Organocatalysts Effect on the Stereoselectivity of [2,3]-Wittig Rearrangement

Article abstract of DOI:10.1002/ejoc.201801697

The organocatalytic [2,3]-Wittig rearrangement of allyloxyketones was investigated. Extensive screening of chiral amine organocatalysts showed that small pyrrolidine-based catalysts or simple phenylethylamine with the primary amino group were the most effective ones. Interestingly, CF₃-derived pyrrolidine affords the rearrangement product with an opposite absolute configuration to the product obtained by using the corresponding non-fluorinated proline derived catalysts. Mechanistic and computational investigations were also performed.

Full text of DOI:10.1002/ejoc.201801697

DOI: 10.1002/ejoc.201801697
Full Paper
Asymmetric Organocatalysis
Organocatalysts Effect on the Stereoselectivity of [2,3]-Wittig
Rearrangement
Tibor Peňaška,[a] Melinda Meyer Mojzes,[a] Juraj Filo,[b] Helena Jurdáková,[b]
Mária Mečiarová,[a] and Radovan Šebesta*[a]
Abstract: The organocatalytic [2,3]-Wittig rearrangement of pyrrolidine affords the rearrangement product with an opposite
allyloxyketones was investigated. Extensive screening of chiral absolute configuration to the product obtained by using the
amine organocatalysts showed that small pyrrolidine-based cat- corresponding non-fluorinated proline derived catalysts. Mech-
alysts or simple phenylethylamine with the primary amino anistic and computational investigations were also performed.
group were the most effective ones. Interestingly, CF3-derived
Introduction
that chiral phosphoric acid activated and organized the reac-
tant for rearrangement via unusual arene CH–O interaction.[9]
A
Sigmatropic rearrangements have found many applications in
the synthesis of bioactive compounds, including natural prod-
ucts and pharmaceutical agents.[1] Organocatalytic rearrange-
ments usually proceed under mild reaction conditions often
with high stereoselectivities.[2] Recently, various organocatalytic
transformations utilizing enantioselective rearrangements have
been described, such as Cloke–Wilson rearrangement, a 1,3-
alkyl shift in alkyl aryl ethers, Smiles rearrangement, semi-
pinacol, acyloin, or Piancatelli rearrangements.[3]
Typical sigmatropic rearrangements are 6π-electron reac-
tions, proceeding via 6-membered cyclic transition states. Vari-
ous organocatalysts can stabilize these transition states, which
leads to rate acceleration and stereoinduction. Claisen rear-
rangement of allyl vinyl ethers was accelerated by hydrogen
bonding to achiral diaryl (thio)urea catalysts.[4] A computational
study showed that thioureas were able to lower the activation
barrier for Claisen rearrangement based on a bis(hydrogen)
bond interaction with the ether oxygen atom.[5] Claisen rear-
rangements of ester-substituted allyl vinyl ethers, as well as cy-
clic O-allyl ꢀ-keto esters catalyzed by chiral guanidinium ions,
gave branched allylation products in high yields with high en-
antio- and diastereocontrol.[6,7] Enantioselective Coates–Claisen
rearrangement catalyzed by a chiral NHC-catalyst was a key
step in a highly enantioselective annulation to give dihydro-
pyranone products with high enantiomeric purities.[8] DFT stud-
ies of aza-Claisen rearrangement of 3-aminoindoles indicated
chiral imidazole catalyst was successfully applied to the enan-
tioselective Black rearrangement with high yields and ee up to
88 %.[10] An asymmetric aza-Cope rearrangement catalyzed by
chiral phosphoric acids afforded primary homoallylic amines in
good yields with ee up to 94 %.[11] Synthesis of chiral 2,2′-
diamino-1,1′-binaphthalenes, BINOLs, and other biaryls was
achieved through an atroposelective [3,3]-sigmatropic rear-
rangement catalyzed by chiral phosphoric acids.[12,13]
