Sn?Li Transmetalation of α-Aminoorganostannanes for the Stereoselective Synthesis of Substituted Dehydropiperidines and Dehydroazepanes

Article abstract of DOI:10.1002/adsc.201900349

A highly diastereoselective synthesis of (R,S) or (S,S) 2,6-disubstituted dehydropiperidines and 2,7-disubstituted dehydroazepanes has been developed. The stereochemical preference for the (R,S) or the (S,S) isomer is governed by a tin-lithium exchange/electrophilic trapping sequence combined with a ring-closing metathesis. Their relative order was found to have a dramatic influence on the interaction controlling the epimerization at the anionic center. In each case, the complete stereodivergence of the reactions sequence is explained by considering the stabilization brought by the lithium-carbonyl coordination and rationalized by DFT calculations. (Figure presented.).

Full text of DOI:10.1002/adsc.201900349

Title: Sn-Li Transmetalation of α-Aminoorganostannanes for the
Stereoselective Synthesis of Substituted Dehydropiperidines and
Dehydroazepanes
Authors: Alexandre Lumbroso, Isabelle Beaudet, Jean-Paul Quintard,
Cécile Fraisse, Nicolas Galland, Loic Toupet, and Erwan Le
Grognec
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201900349
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10.1002/adsc.201900349
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Sn-Li Transmetalation of α-Aminoorganostannanes for the
Stereoselective Synthesis of Substituted
Dehydropiperidines and Dehydroazepanes
Alexandre Lumbroso,a Isabelle Beaudet,a Jean-Paul Quintard,a Cécile Fraisse,a
Nicolas Galland,a Loïc Toupet,b Erwan Le Grogneca*
a
Université de Nantes, CNRS, CEISAM, UMR 6230, F-44000 Nantes, France.
e-mail: erwan.legrognec@univ-nantes.fr
Université de Rennes 1, CNRS UMR 6251, Institut de Physique de Rennes, Campus de Beaulieu, 35042
b
Rennes, France.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201######.
interaction controlling the epimerization at the anionic
Abstract. A highly diastereoselective synthesis of (R,S) or
(S,S) 2,6-disubstituted dehydropiperidines and 2,7-
disubstituted dehydroazepanes has been developed. The
stereochemical preference for the (R,S) or the (S,S) isomer is
governed by a tin-lithium exchange/electrophilic trapping
sequence combined with a ring-closing metathesis. Their
relative order was found to have a dramatic influence on the
center. In each case, the complete stereodivergence of the
reactions sequence is explained by considering the
stabilization brought by the lithium-carbonyl coordination
and rationalized by DFT calculations. Keywords: Tin,
Lithium, Sn-Li exchange, Chiral carbanion, DFT
calculations, Ring-closing metathesis, Dehydropiperidines.
polyhydroxylated azepanes are also present in
biological active products and have received some
attention.[5]
Introduction
Functionalized piperidines are widely present in
alkaloids and bioactive compounds, therefore many
methodologies have been developed to prepare these
six-membered ring heterocycles.[1] Moreover,
polyhydroxylated piperidines (named iminosugars or
iminocyclitols) constitute the most attractive
carbohydrate mimetics reported to date and can act as
glycosidase or glycosyltransferase inhibitors.[2] For
these applications, it is essential to control the
stereocenter configuration of the piperidines and
especially at the 2 and 6 positions since they define the
series of sugars they mimic.[3] In this context, the
stereocontrolled synthesis of 2,6-disubstituted
dehydropiperidines, which can be used as precursors
of 2,6-disubstituted piperidines, presents a strong
interest. Having in hand a series of 2-stannylated
dehydropiperidines precursors,[4] we have evaluated
their interest for the stereoselective synthesis of 2,6-
The Sn-Li transmetalation of organostannanes by
organolithium reagents is an efficient reaction which
has been applied to aryltins, heteroaryltins, vinyltins,
allyltins or α-heterosubstituted organotins.[6] When
applied to α-oxygenated organostannanes to prepare α-
oxygenated organolithium reagents, this reaction can
be highly stereoselective when achieved at low
temperature, although sensitive to steric hindrance.[7]
Similarly, α-nitrogenated organolithium reagents can
be obtained by Sn-Li transmetalation from the
corresponding organostannyl precursors. However, in
this case the stereoselectivity is highly dependent on
the temperature, the solvent and the nitrogen
protecting group.[8] Previous studies have shown that a
N-carbamoyl protection allows a stabilization of the
desired lithiated species.[9] Moreover, the Sn-Li
transmetalation
of
2-organostannyl-1,3-
oxazolidinones affords organolithium derivatives
having a higher trend to epimerize into the isomer
allowing the most stabilizing coordination.[10] Based
on these contributions, we assumed that the Sn-Li
disubstituted-3,4-dehydropiperidines
through
a
sequence involving a Sn-Li transmetalation and an
electrophilic trapping. We also considered this
strategy for the synthesis of dehydroazepanes, since
1
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10.1002/adsc.201900349
Advanced Synthesis & Catalysis
transmetalation of 2-stannylated dehydropiperidines
protected as oxazolidinones could afford the
corresponding anionic species with a control of the
stereoselectivity.
