Diastereoselective Electrophilic Trifluoromethylthiolation of Chiral Oxazolidinones: Access to Enantiopure α-SCF3 Alcohols

Article abstract of DOI:10.1002/adsc.201701474

Lithium imide enolates featuring Evans’ chiral oxazolidinone auxiliary were involved in diastereoselective α-trifluoromethylthiolation with electrophilic SCF₃ donors. Diastereopure products were isolated and converted to enantiopure α-SCF₃ alcohols without racemisation. (Figure presented.).

Full text of DOI:10.1002/adsc.201701474

Title: Diastereoselective Electrophilic Trifluoromethylthiolation of Chiral
Oxazolidinones: Access to Enantiopure α-SCF3 Alcohols
Authors: Hélène Chachignon, Evgenii Kondrashov, and Dominique
Cahard
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10.1002/adsc.201701474
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201
Diastereoselective Electrophilic Trifluoromethylthiolation of
Chiral Oxazolidinones: Access to Enantiopure -SCF3 Alcohols
Hélène Chachignon,a Evgeniy V. Kondrashov,a,b and Dominique Caharda*
a
CNRS, UMR 6014 COBRA, Normandie Université, INSA Rouen. 76821 Mont Saint Aignan (France) Fax: (+33)-2-
3145-2959; phone (+33)-2-3552-2466; e-mail: dominique.cahard@univ-rouen.fr
A. E. Favorsky Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1, Favorsky Str., Irkutsk
b
664033, Russia
Received:
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. Lithium imide enolates featuring Evans’ chiral
oxazolidinone auxiliary were involved in diastereoselective
-trifluoromethylthiolation with electrophilic SCF3 donors.
Diastereopure products were isolated and converted to
enantiopure -SCF3 alcohols without racemisation.
Keywords: fluorine; sulfur; trifluoromethylthiolation;
chirality; asymmetric synthesis
reactions, or by means of chiral reagents. The
substrates investigated in these reactions were β-
ketoesters, oxindoles, -sulfenyl carbonyl compounds
and alkenes in cascade cyclisations that gave chiral
SCF3 products with high enantioselectivities. In 2013,
Shen[4] and Rueping[5] groups simultaneously
described the first asymmetric organocatalysed
trifluoromethylthiolations of β-ketoesters mediated by
quinine-based catalysts, unmodified or quaternarised
Introduction
Within the organofluorine chemistry community,
emergent fluorinated substituents are attracting a great
deal of attention because they affect the physico-
chemical and biological properties of molecules most
often in a favourable fashion. Among the emergent
fluorine chemotypes, SCF3 is one of the most
investigated for its high potential in medicinal
chemistry as an exceptional lipophilic group. The
SCF3 motif is present in a number of agrochemicals
and potential drugs yet absent in human prescription
medicines. In these biologically active compounds, the
SCF3 motif is predominantly linked to an sp2 aromatic
carbon and more rarely to an sp3 carbon. The
challenges associated with synthesising SCF3
compounds are manifold; however, a tremendous
growth in that field henceforth enables the access of a
as
phase-transfer
catalysts.
