Synthesis of Nonracemic Allylic Hydroxy Phosphonates via Alkene Cross Metathesis.

Abstract

Organo-phosphorus compounds S 0080 Synthesis of Nonracemic Allylic Hydroxy Phosphonates via Alkene Cross Metathesis. -The alkene cross metathesis can be applied successfully to the synthesis of various allylic hydroxy phosphonates and their hydroxy-protected derivatives. The enantiomeric excess of educts is preserved in the products. -(HE, A.; YAN, B.; THANAVARO, A.; SPILLING*, C. D.; RATH, N. P.; J. Org. Chem. 69 (2004) 25, 8643-8651; Dep. Chem. Biochem., Univ. Mo., St. Louis, MO 63121, USA; Eng.) -Jannicke 20-181

Enantioselective Inhibition of Microbial Lipolytic Enzymes by Nonracemic Monocyclic Enolphosphonate Analogues of Cyclophostin

“…The methods employed were adapted to asymmetric synthesis from the recently reported syntheses of racemic monocyclic analogues 3 ( α )/ 3 ( β ) (Scheme ). First, cross metathesis reaction of the ( R ) or ( S ) 1-(dimethoxyphosphoryl)allyl methyl carbonate 4 with 1-dodecene, using Grubbs second generation catalyst with copper(I) iodide as cocatalyst, , gave the precursor carbonates 6 ( R ) and 6 ( S ), respectively, in good yields (70–79%) as mixture of E and Z isomers in 14:1 ratio (Scheme ). The absolute configurations of the 1-(dimethoxyphosphoryl)allyl methyl carbonates 4 ( R ) and 4 ( S ) were unambiguously assigned by conversion to the well-characterized enantiomers of ( E )-1-(dimethoxyphosphoryl)-3-phenylallyl methyl carbonate 5 ( R ) and 5 ( S ) by Grubbs cross metathesis with styrene.…”

“…Furthermore, the UV absorbing enantiomers of 5 were easily separable on a chiral stationary phase, allowing the enantiomeric excess (>95% ee) to be determined. 24,25 With the fact that both the absolute configuration on the asymmetric carbon and the enantiomeric excess of the starting phosphonate are preserved upon cross metathesis reaction, 22 the resulting phosphono allylic carbonate 6 therefore displays the same (R) configuration with comparable ee to the carbonate 4(R). Palladium(0)-catalyzed reaction of the carbonates 6 with methyl acetoacetate gave the vinyl phosphonates 7 as a 1:1 diastereoisomeric mixture related to the new acetoacetate carbon stereocenter thus formed.…”

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.…”

“…Mobile phase solvents were prepared from HPLC‐grade CH 3 CN and H 2 O containing 0.1% TFA. General procedures for the preparation of racemic and enantiomerically enriched dimethyl (1‐hydroxyallyl)phosphonates 1a , 1b , 1c and ( E )‐dimethyl (1‐hydroxyl‐3‐phenylallyl)phosphonates 2a , 2b , 2c have been previously reported . Compounds 3 were prepared by hydrophosphonylation from the appropriate aldehyde and dimethyl phosphite and were obtained from our in‐house collection .…”

“…The ability to selectively prepare either enantiomer of 1b has led to the synthesis of nematocidal oxylipids and antimicrobial cyclophostins . Palladium coupled cross‐metathesis reactions have been employed for transfer of chirality of α‐hydroxyallylphosphonates to the gamma position of the carbon chain, resulting in enantioselective synthesis of cyclopentanone substituted phosphonate, cyclic ethers, and (S)‐tumerone . Enantiomerically pure dimethoxyphosphorylallyl methyl carbonates 1b can be prepared on a multigram scale from readily available precursors by coupling an asymmetric Pudovik reaction with enzyme catalyzed kinetic resolution .…”