Ring-opening of enantiomerically pure oxa-containing heterocycles with phosphorus nucleophiles

Article abstract of DOI:10.1039/c4ra10432c

Various oxa-containing heterocycles (i.e. enantiopure epoxide- and oxetane-based substrates) were subjected to ring-opening with phosphorus nucleophiles. The ring-opening reactions proceeded smoothly and the resulting 1,2-, and 1,3-phosphino alcohols were

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ARTICLE TYPE
Ring-opening of Enantiomerically Pure Oxa-containing Heterocycles
with Phosphorus Nucleophiles
a
a
a
Héctor Fernández-Pérez, Pablo Etayo, José Luis Núñez-Rico, Bugga Balakrishna, and Anton Vidal-
Ferran*
a
a,b
5
Various oxa-containing heterocycles (i.e. enantiopure epoxide- and oxetane-based substrates) were
subjected to ring-opening with phosphorus nucleophiles. The ring-opening reactions proceeded smoothly
and the resulting 1,2-, and 1,3-phosphino alcohols were efficiently isolated as stable borane complexes.
These derivatives arise from regio- and stereocontrolled syntheses based on ring-opening processes of
oxa-containing heterocycles. The regio- and stereochemistry of the resulting chiral products were
unequivocally confirmed in many cases via single-crystal X-ray diffraction analysis.
1
0
.
Introduction
asymmetrically 1,2-disubstituted epoxides, which have scarcely
4
been explored as substrates in this chemistry, most likely due to
4
5
5
6
6
7
7
5
0
5
0
5
0
5
The design and preparation of enantiomerically pure
phosphorus compounds is of paramount importance in
asymmetric catalysis research. These derivatives have typically
been employed as chiral ligands in diverse transition metal-
the inherent difficulty of regiocontrol. Our group has been using
the regio- and stereocontrolled ring-opening of enantiopure
5
Sharpless epoxyethers by trivalent phosphorus nucleophiles as a
1
2
2
3
3
4
5
0
5
0
5
0
key step for preparing diverse enantiomerically pure P−OP
ligands , which in turn have enabled high enantioselectivity in
1
mediated asymmetric transformations, and more recently in
2
enantioselective organocatalytic processes. In this context, there
1c
6
diverse metal-mediated asymmetric transformations.
is
a demand for stereocontrolled, high-yielding synthetic
We have already reported that ring-opening of the trans-
6a,c−i
strategies enabling straightforward access to structurally diverse
phosphorus derivatives. Enantiomerically pure phosphino
alcohols (also known as hydroxy phosphines) are an attractive
type of phosphorus(III) compounds with major potential for
asymmetric catalysis. Firstly, they are valuable chiral building
blocks that can be easily transformed into other, more elaborate
(
2S,3S)-1-alkoxy-3-phenyl-2,3-epoxides
1
enantiomers trans-(2R,3R)-1-alkoxy-3-phenyl-2,3-epoxides ent-
(or
their
6g,i
1
) with alkali metal dialkyl- or diarylphosphides is highly
regioselective (rr = 94:6 → 99:1 2/3). The products arising from
ring-opening proved to be rather prone to oxidation: thus, in-situ
protection as the borane complexes 2/3 allowed for easier
handling and storage. The resultant borane derivatives of the anti-
phosphino alcohols 2 (the major regioisomeric products) were
isolated with high yield (63−87%) (see Scheme 1). Whilst the
1
ligands—namely, hybrid bidentate phosphorus ligands.
Secondly, they can also be harnessed as direct precursors of
hemilabile P−O ligands, which have found numerous applications
in organometallic asymmetric catalysis.
3
1
minor regioisomers 3 derived from epoxide 1a (R = Me) or 1b
(
Several stereoselective synthetic routes to these targets can be
envisaged and, amongst them, stereocontrolled ring-opening of
oxa-containing heterocycles by trivalent phosphorus nucleophiles
appears to be an attractive route towards enantiomerically pure
phosphino alcohol derivatives. Herein are reported new and
optimised synthetic strategies dealing with the ring-opening of an
array of structurally diverse enantiopure oxa-containing
heterocycles. The regio- and stereochemistry of the resulting
chiral products were unequivocally confirmed in most cases via
single-crystal X-ray diffraction analysis.
1
R = CPh ) and lithium dicyclohexylphosphide were detected by
3
NMR in the corresponding crude mixtures, only the one derived
6h
from 1a could be isolated and fully characterised.
Recent research activities in this field have allowed for the
growth of single crystals of several phosphine-borane alcohols 2
1
and analysis of their structure by X-ray diffraction (2a [R = Me,
2
1
2
1
2
R
= Ph], ent-2b [R = CPh , R = Ph], 2c [R = Me, R = Cy]
3 2 2
2
1
and 2d [R = CPh , R = Cy]). These studies have confirmed
2
7
3
2
6a,c−h
previously published results
on the regio- and absolute
stereo-chemistry of the products derived from the ring-opening of
trans-epoxides: anti-arrangement of the hydroxyl and phosphino
Results and discussion
functionalities, arising from a stereospecific S 2 epoxide ring-
N
opening (inversion at the attacked carbon, and retention at the
other one). This recently obtained crystallographic information is
included herein and can be found in the Supporting Information.
Ring-opening of enantiopure 1,2-disubstituted epoxides
At the onset of our study, we initially selected enantiopure,
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conditions reported for the trans derivative 1a revealed near-
2
3
3
4
5
0
5
0
complete reversion of the previously observed regiochemistry: in
this case the major regioisomer was the phosphine-borane alcohol
9
(rr = 91:9 5/6 ), which was isolated in 80% yield (Scheme 2).
5
The unusual regiochemical outcome found in the ring-opening
product of the cis-epoxyether 4 was unequivocally confirmed by
7
X-ray diffraction analysis (Figure 1, left). This technique enabled
identification of the syn arrangement of the alcohol and the
phosphine-borane groups, and of the absolute (2S,3S)
configuration of these substituents. These results agree with a
stereospecific, S 2 epoxide ring-opening of epoxyether 4 (i.e.
N
inversion at the attacked carbon, and retention at the other one).
The aforementioned results indicate that, under the same
reaction conditions, the regiochemical outcome of the ring
opening of 1,2-disubstituted epoxides is mainly controlled by the
relative disposition of the substituents in the starting epoxides.
There are several literature reports evidencing that cis-1,2-
epoxides generally offer lower regioselectivity than do the
Scheme 1. Ring-opening of Sharpless epoxyethers with trivalent
phosphorus nucleophiles.
