Platinum-catalyzed substitution of allylic fluorides

Article abstract of DOI:10.1021/om201029m

Allyl fluorides are reactive toward Pt-catalyzed alkylation with malonate and likewise toward N- and O-nucleophiles under mild conditions. The reactivity of fluoride as a leaving group equals or exceeds that of the esters and carbonates commonly employed in allylic alkylation. The order of leaving-group ability with Pt catalysts was found to be F ≥ OCO₂Me ? OBz ≥ OAc. This discouraged the application of platinum catalysts for the reverse reaction, fluorination of allylic substrates. Fluoride displacement involves predominant or complete retention of configuration in all the observed cases, and this was confirmed as a general feature of Pt catalysis, the stereochemical integrity being as high or higher as in Pd catalysis for the examples chosen.

Full text of DOI:10.1021/om201029m

Article
pubs.acs.org/Organometallics
Platinum-Catalyzed Substitution of Allylic Fluorides
Elena Benedetto, Massaba Keita, Matthew Tredwell, Charlotte Hollingworth, John M. Brown,*
and Veronique Gouverneur*
́
Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.
S
* Supporting Information
ABSTRACT: Allyl fluorides are reactive toward Pt-catalyzed
alkylation with malonate and likewise toward N- and O-
nucleophiles under mild conditions. The reactivity of fluoride
as a leaving group equals or exceeds that of the esters and
carbonates commonly employed in allylic alkylation. The order
of leaving-group ability with Pt catalysts was found to be F ≥
OCO2Me ≫ OBz ≥ OAc. This discouraged the application of
platinum catalysts for the reverse reaction, fluorination of
allylic substrates. Fluoride displacement involves predominant or complete retention of configuration in all the observed cases,
and this was confirmed as a general feature of Pt catalysis, the stereochemical integrity being as high or higher as in Pd catalysis
for the examples chosen.
C(sp3)−F bonds6 complement the burgeoning activity in
1. INTRODUCTION
Our longstanding interest in the synthesis and chemistry of
catalyzed syntheses of C(sp2)−F bonds.7
The vast majority of allylic substitutions are carried out with
allylic fluorides provided the impetus for our recent studies
palladium or iridium catalysts.8 Many other metals are also
active,9 and we were encouraged to diversify in order to extend
the scope of allyl fluoride chemistry. Despite the close
similarities of many aspects of palladium and platinum
organometallic chemistry, Pt-catalyzed allylic sustitutions are
far less well developed and have never been applied to
organofluorine substrates. The earliest examples were provided
by Kurosawa and then Brown.10 An in-depth analysis of Pt-
catalyzed allylic substitution has been conducted by Williams
and co-workers, in which enantioselectivities comparable to
those for palladium catalysis were demonstrated.11 Their work
was conducted with rac-1,3-diphenylallyl acetate, and the
optimal conditions are shown in Scheme 2. More recently,
platinum-catalyzed allylic amination (86% ee) and allylation of
aldehydes (up to 83% ee) have been reported.12,13 Using
XantphosPtCl2 as the precatalyst, direct amination of allylic
alcohols has been achieved,14 in line with the high efficiency of
platinum complexes as catalysts for allylic amination.15 These
scattered results highlight the unrealized potential for further
examples of Pt catalysis via allylic intermediates.
centered around palladium catalysis.1 First, we demonstrated
that acyclic and cyclic allyl fluorides are reactive under
conditions for malonate substitution and that fluoride is a
better leaving group than acetate but inferior to benzoate or
carbonate (Scheme 1).2 Second, the reverse reaction whereby
Scheme 1. Palladium-Catalyzed Activation and Alkylation of
Allyl Fluorides2
Differences between Pd allyl and Pt allyl chemistry have been
noted. The stability of platinacyclobutanes is well-known,16 and
consequently nucleophilic attack at the central carbon of Pt
allyls with displacement of a 2-halo substituent has been
observed in several cases.17 Similar reactions have been
observed in palladium catalysis and, where comparable, the
Pd and Pt cases show distinct behavior.18 Catalytic allylic
allyl fluorides are themselves synthesized by Pd-catalyzed allylic
substitution was achieved. This reaction works well with p-
nitrobenzoates of primary allylic alcohols under mild
conditions.3 An enantioselective variant for cyclic substrates
employing AgF as fluoride source has been reported by Doyle4
and extended recently to acyclic cases.5 These and other related
developments in the catalytic formation or activation of
Special Issue: Fluorine in Organometallic Chemistry
Received: October 24, 2011
Published: January 20, 2012
© 2012 American Chemical Society
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Scheme 2. Prior Work on the Enantioselective Pt-Catalyzed Allylic Alkylation11
alkylation involves both η2 and η3 ligation of the reacting
fragment (and in some cases also κ1); the relative stability of
intermediate states is distinct for Pd and Pt and will also
depend on electronic factors introduced by the residual ligands
of the catalyst. With some exceptions,19 most of the
computational work to date on catalytic allylic substitution
has been directed toward Pd rather than Pt, reflecting the
respective synthetic input. Herein, we report the result of a
detailed study aimed on investigating the reactivity of allylic
fluorides under Pt catalysis.
Scheme 4. A Further Stereochemical Test in Pt-Catalyzed
Allylic Alkylation
Table 2
b
dr of 3
(syn:anti)
time
(h)
yield of 4
dr of 4
a
entry
3
M
(%)
(syn:anti)
2. RESULTS AND DISCUSSION
1
2
3
4
syn-3
syn-3
anti-3
anti-3
>98:2
>98:2
4:96
Pt
0.5
1
86
71
68
78
>98:2
97:3
A. Stereochemical Study of Pt-Catalyzed Allylic
Alkylation. At the onset of this study we were surprised to
discover the absence of a critical piece of information. Several
authors had suggested a double-inversion mechanism for Pt-
catalyzed allylic substitution with soft nucleophiles, in
accordance with the corresponding Pd-catalyzed transforma-
tion, but formal verification was lacking. We therefore applied
the classical stereochemical probe 1 to platinum catalysis.20 For
a direct comparison, the reaction was also performed with the
corresponding palladium catalyst under the same reaction
conditions. Lactone 1 was subjected to the conditions of
Scheme 3. Pd and Pt catalysts showed comparable reactivity
Pd
Pt
16
4:96
4:96
b
Pd
1
11:89
a
Isolated yields. dr determined by 1H NMR of crude reaction
mixture.
transformation was much slower than for palladium, affording
anti-4 in 68% yield within 16 h (Table 2, entry 3). Pd-catalyzed
substitution of anti-3 was complete in 1 h, yielding 78% of anti-
4. However, a partial loss of configuration occurred from the
starting material (anti-4, dr 89:11), in contrast to the case for
platinum, where the diastereomeric ratio was unchanged.
