Morpholinosulfur trifluoride (morph-DAST)-mediated rearrangement in the fluorination of cyclic α,α-dialkoxy ketones toward 1,2-dialkoxy-1,2-difluorinated compounds

Article abstract of DOI:10.1002/adsc.201000466

The deoxofluorination of cyclic α,α-dialkoxy ketones with morpholinosulfur trifluoride (Morph-DAST) resulted in 1,2-dialkoxy-1,2- difluorinated carbo- and heterocyclic compounds. The reaction proceeds via a 1,2-alkoxy migration leading to mixtures of cis-

Full text of DOI:10.1002/adsc.201000466

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DOI: 10.1002/adsc.201000466
Morpholinosulfur Trifluoride (Morph-DAST)-Mediated
Rearrangement in the Fluorination of Cyclic a,a-Dialkoxy
Ketones toward 1,2-Dialkoxy-1,2-difluorinated Compounds
Riccardo Surmont,a,c Guido Verniest,a,d Alex De Groot,b Jan Willem Thuring,b
and Norbert De Kimpea,*
a
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000
Gent, Belgium
Fax : (+32)-(0)9-264-6243; phone: (+32)-(0)9-264-5951; e-mail: norbert.dekimpe@ugent.be
Johnson&Johnson Pharmaceutical Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30,
b
B-2340 Beerse, Belgium
Aspirant of the Research Foundation – Flanders (FWO-Vlaanderen, Belgium)
Postdoctoral Fellow of the Research Foundation – Flanders (FWO-Vlaanderen, Belgium)
c
d
Received: June 16, 2010; Published online: October 26, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000466.
Abstract: The deoxofluorination of cyclic a,a-dialk-
oxy ketones with morpholinosulfur trifluoride
(Morph-DAST) resulted in 1,2-dialkoxy-1,2-di-
fluorinated carbo- and heterocyclic compounds. The
reaction proceeds via a 1,2-alkoxy migration leading
to mixtures of cis- and trans-isomers.
sulfur trifluoride (Deoxo-Fluor) and morpholinosulfur
trifluoride (Morph-DAST) are powerful nucleophilic
fluorination reagents and are frequently used for the
conversion of alcohols to alkyl fluorides and of ke-
tones to gem-difluorides. In earlier research the use of
Morph-DAST was preferred as a result of its higher
thermal stability and its better efficiency in the trans-
formation of 3-alkoxy-4-piperidinones toward 3-
alkoxy-4,4-difluoropiperidines.[6] In some cases, the
use of deoxofluorination reagents can induce the for-
mation of rearranged products. It has been reported
that b-hydroxy-a-amino acid esters rearrange to a-
fluoro-b-amino acid esters[7] and that 2-alkyl-2-amino
ACHTUNGTRENNUNG
Keywords: deoxofluorination; fluorine; ketones; pi-
peridines; rearrangement reactions
The introduction of fluorine into organic compounds alcohols rearrange to 2-alkyl-2-fluoro amines upon
is one of the most simple structural modifications in treatment with Deoxo-Fluor.[8] Other examples con-
order to influence their bioactivity. The unique physi- sist of the neighbouring group participation of the
cal, chemical and biological properties of fluorine as a indole nucleus in the 3,4-migration of 4-indolyl-3-hy-
substituent in organic compounds and the success of droxypiperidines,[9] the ring expansion of bicyclic
fluorinated compounds in medicinal chemistry have epoxy alcohols toward fluorovinyl ethers,[10] the rear-
dramatically intensified the interest and the research rangement of 2-azabicycloACTHNUTRGNE[NUG 2.2.0]hexan-6-ols to 5-
in organofluorine chemistry.[1] Especially fluorinated fluoro-2-azabicyclo-[2.1.1]hexanes[11] and the rear-
piperidines have become increasingly popular as rangement of b-methoxy homoallyl alcohols to a,b-
building blocks toward bioactive compounds. Many unsaturated aldehydes.[12] The DAST-mediated 1,2-mi-
fluorinated azasugars have been prepared for bio- grations, 1,4-migrations and 1,6-migrations of the
chemical investigations.[2] Recently, we introduced anomeric substituent of saccharides, with or without
new entries toward valuable 2-substituted 3,3- ring contraction, are of special importance in biologi-
difluoro
ACHTUNGTRENNUNG
piperidines[3] and 3-aminomethyl-3-fluoropi- cal studies of deoxofluorinated analogues of carbohy-
peridines[4]
using
N-fluorodibenzenesulfonimide drates.[13] In contrast to alcohols, rearrangements of
(NFSI) as electrophilic fluorination reagent and we ketones have been less investigated. Fluorination of
synthesized new 4-aminomethyl-4-fluoropiperidines the C-2 of aldopyranosid-2-uloses with DAST leads to
via a bromofluorination strategy.[5] The commercially gem-difluorination products or gives 2,5-anhydro-1,2-
available deoxofluorination reagents diethylaminosul- difluorofuranoses as a result of a ring contraction re-
fur trifluoride (DAST), bis-(2-methoxyethyl)amino- action with concomitant introduction of fluorine at C-
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Riccardo Surmont et al.
