Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

Article abstract of DOI:10.3762/bjoc.15.242

New chiral regioisomeric γ-hydroxyphosphine ligands were synthesized from α-pinene. The key transformation was the thermal [2,3]-sigmatropic rearrangement of allyldiphenylphosphinites, obtained from (1R,2R,4S,5R)-3-methyleneneoisoverbanol and (1R,2R,3R,5R)-4-methyleneneoisopinocampheol, to allylphosphine oxides. Hydroxy groups were introduced stereoselectively through a hydroboration–oxidation reaction proceeding from the less hindered site providing a trans relationship between the hydroxy and the phosphine substituents.

Full text of DOI:10.3762/bjoc.15.242

Chiral terpene auxiliaries V: Synthesis of new chiral
γ-hydroxyphosphine oxides derived from α-pinene
Anna Kmieciak and Marek P. Krzemiński*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2019, 15, 2493–2499.
Faculty of Chemistry, Nicolaus Copernicus University in Toruń, 7
Gagarin St., 87-100 Toruń, Poland
doi:10.3762/bjoc.15.242
Received: 08 May 2019
Email:
Accepted: 09 October 2019
Published: 22 October 2019
Marek P. Krzemiński* - mkrzem@chem.umk.pl
* Corresponding author
This article is dedicated to Professor Marek Zaidlewicz on the occasion of
his 80th birthday.
Keywords:
isopinocamphone; monoterpenes; phosphines; [2,3]-sigmatropic
rearrangement; verbanone
Associate Editor: S. Bräse
© 2019 Kmieciak and Krzemiński; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
New chiral regioisomeric γ-hydroxyphosphine ligands were synthesized from α-pinene. The key transformation was the thermal
[2,3]-sigmatropic rearrangement of allyldiphenylphosphinites, obtained from (1R,2R,4S,5R)-3-methyleneneoisoverbanol and
(1R,2R,3R,5R)-4-methyleneneoisopinocampheol, to allylphosphine oxides. Hydroxy groups were introduced stereoselectively
through a hydroboration–oxidation reaction proceeding from the less hindered site providing a trans relationship between the
hydroxy and the phosphine substituents.
Introduction
Chiral phosphorus compounds, despite many years of research, organometallics with chlorophosphines, the reaction of metal
still enjoy unflagging interest of many research groups [1]. phosphides with haloalkanes, and transition-metal-catalyzed
Compounds with a phosphorus atom attached to a stereogenic cross-coupling reactions to form C–P bonds are the most widely
carbon center in acyclic and cyclic structures play an important used methods for the synthesis of phosphines [13,14]. Since
role as chiral ligands in transition metal complexes [2]. They phosphines are easily oxidized to phosphine oxides, the addi-
were applied to various catalytic asymmetric reactions [3,4], tion of phosphine oxide P–H nucleophiles were also realized
such as hydrogenations [3-6], conjugated additions to enones [15]. The phosphine oxide group can also be introduced starting
[7], and allylic alkylations [8,9]. Another direction of research from allylic alcohols employing the rearrangement of allylic
is the use of phosphines in organocatalysis [10,11] and bifunc- diphenylphosphinites to allylphosphine oxides [16,17].
tional catalysis [12].
Recently, we have shown the synthesis and applications of
Several methods were developed to introduce the phosphine chiral PHOX ligands that were obtained from readily available
functionality to organic molecules. The reaction of natural (1S)-β-pinene and (1S)-α-pinene [18]. We applied these
2493

Beilstein J. Org. Chem. 2019, 15, 2493–2499.
ligands for the formation of the ruthenium complexes, which aldehyde in the presence of sodium carbonate to give (+)-3-
were successfully used as catalysts in asymmetric transfer methyleneverbanone (5) in 57% yield from 3. α,β-Unsaturated
hydrogenation of prochiral ketones.
ketone 5 was exclusively reduced to allylic alcohol
(1R,2R,4S,5R)-3-methyleneneoisoverbanol (6), using the Luche
In continuation of our studies on the synthesis of monoterpene method [24]. 1,2-Reduction of enone 5 was achieved with sodi-
derived ligands, we have utilized commercially available (1R)- um borohydride in the presence of cerium(III) chloride in meth-
α-pinene and (1S)-β-pinene to obtain regioisomeric exocyclic anol in 88% yield (Scheme 1).
and endocyclic allylic alcohols, which were applied for the syn-
thesis of γ-hydroxydiphenylphosphine ligands. To the best of The synthesis of allylic alcohol 11, a regioisomer of 6, started
our knowledge, only Knochel and co-workers synthesized again from (1R)-α-pinene (1, Scheme 2). Hydroboration of
diphosphines with a pinane framework [19].
