Synthesis of Nonracemic Allylic Hydroxy Phosphonates via Alkene Cross Metathesis

Abstract

Allylic hydroxy phosphonates and their derivatives can be interconverted by using cross metathesis with second generation Grubbs catalyst. The absolute stereochemistry of the starting phosphonate is conserved in the product. Cross metathesis reaction of the acrolein-derived phosphonate 2a yields a series of functionalized allylic hydroxy phosphonates. However, the cross metathesis reaction is often accompanied by competing dimerization and alkene migration reactions leading to a reduction in yield. The cinnamaldehyde- and crotonaldehyde-derived phosphonates 2b and 2c were also examined. In general, the metathesis reactions of phosphonates 2b and 2c are considerably slower than those for phosphonate 2a leading to mixtures. Several hydroxyl-protected derivatives of the phosphonate 2a (methyl carbonate 3a, acetate 4a, N-tosyl carbamate 5a, TBDMS 6a, and acetoacetate 7a) undergo metathesis without competing side reactions to give substituted allylic phosphonates in good to excellent yield.

Relay cross metathesis reactions of vinylphosphonates

“…Not surprisingly, the terminal vinylphosphonate 15 underwent smooth cross metathesis with either 1-hexene or 1-heptene using our standard conditions (2% Grubbs II, 4% CuI, CH 2 Cl 2 reflux) [2,26–27] to give the substituted vinylphosphonates 12a or 12b in good yield. In contrast, when vinylphosphonate 12a was subjected to a cross metathesis reaction with methyl acrylate, the cross metathesis product 16a was formed in low yield (~11%) as part of a complex mixture.…”

Trapping hemiacetals with phosphono substituted palladium π-allyl complexes for the synthesis of substituted cyclic ethers

“…using the Grubbs second generation catalyst and copper(I) iodide as co-catalyst to give phosphonate 15 . 1,9 The oxazolidinone auxiliary was reductively cleaved using lithium borohydride 10 to yield the alcohol 16 , which was oxidized using Dess Martin periodinane 11 to the corresponding aldehyde 17 . The aldehyde was cyclized with Pd(PPh 3 ) 4 in aqueous THF at 40°C to give the corresponding hemiacetal, which was acetylated to give the acetoxy acetal 18 .…”

Synthesis of new β- and γ-aminopyrrolidinephosphonates via 1,3-dipolar cycloaddition of substituted vinylphosphonates

“…Subsequent Lindlar hydrogenation (5 wt % Pd on CaCO 3 ) of the latter afforded the cis-c-aminophosphonate 9c in good yield. 16 trans-Aminovinylphosphonate 12c was prepared selectively by cross-metathesis of allyl amide 10 and vinylphosphonate 11 using Grubbs II catalyst (5 mol %) 17 in dichloromethane at reflux for 20 h (Scheme 4). 18 Assignment of the stereochemistry of 9c and 12c was confirmed by the analysis of 3 J coupling constants between H-3 and the phosphorus atom.…”