Two features that contrast Pd and Pt catalysis are apparent
from these results. First, the turnover rate is retarded in the
platinum case for anti-3. Second, there is a diminution of
stereoselectivity under palladium catalysis for anti-3. A
thorough study of the mechanism of cyclohexenyl acetate
allylation with Trost’s catalyst21 shows by DFT calculations that
the leaving group departs anti to palladium along an axial
trajectory. The TS structures derived in the same work by DFT
show that the ring conformation resembles the Pd allyl
intermediate. On this basis the first observation could be
explained if formation of the η3-allyl is the turnover-limiting
stage for platinum with anti-3, but trapping of this allyl complex
is turnover-limiting for palladium, as is normally observed. In
Pd catalysis, it was shown that with more reactive leaving
groups (such as carbonate) the rate-limiting step of the reaction
is normally the attack of the nucleophile on the π-allyl
intermediate (Scheme 5).22
Scheme 3. Initial Test for the Stereochemical Course of Pt-
Catalyzed Allylic Alkylation
Table 1
a
b
entry
M
Pt
yield of 2 (%)
dr of 2 (syn:anti)
1
2
79
>98:2
>98:2
Pd
>99
a
b
1
Isolated yields. dr determined by H NMR of the crude reaction
mixture.
and stereoselectivity, affording 2 in high yields within 30 min,
with complete retention of configuration (Table 1). This result
confirms that Pt-catalyzed allylic substitutions with soft
nucleophiles proceed with overall retention of configuration
at the reactive center.
The partial loss in stereoselectivity exhibited by Pd(PPh3)4
may be due to its propensity for epimerization at the allyl stage
promoted by a second Pd(0) species, according to the
proposals of Backvall and co-workers.23 In further work from
̈
Scheme 4 reports a more detailed analysis using both the syn
and anti diastereomers of ester 3. Under standard conditions,
the substitution of the diastereomerically pure syn-3 occurred in
comparable reaction times for Pt(PPh3)4 and Pd(PPh3)4, giving
syn-4 with complete retention of configuration, in 86% and 71%
yields, respectively (Table 2, entries 1 and 2). When the
reaction was carried out with anti-3, employed as a
diastereomeric mixture (dr 96:4), the platinum-catalyzed
the same group, conformational and stability differences
between the diastereomeric η3-allyls formed from syn- and
anti-3 were noted.24 This would clearly affect their lifetime and
hence the relative ease of epimerization.
We have thus demonstrated, for the first time, that Pt-
catalyzed allylic alkylation follows the same stereochemical
pathway as Pd catalysis. The two metals show substrate-
dependent reactivity and selectivity; platinum gives higher
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Scheme 5. Analysis of the Stereochemical Course of Pd- and Pt-Catalyzed Allylic Alkylation
Scheme 6. Internal Test for Relative Leaving Group Ability with anti-5
Table 3
substrate
anti-5
dr of anti-5
(anti:syn)
amt of Nu
(equiv)
time yield of anti-
dr of anti-6
b
yield of anti-
dr of anti-7
b
yield of anti-
dr of anti-8
b
a
a
a
entry
(h)
6
(%)
(anti:syn)
7
(%)
(anti:syn)
8
(%)
(anti:syn)
1
2
3
4
5
6
anti-5a
93:7
91:9
96:4
96:4
97:3
90:10
2
24
4
40
86:14
91:9
5
>98:2
94:6
9
6
67:33
33:67
91:9
c
anti-5a
1.2
2
31
38
28
25
12
14
anti-5b
anti-5b
anti-5c
24
24
24
3
75:25
83:17
83:17
86:14
11
13
11
8
83:17
95:5
21
1.2
2
4
64
12
67:33
94:6
>98:2
d
anti-5c
1.2
>98:2
75:25
a
b
c
d
Isolated yields. dr determined by 1H NMR of isolated products. anti-5a was recovered in 6% yield (dr >98:2). anti-5c was recovered in 25% yield
(dr 75:25).
levels of diastereoselectivity than palladium catalysis with anti
derivatives.
B. Reactivity of the Cyclohexenyl Fluoride anti-5
under Pt Catalysis. We now turn our attention to the leaving-
̀
group ability of fluoride vis-a-vis commonly used alternatives
fluorinated product 7 resulting from displacement of acetate
was isolated in 5% yield, entirely as the anti diastereoisomer.
The product anti-8 was obtained in 9% yield as a mixture of
diastereomers (dr 67:33 anti:syn). The reaction with anti-5a
was repeated, employing 1.2 equiv of sodium dimethyl
malonate and a shorter reaction time, in an attempt to avoid
the formation of the disubstituted product anti-8 so as to have
better understanding of the diastereoselectivity of the first step
(Table 3, entry 2). The reaction was quenched after 4 h, with
the starting material recovered in 6% yield as a single
diastereoisomer (dr >98:2). However, it was not possible to
stop the reaction at the first substitution step, and 6% of 8 was
also formed. The product 8 was isolated mainly as the syn
isomer with a diastereomeric ratio of 67:33. This result proved
our hypothesis of the higher reactivity of the syn isomer of
intermediates 6 and 7 with respect to the anti counterparts.
anti-6a was isolated in 31% yield, with the same diastereomeric
ratio as the reactant. The 14% yield of intermediate anti-7 was
afforded with an increased diastereomeric ratio with respect to
anti-5a, as previously observed in entry 1. Overall, the retention
pathway is less compromised than in Pd catalysis, albeit under
different conditions (CH2Cl2 vs THF and (allyl)Pd(PPh3)2BF4
as catalyst in the earlier work).2 Similar results were obtained
with 5b and 5c, but in contrast to the Pd case both benzoate
under platinum catalysis. For this purpose, allylic fluoride 5,
carrying competing anti-disposed leaving groups (OAc, anti-5a;
OBz, anti-5b; OCO2Me, anti-5c) was selected, on the basis of
the earlier work involving Pd catalysis.2 The reactions were
carried out under catalytic conditions similar to those described
above and run to complete conversion (as determined by TLC)
or for a maximum of 24 h (Scheme 6; Table 3).
When the reaction was carried out with the acetate anti-5a
and 2 equiv of nucleophile, after 24 h the major product
isolated was the intermediate anti-6a, derived by the displace-
ment of the fluoride, in 40% yield, with predominant retention
of configuration (Table 3, entry 1). Complete analysis of the
stereochemical course is complicated by the fact that the first
intermediate is reactive, and in both the first and second steps
the syn isomer is more reactive. This parallels the results in Pd
chemistry.2 Since the syn isomer in both intermediate products
6 and 7 is more reactive than the anti isomer, the
diastereomeric ratio (Table 3) understates the extent of
stereochemical leakage along the inversion route. The minor
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Scheme 7. Internal Test for Relative Leaving Group Ability with syn-5
Table 4
a
a
substrate
syn-5
dr of 5
(syn:anti)
amt of Nu
(equiv)
time
(h)
yield of syn-5
dr of 5
(syn:anti)
yield of syn-8
dr of syn-8
c
yield of byproducts(%)
b
a
entry
(%)
(%)
(syn:anti)
(9:10)
1
2
3
4
syn-5a
syn-5b
syn-5c
syn-5b
88:12
94:6
2
24
24
10
3
6
19
19
34
88:12
80:20
>98:2
39
38
69
>98:2
>98:2
98:2
7 (1:1)
9 (1:1)
6 (1:1)
4 (1:1)
2
97:3
2
67:33
1.2
33:67
27
>98:2
a
b
c
1
1
Isolated yields. dr determined by H NMR of recovered starting material. dr determined by H NMR of isolated products.
and carbonate were inferior leaving groups to fluoride, with
anti-6 being the predominant product. It was noted that more
of the double-substitution product 8 was obtained with
carbonate as leaving group. The relative reactivity of the
leaving groups under study is less clear-cut for Pt, compared to
Pd catalysis for anti-5 as reactants. It was, however, possible to
determine a scale of reactivity: F ≥ OCO2Me ≫ OBz ≥ OAc.
