Base-Catalyzed Stereospecific Isomerization of Electron-Deficient Allylic Alcohols and Ethers through Ion-Pairing

Article abstract of DOI:10.1021/jacs.6b08350

A mild base-catalyzed strategy for the isomerization of allylic alcohols and allylic ethers has been developed. Experimental and computational investigations indicate that transition metal catalysts are not required when basic additives are present. As in the case of using transition metals under basic conditions, the isomerization catalyzed solely by base also follows a stereospecific pathway. The reaction is initiated by a rate-limiting deprotonation. Formation of an intimate ion pair between an allylic anion and the conjugate acid of the base results in efficient transfer of chirality. Through this mechanism, stereochemical information contained in the allylic alcohols is transferred to the ketone products. The stereospecific isomerization is also applicable for the first time to allylic ethers, yielding synthetically valuable enantioenriched (up to 97% ee) enol ethers.

Full text of DOI:10.1021/jacs.6b08350

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Article
Base-Catalyzed Stereospecific Isomerization of Electron-
Deficient Allylic Alcohols and Ethers through Ion-Pairing
Samuel Martinez-Erro, Amparo Sanz-Marco, Antonio Bermejo Gómez,
Ana Vázquez-Romero, Mårten S.G. Ahlquist, and Belen Martin-Matute
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b08350 • Publication Date (Web): 16 Sep 2016
Downloaded from http://pubs.acs.org on September 16, 2016
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Journal of the American Chemical Society
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Base-Catalyzed Stereospecific Isomerization of Electron-
Deficient Allylic Alcohols and Ethers through Ion-Pairing
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Samuel Martinez-Erro,a‡ Amparo Sanz-Marco,a‡ Antonio Bermejo Gómez,a Ana Vázquez-Romero,a
Mårten S. G. Ahlquist,b and Belén Martín-Matutea*
a Department of Organic Chemistry, Stockholm University, Stockholm, SE-10691, Sweden.
b Division of Theoretical Chemistry & Biology, School of Biotechnology, KTH Royal Institute of Technology, Stockholm,
SE-10691, Sweden.
Allylic alcohols • Allylic ethers • Base catalysis • stereospecific • Ion pair
Supporting Information
ABSTRACT: A mild base-catalyzed strategy for the isomerization of allylic alcohols and allylic ethers has been developed. Ex-
perimental and computational investigations indicate that transition metal catalysts are not required when basic additives are pre-
sent. As in the case of using transition metals under basic conditions, the isomerization catalyzed solely by base also follows an
sterospecific pathway. The reaction is initiated by a rate-limiting deprotonation. Formation of an intimate ion pair between an al-
lylic anion and the conjugate acid of the base results in efficient transfer of chirality. Through this mechanism, stereochemical in-
formation contained in the allylic alcohols is transferred to the ketone products. The sterospecific isomerization is also applicable
for the first time to allylic ethers, yielding synthetically valuable enantioenriched (up to 97% ee) enol ethers.
chiral allylic alcohols as those reported for the metal/base sys-
1. INTRODUCTION
tem.4 Herein, we report the first base-catalyzed sterospecific
Allylic alcohols are readily accessible building blocks, and
isomerization of allylic alcohols and also of allylic ethers
they are versatile synthons of carbonyl compounds via isomer-
(Scheme 1). The isomerizations are mediated by catalytic
ization reactions. In the vast majority of instances, these are
,
amount of the base 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD).
mediated by transition metal complexes.1 2 Basic additives, in
catalytic or stoichiometric amounts, are also needed in numer-
Mechanistic experimental and theoretical investigations have
been carried out allowing us to propose a mechanistic isomeri-
ous transition metal-mediated isomerizations. The base is pos-
zation pathway accounting for the efficient transfer of chirali-
tulated to deprotonate the substrate alcohol, which can subse-
quently coordinate to the metal center forming transition metal
ty.
alkoxides, key intermediates in the proposed catalytic cycles.
2b-c,2h-i,
3
With chiral metal catalysts, the synthesis of chiral ke-
Scheme 1. Sterospecific base-catalyzed isomerization of
allylic alcohols and ethers
tones2a,g and aldehydes,2f-i with stereogenic centers at Cβ has
been accomplished. An important related approach was re-
ported recently by Cahard, Renaud and co-workers,4 who
isomerized chiral γ-trifluoromethylated allylic alcohols steros-
pecifically using a non-chiral Ru complex together with
Cs2CO3. Metal-free base-mediated protocols are much less
common in the literature.5 These are highly dependent on the
substrate structure (e.g., R1 = R3 = Ar), and require stoichio-
metric amounts, or excess, of the base. Metal-free chiral ver-
sions have not been reported.
