1,4-addition of TMSCCl3 to nitroalkenes: Efficient reaction conditions and mechanistic understanding

Article abstract of DOI:10.1002/chem.201402394

Improved synthetic conditions allow preparation of TMSCCl₃ in good yield (70 %) and excellent purity. Compounds of the type NBu₄X [X=Ph₃SiF₂ (TBAT), F (tetrabutylammonium fluoride, TBAF), OAc, Cl and Br] act as catalytic promoters for 1,4-additions to a range of cyclic and acyclic nitroalkenes, in THF at 0-25 °C, typically in moderate to excellent yields (37-95 %). TBAT is the most effective promoter and bromide the least effective. Multinuclear NMR studies (¹H, ¹⁹F, ¹³C and ²⁹Si) under anaerobic conditions indicate that addition of TMSCCl₃ to TBAT (both 0.13 M) at -20 °C, in the absence of nitroalkene, leads immediately to mixtures of Me₃SiF, Ph₃SiF and NBu₄CCl₃. The latter is stable to at least 0 °C and does not add nitroalkene from -20 to 0 °C, even after extended periods. Nitroalkene, in the presence of TMSCCl₃ (both 0.13 M at -20 °C), when treated with TBAT, leads to immediate formation of the 1,4-addition product, suggesting the reaction proceeds via a transient [Me ₃Si(alkene)CCl₃] species, in which (alkene) indicates an Si O coordinated nitroalkene. The anaerobic catalytic chain is propagated through the kinetic nitronate anion resulting from 1,4 CCl₃ ^- addition to the nitroalkene. This is demonstrated by the fact that isolated NBu₄[CH₂=NO₂] is an efficient promoter. Use of H₂C=CH(CH₂)₂CH=CHNO ₂ in air affords radical-derived bicyclic products arising from aerobic oxidation. Understanding TMSCCl₃: The synthesis and reactivity of TMSCCl₃ has been investigated. The mechanism of 1,4-CCl₃ addition to nitroalkenes begins with nitroalkene coordination, followed by the attack of an external fluoride ion, and does not involve the formation of NBu₄[Me₃SiFCCl₃] (see figure).

Full text of DOI:10.1002/chem.201402394

DOI: 10.1002/chem.201402394
Full Paper
&
Synthetic Methods
1,4-Addition of TMSCCl3 to Nitroalkenes: Efficient Reaction
Conditions and Mechanistic Understanding
Na Wu, Benoit Wahl, Simon Woodward,* and William Lewis[a]
Abstract: Improved synthetic conditions allow preparation
of TMSCCl3 in good yield (70%) and excellent purity. Com-
pounds of the type NBu4X [X=Ph3SiF2 (TBAT), F (tetrabutyl-
ammonium fluoride, TBAF), OAc, Cl and Br] act as catalytic
promoters for 1,4-additions to a range of cyclic and acyclic
nitroalkenes, in THF at 0–258C, typically in moderate to ex-
cellent yields (37–95%). TBAT is the most effective promoter
and bromide the least effective. Multinuclear NMR studies
(1H, 19F, 13C and 29Si) under anaerobic conditions indicate that
addition of TMSCCl3 to TBAT (both 0.13m) at À208C, in the
absence of nitroalkene, leads immediately to mixtures of
Me3SiF, Ph3SiF and NBu4CCl3. The latter is stable to at least
08C and does not add nitroalkene from À20 to 08C, even
after extended periods. Nitroalkene, in the presence of
TMSCCl3 (both 0.13m at À208C), when treated with TBAT,
leads to immediate formation of the 1,4-addition product,
suggesting the reaction proceeds via a transient [Me3Si-
(alkene)CCl3] species, in which (alkene) indicates an Si···O co-
ordinated nitroalkene. The anaerobic catalytic chain is propa-
gated through the kinetic nitronate anion resulting from 1,4
À
CCl3 addition to the nitroalkene. This is demonstrated by
the fact that isolated NBu4[CH2=NO2] is an efficient promoter.
