Preparation and structures of 2-substituted 5-benzyl-3-methylimidazolidin- 4-one-derived iminium salts, reactive intermediates in organocatalytic transformations involving α,β-unsaturated aldehydes

Article abstract of DOI:10.1002/hlca.201400110

Preparations of the title compounds, 5-7 (Scheme 1 and Table 1), of their ammonium salts, 9-11 (Scheme 2 and Table 2), and of the corresponding cinnamaldehyde-derived iminium salts 12-14 (Scheme 3 and Table 3) are reported. The X-ray crystal structures of 15 cinnamyliminium PF₆ salts have been determined (Table 4). Selected ¹H-NMR data (Table 5) of the ammonium and iminium salts are discussed, and structures in solution are compared with those in the solid state. Copyright

Full text of DOI:10.1002/hlca.201400110

Helvetica Chimica Acta – Vol. 97 (2014)
751
Preparation and Structures of 2-Substituted 5-Benzyl-3-methylimidazolidin-
4-one-Derived Iminium Salts, Reactive Intermediates in Organocatalytic
Transformations Involving a,b-Unsaturated Aldehydes
by Urosˇ Grosˇelj*
Department of Organic Chemistry, Faculty of Chemistry and Chemical Technology, University of
ˇ
ˇ
Ljubljana, Askerceva cesta 5, P.O. Box 537, SI-1000 Ljubljana
(fax: þ 38612419220, e-mail: uros.groselj@fkkt.uni-lj.si)
and
Albert Beck, W. Bernd Schweizer, and Dieter Seebach
Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zꢀrich,
Hçnggerberg HCI, Vladimir-Prelog-Weg 3, CH-8093 Zꢀrich
(fax: þ 41446321144; e-mail: seebach@org.chem.ethz.ch)
Preparations of the title compounds, 5 – 7 (Scheme 1 and Table 1), of their ammonium salts, 9 – 11
(Scheme 2 and Table 2), and of the corresponding cinnamaldehyde-derived iminium salts 12 – 14
(Scheme 3 and Table 3) are reported. The X-ray crystal structures of 15 cinnamyliminium PF6 salts have
1
been determined (Table 4). Selected H-NMR data (Table 5) of the ammonium and iminium salts are
discussed, and structures in solution are compared with those in the solid state.
1. Introduction. – We were the first1) to isolate and structurally characterize
cinnamaldehyde-derived iminium salts prepared from 2-(tert-butyl)-3-methylimidazo-
lidin-4-one (2), (5S)-5-benzyl-2,2,3-trimethylimidazolidin-4-one (7e), and (2S,5S)-5-
benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (7c)2). Such iminium ions are reac-
tive intermediates in organocatalysis [4][5]. Details of our single-crystal X-ray
structures revealed a striking resemblance with those of the corresponding DFT-
calculated crotonaldehyde-derived reactive intermediates [6]. By NMR analyses,
Tomkinson and co-workers and our group have also identified the preferred
conformation in solution of the benzylic C,C-bond in these iminium ions [1][5]. The
ensuing enthusiasm quickly resulted in the preparation of a statistically significantly
large number of cinnamaldehyde-derived imidazolidin-1-ium salts. The obtained data
raised questions, regarding the stereochemical models for additions to a,b-unsaturated
aldehydes, on the role of the (E)- and (Z)-iminium intermediates [7][8], and the
conformation of the benzyl (Bn) substituent [9]. In parallel, synthesis and structural
1
)
)
Independently, Tomkinson and co-workers have published preparation of the PF6-iminium salt from
7e and cinnamaldehyde [1].
Compounds 7e and 7c are frequently referred to as MacMillanꢂs first- and second-generation (cf. [2]
and [3], resp.) imidazolidinone organocatalysts, respectively.
2
ꢁ 2014 Verlag Helvetica Chimica Acta AG, Zꢀrich

752
Helvetica Chimica Acta – Vol. 97 (2014)
characterization of diarylprolinol-derived iminium salts took place [10]. The ease of
preparation of imidazolidinone- and diarylprolinol-derived reactive iminium inter-
mediates and their stability were used in various mechanistic studies and for
development of modified imidazolidinone- and diarylprolinol-based organocatalysts
[11]. Herein, we report all experimental details regarding the synthesis and structural
characterization of imidazolidinones, their ammonium salts, and cinnamaldehyde-
derived iminium salts, having remained undisclosed in previous publications. We also
discuss herein the conformations of the iminium salts in the solid state and in solution.
2. Preparation of Imidazolidinones, and Corresponding Ammonium Salts and
Cinnamaldehyde-Derived Iminium Salts. – The only C(5)-unsubstituted imidazolidi-
none, 2-(tert-butyl)-3-methylimidazolidin-4-one [12] (2), was prepared via BF3 · Et2O-
mediated Boc deprotection [13] of Boc-BMI [12] (1) (Scheme 1). All 5-benzyl-3-
methyl-1,3-imidazolidin-4-ones, 4 – 7, were prepared from (S)-2-amino-N-methyl-3-
phenylpropanamide, the N-methyl amide 3 of phenylalanine [14], in a cyclocondensa-
tion reaction with various aldehydes and ketones (Conditions A – E; Scheme 1 and
Table 1). The only C(2)-unsubstituted imidazolidinone, (S)-5-benzyl-3-methylimida-
zolidin-4-one (5) was prepared from 3 and aqueous HCHO in the presence of freshly
activated 4-ꢃ molecular sieves (MS) in toluene (Conditions B; Scheme 1 and Table 1).
An attempt to prepare 5 from a mixture of paraformaldehyde and 1,3,5-trioxane, and
amide 3 under similar reaction conditions resulted in the formation of the bis-
imidazolidinone 4 (Conditions A; Scheme 1). In most cases, the reaction of the
phenylalanine amide 3 with an aldehyde or a ketone was carried out in anhydrous
EtOH with or without catalytic amounts of TsOH · H2O under Ar in the presence of
freshly activated 4-ꢃ MS (suspended in the gas phase [15]). In this manner, compounds
6a, 6d – 6j, and 7a, 7d – 7j were prepared (Conditions C; Scheme 1 and Table 1).
Similarly, 2-iPr- (6b, 7b) and 2-tBu-substituted imidazolidinones, 6c and 7c, respectively
[3], were prepared from 3 and isobutyraldehyde or pivalaldehyde, respectively, using a
slightly modified literature procedure [16] in anhydrous benzene or toluene, in the
presence of FeCl3 (Conditions D; Scheme 1 and Table 1). The reaction of 3 with
propanal gave, besides the expected 2-Et-substituted imidazolidinones 6a and 7a, also
the side-products 6a’ and 7a’. The formation of 6a’/7a’ can be explained by the initial
aldol condensation of propanal to (E)-2-methylpent-2-enal, followed by cyclization
(Conditions E; Scheme 1 and Table 1). The reaction of amide 3 with 2,3-dihydro-1H-
inden-1-one furnished, besides the desired spiro-imidazolidinone 7j, also the imine 8j.
The trans- and cis-diastereoisomers, 6 and 7, respectively, could in all cases be separated
by column chromatography, as a rule of thumb, the trans-isomer 6 is eluted first,
followed by the cis-isomer 7.
Most of the imidazolidinones prepared were converted to the corresponding BF4ꢀ
and/or PFꢀ6 ammonium salts, 9 and 10, and 11, respectively, by simply mixing the
corresponding Et2O solutions of an imidazolidinone, 2, 6, or 7, and of HBF4 or HPF6
(Scheme 2 and Table 2); there was no cis/trans-equilibration in this salt-forming
process. The vast majority of ammonium salts precipitated from the reaction mixture,
the precipitate was collected by filtration, washed with Et2O, and dried under high
vacuum. For workup of the products that did not precipitate from the reaction mixture,
see the Exper. Part. The BFꢀ4 ammonium salt of cis-5-benzyl-2-(tert-butyl)imidazoli-

Helvetica Chimica Acta – Vol. 97 (2014)
753
Scheme 1. Preparation of Imidazolidinones 2, 4 – 7, and of Amide 8j. For R and R’, see Tables 1 and 2,
and Exper. Part.
dinone 10b turned out to be very hygroscopic, and the cis-5-benzyl-2-(tert-butyl)-2-
methylimidazolidinone-derived PFꢀ6 ammonium salt 11m decomposed in solution but
was stable in the solid state. After prolonged standing (6 months or more at r.t.) PF6ꢀ

754
Helvetica Chimica Acta – Vol. 97 (2014)
Table 1. Preparation of Imidazolidinones 6 and 7. For the particular procedure used, see Scheme 1
and Exper. Part. Yields refer to isolated and purified products; enantiomer ratios (er) were determined
by HPLC analysis with Chiralcel OD-H or Chiralpak AD-H columns and hexane/iPrOH mixtures as
mobile phase.
Reaction
Condi-
tions
Ketone/aldehyde
trans-Product 6
(yield [%], er)
cis-Product 7
(yield [%], er)
3 ! 6a, 7a, 6a’, 7a’
E
12, > 99.5 : 0.5
12, > 99.5 :0.5
4
7
3 ! 6b, 7b
D
26
28
3 ! 6c, 7c [16]
3 ! 7d [17]
D
C
29
13
35
–
3 ! 7e [2]
3 ! 6f, 7f
C
C
85
–
24, > 99 : 1
29, > 99.5 :0.5
3 ! 6g, 7g
C
40
38
3 ! 7h [18]
3 ! 6i, 7i
C
C
41
33
–
28
3 ! 7j
C
41
–
ammonium and iminium salts started to decompose (with formation of HF), in spite of
their storage in an anhydrous Ar atmosphere.
According to a modified procedure of Leonard and Paukstelis [19], the BFꢀ4 and
PFꢀ6 ammonium salts, 9 and 10, and 11, respectively, were used in the preparation of the
corresponding iminium salts 12 – 14. Thus, mixing of an ammonium salt in anhydrous
EtOH with cinnamaldehyde in the presence of catalytic amounts of Et3N under Ar
afforded the iminium salt as a filterable solids. Only in the case of trans-5-benzyl-(2-tert-
butyl)-imidazolidin-1-ium salt 11d, the reaction with cinnamaldehyde, after prolonged
reaction time, yielded transamination products: 5-benzyl-2-styrylimidazolidin-1-ium
salts (E)- and (Z)-14f. Under thermodynamic conditions in solution, most of the
isolated iminium salts existed as mixtures of the major (E)- and the minor (Z)-
diastereoisomers (NMR analysis). Only in the C(2)-unsubstituted iminium salt 14a, the