Preliminary experiments indicate that the conditions employed
here, with Pd(PPh3)4 instead of Pt(PPh3)4 as catalyst, in THF
and using 5a−c as substrate provide lower levels of the
anomalous inversion pathway than was previously ob-
served.21,25
entry 4). However, the outcome was unchanged with respect to
the previous results (Table 4, entry 2). The disubstituted
product syn-8 was recovered in 27% yield as a single
diastereoisomer, and unreacted syn-5b (34%) was isolated
mainly as the anti diastereoisomer. Use of a decreased amount
of nucleophile and shorter reaction time for syn-5b did not
avoid the formation of byproducts 9 and 10 (4%). Due to the
high reactivity of intermediates syn-6 and syn-7, the study
carried out on syn-5 derivatives was unable to validate the
leaving group propensity established for anti-5 (Table 3).
Intermediate 6b was synthesized independently in both syn
and anti diastereomeric forms27 and subjected to Pt(PPh3)4
catalyst with 1.7 equiv of nucleophile in THF at room
temperature (Scheme 8). As expected, it was found that syn-6b
C. Reactivity of the Cyclohexenyl Fluoride syn-5
under Pt Catalysis. Both in Pd-catalyzed and now in Pt-
catalyzed allylic alkylation, the minor syn isomer of 5 was the
more reactive of the pair, encouraging a separate analysis. The
synthetic strategy for the preparation of derivatives syn-5a−c
was identical with that for their anti counterparts, employing
the syn-γ-hydroxyallylsilane precursor.26 Electrophilic fluorode-
silylation of the anti-allylsilane was significantly less stereo-
selective, affording the final products with low diastereomeric
purity and requiring careful chromatography prior to isolation.
The outcomes of Pt-catalyzed reactions of syn-5a−c under the
optimized conditions were similar to one another, when an
excess of sodium dimethyl malonate (2 equiv) was used (Table
4, entries 1−3). In all three cases, syn-8 was the only isolable
product, resulting from the substitution of both groups with
retention of configuration. There was no loss in diastereose-
lectivity, showing that both substitutions occurred with
complete stereocontrol. A small amount of starting material
was also recovered in each case; interestingly, substrates syn-5a
and syn-5c were recovered without detectable stereochemical
leakage (Table 4, entries 1 and 3), whereas syn-5b (Table 4,
entry 2) had epimerized to an extent (4:1). Two inseparable
byproducts were also isolated from the reaction mixtures,
tentatively assigned as diene 9 and ether 10 by MS (Scheme 7).
The intermediate compounds syn-6a−c and syn-7 were not
seen and were presumed to be too reactive. In an attempt to
isolate these intermediates, the substitution of syn-5b was
repeated with a decreased quantity of sodium dimethyl
malonate (1.2 equiv) and quenched within 3 h, when TLC
showed complete consumption of starting material (Table 4,
Scheme 8. Stereoselectivity in Allylic Alkylation of
Intermediate 6
Table 5
a
dr of 6b
(syn:anti)
time
(h)
yield of 8
dr of 8
a
entry
6b
(%)
(syn:anti)
1
2
syn-6b
>98:2
24
30
>99
37
>98:2
b
anti-6b
<2:98
<2:98
a
b
1
Ratios determined by H NMR of crude reaction mixture. anti-6b
was recovered in 63% (dr >98:2).
is more reactive than the anti-6b and is fully converted into the
final product syn-8 as a single diastereoisomer after 24 h (Table
5, entry 1). anti-6b, isolated in 37% yield with unchanged
diastereomeric ratio, was recovered after 30 h when the reaction
with anti-6b was carried out under the same catalytic
conditions. This control experiment also demonstrated the
absence of epimerization of anti-6b (Table 5, entry 2). These
results confirm that substitution of the benzoate leaving group
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occurs with complete retention of configuration under platinum
catalysis, in line with previous results (Schemes 3 and 4).
D. Tests for Competing Epimerization. Allylic fluorides
anti-5b and syn-5b were subjected to catalytic conditions in the
absence of malonate anion. The 1H NMR of the crude mixture
indicated that with the derivative anti-5b no epimerization
occurred under the reaction conditions after stirring the
solution for 24 h (Table 6, entry 1). However, syn-5b does
epimerize to a measurable extent (Table 6, entry 2).
Chart 1. Relative Concentrations of syn-5b and anti-5b
a
Determined by 19F NMR
Table 6. Epimerization Test for anti- and syn-5b, anti- and
syn-6b, and anti- and syn-7
substrate dr recovered substrate recovered substrate
a
entry substrate
(anti:syn)
yield (%)
dr (anti:syn)
1
2
3
4
5
6
anti-5b
syn-5b
anti-6b
syn-6b
anti-7
syn-7
96:4
>99
>99
>99
96:4
20:80
>98:2
<2:98
>98:2
25:75
>98:2
17:83
>98:2
b
86
>99
a
b
Reaction carried out on 5b (syn:anti 80:20) under the reaction
8:92
1
0
conditions of entry 4, Table 4.
a
b
Ratio determined by H NMR of the crude reaction mixture. The
rest of the substrate was converted into diene 9 (Scheme 7).
Scheme 9. Probe for the Generality of Pt-Catalyzed Allylic
Substitutions
When anti-6b was subjected to these conditions, the
substrate was recovered with an unchanged diastereomeric
ratio (Table 6, entry 3). However, when the reaction was
carried out with syn-6b, 86% of substrate was detected with a
significant erosion of dr and 14% of diene 9 was also formed by
β-hydride elimination at the π-allyl platinum complex
intermediate (Table 6, entry 4). For syn-7, elimination to 9
was complete (Table 6, entry 6). Hence, the formation of the
byproduct 9 observed in the reactions of derivatives syn-5a−c
(Table 4) is likely the result of β-hydride elimination from the
intermediates syn-6b and syn-7.
Table 7. Results of C−F Activation with Different
Nucleophiles
E. Kinetic Study by 19F NMR. The Pt-catalyzed reaction of
5b (syn:anti 80:20) was followed in situ by 19F NMR under the
conditions shown in Scheme 7. Spectra were recorded every 5
1
min over 1.5 h, and H NMR spectra were recorded early and
late in the sequence. Under these conditions the syn isomer
peak at −171.6 ppm disappeared far more rapidly than the anti
isomer peak at −173.0 ppm (Chart 1), consistent with the
experimental observations described above (Tables 3 and 4).