Use of H2C=CH(CH2)2CH=CHNO2 in air affords radical-derived
bicyclic products arising from aerobic oxidation.
Introduction
Despite its potential for use in organic synthesis, applications
of TMSCCl3 (TMS=SiMe3) have been far narrower in scope
than those of closely related TMSCF3 (Ruppert–Prakash re-
agent).[1] Two reasons can be identified as the origins of this
situation. Firstly, all present literature preparations of TMSCCl3
provide either low-to-modest isolated yields,[2] or rely on ex-
treme low-temperature protocols (typically À110 8C),[2] limiting
easy access to this reagent. Secondly, most applications of
TMSCCl3 require its “activation” by a silylphilic promoter, typi-
cally a fluoride ion. The intimate mechanism(s) by which this
process proceeds are presently based on ad hoc suggestions
rather than tangible data. In such environments it is possible
to select reaction conditions that may not be mechanistically
optimal. Although TMSCCl3 is known to participate in a small
number of 1,2-additions to aldehydes,[3] ketones[3] and imine
derivatives (Scheme 1),[4] 1,4 addition modes are practically un-
known and are limited to just six examples, with modest
yields, in a single paper by Cunico and Zhang.[5] We were inter-
ested to identify improved experimental conditions for such
reactions and to understand the underlying mechanism of 1,4-
addition of TMSCCl3. New access to b-CCl3-substituted nitroal-
Scheme 1. Known 1,2- versus 1,4-additions of TMSCCl3. Boc=tert-butoxy-
carbonyl.
kanes is of interest, and Sosnovskikh et al., and others,[6] have
developed a range of unusual and useful methods around this
motif.
[a] Dr. N. Wu,+ Dr. B. Wahl,+ Prof. Dr. S. Woodward, Dr. W. Lewis
School of Chemistry, University of Nottingham, University Park
Nottingham NG7 2RD (UK)
Fax: (+44)115-951-3564
E-mail: simon.woodward@nottingham.ac.uk
[+] These authors contributed equally to this work
Results and Discussion
For the conjugate-addition mechanistic investigations we re-
quired access to large amounts of highly pure TMSCCl3. Un-
fortunately, current literature preparations[2] have significant
limitations, either in yield, purity of reagent attained, reprodu-
cibility or the need for special conditions. These issues are due
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402394.
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to the fragility of MCCl3 (typically M=Li or Na) intermediates.
Facile decomposition of these intermediates leads to dichloro-
carbene-derived byproducts. We reasoned that the use of low-
cost TMSCl (ca. E 0.1 per mL) as a co-solvent (5 equiv) would
Table 1. Promoter comparison for TMSCCl3 addition to 1a.[a]
À
significantly enhance CCl3 capture, improving the TMSCCl3
yield. Addition of LiHDMS (lithium hexamethyl disilazide) in
hexane/THF (65:20) to a chloroform/TMSCl (12:64) mixture at
À658C, followed by slow warming to ambient temperature
proved optimal. After an appropriate workup, Kugelrohr subli-
mation routinely afforded pristine material in 64–70% yield on
a >10 g scale. The nitroolefins, 1, for our study were prepared
by using a one-pot procedure by Dauzonne and Royer,[7] a con-
densation method by Andrew and Raphael[8] or by using
a very recent AgNO2 method by Maiti et al.[9] (Scheme 2). The
Entry
Promoter
Solvent
2a [%]
Rate (rel.) [sÀ1
]
1
2
3
4
5
6
7
8
9
CsF
NBu4Cl
NBu4OAc
NBu4F
NBu4Ph3SiF2
NBu4Br
NBu4Cl
NBu4OAc
NBu4F
either[b]
THF
THF
THF
<10[c]
>95
>95
>95
>95
37
>95
>95
>95
>95
n.d.
n.d.
n.d.
n.d.
n.d.
