Control of the ambident reactivity of the nitrite ion

Article abstract of DOI:10.1039/c2ob26980e

In previous studies, it was reported that a neighbouring equatorial ester group is essential for a good yield of nitrite-mediated triflate inversion, whereas with neighbouring benzyl ether groups or axial ester groups, mixtures are generally produced. In

Full text of DOI:10.1039/c2ob26980e

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Control of the ambident reactivity of the nitrite ion†
Hai Dong,*a,b Martin Rahm,b,c Niranjan Thota,b Lingquan Deng,b Tore Brinckb and
Olof Ramström*b
Cite this: Org. Biomol. Chem., 2013, 11,
648
In previous studies, it was reported that a neighbouring equatorial ester group is essential for a good
yield of nitrite-mediated triflate inversion, whereas with neighbouring benzyl ether groups or axial ester
groups, mixtures are generally produced. In the present study, the origin of this difference was addressed.
The ambident reactivity of the nitrite ion has been found to be the cause of the complex product for-
mation observed, which can be controlled by a neighbouring equatorial ester group. Both N-attack and
O-attack occur in the absence of the ester group, whereas O-attack is favoured in its presence. A neigh-
bouring group assistance mechanism is proposed, in addition to steric effects, based on secondary inter-
actions between the neighbouring ester group and the incoming nucleophile. High-level quantum
mechanical calculations were carried out in order to delineate this effect. The theoretical results are in
excellent agreement with experiments, and suggest a catalytic role for the neighbouring equatorial ester
group.
Received 7th June 2012,
Accepted 7th November 2012
DOI: 10.1039/c2ob26980e
www.rsc.org/obc
mixtures of nitro- and nitrite compounds are generally formed
in the reactions.
Introduction
The ambident reactivity of nucleophiles and electrophiles is a
The reactivity of the nitrite ion has been adopted in a
general and long withstanding issue in chemistry, and its highly useful transformation, the Lattrell–Dax reaction.3 In
elusive nature is repeatedly addressed in modern selective syn- the reaction, the anion is used as a reagent in epimerization
thesis.1 Many intriguing examples involving ambident species reactions, where structures with inverse hydroxyl configur-
have been reported, where reaction control presents continu- ation can be produced under mild conditions. This substi-
ous challenges. The ambident reactivity of the nitrite ion is tution reaction proceeds through an unstable nitrite ester
one such example that has been discussed extensively, and the intermediate,4 which is subsequently transformed into the
reactivity has been shown to depend on a variety of effects.2 epi-hydroxy structure. We found that a neighboring equatorial
The Hard–Soft Acid–Base (HSAB) principle, and the pertur- ester group plays a key role in the reaction, resulting in good
bation molecular orbital (PMO) theory, have generally been inversion yields for a series of carbohydrate structures.5 With
applied in order to explain how nitrite- or nitro-products are benzyl ether groups or neighboring axial ester groups, on the
generated, but a recent study from Mayr and co-workers con- other hand, mixtures are generally produced,5,6 independent
clude that the rationalization of ambident reactivity by the of the solvent polarity (DMF, MeCN, CH2Cl2, PhMe). Ring con-
HSAB or the Klopman–Salem concept had to be abandoned.1c traction and elimination products were often found in those
Instead, Marcus theory has been proposed to explain the reac- complex mixtures.7 Though these findings have been used to
tivity patterns.2b As a consequence of the ambident nature, expand the utility of this highly useful reaction in carbo-
hydrate synthesis,8 the origin of the differences is still not
clear. In the present study, this reaction has been used to
aHuazhong University of Science and Technology, School of Chemistry and Chemical
delineate
a
neighbouring group assistance governing
Engineering, Luoyu Rd 1037, 430074 Wuhan, P. R. China.
the outcome of the reaction. We report a new mechanism
that is based on the nature of the neighboring groups,
where different carbohydrate structures have been used
as examples. The origin of this difference was addressed,
and two hypotheses were challenged; firstly, the ambident
reactivity of the nitrite ion is the cause of the complex
product formation observed, and secondly, the N/O
selectivity is controlled by the neighboring equatorial ester
group.
