Antipodal diastereoselectivity has previously been noted
in dihydroxylation reactions under Upjohn and Donohoe
conditions in reactions of substrates that are conforma-
tionally constrained (often cyclic) and which invariably
possess an allylic hydrogen-bond-donor functionality.11,18
In these systems, the opposing diastereofacial selectivities
of these dihydroxylation procedures are therefore ascribed
to the ability of the OsO4/TMEDA complex to participate
as a hydrogen-bond acceptor,11 while reaction under
Upjohn conditions typically proceeds under steric or
stereoelectronic control.19 In contrast, the diastereofacial
selectivities of both of these dihydroxylation procedures
when applied to conformationally more labile systems are
generally much lower.20 Therefore, not only are the high
levels of diastereoselectivity elicited in both the dihydrox-
ylation reactions of R-hydroxy-β-amino ester 6 remark-
able, but also the diastereodivergence, especially given that
diastereoselective dihydroxylation of β-amino ester 5
and R-hydroxy-β-amino ester 6 with OsO4/TMEDA
(Donohoe conditions), demonstrates that the presence
of the (homoallylic) R-hydroxyl group is not a prere-
quisite for determining the diastereofacial selectivity.
The potential for elaboration of the amino triols result-
ing from these highly diastereoselective and stereodiver-
gent dihydroxylation reactions to the corresponding
3,6-dideoxy-3-aminohexoses was next explored. Treatment
of 11 with TFA resulted in cyclization to give lactone 12 as
a single diastereoisomer (>99:1 dr) in 73% isolated yield.
The relative configurations of the stereocenters around the
Scheme 3. Dihydroxylation of R-Hydroxy-β-amino Ester 6
1
proceeded with antipodal diastereofacial selectivity to give
triol 11 in 95:5 dr, and in 81% isolated yield as a single
diastereoisomer (>99:1 dr) after chromatographic purifi-
cation (Scheme 3). The relative configuration within 11
was unambiguously established by single crystal X-ray
diffraction analysis,17 with the absolute (2R,3R,4S,5S,RR)-
configuration being assigned from the known configura-
tion of the (R)-R-methylbenzyl stereocenter. In this case,
therefore, the presence of the R-hydroxy group within
R-hydroxy-β-amino ester 6 not only reverses the (modest)
diastereofacial bias noted upon dihydroxylation of β-amino
ester 5 but also confers excellent diastereoselectivity on the
dihydroxylation process.
lactone ring within 12 were assigned by H NMR NOE
analysis, with the absolute (3R,4S,5S,10S,RR)-configura-
tion of 12 being assigned from the known absolute config-
uration of the (R)-R-methylbenzyl stereocenter (and the
(11) Donohoe, T. J.; Moore, P. R.; Waring, M. J.; Newcombe, N. J.
Tetrahedron Lett. 1997, 38, 5027. Donohoe, T. J.; Blades, K.; Moore,
P. R.; Winter, J. J. G.; Helliwell, M.; Stemp, G. J. Org. Chem. 1999, 64,
2980. Donohoe, T. J. Synlett 2002, 1223. Donohoe, T. J.; Blades, K.;
Moore, P. R.; Waring, M. J.; Winter, J. J. G.; Helliwell, M.; Newcombe,
N. J.; Stemp, G. J. Org. Chem. 2002, 67, 7946.
(12) Davies, S. G.; Smyth, G. D.; Chippindale, A. M. J. Chem. Soc.,
Perkin Trans. 1 1999, 3089.
(13) Treatment of diol 7 with TFA-promoted lactonization to give 8
as the major product. The absolute configuration within lactone 8 has
previously been unambiguously established by conversion to methyl
D-3-epi-daunosaminide hydrochloride; see ref 12.
(14) Crystallographic data (excluding structure factors) have been
deposited with the Cambridge Crystallographic Data Centre as supple-
mentary publication number CCDC 814127.
(15) VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett.
1976, 17, 1973.
(16) Crystallographic data (excluding structure factors) have been
deposited with the Cambridge Crystallographic Data Centre as supple-
mentary publication number CCDC 805287.
(17) Crystallographic data (excluding structure factors) have been
deposited with the Cambridge Crystallographic Data Centre as supple-
mentary publication number CCDC 805286.
(18) A homoallylic hydroxyl group proved to be only a modest
directing group for the OsO4/TMEDA complex in a range of cyclic
systems, with generally poor diastereodivergency between the two
dihydroxylation protocols being noted, see: Donohoe, T. J.; Mitchell,
L.; Waring, M. J.; Helliwell, M.; Bell, A.; Newcombe, N. J. Org. Biomol.
Chem. 2003, 1, 2173.
(19) Cha, J. K.; Christ, W. J.; Kishi, Y. Tetrahedron Lett. 1983, 24,
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Cha, J. K.; Kin, N.-S. Chem. Rev. 1995, 95, 1761.
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S. G.; Nicholson, R. L.; Price, P. D.; Roberts, P. M.; Savory, E. D.;
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(9) Towson, J. C.; Weismiller, M. C.; Lal, G. S.; Sheppard, A. C.;
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