THF
toluene
toluene
toluene
toluene
toluene
2.6ꢂ10À5 (0.03)
7.6ꢂ10À4 (1.0)
1.4ꢂ10À3 (1.8)
2.0ꢂ10À3 (2.7)
2.5ꢂ10À3 (3.3)
10
NBu4Ph3SiF2
[a] Carried out on 0.3 mmol 1a (0.06m). Yield data obtained from GC
analysis in the presence of an internal standard (1-methylnaphthalene,
25 mL, 0.18 mmol). [b] Use of either solvent resulted in inefficient cataly-
sis; [c]>95% of 2a could only be attained after 24 h in THF with excess
CsF (3.75 equiv). n.d.=not determined.
ene, entries 6–10) solvents. The less-silylophilic promoter,
NBu4Br, led to a very slow turnover. Due to the speed of the re-
actions in THF at 208C no rate estimates could be attained (en-
tries 2–5). However, approximate initial rates (based on conver-
sion in the first 20 sec) could be attained in toluene, confirm-
ing the high efficacy of TBAT; in the absence of any promoter
no reaction occurred. The spectroscopic properties of 2a are in
accord with 1,4-addition of the trichloromethyl group. In par-
ticular, a characteristic multiplet is seen at dH =5.56 ppm in the
1H NMR spectrum, correlating to the 13C NMR CH signal a to
the nitro group at dC =80.7 ppm. The b-CH group is diagnosti-
cally shifted to lower frequency (dC =56.3 ppm in 2a) com-
pared with its C=CH precursor (dC =139.2 ppm in 1a), whereas
a low-intensity quaternary signal at dC =100.8 ppm is assigned
to CCl3 and the molecular ion of 2a shows the expected Cl3
isotope pattern.
The conditions of Table 1 (entry 5) could be applied to
a range of nitroalkene substrates, leading to various 1,4-addi-
tion products in 37–95% isolated yields (Scheme 3). For the
acyclic systems reversal of the addition mode proved optimal.
The connectivity of 2d could be confirmed by an X-ray crys-
tallographic study (Figure 1). In comparison, the 27 structures
in the Cambridge Crystallographic Database[6] showing the
same NO2CaHCbHCCl3 motif have: NÀCa 1.49–1.53, CaÀCb 1.52–
1.55 and CbÀCCl3 1.51–1.57 ꢁ; N- Ca-Cb 105.8–117.1 and Ca-Cb-
CCl3 111.2–117.1 o. Two closely related six-ring structures
(CIBGIF and HACJAY) show anti arrangements, as in 2d, but
a syn motif is also known (QEMZUE).[6]
Scheme 2. Preparation of nitroalkene starting materials. TEMPO=2,2,6,6-
tetramethylpiperidine N-oxide; Cy=cyclohexyl.
advantage of the former two methods, although the yields are
often modest, is that they are technically simple and provide
a direct route to the 3-nitro-2H-chromenes and styrenyl sys-
tems, respectively. The advantage of the latter procedure is its
wide and general scope. Initial studies on substrate 1a
(Table 1) confirmed the findings of Cunico and Zhang,[5] but in-
dicated that CsF is an unreliable promoter because of its low
solubility in organic solvents. Soluble NBu4X [X=Cl, OAc, F and
especially Ph3SiF2 (TBAT)] were found to be efficient promoters
at 5 mol% in both polar (THF, entries 2–5) and non-polar (tolu-
The following scope and limitation comments should be
made: i) Addition of TMSCCl3 to the substrate and TBAT cata-
lyst was appropriate for a-substituted substrates 1a–e and 1q.
However, for terminal nitroalkenes (1 f–p) the alkene needed
to be added slowly (over 1 h) to TMSCCl3/TBAT mixtures to
avoid polymerisation, which led to unacceptable yields of 2. ii)
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strate 1r was used to provide
potential intramolecular radical
trapping sites. The standard re-
action conditions (slow addition
of 1r to TMSCCl3/TBAT under
argon) led to trace amounts
(15%) of bicyclic 2r, and the ma-
jority of the starting material re-
mained unconverted after the
typical reaction time of 1–16 h
(Scheme 4). However, if the reac-
tion was conducted under aero-
bic conditions 2r became the
major product. TMSCCl3 solu-
tions in THF, in the presence of
TBAT and O2 (one molar equiva-
lent of oxygen injected into
a sealed reaction), were analysed
by 29Si NMR spectroscopy and
revealed a significant amount of
a single silicon-containing spe-
cies
showing
dSi =7.4 ppm.