The sigmatropic [2,3]-rearrangements are 6π-electron rear-
rangements proceeding via 5-membered cyclic transition
state.[14] The Wittig [2,3]-rearrangement is a transformation of
allyl ethers to homoallylic alcohols. Strong bases and low tem-
peratures, typical for classical reaction conditions, can be
avoided using organocatalysis. Gaunt and co-workers described
the first organocatalytic sigmatropic [2,3]-Wittig rearrangement
catalyzed with pyrrolidine.[15] Allyloxy ketones were activated
through enamine formation under mild reaction conditions,
and the corresponding hydroxy ketones were obtained with the
yield up to 92 % and d.r. ranging from 1:1 to 8:1. An enantio-
selective example of this reaction with chiral diamine was de-
scribed, which afforded the corresponding hydroxy ketone in
75 % yield, d.r. 2:1, and 60 % ee. Sigmatropic [2,3]-Wittig rear-
rangement of allyloxy carbonyl compounds have also been
studied using phase-transfer organocatalysis with chiral quater-
nary ammonium salts derived from cinchonidine.[16] An enan-
tioselective [2,3]-rearrangement of oxindole derivatives cata-
lyzed by squaramide catalyst provided 3-hydroxy-3-substituted
oxindoles in medium diastereomeric and high enantiomeric
purities (ee up to 97 %).[17] [2,3]-Wittig rearrangement of α-allyl-
oxymalonates has been catalyzed through noncovalent interac-
tions with chiral thioureas, which engaged both the reactive
anion and the corresponding cation of a base.[18] Rearrange-
ment of similar substrates has also been catalyzed with highly
basic cyclopropenimines.[19] An isothiourea promoted the cata-
lytic asymmetric [2,3]-rearrangement of allylic quaternary
[a] Department of Organic Chemistry, Faculty of Natural Sciences,
Comenius University in Bratislava
Mlynská dolina, Ilkovičova 6, 842 15 Bratislava, Slovakia
E-mail: radovan.sebesta@uniba.sk
www.radovansebesta.com
[b] Institute of Chemistry, Faculty of Natural Sciences,
Comenius University in Bratislava
Mlynská dolina, Ilkovičova 6, 842 15 Bratislava, Slovakia
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201801697.
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ammonium salts to give syn-α-amino acid derivatives with ex- syn/anti ratio = 71:29, without any enantioselectivity when
cellent diastereo- and enantioselectivity.[20] Lewis acid mediated amine C2b was used as a catalyst (Table 1, entry 4). Reaction
or metal-catalyzed Wittig rearrangements were also devel- with catalyst C2d proceeded with 100 % conversion, and prod-
oped.[21]
In this context, we decided to study mechanistic details, in
particular, the effect of enamine-type organocatalyst structure,
on [2,3]-Wittig rearrangement of allyloxy ketones.
uct 6a was isolated with 84 % yield, syn/anti = 67:33 and 56 %
ee. Our results agree with those described in the literature[15]
for similar ketone (75 % yield, d.r. 67:33 and 60 % ee). Next, the
reaction was carried out at 5 °C for four days, but it had only a
small effect. We obtained ketone 6a in the same yield, dia-
stereoselectivity was slightly improved to 78:22, and enantio-
selectivity remained the same (Table 1, entries 5 and 6).
Results and Discussion
Allyloxy ketones 5a–f, substrates for [2,3]-Wittig rearrangement,
were prepared from α,ꢀ-unsaturated aldehydes in a three-step
synthesis (Scheme 1). Cinnamyl alcohol, required for the synthe-
sis of substrate 5a, was commercially available. Reduction of
aldehydes 1a–c provided alcohols 2a–c with 62–96 % yields.
Reactions of alcohols with 2-chloro-1-morpholinoethan-1-one
proceeded with 77–93 % yields. Nucleophilic substitutions with
Grignard reagents gave corresponding allyloxy ketones 5a–e in
the yields of 68–94 %. Ketone 5f was prepared in only trace
amount.
