COMMUNICATIONS
K. Sakamoto, Y. Hamada, A. Mitsutome, J. Otera, Tetrahedron 1999,
55, 2899; h) cationic organotin dimer: K. Sakamoto, Y. Hamada, H.
Akashi, A. Orita, J. Otera, Organometallics 1999, 18, 3555.
After pivalation, it is often difficult to separate the pivalate
esters from the remaining pivalic anhydride by column
chromatography because of their similar polarity. In our
protocol, methanol was added after consumption of the
alcohol in order to convert the remaining anhydride to methyl
pivalate. Bi(OTf)3 effected the methanolysis of the pivalic
anhydride quantitatively at 508C where methanol as well as
CH2Cl2 was used without purification. The product pivalate
esters could be readily isolated from the crude product
mixture by simple filtration through a thin pad of silica gel
with hexane as the solvent. The pivalate esters thus obtained
were of sufficient purity. Methanolysis of the excess anhydride
in the presence of Sc(OTf)3 or Me3SiOTf[9] under the same
reaction conditions was not complete. Apparently, Bi(OTf)3 is
superior to the other metal triflates.
The pivalation of a mandelic ester proceeded with complete
retention of the configuration (entry 8). Furthermore, this
pivalation method was applicable to a sugar having an acetal
as protecting group, which can not survive in the Me3SiOTf
protocol (entry 10).[2e] The acylation of a nucleoside with
Bi(OTf)3/(tBuCO)2O led quantitatively to the triply pivalated
nucleoside despite the existence of an amide function
(entry 11). In all the trials for pivalation, CH2Cl2 could be
used directly from the bottle without purification.
[3] A. Orita, A. Mitsutome, J. Otera, J. Org. Chem. 1998, 63, 2420.
[4] Both Sc(OTf)3 and Sc2O3, which is a starting material for the triflate,
can be purchased from Aldrich. The price of Sc2O3 is $159.9 for 5 g
(72.5 mmol). Bi2O3, the starting compound for Bi(OTf)3, is also
commercially available, and its price is cheaper: $187.1 for 250 g
(1.07 mol). Bi(OTf)3 is accessible alternatively by the reaction of Ph3Bi
($57.3, 25 g, 56.8 mmol) and TfOH. In this study, Bi(OTf)3 was
prepared as a tetrahydrate according to this procedure. M. Labrouil-
lere, C. Le Roux, H. Gaspard, A. Laporterie, J. Dubac, Tetrahedron
Lett. 1999, 40, 285, and references therein.
[5] a) J. R. Desmurs, M. Labrouillere, C. Le Roux, H. Gaspard, A.
Â
Laporterie, J. Dubac, Tetrahedron Lett. 1997, 38, 8871; b) S. Repichet,
C. Le Roux, J. Dubac, J. R. Desmurs, Eur. J. Org. Chem. 1998, 2743.
[6] B. Garrigues, F. Gonzaga, H. Robert, J. Dubac, J. Org. Chem. 1997, 62,
4880.
[7] H. Laurent-Robert, C. Le Roux, J. Dubac, Synlett 1998, 1138.
[8] For the acetylation of the 12a-hydroxy group of methyl cholate,
prolonged heating in Ac2O/pyridine or addition of an excess amount of
4-pyrrolidinopyridine is needed: G. Höfle, W. Steglich, Synthesis 1971,
619.
[9] A similar methanolysis was reported in the Me3SiOTf protocol,[2e] but
we could not reproduce this result.
In conclusion, a powerful and versatile acylation method
has been developed based on Bi(OTf)3 and acid anhydride.
This method has several advantages: the catalyst is cheap and
easy to handle, a variety of primary, secondary, and tertiary
alcohols can be transformed, and the operations are simple
because neither dry reaction conditions nor lowering of the
reaction temperature for tertiary alcohols is required. The
reactivity of Bi(OTf)3 can be modified, if necessary, by
changing the coordinating character of the cosolvent.