The only other observed change was the appearance of a new
peak at −165.8 ppm, consistent with the formation of syn-7
during the course of the reaction. This peak was never more
intense than 1% of the total integral. During the reaction a weak
shoulder appears and then disappears on the high-field side of
the main syn-5 peak at −171.6 ppm; this is close to the
observed chemical shift of anti-7.
a
b
At reflux for 16 h. At reflux for 4 h.
F. Survey of the Scope of Pt-Catalyzed Substitution of
Allyl Fluoride 11. As a test of the generality of Pt-catalyzed
substitution of fluorides, the reactivity of 11 with various
nucleophiles was studied under standard conditions (Scheme
9). In each case good yields were obtained without
complications (Table 7). A control reaction was run in the
absence of catalyst with C-, N- and O-nucleophiles, proving
that the transformation proceeds only through Pt catalysis. In
fact, after 16 h at room temperature neither product 12a nor
12b was detected, but full recovery of starting material was
realized (Table 7, entries 1 and 2). Similarly, when the reaction
was carried out with phenoxide as nucleophile in the absence of
Pt(PPh3)4, after 7 h at reflux only unreacted allylic fluoride was
recovered (Table 7, entry 6).
3. CONCLUSIONS
In conclusion, we have confirmed that Pt-catalyzed allylic
alkylation occurs with overall retention of configuration, with
somewhat higher stereochemical integrity than for palladium.
For the main part of the work, we have determined the relative
leaving ability of a variety of commonly used anionic leaving
groups in Pt-catalyzed allylic alkylation. Under optimized
conditions, we found the relative reactivity to be F ≥ OCO2Me
≫ OBz ≥ OAc. This stands in contrast to the palladium-
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A solution of sodium dimethyl malonate (0.34 mmol) in THF (1 mL),
prepared from dimethyl malonate (51.6 mL, 0.34 mmol) and NaH
(60% in mineral oil, 13.6 mg, 0.34 mmol), was added to a stirred
solution of Pt(PPh3)4 (0.01 mmol, 5%) in THF (1 mL), followed by
the addition of the allylic substrate (0.2 mmol). The reaction mixture
was stirred at room temperature and monitored by TLC. The reaction
was quenched by addition of distilled water and the aqueous layer
extracted two times with Et2O. The combined organic layers were
dried over MgSO4, and the solvent was removed in vacuo.
Procedure for Pd-Catalyzed Allylic Alkylation. A solution of
sodium dimethyl malonate (0.34 mmol) in THF (1 mL), prepared
from dimethyl malonate (51.6 mL, 0.34 mmol) and NaH (60% in
mineral oil, 13.6 mg, 0.34 mmol), was added to a stirred solution of
Pd(PPh3)4 (0.01 mmol, 5%) in THF (1 mL), followed by the addition
of the allylic substrate (0.2 mmol). The reaction mixture was stirred at
room temperature and monitored by TLC. The reaction was
quenched by addition of distilled water and the aqueous layer
extracted two times with Et2O. The combined organic layers were
dried over MgSO4, and the solvent was removed in vacuo.
catalyzed transformation, where carbonate is the best leaving
group and fluoride more reactive only than acetate.2 A study on
the stereochemical outcome of the fluoride displacement was
made, and it was found that overall retention of configuration is
favored with Pt(PPh3)4 as catalyst in THF. Less of the
competing inversion pathway was observed than previously
reported for palladium catalysis in CH2Cl2.2 For the Pt-
catalyzed transformation the levels of diastereoselectivity were
found to be dependent on the starting geometry, affording
better results with syn-3 and syn-5 than with their anti isomers.
On the basis of the high reactivity of allylic fluorides under Pt
catalysis, we conclude that platinum-catalyzed allylic fluorina-
tion will be highly challenging, in contrast to what has been
achieved with palladium catalysis.3 Some preliminary experi-
ments with allylic p-nitrobenzoates under palladium optimized
reaction conditions reinforced this view, and the desired
fluoride was not detected. In addition to being a contribution to
allyl fluoride chemistry, this work reinforces and extends our
knowledge of the distinct chemistry of palladium and platinum
as applied to allylic alkylation. By comparison, the initial and
final η2-bound states are more highly stabilized for Pt than for
Pd; indeed, simple alkene complexes are commonplace in Pt
chemistry but are far less common in Pd chemistry. Under
catalytic turnover conditions, the alkene product from allylic
alkylation forms an observable complex with Pt.10b Applying
these observations, together with the Hammond postulate,
suggests that the transition state for η3-allyl formation from the
reactant η2 complex is later for Pt than for Pd. This factor could
well be responsible for the striking change in the order of
leaving-group reactivity between the two metals.
The reactions carried out on 1, syn-3, and anti-3 gave the desired
products 2, syn-4, and anti-4, respectively, presented in Tables 1 and 2.
syn-5-(1,3-Dimethoxy-1,3-dioxopropan-2-yl)cyclohex-3-ene-1-
1
carboxylic acid (2). H NMR (400 MHz, CDCl3): δ 5.81−5.76 (1H,
m), 5.55 (1H, dm, J = 10 Hz), 3.75 (6H, s), 3.30 (1H, d, J = 9 Hz),
3.06−3.00 (1H, m), 2.71−2.63 (1H, m), 2.35 (1H, dm, J = 18 Hz),
2.26−2.19 (1H, m), 2.16 (1H, dm, J = 12 Hz), 1.49 (1H, dd J = 12 Hz,
24 Hz). 13C NMR (100 MHz, CDCl3): δ 180.9, 168.5, 127.4, 127.1,
56.3, 52.5, 39.2, 35.9, 29.1, 27.4. IR (CH2Cl2) ν 2954.8, 1731.9,
1253.8, 1157.5. HRMS: m/z calcd for C12H16O6 [M + Na]+ 279.0839,
found 279.0843.
Dimethyl syn-[5-(Methoxycarbonyl)cyclohex-2-en-1-yl]malonate
1
(syn-4). H NMR (400 MHz, CDCl3): δ 5.79−5.74 (1H, m), 5.53
(1H, dm, J = 10.1 Hz), 3.74 (6H, s), 3.68 (3H, s), 3.28 (1H, d, J = 5.6
Hz), 3.04−2.96 (1H, m), 2.29 (1H, dm, J = 15.9 Hz), 2.23−2.14 (1H,
m), 2.10 (1H, dm, J = 12.6 Hz), 1.46 (1H, dd, J = 24.0, 12.6 Hz). 13C
NMR (100 MHz, CDCl3): δ 175.5, 168.5, 127.4, 127.3, 56.4, 52.5,
51.7, 39.3, 36.0, 29.3, 27.6. Data are in agreement with those in the
literature.20
4. EXPERIMENTAL SECTION
General Procedures. Solvents were purchased from Fisher or
Rathburn. When dry solvents were required, they were purified by
expression through an activated alumina column built according to the
procedures described by Pangborn and Grubbs.29 Glassware was oven-
dried or heated in vacuo, where required. Chemicals were purchased
from Aldrich, Lancaster Synthesis, Fisher, Acros, BDH, Eastman, or
Alfa Aesar and used as received. Reactions involving air-sensitive
reagents or intermediates were performed under a dry nitrogen
atmosphere using standard vacuum line techniques.