10
5
0
5
Whilst a number of examples of ring-opening of trans-1,2-
corresponding trans isomers, though a near-complete reversion
of the regiochemical outcome between a cis- and trans-
disubstituted epoxide was unexpected. A proven justification to
disubstituted epoxides with phosphorus nucleophiles have been
,6a,c−h
4
published thus far
(most of them from our research group),
studies of this chemistry involving their cis-analogues is, to the 45 the reversion of the regiochemical outcome cannot be provided.
best of our knowledge, unreported. With the reactivity studies of
the ring-opening of trans-epoxyethers 1 in hand, the authors then
turned their attention to the ring-opening of the cis-analogue 4, as
they considered that this chemistry would be a promising route to
However, the authors hypothesise that this behaviour may be a
combination of electronic and steric effects. Ring-opening at the
benzylic position may predominate in trans-epoxides 1 due to
stabilisation of the transition state by resonance effects involving
1
P−OP ligands being stereochemically different to those 50 the attacked carbon and the coplanar phenyl ring (Scheme 2). On
6
previously reported. It was envisioned that cis-1,2-disubstituted
epoxyethers should provide enantiomerically pure phosphine-
borane alcohol derivatives having a syn relative configuration of
the phosphorus and hydroxyl groups.
the contrary, such resonance stabilisation effects cannot probably
1
be met in the ring-opening of cis-epoxide 4, as the CH OMe
2
group prevents the phenyl ring adopting the required
conformation in the corresponding transition state for effective
resonance effects (Scheme 2). Such rationalisation has been
55
1
1
reported for the ring-opening of related epoxides.
Ring-opening of trisubtituted epoxides
With regard to other types of epoxides as starting materials for
this chemistry, we turned our attention to natural products, as the
chiral pool remains an attractive and economic source for
enantiomerically pure, highly functionalised compounds. For
instance, diastereomeric mixtures of limonene oxides 7 have been
6
6
7
7
0
5
0
5
1
2
subjected to ring-opening with phosphorus nucleophiles, and
the expected phosphino alcohols were isolated as air-sensitive
solids that required immediate transformation into the
12a
corresponding phosphine oxides or into a number of metal
12b
complexes. Unfortunately, the resulting products preserve the
original C=C bond from the limonene skeleton, which might pose
a problem in future applications of these compounds (or their
derivatives) as catalysts in transformations involving reagents
that normally add to carbon-carbon unsaturated bonds.
Interestingly, ring-opening reactions of the saturated limonene
oxide’s analogue 8 (also known as carvomenthene oxide, 8,9-
dihydrolimonene 1,2-epoxide or p-menthene oxide) by
phosphorus nucleophiles have not been reported in the literature.
The required epoxide 8 was prepared following a reported
Scheme 2. Regio-alternation observed upon ring-opening of the trans-
procedure from limonene oxide
7
by chemoselective
20
2
1,2-epoxide 1a (top) and the cis-1,2-epoxide 4 (bottom) with KPPh .
hydrogenation of 7 in THF using catalytic amounts of PtO
2
13
The enantiopure cis-1,2-epoxide 4 was readily prepared
8
(Scheme 3). The desired enantiopure carvomenthene oxide 8
following reported synthetic methodologies. The ring-opening of 80 was obtained in quantitative yield and in the original
1
diastereomeric ratio (47:53 cis/trans, as determined by H NMR).
enantiopure cis-1,2-epoxide 4 with KPPh2 under the reaction
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Ring-opening of enantiopure monosubstituted epoxides
Altough ring-opening of enantiopure monosubstituted
epoxides by trivalent phosphorus nucleophiles has already been
1
4
3
4
4
5
5
6
5
0
5
0
5
0
studied, we also turned our attention to the ring-opening of the
terminally-monosubstituted styrene oxide 10. Several research
groups have reported the use of the diphenylphosphide anion for
12c,15
ring-opening of racemic
or enantiomerically pure styrene
16
15c
oxide. With the exception of Pellon , who described the
reaction as being totally regioselective, no regioselectivity issues
were considered by the authors, who simply accounted for the
formation of the regioisomer resulting from nucleophilic attack of
MPPh2 at the unsubstituted carbon of styrene oxide. Among
literature reports, only Muller et al. took into account the
formation of regioisomeric mixtures of ring-opened products
Figure 1 (Left) Crystal structure of 5. (Right) Crystal structure of 9
ORTEP drawings showing thermal ellipsoids at 50% probability). Non-
relevant hydrogen atoms have been omitted for clarity.
(
5
However, the resultant carvomenthene oxide diastereoisomers
could not be separated by silica gel column chromatography.
Ring-opening of enantiomerically pure (4S)-carvomenthene 1,2-
epoxides 8 (as diastereoisomeric mixture: ca. 1:1 cis/trans) with
derived from (S)-10 and LiPPh . They found a regioisomer ratio
2
31
(
rr) of 70:30, which they determined by P NMR analysis of the
12a
crude mixture.
Prompted by the lack of systematic investigation into the
regio- and stereochemistry of the ring-opening of
KPPh (0.53 equiv. with respect to the overall mixture; 1.0 equiv.
2
1
1
2
2
0
5
0
5
with respect to trans-8) proceeded smoothly at −78 ºC to 0 ºC
enantiomerically pure styrene oxide 10 with MPPh , the authors
2
(Scheme 3). Diastereoisomer cis-8 remained mostly unreacted
of the present article revisited this transformation. Using Muller’s
under ring-opening conditions and could be easily separated from
product 9 by column chromatography. The ring-opening reaction
was totally regioselective and proceeded exclusively through
attack of C-2 in trans-8 by diphenylphosphide. After in situ
protection, the enantiopure borane-protected 1,2-phosphino
alcohol 9 was isolated in 74% yield as a single regioisomer.
Structural characterisation of 9 with standard spectroscopic
techniques was complemented with X-ray diffraction analysis
12a
procedure as a reference and the general conditions indicated in
Scheme 4, we studied the influence of the diphenylphosphide
source, and the order of addition between the nucleophile
(
(
HPPh /nBuLi or KPPh ) and the electrophile ((S)-styrene oxide
2 2
17
10) ). The results are summarised in Table 1.
As shown in Table 1, all the ring-opening reactions were
highly regioselective (rr = 88:12 → 97:3 11/12), enabling gram
scale isolation of the phosphine-borane alcohol 11, which was
formed by nucleophilic attack of diphenylphosphide anions at the
unsubstituted carbon of (S)-styrene oxide 10, in high yield
(Figure 1, right), which confirmed both the regiochemistry and
the absolute configuration of the resultant product. The chair-like
conformation observed in the solid state (Figure 1, right) for the
borane-protected phosphino alcohol 9 evidenced the 1,2-diaxial-
trans orientation of the hydroxyl and phosphine-borane
functionalities at C-1 and C-2, respectively, in the cyclohexane
ring in the solid state, with the isopropyl substituent at the C-4
stereocentre exhibiting an equatorial disposition.