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1 and C-2,[14] and does not lead to 2-alkoxy-1,2-di- contained the cis- and the trans-isomers of 3,4-di-
fluorotetrahydropyrans via a 1,2-alkoxy migration as fluoro-3,4-dimethoxypiperdine 6a. The high value for
1
initially thought.[15] In contrast to the latter monoace- the JF,C coupling constant clearly indicates fluoroalk-
tals of a-ketoaldehydes, the deoxofluorination of oxy substitution for these two vicinal carbons.[17] The
monoacetals of 1,2-diketones was not investigated 19F NMR spectrum of the mixture revealed eight sig-
before and it was decided to further investigate this nals, which were assigned to eight different fluorine
reaction. The products formed through gem-difluori- atoms from four structures, namely the cis- and trans-
nation should be easily hydrolyzed into a,a-difluori- piperidines 6a, each with their two Boc-rotamers. At-
nated ketones. Recently, a convenient synthetic route tempts to N-deprotect piperidine 6a in order to avoid
toward 3,3-difluoro-4-piperidinone 8, a compound the Boc-rotamers and to confirm the structure failed
with high potential in medicinal chemistry, starting and only gave rise to complex reaction mixtures. The
from ethyl bromodifluoroacetate was developed.[16] use of Morph-DAST was preferred above DAST for
Prior to developing this synthetic route, it was consid- its very clean conversion of 3-piperidinone 1a into
ered to evaluate the deoxofluorination of 4,4-dime- 3,4-difluoro-3,4-dimethoxypiperidine 6a. Upon purifi-
thoxy-3-piperidinone 1a.
cation of 3,4-difluoro-3,4-dimethoxypiperidine 6a via
When 4,4-dimethoxy-3-piperidinone 1a was treated silica gel chromatography no decomposition of the
with 3 equivalents of diethylaminosulfur trifluoride or product was observed, resulting in a good yield of
morpholinosulfur trifluoride in dichloromethane at 78%. However, the cis- and trans-isomers could not
À788C, no geminal difluorination toward 3,3-difluoro- be separated via column chromatography. The mecha-
4,4-dimethoxypiperidine 7 was observed after 15 h at nism of the reaction of a,a-dialkoxy ketones with
room temperature. Instead, the obtained product was deoxofluorination reagents is more complex as com-
identified as 3,4-difluoro-3,4-dimethoxypiperidine 6a pared to the reaction with b,b-dialkoxy alcohols be-
as a result of a 1,2-alkoxy migration (Scheme 1).
cause it involves at least two reactions where different
Gas chromatography-mass spectrometry (GC-MS) processes can compete. With respect to the obtained
and LC-MS analyses of the crude mixture of 6a re- ~1:1 mixture of cis- and trans-6a, it cannot be con-
vealed that all starting material was converted and cluded if the fluorine initially attacks the carbonyl
that two compounds were formed having the same group (pathway A), if the 1,2-MeO migration takes
molecular weight. After studying the 13C NMR spec- place in the first stage of the reaction (pathway B) or
trum, which does not show a triplet around 110 ppm if a combination of both pathways occurs.
