Optically Active Alkylphosphonates

Up to now, our study on all these chiral 1-substituted alkylphosphonates only limited to their racemic forms. Considering the importance of chirality for herbi-cidal active, it would be very interesting to examine the contribution of the optical counterparts to their biological activity. As our work aimed at the herbicidal effect of the optically active isomer of chiral 1-substituted alkylphosphonates, we first attempted to set up an efficient method to prepare the isomers of 1-substituted alkylphosphonates with optical activity. 

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The ready alkylation of sodium phosphonate carbanions with chloro- or bromoacetates in THF provides a useful access to dialkyl 2-(alkoxycarbonyl)ethylphosphonates bearing a variety of alkyl, aryl, cyano, keto, or phosphoryl groups at the cx-carbon (Scheme 8.43). By using a chiral auxiliary, the alkylation of phosphorus-stabilized benzylic carbanions with bromoacetate proceeds with high diastereoselectivity to provide an easy access to optically active alkylphosphonic acids. ... 

The characteristics and differences of enantiomers of these alkylphosphonates lA and IC will be examined on the basis of the study of herbicidal activity, crop safety, toxicity and environmental safety. At this stage, several optically active alkylphosphonates in the lA and IC series were tested for their enantiomeric selectivity in herbicidal activity and acute aquatic toxicity. In this section, the synthesis and herbicidal activity of optically active alkylphosphonates lA and IC are introduced. The differences of enantiomers of these alkylphosphonates lA and IC together with their racemates are discussed. 

In order to investigate enantiomeric selectivity of chiral alkylphosphonates in the lA and IC series, the herbicidal activity of several optically active alkylphosphonates as typical compounds were evaluated by a preliminary bioassay. 

In the asymmetric addition to alkenylphosphonate 33 (Eq. 2) [25], the yield is dependent on the amount of water present. The combination of boroxine and water (1 equiv. relative to boron) gave a high yield of the desired product 34, with 96% enantiomeric excess. The alkylphosphonate 34 can be used as a chiral building block for the synthesis of optically active alkenes, using a Horner-Emmons type of reaction. 

It is important to point out that all these substituted alkylphosphonates lA-IJ and IVC-IVE have a chiral carbon in their molecular skeletons, which contains different optically active isomers. It was well demonstrated that the absolute... 

Scheme 1.34 Several kinds of optically active 1-(substituted phenoxyacetoxy)alkylphosphonates...

All substituted alkylphosphonates lA-IJ and IVC-IVE studied or reported previously were only based on their racemic forms. Considering the importance of chirality for herbicidal active, the synthesis and the biological activities of their optical counterparts would be very important. The methods of asymmetric synthesis of both chiral 1-hydroxyphosphonates and cyclic 1-hydroxy phosphonates, and several optically active 1 -(substituted phenoxyacetoxy)alkylphosphonates were hence set up. So far, several series of optically active 1-(substituted phenoxyacetoxy) alkylphosphonates including lA, IC, IE, IF series were prepared (Scheme 1.34) and their biological activities were evaluated. Their asymmetric synthesis, enantiomeric selectivity in herbicidal activity, acute aquatic toxicity, and SAR discussion are summarized in Chap. 6. 

Two asymmetric synthesis strategies including synthetic routes 1 and 2 were considered to prepare the optically active 1-(substituted phenoxyacetoxy)al-kylphosphonates including molecular skeletons of open-chain phosphonates lo and cyclic phosphonates IV. In synthetic route 1, optically active 1-(substituted phen-oxyacetoxy)alkylphosphonates lo or IV could be prepared by the condensation of substituted phenoxyacetyl chlorides MS and optically pure 1-hydroxyalkylphosph-onates M2 or cyclic 1-hydroxyaIkylphosphonates IVB, respectively (Scheme 6.1). 

As stated in Chap. 2, some chiral 1-(substituted phenoxyacetoxy)alkylphosphonates lA, IE, and IF exhibited significant post-emergence herbicidal activity against dicotyledons, but the examination of herbicidal activity was only limited their racemic forms. It would be very interesting to examine the contribution of optical active isomers in their herbicidal activity. 

In order to explore the possible difference between two enantiomers in herbicidal activity, a set of experiments was performed to evaluate optically active 1-(substituted phenoxyacetoxy)alkylphosphonates lA, IE, and IF. The herbicidal bioassay was carried out according to the method mentioned in Chap. 9. The influences of molecular chirality on herbicidal activity are discussed as follows. 

This method using 1,2-unsaturated phosphonates could be applied to synthesize some optically active [-(substituted phenoxyacetoxy (alkylphosphonates, when an alkyl group as was attached to the chiral carbon in the parent structure lo. In this case, several optically active [-(substituted phenoxyacetoxy)alkylphosphonates lA and IC with methyl or ethyl as could be synthesized by the asymmetric hydrogenation of the corresponding prochiral 1,2-unsaturated phosphonates. 

Scheme 6.11 Synthises of optically active l-(substituted phenoxyacetoxy)alkylphosphonates lA and IC...

Based on the optimization for reaction conditions, some optically active (5)-l-(substimted phenoxyacetoxy)alkylphosphonates IC and IA-8 were prepared by using 1 mol% of in situ generated [Rh(COD)2]BF4/(R,R)-Me-DuPhos catalyst in MeOH at 4 atm of H2 for 12 h at 18 °C. The results are listed in Table 6.18. 

This rhodium-catalyzed hydrogenation exhibited a broad substrate scope and excellent levels of enantioselectivity from 91 to 96 % ee. The (/ )- -(substituted phenoxyacetoxy)alkylphosphonates IC and IA-8 were also achieved by using (S,S)-Me-DuPhos as a ligand. A detailed synthetic procedure for optically active IC and IA-8 is introduced in the Sect. 9.1.34 of Chap. 9. 

The structure of the target compounds were characterized by and C NMR, IR, MS and confirmed by elementary analysis. In order to determine the absolute configuration of optically active l-(substimted phenoxyacetoxy)alkylphosphonates IC, (5)-IC-22 was simply deprotected using K2CO3 in MeOH at room temperature for 2 h to afford the corresponding optically active 1-hydroxyalkylphosphonates M2-18, as shown in Scheme 6.13. 

The above results showed that the rhodium-catalyzed hydrogenation of 1-substituted vinylphosphonates exhibited a broad substrate scope and excellent levels of enantioseleclivity, therefore, this method could be applied to prepare other optically active 1-(substituted phenoxyacetoxy)alkylphosphonates, such as other optically active compounds in the lA and IC series. 

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