molecules. 3 The ability to selectively prepare either enantiomer of 1b has led to the synthesis of nematocidal oxylipids 4 and antimicrobial cyclophostins. 5 Palladium coupled crossmetathesis reactions have been employed for transfer of chirality of α-hydroxyallylphosphonates to the gamma position of the carbon chain, 6,7 resulting in enantioselective synthesis of cyclopentanone substituted phosphonate, 8 cyclic ethers, 9 and (S)-tumerone.…”

Synthesis and Reactions of α-Hydroxyphosphonates

“…Due to the bioactivity of α-hydroxyphosphonates 1 , the synthesis of these derivatives is an evergreen topic in organophosphorus chemistry [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. The main approaches to obtain α-hydroxyphosphonates 1 are shown in Scheme 1 .…”

“…In this review, methods “A” and “B” are discussed in detail. Although the asymmetric synthesis of α-hydroxyphosphonates 1 is of special importance [ 4 , 5 , 6 , 7 , 8 ], in this review the discussion is limited to racemic derivatives.…”