of about 250 Hz, which is characteristic for a difluoro-
In order to learn more about the generality of this
methylene group, but instead four double doublets fluorination process, various 6-membered ring deriva-
with carbon-fluorine coupling constants of ~230 Hz tives of 3,4-difluoro-3,4-dimethoxypiperidine 6a were
over one bond (1JF,C) and ~35 Hz over two bonds prepared (Scheme 2). The starting materials for fluo-
(2JF,C), it was concluded that the obtained mixture rination, that is, a,a-dialkoxy ketones 1, were easily
Scheme 2. Synthesis of monocyclic 1,2-difluoro-1,2-dime-
thoxylated 6-membered rings.
[a]
Scheme 1. Deoxofluorination of 1-Boc-4,4-dimethoxy-3-pi-
peridinone 1a.
The cis- and trans-isomers of 6d and 6e were separated
via silica gel chromatography.
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Morpholinosulfur Trifluoride (Morph-DAST)-Mediated Rearrangement
obtained from the corresponding ketones 9[18] via an
a-hydroxylation, mediated by iodosobenzene diace-
tate under basic conditions in MeOH toward a-hy-
droxy ketals 10,[19] followed by a clean Swern oxida-
tion.[20] It should be noted that the crude a,a-dialkoxy
ketones 1a–d (purity >95%) were used in the next re-
action step without further purification because com-
pounds 1 are relatively unstable and decompose on
silica gel.[21] In contrast, compound 1e was successfully
purified via recrystallization from diethyl ether. The
reaction of 2,2-dimethoxycyclohexanone 1b with
Morph-DAST yielded a mixture of cis- and trans-1,2-
difluoro-1,2-dimethoxycyclohexane 6b, which immedi-
ately decomposed after silica gel chromatography.
Consequently, the crude compound 6b (92% purity)
was used for spectral analysis and identification. It
seems that the presence of a heteroatom at the a-po-
sition of dialkoxy ketones 1 stabilizes the fluorinated
products 6, probably due to the inductive effect of the
heteroatom slowing down the expulsion of fluoride by
methoxide. The same trend was observed in the clean
deoxofluorination reaction of 4,4-dimethoxydihydro-
2H-pyran-3(4H)-one 1c yielding 97% of 3,4-difluoro-
3,4-dimethoxytetrahydro-2H-pyran 6c as
a stable
compound after silica gel chromatography. Also 4,4-
dimethoxy-1-tosyl-3-piperidinone 1d was successfully
converted to 3,4-difluoro-3,4-dimethoxy-1-tosylpiperi-
dine 6d in 76% yield, occurring as a stable 66:34 mix-
ture of isomers. In the case of this tosylated derivative
6d, the major and the minor isomers were isolated in
a pure form via silica gel chromatography. As all syn-
Figure 1. Assignment of the trans-configuration of the major
isomers of 6d and 6e.
thesized vicinal difluorinated derivatives 6a–d occur action with the hydrogen atoms H-2b, H-5a, H-5b,
as liquids, a final piperidine derivative was synthe- CH3O-10, CH3O-13.
sized bearing a naphthalene-2-sulfonyl substituent at
1
Furthermore, the 2D H-1H NOESY NMR and 2D
nitrogen to obtain crystalline derivatives. The mixture 1H-19F HOESY NMR analysis of the isolated minor
of cis- and trans-3,4-difluoro-3,4-dimethoxypiperidines isomers of 6d and 6e proved that these minor isomers
6e was separated via silica gel chromatography and possess the cis-configuration (Figure 2). The observed
each isomer was recrystallized to obtain colourless NOE interactions of fluorine atom F-11 of the cis-iso-
crystals for the major isomer and white needles for mers (minor) do not change compared to the interac-
the minor isomer.