(1R)-α-pinene with borane–dimethyl sulfide adduct (BMS) and
crystallization of the product diisopinocampheylborane
(dIpc2BH, 84% yield) allowed to upgrade the enantiomeric
purity of dIpc2BH [25]. Oxidation of the resulting dialkylbo-
Results and Discussion
Synthesis of allylic alcohols
In the first step, commercially available natural (1R)-α-pinene rane with hydrogen peroxide provided enantiomerically pure
(1) was oxidized with lead(IV) acetate to produce (+)- (−)-isopinocampheol (7) in 78% yield. The Brown–Garg
verbenone (2) in 58% yield (Scheme 1) [20]. Hydrogenation of protocol [26] was employed to oxidize 7 with an aqueous solu-
2 with Adams catalyst was carried out in cyclohexane with tion of sodium dichromate and sulfuric acid under biphasic
1 atm of hydrogen. The hydrogen pressure was increased to conditions. (−)-Isopinocamphone (8) was purified by fractional
10 atm for the reaction performed in an autoclave on a larger distillation and isolated in 78% yield. Then, 8 was subjected to
scale maintaining the high selectivity of hydrogen addition from an analogous reaction sequence that was used for (+)-verbanone
the less hindered side of the molecule. (1R,2S,5R)-(+)- (3), i.e., the synthesis of the enone in the first step followed by
Verbanone (3) was obtained in 93% yield. GC analysis of 3 its 1,2-reduction to the allylic alcohol. Thus, Claisen condensa-
showed the presence of cis and trans diastereoisomers in a ratio tion of 8 with ethyl formate gave β-hydroxyenone 9, which was
of 97:3. The hydrogen-addition selectivity is consistent with subjected to transaldolization with formaldehyde producing
earlier literature reports and results from the shielding effect of the corresponding 4-methyleneisopinocamphone (10) in 83%
the gem-dimethyl bridge [21,22].
yield. Luche reduction of the latter compound provided
(1R,2R,3R,5R)-4-methyleneneoisopinocampheol (11) in 84%
yield.
Scheme 1: Synthesis of (1R,2R,4S,5R)-3-methyleneneoisoverbanol
(6).
Scheme 2: Synthesis of (1R,2R,3R,5R)-4-methyleneneoisopinocam-
pheol (11).
In the next step, 3 reacted with sodium methoxide in toluene
and the resulting enolate was condensed with ethyl formate to
give a keto-aldehyde, which tautomerized into the more stable In order to obtain two endocyclic allylic alcohols, (−)-β-pinene
β-hydroxyenone 4 [23]. The intermediate 4 was sufficiently was chosen as the starting material for this synthesis
pure for the subsequent transaldolization reaction with form- (Scheme 3). Thus, β-pinene (12) was reacted with ozone to give
2494

Beilstein J. Org. Chem. 2019, 15, 2493–2499.
(+)-nopinone (13) in 90% yield [27]. In the next step, 13 reacted
with diphenyl diselenide and selenium dioxide in methanol
[28]. The obtained phenyl selenide 14 was oxidized with hydro-
gen peroxide in the presence of pyridine to selenoxide, which
readily undergoes intramolecular syn-elimination to produce
α,β-unsaturated (+)-apoverbenone (15) [28,29]. In the next step,
Luche reduction of 15, proceeding from the less hindered side
of the carbonyl group, gave (1R,4R,5R)-apopinenol (16) in 95%
yield. GC analysis of 16 has shown the presence of the ex-
Figure 1: NOE effects in molecules 16 and 18.