transmetalation reaction of enantiopure N-(α-
tributylstannylorgano)oxazolidin-2-ones (R,S)-4a and
(S,S)-4a. The reaction was conducted at -78°C in THF
in the presence of n-BuLi (1.6 equiv.) and
cyclohexanone was added after 20 min. Under these
standard experimental conditions, the (S,S)-4a
diastereomer afforded the 5a product as a single
diastereomer in 72% yield (Table 1, entry 1). Suitable
monocrystals for X-ray diffraction analysis were
obtained and the absolute configuration was found to
be (R,S), indicating that the configuration of the
stereocenter was preserved through the reactions.
Compound (R,S)-5a was also obtained when the
reaction sequence was carried out with (R,S)-4a,
corresponding in this case to an inversion of
configuration (entry 2), while the yield was found to
be much lower (30%). Starting from the (S,S)-4b
diastereomer, the 7-membered ring analogue, product
5b was selectively obtained as a single isomer in 79%
yield (entry 3), and assigned to be (R,S)-5b by analogy
to (R,S)-5a. This (R,S)-5b diastereomer was also
selectively obtained in 58% yield when the reaction
sequence was carried out starting from (R,S)-4b (entry
4). It indicates a high diastereoselectivity regardless of
the configuration of the carbon bearing the tin moiety
on the stannylated precursor and of the size of the
bicyclic heterocycle. However, since higher yields
were obtained after the transmetalation/trapping
sequence when starting from (S,S)-4 instead of (R,S)-
4, the (S,S)-4 isomer was systematically used in
subsequent studies.
We have previously examined the ring opening of
2-tributylstannyl-1,3-oxazolidines derived from (S)-
vinylglycinol by soft nucleophiles. This procedure
allows an efficient access to 4-tributylstannyl-3-
azadienyl alcohols 2 when alkenylmetals are used in
the presence of a Lewis acid.[11] These latter can be
subsequently converted into the corresponding
oxazolidinones
dehydropiperidines (or dehydroazepanes) 4 by ring
closing metathesis.[4] Following
preliminary
3
leading to the stannylated
a
communication, the aim of the present work is to study
the Sn-Li transmetalation reaction carried out on the
stannylated oxazolidinones 3 and 4 by n-butyllithium
in order to evaluate its diastereoselectivity and to
rationalize the obtained results (Scheme 1).[12]
We first examined the transmetalation reaction of
stannylated oxazolidinones 4 before considering those
of 3.
Under the same experimental conditions (-78°C,
THF), the transmetalation/trapping sequence carried
out on (S,S)-4a proceeded with a good yield and a very
high diastereoselectivity when CO2(g) was the
electrophile.[12] The Sn-Li exchange on (S,S)-4a
followed by electrophilic trapping was also proved to
be efficient with benzaldehyde, isovaleraldehyde and
hexanal as electrophiles, leading selectively to (R,S)
products, but as a couple of diastereomers due to the
lack of diastereoselectivity on the aldehyde
enantiotopic faces. The configuration of the major
diastereomer of 7a was determined by X-ray
diffraction analysis of suitable monocrystals and was
found to be (S,R,S). When the electrophile was
benzaldehyde or isovaleraldehyde, the reaction
temperature was lowered to -90°C to avoid an
intramolecular acyl transfer reaction occurring on one
of the two diastereomers.[13] This transfer results from
an intramolecular attack of the alcoholate on the
oxazolidinone, as it was previously reported for
similar compounds.[14] When hexanal was the
electrophile, a temperature of -100°C was required to
prevent this side reaction. However, these
experimental conditions dramatically impacted the
yield (33%) due to the concomitant formation of the
hydrolysis product 10 resulting of a “frozen” reactivity
of the lithiated intermediate.[13] The absolute
configuration of the 8a and 9a diastereomers were
deduced from the comparison of their NMR spectra
and RF values to those of 7a (see supporting
information).
