thiometaphosphonate 11 (Scheme 3); this, being planar (trig-
onal) and open to attack at either face by the alcohol, will give
the product 12 as the racemate. In this case, the alcohol does not
bond to phosphorus in the rate-limiting step; the unimolecular
pathway will therefore acquire increasing relative importance as
the bimolecular pathway becomes less favourable, i.e. as the
bulk of the alcohol nucleophile increases.
stereochemistry observed with 9 does, we think, support the
view of Jankowski and Quin that metaphosphate intermediates
are involved in the reactions of related amidic acids with
alcohols.
Notes and references
As a test of mechanistic duality the dependence of the
stereochemistry of reaction on the concentration of the
nucleophile was examined. With lower concentrations of
alcohol the non-stereospecific unimolecular pathway should
assume greater importance while higher concentrations should
favour the stereospecific bimolecular pathway. In the event,
reducing the concentration of MeOH or PriOH to 0.05 mol
dm23 gave the product 12 with an enantiomer ratio of 70:30
(R = Me) or 51:49 (R = Pri) and increasing it to 0.80 mol
dm23 gave an enantiomer ratio of 98:2 (R = Me) or 58.5:14.5
(R = Pri). With ButOH the product was practically racemic at
all alcohol concentrations, implying a negligible contribution
from stereospecific bimolecular reaction.§
† The free amidic acid 9 begins to decompose as soon as it is dissolved in
an aprotic solvent. All operations involving solutions of 9 were conducted
with cooling and executed as rapidly as possile. The value of [a]D must be
considered approximate.
‡ The products 12 were isolated from reactions allowed to proceed to 690%
completion and were purified and characterised as their dicyclohex-
ylammonium salts [1H and 31P NMR and IR spectroscopy; mass
spectrometry (ES and 2FAB) including accurate mass measurement].
§ The 31P NMR signals for the diastereoisomeric salts of 12 (R = But) were
not quite fully resolved and in this case the enantiomer ratio is not as precise
(±2% in each component) as for 12 (R = Me) or 12 (R = Pri).
¶ With PriOH and ButOH the substrate 9 and product 12 (salts with
PhMeCHNH2) accounted for only ~ 90% of the 31P{1H} NMR spectrum.
The most prominent of the minor peaks were doublets (JPP 39 Hz) at ca.
dP(C6D6) 67 and 62.5, most likely due to the pyrophosphonate
PhP(S)(O2)OP(S)(NHBut)Ph [m/z (2ES) 384] resulting from reaction of 9
with itself instead of with the alcohol (cf. ref. 3, 5 and 6).
In one case—the 0.20 mol dm23 MeOH reaction—the
dependence of the stereochemistry on the temperature was also
examined. Relative to the reaction at 30 °C (enantiomer ratio of
product 12, 88:12), reducing the temperature increased the
overall stereospecificity of reaction (enantiomer ratio 96:4 at
0 °C) and increasing the temperature reduced it (72:28 at
60 °C). This implies a more ordered transition state for the
stereospecific pathway, consistent with it being of higher
molecularity.
That the monomeric thiometaphosphonate 11 plays an
important part in the reactions of 9 with alcohols seems certain,
but the nature of the competing stereospecific process is less
clear. It shows the characteristics expected of an associative
SN2(P) reaction but so might a dissociative reaction if it
involves preassociation of the substrate and nucleophile.9 Then
the nucleophile will already be in place when the zwitterion 10
decomposes and the thiometaphosphonate is formed. This may
now be trapped stereoselectively, by attack of the alcohol on one
face before the leaving group (H2NBut) has diffused away from
the other. The reactions of 9 with alcohols may therefore
proceed entirely via the thiometaphosphonate, in a free
(liberated) state or associated with the nucleophile. The
1 V. M. Clark, G. W. Kirby and A. Todd, J. Chem. Soc., 1957, 1497; J. G.
Moffatt and H. G. Khorana, J. Am. Chem. Soc., 1961, 83, 649; A. Todd,
Proc. Chem. Soc. London, 1962, 199.
2 N. K. Hamer, J. Chem. Soc., 1965, 46; V. M. Clark and S. G. Warren,
J. Chem. Soc., 1965, 5509.
3 L. D. Quin and S. Jankowski, J. Org. Chem., 1994, 59, 4402.
4 S. Jankowski, L. D. Quin, P. Paneth and M. H. O’Leary, J. Am. Chem.
Soc., 1994, 116, 11675.
5 L. D. Quin, P. Hermann and S. Jankowski, J. Org. Chem., 1996, 61, 3944;
S. Jankowski, L. D. Quin, P. Paneth and M. H. O’Leary, J. Organomet.
Chem., 1997, 529, 23.
6 G. S. Quin, S. Jankowski and L. D. Quin, Phosphorus Sulfur Silicon,
1996, 115, 93.
7 S. Freeman and M. J. P. Harger, J. Chem. Soc., Perkin Trans. 2, 1988,
81.
8 G. R. J. Thatcher and R. Kluger, Adv. Phys. Org. Chem., 1989, 25, 99.
9 W. P. Jencks, Acc. Chem. Res., 1980, 13, 161; Chem. Soc. Rev., 1981, 10,
345.
Communication 9/02222H
932
Chem. Commun., 1999, 931–932