R2
O
R2 OH
TBD(cat)
R3
R1
R3
R1
∗
∗
N
TBD =
N
N
R2 OR4
H
R2 OR4
TBD(cat)
R3
R1
∗
R3
R1
∗
We have previously reported the synthesis of α-
halocarbonyls from allylic alcohols catalyzed by Ir complex-
es.1c, As an on-going part of our investigations, we have now
6
2. RESULTS AND DISCUSSION
attempted to apply this methodology to electron-poor allylic
alcohols, in particular γ-trifluoromethylated substrates. We
have observed that these substrates isomerize efficiently under
basic conditions, even at mild temperature, in the absence of
the metal catalysts. Furthermore, the base-catalyzed isomeriza-
tion achieves the same high levels of sterospecificity with
We started by investigating how the base affected the outcome
of the isomerization of γ-trifluoromethylated allylic alcohol 1a
(Table 1). Cs2CO3, which was also used in the isomerization of
1a in combination with [RuCl2(PPh3)3],4 can itself promote the
isomerization at 60 °C (Table 1, entry 1). Ketone 2a was also
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were achieved when R1 was replaced by CH3 or H (Scheme 2,
Table 1. Base-mediated isomerization of 1a
1
2
3
4
5
6
7
8
2h-i). The effect of varying the olefin substituents was next
studied. Allylic alcohols bearing electron-withdrawing or elec-
tron-donating groups on aryl subtituents at R2 gave the corre-
sponding products in high yields in all cases (Scheme 2, 2j-
m). Replacement of the aromatic group at R2 by H or CH3 was
well tolerated, and alcohols 1o and 1n were isomerized in 95-
99% yields. Alcohols 1p and 1q, with longer fluorinated
chains at R3, were also isomerized in good isolated yields
(62% and 71%, respectively). The isomerization of (E)-1a was
compared to that of its stereoisomer (Z)-1a. The latter smooth-
ly transformed into 2a, but a higher temperature and a longer
reaction time were needed.
Base
OH
O
Toluene,
60 °C, 18 h
F3C
F3C
rac-1a
rac-2a
N
N
N
N
N
N
9
N
N
10
11
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N
H
DMAP
DABCO
DBU
TBD
Interestingly, the fluorinated motif on the olefin can be re-
placed by other non-fluorinated groups; (E)-1r (R2 = H, R3 =
Ph) isomerized in excellent yield. Even aromatic 1s-u with
terminal double bonds isomerized successfully. Allylic alco-
hols (E)- and (Z)-1v, with non-fluorinated substituents on the
double bond, one of them a methyl group, gave lower yields
than those obtained with the related 1a. In contrast, with alco-
hols having two aryl substituents on the double bond (1w, (E)-
1x, (Z)-1x, and (E)-1y), excellent yields were obtained.
Entry
Base (equiv.)
Cs2CO3 (1.2)
NaH (1.2)
Conv. (%)a
Yield (%)b
1
65
25
45
20
2
3c
4
t-BuOK (1.2)
DMAP (1.2)
DABCO (1.2)
DBU (1.2)
>99
<1
33
<1
5
<1
<1
It can therefore be concluded that the substitution pattern is
limited at R1 to either aryl or electron-poor moieties such as
the CF3 group). On the other hand, the R2 and R3 substituents
can be varied to a larger extent; these may be electron-poor
fluorinated groups, but importantly, also aryl groups with var-
ied electron density, or even just hydrogen. It is important to
highlight that TBD is able to isomerize not only fluorinated
and electron poor alcohols, but also alcohols such as 1s-u, for
which transition metal catalysts under basic conditions have
been used.1,2
6
80
80
7d
8d
TBD (1.2)
>99
>99
>99
>99
TBD (0.1)
aBy 19F NMR spectroscopy. bWith an internal standard (I.S.).
cDecomposition products were formed. Under an atmosphere of
d
air.