tions of fluorine atom F-11 of the trans-isomers
Based on detailed 1D NMR spectral analysis, the (major), because both are in equatorial positions. In
configuration of the isolated major and minor isomers contrast, fluorine atom F-14 is now axial in the case
of 6d and 6e could not be assigned with absolute cer- of the cis-isomers (minor of 6d, e) and shows interac-
titude.
tion with the axial hydrogen atoms H-2a and H-6a
Vicinal fluorine-fluorine coupling constants (3JF,F), and with H-5b, CH3O-13. The axial fluorine atom F-
for example, do not follow the Karplus equation and 14 of the cis-isomers (minor) does not couple any-
show different relationships with the dihedral angle more with H-5a, H-2b and CH3O-10.
depending on the substitution pattern of the com-
In order to study the stereoselectivity of the fluori-
1
pound.[22] However, 2D H-1H NOESY NMR and 2D nation, spirocyclic starting materials 1f and 1g were
1H-19F HOESY NMR experiments allowed us to synthesized from the corresponding b-hydroxy-dime-
assign a 3,4-trans relationship between the two fluo- thoxy acetals 10a and 10d by reaction with propane-
rine substituents of the major isomers of 6d and 6e 1,3-diol and ethane-1,2-diol, respectively, followed by
(Figure 1). In these cases, NOE correlations were ob- Swern oxidation (Scheme 3). When 9-Boc-7-oxo-1,5-
served between the equatorial fluorine atom F-11 of dioxa-9-azaspiroACTHNUGTRNEUNG[5.5]undecane 1f was treated with
the trans-isomers (major) and the hydrogen atoms H- Morph-DAST, a 67:33 mixture of cis- and trans- (or
2a, H-2b, CH3O-10, CH3O-13. The equatorial fluorine trans- and cis-) 3,4-dialkoxy-3,4-difluoropiperidine 6f
F-14 of the trans-isomers (major) of 6d, e show inter- was obtained, which is a relatively small improvement
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Scheme 4. Deoxofluorination of 2,2-dimethoxycyclopenta-
none 13.
azaspiroACTHNUTRGNEUG[N 4.5]decane 1g with Morph-DAST resulted in
a ring expansion of the 1,3-dioxolane toward difluori-
nated 1,4-dioxane 6g as a 74:26 mixture of isomers,
which is also a small improvement of the stereoselec-
tivity compared to the fluorination of the monocyclic
1-tosylpiperidine 1d (66:34 mixture). In analogy to
1
the monocyclic compounds 6d and 6e, the 2D H-1H
1
NOESY NMR and 2D H-19F HOESY NMR experi-
ments indicated that the major isomer of the bicyclic
1,4-dioxane 6g is the trans isomer and that the minor
isomer possesses the cis-configuration.
In an attempt to extend the rearrangement method-
ology to 5-membered rings, 2,2-dimethoxycyclopenta-
none 13 was first synthesized from cyclopentanone 11
via hydroxy acetal 12 and subsequent oxidation. The
obtained cyclopentanone 13 was then reacted with
Morph-DAST under the same reaction conditions as
described for the 6-membered rings (Scheme 4). The
reaction proceeded sluggishly, and after 15 h, the re-
action mixture contained 55% of starting material 13
and only 45% of 1,2-difluoro-1,2-dimethoxycyclopen-
tane 14 in a 3:2 ratio of cis/trans isomers (determined
by GC-MS analysis). The slower deoxofluorination of
cyclopentanone 13 as compared cyclohexanone 6b is
most probably due to the increase in torsional strain
when hybridization changes from sp2 to sp3 in the
five-membered ring. This is in accordance with the
quite general higher reactivity of cyclohexanones
during carbonyl addition reactions. In addition, analo-
gously to the unstable 1,2-difluoro-1,2-dimethoxycy-
clohexane 6b, 1,2-difluoro-1,2-dimethoxycyclopentane
14 decomposed rapidly and could not be purified.
Finally the 1,2-migration reaction was evaluated on
acyclic a,a-dimethoxy ketone derivatives (Scheme 5).
Figure 2. Assignment of the cis-configuration of the minor
isomers of 6d and 6e.
Scheme 3. Synthesis of bicyclic 3,4-difluoropiperidines.