Table 1. Screening of pyrrolidine-based organocatalysts in the Wittig rear-
rangement of ketone 5a.
Entry[a] Catalyst Conversion (isolated yield)[%][b] syn/anti-6a[c] ee (syn-6a)[%][d]
1
2
3
4
5
6
7
8
C1
100 (86)
100 (84)
40[e]
62:38
75:25
79:21
71:29
67:33
78:22
63:37
57:43
63:37
63:37
50:50
78:22
56:44
27:73
–
C2a
C2a
C2b
C2d
C2d
C3a
C3b
C4a
C4a
C5b
C8
38
38
0
56
58
0
–22
–60
–60
20
52
6
50
100 (84)
100 (85)[e]
100 (84)
38
9
50
10
11
12
13
14
43[e]
45
36
100 (82)
15
Scheme 1. Synthesis of allyloxy ketones 5a–f.
C9a
C9c
n.d.
With allyloxy ketones 5 in hands, we started to investigate
the effect of chiral organocatalysts on the enantioselectivity of
the Wittig rearrangement. As the reaction proceeds via enamine
activation, we focused primarily on amine-based organocata-
lysts capable of promoting enamine-type reactivity.
[a] Catalyst (0.052 mmol), ketone 5 (0.26 mmol) in MeOH (1 mL), 4 d at r.t.
[b] Conversion was determined by 1H NMR of the crude reaction mixture. [c]
Determined by 1H NMR analysis of the crude reaction mixture. [d] Deter-
mined by chiral HPLC using Chiralcel OJ-H column. [e] Reaction was per-
formed at 5 °C for four days.
We used 20 mol-% of the catalysts, and the reactions were
carried out in methanol at room temperature for four days. Re-
arrangement of ketone 5a catalyzed with pyrrolidine (C1)
reached full conversion and afforded hydroxy ketone 6a in 86 %
yield with syn/anti ratio = 62:38 (Table 1, entry 1). Using (S)-
prolinol (C2a) as a catalyst, product 6a was isolated with 84 %
yield, syn/anti ratio = 75:25 and 38 % ee (syn-6a). The decrease
[2,3]-Wittig rearrangement catalyzed with catalysts C3a and
C9a proceeded with full conversion, hydroxy ketone 6a was
isolated with 84, and 82 % yield, syn/anti ratio was 63:37 and
56:44, respectively, but the product was racemic (Table 1, en-
tries 7 and 13).
Catalysts C3b, C5b, and C8 were less active as conversion
of temperature affected neither diastereo-, nor enantioselec- was only 36–45 %, syn/anti ratio = 50:50–78:22 and 22 % (C3b),
tivity, but the conversion dropped to 40 % (Table 1, entries 2 20 % (C5b) and 52 % ee (C8), respectively (Table 1, entries 8,
and 3). Rearrangement proceeded with 50 % conversion, 11, 12).
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(S)-2-(Trifluoromethyl)pyrrolidine (C4a) catalyzed Wittig rear-
rangement of 5a with 50 % conversion, d.r. 63:37 and high
enantioselectivity (60 % ee). Reaction at 5 °C for four days gave
very similar results (Table 1, entries 9 and 10). Interestingly, cat-
alyst C4a afforded opposite enantiomer of the product in com-
parison to all the other catalysts. Gilmour described a similar
effect of the catalyst C4a in connection with asymmetric ep-
oxidations of cinnamaldehyde.[22] Gauche-effect of fluorous
iminium intermediate substantiated this observation. Surpris-
ingly, the reaction with (S)-2-(trifluoromethyl)piperidine (C4b)
did not work and only starting material was recovered.
Table 2. Screening of primary amine organocatalysts in the Wittig rearrange-
ment of ketone 5a.
Rearrangement with catalyst C9c afforded exclusively an
anti-6a, but unfortunately with only 15 % conversion (Table 1,
entry 14).