reagent
With
Shen’s
trifluoromethylsulfenate
or
N-
(trifluoromethylthio)phthalimide as electrophilic SCF3
donors, high levels of enantioselectivity were reached
for indanone and tetralone-derived substrates while
acyclic substrates proved to be the main limitation of
these reactions, as they showed poor reactivity. Gade
and co-workers reported a method based on metal-
catalysis exploiting copper-boxmi complex and
Shen’s trifluoromethylsulfenate reagent to obtain
numerous trifluoromethylthiolated cyclic β-ketoesters
derived from indanone, tetralone, cyclopentenone as
well as cyclohexenone in excellent yields and with
high enantioselectivities.[6] In 2017, Du and co-
wide panel of molecules featuring a SCF3 group.[1]
A
most fascinating aspect of organofluorine chemistry is
the asymmetric synthesis of enantiopure fluorinated
molecules;[2] in particular, the trifluoromethylthiolated
molecules are currently at the forefront of
innovation.[3] Therefore, the synthesis of compounds
featuring a C(sp3)–SCF3 group with emphasis for
enantiopure ones is of growing interest. Direct
trifluoromethylthiolation[4–15] as well as the use of
trifluoromethylthiolated building blocks[16–18] are two
complementary approaches for the construction of
chiral centres bearing the SCF3 group. The direct
introduction of the electrophilic SCF3 group was
reported through organocatalysis, metal-catalysed
workers
trifluoromethylthiolation of a cycloalkenone β-
ketoesters by means of N-
described
the
enantioselective
trifluoromethylthiosuccinimide and a squaramide
catalyst derived from hydroquinine and D-
glucopyranose in up to 90% ee.[7] The
trifluoromethylthiolation of oxindoles was also
achieved in high enantioselectivities by Rueping[8] and
Shen[9] groups under similar conditions to those they
proposed for β-ketoesters. Tan, Liu and co-workers
1
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10.1002/adsc.201701474
Advanced Synthesis & Catalysis
O
O O
N
O
O
O
described a highly enantioselective approach for the
reaction with various 3-aryl oxindoles in the presence
of a catalytic cinchona alkaloid based on the in situ
O
S
S
S
N
SCF3
N
SCF3
SCF3
generation
of
an
electrophilic
O
O
1b
1a
1c
trifluoromethylthiolation reagent from AgSCF3 and
trichloroisocyanuric acid.[10] The asymmetric
trifluoromethylthiolation of -sulfenyl carbonyl
compounds with N-trifluoromethylthiosuccinimide
and 10 mol% dihydroquinine produced diverse
Figure
1.
Investigated
trifluoromethylthiolation
reagents.[24]
2-one 2a as the substrate. We were delighted to
observe that by means of LiHMDS and in the presence
of N-SCF3 saccharin 1a (Figure 1),[23] substrate 2a was
efficiently converted into the corresponding (Z)-
lithium enolate, ultimately furnishing the expected
trifluoromethylthiolated products as a 67:33 mixture
of diastereomers, in 88% conversion (Table 1, entry 1).
Even though face-selectivity in enolate reaction was
not satisfactory yet, it was noteworthy that both
diastereomers could be successfully separated by silica
gel column chromatography. For this first experiment,
the temperature of the reaction medium, after the
addition of the SCF3 reagent, was allowed to rise to
20 °C before the quench, which probably contributed
to decrease the dr value. Aiming to improve the
diastereoselectivity of the reaction, several
experimental parameters were evaluated. Predictably
enough, quenching the reaction at –78 °C after 5 h
proved to be highly beneficial to the dr value, allowing
a drastic improvement to 94:6 (Table 1, entry 2). On
the other hand, the number of equivalents of the SCF3
reagent showed little impact on either the conversion
dithioketals with excellent enantioselectivities.[11]
number of cascade trifluoromethylthiolation
A
/
cyclisation from functionalised alkenes were reported
by Zhao and co-workers by means of a bifunctional
chiral
sulfide
or
selenide
catalyst
and
(PhSO2)2NSCF3.[12–14] This way, SCF3 lactones and
SCF3 azaheterocycles were obtained with excellent
enantioselectivities.
trifluoromethylthiolation of aldehydes gave
So
far,
only
the
a
disappointing result with 11% ee value as reported by
Wu, Sun and co-workers under organocatalysis in the
presence of the Hayashi-Jorgensen catalyst.[15]
Complementary to the use of chiral catalysts, Shen‘s
group developed chiral trifluoromethylthiolation
reagents, including (1S)-(–)-N-trifluoromethylthio-
2,10-camphorsultam derivatives that were able to
provide high ee values for SCF3 β-ketoesters,
oxindoles and benzofuranones.[19]
From this literature survey, we can observe that high
enantioselectivities of trifluoromethylthiolated tertiary
carbons were obtained provided that substrates
featured an activated position such as in β-ketoesters
or oxindoles. As to trifluoromethylthiolated secondary
carbons, high ee values could be reached in cascade
Table 1. Optimisation of the reaction conditions[a]
O
O
trifluoromethylthiolation
/
cyclisation
from
O
O
*
functionalised alkenes but only a poor 11% ee from
aldehydes under organocatalysis. Based on our own
experience in the construction of trifluoromethylated
carbon centres (C*–CF3) by diastereoselective
electrophilic trifluoromethylation,[20] we surmised that
chiral oxazolidinones[21] could serve as efficient chiral
auxiliaries for the stereocontrolled introduction of the
electrophilic SCF3 group (C*–SCF3). This way,
trifluoromethylthiolated secondary carbons could be
prepared diastereoselectively and possibly in
enantiopure form after diastereomeric enrichment
through chromatographic purification and cleavage of
the auxiliary. To support our strategy, Shen briefly
mentioned one reaction of his trifluoromethylsulfenate
reagent with an enolate derived from an Evans type
oxazolidinethione auxiliary that gave the desired SCF3
product with high diastereoselectivity (d.r. = 50:1)
albeit in 20% yield.[22] Hereafter, we present an in-
depth investigation of the diastereoselective
electrophilic trifluoromethylthiolation of chiral
oxazolidinones that resulted in the preparation of
enantiopure SCF3 products in high yields.