The base-catalyzed isomerization can also be applied to
obtained when NaH and t-BuOK were used, albeit in low (en-
tries 2 and 3). The use of organic bases such as 4-
(dimethylamino)pyridine
,
fluorinated allylic ethers 3a-3d (Scheme 2),8 9 giving access to
(DMAP)
and
1,4-
synthetically valuable enol ethers.10 Even non-fluorinated ter-
minal allylic ethers 3e-f could be isomerized. Enol ethers 4a-
4d were formed as single (Z)-isomers, and 4e and 4f as a 92:8
and 97:3 Z/E mixtures respectively (See SI). Unfortunately,
other allylic substrates such as allyl silyl ethers and allylic
esters did not isomerized under the conditions described here
(See SI, Scheme S1).
diazabicyclo[2.2.2]octane (DABCO)5f did not promote the
isomerization (entries 4 and 5). On the other hand, with the
stronger7 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or with
guanidine base TBD conversions were achieved (entries 6 and
7), especially with TBD. Importantly, TBD was the only base
that could be used in a catalytic amount to give a quantitative
yield of 2a (entry 8, and Table S1). The isomerization works
under at atmosphere of air, and after full conversion is
achieved, a simple aqueous work-up to remove the basic cata-
lyst gives the final products in excellent yields.
We then investigated whether the reaction is sterospecific
(Table 2 and Table S2).4, The isomerization of (R)-1a (99%
11
ee) took place in excellent yield and with an enantiospecificity
(es; % of the product formed by the sterospecific pathway as
opposed to the competing unselective pathway) of 91% (entry
1). The es could be improved to 95% by decreasing the base
loading up to 2.5 mol%, although longer reaction times (18 h
with 5 mol% of TBD and 72 h with 2.5 mol% of TBD) were
needed (entries 2 and 3). Gratifyingly, at 80 ºC the es was
maintained and the reaction was completed in 18 h with a 2.5
mol% of TBD (entry 4). Other solvents were screened to as-
sess the effect on the es (Table 2, entries 5-8). Interestingly, all
solvent tested not only gave decreased es, but also considera-
bly lower yields (entries 5-8). This effect was more pro-
nounced in solvents with higher polarity.
The scope of the reaction (Scheme 2) under the optimized
conditions (Table 1, entry 8) was then investigated. Variation
of the electronic properties of the aryl group at R1 by introduc-
ing either electron-withdrawing or electron-donating groups
gave quantitative yields (84-95% isolated) for all substrates.
Notably, the reactions were much faster with electron-poor
substituents (Scheme 2, 2b-c). The bulkier naphthyl group was
also well tolerated, giving 2f in >99% yield. Excellent yields
were also obtained when the aryl substituent at R1 was re-
placed by the electron-poor CF3 group (2g), although slightly
harsher conditions were required. Significantly lower yields
2
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Scheme 2. Scope
1
2
3
4
5
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9
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60
Yield by 19F NMR spectroscopy (isolated in parenthesis). a80 °C. bTBD (0.2 equiv.), reflux. cBy NMR spectrosco-
py with an internal standard. dVolatile. eConversion.
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Table 2. Base-mediated sterospecific isomerization of 1a Table 3. Sterospecific isomerizations
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1
2
3
4
5
6
7
8
Ph OH
Ph
Ph
O
TBDcat
R2 OR4
R1
R2
O
R2 OR4
R1
(R)-4 (R4 ≠ H)
F3C
F3C
Ph
TBDcat
60- 80 °C
or
(R)-1a (99% ee)
(R)-2a
R3
R3
R1
R3
Toluene
80 °C
(R)-1 (R4 = H) or
(R)-3 (R4 ≠ H)
(R)-2 (R4 = H)
Entry
TBD
t (h) / T
(°C)
2a
ee
es (%)
(mol%)
(%)a
(%)
Solvent
R2 OH
Ph OH
Ph OH
Ph OMe
1
2
3
4
10
Toluene
Toluene
Toluene
Toluene
6 / 60
18 / 60
72 / 60
18 / 80
85
90
93
94
94
91
94
95
95
F3C
R1
R3
Ph
R3
(R)-1p C2F5 (R)-3a CF3
R3
Ph
F3C
Ph
R2
9
5
84
R1
(R)-1a C6H5
=
=
=
R3
=
10
11
12
13
14
15
16
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59
60
(R)-1j p-ClC6H4
(R)-1k p-CF3C6H4
(R)-1l p-MeC6H4
2.5
84
(R)-1b p-BrC6H4
(R)-1c p-CF3C6H4
(R)-1d p-MeC6H4
(R)-1e p-OMeC6H4
(R)-1f 2-Naphthyl
(R)-1q C3F7
(R)-3b C3F7
2.5
82
(R)-1m p-OMeC6H4
1,4-
5
2.5
18 / 80
71
84
85
Dioxane
Ph OPh
6
7
8
2.5
2.5
2.5
THF
18 / 80
18 / 80
18 / 80
30
28
27
74
80
60
75
81
61
F3C
Ph
(R)-3c
CH2Cl2
CH3CN
aIsolated yields.