[a]
trans-6g (major isomer) and cis-6g (minor isomer) were
separated via silica gel chromatography. RSF3 =Morph-
DAST.
of the stereoselectivity compared to the reaction of
the corresponding monocyclic 1-Boc-4,4-dimethoxy-3-
piperidinone 1a with Morph-DAST (56:44 mixture).
The cis- and trans-isomers of compound 6f could not
be separated via silica gel chromatography. Reaction
Scheme 5. Deoxofluorination of acyclic a,a-dimethoxy ke-
of the bicyclic derivative 8-tosyl-6-oxo-1,4-dioxa-8- tones 15.
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Morpholinosulfur Trifluoride (Morph-DAST)-Mediated Rearrangement
3,3-Dimethoxy-2-butanone 15a and 2,2-dimethoxy- Acknowledgements
1,2-diphenylethanone 15b were treated with Morph-
The authors are indebted to the Research Foundation – Flan-
DAST at room temperature or at reflux temperature
in dichloromethane or benzene for various numbers
of days, but in these cases, no fluorinated reaction
products were obtained.
ders (FWO-Flanders), Ghent University (GOA, BOF) and
Johnson&Johnson Pharmaceutical Research & Development,
Division of Janssen Pharmaceutica NV, for financial support.
In conclusion, we have developed a new method
for 1,2-difluorination of monoacetals of cyclic 1,2-di-
ketones via a Morph-DAST-mediated 1,2-alkoxy mi-
gration reaction. The cis-and trans-1,2-dialkoxy-1,2-di-
fluorinated products are obtained in good yields and
are stable in the case of piperidines and tetrahydro-
pyrans.
References
[1] a) D. OꢂHagan, Chem. Soc. Rev. 2008, 37, 308–319;
b) S. Purser, P. R. Moore, S. Swallow, V. Gouverneur,
Chem. Soc. Rev. 2008, 37, 320–330; c) J. T. Welch, S.
Eswarakrishnan, Fluorine in Bioorganic Chemistry,
John Wiley & Sons: New York, 1991, and references
cited herein; d) K. L. Kirk, Org. Process Res. Dev.
2008, 12, 305–321; e) K. Mꢃller, C. Faeh, F. Diederich,
Science 2007, 317, 1881–1886.
Experimental Section
[2] E. Prell, R. Csuk, Bioorg. Med. Chem. Lett. 2009, 19,
5673–5674.
[3] G. Verniest, R. Surmont, E. Van Hende, A. De We-
weire, F. Deroose, J. W. Thuring, N. De Kimpe, J. Org.
Chem. 2008, 73, 5458–5461, and references cited there-
in.
[4] E. Van Hende, G. Verniest, J. W. Thuring, G. Macdon-
ald, F. Deroose, N. De Kimpe, Synlett 2009, 1765–1768.
[5] G. Verniest, K. Piron, E. Van Hende, J. W. Thuring, G.
Macdonald, F. Deroose, N. De Kimpe, Org. Biomol.
Chem. 2010, 8, 2509–2512.
[6] R. Surmont, G. Verniest, A. De Weweire, J. W. Thuring,
G. Macdonald, F. Deroose, N. De Kimpe, Synlett 2009,
1933–1936.
[7] L. Somekh, A. Shanzer, J. Am. Chem. Soc. 1982, 104,
5836–5837.
[8] C. Ye, J. M. Shreeve, J. Fluorine Chem. 2004, 125,
1869–1872.
[9] D. J. Hallett, U. Gerhard, S. C. Goodacre, L. Hitzel,
T. J. Sparey, S. Thomas, M. Rowley, R. G. Ball, J. Org.
Chem. 2000, 65, 4984–4993.
[10] P. Lakshmipathi, D. Grꢄe, R. Grꢄe, Org. Lett. 2002, 4,
451–454.