1) base, THF, –78 °C
N
N
O
O
CF3S
2) SCF3 reagent
THF, –78 °C, 5 h
3a
2a
Entry SCF3
source
Base
equiv)
(1.2 Conversion
d.r.[d]
(%)[b], [c]
88
1[e]
1a (1.1
equiv)
1a (1.1
equiv)
1a (1.2
equiv)
1b (1.1
equiv)
1c (1.1
equiv)
1c (1.1
equiv)
1c (1.1
equiv)
LiHMDS
LiHMDS
LiHMDS
LiHMDS
LiHMDS
NaHMDS
KHMDS
67:33
94:6
2
86
3
82
94:6
4
84
95:5
5
99 (85)
77
93:7
6
77:23
81:19
7
75
[a] Reaction conditions: 2a (0.25 mmol), base, THF, –78 °C,
30 min, then SCF3 source, –78 °C, 5 h and quench at –78 °C.
[b] Determined by 1H NMR analysis. [c] Yield of isolated pure
product is shown in parentheses. [d] Determined by 19F NMR
analysis on crude reaction mixtures. [e] The temperature was
let to increase to 20 °C after addition of the SCF3 source.
Results and Discussion
The reaction conditions were first investigated
using (R)-4-phenyl-3-(3-phenylpropanoyl)oxazolidin-
2
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10.1002/adsc.201701474
Advanced Synthesis & Catalysis
O
O
O
O
of the substrate or the dr (Table 1, entry 3). Different
electrophilic trifluoromethylthiolation reagents were
also screened: it was found out that if the
(PhSO2)2NSCF3 1b gave the best dr (95:5), N-SCF3
phthalimide 1c offered a better compromise between
conversion and diastereoselectivity (Table 1, entries 4
N
O
N
O
CF3S
CF3S
3a
3a2
85%; 93:7 dr
87%; 85:15 dr
and
5).
Replacing
LiHMDS
by
other
O
O
O
O
bis(trimethylsilyl)amide bases was also considered,
but proved to be detrimental to the good processing of
the reaction (Table 1, entries 6 and 7).
N
O
N
O
CF3S
CF3S
Other chiral auxiliaries were evaluated as well;
however, none of them allowed to reach higher
isolated yield and dr value simultaneously than (R)-4-
phenyloxazolidin-2-one (Figure 2).
3a3
92%; 89:11 dr
3a4
73%; 95:5 dr
Figure 2. Screening of chiral auxiliaries.
Table 2. Diastereoselective trifluoromethylthiolation of chiral oxazolidinones.[a]
O
O
O
O
LiHMDS (1.2 equiv)
N-SCF3 phthalimide (1.1 equiv)
R
R
N
N
O
O
CF3S
THF, –78 °C, 7h
3
2
Entry
1
Yield [%][b]
d.r.[c]
93:7
Entry
7
Yield [%][b]
d.r.[c]
85:15
Product 3
Product 3
O
O
O
O
N
N
O
O
72
85
CF3S
CF3S
3a
3g
O
O
O
O
O
CF3S
N
O
O
N
2
3
4
5
6
58
87:13
98:2
72
81
76
79
60
92:8
86:14
63:37
–
8
O
CF3S
3b
3h
O
O
O
N
O
Cl
N
O
77
CF3S
9
CF3S
3c
3i
O
O
O
O
O
N
O
O
N
CF3S
O
61
100:0
96:4
10
11
CF3S
3d
3j
O
O
O
O
N
O
CF3S
N
O
N.R.
F3CS
3e
3k
O
N
O
O
CF3S
98:2
3f
[a] Reaction conditions: 2 (0.25 mmol), LiHMDS (1.2 equiv), THF (0.07 M), –78 °C, 30 min, then N-SCF3 phthalimide 1c
(1.1 equiv), –78 °C, 7 h. [b] Yields of isolated pure products [c] Determined by 19F NMR analysis on crude reaction mixtures.