Entry
ee
TBD
t
Yield
2/4
ee
es
1/3 (%)
(mol%) (h)
2/4 (%)b (%)
(%)a
(R)-1a
1
2
10
10
2.5
2.5
2.5
2.5
5
6
85
92
82
93
76
75
89
60
58
52
81
83
58
42
67
66
73
90
-90
91
91
95
96
98
94
90
89
89
61
98
100
93
96
99
97
99
The sterospecific isomerization was then tested for a variety
of substrates (Table 3). As expected, the same es (91%) was
obtained in the isomerization of (S)-1a (entry 2). (R)-1b and
(R)-1c having electron-poor aryl groups at R1 gave the prod-
ucts with excellent es (96% and 98% respectively, entries 4
and 5). For alcohols with electron-rich R1, (R)-1d and (R)-1e
(entries 6 and 7), longer reaction times were needed to achieve
good yields with es of 94% and 89%, respectively. Naphthyl
substituted (R)-1f gave similar results (entry 8). Lower yields
were obtained in the isomerization of allylic alcohols (R)-1j
and (R)-1k, with electron-poor aromatics at R2 (entries 9-10).
In addition, whereas a p-Cl substituent did not significantly
affect the es (entry 9), a somewhat less efficient transfer of
chirality was achieved when R2 = p-CF3C6H4 (entry 10). On
the other hand, exceptionally high es and good yields were
obtained with alcohols (R)-1l and (R)-1m, with electron-
donating aromatics at R2 (entries 11-12). Good transfer of
chirality was also obtained with substrates bearing various
fluorinated chains at R3 [(R)-1p and (R)-1q, entries 13-14].
(99)
(S)-1a
6
(-99)
(R)-1a
3
18
18
18
96
48
24
48
48
24
48
48
48
48
72
18
94 (99)
94 (99)
95 (99)
92 (99)
88 (99)
87
(99)
(R)-1b
4
(98)
(R)-1c
5
(97)
(R)-1d
6
(98)
(R)-1e
7
(98)
(R)-1f
8
2.5
2.5
5
(98)
(R)-1j
9
86
(97)
(R)-1k
10
11
12
13
14
15
16
17
59
(97)
Importantly, the ee of the products could be increased up to
99% by simple recrystallization. It must be also mentioned
that the isomerizations are also sterospecific when bases such
as Cs2CO3, NaH, t-BuOK and DBU were used (See SI, Table
S1).
(R)-1l
2.5
5
95
(97)
(R)-1m
98
(98)
The isomerization of chiral allylic ethers (R)-3a-c also pro-
ceeded remarkably well with 5 mol% of TBD at 80 °C (97-
99% es, entries 15-17). To the best of our knowledge, this is
the first sterospecific isomerization of allylic ethers to be re-
ported.
The electronic influence of R1 was investigated further. A
Hammett plot under non-competition conditions is shown in
Figure 1. A positive ρ value of 1.87 was obtained, indicating
that a partial negative charge (δ-) is formed in the rate-
determining transition state.12 These results, together with a
large kinetic isotope effect (KIE) of ≥5.0, support a mecha-
nism through a rate-limiting deprotonation of C1.13
(R)-1p
5
92
(99)
(R)-1q
5
95
(99)
(R)-3a
5
97
(98)
(R)-3b
5
95
(98)
(R)-3c
5
97
(98)
aIsolated yields. bIn parentheses, ee after recrystallization.
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between 1a-d1 and 1n, with similar reaction rates (Scheme 3d),
1
2
3
4
5
6
7
8
it can be concluded that the main reaction pathway involves an
intramolecular 1,3-H/D shift, since only 4% of D was detected
at C3 in 2n.
TBD (0.1 equiv.)