Helvetica Chimica Acta – Vol. 97 (2014)
755
Scheme 2. Preparation of the Ammonium Salts 9, 10, and 11. For R and R’, see Tables 1 and 2, and Exper.
Part.
Table 2. Prepared BFꢀ4 and PFꢀ6 Imidazolidin-2-ium Salts 10 and 11 (cf. Scheme 2). The yields refer to
isolated and purified products.
Reaction
Xꢀ
R
R’
Yield [%]
6c ! 10a
7c ! 10b
7e ! 10c
5 ! 11a
BFꢀ4
BFꢀ4
BFꢀ4
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
H
tBu
H
Me
H
H
H
tBu
H
86
67
83
83
85
82
97
58
56
74
93
71
86
88
87
87
38
97
tBu
Me
H
Et
iPr
H
tBu
7a ! 11b
7b ! 11c
6c ! 11d
7c ! 11e
7a’ ! 11f
7d ! 11g
7e ! 11h
6f ! 11i
7f ! 11j
6g ! 11k
7g ! 11l
7h ! 11m
6i ! 11n
7i ! 11o
(2E)-Pent-2-en-2-yl
Ph
H
H
Me
Me
CH2F
Me
iPr
tBu
Me
Ph
Me
CH2F
Me
iPr
Me
Me
Ph
Me
7j ! 11p
PFꢀ6
56
(Z)-isomer predominated (Scheme 3 and Table 3). It is worth mentioning that all but
one of the iminium salts 12 – 15 could be prepared in analytically pure form (see Exper.
Part). In the solid state and if properly stored (pre-dried in high vacuum, stored under
Ar), these cinnamaldehyde-derived iminium salts were ꢄbench-stableꢂ. Under anhy-

756
Helvetica Chimica Acta – Vol. 97 (2014)
Scheme 3. Preparation of the Iminium salts 12 – 15. For R and R’, see Table 3 and Exper. Part.
drous conditions, decomposition of the iminium salts was negligible even in solution. In
an attempt to prepare single crystals for X-ray-analysis of the C(2)-unsubstituted
iminium salt 14a by slowly condensing Et2O into an acetone solution, unexpectedly, the
acetone-derived iminium salt 15 was obtained and characterized by single-crystal X-ray

Helvetica Chimica Acta – Vol. 97 (2014)
757
Table 3. Preparation of Imidazolidin-1-ium Salts 13 and 14. The yields refer to isolated and purified
products. All products 13 and 14 are crystalline. The crystals generally consist of (E)-isomers (cf.
Table 4). In solution, equilibration with the (Z)-isomers occurs. The (E)/(Z) ratios were determined in
various NMR solvents (cf. Table 5); for details, see Exper. Part.
Reaction
Xꢀ
R (cis)
R’ (trans)
Yield [%]
(E)/(Z)
10c ! 13a
11a ! 14a
11b ! 14b
11c ! 14c
11e ! 14d
11f ! 14e
11d ! 14f
11g ! 14g
11h ! 14h
11i ! 14i
BFꢀ4
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
PFꢀ6
Me
H
Me
H
H
H
H
H
H
H
Me
CH2F
Me
iPr
Me
Me
Ph
Me
44
83
77
85
58
67
34
57
76
86
76
73
92
20
95
91
97: 3
31 : 69
79 : 21
87: 13
95 : 5
65 : 35
72 : 28
67: 33
98 : 2
> 99 : 1
> 99 : 1
> 99 : 1
> 99 : 1
> 99 : 1
89 : 11
76 : 24
Et
iPr
tBu
(2E)-Pent-2-en-2-yl
(E)-2-Phenylethenyl)
Ph
Me
Me
CH2F
Me
iPr
tBu
Me
Ph
11j ! 14j
11k ! 14k
11l ! 14l
11m ! 14m
11n ! 14n
11o ! 14o
11p ! 14p
PFꢀ6
79 : 21
90
analysis (Scheme 3). This unique event has not been observed when preparing single
crystals of any one of the other iminium salts, using acetone as one of the co-solvents for
crystal growth.
From Table 3, one can clearly see how the substituents at C(2) control the
configuration of the exocyclic N¼C bond of the iminium salts (the (E)/(Z)-ratio under
thermodynamic conditions). A good control of the configuration of the a,b-
unsaturated iminium intermediate is one of the prerequisites for high stereoselectivity
t
of corresponding imidazolidinone-catalyzed organocatalytic reactions. A large Bu
group at C(2) of iminium salts 12 and 14d enforces predominantly the (E)-
configuration of the exocyclic N¼C bond (Scheme 3 and Table 3). Not surprisingly,
the corresponding imidazolidinones 2 [20] and 7c [3][20] are well-established,
commercially available organocatalysts. Reducing the steric bulk of the substituent
at C(2) in the series tBu, iPr, Et, H results in decreased (E)/(Z)-control and eventually
leads to the (Z)-diastereoisomer (R ¼ H) as the major isomer. A substituent with a less
bulky a-sp2-hybridized C(2)-atom leads to diminished (E)/(Z)-control (14e – 14g and
14n – 14p; Table 3). On the other hand, the reduction of steric strain (1,5-repulsion
[21]) imposed by the substituent at C(2) is crucial for the performance of (2S,5S)-5-
benzyl-3-methyl-2-(5-methylfuran-2-yl)imidazolidin-4-one [17], designed for enantio-
selective catalytic DielsꢀAlder reactions with simple a,b-unsaturated ketones. One can
only guess how much fine-tuning has been invested in the ꢄdesignꢂ of this catalyst. Two
geminal substituents at C(2) provide perfect (E)/(Z)-control of the corresponding
cinnamyl-iminium ion (14h – 14m; Table 3), which is evident in the case of the

758
Helvetica Chimica Acta – Vol. 97 (2014)
benchmark catalyst 7e (!11h ! 14h) [2]. Of course, placing a large group, such as iPr,
in the 2-trans-position would counteract the selective attack of the nucleophile from the
side anti to the Bn group. Finally, if one of the two geminal groups is replaced by a
substituent bearing a a-sp2-hybridized C-atom, the (E)/(Z)-control falters once
again3).
3. Preparation of Single Crystals of Iminium Salts for X-Ray Analysis. – All the
single crystals of iminium salts (BF4ꢀ and PFꢀ6 ) for X-ray analysis have been prepared by
slow diffusion of Et2O or petroleum ether, in a large outer container, into a solution of
the iminium salt in acetone and/or CH2Cl2 in a smaller container. The small container
was positioned inside the larger one. The relative volume of Et2O or petroleum ether
was much bigger compared to that of acetone and/or CH2Cl2. All the solvents and
glassware used were rigorously dried to ensure anhydrous conditions and prevent
hydrolysis, and all crystallizations were performed under Ar at room temperature. The
slow diffusion of Et2O or petroleum ether caused gradual change in the solvent
composition and thus polarity, which eventually induced the crystal formation and slow
growth. The structures of the iminium ions, salts of which are described herein, have
been discussed in our previous papers [4][5][7][9][10]. Besides the non-benzylated
salt 12, the altogether 14 structures of 5-benzyl-1-cinnamyl-3-methylimidazolidinone
iminium salts, 14 and 15, shown in Table 4, fall into three distinct categories
A – C (Fig. 1), according to the conformation of the Bn group at C(5). A fourth
conformation D with a pentafluoro-substituted Bn group has been discovered only
recently [11g] (Fig. 1). In the acetone-derived C(2)-unsubstituted iminium salt 15, the
Bn group has conformation A, with the Ph group over the heterocycle. This same
conformation is present in most other C(2)-substituted iminium salts. In the crystal of
the enantiomerically pure form of the (E)-cis-2-Ph-substituted iminium salt 14g, the Bn
group adopts conformation A (non-centrosymmetric space group P212121), while in the
crystal of the racemate conformation B was adopted (centrosymmetric space group
P21/c), with the benzene ring over the p-system. The substituents at C(2) affect, besides
Fig. 1. The four conformations A – D of the benzyl group of cinnamaldehyde-derived iminium salts found
experimentally. For discussion and DFT calculations of the conformations A – D, see our previous report
and refs. cit. therein [9].
3
)
Note that this discussion is a ꢄthermodynamic oneꢂ, suggesting that the thermodynamically more
stable (E)-isomer dictates the stereochemical course of the catalytic reaction. We have, however,
shown that the (Z)-isomer may be the kinetically preferred diastereoisomer [7].

Helvetica Chimica Acta – Vol. 97 (2014)
759
Table 4. X-Ray Crystal Structures of Cinnamaldehyde-Derived 4-Oxoimidazolidin-1-ium Salts 12, 14, and
15, Ordered According to Their Conformations A – C. PF6 Counteranions are omitted for clarity.
Crystal structures with conformation A
CCDC 990626
CCDC 990627
CCDC 990628
CCDC 711496 [5]
CCDC 990629

760
Helvetica Chimica Acta – Vol. 97 (2014)
Table 4 (cont.)
CCDC 711494 [5]
CCDC 990630
CCDC 990631
CCDC 990632
Crystal structures with conformation B
CCDC 990633

Helvetica Chimica Acta – Vol. 97 (2014)
761
Table 4 (cont.)
CCDC 711495 [5]
CCDC 990634
Crystal structures with conformation C
CCDC 990635
CCDC 990636
Crystal structure without 5-Bn substituent
CCDC 695937 [4]