General Procedure for the Deoxofluorination of a,a-
Dialkoxy Ketones 1
In a 50-mL flask, 0.50 g (1.93 mmol, 1.0 equiv.) of tert-butyl
4,4-dimethoxy-3-oxopiperidine-1-carboxylate 1a was dis-
solved in 25 mL of dry CH2Cl2. The solution was cooled to
À788C under N2 atmosphere and 1.01 g (5.79 mmol,
3.0 equiv., 0.7 mL) of Morph-DAST (morpholinosulfur tri-
fluoride) was added dropwise. The reaction mixture was al-
lowed to warm to room temperature and was stirred for
15 h. The mixture was diluted with 20 mL of CH2Cl2 and
was carefully quenched with 20 mL of aqueous saturated
NaHCO3 at 08C. The separated aqueous phase was extract-
ed with CH2Cl2 (2ꢁ20 mL) and the combined organic
phases were dried over MgSO4. After filtration, the solvent
was evaporated in vacuo and the concentrate was purified
by flash chromatography over silica gel (hexane/EtOAc 9:1,
Rf =0.38) affording tert-butyl 3,4-difluoro-3,4-dimethoxypi-
peridine-1-carboxylate 6a (yield: 0.42 g, 1.51 mmol; 78%;
cis-trans isomerism: major/minor 56:44 + each isomer con-
sists of two Boc-rotamers). Colourless oil. 1H NMR
(CDCl3): d=1.42 (9H, s, 3ꢁCH3), 1.74–2.10 (2H, m, CH2),
3.11–3.37 (2H, m, NCH2), 3.45, 3.48, 3.50 (2ꢁMeO), 3.53–
3.89 (2H, m, NCH2); 19F NMR (CDCl3): d=À130.6, À132.4,
À132.7, À133.4, À137.0, À137.8, À138.4, À139.2 (2F, 8 ꢁ s,
2ꢁCF); 13C NMR (CDCl3): d=28.2 (3ꢁCH3), 29.5, 30.0,
30.4, 31.3 (4ꢁd, J=27.7 Hz, 27.7 Hz, 27.7 Hz, 23.1 Hz, CH2),
39.5, 40.5 (2ꢁs, NCH2CH2), 43.9, 44.5, 45.6, 45.9 (4ꢁd, J=
45.0 Hz, 38.1 Hz, 35.8 Hz, 35.8 Hz, NCH2CF), 50.4 (m,
MeO), 51.3 (m, MeO); 80.5 (OCq); 109.0 (ddm, J=
231.3 Hz, 26.0 Hz, CF); 110.3 (ddm, J=230.8 Hz, 26.0 Hz,
CF), 154.1, 154.2 (2ꢁs, C=O); IR (ATR): n=2977, 1697 (C=
O), 1421, 1366, 1279, 1233, 1204, 1153, 1102, 1072, 1051, 936,
890, 822, 767, 718 cmÀ1; GC-MS (EI): m/z (%)=281 (M+,
5), 266 (M+ÀMe, 1); 241 (M+À2HF, 1), 222 (16), 210 (13),
206 (17), 190 (12), 186 (23), 176 (9), 161 (22), 146 (16), 131
(56), 118 (23), 104 (4), 93 (11), 89 (10), 76 (15), 57 (100), 42
(18); MS (ES+): m/z (%)=182 (MÀBoc+ +2H+, 5), 186
[11] G. R. Krow, G. Lin, K. P. Moore, A. M. Thomas, C. De-
Brosse, C. W. Ross, H. G. Ramjit, Org. Lett. 2004, 6,
1669–1672.
[12] S. Canova, V. Bellosta, S. Mignani, A. Bigot, J. Cossy,
Org. Lett. 2006, 8, 2091–2094.
[13] a) K. C. Nicolaou, T. Ladduwahetty, J. L. Randall, A.