OH
O
Toluene
60 °C
F3C
F3C
1
To further test the proposed mechanism via deprotonation of
the C1−H bond, we studied the isomerization with DFT
(B3LYP-D3/aug-cc-pVTZ) (Figure 2). In agreement with the
experimental studies, the deprotonation was found to be the
rds, with an activation free energy of 19.6 kcal/mol (TSI), rela-
tive to the hydrogen bonded pre-reactive complex. After this
first step, an intimate ion pair14 composed of the allylic anion
and the protonated base is formed. The computational calcula-
tions suggest that the anion can be protonated either intramo-
lecularly (TSIIa) by the hydroxyl group, or intermolecularly by
the conjugate acid of TBD (TSIIb). Both pathways have simi-
larly low activation energies (~4 kcal/mol). This explains the
low deuterium content at C3 in the ketone product obtained
upon isomerizing 1a-d1 (Scheme 3a).
3
1
3
2
2
X
X
9
10
11
12
13
14
15
16
17
18
The theoretical studies also shed light onto the enantiospeci-
ficity of the reaction. The formation of the intimate ion pair
prevents racemization of the allylic anion, which would result
in inefficient transfer of chirality. Indeed, increasing the polar-
ity of the solvent resulted in lower es values, due to insuffi-
cient ion pairing (vide supra, Table 2 and Table S2). Further-
more, the presence of a strong electron-withdrawing group on
the phenyl ring at R2 (i.e. 2k) results in poorer transfer of chi-
rality. This may be due to formation of a more stable allylic
anion in this instance, what enables rotation with subsequent
partial loss of stereochemical information. A similar mecha-
nistic rationale has been proposed for a proton migration with
chirality transfer mediated by DBU.15
Figure 1. Hammett plot.
19
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60
The isomerization of 1a-d1 (96% D) afforded 2a-d with only
68% of DTOT (20% at C2 and 48% C3 distributed in a mixture
of 2a-d0 (32%), 2a-d1 (47%), 2a-d2 (17.6%) and 2a-d3 (3.4%),
Scheme 3a and SI). In an attempt to understand the net low
amount of D at C3, 1a was treated with partially deuterated
TBD (N-d1-TBD, Scheme 3b). Notably, 6% of D was found at
C3 in 2a, indicating that the H at C3 in Scheme 3a originates to
some extent from the base. Importantly, in the isomerization
of 1a-d1, the D content at C1 (i.e., 96%) remains constant in the
starting alcohol as the reaction proceeds, thus the deprotona-
tion step is irreversible. The isomerization of ether 3a-d1 (96%
D, Scheme 3c) gave 4a-d1 with 78% D, which is only slightly
lower than the expected 86% D. This might be due to traces of
water in the reaction medium. From a crossover experiment
The isomerization mechanism proposed here differs from
that proposed for the Ru-catalyzed isomerization of trifluoro-
methylated allylic alcohols in the presence of base.4 In the
latter, after a β-hydride elimination step yielding a ruthenium
hydride species and an enone intermediate, it was proposed
Scheme 3. Deuterium labeling studies
5
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that a migratory insertion from a single face accounted for the valuable synthetic intermediates in organic synthesis. Experi-
1
2
3
4
5
6
7
8
efficient chirality transfer. Overall, this resulted in a formal
Ru-catalyzed intramolecular suprafacial hydride shift. We
have demonstrated here that for these particular electron-poor
alcohols, the sterospecific isomerization can be simply medi-
ated by a base through a deprotonation / protonation sequence
that occurs at mild reaction conditions. Importantly, the base-
mediated reaction can account for the same levels of enanti-
ospecificity. The best results during our investigations were
obtained with TBD, which could be used in loadings as low as
2.5 mol%. Other bases such as Cs2CO3, NaH, of DBU also
mediated the sterospecific isomerization of allylic alcohols,
although in stoichiometric amounts. It is important to mention
mental and computational investigations indicate that the
transfer of the chirality only occurs upon formation of an inti-
mate ion pair after the rate limiting deprotonation step. This
study represents a unique example in which organic ion-
pairing enables transfer of chirality in readily available chiral
organic allylic substrates using a simple non-chiral base.