Scheme 1. Preparation and transmetalation of stannylated
oxazolidinones 3 and 4.
Results
Transmetalation of stannylated oxazolidinones 4.
Our investigations first focused on the Sn-Li
2
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10.1002/adsc.201900349
Advanced Synthesis & Catalysis
Table 1. Sn-Li transmetalation followed by an electrophilic trapping of 4a and 4b.
[a] The (R,S) absolute configuration was confirmed by X-ray analysis.
[b] dr was determined by GC on the crude products.
[c] CO2(g) was used as electrophile followed by an esterification (TMSCHN2 (1.3 equiv.), C6H6:MeOH = 4:1).
[d] Benzaldehyde was used as electrophile and the temperature was lowered to -90°C; the configuration of the major compound 7a was
determined to be (S,R,S) by X-ray diffraction analysis.
[
e] Isovaleraldehyde was used as electrophile and the temperature was lowered to -90°C.
[
f] Hexanal was used as electrophile and the temperature was lowered to -100°C; dr was determined by 1H NMR analysis.
[
g] Products resulting of an intramolecular acyl transfer reaction obtained when the reaction conditions were not optimized[13]
3
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10.1002/adsc.201900349
Advanced Synthesis & Catalysis
Transmetalation of stannylated oxazolidinones 3.
We then turned our attention to N-(α-
tributylstannylorgano) oxazolidin-2-ones 3a.
diastereoselectivity was observed for the addition on
the enantiotopic faces of these aromatic or aliphatic
aldehydes (dr = 58/42, 50/50 and 50/50, respectively).
All these diastereomers were separated by column
chromatography on silica gel. The absolute
configuration of (S,S,S)-14a was based on that of
(S,S,S)-7a (vide infra), and those of 15a and 16a were
deduced from the comparison of their NMR spectra
and their RF with those of 14a.
Finally, we have considered the introduction of an
n-alkyl chain. While no reaction occurred when
1-iodohexane was used to trap the organolithium
species, the desired coupling product 17a was obtained
with a moderate R,S selectivity if the organolithium
intermediate was in situ converted into the
corresponding organocopper reagent. The use of
CuCN. 2 LiCl afforded 17a in 71% yield with a
(R,S)/(S,S) selectivity of 65/35, while CuCN or
pentynyl copper furnished low yields and minor
stereoselectivity improvement (70/30 and 87/13 ratios,
respectively, see supporting information).
A
similar Sn-Li transmetalation/electrophilic trapping
procedure was applied to these derivatives and the
obtained results are presented in Table 2. With
cyclohexanone as electrophile, diastereomer (R,S)-3a
afforded product 11a in 71% yield as a single
diastereomer (entry 1). Suitable monocrystals from
11a were obtained for X-ray diffraction analysis,
allowing the determination of its (S,S) absolute
configuration, meaning that the configuration was
preserved under these experimental conditions.
Starting from the (S,S)-3a diastereomer, the yield was
found to be strongly lowered (entry 2, 47%), but (S,S)-
11a was obtained once more as a unique isomer when
the reaction temperature was maintained at -78°C
(corresponding to a complete inversion of the
configuration). The achievement of this reaction
at -100°C afforded 11a in good yield (77%), but as a
mixture of diastereomers (entry 3, (S,S)/(R,S) = 26/74)
due to a partial epimerization of the chiral anionic
center. Since higher yields were obtained after the
transmetalation/trapping sequence when starting from
(R,S)-3a instead of (S,S)-3a, the (R,S)-3 isomers were
used in subsequent studies.
Starting from the (R,S)-3b diastereomer, bearing a
butenyl group instead of an allyl group, product 11b
was also selectively obtained as a single isomer in
good yield (entry 4, 82%). It was identified to be the
(S,S) diastereomer by analogy to (S,S)-11a. When the
transmetalation was performed on (R,S)-3a and the
nonanone was used as the electrophilic trapping
reagent, the (S,S)-12a product was isolated as a unique
product but in 30% yield only, presumably because of
the enolization reaction induced by the higher steric
hindrance. The electrophilic trapping was also
achieved with CO2(g) and, after esterification under
neutral conditions with TMSCHN2, 13a was obtained
in 76% yield with a strong (S,S) preference [(S,S)-13a
/ (R,S)-13a = 97/3].[12]
Then, we focused on the ring-closing metathesis
reaction of dienyl oxazolidinones 11-17 to prepare the
dehydropiperidines (or dehydroazepanes) similar to
those obtained previously from 4a (or 4b) but with a
different stereochemistry. Both Grubbs 1 and Grubbs
2 catalysts were considered for this reaction and the
results are presented in Table 3.