E-mail: hdong@mail.hust.edu.cn; Fax: (+86) 27-87793242
bRoyal Institute of Technology (KTH), Department of Chemistry, Teknikringen 30,
S-10044 Stockholm, Sweden. E-mail: ramstrom@kth.se; Fax: (+46) 8 7912333
cUniversity of Southern California (USC), Loker Hydrocarbon Research Institute and
Department of Chemistry, Los Angeles, CA 90089-1661, USA
†Electronic supplementary information (ESI) available: 1H and 13C NMR spectra
of compound 4, 5 and 11, IR spectra of compound 5 and 11, 1H and 1H–1H cosy
spectra of triflate compounds, NMR analyse for inversion of compound 3, 10
and 17, Cartesian coordinates, energies and results of frequency calculations.
See DOI: 10.1039/c2ob26980e
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Scheme 1 (a) Examples of inversions with (a) nitrite; (b) acetate.
Results and discussion
In our previous studies, a series of triflates were tested as reac-
tants in the substitution reactions with nitrite (Scheme 1a).
For example, when compound 1 was allowed to react with
nitrite in DMF or acetonitrile, the inversed compound 2 was
isolated in 74% and 82% yield, respectively, whereas the analo-
gous benzyl-protected compound 3 resulted in a complex
mixture.5 If this difference in product distribution is caused by
the ambident nature of the nucleophile, results that are more
independent of the neighboring group would be produced
when non-ambident nucleophilic reagents are used. As can be
seen, this was found to be the case, and good substitution
yields were obtained for compound 3 when acetate was used as
the nucleophile (Scheme 1b). This result supports the first
hypothesis raised, pointing to the ambident nature of nitrite
as the primary cause of mixture formation. Consequently, both
the inversed nitro-product and nitrite-ester were formed by
N/O-attack of nitrite for the epimerization of the substrates
without a neighbouring equatorial ester group. Analogous
reactions were also found in the ring opening of an epoxide by
nitrite.9 In all these cases, the nitro-products were highly
acidic and might exist as the acinitronate, subsequently under-
going elimination of a beta-group to form more complicated
contraction or fragmentation products at high temperature;
whereas the nitrite esters are subsequently transformed into
the hydroxyl groups with trace water. However, only O-attack of
nitrite happened for the epimerization of the substrates with a
neighbouring equatorial ester group, leading to exclusive pro-
ducts with an inversed hydroxyl group. Thus, the isolation of
respective nitro-products from the mixtures will be a direct evi-
dence for the ambident reactivity of nitrite in this Lattrell–Dax
reaction.
Scheme 2 (a) Identified compounds, proposed intermediate 16 and proposed
pathway for product pattern resulting from compound 3. (b) Identified com-
pounds from reactions with 10.
1
information could be obtained from H NMR spectra of inver-
sion with compound 3 (cf. ESI†), suggesting that an unknown
compound and the compound 6 were formed immediately
upon addition of nitrite to the solution. The nitrite-compound
6 was then slowly transformed into compound 7, whereas the
unknown compound relatively quickly reached a maximum
level and gradually disappeared. Two new sets of signals were
formed in the process; one of these was related to nitro-
compound 5, and the other to an unknown fragmentation com-
pound. Very similar results were obtained when compound 10
was used in the reaction (Scheme 2b), where five different com-
pounds could be identified (cf. ESI†). The unexpected com-
pound 11, carrying an equatorial nitro-group, was obtained in
18% yield. The epi-triflate analog of compound 10 was in this
case also tested to corroborate the results, where compound
11, was obtained in 36% yield.
Although not identified, the rapid initial formation of the
unknown compound (16) must point to the axial nitro-com-
pound resulting from N-attack at the triflate center. The un-
expected nitro-compound then arose upon the gradual
disappearance of the unknown compound. Deuterium
exchange experiments involving compound 11 indicated no
deprotonation under the conditions used. No exchange was
thus observed with or without tetrabutylammonium nitrite at
room temperature or even at 60 °C for 5 hours. The results
suggest that compounds carrying a nitro group in the axial
position are unstable and lead to the more stable structures
with the substituents in the equatorial position. Though the
deuterium exchange experiments gave no direct evidence, a
reasonable mechanism for the conversion should involve
The complex mixtures obtained were subsequently further
analyzed (Scheme 2a). From compound 3, three compounds
could initially be identified after purification; compound 5
(50% yield), carrying a nitro-group in the equatorial position,
and epimeric hydroxy-compounds 7 and 9. Nitrite-ester 6
could be discriminated by 1H NMR spectra combined with
1H–1H COSY (cf. ESI†). In a reference experiment using the epi-
triflate analog of compound 3, compounds 5 (41% yield) and 9
were again formed together with compound 8. Further
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Scheme 3 Identified compounds and proposed mechanism for nitrite-
mediated epimerization of compound 17.
deprotonation and reprotonation at the carbon with nitrate.