Wittig [2,3]-rearrangement of ketone 5a with amine C2c, (S)-
proline (C5a), amide C5c, (S)-indoline-2-carboxylic acid (C6),
tetrazole C7, (S)-diphenyl prolinol and its derivatives (C9b, C9d,
and C9e) did not proceed. Starting material was completely
recovered after reactions.
These results suggest that the Wittig rearrangement of ket-
one 5a was strongly affected by the steric effect of substituent
X in catalyst C9a–e structures. The bulkier substituent X was,
the lower conversion was observed. Reaction with C9a (X=H)
proceeded with the full conversion, but the conversion of 5a
dropped to 15 %, when catalysts C9c (X=F) was used. Unre-
acted starting material was completely recovered, when catalyst
C9b (X=OH), C9d (X=OTMS) and C9e (X=OMe) were employed.
Catalysts possessed of an HNAr moiety (C2e and C5c) were in-
active in Wittig rearrangement of ketone 5a.
Due to steric reasons, catalysts with the primary amino
group are often more suitable for activation of ketones than
those with the secondary amino group.[23] Therefore, we exam-
ined several chiral primary amines, including some amino acids
and their derivatives. (S)-Tryptophan (C10a) did not catalyze the
rearrangement and we observed only 6 % conversion of ketone
5a. On the other hand, conversion of 5a with methyl (S)-
tryptophanate (C10b) was under the same conditions 40 %; the
syn/anti ratio was 84:16 and 6 % ee. Extension of the reaction
time from 4 to 6 days slightly increased conversion to 54 %;
diastereoselectivity dropped to 77:23 and ee was 24 %. The n-
butyl amide of (S)-tryptophan (C10c) catalyzed the reaction
with similar selectivity as ester C10b (Table 2, entries 1–3).
Entry[a] Catalyst
Conversion [%][b] syn/anti-6a[c]
ee (syn-6a)[%][d]
1
2
3
4
5
6
7
8
C10a
C10b
C10c
C11
C11
C11
C12
C13
C14
C15
C16
C17
C18
C19
C20
6
83:17
77:23
85:15
73:27
74:26
70:30
75:25
79:21
71:29
n.d.
n.d.
24
32
24
60
44
30
2
40
n.d.
0
–34
n.d.
n.d.
n.d.
54[e]
20
36[f]
64
95[g]
58
53
66
0
9
10
11
12
13
14
15
39
27
6
82:18
86:14
n.d.
4
n.d.
8
64:36
[a] Catalyst (0.052 mmol), ketone 5 (0.26 mmol) in MeOH (1 mL), 4 d at r.t.
[b] Conversion was determined by 1H NMR of the crude reaction mixture.
[c] Determined by 1H NMR analysis of the crude reaction mixture. [d] Deter-
mined by chiral HPLC using Chiralcel OJ-H column. [e] Reaction proceeded
for 6 d at r.t. [f] 5 mol-% of the catalyst was used. [g] 50 mol-% of the catalyst
was used.
Influence of catalyst loading was tested with (S)-1-phenyl-
Using amine C16 conversion of ketone 5a was 39 %, the
ethan-1-amine (C11). Conversion of 5a increased from 36 % syn/anti ratio was 82:18 but the product was racemic (Table 2,
(5 mol-% of C11) to 95 % (50 mol-% of C11). Catalyst loading entry 11). Rearrangement with quinuclidine C17 proceeded
had virtually no effect on diastereoselectivity. The best enantio- with only 27 % conversion, syn/anti ratio = 86:14 and 34 % ee
selectivity (60 % ee) was observed with 20 mol-% of amine C11 (Table 2, entry 12). Also in this case, major enantiomer was
(Table 2, entries 4–6).
opposite to that obtained with other catalysts.