Reactions were monitored by thin-layer chromatography (TLC)
carried out on Merck Kiesegel 60 F254 plates, using UV light (254
nm) as a visualizing agent and KMnO4 stain and heat as developing
agent. Column chromatography was carried out on Merck silica gel
C60 (40−60 mm).
Dimethyl anti-[5-(Methoxycarbonyl)cyclohex-2-en-1-yl]-
1
malonate (anti-4). H NMR (400 MHz, CDCl3): δ 5.80−5.75 (1H,
m), 5.58 (1H, dm, J = 10.1 Hz), 3.73 (6H, s), 3.67 (3H, s), 3.32 (1H,
d, J = 9.6 Hz), 3.04−2.96 (1H, m), 2.65−2.58 (1H, m), 2.27−2.25
(2H, m), 1.97−1.89 (1H, m), 1.77 (1H, dm, J = 14.4 Hz). 13C NMR
(100 MHz, CDCl3): δ 175.4, 168.4, 127.9, 126.7, 56.3, 52.5, 51.8, 35.7,
33.2, 28.0, 27.1. Data are in agreement with those in the literature.20
Procedure for the Electrophilic Fluorodesilylation of
Allylsilanes.2 A solution of the allylsilane (1 equiv) and sodium
bicarbonate (1.2 equiv) in acetonitrile (c = 0.1 M) was treated with
Selectfluor (1.1 equiv) and the mixture stirred at room temperature for
24 h. Distilled water was added and the aqueous layer extracted three
times with diethyl ether. The combined organic layers were washed
with brine and dried over MgSO4, and the solvent was removed in
vacuo.
1H NMR spectra and 13C NMR spectra were recorded on Bruker
DPX400 (400 MHz) or AVC500 (500 MHz) spectrometers. 19F
spectra were recorded on a Bruker DPX400 (376 MHz) spectrometer.
Proton and carbon-13 NMR spectra are reported as chemical shifts (δ)
in parts per million (ppm) relative to the solvent peak using the Bruker
internal referencing procedure (edlock). Fluorine-19 NMR spectra are
referenced relative to CFCl3 in CDCl3. Coupling constants (J) are
reported in units of hertz (Hz) to the nearest 0.1 Hz. Data are
reported as follows: chemical shift, integration, multiplicity (s = singlet,
d = doublet, t = triplet, q = quartet, br = broad, m = multiplet),
coupling constants (Hz). Assignments were aided by the use of COSY,
HMQC, HMBC, HOESY and NOESY experiments as required. Mass
spectra were recorded on Micromass GCT (CI+), and Bruker
MicroTof (ESI+) instruments. Infrared spectra were recorded as liquid
films on NaCl disks using a Bruker Tensor 27 FT-IR spectrometer.
Absorptions are reported in wavenumbers (cm−1). All known
compounds are quoted with two points of reference and are in
agreement with the literature.
anti-4-Fluorocyclohex-2-en-1-yl Acetate (anti-5a). 1H NMR (400
MHz, CDCl3): δ 6.05−6.00 (1H, m), 5.94 (1H, dm, J = 10.4 Hz),
5.34−5.30 (1H, m), 5.08 (1H, dm, J = 48.5 Hz), 2.22−2.09 (2H, m),
2.05 (3H, s), 1.93−1.81 (1H, m), 1.72−1.62 (1H, m);. 13C NMR (100
MHz, CDCl3) δ 170.5, 130.9 (d, J = 9.6 Hz), 130.1 (d, J = 19.2 Hz),
85.4 (d, J = 164.6 Hz), 67.3 (d, J = 2.4 Hz), 26.5 (d, J = 20.0 Hz), 25.1
(d, J = 4.8 Hz), 21.2. 19F{1H} NMR (376 MHz, CDCl3) δ −172.1.
Data are in agreement with those in the literature.2
anti-4-Fluorocyclohex-2-en-1-yl Benzoate (anti-5b). 1H NMR
(400 MHz, CDCl3): δ 8.05−8.03 (2H, m), 7.59−7.55 (1H, m), 7.48−
7.41 (2H, m) 6.12−6.06 (2H, m), 5.61−5.56 (1H, m), 5.15 (1H, dm, J
= 48.5 Hz), 2.33−2.19 (2H, m), 2.04−1.91 (1H, m), 1.88−1.81 (1H,
m). 13C NMR (100 MHz, CDCl3) δ 166.0, 133.0, 131.0 (d, J = 9.6
Hz), 130.2 (d, J = 19.2 Hz), 130.2, 129.6, 128.4, 85.5 (d, J = 165.4
Hz), 67.8 (d, J = 20.0 Hz), 26.6 (d, J = 4.8 Hz), 25.2 (d, J = 9.6 Hz).
19F{1H} NMR (376 MHz, CDCl3): δ −172.2. Data are in agreement
Stereochemical Study of Pt-Catalyzed Allylic Alkylation
(Schemes 3 and 4). Procedure for Pt-Catalyzed Allylic Alkylation.
with those in the literature.2
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1
anti-4-Fluorocyclohex-2-en-1-yl Methyl Carbonate (anti-5c). H
NMR (400 MHz, CDCl3): δ 6.08−5.98 (2H, m), 5.22−5.16 (1H, m),
5.06 (1H, dm, J = 48.3 Hz), 3.79 (3H, s), 2.23−2.10 (2H, m), 1.95−
1.82 (1H, m), 1.80−1.72 (1H, m). 13C NMR (100 MHz, CDCl3): δ
155.2, 130.5 (d, J = 19.2 Hz), 130.1 (d, J = 9.6 Hz), 85.1 (d, J = 164.6
Hz), 71.0 (d, J = 2.4 Hz), 54.8, 26.3 (d, J = 20.8 Hz) 25.0 (d, J = 4.8
Hz). 19F{1H} NMR (376 MHz, CDCl3) δ −172.5. Data are in
agreement with those in the literature.2
Dimethyl [anti-4-(Benzoyloxy)cyclohex-2-en-1-yl]malonate (anti-
6b). 1H NMR (400 MHz, CDCl3): δ 8.04 (2H, br d, J = 7.3 Hz), 7.55
(1H, br t, J = 7.3 Hz), 7.43 (2H, br t, J = 7.6 Hz), 5.88−5.81 (2H, m),
5.54 (1H, m), 3.76 (6H, s), 3.33 (1H, d, J = 8.8 Hz), 3.04 (1H, m),
2.23−2.17 (1H, m), 2.01−1.97 (1H, m), 1.83−1.74 (1H, m), 1.60−
1.54 (1H, m). 13C NMR (100 MHz, CDCl3): δ 168.5, 166.2, 132.9,
131.8, 130.4, 129.6, 128.8, 128.3, 69.2, 56.0, 52.5, 35.2, 27.3, 24.3. IR
(CH2Cl2): ν 3055, 2987, 1735, 1265. HRMS: m/z calcd for
C18H20NaO6 [M + Na]+ 355.1152, found 355.1153.