pected major isomer (1R,4R,5R)-16 (92%) and the minor Synthesis of γ-hydroxyphosphines
isomer (1R,4S,5R)-18 (8%). Diastereomers 16 and 18 can be The key step in the synthesis to introduce a phosphine function-
separated by flash column chromatography on silica gel. For the ality is the thermal [2,3]-sigmatropic rearrangement of an allylic
purpose of this study, (1R,4R,5R)-apopinenol (16) was subject- diphenylphosphinite to the diphenylphosphine oxide
ed to the Mitsunobu reaction to obtain the product with inverted (Scheme 4) [16].
configuration at C4. Alcohol 16 was reacted with diisopropyl
azodicarboxylate, triphenylphosphine, and p-nitrobenzoic acid
in THF [30]. 1H NMR analysis of the crude p-nitrobenzoate 17
revealed a mixture of the predicted p-nitrobenzoate of
apopinenol 18 together with an ester of 16 in a ratio of 79:21.
Attempts to separate p-nitrobenzoates of 18 and 16 by column
chromatography on silica gel failed. The mixture of esters, after
purification, was hydrolyzed with a 5% aqueous solution of
NaOH. GC analysis of the isolated alcohol confirmed the pres-
ence of (1R,4S,5R)-apopinenol (18) and (1R,4R,5R)-16 in a
ratio of 79.5:20.5.
Scheme 4: Synthesis of (1R,2R,3R,4R,5R)-3-((diphenylphos-
phanyl)methyl)isoverbanol (23).
Diphenylphosphinite 19 was formed in the reaction of allylic
alcohol 6 with diphenylphosphine chloride in the presence of
DMAP at −20 ºC. The temperature was raised to induce phos-
phinite’s [2,3]-sigmatropic rearrangement (20) as shown in
Scheme 4. The reaction progress, conversion of 19 into 21, was
monitored by 31P NMR (ROPPh2 δ = 113 ppm; RP(O)Ph2
δ = 30 ppm). The phosphinite 19 disappeared after 48 h at
100 °C. The product was crystallized from heptane to give
phosphine oxide 21 in 92% yield. The allylic diphenylphos-
Scheme 3: Synthesis of allylic alcohols 16 and 18 from β-pinene.
phine oxide 21 was subjected to the hydroboration–oxidation
The structures and stereochemistry of both diastereomeric alco- reaction introducing stereoselectively the hydroxy group.
hols 16 and 18 were confirmed by 2D NMR spectra. All Hydroboration was carried out with an excess of
protons in 16 and 18 were assigned using 1H,1H-COSY spectra. borane–dimethyl sulfide adduct followed by the oxidation step.
The configurations at C4 were established by correlations ob- The standard C–B bond oxidation protocol (H2O2/NaOH)
served in their 1H,1H-NOESY spectra (Figure 1, Supporting proceeded with the low yield (32%). Application of m-chloro-
Information File 1).
perbenzoic acid (mCPBA) as an oxidant, similarly to
2495

Beilstein J. Org. Chem. 2019, 15, 2493–2499.
Knochels findings [19], gave the higher yield (56%) of
(((1R,2R,3R,4R,5R)-4-hydroxypinan-3-yl)methyl)diphenylphos-
phine oxide (22).
Next, phosphine oxide 22 was reduced to the phosphine with
poly(methylhydrosiloxane) in the presence of titanium(IV)
isopropoxide (Scheme 4). The work-up of the reaction mixture
with 25% HF allowed to remove silicon and titanium impuri-
ties and purification of 23 by column chromatography on silica
gel yielded the product in 62%.
4-Methyleneneoisopinocampheol (11) was subjected to the
same reaction sequence as 6 (Scheme 5). The allylphosphine
oxide 26 was obtained after [2,3]-sigmatropic rearrangement of
phosphinite 24. After purification by column chromatography
Scheme 6: Attempted sigmatropic rearrangement of phosphinites 28
and 29.
on silica gel, 26 was obtained in 78% yield. The hydroboration transformation, the thermal [2,3]-sigmatropic rearrangement of
of 26 was carried out with borane–dimethyl sulfide adduct in allyldiphenylphosphinites to allyldiphenylphosphine oxides.
THF at 50 ºC. Oxidation of the alkylborane with mCPBA gave Allylphosphine oxides were further functionalized through a
the desired alcohol 27 in 51% overall yield.
hydroboration–oxidation reaction occurring from the less
hindered side of the molecule to produce γ-hydroxyphosphine
oxide derivatives. It was also shown that phosphine oxide can
be reduced to phosphine without affecting the bicyclic pinane
structure.