(
74−86% yield). This regiochemistry was consistent with
15−16
literature reports:
compound 11 was the major regioisomer.
65
Scheme 4. Ring-opening of (S)-styrene oxide with MPPh2.
Use of commercially available KPPh2 as nucleophile gave
almost complete regioselectivity (rr 11/12 = 97:3), regardless of
the order of addition of the reactants (Table 1, entries 1 and 2).
Under these conditions, the major regioisomer 11 was isolated in
up to 86% yield (entry 2), whereas the minor one, 12, was
isolated in a maximum of only 3% yield (entry 2). The structure
of product 11 could be unambiguously confirmed by X-ray
7
7
8
8
0
5
0
5
7
12a
diffraction analysis. Conversely, when Muller’s procedure was
followed, the minor regioisomer 12 was obtained in a markedly
higher proportion (rr 11/12 = 88:12); this method involved
dropwise addition of nBuLi to a solution of the starting epoxide
1
0 and HPPh in THF previously cooled to −78 ºC (Table 1, entry
2
3
). Using Muller’s procedure, compounds 11 and 12 were
isolated in 74% and 12% yield, respectively, after column
chromatography.
The ee values for regioisomers 11 and 12 varied significantly
depending on the reaction conditions—basically, on the order of
Scheme 3. Hydrogenation of cis/trans-limonene 1,2-epoxides 7 to form
cis/trans-carvomenthene 1,2-epoxides 8 and subsequent ring-opening
3
0
reagent addition, as evidenced by Table 1. Addition of KPPh to
2
with KPPh
2
.
the epoxide 10 proved to be a reliable and robust method for
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Table 1. Regioselective ring-opening of (S)-styrene oxide (10) using alkali metal diphenylphosphides (MPPh
2
; M = K or Li).
b
Major regioisomer (11):
Minor regioisomer (12):
a
rr
11/12)
Entry
Reaction conditions
(
c
d
ee (%)
c
d
ee (%)
Yield
78
Yield
e
e
1
2
3
KPPh
10 added to KPPh
nBuLi added to 10/HPPh
2
added to 10
97:3
97:3
99
96
98
−
−
2
86
3
12
1
86
f
2
88:12
74
98 (> 99)
a
b
For general reaction conditions, see Scheme 4 and the Experimental Section. Regioisomer ratio (rr) determined by H NMR analysis of the crude
f
mixture. Isolated yield of pure compound. Determined by HPLC analysis of isolated pure product using chiral stationary phases. Product not isolated.
c
d
e
5
Compound 12 was isolated in 10% yield and in > 99% ee after two recrystallisations.
obtaining the major regioisomer 11 in enantiomerically pure form
99% ee) on the gram scale (Table 1, entry 1). Surprisingly, the
the same reaction conditions.
(
reverse order of addition was detrimental to the enantiomeric
purity of compounds 11 and 12 (Table 1, entry 2): their
enantiopurity (96% and 86% ee, respectively) was lower than that
10
15
20
25
1
7
of the starting material (99% ee). These results indicate that a
defect of the nucleophile with respect to the epoxide throughout
the reaction (conditions indicated in entry 1) is beneficial for
avoiding erosion of the optical purity of the final products via
undesired processes (i.e. metallation of the carbon alpha to
2
Scheme 5. Ring-opening of (R)-2-phenyloxetane with MPPh .
oxygen and/or S 1 epoxide ring-opening).
N
Conclusions
1
2a
Under Muller’s conditions the ee for either compound 11 or
2 (ca. 98% ee for both compounds; Table 1, entry 3) was very
5
5
Efficient and convenient syntheses of diverse, enantiomerically
pure, borane-protected 1,2-, and 1,3-phosphino alcohols have
been developed. The regioselective ring-opening of diversely
substituted, enantiomerically pure epoxides and oxetanes with
nucleophilic phosphorus reagents provided ready access to
structurally diverse 1,2-, and 1,3-phosphino alcohols derivatives
with full stereocontrol. Noteworthy examples include synthetic
routes starting from chiral pool-derived carvomenthene oxide.
The authors of this work are currently endeavouring to use these
phosphorus derivatives as chiral building blocks for the
1
close to that of the starting material. Interestingly, the
enantiopurity of 12 (isolated under the previous conditions in
1
2% yield and in 97.7% ee, Table 1) was enhanced by
recrystallisation (10% yield, > 99% ee). Accordingly, this study
enabled synthesis of significant quantities of compounds 11 and
12, isolated as single regioisomers in enantiomerically pure form,
under optimised reaction conditions.
60
Ring-opening of enantiopure oxetanes
65 preparation of new ligands for asymmetric catalysis.
Considering the importance of introducing structural and
stereochemical diversity into enantiomerically pure phosphine-
borane alcohols, we finally envisaged that 1,3-phosphino alcohol
derivatives could be available by ring-opening of larger-
membered oxa-containing heterocycles than epoxides (i.e.
oxetanes) with phosphorus nucleophiles. Reports on the ring-
opening of these type of compounds are very scarce in the
3
0
Experimental Section
General Information
All syntheses were done using chemicals as purchased from
7
7
8
0
5
0
commercial sources, unless otherwise stated. All manipulations
and reactions were run under inert atmosphere in anhydrous
solvents by using standard Schlenk-type techniques. Glassware
was dried under vacuum and heated with a heat gun before use.
All solvents were dried by using a Solvent Purification System
(SPS). Silica gel 60 (230−400 mesh) was used for column
35
1
8
literature.
19
Accordingly, the enantiopure (R)-2-phenyloxetane 13 was
selected as the model substrate. Ring-opening of (R)-2-
phenyloxetane 13 with KPPh (1 equiv.) proceeded smoothly at
2
40
45
50
−30 ºC to rt (Scheme 5). Unlike enantiomerically pure styrene
oxide 10, full conversion was not accomplished under these
conditions (68% conv.), however the ring-opening was
regioselective and proceeded through attack at the oxetane
unsubstituted carbon alpha to oxygen. After in situ protection, the
enantiopure borane-protected 1,3-phosphino alcohol 14 was
obtained in 47% yield. The isolated yield of 14 could be
chromatography. NMR spectra were recorded in CDCl unless
3
1
otherwise cited, using a 400 MHz or 500 MHz spectrometer. H
13
NMR and C NMR chemical shifts are quoted in ppm relative to
31
1
residual solvent peaks, whereas P{ H} NMR chemical shifts are
quoted in ppm relative to 85% phosphoric acid in water and
11
1
B{ H} NMR chemical shifts are quoted in ppm relative to
BF ·OEt in CDCl . High resolution mass spectra (HRMS) were
3
2
3
increased up to 63%, respectively, by using 3 equiv. of KPPh2.
recorded by using a ESI method in positive mode. Enantiomeric
excess (ee) values were determined by HPLC, using chiral
stationary phases in a chromatograph equipped with a diode array
The use of LiPPh (generated from HPPh and nBuLi) instead of
2
2
KPPh2 did not bring any advantage, as the conversion and
85
isolated yield were lower than those observed for KPPh under
2
4
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UV detector. Unless otherwise specified, materials were obtained 60 53.4 Hz, Cq arom−P), 130.8 (d, JC−P = 1.1 Hz, CHarom), 130.9 (d,
from commercial suppliers and were used without further
J
= 2.6 Hz, CHarom), 132.9 (d, J = 9.3 Hz, CHarom), 133.3 (d,
C−P
C−P
= 8.9 Hz, CHarom), 141.8 (d, J
purification: cis/trans-(1S/R,2R/S,4S)-limonene 1,2-epoxide (7),
(
J
= 8.4 Hz, Cq arom) ppm.