The overall process for compound 3 is outlined in Scheme 2a.
The reaction between nitrite and compound 17, carrying a
neighboring ester group in the axial position, was also ana-
lyzed (cf. Scheme 3). When this reaction was carried out in
DMF at 50 °C, a very complex mixture was produced that was
difficult to analyze. For this reason, the reaction was instead
analyzed in acetonitrile at room temperature. The reaction
proved in this case very sluggish but column chromatography
and 1H NMR could be used to identify the main species
formed. Hydroxy compound 19 was isolated from this reaction
as a major component, together with lower amounts of its epi-
hydroxy analog 18. No major formation of nitro-compounds
was in this case seen. In analogy to the results for compounds
3 and 10, the axial nitro group would also be unstable, leading
to the more stable equatorial species. In contrast to these
results, when compound 17 was instead tested in d-benzene,
compound 19, and its nitrite precursor 20 were the major pro-
ducts due to supramolecular control.8f All these results
support the first hypothesis raised, that the ambident nature
of the nitrite ion is a major cause for the complex mixture
formation.
Scheme 4 (a) Suggested intramolecular leaving group assistance according to
Thatcher; (b) suggested neighboring group assistance by us.
Furthermore, during the nitrite-mediated inversion of tri-
flate structures with a neighboring equatorial ester group,
neither nitro products nor nitrite products were observed
when the same reactions were performed. Instead, the
inversed hydroxyl group products were always formed in near
quantitative yields. These results indicate that only O-attack
occurred, and the intermediate nitrite products were instantly
transformed to their hydroxy analogs, due to the effect of the
neighboring ester group. The origin of this phenomenon
points to the occurrence of secondary interactions between the
nitrite nucleophile, and the nitrite ester, with the neighboring
ester functionality. As well kinetic effects, statistic effects and
steric reasons play roles in the reaction; but considering the
same pattern for many different structures, these effects are
unlikely to be inclusive.
Fig. 1 (a) Nitrite insertion: oxygen-attack (blue) is assisted by a favorable inter-
action between the nitrite anion and the neighboring equatorial ester group.
This type of interaction is not possible in the case of nitrogen-attack (red) and is
a likely explanation for the kinetic control of the epimerization reaction. (b)
Hydrolysis proceeds rapidly by initial elimination of NO radicals. DFT-M06-2X
and SCS-MP2 energies are reported in kcal mol−1 and bond lengths in Ångström
(Å). Wiberg bond indices are given within parenthesis.
The hydrolysis of alkyl nitrites has been studied and the
mechanism was suggested to be concerted.4a,10 The acid-cata-
lyzed hydrolysis of alkyl nitrites is quite fast, whereas the basic
hydrolysis of alkyl nitrites is an extremely slow process, owing
to the higher electronegativity of nitrogen, and the presence of
a lone pair, compared to the hydrolysis of esters. Furthermore,
an explanation for the rapid transformation of the nitrite inter-
mediates has been proposed by Thatcher and co-workers.11
During the hydrolysis of nitrite esters, intramolecular Lewis
acid or charge transfer catalysis by the β-nitrate group was pro-
posed, in which the β-nitrate substituent assists the departure
of the leaving group. The mechanism was supported by
ab initio and semi-empirical molecular orbital calculations. In
the present case, the analogous five-membered ring mechan-
ism is plausible, where the ester group assists the departure of
the leaving group (Scheme 4a). However, according to our
further quantum chemical study, a seven-membered ring
mechanism seems more reasonable (Scheme 4b).
It is more difficult to explain how the neighboring equator-
ial ester group can restrain the occurrence of an N-attack or
promote the O-attack pathway. A plausible mechanism involves
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secondary interactions between the incoming nitrite and the construction poor measures of interactions dominated by van
neighboring ester group, guiding the reaction towards O-attack der Waals dispersion, and should not be interpreted as such.
(Scheme 4b), subsequently followed by assisted hydrolysis of Calculated bond lengths together with Wiberg bond order ana-
nitrite ester. For this reason, quantum mechanical calculations lyses show TS-O-1 to be a slightly earlier transition state than
were carried out in order to delineate this effect (Fig. 1). The TS-N (Fig. 1). In TS-N the triflate and ester groups maintain
inversion of the 4-O-substituent of a 3-O-acetylated glucoside orientations similar to those in the ground state 1, with one
derivative in acetonitrile was evaluated, where the 2 and oxygen of the triflate coordinated towards the partially positive
6-hydroxyl groups were methylated. Structure optimization and carbonyl carbon of the ester group. Interestingly, in TS-O-1,
frequency analyses were performed using the recent hybrid the ester group is twisted by 50° and the triflate–carbonyl inter-
meta exchange-correlation density functional M06-2X12 in action is broken in favour of a nitrite–carbonyl interaction.
Gaussian 09,13 using a 6-31+G(d,p) basis set, together with an This interaction is not possible in the case of nitrite–nitrogen
implicit treatment of acetonitrile solvent through the SCRF/ attack. A similar twist is also observed in TS-O-2. However, in
PCM approximation. M06-2X includes long-range dispersion this case the ester group is in lessened proximity to the nitrite
effects through empirical means and has been shown highly anion. The noticeable twist of the ester group, which later is
reliable for calculating main group thermochemistry.12,14 Final present in both reaction products, enables long-range attrac-
single-point energies in solution were obtained at the M06-2X/ tive interactions between the face of the ester and the
cc-pVTZ level using Gaussian 09. Solution energies were also approaching nitrite anion in the case of TS-O-1. A rough esti-
evaluated with the Conductor-like Screening Model (COSMO)15 mate of this interaction can be obtained by comparing TS-O-1
and spin component scaled second-order Møller–Plesset with TS-O-2, which are close to identical geometrically except
perturbation theory, at the SCS-MP2/cc-pVDZ16 level, as for the orientation of the nitrite anion. Positioning of the
implemented in the ORCA 2.9 code.15 The MP2 method nitrite anion adjacent to the equatorial ester group reduces
includes ab initio approximations to all relevant long-range the energy by 2 kcal mol−1. These results are in excellent
interactions, i.e. electrostatics, dispersion and induction, and agreement with experiment, and suggest a catalytic role for the
the SCS-approach has been shown to improve the accuracy of ester group that would explain the dependence of the N/O-
MP2 considerably.16 Wiberg bond indices were calculated from selectivity to the group’s placement on the carbohydrate
natural atomic orbitals (NAOs) obtained from the M062X/ backbone.
cc-pVTZ wave functions.
Fig. 1b depicts processes by which rapid hydrolysis of the
The rate difference between two competing reaction bar- intermediate 2, or its equatorial isomer 4, can occur by elimin-
riers can be estimated using Boltzmann statistics and tran- ation of NO radicals through TS-ax and TS-eq, respectively.
sition state theory (TST). As a reference it can be mentioned These processes are likely also affected by interactions with the
that a selectivity of 98% corresponds to a barrier difference of equatorial ester group to some extent. However, as these reac-
only 2.3 kcal mol−1 at 20 °C. Such a difference is close to the tions are not rate determining for the over-all process such
accuracy of even the most advanced quantum mechanical interactions are of no consequence for the obtained product
treatments available for this size of system. The energy of five mixture. More exact details of the hydrolysis mechanism are
conformers of 1 were initially evaluated at the B3LYP/6-31+ likely indeterminate without explicit consideration of neigh-
G(d,p) level. The lowest one was selected for further mechanis- bouring water molecules and solvent interactions. Conse-
tic studies using PCM-M06-2X and COSMO-SCS-MP2 calcu- quently, we can conclude that hydrolysis proceeds with
lations. Whereas only one transition state for nitrogen attack reaction barriers equal to or lower than ∼12 kcal mol−1
was found (cf. TS-N in Fig. 1a), three energetically reasonable These results point to the requirement of an equatorial
.
(ΔG‡ < 25 kcal mol−1) transition states for oxygen attack were ester group for good inversion yields. Leaving group assistance
identified (cf. TS-O-1, TS-O-2 and TS-O-3 in Fig. 1a), with has been proposed, and a secondary interaction exerted by the
TS-O-1 being the lowest at all levels of theory. The accurate equatorial ester group has also been demonstrated in comp-
M06-2X DFT functional provided an activation enthalpy barrier lement to steric effects. The second hypothesis raised is thus
for nitrite–oxygen attack (TS-O-1) that is 0.9 kcal mol−1 lower supported, and the N/O selectivity is in all probability depen-
than the corresponding nitrogen attack (TS-N). The same dent on the neighboring group pattern.