762
Helvetica Chimica Acta – Vol. 97 (2014)
the configuration of the N¼C bond, also the conformation of the benzylic CꢀC bond,
and thus the position of the Ph ring. In the case of the sterically bulky cis-iPr and cis-tBu
groups of the iminium salts 14c and 14d, the Bn group adopted conformation B, with
the Ph group above the cinnamyl-iminium p-system. Finally, the third, eclipsed
conformation C was found in iminium salts bearing trans-Me/cis-iPr groups (i.e., 14l)
and trans-Me/cis-tBu groups (i.e., 14m). In two cases with the conformation A, with the
Ph group above the imidazolidinone ring, the exocyclic N¼C bond had (Z)-
configuration (14o and 14p) (Table 4).
1
4. Comparison of Selected H-NMR Data with Conformations A – C Observed in
the Solid State. – As reported in [5] for the iminium salts of 2,2-dimethylimidazoli-
dinone, (E)-14h, and of the 2-styrylimidazolidinone, (E)-14f, the conformation A of
the Bn group, observed in the solid state, must also be populated in solution: there is a
massive upfield shift of the signals from the cis-Me and the styryl HꢀC(1’) (cf. the
corresponding signals of the ammonium salts 11h, and Figs. 2 and 3 in [5]). The same
observation was made in the NMR spectra of all iminium salts, of which conformation
A was present in the crystal structure: depending on the solvent, there was a more or
less strong shielding of H-atoms in the groups located cis to the Bn group (see the
following pairs of ammonium and (E)- or (Z)-configured iminium salts: 11b/(E)-14b,
11f/(E)-14e, 11g/(E)-14g, 11i/(E)-14i, 11o/(Z)-14o, 11p/(Z)-14p; Tables 4 and 5, and
Exper. Part). Based on these results, we assign the same configuration A of the Bn
group from the 1H-NMR data, also to those (E)- and/or (Z)-configured iminium salts
that did not give suitable single crystals for X-ray-analysis (compare the data for 11f/
(Z)-14e, 11k/(E)-14k, 11n/(E/Z)-14n, 11o/(E)-14o, 11p/(E)-14p in Table 5 and in the
Exper. Part). In the case of (E)- and (Z)-iminium salt 14a, the signals of the cis-H-atom
at C(2) are not subject to an upfield shift, compared to those of the corresponding
ammonium salt 11a, conformation A was assigned, based on the X-ray structure of the
acetone-derived iminium salt 15. In two cases, iminium salts (E)-14c and (E)-14d [5],
the sterically bulky iPr and tBu substituents cause the Ph group to be located over the
iminium p-system in the solid state. That this conformation B was also populated in
solution, could be deduced from the ca. 1-ppm upfield shift of the signal of HꢀC(2’) in
the 1H-NMR spectrum: HꢀC(2’) is situated underneath the Ph group in conformation
B, but not in conformation A (compare the chemical shifts of HꢀC(2’) in (E)-14c and
(E)-14d with that in (E)-14h, and also with that in (Z)-14c). Conformation B was
tentatively assigned also to the cis-(CH2F)-substituted iminium salt (E)-14j [8]. Finally,
a similar degree of shielding of the H-atoms at C(2’) was observed for the iminium salts
(E)-14l and (E)-14m, the solid-state structures of which have the eclipsed benzylic
conformations C. As can be seen from space-filling representations of the crystal
structures of these two compounds (Fig. 5 in [9]), the Ph ring is turned in such a way
1
that it exerts anisotropy on HꢀC(2’). Thus, it appears that, from H-NMR spectra
alone, it is not possible to distinguish between conformations B and C in solution. An
elaborate calculation of the potential energy for rotation around the benzylic CꢀC
bond in the cis-tBu,2-Me-substituted iminium ion (E)-14m revealed a negligible energy
difference between conformations B and C (Fig. 8 in [9]). In the (Z)-iminium salts
14n – 14p bearing a Ph group at C(2), the signals of HꢀC(2’) are subject to a strong
upfield shift, as compared to the corresponding (E)-diastereoisomers (see Table 5).

Helvetica Chimica Acta – Vol. 97 (2014)
763
Table 5. Selected 1H-NMR Data (d [ppm], multiplicity) of Ammonium and Iminium Salts Derived from
Imidazolidinones.
Compound
Solvent,
conformation
HꢀC(1’), HꢀC(2’), HaꢀC(2)
HꢀC(3’)
HbꢀC(2)
4.50 (d)
4.54 (d)
(D6)DMSO, –
8.97 (d), 7.38 (dd), 4.87 (d)
8.21 (d)
5.43 (d)
(D6)Acetone, –
8.85 (dd), ~7.58a); 4.99 (dd)
8.25 (d)
5.62 (dt)
MeCH2
(D6)Acetone, –
HꢀC(1’), HꢀC(2’), MeCH2
HꢀC(3’)
1.63 – 1.76 2.10 – 2.22
(m) (m)
(D6)DMSO, –
8.99 (d), ~7.33a),
8.31 (d)
1.19 – 1.31 1.83 – 1.95
(D6)Acetone, A
(m)
(m)
a
a
8.61 (d), ~7.65a),
8.16 (d)
)
)
(D6)Acetone, –

764
Helvetica Chimica Acta – Vol. 97 (2014)
Table 5 (cont.)
HꢀC(1’), HꢀC(2’), HꢀC(1’’)
HꢀC(3’)
Me2CH
Me2CH
1.04 (d)
2.29 – 2.41 0.92 (d)
(m)
(D6)DMSO, –
8.92 (d), 6.80 (dd), 2.32 – 2.45 1.21 (d)
1.21 (d)
(D6)Acetone, B
8.24 (d)
(m)
8.46 (d), ~7.62a),
8.10 (d)
2.46 – 2.55 1.13 (d)
(m)
1.31 (d)
(D6)Acetone, –
HꢀC(1’), HꢀC(2’), tBu
HꢀC(3’)
1.08 (s)
(D6)DMSO, –
8.92 (d), 6.55 (dd), 1.34 (s)
8.27 (d)
(D6)Acetone, B [5]
b
8.49 (d), b), 8.11 (d)
)
(D6)Acetone, –

Helvetica Chimica Acta – Vol. 97 (2014)
765
Table 5 (cont.)
HꢀC(1’), HꢀC(2’), Me(3’’)
HꢀC(3’)
HꢀC(2’’)
5.85 (td)
1.56 (s)
(D6)DMSO, –
8.86 (d), ~7.42a),
8.34 (d)
1.12 (d)
6.19 – 6.23
(m)
(D6)Acetone, A
8.90 (dt), ~7.68a),
8.25 (d)
~1.07a)
6.55 (td)
HꢀC(2’’)
(D6)Acetone, –
HꢀC(1’), HꢀC(2’), HꢀC(1’’)
HꢀC(3’)
9.73 (d), 6.78 (dd),
7.65 (d)
(D6)Acetone
CDCl3 [22]
6.20 (dd)
6.61 (d)
7.20 (d)
9.08 (d), 7.90 (dd), 4.27 (dd)
8.42 (d)
(D6)Acetone, A [5]
9.18 (dt), ~7.62a),
8.32 (d)
4.35 (dd)
~7.53a)
(D6)Acetone, – [5]

766
Helvetica Chimica Acta – Vol. 97 (2014)
Table 5 (cont.)
HꢀC(1’), HꢀC(2’), Hortho of Ph
HꢀC(3’)
~7.43c)
(D6)DMSO, –
8.88 (d), ~7.53a),
8.30 (d)
~6.95c)
(D6)Acetone, A,
(2R,5S), B, rac
b
9.12 (dt), 7.19 (dd),
8.24 (d)
)
(D6)Acetone, –
HꢀC(1’), HꢀC(2’), MeꢀC(2) MeꢀC(2)
HꢀC(3’)
1.52 (s)
1.66 (s)
(D6)DMSO, – [5]
9.33 (dd), ~7.73a), 0.75 (s)
8.25 (d)
1.74 (s)
(D6)DMSO, A [5]
b
b
b
9.16 (d), b),
)
)
)
(D6)DMSO, – [5]

Helvetica Chimica Acta – Vol. 97 (2014)
767
Table 5 (cont.)
HꢀC(1’), HꢀC(2’), HaHbCF
HꢀC(3’)
HaHbCF MeꢀC(2)
4.90 (dd)
5.02 (dd) 1.90 (d)
(D6)Acetone, –
9.27 (dd), 7.93 (dd), 4.86 (dd)
8.53 (d)
4.98 (dd) 0.94 (d)
(D6)Acetone, A
HꢀC(1’), HꢀC(2’), HaHbCF
HꢀC(3’)
HaHbCF Me
4.70 (dd)
4.82 (dd) 1.55 (d)
(D6)DMSO, –
(D6)Acetone, –
9.19 (d), 7.20 (dd), 4.18 (dd)
8.31 (d)
4.68 (dd) 2.02 (d)
HꢀC(1’), HꢀC(2’), HꢀC(1’’)
HꢀC(3’)
MeꢀC(2)
2.18 – 2.31 1.56 (s)
(m)
(D6)DMSO, –
9.15 (dd), 7.94 (dd), 2.39 – 2.52 0.99 (s)
8.55 (d) (m)
(D6)Acetone, –

768
Helvetica Chimica Acta – Vol. 97 (2014)
Table 5 (cont.)
HꢀC(1’), HꢀC(2’), HꢀC(1’’)
HꢀC(3’)
MeꢀC(2)
2.23 – 2.37 1.57 (s)
(m)
(D6)DMSO, –
9.09 (dd), 6.93 (dd), 2.34 – 2.46 2.01 (s)
(D6)Acetone, C
8.37 (d)
(m)
HꢀC(1’), HꢀC(2’), tBu
HꢀC(3’)
MeꢀC(2)
1.53 (s)
1.09 (s)
(D6)DMSO, –
9.26 (d), 6.59 (dd), 1.17 (s)
8.35 (d)
1.96 (s)
(D6)DMSO, C
HꢀC(1’), HꢀC(2’), Hortho of Ph MeꢀC(2)
HꢀC(3’)
b
)
2.11 (s)
(D6)DMSO, –
(D6)DMSO, –
b
8.86 (dd), ~7.72a)c),
8.18 (d)
)
1.26 (s)

Helvetica Chimica Acta – Vol. 97 (2014)
769
Table 5 (cont.)
HꢀC(1’), HꢀC(2’), Hortho of Ph MeꢀC(2)
HꢀC(3’)
b
9.16 (d), 6.67 (dd),
8.13 (d)
)
1.36 (s)
(D6)DMSO, –
HꢀC(1’), HꢀC(2’), Hortho of Ph MeꢀC(2)
HꢀC(3’)
~7.49c)
2.02 (s)
(D6)DMSO, –
9.17 (dd), ~7.40a), ~7.09c)
8.26 (d)
2.37 (s)
(D6)Acetone, –
b
9.35 (dd), 6.73 (dd),
8.37 (d)
)
2.40 (s)
(D6)Acetone, A
HꢀC(1’), HꢀC(2’), Hortho of Ph
HꢀC(3’)
~7.40b)
(D6)DMSO, –

770
Helvetica Chimica Acta – Vol. 97 (2014)
Table 5 (cont.)
HꢀC(1’), HꢀC(2’), Hortho of Ph
HꢀC(3’)
5.13 (d)
(D6)Acetone, –
8.61 (dd), 7.91 (dd),
8.44 (d)
9.41 (dd), 6.25 (dd), 4.90 (d)
8.37 (d)
(D6)Acetone, A
c
a) Extracted from 2D HSQC spectra. b) Overlapped by other signals or not detected. ) Extracted from
1D-NOE recordings in (D6)Acetone.
The configurational assignments of the key compounds, the iminium salts 14, and
the assignments of ortho-H-atoms of the Ph group of compounds 11g and 11o were
derived from steady-state NOE difference NMR experiments (for details see Fig. 2 and
Exper. Part).
Novel imidazolidinones were characterized only partially. On the other hand,
ammonium and iminium salts were fully characterized, in most cases with correct
elemental analyses. The cis/trans-configurations of the 2,5-disubstituted imidazolidi-
nones and the corresponding ammonium salts were confirmed indirectly via X-ray
structural characterization of the respective iminium salts.
5. Conclusions. – The preparation of a large number of phenylalanine-derived cis-
and trans-imidazolidinones in pure form and of the corresponding ammonium and
cinnamyl iminium salts has enabled us to perform a detailed structural analysis by X-
ray-diffraction and NMR methods. The X-ray data of altogether 15 iminium salts
provide statistically relevant information4) about the structural energy minima of the
4
)
In several publications, a single, accidentally obtained X-ray structure is used to draw general
structural and mechanistic conclusions. In the present case, the many X-ray structures (this paper
and [1][4][5][7 – 9][11g]) led to the discovery of four different conformations (Fig. 1) around the
benzylic bond, and of the two different configurations of the exocyclic C¼N bond of cinnamylidene
imidazolidinones.