The synthesis of diastereomeric endocyclic allylic alcohols
from (−)-β-pinene was also carried out. Unfortunately, due to
the probably too rigid bicyclic structure of the diphenylphos-
phinites, they did not undergo the sigmatropic rearrangement to
the corresponding phosphine oxides. Further research and appli-
cation of the obtained ligands are in progress.
Experimental
Diphenyl(((1R,2R,5S)-δ-pinen-3-
Scheme 5: Synthesis of (((1R,2R,3S,4S,5S)-3-hydroxypinan-4-
yl)methyl)diphenylphosphine oxide (27).
yl)methyl)phosphine oxide (21)
Finally, diastereomeric endocyclic allylic alcohols 16 and 18
were treated with chlorodiphenylphosphine in the presence of
DMAP to produce diphenylphosphinites 28 and 29 (31P NMR:
ROPPh2 δ = 107 ppm), respectively (Scheme 6). Attempts to
carry out a sigmatropic rearrangement in toluene at 100 ºC as
well as in xylene at 140 ºC failed. The formation of the phos-
phine oxide products was not observed by 31P NMR analysis.
The probable reason for the lack of the rearrangement reaction
may be the rigid bicyclic structure of the substrate and steric
hindrance on one side of the molecule caused by the gem-
dimethyl bridge.
Allylic alcohol 6 (0.831 g, 5 mmol) and 4-dimethylamino-
pyridine (0.645 g, 5.3 mmol) were placed in a Schlenk flask.
These compounds were dissolved in toluene (10 mL) under
nitrogen. The solution was cooled below –20 °C and
diphenylphosphine chloride (1.106 g, 5 mmol) was added drop-
wise. After the removal of the cooling bath, the solution was
stirred for 24 h at 100 °C. After this time, the 31P NMR spec-
trum has shown incomplete conversion of the substrate. Conse-
quently, heating was continued until the 31P NMR spectrum
showed complete substrate conversion (48 h). Warm toluene
(10 mL) was added to the reaction mixture and the solution was
filtered through a pad of celite. The precipitate was washed with
another portion of warm toluene (10 mL). The solvent was re-
moved using a rotary evaporator to give the phosphine oxide.
After crystallization from heptane, phosphine oxide 21 (1.612 g,
Conclusion
Regioisomeric exocyclic allylic alcohols were synthesized from
natural α-pinene. (1R,2R,4S,5R)-3-Methyleneneoisoverbanol
and (1R,2R,3R,5R)-4-methyleneneoisopinocampheol were syn-
thesized using known procedures. They were used in the key
92%) was obtained as a white solid, mp 127–131 °C,
(c 2.4, CHCl3); 1H NMR (700 MHz, CDCl3) δ 0.87 (d, J =
−98
2496

Beilstein J. Org. Chem. 2019, 15, 2493–2499.
8.5 Hz, 1H), 0.89 (s, 3H, CH3), 1.14 (d, J = 7.5 Hz, 3H, CH3), (m, 1H), 2.05–2.13 (m, 2H), 2.30–2.46 (m, 3H), 2.54–2.61 (m,
1.20 (s, 3H, CH3), 1.95–1.96 (m, 2H), 2.23 (dt, J = 8.4, 5.6 Hz, 1H), 4.02 (d, J = 4.2 Hz, 1H), 7.46–7.58 (m, 6H), 7.74–7.82 (m,
1H), 2.56 (s, 1H), 3.08–3.12 (m, 1H), 3.20–3.25 (m, 1H), 5.97 4H); 13C NMR (100 MHz, CDCl3) δ 16.84, 23.18, 25.39, 27.79,
(s, 1H), 7.45–7.48 (m, 4H), 7.49–7.53 (m, 2H), 7.76–7.80 (m, 32.13 (d, J = 69.1 Hz), 36.32 (d, J = 12.7 Hz), 37.52 (d, J =
4H); 13C NMR (100 MHz, CDCl3) δ 16.78 (d, J = 1.6 Hz), 4.0 Hz), 39.48, 47.36, 48.80, 75.87, 128.74 (d, J = 9.5 Hz),
23.73, 27.11, 33.52, 34.29 (d, J = 4.0 Hz), 38.22 (d, J = 4 Hz), 128.86 (d, J = 10.3 Hz), 130.45 (d, J = 9.5 Hz), 131.08 (d, J =
42.30 (d, J = 5.6 Hz), 42.31, 48.33, 128.33 (d, J = 11.9 Hz), 8.7 Hz), 131.22 (d, J = 97.7 Hz), 131.91 (d, J = 3.2 Hz) 131.94
128.51 (d, J = 11.9 Hz), 129.09, 129.19, 130.84 (d, J = 9.5 Hz), (d, J = 3.2 Hz), 133.40 (d, J = 100.9 Hz); 31P NMR (162 MHz,
131.23 (d, J = 8.7 Hz), 131.60 (d, J = 8.7 Hz), 131.64 (d, J = CDCl3) δ 37.62; anal. calcd for C23H29O2P: C, 74.98; H, 7.93;
9.0 Hz), 135.87 (d, J = 8.0 Hz), 135.90 (d, J = 9.5 Hz); found: C, 74.67; H, 8.07.
31P NMR (162 MHz, CDCl3) δ 31.76; anal. calcd for
C23H27OP: C, 78.83; H, 7.77; found: C, 78.73; H, 7.61.
(1R,2R,3R,4R,5R)-3-((Diphenylphos-
phanyl)methyl)isoverbanol (23)
(((1R,2R,3R,4R,5R)-4-Hydroxypinan-3-
yl)methyl)diphenylphosphine oxide (22)
Phosphine oxide 22 (0.221 g, 0.6 mmol) was dissolved in dry
toluene (2 mL) in a Schlenk flask under nitrogen. Then,
Phosphine oxide 21 (1.402 g, 4 mmol) was dissolved in THF poly(methylhydrosiloxane) (PMHS, 0.3 mL) and titanium(IV)
(13 mL) under nitrogen. BMS (10 M, 0.8 mL, 8 mmol) was isopropoxide (0.672 g, 0.7 mL, 2.4 mmol) were added drop-
added dropwise to the reaction mixture. The mixture was stirred wise to the solution. The reaction mixture was stirred for 24 h at
for 24 h at 50 °C. After this time, the solution was cooled to 100 °C, cooled, and poured into a solution of 48% hydrofluoric
room temperature and methanol (6 mL) was carefully added acid (3.6 mL) and water (3 mL). The mixture was stirred
until the gas evolution ceased. Solvents were removed using a overnight and the layers were separated. The aqueous layer was
rotary evaporator and the resulting intermediate was dissolved extracted with toluene (2 × 10 mL). The combined organic
in dichloromethane (6 mL). meta-Chloroperbenzoic acid (75%, layers were washed with 5% sodium bicarbonate (5 mL) and
2.301 g, 10 mmol) was dissolved in dichloromethane (10 mL), brine (5 mL). After drying the solution with anhydrous magne-
cooled in a dry ice–acetone bath, and the intermediate solution sium sulfate and filtration, the solvent was evaporated and the
was added dropwise. After 3 h, the mixture was filtered, 10% product was purified by flash chromatography on silica gel
sodium metabisulphite (15 mL) was added to the filtrate, and (hexane/ethyl acetate 80:20). Phosphine 23 (0.131 g, 62%) was
the mixture was stirred for 10 min. The layers were separated, obtained as a colorless oil. 1H NMR (700 MHz, CDCl3) δ 0.93
the organic layer was washed with 1 M NaOH (2 × 15 mL), (s, 3H, CH3), 1.14 (d, J = 7.7 Hz, 3H, CH3), 1.23 (s, 3H, CH3),
brine (10 mL), and dried over anhydrous magnesium sulfate. 1.38 (d, J = 10.1 Hz, 1H), 1.92–1.96 (m, 1H), 1.98 (m, 1H),
The solution was filtered, the solvent evaporated on a rotary 2.06–2.12 (m, 2H), 2.28–2.33 (m, 1H), 2.36–2.40 (m, 1H),
evaporator and the product was purified by flash chromatogra- 2.41–2.47 (m, 1H), 4.03 (d, J = 6.2 Hz, 1H), 7.33–7.39 (m, 6H),
phy on silica gel (dichloromethane/diethyl ether 10:90). Phos- 7.46–7.51 (m, 4H); 13C NMR (176 MHz, CDCl3) δ 16.35 (d,
phine oxide 22 (0.825 g, 56%) was obtained as an oil.