1
syn-4-Fluorocyclohex-2-en-1-yl Acetate (syn-5a). H NMR (400
Dimethyl {anti-4-[(Methoxycarbonyl)oxy]cyclohex-2-en-1-yl}-
MHz, CDCl3): δ 6.03−5.98 (1H, m), 5.95−5.91 (1H, m), 5.24−5.19
(1H, m), 4.96 (1H, dm, J = 51.5 Hz), 2.07 (3H, s), 2.04−1.92 (1H,
m), 1.90−1.84 (3H, m). 13C NMR (100 MHz, CDCl3): δ 170.6, 131.7
(d, J = 9.6 Hz), 129.3 (d, J = 19.2 Hz), 84.8 (d, J = 164.6 Hz), 67.7 (d,
J = 3.2 Hz), 25.9 (d, J = 21.6 Hz), 24.0 (d, J = 4.0 Hz), 21.2. 19F{1H}
NMR (376 MHz, CDCl3): δ −170.5. IR (CH2Cl2): ν 3055, 2987,
1732, 1422, 1265. HRMS: m/z calcd for C8H15FNO2 [M + NH4]+
176.1087, found 176.1087.
1
malonate (anti-6c). H NMR (500 MHz, CDCl3): δ 5.80 (2H, s),
5.17−5.13 (1H, m) 3.78 (3H, s), 3.75 (6H, s), 3.30 (1H, d, J = 8.8
Hz), 2.99−2.97 (1H, m), 2.14−2.10 (1H, m), 1.95−1.92 (1H, m),
1.75−1.69 (1H, m), 1.52−1.44 (1H, m). 13C NMR (100 MHz,
CDCl3): δ 168.4, 155.4, 132.1, 128.0, 72.5, 55.9, 54.7, 52.6, 35.0, 27.1,
24.0. IR (CH2Cl2): ν 3055, 2987, 1742, 1265. HRMS: m/z calcd for
C13H18NaO7 [M + Na]+ 309.0945, found 309.0944. The relative
stereochemistry of anti-6c has been determined by NOESY studies.
syn-4-Fluorocyclohex-2-en-1-yl Benzoate (syn-5b). 1H NMR (400
MHz, CDCl3): δ 8.08−8.05 (2H, m), 7.60−7.56 (1H, m), 7.47−7.44
(2H, m) 6.10−6.05 (2H, m), 5.52−5.48 (1H, m), 5.03 (1H, dm, J =
47.3 Hz), 2.19−2.11 (1H, m), 2.06−1.94 (3H, m). 13C NMR (100
MHz, CDCl3): δ 166.0, 133.1, 131.8 (d, J = 9.5 Hz), 130.2, 129.7,
129.5 (d, J = 19.1 Hz), 128.4, 84.9 (d, J = 164.0 Hz), 68.1 (d, J = 1.9
Hz), 26.0 (d, J = 21.0 Hz), 24.2 (d, J = 3.8 Hz). 19F{1H} NMR (376
MHz, CDCl3): δ −170.4. IR (CH2Cl2): ν 3055, 2987, 1715, 1421,
1265. HRMS: m/z calcd for C13H13FNaO2 [M + Na]+ 243.0792,
found 243.0792.
1
anti-Dimethyl (4-Fluorocyclohex-2-en-1-yl)malonate (anti-7). H
NMR (400 MHz, CDCl3): δ 5.92−5.87 (1H, m), 5.83−5.81 (1H, m),
5.04 (1H, dm, J = 49.0 Hz), 3.75 (6H, s), 3.30 (1H, d, J = 8.8 Hz),
2.99 (1H, m), 2.13−2.06 (1H, m), 1.94 (1H, m), 1.85−1.74 (1H, m),
1.45 (1H, q, J = 10.9, 22.2 Hz). 13C NMR (100 MHz, CDCl3): δ 168.4
(d, J = 4.0 Hz), 132.3 (d, J = 8.8 Hz), 128.6 (d, J = 20.8 Hz), 86.5 (d, J
= 163.8 Hz), 55.7 (d, J = 2.4 Hz), 52.6 (d, J = 1.6 Hz), 35.1 (d, J = 3.2
Hz), 27.9 (d, J = 19.2 Hz), 23.4 (d, J = 6.4 Hz). 19F{1H} NMR (376
MHz, CDCl3): δ −170.6. Data are in agreement with those in the
literature.2
syn-4-Fluorocyclohex-2-en-1-yl Methyl Carbonate (syn-5c). 1H
NMR (400 MHz, CDCl3): δ 6.05−5.97 (2H, m), 5.11−5.06 (1H, m),
4.97 (1H, dm, J = 48 Hz), 3.80 (3H, s), 2.11−2.02 (1H, m), 1.98−1.85
(3H, m). 13C NMR (100 MHz, CDCl3): δ 155.3, 130.8 (d, J = 9.6
Hz), 129.9 (d, J = 20.0 Hz), 84.7 (d, J = 164.6 Hz), 71.4 (d, J = 2.4
Hz), 54.8, 25.7 (d, J = 20.8 Hz,) 24.0 (d, J = 4.8 Hz). 19F{1H} NMR
(376 MHz, CDCl3): δ −171.2. IR (CH2Cl2): ν 3055, 2987, 1746,
1422, 1265. HRMS: m/z calcd for C8H11FNaO3 [M + Na]+ 197.0584,
found 197.0589.
anti-1,4-Bis(dicarboxymethyl)cyclohex-2-ene (anti-8). 1H NMR
(400 MHz, CDCl3): δ 5.62 (2H, s), 3.74 (6H, s), 3.73 (6H, s), 3.27
(2H, d, J = 8.6 Hz), 2.92−2.89 (2H, m), 1.87−1.85 (2H, m), 1.43−
1.38 (2H, m). 13C NMR (100 MHz, CDCl3): δ 169.0, 130.1, 56.9,
52.9, 36.1, 26.5. Data are in agreement with those in the literature.2,30
cis-1,4-Bis(dicarbomethoxymethyl)cyclohex-2-ene (syn-8). 1H
NMR (400 MHz, CDCl3): δ 5.67 (2H, s), 3.72 (12H, s), 3.31 (2H,
d, J = 9.6 Hz), 2.91−2.86 (2H, m), 1.75−1.69 (2H, m), 1.51−1.44
(2H, m). 13C NMR (100 MHz, CDCl3): δ 168.5, 129.8, 56.2, 52.4,
34.6, 23.6. Data are in agreement with those in the literature.2,30
Tests for Competing Epimerization. To a solution of Pt(PPh3)4
(6 mg, 5 mol %) in THF (1 mL) was added the substrate (0.1 mmol),
and the mixture was stirred at room temperature for 24 h. The
solution was diluted with Et2O and filtered through Celite. The solvent
was then removed in vacuo.