difference is 2.7 kcal using the SCS-MP2 method, also in
favour of TS-O-1. These values are closely mirrored in the ther-
mally uncorrected SCF energies (0.5 and 2.4 kcal mol−1
respectively). The free Gibbs energy barriers (at 20 °C and 1 M)
,
Conclusions
are in good agreement with reactions that proceed readily at The ambident reactivity of the nitrite anion in Lattrell–Dax-
ambient conditions (ΔG‡ = 18–22 kcal mol−1, Fig. 1a). The ΔG‡ type epimerization reactions has been studied. It was found
values also predict a kinetic prevalence for oxygen-attack, at that both N- and O-attack occur in the absence of a neighbor-
both levels of theory.
ing equatorial ester group, whereas the N-attack is excluded in
Wiberg bond indices are calculated from the overlap of its presence. A neighbouring group assistance mechanism has
NAOs residing on neighbouring atoms, and are facile measures been proposed, in addition to steric and kinetic effects, based
of covalent interaction. However, such indices are by on secondary interactions with the neighboring equatorial
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ester group and the incoming nucleophile. From these results,
Methyl 2-O-acetyl-3-O-benzyl-4,6-O-benzylidene-β-D-manno-
we have shown that the Lattrell–Dax reaction can be well side (4). 1H NMR (CDCl3, 400 MHz): δ 7.24–7.54 (m, 10 H, 2 ×
incorporated into synthesis, generating various target struc- Bn), 5.65 (d, 1 H, J2,3 3.0 Hz, H2), 5.62 (s, 1 H, O2CHC6H5),
tures in a controllable way.
4.75, 4.64 (d, 2 H, Ja,b 12.1 Hz, OCHaHbC6H5), 4.51 (s, 1 H, H1),
4.35 (dd, 1 H, J6a,6b 10.3 Hz, J6a,5 4.9 Hz, H6a), 4.03 (t, 1 H, J4,3
,
J4,5 9.7 Hz, H4), 3.91 (t, 1H, J6b,5, J6b,6a 10.3 Hz, H6b), 3.73 (dd,
1 H, J3,2 3.0 Hz, J3,4 9.7 Hz, H3), 3.53 (s, 3 H, OMe), 3.34–3.44
(m, 1 H, H5), 2.21 (s, 3 H, OAc); 13C NMR (CDCl3, 125 MHz):
δ 170.6, 137.8, 137.5, 129.1, 128.6, 128.4, 127.9, 127.8, 126.2,
101.7, 100.9, 78.1, 75.7, 71.9, 68.9, 68.6, 67.4, 57.7; [α]2D0 = −71
(c = 0.7, CHCl3); HRMS: calcd For C23H26O7 [M + Na+]:
437.1576. Observed: 437.1594.
Experimental section
General
All commercially available starting materials and solvents were
of reagent grade and dried prior to use. Chemical reactions
were monitored with thin-layer chromatography using
precoated silica gel 60 (0.25 mm thickness) plates. Flash
column chromatography was performed on silica gel 60
(0.040–0.063 mm). Optical rotations were measured at the
sodium D line at ambient temperature. 1H and 13C spectra
were recorded with a 400 MHz or 500 MHz instrument at
298 K in CDCl3 and CD3CN, using the residual signals from
CHCl3 (1H: δ = 7.26 ppm; 13C: δ = 77.2 ppm) and CHD2CN
(1H: δ = 1.94 ppm; 13C: δ = 118.3 ppm) as internal standard.
1H peak assignments were made by first order analysis of the
spectra, supported by standard 1H–1H correlation spectroscopy
(COSY). IR spectra were recorded from 400 to 4000 cm−1 at
ambient temperature.
Methyl 3-O-benzyl-4,6-O-benzylidene-2-deoxy-2-nitro-β-D-glu-
coside (5). 1H NMR (CD3CN, 500 MHz): δ 7.24–7.54 (m, 10 H,
2 × Bn), 5.68 (s, 1 H, O2CHC6H5), 4.90 (d, 1 H, J1,2 8.1 Hz, H1),
4.84, 4.60 (d, 2 H, Ja,b 11.3 Hz, OCHaHbC6H5), 4.57 (dd, 1 H,
J2,1 8.1 Hz, J2,3 10.1 Hz, H2), 4.36 (dd, 1 H, J3,2 10.1 Hz, J3,4
9.4 Hz, H3), 4.32 (dd, 1 H, J6a,6b 10.3 Hz, J6a,5 4.9 Hz, H6a), 3.83
(t, 1 H, J4,3, J4,5 9.4 Hz, H4), 3.82 (t, 1H, J6b,5, J6b,6a, 10.2 Hz,
H
6b), 3.60–3.68 (m, 1 H, H5), 3.47 (s, 3 H, OMe.); 13C NMR
(CD3CN, 125 MHz): δ 138.6, 138.5, 130.0, 129.3, 129.2, 129.0,
128.9, 127.1, 102.1, 101.8, 90.7, 81.8, 78.3, 75.0, 68.8, 67.1,
57.9; FTIR (KBr, cm−1): strong absorption at 1550 and
1365 cm−1; [α]D20 = −16 (c = 0.3, CHCl3); HRMS: calcd For
C21H23NO7 [M + Na+]: 424.1372. Observed: 424.1370.