J = 3.5 Hz), 23.02, 25.07, 27.97, 30.17 (d, J = 11.8 Hz), 35.34
(d, J = 6.9 Hz), 39.04 (d, J = 11.1 Hz), 39.80, 48.09, 48.88,
In a second oxidation procedure, methanol (5 mL) and a 3 M 77.23, 128.49 (d, J = 6.9 Hz), 128.50 (d, J = 6.9 Hz), 128.70,
solution of sodium hydroxide (2.7 mL, 8.1 mmol) were care- 128.75, 128.88 (d, J = 11.8 Hz), 132.73 (d, J = 18.0 Hz), 132.81
fully added. After cooling to 0 °C, a 30% solution of hydrogen (d, J = 18.0 Hz), 138.14 (d, J = 9.0 Hz); 31P NMR (283.5 MHz,
peroxide (1.2 mL, 12 mmol) was added dropwise to the reac- CDCl3) δ −18.78; anal. calcd for C23H29OP: C, 78.38; H, 8.29;
tion mixture. The solution was stirred for 30 minutes at rt and found: C, 78.55; H, 8.34.
1 h at 50 °C. After this time, potassium carbonate was added to
saturate the solution. The layers were separated and the aqueous
Diphenyl (((1R,2S,5R)-δ-pinen-4-
layer was extracted with diethyl ether (2 × 20 mL). The yl)methyl)phosphine oxide (26)
combined organic layers were washed with brine (15 mL), dried Unsaturated phosphine oxide 26 was obtained applying the pro-
with anhydrous magnesium sulfate, filtered and the solvents cedure described for 21. Allylic alcohol 11 (0.333 g, 2 mmol),
were removed using a rotary evaporator. The product was puri- DMAP (0.280 g, 2,3 mmol), diphenylphosphine chloride
fied by column chromatography on silica gel (dichloromethane/ (0.441 g, 2 mmol), and toluene (5 mL) were used for the reac-
diethyl ether 10:90). 22 (0.472 g, 32%) was isolated as a white tion. The crude product was purified on silica gel (eluent:
solid (mp 179–183 °C,
(400 MHz, CDCl3) δ 0.91 (s, 3H, CH3), 1.05 (d, J = 7.3 Hz, 3H, mp 62–66 °C,
−39 (c 3.0, CHCl3); 1H NMR dichloromethane/diethyl ether 10:90) to give 26 (0.547 g, 78%),
−14 (c 2.0, CHCl3); 1H NMR (700 MHz,
CH3), 1.22 (s, 3H, CH3), 1.38 (d, J = 9.3 Hz, 1H), 1.87–1.93 CDCl3) δ 0.71 (s, 3H, CH3), 0.78 (d, J = 7.1 Hz, 3H, CH3), 0.87
2497

Beilstein J. Org. Chem. 2019, 15, 2493–2499.
ORCID® iDs
(d, J = 9.0 Hz, 1H), 1.18 (s, 3H, CH3), 1.71 (m, 1H), 2.06 (dt,
J = 9.0 Hz, 5.6 Hz, 1H), 2.20 (td, J = 5.5, 1.4 Hz, 1H), 2.30 (m,
1H), 3.03–3.13 (m, 2H), 5.16 (m, 1H), 7.42–7.46 (m, 4H),
7.47–7.51 (m, 2H), 7.72–7.78 (m, 4H); 13C NMR (176 MHz,
CDCl3) δ 18.22 (d, J = 4.2 Hz) 20.59, 26.31, 27.60 (d, J = 2.1),
34.73 (d, J = 2.1 Hz), 38.91 (d, J = 68.0 Hz), 40.94 (d, J =
1.4 Hz), 46.41, 47.73 (d, J = 2.8 Hz), 128.27 (d, J = 11.8 Hz),
128.44 (d, J = 11.8 Hz), 128.83 (d, J = 11.8 Hz), 130.87 (d, J =
9.0 Hz), 131.17 (d, J = 9.0 Hz), 131.49 (d, J = 2.8 Hz), 131.54
(d, J = 2.1 Hz), 132.95 (d, J = 97.8 Hz), 133.70 (d, J =
96.4 Hz), 137.43 (d, J = 10.4 Hz); 31P NMR (283.5 MHz,
CDCl3) δ 29.93; anal. calcd for C23H27OP: C, 78.83; H, 7.77;
found: C, 78.97; H, 7.51.