Remarkable In/out Inversions at Bridgehead
Phosphorus Atoms**
Roger W. Alder* and David Read
Phosphanes are more pyramidal and invert much less
readily than amines. The C-P-C angles for trialkylphosphanes
are typically about 1008 and they have inversion barriers
around 150 kJmolÀ1,[1] hence temperatures of well over 1008C
are required for the racemization of chiral phosphanes. In
medium-sized bicyclic ring systems[2] in/out isomerism[3] is
possible, and bridgehead nitrogen atoms are known to adopt
whichever arrangement is more stable.[4] Thus 1,4-diazabicy-
clo[2.2.2]octane is out,out, 1,6-diazabicyclo[4.4.4]tetradecane
is in,in,[5] 1,5-diazabicyclo[3.3.3]undecane has nearly planar
nitrogen atoms,[6] and 1,9-diazabicyclo[7.3.1]tridecane is in,
out.[7] We expected that in related phosphorus compounds
in,out and in,in isomers would become preferred to out,out
isomers as the ring systems became larger, and also that
unstable isomers might be isolated as a result of the high
inversion barriers for phosphanes. We find however that these
barriers are much lower than expected. We focus here on a
Experimental Section
Representative procedure for pivalation (entry 8, Table 3): A CH2Cl2
solution (3 mL, unpurified and wet) of methyl (R)-mandelate (166.2mg,
1.0 mmol) and (tBuCO)2O (299.4 mg, 1.5 mmol) was stirred at 258C in the
presence of Bi(OTf)3 (21.8 mg, 3.0 mol%, calculated as the tetrahydrate)
for 4 h. MeOH (10 mL, unpurified and wet) was added and the mixture was
stirred at 508C for 7 h. The mixture was passed through a pad of silica gel
with hexane as the solvent and the filtrate was evaporated. Ethyl acetate
(30 mL) was added to the crude product, and the organic layer was washed
three times with aqueous NaHCO3 and dried (MgSO4). Evaporation
furnished the pure pivalate ester (97% yield, 242.8 mg).
Received: April 14, 2000
Revised: June 5, 2000 [Z14996]
[1] W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, 3rd
ed., Wiley, New York, 1999, p. 150.
[*] Prof. R. W. Alder, Dr. D. Read
School of Chemistry
[2] Acetylation of alcohols with Ac2O in the presence of a) DMAP: W.
Steglich, G. Höfle, Angew. Chem. 1969, 81, 1001; Angew. Chem. Int. Ed.
Engl. 1969, 8, 981; b) Bu3P: E. Vedejs, N. S. Bennet, L. M. Conn, S. T.
Diver, M. Gingras, S. Lin, P. M. Oliver, M. J. Peterson, J. Org. Chem.
1993, 58, 7286; c) aminophosphane superbase: B. A. DꢁSa, J. G.
Verkade, J. Org. Chem. 1996, 61, 2963; d) Sc(OTf)3: K. Ishihara, M.
Kubota, H. Kurihara, H. Yamamoto, J. Org. Chem. 1996, 61, 4560;
e) Me3SiOTf: P. A. Procopiou, S. P. D. Baugh, S. S. Flack, G. G. A.
Inglis, J. Org. Chem. 1998, 63, 2342; f) In(OTf)3: K. K. Chauhan, C. G.
Frost, I. Love, D. Waite, Synlett 1999, 1743; g) distannoxane: A. Orita,
University of Bristol
Bristol BS81TS (UK)
Fax : (44)117-9298611
[**] We thank Dr. J. M. Oliva (Institute of Materials Sciences of
Barcelona, CSIC) for the calculations on 12 and 13, the EPSRC for
a
quota studentship to D.R., and the EPSRC National Mass
Spectrometry Service for high-resolution electrospray spectra.
Angew. Chem. Int. Ed. 2000, 39, No. 16
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