C−P
P{ H} NMR (162 MHz, CDCl3):
C−P
8 19
S)-styrene oxide (10). Compounds 4 and 13 were prepared
31
1
δ
=
22.5−25.0 (m,
11
1
5
according to the cited literature procedures.
Ph P→BH ) ppm. B{ H} NMR (128 MHz, CDCl ): δ =
(−40.5)−(−35.7) (m, Ph P→BH ) ppm. HRMS (ESI ): m/z calcd.
2
3
3
+
65
2
3
+
X-Ray Data: Single crystals of enantiopure compounds 2a, ent-
for C22H26BO PNa [M + Na] 386.1698; found 386.1687.
2
2
b, 2c, 2d, 5, and 11 suitable for X-ray diffraction analysis were
grown by slow diffusion of n-hexane into EtOAc solutions of
cis/trans-(1S/R,2R/S,4S)-carvomenthene
1,2-epoxide
(8):
1
1
2
2
3
3
4
4
5
5
0
5
0
5
0
5
0
5
0
5
each compound at room temperature. Single crystals of
Adams’ catalyst PtO (140 mg, ca. 3% w/w) was loaded into a
2
enantiopure compound 9 suitable for X-ray diffraction analysis 70 two-necked flask containing a solution of a 47:53 cis/trans
were grown by slow diffusion of n-hexane into DCM solutions of
the compound at room temperature. For more details on the X-
Ray analysis see the Supporting Information. CCDC 931316-
931319, 931321, 931323 and 931325 contain the supplementary
diastereomeric mixture of 7 (4.65 g, 30.2 mmol) in anhydrous
THF (68.0 mL). The reaction flask was connected to a H2
balloon, and the reaction mixture was vigorously stirred under
atmospheric pressure of H for 15 h at room temperature. After
2
crystallographic data for this paper. These data can be obtained 75 this period, the reaction mixture was diluted with hexanes (20
®
free of charge from the Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
mL) and filtered through a Celite 521 pad, which was washed
with EtOAc (60 mL). The filtrate was concentrated under vacuum
to afford 4.68 g (100% isolated yield) of pure carvomenthene 1,2-
epoxide 8 as a colorless liquid. Compound 8 was obtained as a
(1S,2S)-2-(Diphenylphosphino borane)-3-methoxy-1-phenyl-
1
-propanol (5): A 0.5 M solution of KPPh in THF (7.4 mL, 3.72 80 diastereomeric mixture comprising cis-8 and trans-8 in a cis/trans
2
1
ratio of 47:53 (determined by H NMR). The physical and
mmol) was added dropwise by syringe (over 5 min) to a flame-
dried Schlenk flask under Ar atmosphere containing a solution of
8
the cis-(2R,3S)-1,2-epoxy methyl ether 4 (0.51 g, 3.10 mmol) in
spectroscopic data obtained for this diastereomeric mixture agree
13
with literature reports.
anhydrous THF (25.0 mL) cooled to −30 ºC. The mixture was
stirred for 1 h, and then allowed to slowly reach room 85 (1R,2R,4S)-2-(Diphenylphosphino
borane)-4-isopropyl-1-
temperature, which took ca. 4 h. It was then stirred for another 1
methyl-cyclohexanol (9): A 0.5 M solution of KPPh in THF
2
h at room temperature. After this time, a 1.0 M solution of
(27.5 mL, 13.7 mmol) was added dropwise by syringe (over 15
min) to a flame-dried Schlenk flask under Ar atmosphere
containing a solution of a 47:53 cis/trans diastereomeric mixture
BH ·THF in THF (9.3 mL, 9.30 mmol) was added dropwise
3
(over ca. 15 min) by syringe to the reaction mixture previously
cooled to −10 ºC. The mixture was stirred for 30 min at −10 ºC, 90 of 8 (4.00 g, 25.9 mmol of mixture containing 13.7 mmol of
and then allowed to warm to room temperature. It was then
stirred for another 1 h. The reaction mixture was carefully
quenched with water (25 mL) and diluted with EtOAc (15 mL).