Scheme 3. Isolated addition products from TBAT-catalysed (5 mol%) additions of TMSCCl3 to nitroalkenes 1.
Based on comparison with litera-
Figure 1. Molecular structure of 2d. Selected interatomic distances and
angles: C(1)ÀC(4) 1.556, C(3)ÀC(4) 1.544, N(1)ÀC(3) 1.519 ꢁ; C(1)-C(4)-C(3)
109.2, N(1)-C(3)-C(4) 111.3 o. Dihedral angle N(1)-C(3)-C(4)-C(1) 115.4 o.
Scheme 4. Aerobic cyclisation of substrate 1r.
Acyclic a-substituted nitroalkenes led to very poor reactions
and this substrate class was not further pursued; b-substitution
provided clean products (e.g. 2m), but in reduced yield. iii) Al-
though alkyl, ether, ester, alkene and CÀF functional groups
were tolerated in various degrees, some aryl bromide-contain-
ing substrates (e.g. 8-bromo-3-nitro-2H-chromene) and benzyl-
ic (E)-BnCH=CHNO2 were not tolerated and led only to decom-
position. Given the known relative stability of the CCl3 radical,
and its propensity to add to unsaturated systems (Kharasch
et al.[10]), tests were carried out to assess the veracity of such
reaction pathways. Firstly, it was observed that the presence of
the known radical inhibitors hydroquinone or butylated hy-
droxytoluene (BHT) did not prevent TBAT-catalysed additions
to 1d under strictly anaerobic conditions. Secondly, the sub-
ture silicon NMR shift values[11] we assigned this new species as
TMS2O. One explanation for the formation of 2r is reaction of
TMSCCl3 (in the presence of TBAT) with O2, leading to TMS2O2
and CCl3 radicals that cascade to 2r, via 3 and 4. Although we
could not detect any TMS2O2 peroxide (dSi ꢀÀ27 ppm[12]) in air
or in O2-exposed samples of TMSCCl3, in the presence or ab-
sence of TBAT, the latter was rapidly converted to TMS2O. It is
likely that any peroxide would be both generated and decom-
posed as shown in Scheme 4. The siloxane can also be gener-
ated from TMSOH generated by elimination from 4. Literature
bicycles related to 2r have been generated, either by oxidation
of nitronate anions[13] or through nitrile oxide formation and
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subsequent [2+3] cycloaddition chemistry,[13] from the expect-
ed 1,4-addition product 5. Although we cannot completely ex-
clude such possibilities, such approaches normally require
stronger oxidants than molecular oxygen or prolonged heating
at 608C.[13] The connectivity of 2r could be confirmed by an X-
ray crystallographic study on its dehydrochlorination product
2r’, obtained through simple MgSO4 drying/recrystallisation of
2r (Figure 2). Formation of the C=CCl2 bond is also evident in
the 13C NMR spectrum, in which the diagnostic CCl3 signal at
dC =99.4 ppm in 2r is replaced by two quaternary alkene sig-
nals (dC =121.4 and 126.7 ppm). Both 2r and 2r’ have a C=N
tions of 0.125m in THF/[D6]benzene (5:1) at À208C offered the
best compromise with respect to solubility, 29Si sensitivity and
attainment of O2-free conditions. Temperatures of À208C are
also the lowest at which viable catalytic reactions are possible,
indicating that the reactions should be slowed to only primary