The absolute configuration of all products listed in
Table 3 were determined thanks to X-ray diffraction of
suitable monocrystals of (S,S)-5a, (S,S)-5b and
(S,S,S)-7a. These reactions were monitored by TLC
and conversion rates over 90% were observed for the
formation of the six membered rings with isolated
yields in the range of 80-95% using Grubbs 1 catalyst
at 25°C for 1 to 3h or Grubbs 2 catalyst at 40°C for 1
to 6h. For the ring-closing metathesis of (S,S)-11b with
Grubbs 2 catalyst at 40°C, the formation of a minor
side product (identified as a regioisomer resulting from
the migration of the double bond in the ring) was
observed along with the formation of the expected one
(Scheme 2). The (S,S)-5b/(S,S)-5b’ ratio was found to
be 89/11 by 1H NMR. The attempts to separate (S,S)-
5b’ from (S,S)-5b were unsuccessful. However, by
using Grubbs 1 (10 mol %) at room temperature for
12h, the (S,S)-5b product was obtained exclusively in
51% isolated yield (Scheme 2). Such an isomerization
has been previously observed and explained by a
reversible addition of a ruthenium hydride complex on
the double bond.[4,15]
We then looked at the use of aldehydes as
electrophiles and, taking into account the possible
occurrence of an intramolecular acyl transfer, the
reaction temperature was fixed to -90°C. Starting from
(R,S)-3a, the reaction products were obtained with an
exclusive (S)-configuration at the previous anionic
center whatever the nature of the aldehyde
(benzaldehyde, isovaleraldehyde or hexanal). In every
cases, the (S,S)-products were obtained selectively in
good
yields
(74-81%).
Unfortunately,
no
Scheme 2. Ring-closing metathesis of (S,S)-11b using Grubbs 1 or Grubbs 2 catalysts.
4
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10.1002/adsc.201900349
Advanced Synthesis & Catalysis
Table 2. Sn-Li transmetalation followed by an electrophilic trapping of 3a and 3b.
[a] The ratio anti/syn was determined by GC on the crude; anti/syn are defined by the relative position of the allyl (or butenyl) and the vinyl
moieties; the configuration of the anti isomer is (S,S) if electrophile is a ketone, an aldehyde or CO2 and (R,S) with a n-alkyl iodide.
[b] The reaction was carried out at -100°C.
[c] The reaction temperature was increased from -78°C to -50°C for dissolving nonanone.
[d] CO2(g) was used and the crude was treated with TMSCHN2 (1.3 equiv.), C6H6:MeOH=4:1.
[e] The reaction temperature was -90°C to avoid the intramolecular acyl transfer reaction.
[f] Diastereomers were separated by column chromatography on silica gel. The absolute configuration of (S,S,S)-14a (the minor one) was
deduced from that of (S,S,S)-7a determined by X-ray diffraction. The absolute configurations of 15a and 16a were deduced from the
comparison of their NMR data and RF.
[g] Determined by NMR on the crude.
[h] Unseparated mixture of diastereomers; CuCN.2LiCl (0.5 equiv.) and 1-iodohexane (1.8 equiv.) were used; the configuration of 17a was
deduced from that of 19a.
5
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10.1002/adsc.201900349
Advanced Synthesis & Catalysis
Table 3. Ring-closing metathesis of dienyloxazolidinones 11-17.
[a] 10 mol% of Grubbs catalyst used.
[b]
The diastereomers (R,S)-19a and (S,S)-19a were separated by chromatography. Their absolute configurations were confirmed by
NOESY NMR experiments.
6
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10.1002/adsc.201900349
Advanced Synthesis & Catalysis
solvent effects, the intermediate B was found 1.5
kcal/mol less stable than A (Scheme 3). It means that
under thermodynamic control, the occurrence of an
equilibrium between the
syn and anti-organolithium intermediates will result in
a high prevalence of the anti-isomer (A) which would
represent about 99 % of the total population. When the
reaction is carried out at -100°C, the reaction remains
partially under kinetic control affording a 3/1 mixture
of diastereomers.