Helvetica Chimica Acta – Vol. 97 (2014)
771
Fig. 2. Configurational assignments of compounds 8j, 11, and 14, derived from steady-state NOE
difference NMR recordings (see the red arrows)

772
Helvetica Chimica Acta – Vol. 97 (2014)
iminium ions, which are intermediates of organocatalytic Michael additions to, and
DielsꢀAlder reactions of cinnamaldehydes. Delicate effects of the substitution pattern
on the configuration of the exocyclic iminium bond ((E) or (Z)) and on the
conformation of the benzylic bond ((þ)-sc, (ꢀ)-sc, ac, or ap) in solution have been
unraveled by the NMR analysis.
Experimental Part
General. All reactions were performed under Ar in dried glassware using anh. solvents except when
using aq. reagents. All chemicals were reagent grade and used as supplied, unless stated otherwise.
Solvents for extractions and chromatography were technical grade and were distilled prior to use. Sat.
hydrocarbon solvents were kept over Na wire. Extracts were dried over technical-grade MgSO4. TLC:
Precoated Merck silica gel 60 F254 plates (0.25 mm). Column chromatography (CC): Fluka silica gel 60
(230 – 400 mesh). M.p.: Bꢀchi 510 melting point apparatus and are uncorrected. Optical rotations: Jasco
P-2000 polarimeter. IR Spectra: as neat solid/oil on a PerkinElmer Precisely Universal ATR Sampling
1
Accessory; in cmꢀ1. H- and 13C-NMR spectra: Bruker AVANCE (at 300 and 75 MHz, resp.), DRX (at
400 and 101 MHz, resp.), AV (at 400 and 101 MHz, resp.), or Varian Gemini-300 (at 300 and 75 MHz,
resp.) spectrometer; chemical shifts (d) are reported in ppm relative to TMS (0.00 ppm). High-resolution
(HR) MS: performed by the MS service at the Laboratory for Organic Chemistry, ETH Zꢀrich on a
IonSpecUltima 4.7-T-FT Ion Cyclotron Resonance (ICR; HR-MALDI, in 2,5-dihydroxybenzoic acid
matrix) spectrometer. Elemental analyses: performed in the Microanalytical Laboratory at the
Laboratory for Organic Chemistry, ETH Zꢀrich.
(S)-2-Amino-N-methyl-3-phenylpropanamide (3) was prepared as described in [14].
(2R)-2-(tert-Butyl)-3-methylimidazolidin-4-one (2) [12]. Prepared from Boc-BMI (1; 5.12 g,
20.0 mmol) as described in [13]. The crude product was purified by CC (AcOEt/hexane 2 :1). Fractions
containing the product were combined, and volatile components were evaporated in vacuo to give 2.
Yield: 2.91 g (93%). Yellowish oil. 1H-NMR (300 MHz, CDCl3): 0.98 (s, tBu); 2.02 (br. s, NH); 2.96 (s,
MeN); 3.44 (d, J ¼ 16.1, 1 H, CH2); 3.52 (d, J ¼ 16.2, 1 H, CH2); 4.13 (s, 1 H).
(5S,5’S)-1,1’-Methanediylbis(5-benzyl-3-methylimidazolidin-4-one) (4). A mixture of 3 (4.50 g,
25.25 mmol), paraformaldehyde (1.15 g), 1,3,5-trioxane (2.00 g, 22.20 mmol), and TsOH · H2O (480 mg,
2.52 mmol) in anh. toluene (50 ml) under Ar was heated under reflux under DeanꢀStark conditions using
freshly activated 4-ꢃ molecular sieves (MS) for 12 h. The reaction mixture was diluted with AcOEt
(200 ml), and the resulting mixture was washed with NaHCO3 (aq. sat., 50 ml) and twice with H2O
(30 ml). The org. phase was dried (MgSO4), filtered, and volatile components were evaporated in vacuo.

Helvetica Chimica Acta – Vol. 97 (2014)
773
The residue was purified by CC: with 1. AcOEt/hexane 1:1 to elute the nonpolar impurities; 2. AcOEt to
elute the product. Fractions containing the product were combined, and volatile components were
evaporated in vacuo to give 4. Yield: 3.50 g (70%). White solid. M.p. 62 – 708. [a]rD:t: ¼ ꢀ134.5 (c ¼ 0.61,
CH2Cl2). IR: 2932w, 1635s, 1496w, 1452m, 1396w, 1357m, 1305m, 1274w, 1228m, 1144w, 1064m, 992m,
954m, 875w, 815w, 725s, 697s, 634m. 1H-NMR (400 MHz, (D6)DMSO): 2.79 (s, 2 ꢁ MeN); 2.87 (dd, J ¼
9.5, 14.6, 2 ꢁ 1 H, CH2); 3.14 (dd, J ¼ 5.2, 14.7, 2 ꢁ 1 H, CH2); 4.01 (s, CH2); 4.07 (dd, J ¼ 5.3, 9.6, 2 ꢁ
HꢀC(5)); 4.33 (d, J ¼ 15.2, 2 ꢁ 1 H, H2ꢀC(2)); 4.80 (d, J ¼ 15.1, 2 ꢁ 1 H, CH2(2)); 7.11 – 7.18 (m, 1 arom.
H); 7.20 – 7.32 (m, 4 arom. H). 13C-NMR (101 MHz, (D6)DMSO): 34.0; 36.3; 62.5; 64.0; 80.4; 125.6;
127.8; 129.0; 140.0; 174.5. HR-ESI-MS: 415.2104 (100, [M þ Na]þ, C23H28N4NaO2þ ; calc. 415.21045).
Anal. calc. for C23H28N4O2 (392.49): C 70.38, H 7.19, N 14.27; found: C 70.14, H 7.31, N 13.89.
(5S)-5-Benzyl-3-methylimidazolidin-4-one (5). To a soln. of 3 (1.84 g, 10.35 mmol) in anh. toluene
(50 ml), containing freshly activated 4-ꢃ MS (20 g), was added HCHO (0.8 ml, 37% in H2O), and the
mixture was stirred at r.t. for 3 d. A white precipitate formed. Then, the mixture was heated under reflux
for 5 h, the white precipitate dissolved, and the reaction mixture turned yellow. The mixture was filtered
through a short plug of Celiteꢅ and washed up with AcOEt (100 ml). Volatile components were
evaporated in vacuo and the residue was purified/separated by CC with 1. AcOEt to elute the nonpolar
impurities; 2. AcOEt/EtOH 10 :1 to elute 5. Yield: 754 mg (38%). Yellow-orange solid. 1H-NMR
(400 MHz, CDCl3): 2.04 (br. s, NH); 2.77 (s, MeN); 2.93 (dd, J ¼ 7.2, 14.0, 1 H, CH2); 3.11 (dd, J ¼ 4.2,
14.1, 1 H, CH2); 3.71 (dd, J ¼ 4.3, 6.9, HꢀC(5)); 4.00 (dd, J ¼ 0.7, 7.0, 1 H, CH2(2)); 4.19 (d, J ¼ 6.9, 1 H,
CH2(2)); 7.14 – 7.32 (m, 5 arom. H). 13C-NMR (101 MHz, CDCl3): 27.7; 37.3; 60.5; 65.0; 126.7; 128.5;
129.5; 137.4; 174.3.
Preparation of Compounds 6a, 6a’, 6f, 6g, 6i, 7a, 7a’, 7d, 7e, 7f, 7g, 7h, 7i, and 7j and Omide 8j. General
Procedure 1 (GP 1). To a soln. of 3 (1 equiv.) with or without TsOH · H2O (0.1 equiv.) in anh. EtOH (V1)
under Ar was added the corresponding aldehyde/ketone (x equiv.), and the resulting mixture was heated
under reflux under DeanꢀStark conditions using freshly activated 4-ꢃ MS for t1 h. Volatile components
were evaporated in vacuo and the residue was purified/separated by CC to give the desired compounds.
(2R,5S)-5-Benzyl-3-methyl-2-[(2E)-pent-2-en-2-yl]imidazolidin-4-one (6a’), (2S,5S)-5-Benzyl-3-
methyl-2-[(2E)-pent-2-en-2-yl]imidazolidin-4-one (7a’), (2R,5S)-5-Benzyl-2-ethyl-3-methylimidazoli-
din-4-one (6a), and (2S,5S)-5-Benzyl-2-ethyl-3-methylimidazolidin-4-one (7a). Prepared from 3
(3.38 g, 18.96 mmol) and propanal (1.82 ml, 24.65 mmol). GP 1: V1 50 ml; t1 21 h; CC (AcOEt) to
elute/separate 6a’, 7a’, 6a, and 7a.
Data of 6a’. Eluted first. Yield: 350 mg (7%). Light-yellow oil. 1H-NMR (400 MHz, CDCl3): 0.95 (t,
J ¼ 7.6, MeCH2); 1.45 (d, J ¼ 1.1, Me); 1.93 (br. s, NH); 1.98 – 2.07 (m, MeCH2); 2.59 (s, MeN); 2.86 (dd,
J ¼ 7.6, 13.8, 1 H, CH2); 3.09 (dd, J ¼ 3.9, 13.8, 1 H, CH2); 3.89 – 3.94 (m, CH); 4.33 (d, J ¼ 2.0, CH); 5.41
(td, J ¼ 1.2; 7.1, CH); 7.18 – 7.30 (m, 5 arom. H). 13C-NMR (101 MHz, CDCl3): 9.2; 13.6; 20.9; 26.3; 39.0;
60.2; 81.2; 126.5; 128.3; 129.4; 132.1; 133.8; 137.7; 173.6.