After the phases were separated, the resulting aqueous phase was
trans-8) in anhydrous THF (40.0 mL) cooled to −78 ºC. The
mixture was stirred for 1 h, and then allowed to slowly reach 0
ºC, which took around 4 h. It was then stirred for another 1 h at 0
ºC. After this time, a 1.0 M solution of BH ·THF in THF (41.2
3
extracted with EtOAc (2 x 25 mL). The combined organic layers 95 mL, 41.2 mmol) was added dropwise (over ca. 30 min) by
were washed with brine (2 x 50 mL), dried over anhydrous
syringe to the previous reaction mixture maintained at 0 ºC. The
mixture was subsequently allowed to warm to room temperature,
and then stirred for another 1 h. The reaction mixture was
carefully quenched with water (100 mL) and diluted with EtOAc
MgSO , filtered, and concentrated under reduced pressure. Based
4
1
31
on H and P{ H} NMR analyses, the crude product was found
1
to comprise a 91:9 mixture of compound 5 and compound 6,
respectively. Purification of the resulting residue by silica gel 100 (50 mL). After the phases were separated, the resulting aqueous
®
column chromatography (CombiFlash system, 40 g SiO2
cartridge, 1st eluent: hexanes, 2nd eluent: 20:80 EtOAc/hexanes,
phase was extracted with EtOAc (2 x 80 mL). The combined
organic layers were washed with brine (2 x 150 mL), dried over
3
rd eluent: 50:50 EtOAc/hexanes) afforded 0.91 g (80% isolated
yield) of pure borane-protected phosphino alcohol 5 (major
regioisomer) as sticky foamy white solid. The minor 105 confirmed the complete regioselectivity of the ring-opening
anhydrous MgSO , filtered, and concentrated under reduced
4
1
31
1
pressure. H and P{ H} NMR analyses of the crude mixture
a
regioisomer 6 could only be isolated in impure form and small
process to the formation of compound 9 as a single regioisomer
and evidenced that the diastereoisomer cis-8 of the starting
epoxide remained unreacted. Purification of the resulting residue
quantities (ca. 30 mg, ca. 3% isolated yield). Data for the major
2
5
regioisomer 5: [
α]D = +78.4 (c 1.24, CHCl ). IR (neat): υ =
3
-1 1
®
3486 (O−H), 2382 (B−H, BH ) cm . H NMR (400 MHz,
by silica gel column chromatography (CombiFlash system, 120
3
CDCl ): δ = 0.72−1.76 (m, 3H, BH ), 2.82−2.99 (m, 1H, OH), 110 g SiO2 cartridge, 1st eluent: hexanes, 2nd eluent: 10:90
3
3
2
5
5
.88 (s, 3H, OMe), 3.00−3.23 (m, 3H, CH OMe and CH−PPh ),
EtOAc/hexanes, 3rd eluent: 30:70 EtOAc/hexanes) afforded 3.59
2
2
.19 (bdd, J = 8.6 and 8.6 Hz, 1H, CH−OH), 7.22−7.39 (m, 5H,
Harom), 7.39−7.52 (m, 6H, 6Harom), 7.74−7.93 (m, 4H, 4Harom
g (74% isolated yield) of pure borane-protected phosphino
2
6
)
alcohol 9 as a foamy white solid. M.p. 49.0−51.6 ºC. [
α]D
=
13
1
ppm. C{ H} NMR (100 MHz, CDCl ): δ = 44.4 (d, J = 31.4
−42.1 (c 0.86, CHCl ). IR (neat): υ = 3483 (O−H), 2389 (B−H,
3
C−P
3
-
1 1
Hz, CH−PPh ), 58.2 (OMe), 69.5 (CH −OMe), 73.0 (d, J = 1.5 115 BH ) cm . H NMR (500 MHz, CDCl ): δ = 0.64 (d, J = 6.6 Hz,
2
2
C−P
3
3
Hz, CH−OH), 126.7 (CHarom), 128.0 (CHarom), 128.3 (d, JC−P
=
3H, CH(Me) ), 0.82 (d, J = 6.7 Hz, 3H, CH(Me) ), 0.97−1.56 (m,
2
2
1
0.0 Hz, CHarom), 128.3 (CHarom), 128.4 (d, J = 10.5 Hz,
3H, BH ), 1.15 (s, 3H, Me−C−OH), 1.39−1.53 (m, 3H, CH and
C−P
3
2
CHarom), 128.9 (d, J
= 53.2 Hz, Cq arom−P), 129.5 (d, JC−P
=
CH−CH(Me) ), 1.55−1.71 (m, 3H, CH and CH(Me) ), 1.76−1.94
C−P
2
2
2
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DOI: 10.1039/C4RA10432C
(
m, 2H, CH ), 2.56 (bs, 1H, OH), 3.00 (ddd, J = 13.0, 8.9 and 3.9 60 Hz, CHarom), 129.5 (d, J = 57.4 Hz, Cq arom−P), 131.3 (d, JC−P
=
=
=
2
C−P
2.1 Hz, CHarom), 131.5 (d, J = 2.0 Hz, CHarom), 132.0 (d, J
Hz, 1H, CH−PPh ), 7.40−7.55 (m, 6H, 6Harom), 7.75−7.91 (m,
4
2
C−P
9.7 Hz, CHarom), 132.4 (d, J = 9.2 Hz, CHarom), 143.8 (d, J
C−P
13
1
H, 4Harom) ppm. C{ H} NMR (125 MHz, CDCl ): δ = 20.3
CH(Me) ), 20.4 (CH(Me) ), 24.9 (CH ), 26.6 (Me−C−OH), 28.1
3
C−P
C−P
31
1
(
11.3 Hz, Cq arom) ppm. P{ H} NMR (202 MHz, CDCl ): δ =
3
11 1
14.3−16.1 (m, Ph P→BH ) ppm. B{ H} NMR (160 MHz,
2
2
2
5
0
5
0
5
0
5
0
5
0
5
(CH ), 28.3 (CH(Me) ), 37.0 (d, J
= 5.2 Hz, CH ), 39.1 (d,
2
2
C−P
2
2
3
J
= 5.1 Hz, CH−CH(Me) ), 41.8 (d, JC−P = 27.5 Hz, 65 CDCl ): δ = (−41.0)−(−37.0) (m, Ph P→BH ) ppm. HRMS
C−P
2
3
+ +
2
3
CH−PPh ), 73.1 (d, J = 4.5 Hz, C−OH), 128.0 (d, JC−P = 53.7
Hz, Cq arom−P), 128.5 (d, JC−P = 9.9 Hz, CHarom), 128.7 (d, JC−P
(ESI ): m/z calcd. for C H BOPNa [M + Na] 342.1435; found
20 22
2
C−P
=
342.1419.
9
.5 Hz, CHarom), 130.1 (d, J
= 56.5 Hz, Cq arom−P), 130.9 (d,
C−P
= 2.4 Hz, CHarom), 131.3 (d, J = 2.1 Hz, CHarom), 132.1 (d,
1
1
2
2
3
3
4
4
5
5
J
C−P
(R)-2-(Diphenylphosphino borane)-2-phenylethanol (12; see
= 8.8 Hz, CHarom) ppm. 70 Table 1, entry 3): A 2.5 M solution of nBuLi in hexanes (6.5 mL,
C−P
= 8.2 Hz, CHarom), 134.0 (d, J
J
C−P
P{ H} NMR (162 MHz, CDCl3):
C−P
3
1
1
δ
=
17.0−21.2 (m,
16.3 mmol) was added dropwise by syringe (over 15 min) to a
flame-dried Schlenk flask under Ar atmosphere containing a
solution of (S)-styrene oxide 10 (2.00 g, 16.3 mmol) and HPPh2
(2.8 mL, 16.3 mmol) in anhydrous THF (40.0 mL) cooled to −78
ºC. The mixture was stirred for 1 h, and then allowed to slowly
reach 0 ºC, which took around 4 h. It was then stirred for another
1
1
1
Ph P→BH ) ppm. B{ H} NMR (128 MHz, CDCl ): δ =
2
3
3
+
(
−40.2)−(−32.2) (m, Ph P→BH ) ppm. HRMS (ESI ): m/z calcd.
2
3
+
for C H BOPNa [M + Na] 376.2218; found 376.2234.