When 1-iodohexane was used as electrophile
(Table 2 and supporting information), the conversion
of the organolithium intermediate into an
organocopper reagent is required. It induces a dramatic
effect on the diastereoselectivity of the reaction,
presumably due to a modification of the reaction
mechanism of the copper intermediate with the
electrophile, which may proceed by a single electron
transfer.[17],[18]
When considering the transmetalation of the
fused ring systems tributylstannyl dehydropiperidine /
oxazolidinone 4a, an enhanced selectivity is observed.
It leads to the cis (R,S)-product as unique diastereomer
regardless of the configuration of the stannylated
precursor, but with a drop in the yield when starting
from the trans stannylated precursor (Table 1). In these
cases, no trace of trans product can be observed by
achieving the transmetalation of trans (R,S)-4a at
temperatures as low as -100°C, indicating a strong
preference for the cis-configuration in the anionic
species. The situation is similar in dehydroazepanes
series. The cis isomer is selectively obtained
regardless of the configuration of 4b, with a drop in
the yields when starting from the trans precursor
(Table 1, entries 3,4).
Discussion
The results displayed in Table 2 indicate that the
sequence involving a Sn-Li transmetalation reaction
with n-BuLi followed by an electrophilic trapping
applied to 3a proceeds with a very high anti selectivity
regardless of the configuration of 3a. When the
reaction is carried out at -78°C on diastereomer (R,S)-
3a, the reaction leads selectively to the anti (S,S)-
product. Starting from diastereomer (S,S)-3a, the
selectivity is found to be temperature dependent.
At -78°C or at -90°C, the anti (S,S)-product is also
selectively obtained, while a mixture of syn and anti
products in a 3/1 ratio was obtained when the reaction
is performed at -100°C. This high diastereoselectivity
can be explained by the occurrence of
a
thermodynamic resolution. Under the experimental
conditions, the configurational stability of
intermediates A and B is dependent on the relative
position of the allyl (or butenyl) and the vinyl moieties
(Scheme 3). When the reaction is carried out at -78°C
on (R,S)-3a, the initially generated organolithium
intermediate A is the more stable one and does not
epimerize significantly into B. Therefore, intermediate
A is trapped by the electrophile with complete
retention of configuration. A similar reasoning can be
held for (R,S)-3b. On the other hand, when starting
from (S,S)-3a, the more sterically hindered
organolithium intermediate B is initially generated. At
-78°C, it epimerizes and leads to A along with side
reaction products before the electrophilic trapping.
The epimerization of the stereogenic centre is fast and
the ratio of the product is a reflection of the ratio of the
diastereomeric organolithium complexes.[16] When the
reaction is carried out at a lower temperature, the
epimerization is slowed down and can be partially
avoided, affording mixture of the two diastereomers.
This qualitative mechanism based on the experimental
results is fully supported by DFT calculations at the
BMK/cc-pVDZ level of theory. Based on computed
free energies at -78°C, and taking into account the
This high stereoselectivity can be explained by
considering the structure of the organolithium
intermediate. The cis-isomer furnished an intermediate
which adopts a “ridge tile” shape and places the
lithium in an adequate position for an intramolecular
coordination with the oxazolidinone carbonyl.
Scheme 3. Equilibration of organolithium species generated from (R,S)-3a and (S,S)-3a, and their computed structures at
the BMK/cc-pVDZ level of theory.
7
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10.1002/adsc.201900349
Advanced Synthesis & Catalysis
Scheme 4. Equilibration of organolithium species generated from (R,S)-4a and (S,S)-4a, and their computed structures at
the BMK/cc-pVDZ level of theory
Indeed, the quantum mechanical calculations predict a
short Li…O distance, 1.896 Å (Scheme 4, intermediate
C), away below the sum of the van der Waals radii of
lithium and oxygen (3.33 Å).
followed by a ring-closing metathesis, the (S,S)-trans
2,6-disubstituted dehydropiperidines are exclusively
obtained, while the inversion of the reaction sequence
affords (R,S)-cis 2,6-disubstituted dehydropiperidines.
The same strategy remains valid in dehydroazepanes
series. Application of this methodology to the
synthesis of bioactive polysubstituted piperidines and
iminosugars C-glycosides is currently under
investigation.
In the lithiated species obtained from the trans-
isomer, the relative orthogonal positions of lithium and
oxazolidinone carbonyl does not allow such stabilizing
coordination (Scheme 4, intermediate D). According
to the free energies calculated at the BMK/cc-pVDZ
level of theory, the intermediate D is less stable than C
by 14.7 kcal/mol in THF at -78°C. Therefore, while cis
configuration is completely maintained when starting
from cis-4a, a complete epimerization arises when
starting from trans-4a. Here again, the epimerization
reaction occurs very fast under the experimental
conditions used.