774
Helvetica Chimica Acta – Vol. 97 (2014)
Data of 7a’. Eluted second. Yield: 204 mg (4%). Light-yellow oil. 1H-NMR (300 MHz, CDCl3): 0.94
(td, J ¼ 1.6, 7.5, MeCH2); 1.15 (s, Me); 1.77 (br. s, NH); 1.96 – 2.08 (m, MeCH2); 2.62 (s, MeN); 2.96 – 3.20
(m, CH2); 3.75 (br. s, CH); 4.57 (s, CH); 5.50 (t, J ¼ 7.0, CH); 7.15 – 7.32 (m, 5 arom. H). 13C-NMR
(101 MHz, CDCl3): 8.8; 13.7; 21.1; 26.7; 37.7; 59.9; 80.9; 126.7; 128.6; 129.6; 131.3; 135.1; 137.5; 174.1.
Data of 6a. Eluted third. Yield: 506 mg (12%, < 99% ee). Yellow oil. [a]rD:t: ¼ ꢀ94.4 (c ¼ 0.30,
CH2Cl2). HPLC (Chiralpak AD-H; hexane/iPrOH 98 :2; flow rate, 1.0 ml/min; l 205 nm): tR [min] 22.2
(minor); 27.5 (major). IR (NaCl): 3322, 2965, 2925, 2876, 1694, 1496, 1454, 1434, 1403, 1347, 1277, 1116,
1089, 990, 937, 750, 702. 1H-NMR (500 MHz, CDCl3): 0.86 (t, J ¼ 7.4, MeCH2); 1.42 – 1.52 (m, 1 H,
MeCH2); 1.63 – 1.72 (m, 1 H, MeCH2); 1.92 (br. s, NH); 2.73 (s, MeN); 2.93 (dd, J ¼ 7.1, 13.9, 1 H, CH2);
3.08 (dd, J ¼ 4.2, 13.9, 1 H, CH2); 3.82 – 3.86 (m, CH); 4.02 – 4.06 (m, CH); 7.21 – 7.32 (m, 5 arom. H).
13C-NMR (75 MHz, CDCl3): 6.9; 25.9; 26.3; 37.8; 59.6; 74.7; 126.1; 127.9; 129.1; 137.3; 173.7. HR-EI-MS:
219.1493 [M þ H]þ, C13H19N2O; calc. 219.1497.
Data of 7a. Eluted fourth. Yield: 514 mg (12%, < 99% ee). Yellow oil. [a]rD:t: ¼ ꢀ56.3 (c ¼ 0.32,
CH2Cl2). HPLC (Chiralpak AD-H; hexane/iPrOH 96 :4; flow rate, 1.0 ml/min, l 205 nm): tR [min] 14.9
(major); 16.0 (minor). IR (NaCl): 3332, 2965, 2926, 1694, 1496, 1481, 1454, 1436, 1405, 1349, 1277, 1089,
995, 748, 701.1H-NMR (300 MHz, CDCl3): 0.66 (t, J ¼ 7.5, MeCH2); 1.23 – 1.39 (m, 1 H, MeCH2); 1.63 –
1.77 (m, 1 H, MeCH2); 2.22 (br s, NH); 2.76 (s, MeN); 3.01 (dd, J ¼ 6.8; 14.1, 1 H, CH2); 3.16 (dd, J ¼ 4.4,
14.1, 1 H, CH2); 3.70 – 3.76 (m, CH); 4.29 (ddd, J ¼ 1.2; 2.6; 6.5, CH); 7.19 – 7.33 (m, 5 arom. H).
13C-NMR (75 MHz, CDCl3): 6.2; 25.6; 26.6; 37.3; 59.9; 74.2; 126.5; 128.3; 129.3; 137.1; 174.2. EI-HRMS:
219.1490 [M þ H]þ, C13H19N2Oþ; calc. 219.1497.
(2S,5S)-5-Benzyl-3-methyl-2-phenylimidazolidin-4-one (7d) [17]. Prepared from
3 (4.84 g,
27.18 mmol) and PhCHO (3.57 ml, 35.33 mmol). GP 1: V1 50 ml; t1 20 h; CC with 1. AcOEt/hexane
2 :1 to elute unreacted PhCHO and other nonpolar impurities; 2. AcOEt to elute 7d. Yield: 978 mg
(13%) Yellowish oil. 1H-NMR (300 MHz, CDCl3): 1.83 (t, J ¼ 8.5, NH); 2.55 (s, MeN); 3.14 (dd, J ¼ 4.7,
14.1, 1 H, CH2); 3.25 (dd, J ¼ 5.7, 14.1, 1 H, CH2); 3.82 – 3.91 (m, HꢀC(5)); 5.13 (d, J ¼ 6.8, HꢀC(2));
6.80 – 6.86 (m, 2 arom. H); 7.19 – 7.35 (m, 8 arom. H).
(5S)-5-Benzyl-2,2,3-trimethylimidazolidin-4-one (7e) [2]. Prepared from 3 (2.20 g, 12.35 mmol) and
Me2CO (3 ml, 40.9 mmol). GP 1: V1 30 ml; t1 18 h; CC (AcOEt/hexane 2 :1): 7e. Yield: 2.29 g (85%)
Yellowish oil. 1H-NMR (300 MHz, CDCl3): 1.16 (s, Me); 1.26 (d, J ¼ 1.7, Me); 1.66 (br s, NH); 2.75 (d, J ¼
0.6, MeN), 3.00 (dd, J ¼ 6.8, 14.1, 1 H, CH2); 3.15 (dd, J ¼ 4.5, 14.1, 1 H, CH2); 3.79 (dd, J ¼ 4.7, 6.5, CH);
7.18 – 7.33 (m, 5 arom. H).
(2R,5S)-5-Benzyl-2-(fluoromethyl)-2,3-dimethylimidazolidin-4-one (6f) and (2S,5S)-5-Benzyl-2-
(fluoromethyl)-2,3-dimethylimidazolidin-4-one (7f). Prepared from 3 (2.02 g, 11.33 mmol) and 1-

Helvetica Chimica Acta – Vol. 97 (2014)
775
fluoropropan-2-one (1.00 g, 13.15 mmol). GP 1: V1 50 ml; t1 16 h; 6f/7f 1:0.64; CC with 1. AcOEt/hexane
2 :1 to elute 6f; 2. AcOEt to elute 7f.
Data of 6f. Yield: 794 mg (29%, < 99% ee). Yellowish oil. [a]rD:t: ¼ ꢀ65.2 (c ¼ 0.32, CH2Cl2). HPLC
(Chiralcel OD-H, hexane/iPrOH 95 :5; flow rate, 1.0 ml/min; l 205 nm): tR [min] 18.0 (major); 25.8
(minor). IR (NaCl): 3492, 3320, 3028, 2980, 2931, 1694, 1496, 1454, 1430, 1402, 1283, 1145, 1086, 1031,
750, 702. 1H-NMR (300 MHz, CDCl3): 1.08 (d, J ¼ 2.4, Me); 1.78 (br. s, NH); 2.82 (s, MeN); 3.04 (dd, J ¼
6.3, 14.2, 1 H, CH2); 3.12 (dd, J ¼ 4.7, 14.2, 1 H, CH2); 3.85 (t, J ¼ 5.5, HꢀC(5)); 4.13 (dd, J ¼ 9.6, 17.4, 1 H,
CH2F); 4.29 (dd, J ¼ 9.6, 17.6, 1 H, CH2F); 7.18 – 7.34 (m, 5 arom. H). 13C-NMR (75 MHz, CDCl3): 21.0
(d, J ¼ 2.5); 25.6 (d, J ¼ 2.0); 37.6; 59.4 (d, J ¼ 0.8); 75.9 (d, J ¼ 18.3); 86.1 (d, J ¼ 180.0); 126.8; 128.5;
129.4; 136.7; 173.7. HR-EI-MS: 237.1410 [M þ H]þ, C13H18FN2O; calc. 237.1403).
Data of 7f. Yield: 657 mg (24%, < 98% ee) Yellowish oil. [a]rD:t: ¼ ꢀ93.8 (c ¼ 0.18, CH2Cl2). HPLC
(Chiralcel OD-H; hexane/iPrOH 95 :5; flow rate, 1.0 ml/min, l 205 nm): tR [min] 22.0 (major); 25.4
(minor). IR (NaCl): 3332, 3029, 2980, 2931, 1694, 1496, 1454, 1434, 1402, 1288, 1088, 1032, 1006, 750, 701.
1H-NMR (300 MHz, CDCl3): 1.32 (d, J ¼ 2.8, Me); 1.97 (br. s, NH); 2.81 (dd, J ¼ 8.6, 13.9, 1 H, CH2); 2.85
(s, MeN); 3.18 (dd, J ¼ 3.8, 13.9, 1 H, CH2); 3.85 – 3.92 (m, HꢀC(5)); 3.95 (dd, J ¼ 10.0; 47.8, 1 H, CH2F);
4.15 (dd, J ¼ 10.0, 47.6, 1 H, CH2F); 7.19 – 7.33 (m, 5 arom. H). 13C-NMR (75 MHz, CDCl3): 21.0 (d, J ¼
1.7); 25.7 (d, J ¼ 2.4); 39.0; 59.4; 76.3 (d, J ¼ 18.9); 86.2 (d, J ¼ 180.6); 126.6; 128.5; 129.6; 138.0; 173.2.
HR-EI-MS: 237.1406 [M þ H]þ, C13H18FN2Oþ; calc. 237.1403.
(2R,5S)-5-Benzyl-2,3-dimethyl-2-(propan-2-yl)imidazolidin-4-one (6g) and (2S,5S)-5-Benzyl-2,3-
dimethyl-2-(propan-2-yl)imidazolidin-4-one (7g). Prepared from 3 (3.42 g, 19.19 mmol), 3-methylbu-
tan-2-one (2.47 ml, 23.03 mmol), and TsOH · H2O (130 mg, 0.863 mmol). GP 1: V1 50 ml; t1 24 h; CC with
1. AcOEt/hexane 1:1 to elute 6g; 2. AcOEt to elute 7g.
1
Data of 6g. Yield: 1.80 g (38%). Yellowish oil. H-NMR (400 MHz, CDCl3): 0.74 (d, J ¼ 6.7, 3 H,
Me2CH); 0.89 (d, J ¼ 6.7, 3 H, Me2CH); 0.91 (s, Me); 1.38 (br. s, NH); 1.75 – 1.86 (m, Me2CH); 2.69 (d,
J ¼ 0.6, MeN); 3.03 (dd, J ¼ 5.0, 14.1, 1 H, CH2); 3.09 (dd, J ¼ 5.6, 14.1, 1 H, CH2); 3.79 (t, J ¼ 5.1,
HꢀC(5)); 7.18 – 7.25 (m, 3 arom. H); 7.26 – 7.32 (m, 2 arom. H). 13C-NMR (101 MHz, CDCl3): 16.4; 16.7;
25.3; 25.3; 35.1; 38.3; 60.6; 80.3; 126.8; 128.6; 129.8; 137.1; 173.2.
1
Data of 7g. Yield: 1.90 g (40%). Yellowish oil. H-NMR (400 MHz, CDCl3): 0.44 (d, J ¼ 6.8, 3 H,
Me2CH); 0.87 (d, J ¼ 6.9, 3 H, Me2CH); 1.27 (s, Me); 1.54 (br. d, J ¼ 6.4, NH); 1.76 – 1.88 (m, Me2CH);
2.70 (d, J ¼ 0.5, MeN); 3.00 (dd, J ¼ 7.0, 13.8, 1 H, CH2); 3.13 (dd, J ¼ 4.2; 13.8, 1 H, CH2); 3.79 (br. d, J ¼
3.2, HꢀC(5)); 7.17 – 7.32 (m, 5 arom. H). 13C-NMR (101 MHz, CDCl3): 15.5; 16.4; 23.1; 25.3; 33.6; 37.3;
58.7; 79.8; 126.7; 128.6; 129.7; 137.7; 173.2.
(2S,5S)-5-Benzyl-2-(tert-butyl)-2,3-dimethylimidazolidin-4-one (7h) [18]. Prepared from 3 (3.22 g,
18.06 mmol) and 3,3-dimethylbutan-2-one (4.48 ml, 36.11 mmol; GP 1: V1 50 ml; t1 23 h; CC with 1.
AcOEt/hexane 1:1 to elute nonpolar impurities; 2. AcOEt to elute 7h. Yield: 1.95 g (41%). Yellowish oil.
1H-NMR (300 MHz, CDCl3): 0.81 (s, tBu); 1.24 (s, Me); 1.61 (br. d, J ¼ 9.5, NH); 2.86 (s, MeN); 3.04 (dd,
J ¼ 6.8, 13.7, 1 H, CH2); 3.13 (dd, J ¼ 4.4; 13.7, 1 H, CH2); 3.68 – 3.78 (m, CH); 7.18 – 7.34 (m, 5 arom. H).