22
32
75
(
S)-2-(Diphenylphosphino borane)-1-phenylethanol (11; see
Table 1, entry 1): A 0.5 M solution of KPPh in THF (32.6 mL,
2
1 h at 0 ºC. After this time, a 1.0 M solution of BH ·THF in THF
3
1
6.3 mmol) was added dropwise (over 15 min) by syringe to a
(16.3 mL, 16.3 mmol) was added dropwise (over ca. 30 min) by
flame-dried Schlenk flask under Ar atmosphere containing a
syringe to the previous reaction mixture maintained at 0 ºC. The
solution of (S)-styrene oxide 10 (2.00 g, 16.3 mmol) in anhydrous 80 mixture was subsequently allowed to warm to room temperature,
THF (40.0 mL) cooled to −78 ºC. The mixture was stirred for 1 h,
and then allowed to slowly reach 0 ºC, which took ca. 4 h. It was
then stirred for another 1 h at 0 ºC. After this time, a 1.0 M
and then stirred for another 1 h. The reaction mixture was
carefully quenched with water (100 mL) and diluted with EtOAc
(50 mL). After the phases were separated, the resulting aqueous
phase was extracted with EtOAc (2 x 80 mL). The combined
solution of BH ·THF in THF (16.3 mL, 16.3 mmol) was added
3
dropwise (over ca. 30 min) by syringe to the previous reaction 85 organic layers were washed with brine (2 x 150 mL), dried over
mixture, maintained at 0 ºC. The mixture was subsequently
allowed to warm to room temperature, then stirred for another 1
h, carefully quenched with water (100 mL) and diluted with
EtOAc (50 mL). After the phases were separated, the aqueous
anhydrous MgSO , filtered, and concentrated under reduced
4
1
pressure. Based on H NMR analysis, the crude product was
found to comprise an 88:12 mixture of compound 11 and
compound 12, respectively. Purification of the resulting residue
®
phase was extracted with EtOAc (2 x 80 mL). The combined 90 by silica gel column chromatography (CombiFlash system, 120
organic layers were washed with brine (2 x 150 mL), dried over
g SiO2 cartridge, 1st eluent: hexanes, 2nd eluent: 10:90
EtOAc/hexanes, 3rd eluent: 30:70 EtOAc/hexanes) afforded 3.85
g (74% isolated yield) of pure borane-protected phosphino
alcohol 11 (major regioisomer) as a crystalline white solid and
anhydrous MgSO , filtered, and concentrated under reduced
4
1
pressure. Based on H NMR analysis, the crude product was
found to comprise a 97:3 mixture of compound 11 and compound
1
2, respectively. Purification of the resulting residue by silica gel 95 0.60 g (12% isolated yield) of pure borane-protected phosphino
®
column chromatography (CombiFlash system, 120 g SiO2
cartridge, 1st eluent: hexanes, 2nd eluent: 10:90 EtOAc/hexanes)
afforded 4.06 g (78% isolated yield) of pure borane-protected
phosphino alcohol 11 (major regioisomer) as a crystalline white
alcohol 12 (minor regioisomer) as a foamy white solid. The
enantiomeric purity of the isolated pure compounds 11 and 12
was determined to be 97.6% ee (S enantiomer) and 97.7% ee (R
enantiomer), respectively, by HPLC analysis on chiral stationary
solid. The minor regioisomer 12 was not isolated. The 100 phases. Two subsequent recrystallisations from diluted solutions
enantiomeric purity of the isolated pure compound 11 was
determined to be 99.0% ee by HPLC analysis on a chiral
stationary phase. HPLC conditions were optimised for the
of 12 in the solvent mixture 1:4 Et O/n-hexane (150 and 100 mL
2
of mixture used for the first and second recrystallisation,
respectively) by refrigerating the latter solutions overnight at 5 ºC
furnished the minor regioisomer 12 with 10% yield (0.50 g
racemate of 11, prepared from racemic styrene oxide rac-10 and
®
are the following ones: Daicel Chiralpak AD-H (25 cm x 0.46 105 isolated) and in greater than 99% ee. HPLC conditions were
cm x 5 µm), 95:5 n-hexane/2-propanol, 1.0 mL/min, 216 nm,
optimised for the racemate of 12, prepared from racemic styrene
®
oxide rac-10, and comprise: Daicel Chiralcel OD-H (25 cm x
t (R) = 33.4 min, t (S) = 40.1 min. Data for the major regioisomer
R
R
2
6
1
1: M.p. 94.4−99.3 ºC. [
α
]D = +46.2 (c 1.10, CHCl ). IR (neat):
0.46 cm x 5 µm), 95:5 n-hexane/2-propanol, 1.0 mL/min, 216
nm, t (S) = 20.7 min, t (R) = 23.6 min. Data for the minor
3
-
1 1
υ = 3507 (O−H), 2407 and 2366 (B−H, BH ) cm . H NMR (500
MHz, CDCl ): δ = 0.85−1.70 (m, 3H, BH ), 2.69 (ddd, J = 14.9, 110 regioisomer 12: M.p. 103.5−107.0 ºC. [α]D = −161.2 (c 1.11,
1
8
9
3
R
R
26
3
3
-1 1
2.7 and 2.4 Hz, 1H, CHH−PPh ), 2.79 (ddd, J = 14.9, 9.7 and
CHCl ). IR (neat): υ = 3416 (O−H), 2399 (B−H, BH ) cm . H
2
3
3
.0 Hz, 1H, CHH−PPh ), 3.03 (bs, 1H, OH), 5.12 (ddd, J = 9.7,
NMR (500 MHz, CDCl ): δ = 0.69−1.49 (m, 3H, BH ), 1.79 (bs,
2
3
3
.6 and 2.4 Hz, 1H, CH−OH), 7.25−7.31 (m, 1H, 1Harom),
1H, OH), 4.01 (ddd, J = 14.2, 8.9 and 5.1 Hz, 1H, CH−PPh2),
4.06−4.16 (m, 1H, CHH−OH), 4.24−4.34 (m, 1H, CHH−OH),
7.31−7.38 (m, 4H, 4H ), 7.43−7.57 (m, 6H, 6Harom), 7.70−7.78
arom
3
1
1
(
m, 4H, 4Harom) ppm. C{ H} NMR (125 MHz, CDCl ): δ = 37.1 115 7.15−7.27 (m, 7H, 7Harom), 7.32−7.39 (m, 3H, 3H ), 7.50−7.61
3
arom
1
3
1
(
d, J
= 34.0 Hz, CH −PPh ), 69.6 (CH−OH), 125.5 (CHarom),
(m, 3H, 3Harom), 7.91−7.98 (m, 2H, 2Harom) ppm. C{ H} NMR
(125 MHz, CDCl ): δ = 46.2 (d, J = 29.2 Hz, CH−PPh ), 62.9
C−P
27.9 (CHarom), 128.6 (CHarom), 128.8 (d, J
2
2
1
= 55.5 Hz, Cq
C−P
= 10.2 Hz, CHarom), 129.0 (d, J
3
C−P
2
arom−P), 128.9 (d, J
= 10.1
(d, J
= 10.4 Hz, CH −OH), 127.5 (d, J = 55.7 Hz, Cq
C−P
C−P
C−P
2
C−P
6
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DOI: 10.1039/C4RA10432C
arom−P), 127.7 (d, JC−P = 2.0 Hz, CHarom), 128.0 (d, JC−P = 53.7
1
See, for example, the following references and those cited therein: (a)
A. Börner, ed., Phosphorus Ligands in Asymmetric Catalysis, 1st
edn., Wiley-VCH, Weinheim, 2008; Vols. I-III; (b) P. W. N. M. van
Leeuwen, P. C. J. Kamer, C. Claver, O. Pamies and M. Dieguez,
Chem. Rev., 2011, 111, 2077; (c) H. Fernández-Pérez, P. Etayo, A.
