Angewandte
Chemie
when compared to 3q) thus directed the stereoselectivity
towards the trans carbonate.
Interestingly, the catalyst systems based on 1 or 2 tolerate
a number of useful functional groups, including ether (3b),
oxirane (3d, 3r), endo- and exo-cyclic double bonds (3 f, 3j,
and 3q), trimethoxysilyl (3l), and ester (3m) moieties.
Remarkably, the tetracyclic carbonate product 3d was
obtained from the corresponding bis(oxirane) derivative
without affecting the other epoxide unit and thus provides
clean access to a bifunctional intermediate.[20] The prepara-
tion of the substituted bicyclic carbonates 3h–3m is note-
worthy; for these products, analysis by NMR spectroscopy
was more challenging owing to the presence of three
stereocenters in these molecules; however, for a representa-
tive example, we were able to separate the set of diastereo-
isomers (3m) by column chromatography (Figure S1) and
analyzed one of these (the minor isomer 3ma; ester group
equatorial) by X-ray analysis.[21] The other, major diastereo-
isomer 3mb (ester group axial) was isolated as a viscous liquid
(for details, see the Supporting Information). The combined
data was used to assign the configurations of both isomers
that are present in the isolated product and also confirmed the
cis nature of the carbonate unit.
The next step involved the formation of the cis-diol
products from the carbonate precursors 3a–3r by treatment
with a suitable base. Most diol targets were readily formed in
good to excellent yields (Figure 2). The deprotection of
carbonate 3l was complicated as the resulting product was
difficult to analyze because it was formed as a mixture of
rather insoluble components. It is likely that the silyloxy
fragment gave rise to insoluble gels through cross-hydrolysis.
However, basic deprotection of 3m could be carried out with
a weaker base (K2CO3), selectively giving cis diol 4m in high
yield (80%). The yield of tetraol 4h (40%) was lower than
generally observed for the other diol products as its isolation
was more difficult. The oxirane group in 4d (89%) surpris-
ingly remained unaffected under basic conditions showing
again its high stability. The relative cis configuration in these
diols was further supported by X-ray analysis of diol
derivatives 4c and 4q (Figure 2, insets).[21] These results
clearly show the generality of this approach towards poten-
tially useful cyclic cis-diol scaffolds.
Figure 2. Formation of the cis-diol products 4a–4r from precursors
3a–3r. Reaction conditions: NaOH (5 equiv) in H2O, 3 h, RT. For 4m,
K2CO3 (3 equiv in MeOH) was used. Yields of isolated products are
given. Unless otherwise specified, the diol configuration was >98%
cis. Reported d.r. values were determined by 1H and/or 13C NMR
spectroscopy and relate to the relative configuration of the carbonate
unit and the C6 ring substituent, except for in the case of 4r. Further
details for the analysis of 4r are provided in the Supporting Informa-
tion. Fg=functional group.
as a temporary protecting group. These attractive features
combined with the simple operational characteristics of this
catalytic method (no special precautions required) may give
a valuable starting point for the synthesis of tri- and even
tetra-substituted cis-diol synthons and may stimulate the
advancement of alternative asymmetric preparations of this
important class of organic compounds.
In summary, we have presented an efficient and practical
method towards the formation of cyclic cis diols with ample
scope and functional group tolerance. These synthons were
afforded in high yield and (diastereo)selectivity with the
preparation of their cis-configured organic carbonate precur-
sors being the key to success. The selective formation of cyclic
carbonate versus poly(carbonate) (see Scheme 1) from the
cyclic epoxides suggests that two consecutive SN2 reactions
take place, thus preserving the initial relative configuration of
the two carbon centers in the oxirane unit and leading to cis-
diol formation after basic treatment. This double-inversion
mechanistic pathway has been independently studied and
proposed by various groups.[22]
Experimental Section
Typical procedure for organic carbonate formation: A 30 mL stainless
steel autoclave was charged with the epoxide precursor (0.5 g) along
with the correct loadings of catalyst, co-catalyst, and MEK (0.5 mL).
The autoclave was subjected to three cycles of pressurization and
depressurization with CO2 (0.5 MPa, 5 bar) before final pressure
stabilization (1.0 MPa, 10 bar). The autoclave was sealed and heated
to the required temperature for 18–66 hours. Afterwards, an aliquot
of the crude reaction mixture was collected and analyzed by 1H NMR
spectroscopy to determine the reaction conversion (solvent: CDCl3).
Then, the product was isolated/purified by filtration through a silica
pad or by column chromatography on silica gel.
The current approach is characterized by the use of easily
accessible, air-stable, and powerful catalysts that are derived
from aminotriphenolate complexes and incorporate inexpen-
sive and earth-abundant metals, and the use of carbon dioxide
Typical deprotection procedure: The respective carbonate
(1 mmol) was dissolved in NaOH (5 mL, 1m). The mixture was left
stirring for 2–3 hours until complete dissolution of the starting
material and formation of a homogeneous, pale yellow solution was
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
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