776
Helvetica Chimica Acta – Vol. 97 (2014)
(2R,5S)-5-Benzyl-2,3-dimethyl-2-phenylimidazolidin-4-one (6i) and (2S,5S)-5-Benzyl-2,3-dimethyl-
2-phenylimidazolidin-4-one (7i). Prepared from 3 (4.46 g, 25.05 mmol), acetophenone (3.22 ml,
27.56 mmol), and TsOH · H2O (200 mg, 1.051 mmol). GP 1: V1 50 ml; t1 23 h; CC with 1. AcOEt/hexane
1:2 to elute nonpolar impurities; 2. AcOEt/hexane 1:1 to elute 6i; 3. AcOEt to elute 7i.
Data of 6i. Yield: 2.03 g (28%). Colorless oil. 1H-NMR (400 MHz, CDCl3): 1.55 (s, Me); 2.02 (br. s,
NH); 2.73 (d, J ¼ 0.4, MeN); 3.00 (dd, J ¼ 7.2, 13.9, 1 H, CH2); 3.15 (dd, J ¼ 4.2, 13.9, 1 H, CH2); 3.86 (dd,
J ¼ 4.3, 7.0, HꢀC(5)); 7.17 – 7.36 (m, 10 arom. H). 13C-NMR (101 MHz, CDCl3): 26.1; 26.2; 38.3; 59.3;
78.6; 125.1; 126.7; 128.1; 128.5; 128.9; 129.7; 137.6; 142.8; 173.7.
Data of 7i. Yield: 2.32 g (33%). Colorless oil. 1H-NMR (400 MHz, CDCl3): 1.70 (s, Me); 1.98 (br. s,
NH); 2.52 (s, MeN); 3.08 (dd, J ¼ 4.7, 14.0, 1 H, CH2); 3.26 (dd, J ¼ 5.6, 14.0, 1 H, CH2); 3.91 (br. s,
HꢀC(5)); 6.85 – 6.90 (m, 2 arom. H); 7.16 – 7.32 (m, 8 arom. H). 13C-NMR (101 MHz, CDCl3): 22.8; 26.2;
36.5; 59.6; 79.0; 126.0; 126.9; 128.5; 128.8; 128.9; 129.9; 136.8; 142.0; 173.7.
(2S)-2-[(E)-2,3-Dihydro-1H-inden-1-ylideneamino]-N-methyl-3-phenylpropanamide (8j) and
(2S,5S)-5-Benzyl-2’,3’-dihydro-3-methyl-4H-spiro[imidazolidine-2,1’-inden]-4-one (7j). Prepared from
3 (3.53 g, 19.81 mmol), 2,3-dihydro-1H-inden-1-one (3.14 g, 23.77 mmol), and TsOH · H2O (160 mg,
0.841 mmol). GP 1: V1 70 ml; t1 24 h; CC with 1. AcOEt/hexane 1:1 to elute nonpolar impurities; 2.
AcOEt to elute/separate 8j (first fraction) and 7j (second fraction). Mixed fractions of compounds 8j and
7j were re-separated by CC (AcOEt).
Data of 8j. Yield: 700 mg (12%). Colorless oil that turns black after some time even when stored
1
under Ar. H-NMR (400 MHz, CDCl3): 1.46 (ddd, J ¼ 4.0, 9.0, 18.0, 1 H, CH2); 2.37 (ddd, J ¼ 3.8, 8.9,
18.0, 1 H, CH2); 2.60 – 2.70 (m, 1 H, CH2); 2.78 – 2.87 (m, 1 H, CH2); 2.85 (d, J ¼ 5.0, MeNH); 2.93 (dd,
J ¼ 9.7, 13.1, 1 H, CH2); 3.41 (dd, J ¼ 2.9, 13.1, 1 H, CH2); 4.18 (dd, J ¼ 2.9, 9.7, HꢀC(5)); 7.08 (br. s,
MeNH); 7.09 – 7.18 (m, 5 arom. H); 7.25 – 7.33 (m, 2 arom. H); 7.39 (td, J ¼ 1.2, 7.4, 1 arom. H); 7.85 (d, J ¼
7.6, 1 arom. H). 13C-NMR (101 MHz, CDCl3): 25.9; 28.1; 28.2; 41.2; 68.5; 122.4; 125.7; 126.4; 126.9; 128.1;
130.0; 131.6; 138.7; 139.3; 150.0; 173.6; 175.6. HR-ESI-MS: 293.1648 (100, [M þ H]þ, C19H21N2Oþ; calc.
293.16484).
1
Data of 7j. Yield: 2.40 g (41%). Orange-brown oil. H-NMR (400 MHz, CDCl3): 1.84 (br. s, NH);
2.16 – 2.21 (m, CH2); 2.57 (d, J ¼ 0.5, MeN); 2.84 – 2.92 (m, 1 H, CH2); 2.98 – 3.08 (m, 1 H, CH2); 3.08 (dd,
J ¼ 5.0, 14.1, 1 H, CH2); 3.31 (dd, J ¼ 5.1, 14.1, 1 H, CH2); 3.88 (t, J ¼ 4.9, HꢀC(5)); 6.19 (d, J ¼ 7.5, 1 arom.
H); 7.02 – 7.09 (m, 1 arom. H); 7.18 – 7.33 (m, 7 arom. H). 13C-NMR (101 MHz, CDCl3): 26.0; 29.1; 35.5;
36.5; 59.4; 88.0; 122.5; 125.3; 127.0; 127.4; 128.9; 129.7; 130.0; 136.5; 141.7; 144.3; 174.1.