General synthesis of triflate derivatives
Methyl
2,3,6-tri-O-benzyl-4-deoxy-4-nitro-β-D-glucoside
(11). 1H NMR (CD3CN, 400 MHz): δ 7.16–7.37 (m, 15 H, 3 ×
Bn), 4.92, 4.70 (d, 2 H, Ja,b 11.9 Hz, OCHaHbC6H5), 4.82, 4.53
(d, 2 H, Jc,d 10.8 Hz, OCHcHdC6H5), 4.72 (t, 1 H, J4,3, J4,5
10.3 Hz, H4), 4.84, 4.60 (d, 2 H, Je,f 11.3 Hz, OCHeHfC6H5), 4.41
(d, 1 H, J1,2 7.8 Hz, H1), 4.23 (dd, 1 H, J3,2 9.1 Hz, J3,4 10.3 Hz,
H3), 3.93–3.99 (m, 1 H, H5), 3.65 (dd, 1 H, J6a,6b 10.8 Hz, J6a,5
3.5 Hz, H6a), 3.58 (s, 3 H, OMe), 3.56 (dd, 1H, J6b,6a 10.8 Hz,
J6b,5 4.0 Hz, H6b), 3.46 (dd, 1 H, J2,1, 7.8 Hz, J2,3 9.1 Hz, H2);
13C NMR (CDCl3, 125 MHz): δ 138.1, 137.5, 137.4, 128.7, 128.6,
128.5, 128.2, 128.1, 128.0, 127.9, 104.9, 87.1, 81.8, 80.4, 75.9,
75.0, 74.0, 72.5, 68.9, 57.5; FTIR (KBr, cm−1): strong absorption
at 1550 and 1365 cm−1; [α]D20 = −10 (c = 0.7, CHCl3); HRMS:
calcd For C28H31NO7 [M + Na+]: 516.1998. Observed: 516.2008.
To a solution of the suitably O-protected methyl β-D-glycoside,
carrying an unprotected OH at C2, C3 or C4 (0.94 mmol), in
CH2Cl2 (5 mL) was added pyridine (0.65 mL) at −20 °C. Tri-
fluoromethanesulfonic anhydride (0.53 g, 1.88 mol) in CH2Cl2
(2 mL) was added dropwise, and the mixture was stirred while
allowing to warm from −20 °C to 10 °C over 2 h. The resulting
mixture was subsequently diluted with CH2Cl2 and washed
with 1 M HCl, aqueous NaHCO3, water, and brine. The organic
phase was dried with MgSO4 and concentrated in vacuo at low
temperature. The residue could be identified by 1H NMR in
quantitative yield and was used directly in the next step or in
further 1H NMR-experiments without further purification.
General inversion of triflate derivatives
TBANO2 (5 equiv.) was added to a solution of the protected tri-
flate residue (200 mg) in solvents (DMF, MeCN, CH2Cl2, PhMe)
(2.0 mL). After stirring at 20 °C–50 °C for 1–6 h, the mixture
was diluted with CH2Cl2 and washed with brine. The organic
phase was dried with MgSO4 and concentrated in vacuo. Purifi-
cation of the residue by flash column chromatography (3 : 1 to
1 : 1 hexane–ethyl acetate) afforded the inversion products.
Acknowledgements
This work was supported by the Fundamental Research Funds
for the Central Universities (HUST: 2012QN146), the National
Nature Science Foundation of China (Nos. 21272083), the
Chutian Project-Sponsored by Hubei Province, the Swedish
Research Council and the Royal Institute of Technology.
General inversion of triflate derivatives in d-solvents
TBANO2 (5 equiv.) was added to a solution of the purified tri-
flate residue (5 mg) in d-solvents (MeCN, benzene) (0.5 mL).
The reaction was performed in NMR-tube at room temperature
for 0–48 h. 1H NMR spectra were recorded with a Bruker
Avance 400 instrument or Bruker DMX 500 instrument at
298 K, using the residual signals from d-acetonitrile and
d-benzene as internal standard.
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