Nucleophilic additions on acetyldioxanes derived from (?)-(1R)-myrtenal used as chiral auxiliaries: substituent effects on the stereochemical outcome

Article abstract of DOI:10.1016/j.tetasy.2017.07.008

The synthesis of acetyldioxanes 4 and 9a starting from (?)-(1R)-myrtenal is described. The products were treated with a representative series of nucleophilic reagents (RMgX, RLi, NaBH₄ and LiAlH₄) to assess the effect of the substituent at C-3 on the stereochemical outcome. It was observed that the nucleophiles preferred the re-face of the C[dbnd]O group when the equatorial substituent at C-3 was a methyl group, whereas a phenyl group at the same position induced the addition through the si-face, thus allowing access to either desired stereochemistry of a final product. This behavior suggests that the formation of the expected Cram-chelated coordination complex takes a coplanar orientation with the C-3 equatorial substituent. Moreover, Grignard reagents were the most stereoselective nucleophiles. The stereochemistry of the addition was established by X-ray diffraction and chemical correlation.

Full text of DOI:10.1016/j.tetasy.2017.07.008

Tetrahedron: Asymmetry xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Nucleophilic additions on acetyldioxanes derived from (ꢀ)-(1R)-
myrtenal used as chiral auxiliaries: substituent effects on the
stereochemical outcome
a
b
c
d
Elvia Becerra-Martínez , Francisco Ayala-Mata , Pedro Velázquez-Ponce , Manuel E. Medina ,
b
e
b,
⇑
Hugo A. