A case study on the resolution of the 1-i-Butyl-3-methyl-3-phospholene 1-oxide via diastereomeric complex formation using TADDOL derivatives and via diastereomeric coordination complexes formed from the calcium salts of O,O′-Diaroyl-(2R,3R)-tartaric acids

Article abstract of DOI:10.1002/hc.21218

The resolution of 1-i-butyl-3-methyl-3-phospholene 1-oxide was studied applying TADDOL [(-)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane], spiro-TADDOL [(-)-(2R,3R)-α,α,α′,α′-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol], or the acidic and neutral Ca²⁺ salts of (-)-O,O′-dibenzoyl- and (-)-O,O′-di-p-toluoyl- (2R,3R)-tartaric acid as the resolving agent. The absolute configuration of the P-asymmetric center was determined by circular dichroism spectroscopy and related quantum chemical calculations. In one instance, the single crystal of the diastereomeric complex incorporating i-butyl-3-phospholene oxide and spiro-TADDOL was subjected to X-ray analysis, which suggested a feasible hypothesis for the efficiency of the resolution process under discussion that may be an example for the solvent-inhibited resolution.

Full text of DOI:10.1002/hc.21218

Heteroatom Chemistry
Volume 26, Number 1, 2015
A Case Study on the Resolution of the
1-i-Butyl-3-methyl-3-phospholene 1-Oxide via
Diastereomeric Complex Formation Using
TADDOL Derivatives and via Diastereomeric
Coordination Complexes Formed from the
Calcium Salts of O,Oꢀ-Diaroyl-(2R,3R)-
tartaric Acids
Pe´ter Bagi,1 Andra´s Fekete,1 Miha´ly Ka´llay,2,3 Do´ra Hessz,4
Miklo´s Kubinyi,3,4 Tama´s Holczbauer,5 Ma´tya´s Czugler,5
Eleme´r Fogassy,1 and Gyo¨rgy Keglevich1
1Department of Organic Chemistry and Technology, Budapest University of Technology and
Economics, 1521 Budapest, Hungary
2MTA-BME Lendu¨ let Quantum Chemistry Research Group, Department of Physical Chemistry and
Materials Science, Budapest University of Technology and Economics, 1521 Budapest, Hungary
3Department of Physical Chemistry and Materials Science, Budapest University of Technology and
Economics, 1521 Budapest, Hungary
4Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences,
Hungarian Academy of Sciences, 1519 Budapest, Hungary
5Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of
Sciences, 1519 Budapest, Hungary
Received 13 June 2014; revised 9 July 2014
(2R,3R)-tartaric acid as the resolving agent. The
ABSTRACT: The resolution of 1-i-butyl-3-methyl-3-
absolute configuration of the P-asymmetric center
phospholene 1-oxide was studied applying TADDOL
was determined by circular dichroism spectroscopy
[(−)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-
and related quantum chemical calculations. In one
dimethyldioxolane], spiro-TADDOL [(−)-(2R,3R)-
instance, the single crystal of the diastereomeric
α,α,αꢀ,αꢀ-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-
complex incorporating i-butyl-3-phospholene oxide
dimethanol], or the acidic and neutral Ca2+ salts
and spiro-TADDOL was subjected to X-ray analysis,
of (−)-O,Oꢀ-dibenzoyl- and (−)-O,Oꢀ-di-p-toluoyl-
which suggested a feasible hypothesis for the efficiency
of the resolution process under discussion that may
be an example for the “solvent-inhibited” resolu-
Correspondence to: Gyo¨rgy Keglevich; e-mail: gkeglevich@
mail.bme.hu.
ꢁC
tion.
2014 Wiley Periodicals, Inc. Heteroatom
Supporting Information is available in the online issue at
www.wileyonlinelibrary.com.
Chem. 26:79–90, 2015; View this article online at
wileyonlinelibrary.com. DOI 10.1002/hc.21218
ꢁC
2014 Wiley Periodicals, Inc.
79

80 Bagi et al.
INTRODUCTION
In a previous paper, we reported a method for the
preparation of 1-i-butyl-3-methyl-3-phospholene 1-
oxide (1) in enantiopure form using spiro-TADDOL
[(−)-3] as the resolving agent [31]. However, the ef-
ficiency of this approach remained low. So in this
paper, the results of our detailed study on the res-
olution of 1-i-butyl-3-methyl-3-phospholene 1-oxide
(1) are reported applying a series of resolving agents,
such as the TADDOL-derivatives [(−)-2 and (−)-
3] and the Ca2+ salts of dibenzoyl- or di-p-toluoyl-
tartaric acid [(−)-4 – (−)-7] (Fig. 1). The absolute P-
configuration of the enantiomerically pure 1-i-butyl-
3-methyl-3-phospholene 1-oxide (1) is evaluated by
theoretical methods.
The optically active P(III)-compounds bearing an
asymmetric center on the phosphorous atom are
of great importance, as they may be potential lig-
ands in transition metal catalysts used in asymmet-
ric syntheses (e.g., hydrogenation and hydroformy-
lation) [1,2].
Among the P-ligands, the P-heterocyclic phos-
phines form a representative class [3]. The methods
for the preparation of optically active P-chiral com-
pounds, including P-heterocycles, were summarized
in the review of Pietrusiewicz and Zablocka [4], as
well as in the book of Grabulosa [5]. Tang et al.
elaborated the resolution of the key intermediate
of bisdihydrobenzooxaphosphole and phosphino-
dihydrobenzooxaphosphole ligands (BIBOP and
POP) by forming covalent diastereomers from the
t-butyl-hydroxy-benzodihydrooxaphosphole oxide
with menthyl chloroformate. The diastereomers
were separated and then hydrolyzed to afford enan-
tiopure t-butyl-hydroxy-benzodihydrooxaphosphole
RESULTS AND DISCUSSION
Resolution of 1-i-Butyl-3-methyl-3-phospholene
1-Oxide (1) with TADDOL Derivatives [(−)-2
and (−)-3]
The resolution of the 1-i-butyl-3-methyl-3-
phospholene 1-oxide (1) was first attempted
with TADDOL derivatives [(−)-2 and (−)-3]. Ac-
cording to the procedure reported first by our
research group [24, 25], 3-phospholene oxide (1)
and TADDOL or spiro-TADDOL [(−)-2 or (−)-3]
were dissolved in hot ethyl acetate. The addition
of hexane to this reaction mixture resulted in
the precipitation of the diastereomeric complex
(R)-1·TADDOL or (S)-1·spiro-TADDOL. Alcohols
were also found to be suitable solvents for the
resolution of 3-phospholene oxides with TADDOL
derivatives [(−)-2 or (−)-3] [29, 30], so the reso-
lution of 1-i-butyl-3-phospholene oxide (1) was
also attempted with TADDOL derivatives (−)-2
and (−)-3 in methanol, ethanol, or isopropanol. In
these instances, the racemic 3-phospholene oxide
(1) and the resolving agent [(−)-2 or (−)-3] were
dissolved in the hot alcohol. The diastereomer
(R)-1·(spiro-TADDOL)2 or (R)-1·(spiro-TADDOL)7
then precipitated on cooling down the reaction
mixture to 26°C (Scheme 1). In all experiments,
a 3-h time was allowed for the crystallization.
The first generation of the solid product was pu-
rified further by two recrystallizations from the
corresponding solvent. The composition of the
diastereomers was determined by 1H NMR. The
enantiomeric excess (ee) was established by chiral
GC after recovering the enantiomeric mixture of the
3-phospholene oxide (1) from a small sample of the
diastereomeric mixture by preparative thin-layer
chromatography (TLC) (silica gel, 3% methanol
in dichloromethane). The enantiomeric mixtures
of the i-butyl-3-phospholene oxide (1) could be
oxide
[6, 7].
Pietrusiewicz
and
his
co-
workers separated the enantiomers of phenyl-
hexahydrocyclopenta[b]phosphole by reacting it
with menthyl bromoacetate. The covalent diastere-
omeric salts were separated, and then the optically
active
phenyl-hexahydrocyclopenta[b]phosphole
was obtained in two steps [8].
The enantiomers of several 4-, 5-, and 6-
membered P-chiral heterocyclic phosphonium salts
were separated via the formation of diastereomeric
salts using the silver salts of dibenzoyl-tartaric
acid, camphorsulfonic acid, or menthoxy-acetic acid
[9–14].
Some heterocyclic mono- and bisphosphine ox-
ides were resolved via the formation of diastere-
omeric molecular complexes using the dibenzoyl tar-
taric acid [4, 15, 16]. The palladium(II) complexes
of phenylethylamine or naphtylethylamine found
widespread application for the synthesis of enan-
tiopure mono- and bidentate heterocyclic P(III)-
compounds including bis-phosphanorbornadienyl
via the formation of the corresponding diastere-
omeric coordination complexes [17–22].
In the recent years, our research group elabo-
rated resolution methods for the preparation of 3-
phospholene oxides, as well as a few six-membered
P-heterocycles in optically active form. The enan-
tiomers of the heterocyclic phosphine oxides were
separated via the diastereomeric molecular complex
formation using TADDOL derivatives [23] or via di-
astereomeric coordination complexes applying the
Ca2+ salts of dibenzoyl- or di-p-toluoyl-tartaric acid
[24–30].
Heteroatom Chemistry DOI 10.1002/hc

Case Study on the Resolution of the 1-i-Butyl-3-methyl-3-phospholene 1-Oxide via Diastereomeric Complex Formation 81
FIGURE 1 1-i-Butyl-3-methyl-3-phospholene oxide (1) and resolving agents [(−)-2-(−)-7] used in this study.
SCHEME 1 General procedure for the resolution of racemic 1-i-butyl-3-methyl-3-phospholene 1-oxide (1) using TADDOL
derivatives [(−)-2 and (−)-3].
obtained from the diastereomeric mixture by col-
umn chromatography (using silica gel and a 97:3
mixture of dichloromethane and methanol). The
results are summarized in Table 1.
(1) was attempted with TADDOL [(−)-2] applying
alcohols as the solvent.
The ratio of i-butyl-3-phospholene oxide (1) and
the resolving agent [(−)-2 or (−)-3] in the diastere-
omers was 1:1, 1:2, or 1:7, which was influenced
by the solvent (Table 1). The (R)-1·(spiro-TADDOL)7
composition of the diastereomeric complex is rather
unusual (Table 1, entry 3). In this case, the formation
of an inclusion diastereomeric complex was as-
sumed contrary to the other instances, when the cor-
responding diastereomers comprised the i-butyl-3-
phospholene oxide (1) and the resolving agent [(−)-2
or (−)-3] in a stoichiometric ratio of 1:1 or 1:2 (Ta-
ble 1, entries 1,2, 4 and 5).
The solvent also influenced which enantiomer
of the i-butyl-3-phospholene oxide [(R)-1 or (S)-1]
was incorporated in the diastereomer using spiro-
TADDOL [(−)-3] as the resolving agent. Ap-
plying spiro-TADDOL [(−)-3], the (S)-i-butyl-3-
phospholene oxide [(S)-1] could be obtained in a
mixture of ethyl acetate and hexane (Table 1, entry
2), whereas using methanol, ethanol, or isopropanol
as the solvent, the other enantiomer [(R)-1] could be
separated (Table 1, entries 3–5).
The resolution of the 1-i-butyl-3-methyl-3-
phospholene 1-oxide (1) with TADDOL derivatives
[(−)-2 or (−)-3] could be accomplished in a mix-
ture of ethyl acetate and hexane with limited suc-
cess, as the maximum ee and resolving capability
were, after two recrystallizations, 35% and 0.10, re-
spectively, (Table 1, entries 1 and 2). However, ap-
plying spiro-TADDOL [(−)-3] in alcohols led to enan-
tiomeric mixtures of i-butyl-3-phospholene oxide (1)
exhibiting ee values of 67–96% and resolving ca-
pabilities of 0.05–0.41 after two recrystallizations
(Table 1, entries 3–5). The highest resolving capa-
bility value (S = 0.41) was achieved using spiro-
TADDOL [(−)-3] in ethanol after two recrystalliza-
tions. The ee of 87% was improved further by a third
recrystallization of the diastereomeric complex to
afford the (R)-1-i-butyl-3-phospholene oxide [(R)-1]
with an ee of 96% and in a yield of 26% (Table 1,
entry 4). No crystalline diastereomers were formed,
when the resolution of i-butyl-3-phospholene oxide
Heteroatom Chemistry DOI 10.1002/hc

82 Bagi et al.
TABLE 1 Resolution of 1-i-Butyl-3-methyl-3-phospholene 1-Oxide (1) Using TADDOL Derivatives [(−)-2 and (−)-3]
Resolving
Agent
Diastereomeric
Complexb
Yield
Enantiomeric
Absolute
Entry
Equivalent
Solventsa
(%)c,d
Excess (%)e,d S (–)f,d Configurationg
1
TADDOL
Spiro-TADDOL
0.5
2×EtOAc/
(1)·(2)
(73)
(7)
35
(7)
25
(71)
96
(0.05)
(R)
10×hexane
14
(90)
39
(14)
5
0.05
(0.06)
0.10
(0.10)
0.05
2
0.5
0.5
1
2×EtOAc/
10×hexane
6×MeOH
(1)·(3)
(1)·(3)7
(1)·(3)2
(S)
(R)
(R)
3 [31] Spiro-TADDOL
4
Spiro-TADDOL
6×EtOH
(88)
47
(51)
87
(0.45)
0.41
[26]h
(74)
19
[96]h
(11)
67
[0.25]h
(0.08)
0.13
5
Spiro-TADDOL
1
6×iPrOH
(1)·(3)2
(R)
aMixture of solvents for the crystallization and recrystallizations (mL of solvent/g of resolving agent).
bThe ratio of 1 and (−)-2 or (−)-3 was determined by 1H NMR.
cBased on the half of the racemate 1 that is regarded to be 100% for each antipode.
d Results obtained after the first crystallization are shown in parantheses, while results obtained after two recrystallizations are shown without
parantheses.
eDetermined by chiral GC.
fResolving capability, also known as the Fogassy parameter [S = (yield/100) × (ee/100)] [32].
gThe absolute configuration of 1 was determined by X-ray analysis and CD spectroscopy.
hAfter three recrystallizations.
The successful resolutions of the i-butyl-3-
phospholene oxide (1) with Ca(H-DBTA)2 [(−)-4]
or Ca(H-DPTTA)2 [(−)-5] afforded the (R)-1-i-butyl-
3-phospholene oxide [(R)-1] in excess, in which
cases the ee was 22–73%, and the resolving capa-
bility value decreases in the range of 0.02–0.17 after
two recrystallizations (Table 2). The application of
Ca(H-DBTA)2 [(−)-4] as the resolving agent in a
mixture of ethanol and acetonitrile did not lead to
the successful resolution of i-butyl-3-phospholene
oxide (1) (Table 2, entry 3). The application of
the acidic Ca2+ salt of the (−)-O,Oꢀ-di-p-toluoyl-
(2R,3R)-tartaric acid [(−)-5] seemed to be more fa-
vorable than that of the dibenzoyl-derivative [(−)-4],
as higher ee values (60–73% vs. 0–29%) and re-
solving capability values (0.04–0.17 vs. 0.00–0.05)
could be obtained with the former resolving agent
[(−)-5] (compare entries 1–3 and 4–6 of Table 2).
The 1H NMR study of the diastereomeric com-
plexes revealed that in all but one case, the resolv-
ing agents Ca(H-DBTA)2 [(−)-4] and Ca(H-DPTTA)2
[(−)-5] incorporated two molecules of the (R)-i-
butyl-3-phospholene oxide [(R)-1].
Resolution of 1-i-Butyl-3-methyl-3-phospholene
1-Oxide (1) with Calcium Hydrogen
(−)-O,Oꢀ-Dibenzoyl- or
(−)-O,Oꢀ-Di-p-toluoyl-(2R,3R)-tartrate [(−)-4 or
(−)-5]
The acidic calcium salts of the (−)-O,Oꢀ-dibenzoyl-
or (−)-O,Oꢀ-di-p-toluoyl-(2R,3R)-tartaric acid [(−)-4
or (−)-5] were also suitable resolving agents to sep-
arate the enantiomers of the i-butyl-3-phospholene
oxide (1). Resolving agents (−)-4 and (−)-5 were
synthesized by the reaction of CaO with (−)-O,Oꢀ-
dibenzoyl- or (−)-O,Oꢀ-di-p-toluoyl-(2R,3R)-tartaric
acid. The Ca(H-DBTA)2 [(−)-4] was prepared
in advance as described earlier [26], whereas
the Ca(H-DPTTA)2 [(−)-5] was always formed in
situ.
In the resolution experiments, the i-butyl-3-
phospholene oxide (1) dissolved in ethanol, ethyl ac-
etate, or acetonitrile was added to the hot ethanolic
solution of Ca(H-DBTA)2 or Ca(H-DPTTA)2 [(−)-4
or (−)-5]. On cooling the mixture to 26°C, the crys-
talline diastereomer precipitated that was filtered af-
ter a 24 h of crystallization. The diastereomer sepa-
rated was purified by two digestions (i.e., by stirring
the crystals in the corresponding solvent at 26°C).
To recover the enantiomeric mixture of the i-butyl-
3-phospholene oxide (1), the dichloromethane so-
lution of the diastereomer was treated with 10%
aqueous ammonia (Scheme 2). The ee of the 3-
phospholene oxide (1) was determined by chiral GC.
The results are shown in Table 2.
Resolution of 1-i-Butyl-3-methyl-3-phospholene
1-Oxide (1) with Calcium (−)-O,Oꢀ-Dibenzoyl-
and (−)-O,Oꢀ-Di-p-toluoyl-(2R,3R)-tartrate
[(−)-6 and (−)-7]
The resolution of the i-butyl-3-phospholene oxide
(1) was also attempted with CaDBTA or CaDPTTA
[(−)-6 or (−)-7] (Scheme 3). The results of the
Heteroatom Chemistry DOI 10.1002/hc

Case Study on the Resolution of the 1-i-Butyl-3-methyl-3-phospholene 1-Oxide via Diastereomeric Complex Formation 83
SCHEME 2 General procedure for the resolution of racemic 1-i-butyl-3-methyl-3-phospholene 1-oxide (1) using Ca(H-DBTA)2
or Ca(H-DPTTA)2 [(−)-4 or (−)-5].
TABLE 2 Resolution of 1-i-Butyl-3-methyl-3-phospholene 1-Oxide (1) Using Ca(H-DBTA)2 [(−)-4] or Ca(H-DPTTA)2 [(−)-5]
Resolving
Agent
Diastereomeric
Complexb
Yield
Enantiomeric
Absolute
Entry
Equivalent
Solventsa
(%)c,d Excess (%)e,d S (–)f,d Configurationg
1
Ca(H-DBTA)2
Ca(H-DBTA)2
0.375 6×EtOH
Ca3(1)4(H-DBTA)6
(74)
22
(65)
7
(18)
22
(12)
29
(0.13)
0.05
(0.08)
0.02
(R)
(R)
2
0.25
3×EtOH/3×EtOAc Ca(1)2(H-DBTA)2
3
4
Ca(H-DBTA)2
Ca(H-DPTTA)2
0.25
0.25
3×EtOH/3×MeCN Ca(1)2(H-DBTA)2
6×EtOH/10% H2O Ca(1)2(H-DPTTA)2
(80)
(48)
16
(Racemic)
(42)
60
(0.00)
(0.20)
0.10
–
(R)
5
6
Ca(H-DPTTA)2
Ca(H-DPTTA)2
0.25
0.25
3×EtOAc/3×EtOH/ Ca(1)2(H-DPTTA)2
(56)
23
(48)
5
(39)
73
(38)
71
(0.22)
0.17
(0.18)
0.04
(R)
(R)
10% H2O
3×MeCN/3×EtOH/ Ca(1)2(H-DPTTA)2
10% H2O
aMixture of solvents for the crystallization and recrystallizations (mL of solvent/g of resolving agent).
bThe ratio of 1 and (−)-2 or (−)-3 was determined by 1H NMR.
cBased on the half of the racemate 1 that is regarded to be 100% for each antipode.
d Results obtained after the first crystallization are shown in parantheses, while results obtained after two recrystallizations are shown without
parantheses.
eDetermined by chiral GC.
fResolving capability, also known as the Fogassy parameter [S = (yield/100) × (ee/100)] [32].
gThe absolute configuration of 1 was determined by X-ray analysis and CD spectroscopy.
SCHEME 3 General procedure for the resolution of racemic 1-i-butyl-3-methyl-3-phospholene 1-oxide (1) using CaDBTA or
CaDPTTA [(−)-6 or (−)-7].
successful resolutions leading to crystalline diastere-
omers are summarized in Table 3.
tion of the diastereomers were carried out according
to the procedure described for the acidic (−)-O,Oꢀ-
dibenzoyl- or (−)-O,Oꢀ-di-p-toluoyl-(2R,3R)-tartaric
acid [(−)-4 or (−)-5] (Scheme 3). However, in two ex-
periments, the diastereomers were purified by only
one recrystallization (Table 3, entries 1 and 4).
Applying the CaDBTA [(−)-6] or CaDPTTA
[(−)-7] as the resolving agent, the resolving
The resolving agents CaDBTA or CaDPTTA
[(−)-6 or (−)-7] were always prepared in situ by re-
acting CaO with DBTA or DPTTA in a 1:1 molar
ratio, similarly to the preparation of Ca(H-DBTA)2
[(−)-4] and Ca(H-DPTTA)2 [(−)-5]. The resolution
of racemic phospholene oxide 1 and the separa-
Heteroatom Chemistry DOI 10.1002/hc

84 Bagi et al.
TABLE 3 Resolution of 1-i-Butyl-3-methyl-3-phospholene 1-Oxide (1) with Ca(DBTA) [(−)-6] or Ca(DPTTA) [(−)-7]
Resolving
Entry Agent
Diastereomeric
Complexb
Yield
Enantiomeric
Absolute
Equivalent
Solventsa
(%)c,d
Excess (%)e,d S (–)f,d Configurationg
1
2
CaDBTA
CaDBTA
0.5
3×EtOAc/3×EtOH/
Ca(1)(DBTA)
Ca(1)(DBTA)
(73)
(3)
(0.02)
(R)
7h
17h
(racemic)
(2)
0.01h
(0.00)
(0.01)
0.14
10%H2O
0.5
3×MeCN/3×EtOH/
(57)
(74)
29
(58)
3h
–
(R)
10% H2O
3
4
CaDPTTA
CaDPTTA
1.25
0.5
6×EtOH/10% H2O
3×EtOAc/3×EtOH/
10% H2O
Ca5(1)2(DPTTA)5
Ca(1)(DPTTA)
50
(53)
81h
(0.30)
0.02h
(R)
aMixture of solvents for the crystallization and recrystallizations [mL of solvent/g of resolving agent].
bThe ratio of 1 and (−)-2 or (−)-3 was determined by 1H NMR.
cBased on the half of the racemate 1 that is regarded to be 100% for each antipode.
d Results obtained after the first crystallization are shown in parantheses, while results obtained after two recrystallizations are shown without
parantheses.
eDetermined by chiral GC.
fResolving capability, also known as the Fogassy parameter [S = (yield/100) × (ee/100)] [32].
gThe absolute configuration of 1 was determined by X-ray analysis and CD spectroscopy.
hThe diastereomeric complex was purified with one recrystallization.
capability values fell in the range of 0.01–0.14,
and the enantiomeric mixtures containing the (R)-i-
butyl-3-phospholene oxide [(R)-1] were obtained in
an ee of 17–81% (Table 3, entries 1, 3, and 4). How-
ever, in one instance, the resolution attempt with
CaDBTA [(−)-6] afforded racemic 3-phospholene ox-
ide (1) (Table 3, entry 2). Comparing the two resolv-
ing agents, CaDBTA [(−)-6] and CaDPTTA [(−)-7],
the use of CaDPTTA [(−)-7] afforded the (R)-i-butyl-
3-phospholene oxide [(R)-1] in a higher ee and re-
solving capability (compare entries 1 and 2 and 3
and 4 of Table 3).
Comparing the results of the resolutions with the
FIGURE 2 Atomic displacement representation of the asym-
neutral Ca2+ salts of (−)-O,Oꢀ-dibenzoyl- and (−)-
metric unit of the (1)/spiro-TADDOL [(−)-3]/isopropanol
O,Oꢀ-di-p-toluoyl-(2R,3R)-tartaric acid [(−)-6 and
(1:2:1) inclusion complex with the principal H-bridges shown
in dotted lines (H atoms less of the –OH ones are omitted for
clarity).
(−)-7] with those performed with the corresponding
acidic Ca2+ salts [(−)-4 and (−)-5], it can be con-
cluded that the application of Ca(H-DBTA)2 [(−)-4]
and Ca(H-DPTTA)2 [(−)-5] is more advantageous, as
configuration for all chiral centers, reveals a wealth
higher resolving capability could be obtained with
of information. Among others, such are the rather
these agents (compare Table 2, entries 1–3, with Ta-
well-defined H-bonding pattern and the identity of
ble 3, entries 1 and 2, or Table 2, entries 4–6, with
the components of a multiple supramolecular ag-
Table 3, entries 3 and 4).
gregate. Five O–H···O type H-bridges fuse these four
independent molecules into a tight associated bun-
dle of molecules. The so formed associate has many
Single-Crystal X-Ray Analysis of the
of the polar (hydrophilic) groups turned inward and
Diastereomeric Complex Incorporating
toward each other, whereas the outer surface of the
(R)-i-Butyl-3-phospholene Oxide (1),
associate remains largely hydrophobic.
Spiro-TADDOL, and Isopropanol in a Ratio of
H-bonding dimensions (cf. Table 4 in the Sup-
1:2:1
porting Information) are all well defined and com-
The structure in the crystallographic asym-
metric unit (Fig. 2) of the 1-i-butyl-3-methyl-
ply with expectations. The H-bonding pattern retains
the well-known internal H-bridge structure of the
resolving tool, providing thus a single-donor func-
tion only for H-bridging from each spiro-TADDOL
[(−)-3] host molecules. Also the appearance of two
3-phospholene
1-oxide
(1)/spiro-TADDOL
[(−)-3]/isopropanol (1:2:1) inclusion complex,
apart from confirming an overall “(R)” absolute
Heteroatom Chemistry DOI 10.1002/hc

Case Study on the Resolution of the 1-i-Butyl-3-methyl-3-phospholene 1-Oxide via Diastereomeric Complex Formation 85
independent hosts is a frequently observed stoi-
are the 1-n-butyl-3-methyl-3-phospholene oxide [28]
and the 1-n-propoxy-3-methyl-3-phospholene oxide
[29] guest containing crystal structures. This ratio
is violated here by the inclusion of the solvent i-
PrOH instead of a second phospholene. Thus, one
may reasonably suppose that the stoichiometry of
this crystal structure is the reason for the overall
weaker yield of the resolution (Table 1, entry 5).
To analyze this hypothesis further, a quick study
of the intermolecular interaction energies in the
(1)/spiro-TADDOL [(−)-3]/isopropanol (1:2:1) inclu-
sion crystal complex was done by using program
RPLUTO [33]. The results seem to support the com-
petitive nature of the i-PrOH solvent molecule in-
cluded. The calculation of the empirical potential
energy [33, 34] shows the following. Among the top
eight strongest of the total 178 intermolecular con-
tacts, the interaction energy of the spiro-TADDOL
[(−)-3] with the i-PrOH solvent is −10.3 kcal/mol,
and that with the 3-phospholene oxide (1) guest
target is −8.7 kcal/mol (see Fig. 5 in the Support-
ing Information). The 1.6 kcal/mol more negative
potential energy of the i-PrOH solvent as com-
pared to that of the 3-phospholene oxide (1) in-
dicates somewhat preferential binding of the sol-
vent. Those top eight interactions, including the two
above-mentioned ones account over 40% of the total
interaction energy calculated for the crystal. Even
chiometry feature in this line of experiments. How-
ever, a conspicuous feature is the inclusion of
the solvent media used both in the resolution (cf.
Table 1) and in the crystallization of this associate
product. The space filling representation of the two
spiro-TADDOL [(−)-3] hosts shows that not only the
H-bridging capacity of the included solvent is fully
exploited, but it also fits well with its apolar tail into
the aromatic surroundings from the delimiting ben-
zene groups of the two hosts (Fig. 3).
A possible C–H···π interaction may also help in
the construction of this intricate complex. Such at-
tractive interaction is best illustrated by the methyl
C–H··· ring center short distance and its geome-
try (see C2S–H2S···Cg12, last entry in Table 4 in
the Supporting Information). The visibly important
role of the included i-PrOH solvent in sustaining
the H-bridging system and its fit for the apolar re-
gions qualify this guest molecule to compete for
the binding sites of the spiro-TADDOL [(−)-3] re-
solving agent. In our case, the quaternary system
shown in Fig. 3 was formed as in the crucial step
of the resolution that is the crystallization of the
less soluble associate. This directs attention to the
altered stoichiometry from the frequently observed
2:2 host/guest ratio. Two examples from our recent
studies with 2:2 resolving host–target guest ratio
FIGURE 3 Space filling representation of the two spiro-TADDOL [(−)-3] hosts with the other two components (1 and i-PrOH
molecules) in atomic displacements for the non-H atoms and visible H-bridges (broken lines). A short C—H···π contact from
the i-PrOH to a close phenyl ring is shown in green broken line.
Heteroatom Chemistry DOI 10.1002/hc

86 Bagi et al.
considering that these potentials are empirical and
somewhat approximate in nature, these figures make
it highly probable that the included i-PrOH solvent is
indeed an effective competitor in the crystallization
process. Thus, the idea of the competitive inhibition
at the crucial resolution step appears to be reason-
able.
CD Spectra of 1-i-Butyl-3-methyl-3-phospholene
1-Oxide (1)
Though the title compound (1) is relatively small,
considering its flexible structure, the occurrence of
numerous stable conformers could be expected at
room temperature, whose circular dichroism (CD)
spectra may be rather different. To accurately deter-
mine the proportion of the various conformers of 1
and to compute their spectral properties, molecular
mechanics (MM), density functional theory (DFT),
and direct random phase approximation (dRPA) cal-
culations have been carried out.
First, a systematic MM conformation analy-
sis was performed and 57 stable conformers were
found. The conformers that lie at most at 13 kJ/mol
above the lowest energy were selected, and their
geometries were optimized at the DFT level. Since
the accurate knowledge of the relative energies of
the conformers is the prerequisite of the calcu-
lation of reliable CD spectra, single-point energy
calculations were performed at the DFT-optimized
geometries with the dRPA method, which is known
to provide accurate conformational energies. Rely-
ing on these calculations, eight conformers were
identified that lie within 8 kJ/mol relative to the most
stable one. Finally, excitation energies as well as os-
cillator and rotator strengths were computed for the
FIGURE 4 DFT-optimized geometry for the most stable con-
former of (R)-1-i-butyl-3-methyl-3-phospholene 1-oxide [(R)-
1]. Characteristic bond lengths (in A), angles, and torsion an-
gles (in degree) are as follows: P1–O1 1.512, P1–C1 1.837,
C1–C2 1.508, C2–C3 1.492, C2–C4 1.338, C4–C5 1.500,
C5–P1 1.836, P1–C6 1.822, C6–C7 1.532, C7–C8 1.525,
C7–C9 1.526, C1–P1–C5 95, O1–P1–C6 113, O1–P1–C6–
C7 45, O1-P1-C1-C2 107.
˚
FIGURE 5 Measured and calculated (a) UV and (b) CD spectra of (R)-1-i-butyl-3-phospholene oxide [(R)-1].
Heteroatom Chemistry DOI 10.1002/hc

Case Study on the Resolution of the 1-i-Butyl-3-methyl-3-phospholene 1-Oxide via Diastereomeric Complex Formation 87
selected conformers with the time-dependent DFT
25.3 min for (R)-1 and 25.8 min for (S)-1. Optical
rotations were determined on a Perkin-Elmer 241
polarimeter.
The UV and CD spectra were measured in an
acetonitrile solution at 25°C. The UV spectra were
recorded on an Agilent 8453 diode array spectrome-
ter and the CD spectra were taken on a Jasco J-810
spectropolarimeter.
(TD-DFT) method, and the simulated absorption and
CD spectra of the individual conformers were Boltz-
mann weighted to enable a direct comparison with
the corresponding experimental spectra. The opti-
mized geometry of the most stable conformer is dis-
played in Fig. 4, whereas the theoretical and experi-
mental spectra are presented in Fig. 5.
The agreement of the measured and computed
absorption spectra of the compound is good and
justifies the selection of the theoretical model. The
structure of the experimental and theoretical CD
spectra is very similar, though the spectra are some-
what shifted relative to one another. The sign of the
dominant peaks in the two spectra are identical; con-
sequently, the absolute configuration of the enan-
tiomer obtained by resolution is identical to that of
the enantiomer considered in the calculations.
1-i-Butyl-3-methyl-3-phospholene 1-oxide (1)
[31], (–)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-
2,2-dimethyldioxolane
[(−)-2],
(–)-(2R,3R)-
α,α,αꢀ,αꢀ-tetraphenyl-1,4-dioxaspiro[4.5]decan-
2,3-dimethanol [(−)-3] [35], and calcium hydrogen
(−)-O,Oꢀ-dibezoyl-(2R,3R)-tartrate [(−)-4] [26] were
synthesized as described earlier. (–)-O,Oꢀ-Dibenzoyl-
and (–)-O,Oꢀ-di-p-toluoyl-(2R,3R)-tartaric acid were
purchased from Aldrich.
Resolution of 1-i-Butyl-3-methyl-3-phospholene
1-Oxide (1) with TADDOL [(−)-2]
(Representative Procedure I)
CONCLUSIONS
The resolution of 1-i-butyl-3-methyl-3-phospholene
1-oxide (1) was accomplished applying TADDOL
derivatives (−)-2 and (−)-3 along with the acidic and
neutral Ca2+ salts of (−)-O,Oꢀ-dibenzoyl- or (−)-O,Oꢀ-
di-p-toluoyl-(2R,3R)-tartaric acids [(−)-4 to (−)-7] as
the resolving agents. An efficient resolution method
was elaborated for the preparation of optically ac-
tive i-butyl-3-phospholene oxide (1) using spiro-
TADDOL as the resolving agent and ethanol as the
solvent. The absolute configuration of the enantiop-
ure i-butyl-3-phospholene oxide (1) was determined
by X-ray crystallography and CD spectroscopy com-
bined by theoretical calculations. Both the yield of
the resolution and the Fogassy parameter are linked
with the appearance and role of the applied i-PrOH
solvent in the (1)/spiro-TADDOL [(−)-3]/isopropanol
(1:2:1) inclusion complex crystal. The idea that the
included solvent has a negative influence on the out-
come of the resolution is also supported by the in-
spection of the interaction energies in the crystal.
To the solution of 0.11 g (0.63 mmol) of racemic 1-i-
butyl-3-methyl-3-phospholene 1-oxide (1) and 0.15 g
(0.32 mmol) TADDOL [(−)-2] in 0.30 mL of hot
ethyl acetate, 1.5 mL of hexane was added, where-
upon the crystalline diastereomer (R)-1·(TADDOL)
appeared immediately. After standing at 26°C for
3 h, the crystals were filtrated to afford 0.15 g (73%)
of (R)-1·(TADDOL) in a diastereomeric excess (de)
of 7%. The diastereomer (R)-1·(TADDOL) was pu-
rified further by two recrystallizations in a mixture
of 0.30 mL of ethyl acetate and 1.5 mL of hexane
to afford 0.034 g (18%) of (R)-1·(TADDOL) in a de
of 35%. 0.0078 g (14%) of (R)-1-i-butyl-3-methyl-3-
phospholene 1-oxide [(R)-1] was recovered in an ee
of 35% from (R)-1·(TADDOL) by column chromatog-
raphy (silica gel, 3% methanol in dichloromethane)
(Table 1, entry 1).
Resolution of 1-i-Butyl-3-methyl-3-phospholene
1-Oxide (1) with spiro-TADDOL [(−)-3]
EXPERIMENTAL
The resolution of 1-i-butyl-3-methyl-3-phospholene
1-oxide (1) was also accomplished with spiro-
TADDOL [(−)-3] in ethyl acetate–hexane, methanol,
ethanol, or isopropanol according to Representa-
tive Procedure I. When alcohols were used, the
racemic 1-i-butyl-3-methyl-3-phospholene 1-oxide
(1) and the spiro-TADDOL [(−)-3] were dissolved in
hot methanol, ethanol, or isopropanol, respectively,
and the corresponding diastereomer precipitated by
cooling down the reaction mixture to 26°C. The
conditions and the results are summarized in
Table 1. The specific optical rotation of the
The 31P and 1H NMR spectra were taken on a Bruker
AV-300 or DRX-500 spectrometer operating at 121.5
and 300 or 202.4 and 500 MHz, respectively.
The ee values of the phospholene oxide 1 were
determined by chiral GC on an Agilent 4890D in-
strument equipped with a Supelco BETA DEXTM
120 column (30 m × 0.25 mm, 0.25 μm film, FID
detector, nitrogen as carrier gas, injector 240°C, de-
tector 300°C, head pressure: 15 psi, at 1:100 split
ratio). Retention times of 1 by chiral GC (program: 2
min at 140°C, 1°C/min to 190°C, then kept at 190°C):
Heteroatom Chemistry DOI 10.1002/hc

88 Bagi et al.
(R)-1-i-butyl-3-methyl-3-phospholene 1-oxide [(R)-
1] having an ee of 96% was measured (Table 1, entry
4). [α]2D5 = +7.7 (c 1.3, CHCl3).
of ethyl acetate, and 0.06 mL of water. This led to
0.076 g (27%) of Ca[(R)-1)2(H-DPTTA]2 with a de of
73%. Then, the 2-mL dichloromethane solution of
Ca[(R)-1)2(H-DPTTA]2 was treated with 2 mL of 10%
aqueous ammonia. The organic layer was separated,
dried (Na2SO4), and concentrated to furnish 0.019
g (23%) of (R)-1-i-butyl-3-methyl-3-phospholene 1-
oxide (1) in an ee of 73% (Table 2, entry 5).
Resolution of 1-i-Butyl-3-methyl-3-phospholene
1-Oxide (1) with Calcium Hydrogen
O,Oꢀ-Dibenzoyl-(2R,3R)-tartrate [(−)-4]
(Representative Procedure II)
The
resolution
of
1-i-butyl-3-methyl-3-
0.16
g
(0.94 mmol) of 1-i-Butyl-3-methyl-3-
phospholene 1-oxide (1) was also accomplished
using Ca(H-DPTTA)2 [(−)-5] as the resolving agent
in a mixture of ethanol and water or acetonitrile,
ethanol, and water. The conditions and the results
are summarized in Table 2 (entries 4 and 6).
phospholene 1-oxide (1) in 0.83 mL of ethanol was
added to 0.28 g (0.35 mmol) of Ca(H-DBTA)2·(H2O)2
[(−)-4·(H2O)2] dissolved in 0.83 mL of hot ethanol.
The diastereomeric complex Ca3[(R)-1)4(H-DBTA]6
precipitated on cooling down the reaction mix-
ture gradually to 26°C was separated from the
mother liquor after 24h to provide 0.26 g (74%) of
Ca3[(R)-1)4(H-DBTA]6 in a de of 18%. The diastere-
omer Ca3[(R)-1)4(H-DBTA]6 was purified further by
two digestions (i.e., by stirring the diastereomer
in 1.66 mL of ethanol) to afford 0.086 g (25%) of
Ca3[(R)-1)4(H-DBTA]6 in a de of 22%. To re-
cover the (R)-1-i-butyl-3-methyl-3-phospholene 1-
oxide [(R)-1], the 2 mL dichloromethane solution of
Ca3[(R)-1)4(H-DBTA]6 was extracted with 2 mL of
10% aqueous ammonia. The organic layer was sep-
arated and dried (Na2SO4) and concentrated to fur-
nish 0.017 g (22%) of (R)-1 in an ee of 22% (Table 2,
entry 1).
Resolution of 1-i-Butyl-3-methyl-3-phospholene
1-Oxide (1) with Calcium
O,Oꢀ-Di-benzoyl-(2R,3R)-tartrate and Calcium
O,Oꢀ-Di-p-toluoyl-(2R,3R)-tartrate [(−)-6 and
(−)-7]
The resolution of 1-i-butyl-3-methyl-3-phospholene
1-oxide (1) was also accomplished using CaDBTA
or CaDPTTA [(−)-6 or (−)-7] as the resolving agent
according to Representative Procedure III. The re-
solving agents [(−)-6 or (−)-7] were prepared in situ
by reacting CaO with DBTA or DPTTA in a molar
ratio of 1:1. The conditions and the results are sum-
marized in Table 3.
The
resolution
of
1-i-butyl-3-methyl-3-
phospholene 1-oxide (1) with Ca(H-DBTA)2·(H2O)2
[(−)-4·(H2O)2] was also performed in a mixture of
ethanol and ethyl acetate or ethanol and acetonitrile.
The conditions and the results are summarized in
Table 2 (entries 2 and 3).
X-Ray Measurements
X-ray quality crystals of the 1-i-butyl-3-methyl-
3-phospholene
1-oxide
(1)/spiro-TADDOL
[(−)-3]/isopropanol (1:2:1) inclusion complex
were grown from a saturated isopropanol solution
of 2.3 mg (0.013 mmol) of (R)-1 and 13.5 mg (0.027
mmol) of spiro-TADDOL [(−)-3].
Resolution of 1-i-Butyl-3-methyl-3-phospholene
1-Oxide (1) with Calcium Hydrogen
O,Oꢀ-Di-p-toluoyl-(2R,3R)-tartrate [(−)-5]
(Representative Procedure III)
Crystal data: C80H93O10P, formula weight:
1245.51, colorless, prism, size: 0.35 × 0.30 × 0.25
˚
mm, monoclinic, space group P21, a = 9.4730(2)A,
˚
˚
The mixture of 0.20 g (0.48 mmol) of DPTTA·H2O
and 0.014 g (0.24 mmol) of CaO was dissolved in
a hot mixture of 0.64 mL of ethanol and 0.06 mL
of water. To this hot solution of the in situ formed
Ca(H-DPTTA)2 [(−)-5], 0.17 g (0.97 mmol) of
racemic 1-i-butyl-3-methyl-3-phospholene 1-oxide
(1) was added in 0.64 mL of ethyl acetate. Cooling
down the reaction mixture gradually to 26°C, the
crystalline diastereomer Ca[(R)-1)2(H-DPTTA]2 ap-
peared that was separated from the mother liquor
after 24 h to give 0.16 g (56%) of Ca[(R)-1)2(H-
DPTTA]2 in a de of 39%. The diastereomer Ca[(R)-
1)2(H-DPTTA]2 was purified further by two diges-
tions in a mixture of 0.64 mL of ethanol, 0.64 mL
b = 34.6740(6)A, c = 10.2450(2)A, α = 90°,
3
˚
β = 95.1190(7)°, γ = 90°, V = 3351.72(11) A ,
T = 93(2) K, Z = 2, F(000) = 1336, Dx = 1.234
Mg/m3, μ = 0.846 mm–1. A crystal of the 1-i-butyl-
3-methyl-3-phospholene 1-oxide (1)/spiro-TADDOL
[(−)-3]/isopropanol (1:2:1) inclusion complex was
mounted on a loop. Cell parameters were de-
termined by least squares of the setting angles
of 26,125 (6.61 ࣘ θ ࣘ 71.92°) reflections. In-
tensity data were collected on an R-Axis RAPID
diffractometer (graphite monochromator; Cu Kα
˚
radiation, λ = 1.54178 A) at 93(2) K in the range
6.61ࣘ θ ࣘ 66.59° using ω scans. A total of 33,600
reflections were collected, of which 10,593 were
Heteroatom Chemistry DOI 10.1002/hc

Case Study on the Resolution of the 1-i-Butyl-3-methyl-3-phospholene 1-Oxide via Diastereomeric Complex Formation 89
unique [R(int) = 0.0630, R(σ) = 0.0909]; intensities
computed transitions with heights proportional to
the corresponding calculated oscillator (rotator)
strengths. The spectra of the conformers were Boltz-
mann weighted using the Gibbs energies obtained as
described above. The averaged spectra were normal-
ized so that the height of the biggest peak be identical
to that of the experimental spectra; in addition, the
spectra were shifted by 3 nm to longer wavelengths
so that the position of the most intense band of
the calculated and measured absorption spectra be
identical.
of 7258 reflections were greater than 2σ(I). Com-
pleteness to θ = 0.936. A numerical absorption cor-
rection was applied to the data (the minimum and
maximum transmission factors were 0.76 and 0.82
[36]. The structure was solved by direct methods and
subsequent difference syntheses [37]. Anisotropic
full-matrix least-squares refinement on F2 for all
nonhydrogen atoms yielded R1 = 0.0664 and wR2 =
0.1474 for 7258 [I > 2σ(I)] and R1 = 0.1056 and
wR2 = 0.1928 for all (10,593) intensity data (number
of parameters = 827, goodness-of-fit = 1.093, abso-
lute structure parameter x = –0.01(4) [38], the max-
imum and mean shift/esd is 0.003 and 0.000) [39].
Hydrogen atomic positions were calculated from as-
sumed geometries except the –OH ones that were
located on constrained difference maps and kept
riding. Hydrogen atoms were included in structure
factor calculations but they were not refined. The
isotropic displacement parameters of the hydrogen
atoms were approximated from the U(eq) value of
the atom they were bonded to. All pertinent calcu-
lations including structure validation and plotting
were performed by using program PLATON [40] and
Mercury [41]. A final structure model is deposited
with the Cambridge Crystallographic Data centre un-
der CCDC 1006292. Copies of these data can be ob-
tained free of charge upon application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (fax: 00 44 (0)
1223 336033 or e-mail: deposit@ccdc.cam.ac.uk) or
via www.ccdc.camac.uk/data_request/cif.
ACKNOWLEDGMENT
Authors are grateful for the financial support
from the Hungarian Scientific Research Fund
(OTKA, Grant Nos. K83118, K104769, K108752, and
K75869) Grant No. K75869 covered part of the X-ray
costs.
REFERENCES
[1] Noyori, R. Asymmetric Catalysis in Organic Synthe-
sis; Wiley: New York, 1994.
[2] Imamoto, T. In Handbook of Organophosphorus
Chemistry; Engel, R. (Ed.); Marcel Dekker: New
York, 1992; pp. 1–53.
[3] Kollár, L.; Keglevich, G. Chem Rev 2010, 110, 4257–
4302.
[4] Pietrusiewicz, K. M.; Zablocka, M. Chem Rev 1994,
94, 1375–1411.
[5] Grabulosa, A. P-Stereogenic Ligands in Enantiose-
lective Catalysis; Royal Society of Chemistry: Cam-
bridge, UK, 2010.
[6] Tang, W.; Qu, B.; Capacci, A. G.; Rodriguez, S.; Wei,
X.; Haddad, N.; Narayanan, B.; Ma, S.; Grinberg, N.;
Yee, N. K.; Krishnamurthy, D.; Senanayake, C. H.
Org Lett 2010, 12, 176–179.
[7] Tang, W.; Capacci, A. G.; White, A.; Ma, S.; Ro-
driguez, S.; Qu, B.; Savoie, J.; Patel, N. D.; Wei, X.;
Haddad, N.; Grinberg, N.; Yee, N. K.; Krishnamurthy,
D.; Senanayake, C. H. Org Lett 2010, 12, 1104–
1107.
[8] Pakulski, Z.; Demchuk, O. M.; Frelek, J.; Luboradzki,
R.; Pietrusiewicz, K. M. Eur J Org Chem 2004, 3913–
3918.
[9] Holliman, F. G.; Mann, F. G. J Chem Soc 1947, 1634–
1642.
[10] Hart, F. A.; Mann, F. G. J Chem Soc 1955, 4107–4114.
[11] Corfield, J. R.; Shutt, J. R.; Trippett, S. J Chem Soc,
Chem Commun 1969, 789–790.
[12] Berlin, K. D.; Chen, C.-H. J Org Chem 1971, 36, 2791–
2796.
Theoretical Calculations
In the MM conformational analysis, the MMFF94
[42] force field was used. The DFT and TD-DFT
[43,44] calculations were carried out using the PBE0
[45] functional and the 6–311++G** basis set. Rota-
tor strengths were calculated in the velocity gauge.
All the DFT calculations were performed using the
polarized continuum model [46] with acetonitrile
as the solvent since the experimental spectra were
recorded in the latter. The dRPA energies were com-
puted with the aug-cc-pVTZ basis set and PBE0 or-
bitals. To calculate the 298 K Gibbs energies of the
conformers in the solvent, the gas-phase dRPA ener-
gies were adjusted by temperature corrections, en-
tropy contributions, and Gibbs energies of solvation
evaluated at the DFT level at the corresponding DFT-
optimized geometries. The MM, DFT, and dRPA cal-
culations were performed by the Marvin [47], Gaus-
sian 09 [48], and MRCC [49] packages, respectively.
The theoretical absorption (CD) curves for each
conformer were obtained as superpositions of Gaus-
sian functions placed at the wavelengths of the
[13] Marsi, K. L.; Tuinstra, H. J Org Chem 1975, 40, 1843–
1844.
[14] Gurusamy, N.; Berlin, K. D. J Am Chem Soc 1982,
104, 3114–3119.
[15] Imamoto, T.; Cre´py, K. V. L.; Katagiri, K. Tetrahe-
dron: Asymmetry 2004, 15, 2213–2218.
[16] Liu, D.; Zhang, X. Eur J Org Chem 2005, 646–649.
Heteroatom Chemistry DOI 10.1002/hc