events at this temperature. Representative 29Si NMR spectra
are given in Figure 3. In an initial set of conditions at À208C,
TMSCCl3 (dSi =21.9 ppm) was immediately converted to TMSF
(dSi =32.4 ppm)[15] on addition of TBAT (dSi =À108.8 ppm),[16]
which itself was transformed to Ph3SiF (dSi =À4.1 ppm)[17]
(Figure 3). No other silicon-containing species were present,
except for traces of TMS2O (dSi =7.3 ppm)[11] (which could be
minimised/eliminated by good experimental technique to
eliminate the last traces of O2). The JSiF coupling pattern is indi-
cative of the number of attached fluorine atoms in these spe-
cies. The residual TBAT species, TMSF and Ph3SiF could be cor-
related to signals at dF =À98.9,[17] À158.0[15] and
À170.5 ppm[16] in the 19F NMR spectrum of the reaction mix-
ture at À208C (see the Supporting Information). This account-
ed for >98% of all the fluorine-containing species. The 29Si
and 19F NMR spectra of the same reaction mixture at +208C
show only very slight broadening, indicating that any ex-
change between the species detected is, at best, very slow
under the reaction conditions. At À208C the 13C NMR spectrum
of the TMSCCl3/TBAT mixture, in the methyl region, confirmed
the presence of Me3SiF (dC =À0.4 ppm, JCF =15.5 Hz) and a sin-
glet peak (dC =1.6 ppm) ascribed to the expected exchange
product, NBu4CCl3. This latter compound is stable at À208C in-
definitely, no evidence of formation of tetrachlorethene (dC =
Figure 2. Molecular structure of 2r’. Selected interatomic distances and
angles: N(1)ÀC(6A) 1.258, N(1)ÀO(2) 1.431, C(6)ÀC(7) 1.324 ꢁ; C(6A)-N(1)-O(2)
107.5, C(7)-C(6)-C(6A) 127.1 o.
À
120.7 ppm), or any other CCl3 or dichlorocarbene-derived by-
resonance
(dC =167.6
and
166.5 ppm, respectively). The
structure of 2r’ is reminiscent of
other tetrahydro-3H-cyclopenta-
[c]isoxazoles in the Cambridge
Crystallographic Database.[14]
Despite the aerobic cyclisation
shown in Scheme 4, we could
not attain any evidence for radi-
cal involvement under strict
anaerobic conditions. In particu-
lar, the observation of low, but
reproducible, ee values in the
formation of 2q by using chiral
promoters at low substrate con-
version suggested that a different
reaction mechanism operates
under O2-free conditions. To the
best of our knowledge, no study
of the explicit reaction mode of
TMSCCl3 with NBu4SiPh3F2 (TBAT)
has been carried out, therefore,
we sought to define the non-
radical process by multi-nuclear
Figure 3. 29Si NMR spectra (79.5 MHz, 5:1 THF/[D6]benzene, À208C): a) TMSCCl3 (d=21.9 ppm); b) TBAT
(d=À108.8 ppm, J(SiÀF)=254 Hz); c) a nominal 1:1 mixture of TMSCCl3/TBAT (a slight excess of TBAT was used to
provide a spectral internal standard), TMSF (d=32.4 ppm, J(SiÀF)=275 Hz), TMS2O (d=7.3 ppm), Ph3SiF
NMR studies. Reagent concentra- (d=À4.1 ppm, J(SiÀF)=282 Hz).
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products was seen in the spectra. No reaction was observed
when nitroalkene 1a was added last to the above mixture,
which was then warmed from À20 to 08C (conditions under
which the catalytic reaction is spontaneous).