[d] 1.5 equiv of N-SCF3 phthalimide 1c were used. [e] 1.5 equiv. of N-SCF3 saccharin were used. N.R.: no reaction. [f] The two
diastereomers failed to be separated by column chromatography.
3
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10.1002/adsc.201701474
Advanced Synthesis & Catalysis
Table 3. Diastereoselective trifluoromethylthiolation of -aryl substituted chiral oxazolidinones.[a]
O
O
O
O
LiHMDS (1.2 equiv)
N-SCF3 phthalimide (1.5 equiv)
Ar
Ar
N
N
O
O
CF3S
THF, –78 °C, 7h
3
2
Entry
1
Yield [%][b]
d.r.[c]
87:13
Entry
5
Yield [%][b]
d.r.[c]
81:19
Product 3
Product 3
F
O
O
O
O
77
68
N
N
N
O
O
CF3S
CF3S
3l
3p
MeO
O2N
F3C
O
O
O
O
2
3
4
N
84
72
79
78
81
56
95:5
98:2
80:20
97:3
6
7
O
O
CF3S
CF3S
3m
3q
O
O
O
O
70:30[d]
N
O
N
CF3S
O
CF3S
3n
3r
O
O
MeO
O
O
N
70:30
8
O
CF3S
N
O
CF3S
3o
3s
[a] Reaction conditions: 2 (0.25 mmol), LiHMDS (1.2 equiv), THF (0.07 M), –78 °C, 30 min, then N-SCF3 saccharin 1a (1.5
[d]
equiv), –78 °C, 7 h. [b] Yields of isolated pure products [c] Determined by 19F NMR analysis on crude reaction mixtures.
The two diastereomers failed to be separated by column chromatography. [e] The reaction was conducted on 1 mmol of
substrate.
To explore the scope of the reaction, we synthesised
a large panel of (R)-4-phenyloxazolidinone derivatives
2a-s, starting from the corresponding acyl chlorides,
and then submitted them to our optimised reaction
conditions. Pleasingly, these conditions showed great
compatibility with substrates carrying linear or
branched alkyl chains of diverse lengths (Table 2,
entries 2-6). Indeed, products 3b-f could be isolated
with good yields and excellent dr values (up to 100:0
for 3d). Quite intuitively, oxazolidinone derivatives
featuring bulky R groups offered higher dr values, as
they favour even more greatly the preferential
formation of the (Z)-lithium enolate by steric
hindrance.
The reaction also proceeded smoothly with more
complex substrates, displaying functional groups such
as a terminal C=C double bond, a halogen atom or an
ether or ester moiety (Table 2, entries 7-10).
Nonetheless, it was necessary to slightly tune the
reaction conditions in order to reach satisfactory yields
for the latter. This way, products 3g-i were recovered
with moderate yields and good dr values. On the other
hand, substrate 2j, carrying an ester group, afforded a
more disappointing dr (63:37) for 3j, which may be
attributed to its highly enolisable nature. As for the
limitations of the reaction, it could unfortunately not
be extended to obtain quaternary stereocentres: indeed,
the α-methylated substrate 2k showed no sign of
conversion either in the usual conditions or with
additional heating (Table 2, entry 11).
We next turned our attention to -aryl-substituted
substrates. Nonetheless, when performing the reaction
on (R)-4-phenyl-3-(phenylacetyl)-1,3-oxazolidin-2-
one 2l, a significant decrease of diastereoselectivity
was witnessed. To overcome this issue, the
experimental conditions were slightly tuned.
Fortunately, it was determined that when using 1.5
equivalents of N-SCF3 saccharin 1a as the SCF3 donor
source, the dr value rose from 59:41 to 87:13 (see
Table S1 in Supporting Information). After this short
optimisation, several -aryl substituted oxazolidinone
derivatives carrying diverse functional groups on para
position were submitted to the new reaction conditions,
and were successfully converted into the
corresponding products with moderate to good yields
(Table 3, entries 1-6). As for diastereoselectivity, a
clear tendency was observed: substitution of the
phenyl ring by an electron-withdrawing group lowered
4
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10.1002/adsc.201701474
Advanced Synthesis & Catalysis
O
N
F3CS
O
O
Li
N
Li
O
O
O
O
Re face
O
O
SCF3
O
O
O
LiHMDS
R
R
R
R
N
N
N
O
O
R
H
O
N
O
O
CF3S
shielded Si face
major (Z)-enolate
(R, R)-diastereomer
(R)-auxiliary
Scheme 1. Putative mechanism of the trifluoromethylthiolation reaction
the dr value, while an electron-donating group allowed
it to increase. Additionally, two naphthyl-substituted
product 3q to usual basic hydrolysis conditions. To
avoid the racemisation of the product, a number of
procedures were screened to obtain ester 6, through the
formation of acid 5 (see Table S2 in Supporting
Information). It was finally found out that the loss of
chiral information could not be totally prevented, but
could however be minimised when using LiOH/H2O2
at 0 °C in the shortest amount of time possible. Indeed,
when compound 3q was first reacted with a mixture of
LiOH and H2O2 in THF/H2O at 0 °C for 10 min, then
with TMSCHN2 in DCM / MeOH immediately after a
short treatment, ester 6 was isolated with an overall
yield of 85% and 96:4 enantiomeric ratio (er). An
alternative route to the ester 6 was envisaged by
oxidation of the alcohol 4b into the carboxylic acid
followed by methyl esterification. Eight different
oxidation conditions were tested but unfortunately the
enantiomeric ratio measured for ester 6 was at best
80:20 (see Table S3 in Supporting Information). To
rationalise such facilitated racemisation process, we
evoke the stabilisation of the carbanion in the -
position of the carboxyl group by the SCF3 substituent
through d–p -resonance that causes a significant
acidifying effect propitious to the racemisation
event.[26]
compounds
also
afforded
their
trifluoromethylthiolated counterparts in good yields
and good to excellent dr values (Table 3, entries 7-8).
Special precautions had to be taken for purification of
products 3r and 3s, as epimerisation occurred on the
silica gel column chromatography in basic or neutral
conditions. Nevertheless, adding 1% acetic acid to the
used eluent allowed preventing this phenomenon from
happening. Interestingly, this methodology could be
exploited for the synthesis of ibuprofen and naproxen
SCF3 analogue precursors, respectively 3q and 3s.
Moreover, the reaction could be scaled-up from
0.25 to 1 mmol without negatively impacting the yield
or dr (Table 3, entries 6 and 8).
As for the structure of the obtained
trifluoromethylthiolated compounds, X-Ray analysis
of compound 3a ascertained the major formation of the
(R, R)-diastereomer (Figure 3).[25]
• Accessto alcohols
O
O
NaBH4
R
R
THF/H2O 3:1
N
OH
O
CF3S
CF3S
rt, 16 h
3a: R = Bn
3q: R = 4-iBuC6H4
4a: R = Bn
4b: R= 4-iBuC6H4 93%; 100:0 er
89%; 100:0 er
Figure 3. X-Ray crystal structure of the major diastereomer
of compound 3a.
• Accessto ester through acid
i-Bu
Such information confirmed that the chelated (Z)-
lithium enolate was indeed predominantly formed
when reacting the substrate with LiHMDS, and that it
was subsequently approached by the electrophilic
SCF3 source from the less shielded re face of the imide
enolate, resulting in the generation of a (R)
stereocentre (Scheme 1).
i-Bu
1) LiOH, H2O2
THF/H2O 5:4
0 °C, 10 min
O
O
O
N
OMe
O
CF3S
CF3S
2) TMSCHN2
DCM/MeOH 5:1
rt, 10 min
6
3q
85%; 96:4 er
To further enlighten the synthetic utility of this
method, we turned our attention to the cleavage of the
chiral auxiliary. Pleasingly, in the presence of NaBH4,
major diastereomers of 3a and 3q were faithfully
converted into the corresponding enantiomerically
pure alcohols with full stereoretention as ascertained
by chiral HPLC analysis (Scheme 2). On the other
hand, accessing the optically pure acids and esters was
much more problematic. Indeed, full retention of the
stereointegrity could not be achieved when submitting
i-Bu
O
OH
CF3S
5
Scheme 2. Cleavage of the chiral auxiliary: access to
enantiopure α-SCF3 alcohols and enantioenriched α-SCF3
esters.
5
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10.1002/adsc.201701474
Advanced Synthesis & Catalysis
Conclusion
6155; d) J.-A. Ma, D. Cahard, Chem. Rev. 2008, 108,
PR1.
In conclusion, we conducted a detailed study of the
[3] a) H. Chachignon, E. V. Kondrashov, D. Cahard,
diastereoselective
electrophilic
Fluorine
Notes
2017,
113,
DOI
trifluoromethylthiolation of Evans-type chiral lithium
imide enolates to afford -SCF3-substituted carbonyl
compounds with high to total relative stereocontrol.
The new stereogenic secondary carbon centres that
feature the SCF3 motif are formed via a highly
predictable stereochemical transition-state model.
Cleavage of the chiral auxiliary allowed to obtain
enantiomerically pure -SCF3-substituted alcohols
without racemisation. This synthetic route represents a
great improvement compared to the method via
organocatalytic trifluoromethylthiolation of aldehydes
that afforded only 11% ee for the same compound, i.e.
4a. Despite all our efforts, isolated diastereopure
products could not be transformed into enantiopure
methyl esters because of partial racemisation leading
to 96:4 er at best.
10.17677/fn20714807.2017.04.03; b) M. Li, X.-S. Xue,
J.-P. Cheng, ACS Catal. 2017, 7, 7977–7986.
[4] X. Wang, T. Yang, X. Cheng, Q. Shen, Angew. Chem.,
Int. Ed. 2013, 52, 12860–12864.
[5] T. Bootwicha, X. Liu, R. Pluta, I. Atodiresei, M.
Rueping, Angew. Chem., Int. Ed. 2013, 52, 12856–
12859.
[6] Q.-H. Deng, C. Rettenmeier, H. Wadepohl, L. H. Gade,
Chem. Eur. J. 2014, 20, 93–97.
[7] B.-L. Zhao, D.-M. Du, Org. Lett. 2017, 19, 1036–1039.
[8]M. Rueping, X. Liu, T. Bootwicha, R. Pluta, C. Merkens,
Chem. Commun. 2014, 50, 2508–2511.
[9] T. Yang, Q. Shen, L. Lu, Chinese J. Chem. 2014, 32,
678–680.
Experimental Section
[10] X. L. Zhu, J. H. Xu, D. J. Cheng, L. J. Zhao, X. Y. Liu,
B. Tan, Org. Lett. 2014, 16, 2192–2195.
General procedure for the diasteroselective electrophilic
trifluoromethylthiolation of oxazolidinone derivatives:
LiHMDS (1M solution in THF, 0.30 mmol, 1.2 equiv.) was
added dropwise to a solution of substrate (0.25 mmol, 1.0
equiv.) in 2 mL dry THF cooled down to –78 °C, under
nitrogen atmosphere. After 30 minutes of stirring, a solution
of appropriate SCF3 reagent (0.28 mmol, 1.1 equiv. of N-
SCF3 phthalimide / 0.38 mmol, 1.5 equiv of N-SCF3
saccharin) in 1.5 mL dry THF was slowly added to the
reaction mixture, which was then stirred at –78 °C for 7 h.
The reaction was then quenched by addition of 1.5 mL of
saturated NaHCO3 solution. The reaction mixture was
warmed up to room temperature, diluted with 3 mL of water,
vigorously stirred for 5 minutes, then extracted with EtOAc
(3 x 30 mL). The combined organic layers were washed with
brine, dried over anhydrous Na2SO4 and concentrated under
vacuum. The crude product was purified by silica gel
column chromatography with an appropriate ratio of
cyclohexane and EtOAc as eluent.
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“Ministère de la Recherche et de l’Enseignement Supérieur” for a
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7
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10.1002/adsc.201701474
Advanced Synthesis & Catalysis
FULL PAPER
Diastereoselective Electrophilic
Trifluoromethylthiolation of Chiral
Oxazolidinones: Access to Enantiopure -SCF3
Alcohols
R
OH
O
O
O
O
LiHMDS, THF, –78 °C
CF3
S
R
R
100:0 er
N
N
O
O
O
O
O
CF3
S
O
S
R
N
SCF3
N
SCF3
OMe
Adv. Synth. Catal. Year, Volume, Page – Page
or
CF3
S
O
O
18 examples
96:4 er
56–85 % yield
up to 100:0 dr
Hélène Chachignon, Evgeniy V. Kondrashov, and
Dominique Cahard*
8
This article is protected by copyright. All rights reserved.