90 Bagi et al.
[17] Tani, K.; Brown, L. D.; Ahmed, J.; Ibers, J. A.; Yokota,
M.; Nakamura, A.; Otsuka, S. J Am Chem Soc 1977,
99, 7876–7886.
[18] Duran, E.; Gordo, E.; Granell, J.; Font-Bardia, M.;
Solans, X.; Velasco, D.; Lopez-Calahorra, F. Tetrahe-
dron: Asymmetry 2001, 12, 1987–1997.
[19] Doro, F.; Lutz, M.; Reek, J. N. H.; Spek, A. L.;
van Leeuwen, P. Eur J Inorg Chem 2008, 1309–
1317.
[20] Robin, F.; Mercier, F.; Ricard, L.; Mathey, F.; Spag-
nol, M. Chem Eur J 1997, 3, 1365–1369.
[21] Bienewald, F.; Ricard, L.; Mercier, F.; Mathey,
F. Tetrahedron: Asymmetry 1999, 10, 4701–
4707.
[22] He, G.; Mok, K. F.; Leung, P.-H. Organometallics
1999, 18, 4027–4031.
[23] Seebach, D.; Beck, A. K.; Heckel, A. Angew Chem, Int
Ed 2001, 40, 92–138.
[24] Nova´k, T.; Schindler, J.; Ujj, V.; Czugler, M.; Fogassy,
E.; Keglevich, G. Tetrahedron: Asymmetry 2006, 17,
2599–2602.
[37] Burla, M. C.; Caliandro, R.; Camalli, M.; Carrozzini,
B.; Cascarano, G. L.; Giacovazzo, C.; Mallamo, M.;
Mazzone, A.; Polidori, G.; Spagna, R. J Appl Crystal-
logr 2012, 45, 357–361.
[38] Flack, H. Acta Crystallogr, Sect A 1983, 39, 876–881.
[39] Sheldrick, G. M. Acta Crystallogr, Sect A 2008, 64,
112–122.
[40] Spek, A. Acta Crystallogr, Sect D 2009, 65, 148–155.
[41] Macrae, C. F.; Bruno, I. J.; Chisholm, J. A.; Edgington,
P. R.; McCabe, P.; Pidcock, E.; Rodriguez-Monge, L.;
Taylor, R.; van de Streek, J.; Wood, P. A. J Appl Crys-
tallogr 2008, 41, 466–470.
[42] Halgren, T. A. J Comput Chem 1999, 20, 720–729.
[43] Adamo, C.; Barone, V. J Chem Phys 1999, 110, 6158–
6170.
[44] Stratmann, R. E.; Scuseria, G. E.; Frisch, M. J. J
Chem Phys 1998, 109, 8218–8224.
[45] Perdew, J. P.; Burke, K.; Ernzerhof, M. Phys Rev Lett
1996, 77, 3865–3868.
[46] Miertusˇ, S.; Scrocco, E.; Tomasi, J. Chem Phys 1981,
55, 117–129.
[25] Nova´k, T.; Ujj, V.; Schindler, J.; Czugler, M.; Kubinyi,
M.; Mayer, Z. A.; Fogassy, E.; Keglevich, G. Tetrahe-
dron: Asymmetry 2007, 18, 2965–2972.
[26] Ujj, V.; Schindler, J.; Nova´k, T.; Czugler, M.; Fogassy,
E.; Keglevich, G. Tetrahedron: Asymmetry 2008, 19,
1973–1977.
[27] Ujj, V.; Bagi, P.; Schindler, J.; Madara´sz, J.; Fogassy,
E.; Keglevich, G. Chirality 2010, 22, 699–705.
[28] Bagi, P.; Laki, A.; Keglevich, G. Heteroatom Chem
2013, 24, 179–186.
[29] Bagi, P.; Fekete, A.; Ka´llay, M.; Hessz, D.; Kubinyi,
M.; Holczbauer, T.; Czugler, M.; Fogassy, E.; Kegle-
vich, G. Chirality 2014, 26, 174–182.
[30] Bagi, P.; Ka´llay, M.; Hessz, D.; Kubinyi, M.;
Holczbauer, T.; Czugler, M.; Fogassy, E.; Kegle-
vich, G. Tetrahedron: Asymmetry 2014, 25, 318–
326.
[31] Bagi, P.; Kova´cs, T.; Szilva´si, T.; Pongra´cz, P.;
Kolla´r, L.; Drahos, L.; Fogassy, E.; Keglevich, G. J
Organomet Chem 2014, 751, 306–313.
[47] Marvin 6.1.0, ChemAxon. Available at: http://www.
chemaxon.com. (accessed on June 10, 2014).
[48] Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria,
G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.;
Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji,
H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov,
A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai,
H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.;
Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.;
Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Nor-
mand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.;
Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam,
J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.;
Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann,
R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli,
C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.;
Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannen-
¨
berg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.;
[32] Sheldon, R. A. Chirotechnology; Marcel Dekker: New
York, 1993.
[33] Gavezzotti, A. Acc Chem Res 1994, 27, 309–314.
[34] Gavezzotti, A. Crystallogr Rev 1998, 7, 5–121.
[35] Beck, A. K.; Bastani, B.; Plattner, D. A.; Petter, W.;
Seebach, D.; Braunschweiger, H.; Gysi, P.; Lavecchia,
L. Chimia 1991, 45, 238–244.
Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J.
Gaussian 09, Revision B.01; Gaussian: Wallingford,
CT, 2010.
[49] MRCC, a quantum chemical program suite written
by M. Ka´llay, Z. Rolik, I. Ladja´nszki, L. Szegedy, B.
Lado´czki, J. Csontos, and B. Kornis. See also Rolik,
Z.; Szegedy, L.; Ladja´nszki, I.; Lado´czki, B.; Ka´llay,
M. J Chem Phys 2013, 139, 094105. Available at:
www.mrcc.hu. (accessed on June 10, 2014).
[36] Rigaku/MSC. CrystalClear and CrystalStructure;
Rigaku/MSC: Woodlands, TX, 2006.
Heteroatom Chemistry DOI 10.1002/hc