By contrast to amino alcohol C2a with the secondary amino
group, Wittig [2,3]-rearrangement with amino alcohols having
primary amino groups C18, C19 and C20 proceeded with only
very low conversions (Table 2, entries 13–15).
Several other organocatalysts, such as MacMillan imidazol-
idinones, a thiourea or squaramide were also tested but af-
forded little or no conversion.
Wittig rearrangement of 5a catalyzed with primary amines
C12, C13 and C14 proceeded with conversions 53–66 %,
syn/anti ratio up to 79:21 and 30 % ee (C12), 2 % ee (C13), and
40 % ee (C14). With 100 mol-% of C13 and C12, reaction
reached full conversion. Surprisingly, diastereoselectivity
dropped and a lot of unidentified side products bared from the
isolation of product 6a. Using catalyst C15, only starting mate-
rial was detected in the crude reaction mixture after the reac-
tion (Table 2, entries 7–10).
The solvent screening was performed with ketone 5a and
(S)-1-phenylethan-1-amine (C11) as a catalyst. The reaction did
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not proceed under solvent-free conditions (Table 3, entry 1).
Rearrangement in methanol proceeded with the conversion of
64 % and the product 6a was isolated in 50 % yield with d.r.
74:26 and 60 % ee (Table 3, entry 2). Comparable results were
obtained in ethylene glycol. The reaction in isopropanol and
trifluoroethanol ran with the conversion of 26 and 18 %, respec-
tively (Table 3, entries 4 and 5). Conversion of 58 %, d.r. 71:29
and 60 % ee were observed in ionic liquid 1-ethyl-3-methylimid-
azolium octyl sulfate (Table 3, entry 6). Other solvents such as
water, ethyl acetate, acetonitrile tert-butyl methyl ether, or ethyl
L-lactate were less suitable for this reaction (Table 3, entries 7–
11). The reaction did not proceed in dichloromethane, THF,
deep eutectic solvents cholinium chloride/urea (1:2), and
ChCl/glycerol (2:1) (Table 3, entries 12–14).
Table 3. Solvent screening of the Wittig rearrangement of ketone 5a using
catalyst C11.
Entry[a] Solvent
Conversion (yield) syn/anti-6a[c] ee (syn-6a)
[%][b]
[%][d]
1
2
3
4
5
6
7
8
no solvent
MeOH
0
n.d.
n.d.
60
60
n.d.
n.d.
60
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
64 (50)[e]
74:26
71:29
60:40
69:31
71:29
75:25
67:33
50:50
50:50
57:43
n.d.
Ethylene glycol
iPrOH
CF3CH2OH
[emim]C8H17SO3H[f]
H2O
50
26
18
58
21
21
23
12
11
0
Scheme 2. Substrate scope of the Wittig rearrangement catalyzed by amine
C11; in parentheses yields obtained with pyrrolidine (C1).
(–)-Ethyl L-lactate
9
Ethyl acetate
Acetonitrile
tert Butyl methyl ether
CH2Cl2
10
11
12
13
14
THF
0
0
n.d.
n.d.
DES[h]
[a] Catalyst (0.052 mmol), ketone 5 (0.26 mmol) in a solvent (1 mL), 4 d at r.t.
[b] Conversion was determined by 1H NMR of the crude reaction mixture. [c] Deter-
mined by 1H NMR analysis of the crude reaction mixture. [d] Determined by chiral
HPLC using Chiralcel OJ-H column. [e] Average of two values. [f] 1-Ethyl-3-methyl-
imidazolium octyl sulfate. [h] Two deep eutectic solvents were tried: ChCl/urea (1:2)
and ChCl/glycerol (2:1).
Substrate screening was performed with pyrrolidine (C1) and
chiral primary amine C11 under optimum reaction conditions
(Scheme 2a). Rearrangement of 5a proceeded with pyrrolidine
with full conversion, and product 6a was isolated with 84 %
yield. Using chiral catalyst C11, conversion and yield decreased
to 64 and 50 %. However, diastereoselectivity was slightly better
with chiral amine C11, and syn-6a was obtained with 60 % ee.