Experimental Section
The general procedures are fully described in supporting
information.
Preparation and Characterization of Compounds
The last part of the study (Table 3) points out the
possibility to convert efficiently adducts 11a-17a and
11b into the corresponding dehydropiperidines and
dehydroazepanes through ring-closing metathesis.
Therefore, since adducts 11a-16a and 11b were
obtained selectively as anti isomers, this strategy
opens the route to trans dehydropiperidines.
Organotin precursor 1 was obtained by a transacetalisation
reaction[11a,19] between diethoxymethyltributyltin and
(S)-vinylglycinol protected as N-CO2Me.[20] Details of the
procedure have been previously reported[4] together with
the identification of cis and trans isomers which was
established on the basis of their NMR data.[21] Compound
2 was obtained by ring opening of 1 by soft alkenylmetals
in the presence of Lewis acids and converted into
oxazolidinone 3 before being submitted to ring-closing
metathesis to afford 4. Compounds 2-4 have been already
prepared and fully characterized.[4]
Conclusion
The control of the configurational stability of the
organolithium species obtained by transmetalation of
stannylated oxazolidinones 3 and 4 by n-butyllithium
allowed a highly diastereoselective synthesis of 2,6-
General procedure for Sn-Li transmetalation and
electrophilic trapping of 3 or 4.
disubstituted
dehydropiperidines
(and
2,7-
disubstituted dehydroazepanes). The stereochemical
trends are rationalized by considering the difference of
stabilization brought by the lithium-carbonyl
coordination, which was estimated by DFT
calculations as 1.5 kcal/mol for the organolithium
species derived from 3a and as 14.7 kcal/mol for the
organolithium species derived from 4a.
Thus, an efficient stereodivergent synthesis of (S,S)-
trans or (R,S)-cis 2,6-disubstituted dehydropiperidines
has been achieved starting from 3a. Using the reaction
sequence: Sn-Li transmetalation/electrophilic trapping
In a Schlenk tube, stannyl oxazolidinone (1 mmol) was
dissolved in THF (10 mL) and the solution was cooled
to -78°C and kept under argon before slow dropwise
addition of n-butyllithium (1 mL, 1.6 M in hexanes, 1.6
mmol) to the solution which turned to a slight yellow colour.
Once this addition was complete, the solution was allowed
to stir for 20 min at -78°C before dropwise addition of
electrophile (2 mmol). The reaction was quenched at -78°C
by addition of saturated aqueous NH4Cl after 20 min. The
aqueous phase was extracted with diethyl ether (3 x 20 mL)
and the combined organic extracts were dried (MgSO4),
8
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10.1002/adsc.201900349
Advanced Synthesis & Catalysis
filtered, and concentrated under vacuum. Purification was
carried out by flash chromatography on silica gel.
[4]
[5]
A. Lumbroso, V. Coeffard, D. Gatineau, S. Stecko,
I. Beaudet, J.-P. Quintard, E. Le Grognec, Eur. J.
Org. Chem. 2016, 5146-5159.
a) Y. Troin, M.-E. Sinibaldi, in Asymmetric
Synthesis of Nitrogen Heterocycles (Ed.: J. Royer),
Wiley, Weinheim, 2009, pp. 139-186; b) A. G.
Meyer, J. A. Smith, C. Hyland, C. C. Williams, A.
C. Bissember, T. P. Nicholls, in Progress in
Heterocyclic Chemistry, Vol. 28 (Eds.: G. W.
Gribble, J. A. Joule), Elsevier, 2016, pp. 579-622.
a) M. Pereyre, J.-P. Quintard, A. Rahm, Tin in
Organic Synthesis, Butterworths, London, 1987; b)
C. Rim, D. Y. Son, Arkivoc 2006, 265-291.
a) W. C. Still, C. Sreekumar, J. Am. Chem. Soc.
1980, 102, 1201-1202; b) J. S. Sawyer, T. L.
Macdonald, G. J. McGarvey, J. Am. Chem. Soc.
1984, 106, 3376-3377; c) J. S. Sawyer, A.
Kucerovy, T. L. Macdonald, G. J. McGarvey, J.
Am. Chem. Soc. 1988, 110, 842-853; d) P.
Lesimple, J.-M. Beau, P. Sinay, J. C. S. Chem.
Commun. 1985, 894-895; e) D. S. Matteson, P. B.
Tripathy, A. Sarkar, K. M. Sadhu, J. Am. Chem.
Soc. 1989, 111, 4399-4402; f) K. Tomooka, T.
Igarashi, M. Watanabe, T. Nakai, Tetrahedron
Lett. 1992, 33, 5795-5798; g) K. Tomooka, N.
Komine, T. Nakai, Tetrahedron Lett. 1997, 38,
8939-8942.
General procedure for ring closing metathesis of
dienyloxazolidinones 11-17 into bicyclic oxazolidinones
5-9 and 18-19.
To a solution of dienyloxazolidinones (0.65 mmol) in
dichloromethane (c = 0.005 mol.L-1) was added Grubbs
catalyst (0.032 mmol) and the reactive mixture was stirred
at 25°C for Grubbs 1 catalyst and 40°C for Grubbs 2
catalyst. After complete conversion, DMSO (0.11 mL,
1.62 mmol) was added and the solution was stirred
overnight. The reaction mixture was concentrated under
reduced pressure and the purification was carried out by
flash chromatography on silica gel.
[6]
[7]
All the characterization data and NMR spectra of new
compounds are given in supplementary information.
CCDC 718901, 723326 and 736227 contain the
supplementary crystallographic data for this paper. These
data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
[8]
a) R. E. Gawley, Q. Zhang, J. Am. Chem. Soc.
1993, 115, 7515-7516; b) R. E. Gawley, Q. Zhang,
Tetrahedron 1994, 50, 6077-6088; c) I. Coldham,
R. Hufton, D. J. Snowden, J. Am. Chem. Soc. 1996,
118, 5322-5323; d) J. M. Chong, S. B. Park, J. Org.
Chem. 1992, 57, 2220-2222; e) V. Coeffard, I.
Beaudet, J.-P. Quintard, E. Le Grognec, Chirality
2010, 22, 864-869; f) J.-P. Quintard, E. Le
Grognec, in Comprehensive Chirality, Vol. 3 (Eds.:
E. M. Carreira, H. Yamamoto), Elsevier,
Amsterdam, 2012, pp. 751-779.
Acknowledgements
We gratefully acknowledge the Université de Nantes, the “Centre
National de la Recherche Scientifique” (CNRS). A.L.
acknowledges the “Institut de Chimie des Substances Naturelles,
ICSN” for a PhD grant.
References
[9]
P. Beak, A. Basu, D. J. Gallagher, Y. S. Park, S.
Thayumanavan, Acc. Chem. Res. 1996, 29, 552-
560.
[1]
a) F.-X. Felpin, J. Lebreton, Curr. Org. Chem.
2004, 1, 83-109; b) J. Cossy, Chem. Rec. 2005, 5,
70-80; c) N. Toyooka, in Asymmetric Synthesis of
Nitrogen Heterocycles (Ed.: J. Royer), Wiley,
Weinheim, 2009, pp. 95-138; d) R. Vardanyan, in
Piperidine-Based Drug Discovery (Ed.: R.
Vardanyan), Elsevier, 2017, pp. 299-332; e) P.
Goel, O. Alam, M. J. Naim, F. Nawaz, M. Iqbal,
M. I. Alam, Eur. J. Med. Chem. 2018, 157, 480-
502.
a) N. Asano, R. J. Nash, R. J. Molyneux, G. W. J.
Fleet, Tetrahedron Asymmetry 2000, 11, 1645-
1680; b) V. H. Lillelund, H. H. Jensen, X. Liang,
M. Bols, Chem. Rev. 2002, 102, 515-554; c) P.
Compain, O. R. Martin, Iminosugars: Past,
Present and Future, John Wiley & Sons, Ltd,
2008.
[10]
a) W. H. Pearson, A. C. Lindbeck, J. Am. Chem.
Soc. 1991, 113, 8546-8548; b) W. H. Pearson, A.
C. Lindbeck, J. W. Kampf, J. Am. Chem. Soc.
1993, 115, 2622-2636; c) K. Brickmann, R.
Brückner, Chem. Ber. 1993, 126, 1227; d) V.
Coeffard, E. Le Grognec, I. Beaudet, M. Lepeltier,
V. Léat-Crest, J.-P. Quintard, Synthesis 2006,
4151-4158.
a) V. Coeffard, J.-C. Cintrat, E. Le Grognec, I.
Beaudet, J.-P. Quintard, J. Organomet. Chem.