1-tert-Butyl-4-(3-fluoroprop-1-en-2-yl)benzene (11). 1H NMR
(400 MHz, CDCl3): δ 7.40 (4H, s), 5.60 (1H, s), 5.39 (1H, s), 5.25
(2H, d, JH−F = 47.2 Hz), 1.34 (9H, s). 13C NMR (100 MHz, CDCl3):
δ 151.3, 142.7 (d, J = 14.4 Hz), 134.3, 128.2, 125.5 (4H, d, J = 8.0),
114.5 (d, J = 10.4 Hz), 84.4 (d, J = 168.6 Hz), 34.6, 31.2. 19F{1H}
NMR (376 MHz, CDCl3): δ −212.8. Data are in agreement with those
in the literature.3
The reactions carried out on anti-5b and syn-5b, anti-6b and syn-6b,
anti-7 and syn-7 gave the results indicated in Table 6.
Reactivity of Cyclohexenyl Fluorides anti- and syn-5 and
anti- and syn-6 under Pt Catalysis (Schemes 6−8). Procedure
for Pt-Catalyzed Allylic Alkylation of 5a−c and 6b. A solution of
sodium dimethyl malonate (2, 1.2, or 1.7 equiv) in THF (0.1 M),
prepared from dimethyl malonate (2, 1.2, or 1.7 equiv) and NaH (2,
1.2, or 1.7 equiv), was added to a stirred solution of Pt(PPh3)4 (5 mol
%) in THF (0.1 M), followed by the addition of the allylic substrate (1
equiv). The reaction mixture was stirred at room temperature, until
TLC indicated complete conversion of the starting material (in any
case, not over 24 h). The reaction was quenched by addition of
distilled water and the aqueous layer extracted two times with Et2O.
The combined organic layers were dried over MgSO4, and the solvent
was removed in vacuo.
cis-Dimethyl(4-fluorocyclohex-2-en-1-yl) malonate (syn-7). Sub-
strate syn-7 was prepared by palladium-catalyzed allylic alkylation of
syn-5c.25 1H NMR (400 MHz, CDCl3): δ 5.96−5.90 (2H, m), 4.92
(1H, dm, J = 50.0 Hz), 3.76 (6H, s), 3.36 (1H, d, J= 9.1 Hz), 2.91−
2.82 (1H, m), 2.14−2.03 (1H, m), 1.85−1.67 (2H, m), 1.62−1.52
(1H, m); 13C NMR (100 MHz, CDCl3): δ 168.5 (d, J = 10.4 Hz),
134.9 (d, J = 10.4 Hz), 126.3 (d, J = 16.8 Hz), 83.7 (d, J = 163.0 Hz),
55.8 (d, J = 4.0 Hz), 52.5 (d, J = 1.6 Hz), 35.7 (d, J = 3.2 Hz), 28.1 (d,
J = 21.6 Hz), 21.6; 19F{1H} NMR (376 MHz, CDCl3): δ −165.0; IR
(CH2Cl2): ν 3055, 2987, 1735, 1422, 1266. Data are in agreement with
those in the literature.4
Kinetic Study by 19F NMR. Following the general procedure, the
reaction was carried out in an NMR tube in d8-THF on 16 mg (0.1
mmol) of 5a (syn:anti 80:20) for 24 h. 19F NMR spectra were
recorded every 5 min over 1.5 h, and 1H NMR spectra were recorded
early and late in the sequence. Relative concentrations of syn-5b and
anti-5b, calculated by integration of their fluorine peaks (at −171.6
and −173.0 ppm, respectively) against time, are reported in Chart 1.
Pt-Catalyzed Substitution of Allyl Fluoride 11. Dimethyl [2-
(4-tert-Butylphenyl)prop-2-en-1-yl]malonate (12a). A solution of
sodium dimethyl malonate (0.34 mmol) in THF (1 mL), prepared
from dimethyl malonate (39 μL, 0.34 mmol) and NaH (60% in
mineral oil, 13.6 mg, 0.34 mmol), was added to a stirred solution of
Pt(PPh3)4 (0.01 mmol, 5 mol %) in THF (1 mL), followed by the
addition of 11 (38 mg, 0.2 mmol). The reaction mixture was stirred at
The reactions carried out on anti-5a−c and syn-5a−c gave the
products anti-6a−c, anti-7, anti-8, and syn-8 as indicated in Tables
3−5. When the reaction was carried out with syn-5a−c, an inseparable
1
mixture of 9 and 10 (1:1) was isolated. 9 has been identified by H
NMR and 13C NMR; data are in agreement with those in the
literature.28 Meanwhile, 10 was tentatively assigned by MS-GCT (m/z
[M + NH4]+ 260.15).
Dimethyl [anti-4-Acetoxycyclohex-2-en-1-yl]malonate (anti-6a).
1H NMR (400 MHz, CDCl3): δ 5.78−5.70 (2H, m), 5.27 (1H, m)
3.74 (6H, s) 3.28 (1H, d, J = 8.8 Hz), 2.97 (1H, m), 2.08−2.04 (1H,
m) 2.04 (3H, s), 1.89 (1H, m), 1.66−1.57 (1H, m) 1.50−1.42 (1H,
m). 13C NMR (100 MHz, CDCl3): δ 170.7, 168.4, 131.6, 128.7, 68.7,
56.0, 52.5, 35.1, 27.2, 24.2, 21.3. Data are in agreement with those in
the literature.2
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room temperature for 1 h. The reaction was quenched by addition of
distilled water and the aqueous layer extracted two times with Et2O.
The combined organic layers were dried over MgSO4 and solvent
removed in vacuo. Silica gel column chromatography (hexane−diethyl
ether, 7:3) yielded 12a (56 mg, 91%) as a colorless oil. 1H NMR (400
MHz, CDCl3): δ 7.38−7.31 (4H, m), 5.31 (1H, d, J = 1.0 Hz), 5.10
(1H, d, J = 1.0 Hz), 3.70 (6H, s), 3.57 (1H, t, J = 7.6 Hz), 3.13 (2H,
dd, J = 7.6, 0.9 Hz), 1.33 (9H, s). 13C NMR (100 MHz, CDCl3): δ
169.4, 153.7, 150.8, 144.4, 136.8, 125.9, 125.4, 114.1, 52.5, 50.8, 34.6,
31.3. IR (CH2Cl2): ν 3055, 2966, 1736, 1266. HRMS: m/z calcd for
C18H24NaO4 [M + Na]+ 327.1567, found 327.1567.
Pt-Catalyzed Allylic Amination of 11. A solution of amine (0.34
mmol) and 11 (38 mg, 0.2 mmol) in THF (1 mL) was added to a
stirred solution of Pt(PPh3)4 (0.01 mmol, 5%) in THF (1 mL). The
reaction was stirred at room temperature for 1 h. Distilled water was
added and the aqueous layer extracted two times with Et2O. The
combined layers were dried over MgSO4, and the solvent was removed
in vacuo.