Similar results were obtained with substrate 5b, but with chiral
catalyst C11 conversion and yield decreased to 31 and 25 %
(Scheme 2b).
Wittig [2,3]-rearrangement of 5c did not proceed with pyrrol-
idine as a catalyst. 2-(Cinnamyloxy)-1-cyclopentylethan-1-one
as well as 1-(cinnamyloxy)pent-4-en-2-one were also unreactive
under these conditions. Catalyst C11 afforded hydroxy ketone
6c in trace amounts without any diastereoselectivity. The yields
of 6d and 6e also decreased, when we used catalyst C11. Using
chiral catalyst product 6d was obtained with syn/anti ratio of
79:21 and 60 % ee (syn-6d). Similarly, syn/anti ratio for 6e was
73:27 and 60 % ee (syn-6e)(Scheme 3b). The product of Witting
rearrangement was easily converted into the corresponding ox-
Scheme 3. a) Mechanism of amine-catalyzed Wittig rearrangement of allyloxy
ketones. b) Key NOESY interactions in syn-6e; c) imine derived from product
6a and catalyst C11 observed by NMR; d) normalized experimental and
M06/TZVP calculated CD spectra of anti-6e.
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ime. Oxime 7a was prepared from ketone 6a under mild reac-
tion conditions in quantitative yield (Scheme 2c).
Mechanistic Investigations
A relative configuration of Wittig rearrangement products was
determined by NOESY of the product 6e. The key highlighted
interactions are shown in Scheme 3b. An intramolecular
hydrogen bond between the hydroxy and ketone group was
determined by the 1H NMR (doublet for hydrogen in the
hydroxy group) and IR spectrum (3447 cm–1, weak and broad
signal). The interactions between protons with chemical shifts
of 3.78 and 4.52 ppm confirm that a major molecule is syn-
isomer. Comparison of experimental and DFT calculated CD
spectra of minor diastereomer (anti-6e) suggests that its abso-
lute configuration is (2R, 3S) (Scheme 3d); for details see Sup-
porting information.
Scheme 4. a) 3D structures of (E) and (Z)-enamines generated from ketone
5a and C11 obtained by ωB97XD/6-31G*. Energies obtained by M06–2X/6-
311+G**. b) Proposed transition state leading to major syn-diastereomer of
Wittig rearrangement product 6.
Probable enamine or imine intermediates were observed by
LC-MS analysis ([M + H]+ m/z 244.3) from a sample of a crude
reaction mixture – ketone 5a catalyzed by pyrrolidine (C1)
(Scheme 3a).
We also observed new signals in a mixture of 5a and catalyst
C11 in [D4]methanol. These forming proton signals [4.62 (dd)
an 4.41 (d) ppm] interact with a carbon (169.8 ppm, probably
C=N) in HMBC spectrum. The carbons (58.0 and 78.3 ppm) were
paired with specific hydrogens by HSQC spectrum. A probable
intermediate is shown in Scheme 3c.
Quantum-chemical calculations show that corresponding
alkyloxyenamines are more stable in its (Z)-configuration than
(E)-configuration. DFT calculation at ωB97X-D/6-31G*//M06–2X/
6-311+G** level showed that pyrrolidine derived (Z)-enamine
was 3.8 kJ mol–1 more stable than (E)-configured one. A similar
difference was found also for C11-derived enamines
(Scheme 4a). (Z)-enamines are likely stabilized by orbital inter-
actions
idine (C8), which possess of secondary and tertiary amino
groups, amino alcohol C2a, (S)-1-phenylethan-1-amine (C11)
and (S)-2-(trifluoromethyl)pyrrolidine (C4a). Reaction with C4a
afforded in excess opposite enantiomer of syn-6a.