Panossian and A. Vidal-Ferran, Chem. Rev., 2011, 111, 2119; (d) J.
Wassenaar and J. N. H. Reek, Org. Biomol. Chem., 2011, 9, 1704; (e)
S. Luehr, J. Holz and A. Boerner, ChemCatChem, 2011, 3, 1708; (f)
P. Etayo and A. Vidal-Ferran, Chem. Soc. Rev., 2013, 42, 728; (g) M.
Raynal, P. Ballester, A. Vidal-Ferran and P. W. N. M. van Leeuwen,
Chem. Soc. Rev., 2014, 43, 1660; (h) M. Raynal, P. Ballester, A.
Vidal-Ferran and P. W. N. M. van Leeuwen, Chem. Soc. Rev., 2014,
Hz, Cq arom−P), 128.2 (d, JC−P = 10.2 Hz, CHarom), 128.4 (d, JC−P
=
1
.7 Hz, CHarom), 129.0 (d, J = 10.0 Hz, CHarom), 129.9 (d, J
C−P
C−P
C−P
C−P
=
4.6 Hz, CHarom), 131.0 (d, J = 2.6 Hz, CHarom), 131.5 (d, J
C−P
5
= 2.0 Hz, CHarom), 132.8 (d, J = 8.7 Hz, CHarom), 132.9 (d, J
C−P
3
1
1
=
8.6 Hz, CHarom), 134.0 (d, J
= 1.7 Hz, Cq arom) ppm. P{ H}
C−P
NMR (202 MHz, CDCl ): δ = 21.2−22.7 (m, Ph P→BH ) ppm.
3
2
3
1
1
1
B{ H} NMR (160 MHz, CDCl ): δ = (−48.9)−(−38.2) (m,
3
+
Ph P→BH ) ppm. HRMS (ESI ): m/z calcd. for C H BOPNa
2
3
20 22
+
[M + Na] 342.1435; found 342.1425.
1
1
2
2
3
3
0
5
0
5
0
5
(
R)-3-(Diphenylphosphino borane)-1-phenyl-1-propanol (14):
4
3, 1734.
A 0.5 M solution of KPPh in THF (2.2 mL, 1.14 mmol) was
2
2
3
See, for example, the recent review and the references cited therein:
C. Gomez, J.-F. Betzer, A. Voituriez and A. Marinetti,
ChemCatChem, 2013, 5, 1055.
added dropwise by syringe (over 5 min) to a flame-dried Schlenk
flask under Ar atmosphere containing a solution of the (R)-2-
phenyloxetane 13 (0.051 g, 0.38 mmol) in anhydrous THF (3.2
mL) cooled to −30 ºC. The mixture was stirred for 1 h, and then
allowed to slowly reach room temperature, which took ca. 4 h. It
was then stirred for another 1 h at room temperature. After this
See, for example, the recent reviews on hemilabile P−O ligands that
follow and the references cited therein: (a) D. K. Dutta and B. Deb,
Coord. Chem. Rev., 2011, 255, 1686; (b) W.-H. Zhang, S. W. Chien
and T. S. A. Hor, Coord. Chem. Rev., 2011, 255, 1991.
4
For seminal reports, see: (a) H. Brunner and A. Sicheneder, Angew.
Chem. Int. Ed. Engl., 1988, 100, 718; (b) F. Gorla, A. Togni, L. M.
Venanzi, A. Albinati and F. Lianza, Organometallics, 1994, 13,
time, a 1.0 M solution of BH ·THF in THF (1.14 mL, 1.14 mmol)
3
was added dropwise (over ca. 15 min) by syringe to the reaction
1
Prepared according to the literature procedures described in: A.
607.
mixture previously cooled to −10 ºC. The mixture was stirred for
1
5
6
h at −10 ºC, and then allowed to warm to room temperature. It
Vidal-Ferran, A. Moyano, M. A. Pericàs and A. Riera, J. Org. Chem.,
1
was then stirred for another 3 h. The reaction mixture was
carefully quenched with water (3 mL) and diluted with EtOAc (5
mL). After the phases were separated, the resulting aqueous
phase was extracted with EtOAc (2 x 5 mL). The combined
organic layers were washed with brine (2 x 6 mL), dried over
997, 62, 4970.
(a) H. Fernández-Pérez, M. A. Pericàs and A. Vidal-Ferran, Adv.
Synth. Catal., 2008, 350, 1984; (b) S. M. A. Donald, A. Vidal-Ferran
and F. Maseras, Can. J. Chem., 2009, 87, 1273; (c) H. Fernández-
Pérez, S. M. A. Donald, I. J. Munslow, J. Benet-Buchholz, F.
Maseras and A. Vidal-Ferran, Chem. Eur. J., 2010, 16, 6495; (d) A.
Panossian, H. Fernández-Pérez, D. Popa and A. Vidal-Ferran,
Tetrahedron: Asymmetry, 2010, 21, 2281; (e) H. Fernández-Pérez, P.
Etayo, J. L. Núñez-Rico and A. Vidal-Ferran, Chim. Oggi, 2010, 28,
XXVI; (f) J. L. Núñez-Rico, H. Fernández-Pérez, J. Benet-Buchholz
and A. Vidal-Ferran, Organometallics, 2010, 29, 6627; (g) P. Etayo,
J. L. Núñez-Rico, H. Fernández-Pérez and A. Vidal-Ferran, Chem.
Eur. J., 2011, 17, 13978; (h) P. Etayo, J. L. Núñez-Rico and A.