ture down to À208C. Further cooling of the reaction was not
possible because of the formation of non-homogeneous sam-
ples, and heating the sample was not possible. However, the
data are generally in accord with attack of an external nucleo-
phile, in this case fluoride ions (either directly or indirectly
from TBAT[18]), on 6, triggering CCl3 transfer, presumably
through a chair-like transition state, leading to 7. Finally, due
to the strength of the SiÀF bond in TMSF (and the clear lack of
exchange with this species in the NMR studies) it is nitronate 8
that is expelled and detected spectroscopically. If the conclu-
sions of the stoichiometric reac-
In a separate set of conditions, nitroalkene 1a was first
added to TMSCCl3 at À208C. The 1H NMR spectrum in the
region dH =6.8–8.0 ppm contains the aryl and alkene signals of
1a (see Figure 4a,b). The signal of TMSCCl3 is at dH =0.20 ppm
(not shown in Figure 4). The equivalent 13C NMR spectra con-
firm <5% reaction of alkene and TMSCCl3 because only the
tions shown in Scheme 5 can be
translated to the catalytic reac-
tions, three clear predictions can
be made: i) Nitronate anions
themselves should be excellent
promoters of the reaction. ii) If
the concentration of nitronate
(or indeed any other anionic
promoter nucleophile) builds up
over time, a wide range of nucle-
ophilic promoters (NuÀ) will be
available to replace fluoride (FÀ)
in the key conversion of 6 into 7
(Scheme 5). iii) Under such con-
ditions, the ee value of the 1,4-
addition product, produced by
an asymmetric source of NuÀ
should decrease over time (due
to competition with an increas-
ingly populated pool of promot-
er anions). To check these sup-
positions
we
prepared
NBu4[CH2=NO2] from nitrome-
thane and found that it does
indeed promote rapid quantita-
tive conversion of 1a into 2a.
1
Figure 4. Partial H NMR spectra (5:1 THF/[D6]benzene, À208C): a) alkene 1a; b) a nominal 1:1 mixture of alkene
*
1a and TMSCCl3; c) After addition of 1 equiv of TBAT to mixture (b). Signals due to TBAT are marked ( ), those
due to Ph3SiF (&) and those due to the proposed nitronate product 8 (D).
characteristic peaks of 1a and TMSCCl3, at dC =À4.5 ppm are
present. The 29Si NMR spectrum of the reaction mixture shows
only the presence of TMSCCl3. Subsequent addition of TBAT at
À208C to this mixture leads to partial (38%), but immediate,
conversion of 1a into a new compound with 1H (Figure 4c)
and 13C NMR spectra (see the Supporting Information) that are
closely related to those of the addition product 2a. This new
species is assigned as nitronate 8 (Scheme 5). In some experi-
ments traces of a new species could be detected before the
addition of TBAT (See Figure 4b). This species could only be
identified as a product of nitroalkene decomposition, or spe-
cies 6 (see below).
Overall, the data from the stoichiometric NMR experiments
are in accord with Scheme 5. Once formed, NBu4CCl3 is insuffi-
ciently nucleophilic to directly attack the nitroalkene and equi-
libration back to TMSCCl3 is not possible. Rather, the nitroal-
kene binds TMSCCl3 by means of an electron-rich NÀO contact,
providing 6. We could detect no exchange broadening of the
minor signals observed in Figure 4b from ambient tempera-
Scheme 5. Mechanistic proposal from stoichiometric NMR studies.
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The chiral complex [Ni(Duphos)2](acac)2 (Duphos=(R,R)-methyl-
Duphos, CAS [147253-67-6]; acac=acetylacetonate) was found
to be an, albeit poor, promoter of asymmetric trichlomethyla-
tion of 1q (see the Supporting Information). Nevertheless, the
ee value of 2q formed by using this catalyst (10 mol%) does
decrease reproducibly from 15 to <1% over 20 h, in line with
predictions. The bifunctional chiral catalyst by Takemoto
et al.[19] (10 mol%), associated with TBAF as a co-promoter
(10 mol%), also led to a decrease in the ee value of 2q over
time (from 26% to <1%). Based on all of the data it seems
likely that Scheme 6 is the most rational description of the cat-
alytic cycle. The nitronate product, 8, can either act as a pro-
moter itself or leave the promoter pool by means of a reaction
with either TMSX (X=CCl3 or Nu, if Nu is a suitable leaving
group).
tent with pre-coordination of the nitroalkene to the silicon re-
agent before its promotion by a silylphilic nucleophile. At-
tempts to develop asymmetric versions of this reaction will
prove to be challenging for mechanistic reasons. The kinetical-
ly derived nitronate product of the reaction is itself a highly ef-
fective chain carrier, and attaining a competitive chiral catalyst
or alternative conditions will be critical for success. Investiga-
tions into such approaches and the use of other acceptors are
underway.