Anna Kmieciak - https://orcid.org/0000-0003-0002-0338
Marek P. Krzemiński - https://orcid.org/0000-0002-4337-5676
References
1. Börner, A., Ed. Phosphorus Ligands in Asymmetric Catalysis:
Synthesis and Applications; Wiley-VCH: Weinheim, Germany, 2008.
2. Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds. Comprehensive
Asymmetric Catalysis, and Supplements 1 and 2; Springer-Verlag:
Berlin, Germany, 2004.
3. Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029–3070.
doi:10.1021/cr020049i
4. Chen, X.-S.; Hou, C.-J.; Hu, X.-P. Synth. Commun. 2016, 46, 917–941.
doi:10.1080/00397911.2016.1171362
5. Hoyt, J. M.; Shevlin, M.; Margulieux, G. W.; Krska, S. W.; Tudge, M. T.;
Chirik, P. J. Organometallics 2014, 33, 5781–5790.
doi:10.1021/om500329q
(((1R,2R,3S,4S,5S)-3-Hydroxypinan-4-
yl)methyl)diphenylphosphine oxide (27)
6. Padevět, J.; Schrems, M. G.; Scheil, R.; Pfaltz, A.
Beilstein J. Org. Chem. 2016, 12, 1185–1195. doi:10.3762/bjoc.12.114
7. Chen, Y.-R.; Duan, W.-L. Org. Lett. 2011, 13, 5824–5826.
doi:10.1021/ol2024339
8. Guerrero Rios, I.; Rosas-Hernandez, A.; Martin, E. Molecules 2011, 16,
970–1010. doi:10.3390/molecules16010970
9. Zhong, F.; Luo, J.; Chen, G.-Y.; Dou, X.; Lu, Y. J. Am. Chem. Soc.
2012, 134, 10222–10227. doi:10.1021/ja303115m
10.Wei, Y.; Shi, M. Acc. Chem. Res. 2010, 43, 1005–1018.
doi:10.1021/ar900271g
11.Xiao, Y.; Sun, Z.; Guo, H.; Kwon, O. Beilstein J. Org. Chem. 2014, 10,
2089–2121. doi:10.3762/bjoc.10.218
12.Wang, T.; Han, X.; Zhong, F.; Yao, W.; Lu, Y. Acc. Chem. Res. 2016,
49, 1369–1378. doi:10.1021/acs.accounts.6b00163
13.Wauters, I.; Debrouwer, W.; Stevens, C. V. Beilstein J. Org. Chem.
2014, 10, 1064–1096. doi:10.3762/bjoc.10.106
14.Tappe, F. M. J.; Trepohl, V. T.; Oestreich, M. Synthesis 2010,
3037–3062. doi:10.1055/s-0030-1257960
15.Jaklińska, M.; Cordier, M.; Stankevič, M. J. Org. Chem. 2016, 81,
1378–1390. doi:10.1021/acs.joc.5b02337
16.Demay, S.; Volant, F.; Knochel, P. Angew. Chem., Int. Ed. 2001, 40,
1235–1238.
Hydroboration–oxidation of 26 was carried out according to the
procedure described for 22. Unsaturated phosphine oxide 26
(0.350 g, 1 mmol) and BMS (0.2 mL, 10 M, 2 mmol) were used
in the hydroboration reaction. meta-Chloroperbenzoic acid
(75%, 0.575 g, 2.5 mmol) was used in the oxidation reaction.