Helvetica Chimica Acta – Vol. 97 (2014)
777
(2R,5S)-5-Benzyl-3-methyl-2-(propan-2-yl)imidazolidin-4-one (6b) and (2S,5S)-5-Benzyl-3-methyl-
2-(propan-2-yl)imidazolidin-4-one (7b). Prepared according to a slightly modified procedure described
in [16]. To a soln. of 3 (2.22 g, 12.44 mmol) in anh. benzene (50 ml) under Ar at r.t., isobutyraldehyde
(1.15 ml, 12.44 mmol) and FeCl3 (400 mg, 2.47 mmol) were added, and the resulting mixture was heated
under reflux under DeanꢀStark conditions using freshly activated 4-ꢃ MS for 18 h. The mixture was
diluted with AcOEt (150 ml), washed with aq. sat. NaHCO3 soln. (50 ml) and twice with brine (30 ml).
The org. phase was dried (MgSO4), filtered, and volatile components were evaporated in vacuo.
1H-NMR of the residue showed a ratio 6b/7b of 1:0.80. The residue was purified by CC with 1. AcOEt/
hexane 1:1 to elute nonpolar impurities; 2. AcOEt/hexane 2 :1 to elute 6b; 3. AcOEt to elute 7b.
Fractions containing the product were combined, and volatile components were evaporated in vacuo to
give 6b and 7b, resp.
Data of 6b. Yield: 816 mg (28%). Yellowish oil. 1H-NMR (300 MHz, CDCl3): 0.80 (d, J ¼ 6.7, Me);
0.96 (d, J ¼ 6.9, Me); 1.90 – 2.02 (m, CH); 2.73 (s, MeN); 3.01 (dd, J ¼ 6.1; 13.3, 1 H, CH2); 3.15 (dd, J ¼
4.3, 14.0, 1 H, CH2); 3.91 (br. s, CH); 4.06 (br. s, CH); 7.20 – 7.41 (m, 5 arom. H).
Data of 7b. Yield: 770 mg (26%). Yellowish oil. 1H-NMR (300 MHz, CDCl3): 0.45 (d, J ¼ 6.9, Me);
0.94 (d, J ¼ 7.0, Me); 1.94 – 2.05 (m, CH); 2.78 (s, MeN); 3.15 (dd, J ¼ 2.6, 5.4, CH2); 3.87 (t, J ¼ 5.2, CH);
4.39 (d, J ¼ 2.6, CH); 7.20 – 7.35 (m, 5 arom. H).
(2R,5S)-5-Benzyl-2-(tert-butyl)-3-methylimidazolidin-4-one (6c) and (2S,5S)-5-benzyl-2-(tert-bu-
tyl)-3-methylimidazolidin-4-one (7c) [16]. Prepared according to a slightly modified procedure described
in [16]. To a soln. of 3 (2.32 g, 13.02 mmol) in anh. toluene (50 ml) under Ar at r.t., pivalaldehyde
(1.46 ml, 13.02 mmol) and FeCl3 (422 mg, 2.60 mmol) were added, and the resulting mixture was heated
under reflux under DeanꢀStark conditions using freshly activated 4-ꢃ MS for 14 h. The mixture was
diluted with AcOEt (200 ml), and the resulting mixture was washed with aq. sat. NaHCO3 soln. (50 ml)
and twice with brine (30 ml). The org. phase was dried (MgSO4), filtered, and volatile components were
evaporated in vacuo. The residue was purified by CC (AcOEt/hexane 1:1). Fractions containing the
product were combined, and volatile components were evaporated in vacuo to give 6c and 7c, resp.
Data of 6c. Eluted first. Yield: 1.12 g (35%). Yellowish solid. 1H-NMR (300 MHz, CDCl3): 1H-NMR
(300 MHz, CDCl3): 0.90 (s, tBu); 1.87 (br. s, NH); 2.89 (dd, J ¼ 7.1, 14.0, 1 H, CH2); 2.89 (d, J ¼ 0.6, MeN);
3.11 (dd, J ¼ 4.2, 14.0, 1 H, CH2); 3.80 (d, J ¼ 1.8, CH); 3.82 –3.87 (m, CH); 7.19–7.33 (m, 5 arom. H).
Data of 7c. Eluted second. Yield: 930 mg (29%). Yellowish oil. 1H-NMR (300 MHz, CDCl3): 0.83 (s,
tBu); 1.68 (br. s, NH); 2.91 (d, J ¼ 0.5, MeN); 2.93 (dd, J ¼ 7.6, 13.7, 1 H, CH2); 3.15 (dd, J ¼ 4.0, 13.7, 1 H,
CH2); 3.70 (br. s, CH); 4.05 (br. s, CH); 7.16 – 7.34 (m, 5 arom. H).
Preparation of BF4ꢀ Salts 9, 10a, 10b, and 10c. General Procedure 2 (GP 2). To a soln. of a
imidazolidin-4-one (1 equiv.) in dry Et2O (V1) at 08 under Ar was added a soln. of HBF4 · Et2O (1 equiv.)
in dry Et2O (V2) at r.t. during 10 min. The reaction mixture was stirred for additional t1 min at 08 and t2
min at r.t. The precipitate was collected by filtration, washed with dry Et2O (30 ml), and dried on high
vacuum to give BFꢀ4 salts 9, 10a, 10b, and 10c.
(2R)-2-(tert-Butyl)-3-methyl-4-oxoimidazolidin-1-ium Tetrafluoroborate (9). Prepared from 2
(827 mg, 5.29 mmol) and HBF4 · Et2O (726 ml, 5.29 mmol). GP 2: V1 60 ml; V2 20 ml; t1 60 min; t2
60 min. Yield: 1.19 g (92%). Light-yellow solid. M.p. 118 – 1238. [a]rD:t: ¼ ꢀ3.6 (c ¼ 0.75, EtOH). IR:

778
Helvetica Chimica Acta – Vol. 97 (2014)
3202w, 3132w, 2975w, 1716s, 1591m, 1478w, 1449w, 1435w, 1405w, 1382m, 1371w, 1364w, 1334m, 1259w,
1
1152w, 1099s, 1030s, 998s, 984s, 947s, 913s, 830m, 767w, 673s, 653w. H-NMR (300 MHz, (D6)DMSO):
1.01 (s, tBu); 2.89 (s, MeN); 3.71 (d, J ¼ 15.6, 1 H, CH2); 3.80 (d, J ¼ 15.6, 1 H, CH2); 4.62 (s, CH); 8.34
(br. s, NHþ2 ). 13C-NMR (75 MHz, (D6)DMSO): 24.6; 31.0; 36.0; 45.1; 81.5; 168.2. HR-ESI-MS: 157.1335
(100, Mþ, C8H17N2Oþ; calc. 157.13354). Anal. calc. for C8H17BF4N2O (244.04): C 39.37, H 7.02, N 11.48;
found: C 39.09, H 6.94, N 11.48.
(2R,5S)-5-Benzyl-2-(tert-butyl)-3-methyl-4-oxoimidazolidin-1-ium Tetrafluoroborate (10a). Pre-
pared from 6c (1.45 g, 5.88 mmol) and HBF4 · Et2O (807 ml, 5.88 mmol). GP 2: V1 60 ml; V2 20 ml; t1
60 min; t2 15 min. Yield: 1.70 g (86%). Light-brown solid. M.p. 120 – 1228. [a]rD:t: ¼ ꢀ50.0 (c ¼ 0.23,
EtOH). IR: 2977w, 1723m, 1707s, 1570w, 1484w, 1458w, 1430w, 1406w, 1372w, 1352w, 1332w, 1261w,
1234w, 1091s, 1063s, 1035s, 1006s, 983s, 752s, 715w, 702s, 664m. 1H-NMR (300 MHz, CDCl3): 1.10 (s, tBu);
2.95 (s, MeN); 3.33 (dd, J ¼ 6.8, 14.5, 1 H, CH2); 3.47 (dd, J ¼ 3.8, 14.6, 1 H, CH2); 4.38 (s, CH); 4.43 (br. s,
CH); 7.28 – 7.41 (m, 5 arom. H); 7.70 (br. s, 1 H, NHþ2 ); 7.88 (br. s, 1 H, NH2þ ). 13C-NMR (75 MHz,
(D6)DMSO): 24.6; 31.7; 35.4; 36.3; 57.9; 80.2; 127.2; 128.6; 129.5; 135.6; 168.5. HR-ESI-MS: 247.1805
(100, Mþ, C15H23N2Oþ; calc. 247.18049). Anal. calc. for C15H23BF4N2O (334.16): C 53.91, H 6.94, N 8.38;
found: C 53.63, H 6.79, N 8.33.
(2S,5S)-5-Benzyl-2-(tert-butyl)-3-methyl-4-oxoimidazolidin-1-ium Tetrafluoroborate (10b). Pre-
pared from 7c (1.07 g, 4.35 mmol) and HBF4 · Et2O (597 ml, 4.35 mmol). GP 2: V1 50 ml; V2 20 ml; t1
10 min. The resulting precipitate was quickly collected on a dry ceramic frit under Ar, washed with dry
Et2O (20 ml), dried on high vacuum, and stored under Ar (the product is highly hygroscopic!). Yield:
1
t
980 mg (67%). Light-brown solid. H-NMR (300 MHz, CDCl3): 0.75 (s, Bu); 2.98 (s, MeN); 3.34 (dd,
J ¼ 6.3, 14.7, 1 H, CH2); 3.69 (dd, J ¼ 2.4, 14.7, 1 H, CH2); 4.56 (br. s, CH); 4.83 (d, J ¼ 6.4, CH); 5.50 (br. s,
1 H, NHþ2 ); 7.29 – 7.46 (m, 5 arom. H); 8.85 (br. s, 1 H, NH2þ ). 13C-NMR (75 MHz, (D6)DMSO): 25.0;
30.5; 33.7; 33.8; 58.2; 79.4; 127.0; 128.6; 129.1; 136.5; 169.6.
(5S)-5-Benzyl-2,2,3-trimethyl-4-oxoimidazolidin-1-ium Tetrafluoroborate (10c). Prepared from 7e
(463 mg, 2.12 mmol) and HBF4 · Et2O (291 ml, 2.12 mmol). GP 2: V1 100 ml; V2 20 ml; t1 10 min; t2
20 min. Yield: 540 mg (83%). White solid. M.p. 125 – 1278. [a]rD:t: ¼ ꢀ59.3 (c ¼ 0.18, CH2Cl2). IR: 3067w,
1725s, 1612w, 1456w, 1435w, 1411m, 1397s, 1388m, 1371m, 1316w, 1272w, 1259w, 1154w, 1122s, 1058s,
1029s, 999s, 965s, 915m, 762m, 744m, 700s, 672w, 612m. 1H-NMR (400 MHz, (D6)DMSO): 1.47 (s, Me);
1.60 (s, Me); 2.79 (s, MeN); 2.93 (dd, J ¼ 10.5, 15.1, 1 H, CH2); 3.32 (dd, J ¼ 3.3, 15.1, 1 H, CH2); 4.57 (br.
d, J ¼ 5.6, CH); 7.26 – 7.42 (m, 5 arom. H); 9.05 (br. s, 1 H, NHþ2 ); 10.17 (br. s, 1 H, NH2þ ). 13C-NMR
(101 MHz, (D6)DMSO): 22.0; 24.2; 24.9; 34.1; 57.4; 76.7; 127.0; 128.6; 129.1; 136.2; 166.9. HR-ESI-MS:

Helvetica Chimica Acta – Vol. 97 (2014)
779
219.1492 (100, Mþ, C13H19N2Oþ; calc. 219.14919). Anal. calc. for C13H19BF4N2O (306.11): C 51.01, H 6.26,
N 9.15; found: C 50.79, H 6.22, N 9.08.
Preparation of PF6ꢀ Salts 11a – 11p. General Procedure 3 (GP 3). To a soln./emulsion of HPF6 (ca.
60% in H2O, 1.05 equiv.) in Et2O (V1 ) at 08 was added a soln. of imidazolidin-4-one (1 equiv.) in Et2O
(V2) at r.t. during t1 minutes. The reaction mixture was stirred for additional t2 min at 08. The precipitate
was collected by filtration, washed with Et2O (50 ml), and dried: in high vacuum to give 11a – 11p.
(5S)-5-Benzyl-3-methyl-4-oxoimidazolidin-1-ium Hexafluorophosphate (11a). Prepared from 5
(611 mg, 3.21 mmol) and HPF6 (497 ml, 3.37 mmol). (GP 3): V1 80 ml; V2 80 ml; t1 10 min; t2 20 min.
Yield: 900 mg (83%). Yellow solid. M.p. 162 – 1668. [a]rD:t: ¼ ꢀ55.2 (c ¼ 0.13, EtOH). IR: 1689m, 1501w,
1458w, 1417w, 1387w, 1365w, 1287w, 870m, 822s, 750m, 719w, 700m, 677m. 1H-NMR (400 MHz,
(D6)DMSO): 2.84 (s, MeN); 2.96 (dd, J ¼ 10.4, 15.0, 1 H, CH2); 3.31 (dd, J ¼ 3.9, 15.0, 1 H, CH2); 4.31
(dd, J ¼ 3.8, 10.3, HꢀC(5)); 4.50 (d, J ¼ 7.4, 1 H, CH2(2)); 4.54 (d, J ¼ 7.4, 1 H, CH2(2)); 7.27 – 7.43 (m, 5
arom. H); 9.90 (s, NHþ2 ). 13C-NMR (101 MHz, (D6)DMSO): 27.7; 33.8; 58.4; 59.5; 127.3; 128.8; 129.1;
135.6; 166.9. HR-ESI-MS: 191.1179 (100, Mþ, C11H15N2Oþ; calc. 191.11789). Anal. calc. for
C11H15F6N2OP (336.21): C 39.30, H 4.50, N 8.33; found: C 40.35, H 4.44, N 8.28.
(2S,5S)-5-Benzyl-2-ethyl-3-methyl-4-oxoimidazolidin-1-ium Hexafluorophosphate (11b). Prepared
from 7a (500 mg, 2.29 mmol) and HPF6 (354 ml, 2.41 mmol). GP 3: V1 60 ml; V2 60 ml; t1 20 min; t2
40 min. An oily precipitate was formed. The reaction mixture was decanted, and Et2O (100 ml) was
added to the oily residue, followed by scratching with spatula until the oily residue turned to a solid. The
mixture was decanted again, Et2O (100 ml) was added to the residue, followed by vigorous stirring at r.t.
for 15 min. The process was repeated once more, until a fine filterable precipitate was formed. Yield:
710 mg (85%). White solid. M.p. 142 – 1458. [a]rD:t: ¼ ꢀ29.1 (c ¼ 0.28, EtOH). IR: 2922w, 1695m, 1497w,
1457w, 1399w, 1353w, 1284w, 1259w, 1234w, 1090w, 1037w, 950w, 934w, 831s, 791m, 756m, 743m, 706m.
1H-NMR (400 MHz, (D6)DMSO): 0.97 (t, J ¼ 7.4, MeCH2); 1.63 – 1.76 (m, 1 H, MeCH2); 2.10 – 2.22 (m,
1 H, MeCH2); 2.83 (s, MeN); 2.98 (dd, J ¼ 10.5, 15.3, 1 H, CH2); 3.36 (dd, J ¼ 3.6, 15.4, 1 H, CH2); 4.35
(dd, J ¼ 3.2, 10.4, CH); 4.66 (dd, J ¼ 3.0, 9.6, CH); 7.28 – 7.46 (m, 5 arom. H); 9.08 (br. s, 1 H, NHþ2 ); 10.68
(br. s, 1 H, NHþ2 ). 13C-NMR (101 MHz, (D6)DMSO): 7.9; 23.2; 26.9; 33.6; 58.8; 72.7; 127.1; 128.7; 129.0;
136.0; 167.5. HR-ESI-MS: 219.1492 (100, Mþ, C13H19N2Oþ; calc. 219.14919). Anal. calc. for
C13H19F6N2OP (364.27): C 42.86, H 5.26, N 7.69; found: C 43.14, H 5.24, N 7.60.
(2S,5S)-5-Benzyl-3-methyl-4-oxo-2-(propan-2-yl)imidazolidin-1-ium Hexafluorophosphate (11c).
Prepared from 7b (750 mg, 3.23 mmol) and HPF6 (499 ml, 3.39 mmol). GP 3: V1 100 ml; V2 50 ml; t1
20 min; t2 30 min. Yield: 1.01 g (82%). Orange-yellow solid. M.p. 163 – 1678. [a]rD:t: ¼ ꢀ19.6 (c ¼ 0.37,
EtOH). IR: 1689m, 1466w, 1402w, 1362w, 1323w, 1263w, 1229w, 1111w, 1044w, 938w, 830s, 771m, 747w,

780
Helvetica Chimica Acta – Vol. 97 (2014)
711m, 615m. 1H-NMR (400 MHz, (D6)DMSO): 0.92 (d, J ¼ 7.0, Me); 1.04 (d, J ¼ 7.1, Me); 2.29 – 2.41 (m,
CH); 2.83 (s, MeN); 3.09 (dd, J ¼ 9.3, 15.6, 1 H, CH2); 3.32 (dd, J ¼ 4.0, 15.6, CH2); 4.38 (dd, J ¼ 3.8, 9.1,
HꢀC(5)); 4.72 (d, J ¼ 3.7, HꢀC(2)); 7.26 – 7.34 (m, 1 arom. H); 7.35 – 7.44 (m, 4 arom. H); 8.23 (br. s, 1 H,
NHþ2 ); 10.60 (br. s, 1 H, NH2þ ). 13C-NMR (101 MHz, (D6)DMSO): 13.8; 16.5; 27.3; 27.6; 33.7; 58.3; 75.7;
127.0; 128.5; 128.9; 136.2; 168.3. HR-ESI-MS: 233.1648 (100, Mþ, C14H21N2Oþ; calc. 233.16484). Anal.
calc. for C14H21F6N2OP (378.29): C 44.45, H 5.60, N 7.41; found: C 44.74, H 5.69, N 7.14.
(2R,5S)-5-Benzyl-2-(tert-butyl)-3-methyl-4-oxoimidazolidin-1-ium Hexafluorophosphate (11d).
Prepared from 6c (832 mg, 3.38 mmol) and HPF6 (522 ml, 3.55 mmol). GP 3: V1 100 ml; V2 80 ml; t1
30 min; t2 10 min. Yield: 1.29 g (97%). White solid. M.p. 148 – 1508. [a]rD:t: ¼ ꢀ62.8 (c ¼ 0.91, EtOH). IR:
3184w, 1718m, 1705m, 1572w, 1482w, 1457w, 1410w, 1381w, 1342w, 1257w, 1118w, 1054w, 832s, 790w, 756w,
741m, 719w, 701m, 659w. 1H-NMR (400 MHz, (D6)DMSO): 1.03 (s, tBu); 2.96 (s, MeN); 2.97 (dd, J ¼ 8.7,
15.1, 1 H, CH2); 3.28 (dd, J ¼ 4.6, 15.1, 1 H, CH2); 4.40 (dd, J ¼ 4.5, 8.2, CH); 4.60 (s, CH); 7.27 – 7.43 (m, 5
arom. H); 9.29 (br. s, 1 H, NHþ2 ); 9.84 (br. s, 1 H, NH2þ ). 13C-NMR (101 MHz, (D6)DMSO): 24.6; 31.6;
35.3; 36.2; 57.8; 80.2; 127.1; 128.5; 129.5; 135.6; 168.5. HR-ESI-MS: 247.1805 (100, Mþ, C15H23N2Oþ; calc.
247.18049). Anal. calc. for C15H23F6N2OP (392.32): C 45.92, H 5.91, N 7.14; found: C 46.19, H 5.74, N 7.12.
(2S,5S)-5-Benzyl-2-(tert-butyl)-3-methyl-4-oxoimidazolidin-1-ium Hexafluorophosphate (11e). Pre-
pared from 7c (451 mg, 1.83 mmol) and HPF6 (283 ml, 1.92 mmol). GP 3: V1 50 ml; V2 30 ml; t1 40 min; t2
10 min. Yield: 420 mg (58%). Light-brown solid. M.p. 128 – 1308. [a]rD:t: ¼ ꢀ23.0 (c ¼ 0.49, EtOH). IR:
2956w, 1711m, 1694s, 1479w, 1457w, 1412w, 1394m, 1345w, 1331w, 1254w, 1234w, 1128w, 1049w, 1029w,
879w, 857m, 830s, 762w, 742m, 707m, 626w, 617w. 1H-NMR (400 MHz, (D6)DMSO): 1.08 (s, tBu); 2.93 (s,
MeN); 3.13 (dd, J ¼ 8.6, 15.3, 1 H, CH2); 3.28 (dd, J ¼ 4.4, 15.4, 1 H, CH2); 4.24 (dd, J ¼ 3.9, 7.8, CH); 4.52
(s, CH); 7.26 – 7.41 (m, 5 arom. H); 7.97 (br. s, 1 H, NHþ2 ); 10.40 (br. s, 1 H, NH2þ ). 13C-NMR (101 MHz,
(D6)DMSO): 24.9; 30.4; 33.7; 58.1; 79.5; 126.9; 128.5; 129.0; 136.5; 169.7. HR-ESI-MS: 247.1805 (100, Mþ,
C15H23N2Oþ; calc. 247.18049). Anal. calc. for C15H23F6N2OP (392.32): C 45.92, H 5.91, N 7.14; found: C
46.12, H 5.90, N 7.07.
(2S,5S)-5-Benzyl-3-methyl-4-oxo-2-[(2E)-pent-2-en-2-yl]imidazolidin-1-ium Hexafluorophosphate
(11f). Prepared from 7a’ (200 mg, 0.774 mmol) and HPF6 (120 ml, 0.813 mmol). GP 3: V1 40 ml; V2
50 ml; t1 15 min; t2 15 min. Yield: 176 mg (56%). White solid. 1H-NMR (400 MHz, (D6)DMSO): 0.98 (t,
J ¼ 7.5, MeCH2); 1.56 (s, Me); 2.08 – 2.19 (m, MeCH2); 2.66 (s, MeN); 3.04 (dd, J ¼ 9.8, 15.5, 1 H, CH2);
3.32 (dd, J ¼ 3.7, 15.5, 1 H, CH2); 4.36 (dd, J ¼ 3.5, 9.8, HꢀC(5)); 5.10 (s, HꢀC(2)); 5.85 (td, J ¼ 1.3, 7.2,
CH); 7.26 – 7.42 (m, 5 arom. H); 8.67 (br. s, 1 H, NHþ2 ); 10.34 (br. s, 1 H, NH2þ ). 13C-NMR (101 MHz,
(D6)DMSO): 10.3; 13.1; 20.9; 27.1; 34.0; 58.2; 77.2; 126.0; 126.9; 128.5; 128.9; 136.0; 139.9; 168.1.