(3H, td, J = 7.3, 2.0), 5.67 (1H, s), 5.46 (1H, s), 4.95 (2H, s), 1.36
(9H, s). 13C NMR (100 MHz, CDCl3): δ 158.7, 151.1, 142.6, 135.4,
129.5, 128.5, 125.4, 121.0, 114.8, 114.0, 69.8, 34.6, 31.3. IR (CH2Cl2):
ν 1599, 1240, 1015. HRMS: m/z calcd for C19H22O [M + Na]+
289.1563, found 289.1563.
ASSOCIATED CONTENT
* Supporting Information
■
S
Text and figures giving additional synthetic procedures,
characterization data, and NMR spectra of novel compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Fax: (+ 44) 1865-275-644. E-mail: john.brown@chem.ox.ac.
uk (J.M.B.); veronique.gouverneur@chem.ox.ac.uk (V.G.).
■
2-(4-tert-Butylphenyl)-N,N-diethylprop-2-en-1-amine (12b). Fol-
lowing the procedure of platinum-catalyzed amination of 11, the
reaction was carried out with 35 μL of diethylamine. Silica gel column
chromatography (hexane−diethyl ether, 1:1) yielded 12b (45 mg,
92%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.48 (2H, d, J
= 8.5 Hz), 7.36 (2H, d, J = 8.5 Hz), 5.44 (1H, s), 5.26 (1H, s), 3.42
(2H, s), 2.56 (4H, q, J = 7.0 Hz), 1.35 (9H, s), 1.02 (6H, t, J = 7.0
Hz). 13C NMR (100 MHz, CDCl3): δ 150.2, 145.5, 137.7, 125.9,
125.1, 114.1, 57.6, 46.8, 34.5, 31.3, 11.5. IR (CH2Cl2): ν 1265. HRMS:
m/z calcd for C17H27N [M + H]+ 246.2216 found 246.2215.
1-(2-(4-tert-Butylphenyl)allyl)pyrrolidine (12c). Following the
procedure of platinum-catalyzed amination of 11, the reaction was
carried out with 28 μL of pyrrolidine. Silica gel column
chromatography (hexane−diethyl ether, 1:1) yielded 12c (44 mg,
90%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.50 (2H, d, J
= 8.5 Hz), 7.32 (2H, d, J = 8.5 Hz), 5.42 (1H, s), 5.26 (1H, s), 3.48
(2H, s), 2.56 (4H, m), 1.78 (4H, m), 1.33 (9H, s). 13C NMR (100
MHz, CDCl3): δ 150.3, 145.2, 137.6, 125.8, 125.1, 113.7, 60.7, 54.2,
34.5, 31.3, 23.6. IR (CH2Cl2): ν 1265. HRMS: m/z calcd for [M + H]+
244.2060, found 244.2062.
ACKNOWLEDGMENTS
■
We gratefully acknowledge funding from the European Union
(No. FP7-ITN-238434), MNSER, CRUK, EPSRC, and the
Leverhulme Trust. In addition, we thank Dr. Barbara Odell for
the NMR studies on the relative stereochemistry of novel
compounds described herein.
REFERENCES
■
(1) (a) Greedy, B.; Paris, J. M.; Vidal, T.; Gouverneur, V. Angew.
Chem., Int. Ed. 2003, 42, 3291−3294. (b) Thibaudeau, S.; Gouverneur,
V. Org. Lett. 2003, 5, 4891−4893. (c) Thibaudeau, S.; Fuller, R.;
Gouverneur, V. Org. Biomol. Chem. 2004, 2, 1110−1112. (d) Tredwell,
M.; Tenza, K.; Pacheco, M. C.; Gouverneur, V. Org. Lett. 2005, 7,
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4-(2-(4-tert-Butylphenyl)allyl)morpholine (12d). Following the
procedure of platinum-catalyzed amination of 11, the reaction was
carried out on 30 μL of morpholine. Silica gel column chromatography
(hexane−diethyl ether, 6:4) yielded 12d (43 mg, 83%) as a colorless
(3) Hollingworth, C.; Hazari, A.; Hopkinson, M. N.; Tredwell, M.;
Benedetto, E.; Huiban, M.; Gee, A. D.; Brown, J. M.; Gouverneur, V.
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1
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17402−17404.
oil. H NMR (400 MHz, CDCl3): δ 7.52 (2H, d, J = 8.0 Hz), 7.37
(2H, d, J = 8.0 Hz), 5.31 (1H, s), 5.24 (1H, s), 3.72 (4H, t, J = 4.7
Hz), 3.33 (2H, s), 2.51 (4H, m), 1.35 (9H, s). 13C NMR (100 MHz,
CDCl3): δ 150.5, 143.0, 137.3, 125.8, 125.0, 114.9, 67.1, 63.6, 53.6,
34.5, 31.3. IR (CH2Cl2): ν 1266, 1116. HRMS: m/z calcd for [M +
H]+ 260.2009, found 260.2006.
N-(2-(4-tert-Butylphenyl)allyl)benzenamine (12e). Following the
procedure of platinum-catalyzed amination of 11, the reaction was
carried out on 32 mg of aniline for 16 h at reflux. Silica gel column
chromatography (hexane) yielded 12e (38 mg, 72%) as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 7.47 (2H, d, J = 7.3 Hz), 7.41 (2H, d,
J = 7.3 Hz), 7.03 (2H, m), 6.74 (1H, t, J = 7.0 Hz), 6.67 (2H, d, J = 8.5
Hz), 5.53 (1H, s), 5.33 (1H, s), 4.19 (2H, s), 3.95 (1H, NH), 1.37
(9H, s). 13C NMR (100 MHz, CDCl3): δ 151.0, 148.1, 144.3, 136.2,
129.2, 125.7, 125.4, 117.5, 113.0, 112.9, 48.0, 34.6, 31.3. IR (CH2Cl2):
ν 1603, 1265; HRMS: m/z calcd for [M + Na]+ 288.1723 found
288.1723.
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1-tert-Butyl-4(3-phenoxyprop-1-en-2-yl)benzene (12f). A solution
of sodium phenoxide (0.34 mmol) in THF (1 mL), prepared from
phenol (30 μL, 0.34 mmol) and NaH (60% in mineral oil, 13.6 mg,
0.34 mmol), was added to a stirred solution of Pt(PPh3)4 (0.01 mmol,
5%) in THF (1 mL), followed by the addition of 11 (38 mg, 0.2
mmol). The reaction mixture was stirred for 4 h at reflux. Distilled
water was added and the aqueous layer extracted two times with Et2O.
The combined layers were dried over MgSO4, and the solvent was
removed in vacuo. Silica gel column chromatography (hexane) yielded
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12f (54 mg, 99%) as a colorless oil. H NMR (400 MHz, CDCl3): δ
7.48 (2H, d, J = 8.3 Hz), 7.43 (2H, d, J = 8.3 Hz), 7.34 (2H, m), 7.02
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