The product was purified on silica gel (eluent: dichloromethane/
diethyl ether 50:50) to give 27 (0.188 g, 51%). 1H NMR
(400 MHz, CDCl3) δ 0.99 (s, 3H, CH3), 1.04 (d, J = 7.1 Hz, 3H,
CH3), 1.12 (d, J = 10.3 Hz, 1H), 1.21 (s, 3H, CH3), 1.72–1.80
(m, 2H), 2.08–2.20 (m, 2H), 2.31 (ddd, J = 15.2, 7.5, 1.8 Hz,
1H), 2.50–2.63 (m, 2H), 4,33 (dd, J = 9.8, 4.9 Hz, 1H),
7.43–7.56 (m, 6H), 7.69–7.79 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 14.23, 23.27, 27.67, 29.54, 35.36, 37.56 (d, J =
69.1 Hz), 39.22, 48.38 (d, J = 3.2 Hz), 49.03, 49.76 (d, J =
13.5 Hz), 71.47 (d, J = 1.6 Hz), 128.71 (d, J = 5.6 Hz), 128.82
(d, J = 5.6 Hz), 130.39 (d, J = 9.5 Hz), 131.10 (d, J = 9.5 Hz),
131.61 (d, J = 98.6 Hz), 131.82 (d, J = 3.2 Hz), 131.88 (d, J =
2.4 Hz), 133.61 (d, J = 100.1 Hz); 31P NMR (162 MHz, CDCl3)
δ 36.03; anal. calcd for C23H29O2P: C, 74.98; H, 7.93; found:
C, 75.08; H, 7.77.
doi:10.1002/1521-3773(20010401)40:7<1235::aid-anie1235>3.0.co;2-y
17.Boyd, D. R.; Bell, M.; Dunne, K. S.; Kelly, B.; Stevenson, P. J.;
Malone, J. F.; Allen, C. C. R. Org. Biomol. Chem. 2012, 10,
1388–1395. doi:10.1039/c1ob06599h
18.Kmieciak, A.; Krzemiński, M. P. Tetrahedron: Asymmetry 2017, 28,
467–472. doi:10.1016/j.tetasy.2017.02.003
Supporting Information
19.Gavryushin, A.; Polborn, K.; Knochel, P. Tetrahedron: Asymmetry
2004, 15, 2279–2288. doi:10.1016/j.tetasy.2004.05.045
20.Sivik, M. R.; Stanton, K. J.; Paquette, L. A. Org. Synth. 1995, 72,
57–59. doi:10.15227/orgsyn.072.0057
21.Regan, A. F. Tetrahedron 1969, 25, 3801–3805.
doi:10.1016/s0040-4020(01)82913-6
22.Konopelski, J. P.; Sundararaman, P.; Barth, G.; Djerassi, C.
J. Am. Chem. Soc. 1980, 102, 2737–2745. doi:10.1021/ja00528a036
23.Malkov, A. V.; Pernazza, D.; Bell, M.; Bella, M.; Massa, A.; Teplý, F.;
Meghani, P.; Kočovský, P. J. Org. Chem. 2003, 68, 4727–4742.
doi:10.1021/jo034179i
Supporting Information File 1
General information, experimental procedures and
characterization data of the following compounds: 2, 3,
5–8, 10, 11, and 14–18.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-15-242-S1.pdf]
Acknowledgements
We wish to thank for the financial support received from
National Science Centre, grant Preludium 4 No. 2012/07/N/
ST5/02194.
24.Gemal, A. L.; Luche, J. L. J. Am. Chem. Soc. 1981, 103, 5454–5459.
doi:10.1021/ja00408a029
2498

Beilstein J. Org. Chem. 2019, 15, 2493–2499.
25.Brown, H. C.; Singaram, B. J. Org. Chem. 1984, 49, 945–947.
doi:10.1021/jo00179a041
26.Brown, H. C.; Garg, C. P.; Liu, K.-T. J. Org. Chem. 1971, 36, 387–390.
doi:10.1021/jo00802a005
27.Binder, C. M.; Bautista, A.; Zaidlewicz, M.; Krzemiński, M. P.;
Oliver, A.; Singaram, B. J. Org. Chem. 2009, 74, 2337–2343.
doi:10.1021/jo802371z
28.Kawashima, H.; Kaneko, Y.; Sakai, M.; Kobayashi, Y. Chem. – Eur. J.
2014, 20, 272–278. doi:10.1002/chem.201303538
29.Reich, H. J.; Wollowitz, S. Org. React. 1993, 44, 1–296.
doi:10.1002/0471264180.or044.01
30.Dodge, J. A.; Nissen, J. S.; Presnell, M. Org. Synth. 1996, 73,
110–113. doi:10.15227/orgsyn.073.0110
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0). Please note
that the reuse, redistribution and reproduction in particular
requires that the authors and source are credited.
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(https://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.15.242
2499