4. EXPERIMENTAL SECTION
General method for the isomerization of allylic alcohols
and ethers by base. A pressure tube was charged with the
corresponding allylic substrate (0.18 mmol, 1 equiv.), 1,5,7-
triazabicyclo[4.4.0]dec-5-ene (0.018 mmol, 2.5 mg, 0.1
equiv.) and 1.8 mL of toluene. The mixture was allowed to
react at 60 °C overnight and the reaction was quenched with
H2O (5 mL) and extracted with Et2O (3 x 5 mL). The solvent
was removed under reduced pressure to yield the product.
Further information about experimental details and characteri-
zation of new compounds can be found in the Supporting In-
formation.
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that higher yields are obtained with the Ru/Cs2CO3 system
than when Cs2CO3 is used as the sole reagent, thus the Ru
catalyst must play a specific role together with the base in the
former case. Nevertheless, the non-innocent role of basic addi-
tives in the isomerization of electron-poor or aromatic allylic
alcohols must be taken into consideration.
3. CONCLUSION
We have developed the first metal-free base-catalyzed steros-
pecific isomerization of allylic alcohols. The method enables
the transformation of a large variety of aromatic and electron-
deficient allylic alcohols into carbonyl compounds under mild
reaction conditions. We have also presented the first sterospe-
cific isomerization of allylic ethers. This base-catalyzed metal-
free method affords chiral enol ethers, which are also very
ASSOCIATED CONTENT
Supporting Information
1
Experimental details. Copies of H, 13C and 19F NMR spectra.
Chromatograms of racemic and chiral products.
The Supporting Information is available free of charge on the
Figure 2. Free energy profile: isomerization of 1a by TBD.
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AUTHOR INFORMATION
Corresponding Author
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Erbing, E.; Batuecas, M.; Vázquez-Romero, A.; Martín-Matute, B.
* Prof. B. Martín-Matute
E-mail: belen.martin.matute@su.se
Chem. Eur. J. 2014, 20, 10703-10709, and references therein.
(7) Superbases in catalytic reactions: Nacsa, E. D.; Lambert, T. H.
J. Am. Chem. Soc. 2015, 137, 10246-10253.
Author Contributions
(8) Selected recent examples of transition-metal-catalyzed isomeri-
zation of allylic ethers: (a) Courchay, F. C.; Sworen, J. C.; Ghiviringa,
I.; Abboud, K. A.; Wagener, K. B. Organometallics, 2006, 25, 6074-
6086. (b) Varela-Álvarez, A.; Sordo, J. A.; Piedra, E.; Nebra, N.;
Cadierno, V.; Gimeno, J. Chem. Eur. J. 2011, 17, 10583-10599. (c)
Urbala, M. Applied Catalysis, A: General 2015, 505, 382-393.
(9) Scarce examples of base-mediated isomerization of allylic
ethers: (a) Su, C.; Williard, P. G. Org. Lett. 2010, 12, 5378-5381. (b)
Reid, J. P.; McAdam, C. A.; Johnston, A. J. S.; Grayson, M. N.;
Goodman, J. M.; Cook, M. J. J. Org. Chem. 2015, 80, 1472-1498.
(9) Enol ethers as synthetic intermediates: (a) Modern Methods in
Stereoselective Aldol Reactions, First Edition (Ed. R. Mahrwald),
Wiley-VCH, 2013. (b) Kusama, H.; Ebisawa, M.; Funami, H.; Iwa-
sawa, N. J. Am. Chem. Soc. 2009, 131, 16352-16353. (b) Vitale, A.;
Bongiovanni, R.; Ameduri, B. Chem. Rev. 2015, 115, 8835-8866.
(11) Synthesis of chiral allylic alcohols and synthetic applications:
Lumbroso, A.; Cooke, M. L.; Breit, B. Angew. Chem. Int. Ed. 2013,
52, 1890-1932.
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All authors have given approval to the final version of the manu-
script. ‡These authors contributed equally.
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ACKNOWLEDGMENT
This project was supported by the Swedish Research Council
(VR), and the Knut and Alice Wallenberg Foundation. B.M.-M.
was supported by VINNOVA through a VINNMER grant and
A.V.-R. by the Wenner-Gren Foundation through a postdoctoral
grant.
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Metal-Free Enantiospecific Isomerization
Allylic Alcohols
Allylic Ethers
R4
R2
O
R2 OH
N
H
H
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R3
Ph
R3
R1
N
N
H
H
R4
Ph
OR4
R1
R2
O
R2
O
R2
R3
H
H
R3
R3
R1
H
- Catalytic
- Mild conditions
- Broad scope
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