2006, 691, 1488-1497; b) V. Coeffard, I. Beaudet,
M. Evain, E. Le Grognec, J.-P. Quintard, Eur. J.
Org. Chem. 2008, 3344-3351; c) V. Coeffard, E.
Le Grognec, I. Beaudet, M. Evain, J.-P. Quintard,
J. Org. Chem. 2009, 74, 5822-5838.
[2]
[3]
[11]
a) S. Mix, S. Blechert, Adv. Synth. Catal. 2007,
349, 157-160; b) G. Horne, F. X. Wilson, J.
Tinsley, D. H. Williams, R. Storer, Drug Discov.
Today 2011, 16, 107-118; c) P. Compain,
Molecules 2018, 23, 1658.
[12]
[13]
A. Lumbroso, I. Beaudet, L. Toupet, E. Le
Grognec, J.-P. Quintard, Org. Lett. 2013, 15, 160-
163.
Our investigations on the influence of the
temperature and on the absolute configuration of
9
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10.1002/adsc.201900349
Advanced Synthesis & Catalysis
the compounds resulting from the acyl transfer
reaction are reported in supporting information.
[17]
[18]
E. C. Ashby, D. Coleman, J. Org. Chem. 1987, 52,
4554-4565.
S. Mori, E. Nakamura, in Modern Organocopper
Chemistry (Ed.: N. Krause), Wiley-VCH Verlag
GmbH, 2002, pp. 315-346.
a) J.-C. Cintrat, V. Léat, J.-L. Parrain, E. Le
Grognec, I. Beaudet, L. Toupet, J.-P. Quintard,
Organometallics 2004, 23, 943-945; b) J.-C.
Cintrat, V. Leat-Crest, J.-L. Parrain, E. Le
Grognec, I. Beaudet, J.-P. Quintard, Eur. J. Org.
Chem. 2004, 4251-4267.
A. Lumbroso, V. Coeffard, E. Le Grognec, I.
Beaudet, J.-P. Quintard, Tetrahedron Lett. 2010,
51, 3226-3228.
[14]
a) D. A. Evans, M. M. Morrissey, R. L. Dorow, J.
Am. Chem. Soc. 1985, 107, 4346-4348; b) C.
Aciro, S. G. Davies, A. C. Garner, Y. Ishii, M.-S.
Key, K. B. Ling, R. S. Prasad, P. M. Roberts, H.
Rodriguez-Solla, C. O'Leary-Steele, A. J. Russell,
H. J. Sanganee, E. D. Savory, A. D. Smith, J. E.
Thomson, Tetrahedron 2008, 64, 9320-9344.
a) B. Schmidt, J. Org. Chem. 2004, 69, 7672-7687;
b) S. Fustero, M. Sánchez-Roselló, D. Jiménez, J.
F. Sanz-Cervera, C. del Pozo, J. L. Aceña, J. Org.
Chem. 2006, 71, 2706-2714.
a) P. Beak, D. R. Anderson, M. D. Curtis, J. M.
Laumer, D. J. Pippel, G. A. Weisenburger, Acc.
Chem. Res. 2000, 33, 715-727; b) I. Coldham, S.
Dufour, T. F. N. Haxell, J. J. Patel, G. Sanchez-
Jimenez, J. Am. Chem. Soc. 2006, 128, 10943-
10951; c) I. Coldham, J. J. Patel, S. Raimbault, D.
T. E. Whittaker, Chem. Commun. 2007, 4534-
4536; d) I. Coldham, N. S. Sheikh, Top.
Stereochem. 2010, 26, 253-293.
[19]
[15]
[16]
[20]
[21]
a) J.-C. Cintrat, V. Léat-Crest, J.-L. Parrain, E. Le
Grognec, I. Beaudet, L. Toupet, J.-P. Quintard,
Eur. J. Org. Chem. 2004, 4268-4279; b) G.
Casella, F. Ferrante, G. Saielli, Org. Biomol.
Chem. 2010, 8, 2711-2718.
10
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FULL PAPER
Sn-Li Transmetalation of α-Aminoorganostannanes
for the Stereoselective Synthesis of Substituted
Dehydropiperidines and Dehydroazepanes
Adv. Synth. Catal. Year, Volume, Page – Page
Alexandre Lumbroso,a Isabelle Beaudet,a Jean-Paul
Quintard,a Cécile Fraisse,a Nicolas Galland,b Loïc
Toupet,b Erwan Le Grogneca *
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