Experimental Section
Full details of all transformations and associated spectroscopic
data are given in the Supporting Information. Nitroolefins 1a–
e were prepared by Dauzonne and Royer’s one-pot procedure[7]
.
Alkene 1a showed identical spectroscopic properties to previously
reported samples.[20] Compounds 1b–e, previously unreported,
were fully characterised (see the Supporting Information). Nitroole-
fins 1g–l were prepared by Andrew and Raphael’s condensation
method[8] and had identical spectroscopic properties to previously
reported samples.[9,21,22] Nitroolefins 1m–r were prepared by the
AgNO2 method by Maiti et al.,[9] and had identical spectroscopic
properties to previously reported samples.[9,23]
General procedure for trichloromethylation of cyclic
substrates
Trimethyl(trichloromethyl)silane (TMSCCl3; 0.21 g, 1.1 mmol) in THF
(2 mL) was added dropwise to a solution of the cyclic nitroalkene
(1 mmol) and tetrabutylammonium triphenyldifluorosilicate (TBAT;
0.027 g, 5 mol%) in THF (2 mL) under argon at room temperature,
and the reaction mixture was stirred overnight. The mixture was
concentrated in vacuo and then purified by flash chromatography
on silica gel to give the corresponding Michael addition products.
Alternatively, the reactions were quenched with saturated NH4Cl
(aq), extracted with ethyl acetate, dried over anhydrous MgSO4 and
concentrated before purification by chromatography.
Scheme 6. Proposed catalytic cycle.
Finally, the use of the 1,4-addition products, 2, for the forma-
tion of other products was briefly investigated. Treatment of
2a with KOtBu in THF led to the formation of dichlorocyclo-
propane 9 in moderate yield (Scheme 7), through a-CH depro-
tonation. However, the equivalent acyclic systems showed
General procedure for trichloromethylation of acyclic
substrates
The acyclic alkene (1 mmol) in THF (2 mL) was added dropwise,
over a period of one hour, to a so-
lution of trimethyl(trichlorome-
thyl)silane
(TMSCCl3;
0.21 g,
1.1 mmol) and tetrabutylammoni-
um triphenyldifluorosilicate (TBAT;
0.027 g, 5 mol%) in THF (2 mL)
under argon at room temperature,
Scheme 7. Representative reactions of the 1,4-addition products.
and the mixture was stirred over-
night. The mixture was concentrat-
ed in vacuo and then purified by
flash chromatography on silica gel to give the corresponding Mi-
chael addition products.
a distinct preference for b-CH deprotonation. For example, 2 f
led to the formation of dichloroalkene 10 when treated under
the same conditions.
Acknowledgements
Conclusion
Catalytic 1,4-additions of TMSCCl3 to electron-deficient Michael
acceptors have considerable potential for use in organic
chemistry. The mechanistic studies presented here are consis-
We are grateful to the Engineering and Physical Sciences Re-
search Council (EPSRC) for support of this work through grant
EP/K000578/1.
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1105.
Keywords: brønsted base catalysis
addition · reaction mechanisms · trichloromethylation
· catalysis · Michael
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1
19
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Received: February 27, 2014
Published online on && &&, 0000
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FULL PAPER
Understanding TMSCCl3: The synthesis
and reactivity of TMSCCl3 has been in-
vestigated. The mechanism of 1,4-CCl3
addition to nitroalkenes begins with ni-
troalkene coordination, followed by the
attack of an external fluoride ion, and
does not involve the formation of
NBu4[Me3SiFCCl3] (see figure).
&
Synthetic Methods
N. Wu, B. Wahl, S. Woodward,* W. Lewis
&& – &&
1,4-Addition of TMSCCl3 to
Nitroalkenes: Efficient Reaction
Conditions and Mechanistic
Understanding
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Chem. Eur. J. 2014, 20, 1 – 8
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8
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!