Vidal-Ferran, Organometallics, 2011, 30, 6718; (i) J. L. Núñez-Rico,
P. Etayo, H. Fernández-Pérez and A. Vidal-Ferran, Adv. Synth.
Catal., 2012, 354, 3025; (j) J. L. Núñez-Rico and A. Vidal-Ferran,
Org. Lett., 2013, 15, 2066; (k) J. L. Núñez-Rico, H. Fernández-Pérez
and A. Vidal-Ferran, Green Chem., 2014, 16, 1153.
anhydrous MgSO , filtered, and concentrated under reduced
4
1
pressure. Based on H and P{ H} NMR analyses of the crude
31
1
mixture, the regioisomer 15 was not detected. Purification of the
resulting residue by silica gel column chromatography
®
CombiFlash system, 12 g SiO cartridge, 1st eluent: hexanes,
(
2
2
nd eluent: 30:70 EtOAc/hexanes) afforded 0.080 g (63%
isolated yield) of pure borane-protected phosphino alcohol 14 as
a sticky foamy white solid. The physical and spectroscopic data
2
obtained for the compound 14 agree with literature reports.
0
7
8
See the Electronic Supporting Information (ESI) for details.
Acknowledgements
For the experimental procedures leading to 4 and the corresponding
analytical methods, see: X. Caldentey, X. C. Cambeiro and M. A.
Pericàs, Tetrahedron, 2011, 67, 4161. and the relevant references
cited therein.
4
0
The authors thank MINECO (grant CTQ2011-28512), DURSI
grant 2014SGR618) and the ICIQ Foundation for financial
(
support. Dr. J. Benet-Buchholz and E. C. Escudero are
acknowledged for X-ray crystallographic data.
1
31
1
9
1
Regioisomer ratio determined by H and P{ H} NMR analyses of
the crude mixture.
0
For selected examples, see ref 8 and: (a) M. Chini, P. Crotti, L. A.
Flippin, C. Gardelli, E. Giovani, F. Macchia and M. Pineschi, J. Org.
Chem., 1993, 58, 1221; (b) X. Caldentey and M. A. Pericàs, J. Org.
Chem., 2010, 75, 2628.
Notes and references
a
4
5
5
5
0
5
Institute of Chemical Research of Catalonia (ICIQ), Avgda. Països
Catalans 16, 43007 Tarragona, Spain. Fax: (+) 34 977928228; E-mail:
avidal@iciq.cat; Homepage: http://www.iciq.es/portal/359/Vidal.aspx
11 P. Cuadrado, A. M. Gonzalez-Nogal and M. A. Sarmentero, Chem.
Eur. J., 2004, 10, 4491.
b
Catalan Institution for Research and Advanced Studies (ICREA),
Passeig Lluís Companys 23, 08010 Barcelona, Spain. Homepage:
http://www.icrea.cat/Web/ScientificForm.aspx?key=288
12 See, for example, the following references: (a) G. Muller and D.
Sainz, J. Organomet. Chem., 1995, 495, 103; (b) C. Mattheis and P.
Braunstein, J. Organomet. Chem., 2001, 621, 218; (c) D. L. Fox, A.
A. Robinson, J. B. Frank and R. N. Salvatore, Tetrahedron Lett.,
2003, 44, 7579.
†
analysis data of enantiopure compounds 2a, ent-2b, 2c, 2d, 5, 9 and 11,
Electronic Supplementary Information (ESI) available: X-Ray
1
and copies of H, C, P and B NMR spectra for all newly reported
13
31
11
13 K. Mori, Tetrahedron: Asymmetry, 2006, 17, 2133.
14 For selected examples: (a) S. Deerenberg, H. S. Schrekker, G. P. F.
van Strijdonck, P. C. J. Kamer, P. W. N. M. van Leeuwen, J. Fraanje
and K. Goubitz, J. Org. Chem., 2000, 65, 4810; (b) D. J. Brauer, P.
compounds.
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Journal Name, [year], [vol], 00–00 | 7

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DOI: 10.1039/C4RA10432C
Machnitzki, T. Nickel and O. Stelzer, Eur. J. Inorg. Chem., 2000, 65;
c) J. Duran, D. Oliver, A. Polo, J. Real, J. Benet-Buchholz and X.
(
Fontrodona, Tetrahedron: Asymmetry, 2003, 14, 2529; (d) C. Ciardi,
A. Romerosa, M. Serrano-Ruiz, L. Gonsalvi, M. Peruzzini and G.
Reginato, J. Org. Chem., 2007, 72, 7787; (e) C. Hegedüs, H. Gulyás,
A. Szöllosy and J. Bakos, Inorg. Chim. Acta, 2009, 362, 1650.
(a) E. N. Tsvetkov, N. A. Bondarenko, I. G. Malakhova and M. I.
Kabachnik, Synthesis, 1986, 198; (b) H. B. Kagan, M. Tahar and J. C.
Fiaud, Tetrahedron Lett., 1991, 32, 5959; (c) P. Pellon, Tetrahedron
Lett., 1992, 33, 4451; (d) H. B. Kagan, M. Tahar and J. C. Fiaud,
Bioorg. Med. Chem., 1994, 2, 15.
1
5
1
1
6
7
(a) R. Jiang, W. He, P.-a. Wang, X.-y. Li and S.-y. Zhang, Fenzi
Cuihua, 2006, 20, 207; (b) I. Arribas, S. Vargas, M. Rubio, A.
Suarez, C. Domene, E. Alvarez and A. Pizzano, Organometallics,
2
010, 29, 5791.
The enantiomeric purity of (S)-styrene epoxide upon delivery from
the commercial supplier was investigated: the advertised
enantiopurity was 98% ee, which was confirmed (98.5% ee) by
HPLC analysis on a chiral stationary phase. HPLC conditions were
optimised for racemic styrene oxide and then applied to (S)-styrene
®
®
oxide, as received from Aldrich [Daicel Chiralpak IA (25 cm x
.46 cm x 5 µm), 99:1 n-hexane/2-propanol, 0.60 mL/min, 254 nm,
(R) = 9.1 min, t (S) = 10.1 min].
0
t
R
R
1
1
2
8
9
0
To the best of the authors’ knowledge, only one example of ring-
opening of enantiopure oxetanes with phosphides has been reported:
O. Pàmies, M. Diéguez, G. Net, A. Ruiz and C. Claver, Chem.
Commun., 2000, 2383.
For the experimental procedure leading to (R)-2-phenyloxetane 13
and the corresponding analytical methods, see: D. I. Coppi, A.
Salomone, F. M. Perna and V. Capriati, Chem. Commun., 2011, 47,
9918 and the references cited therein.
S. Deerenberg, P. C. J. Kamer and P. W. N. M. van Leeuwen,
Organometallics, 2000, 19, 2065.
8
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DOI: 10.1039/C4RA10432C
TABLE OF CONTENTS ENTRY
Borane complexes of phosphino alcohols were efficiently
obtained by ring-opening of oxa-containing heterocycles with
phosphorus nucleophiles.
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