The best solvent for Wittig [2,3]-rearrangement of ketones
5a–e was found to be methanol. Similar stereoselectivity and
slightly lower yields were achieved in ethylene glycol and 1-
ethyl-3-methylimidazolium octyl sulfate.
Wittig [2,3]-rearrangement of branched ketone (with iso-
propyl and cyclopentyl substituent), as well as allyl ketone, did
not proceed. NMR and MS confirmed the presence of catalyst-
derived enamine and iminium intermediates. DFT calculations
suggest that (Z)-configured enamines derived from allyloxy-
ketones are more stable than corresponding (E)-enamines. The
absolute configuration of products of enantioselective Wittig
rearrangement was determined by comparison of experimental
and DFT calculated CD spectra.
σC(N)–H → σ*C-O and σC(O)–H → σ*C-N. These orbital interac-
tions were proposed by Hayashi and Uchimaru after computa-
tional analysis of related alkyloxyenamines.[24]
Considering the formation of syn-diastereomer as a major
product, the syn-transition state can be postulated (Scheme 4b).
In general, anti-products arising from corresponding anti-TS are
more common for [2,3]-Wittig rearrangements. However, for
enolate [2,3]-Wittig rearrangement preference for syn-products
was also noted by Mikami and Nakai.[25]
Experimental Section
General Procedure for [2,3]-Wittig Rearrangement: The catalyst
(0.052 mmol) was added to a solution of ketone (0.26 mmol) in
MeOH (1 mL). The reaction mixture was stirred for 4 days at room
temperature under nitrogen atmosphere. Subsequently, the reac-
tion was quenched with 0.1
M HCl solution (1 mL). The resulting
mixture was extracted with Et2O (3 × 3 mL). The combined organic
phases were washed with saturated Na2CO3 solution (10 mL) and
saturated NaCl solution (10 mL). The combined organic layers were
dried with MgSO4, drier was filtered off and solvent was removed
in vacuo. Column chromatography on silica gel (hexanes/EtOAc, 3:1)
furnished the title compounds as yellow oils. The products were
obtained as a mixture of diastereoisomers.
Conclusions
Organocatalytic [2,3]-Wittig rearrangement was studied with 40
various organocatalysts. The best chemical yields (above 80 %)
were obtained with pyrrolidine (C1), (S)-prolinol (C2a), (S)-1-
(pyrrolidin-2-ylmethyl)pyrrolidine (C2d), (R)-2-methylpyrrolidine
(C3a) and (S)-2-benzhydrylpyrrolidine (C9a). Regarding dia-
stereoselectivity, (S)-tryptophan and its derivatives (C10a, C10b,
and C10c), primary amine C16, as well as quinuclidine C17 with
the primary amino group, were found to be most suitable. The
Acknowledgments
best enantioselectivity was achieved with (S)-1-(pyrrolidin-2-yl- This work was supported by the Slovak Grant Agency VEGA,
methyl)pyrrolidine (C2d) and (2R,2′R)-1-isopropyl-2,2′-bipyrrol- grant no. VEGA 1/0414/16. This publication is the result of the
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Keywords: Asymmetric catalysis · Organocatalysis ·
Sigmatropic rearrangement · Allylic compounds · Ketones
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Received: November 15, 2018
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Asymmetric Organocatalysis
T. Peňaška, M. M. Mojzes, J. Filo,
H. Jurdáková, M. Mečiarová,
R. Šebesta* ............................................. 1–7
Organocatalysts Effect on the Stereo-
selectivity of [2,3]-Wittig Rearrange-
ment
A range of amine organocatalysts were be preferred for this reaction. Intermedi-
screened in the [2,3]-Wittig rearrangement ates of the reaction were observed by
of allyloxyketones. Sterically unencum- NMR and MS. (Z)-Configured enamines
bered catalysts, such as phenylethylamine are preferred ones based on DFT calcula-
or small pyrrolidine derivatives, seem to tions.
DOI: 10.1002/ejoc.201801697
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
7
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim