C O M M U N I C A T I O N S
99) were observed in the cases of the most electron-withdrawing
4-nitro and 4-carbomethoxy systems 9 and 11. The reactions were
complete at 50% conversion in 6-13 h, leading to recovery of the
(S)-enantiomers 9 and 11 in g99% ee, respectively
To elucidate the effect of functional group compatibility,
3-methoxy and 3-hydroxyphenyl analogues 12 and 13 were also
examined. It was found that both the asymmetric oxidations work
well with excellent enantioselectivity (g99% ee, krel > 99) albeit
with slightly prolonged reaction time (40-48 h). In addition, no
discernible oxidation or homocoupling of the phenolic moiety was
observed. To gain further insights into the steric and electronic
factors of the substrates bearing ortho substituents in the R-aryl
groups, 2-methoxy- and 2-bromophenylmethyl-R-hydroxyphospho-
nates 14 and 15 were chosen as representative examples. The
oxidations proceeded at significantly slower rates (90 and 150 h)
in both cases. In the former case, the reaction was stopped at 50%
conversion (90 h), leading to the recovery of (R)-14 in 99% ee (krel
>99). In marked contrast, a very poor reaction rate and selectivity
factor resulted from the 2-bromophenyl analogue 15 (33% ee,
krel ) 3) at 49% conversion. The severe Coloumbic repulsion
between the lone pair electrons on both Br groups (i.e., 2-BrC6H4
in the substrate and the C3-Br group in the catalyst template) may
be responsible for the erosion of enantiocontrol.
Figure 1. Proposed reactivity difference for the diastereomeric adducts
22 and 22′ formed between vanadyl(V) methoxide 4 and racemic 1.
salicylidene-L-tert-leucine-based vanadyl(V) methoxide complexes,
effecting highly enantioselective and chemoselective aerobic oxida-
tions at ambient temperature. Judicious selection of the C3,C5
substituents in the template allows us to access the optimal vanadyl-
(V) methoxide as the 3,5-dibromo analogue 4. The current protocol
works well for a diverse array of R-aryl- and R-heteroaryl-R-
hydroxyphosphonates, auguring well for its potential applications
in biomedicinal chemistry.
Acknowledgment. We thank the National Science Council of
Taiwan for a generous financial support of this research.
Upon changing the nature of the R-aryl groups from phenyl,
1-naphthyl, to 2-thiophenyl, we observe increasing enantiocontrols
(krel > 99) in the aerobic oxidation processes except in the 2-furanyl
case (krel ) 95) presumably due to the competing coordination of
the oxygen in the 2-furanyl group. Notably, the 1-naphthyl analogue
16 is the slowest-reacting substrate (60 h) among the four cases.
Furthermore, substrates bearing allylic R-substituted systems such
as 19 (R ) trans-cinnamyl) and 20 (R ) trans-crotonyl) were also
examined. Notably, the alkene moieties in 19 and 20 remain intact
without any intervening epoxidation. Both the reactions were
complete in less than 90 h at 49% conversion, leading to (S)-19
and (S)-20 in 95-96% ee (krel > 99). The slower oxidation rate in
19 may be due to the larger steric effect of the phenyl group in the
cinnamyl moiety as compared to methyl group in the crotonyl
moiety of 20. On the other hand, the substrate bearing R-phenyl-
ethynyl group (i.e., 21) is also fairly reactive, and the selectivity
factor for its asymmetric oxidation is 11.
The substrate class was further extended to dibenzyl R-hydroxy-
phosphonates possessing R-alkyl groups of varying steric demands.
Unfortunately, our preliminary study showed that negligible asym-
metric inductions were effected for the substrates bearing R-methyl,
benzyl, i-propyl, and tert-butyl groups at 50% conversion. Never-
theless, the facile conversion of 19 and 20 to the corresponding
saturated analogues by chemoselective hydrogenation8a allows one
to access optically pure R-hydroxyphosphonates possessing R-alkyl
groups.
Supporting Information Available: Characterization data for the
vanadyl(V) methoxide complexes 2-4, kinetic resolution products 1
and 5-21, and oxidation products 5′-21′. This material is available
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On the basis of the structural study of an N-benzylmandelamide
catalyst adduct in the asymmetric oxidation of R-hydroxyamides,14
we propose that the thermodynamically more stable diastereomeric
adduct 22 as shown in Figure 1 is a slower-reacting species toward
oxidation. On the contrary, the sterically more encumbered dia-
stereomeric adduct 22′ is faster reacting for the subsequent R-proton
elimination process leading to R-ketophosphonate-1′ with concomi-
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(16) The asymmetric oxidations of the corresponding dimethyl- and diethyl
phenylhydroxymethylphosphonates by catalyst 4 led to lower selectivities
(ksel ) 49 and 41).
In conclusion, we have documented a new kinetic resolution
process for R-hydroxyphosphonates with the assistance of N-
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