Chucholowski, J. Am. Chem. Soc. 1986, 108, 2466–
2467; b) K. C. Nicolaou, R. M. Rodriguez, H. J. Mitch-
ell, H. Suzuki, K. C. Fylaktakidou, O. Baudoin, F. L.
van Delft, Chem. Eur. J. 2000, 6, 3095–3115; c) S. Cas-
tillon, A. Dessinges, R. Faghih, G. Lukacs, A. Olesker,
T. T. Thang, J. Org. Chem. 1985, 50, 4913–4917; d) P.
Borrachero-Moya, F. Cabrera-Escribano, M. Gꢅmez-
Guillꢄn, F. Madrid-Dꢆaz, Tetrahedron Lett. 1997, 38,
1231–1234; e) A. T. Carmona, P. Borrachero, F. Cab-
rera-Escribano, M. J. Diꢇnez, M. D. Estrada, A. Lꢅpez-
Castro, R. Ojeda, M. Gꢅmez-Guillꢄn, S. Pꢄrez-Garrido,
Tetrahedron: Asymmetry 1999, 10, 1751–1764; f) P.
Borrachero, F. Carera-Escribano, A. T. Carmona, M.
Gꢅmez-Guillꢄn, Tetrahedron: Asymmetry 2000, 11,
2927–2946; g) K. Dax, M. Albert, J. Ortner, B. J. Paul,
(MÀ2HFÀ
G
(CH3)3C+ +
ACHTUNGTRENNUNG
H+, 7), 300 (MÀHF+K+, 20).
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asc.wiley-vch.de
2755

Riccardo Surmont et al.
COMMUNICATIONS
Carbohydr. Res. 2000, 327, 47–86; h) K. Dax, M.
Albert, D. Hammon, C. Illaszewicz, T. Purkarthofer,
M. Tscherner, H. Weber, Monatsh. Chem. 2002, 133,
427–448; i) Y. Vera-Ayoso, P. Borrachero, F. Cabrera-
Escribano, A. T. Carmona, M. Gꢅmez-Guillꢄn, Tetrahe-
dron: Asymmetry 2004, 15, 429–444; j) P.-C. Lin, A. K.
Adak, S.-H. Ueng, L.-D. Huang, K.-T. Huang, J. A. Ho,
C.-C. Lin, J. Org. Chem. 2009, 74, 4041–4048.
[14] M. L. Aghmiz, Y. Dꢆaz, G. H. Jana, M. I. Matheu, R.
Echarri, S. Castillꢅn, M. L. Jimeno, Tetrahedron 2001,
57, 6733–6743.
[15] A. El-Laghdach, R. Echarri, M. I. Matheu, M. I. Bar-
rena, S. Castillꢅn, J. Garcia, J. Org. Chem. 1991, 56,
4556–4559.
[16] R. Surmont, G. Verniest, J. W. Thuring, G. Macdonald,
F. Deroose, N. De Kimpe, J. Org. Chem. 2010, 75, 929–
932.
[18] K. H. Yoo, H. S. Choi, D. C. Kim, K. J. Kim, Y. S. Song,
C. Jin, 2003, 336, 208–215.
[19] a) A. A. Frimer, Synthesis 1977, 578–579; b) C. Kowal-
ski, X. Creary, A. J. Rollin, M. C. Burke, J. Org. Chem.
1978, 43, 2601–2608; c) T. Shono, S. T. Matsamura, Y.
Matsamura, K. Inoue, F. Iwasaki, J. Chem. Soc. Perkin
Trans. 1 1986, 73–77.
[20] a) G. S. Basarab, P. Hill, K. G. Hull, PCT Int. Appl.
WO 2008020222, 2008; Chem. Abstr. 2008, 150, 56130;
b) M. J. Zacuto, D. Cai, Tetrahedron Lett. 2005, 46,
447–450.
[21] B. Kosjek, J. Nti-Gyabaah, K. Telari, L. Dunne, J. C.
Moore, Org. Process Res. Dev. 2008, 12, 584–588.
[22] a) K. Hirao, H. Nakatsuji, H. Kato, J. Am. Chem. Soc.
1973, 95, 31–41; b) J. San Fabian, A. J. A. Westra
Hoekzema, J. Chem. Phys. 2004, 121, 6268–6276; c) P.
Provasi, S. P. A. Sauer, J. Chem. Theory Comput. 2006,
2, 1019–1027.
[17] V. Wray, J. Chem. Soc. Perkin Trans. 2 1976, 1598–
1605.
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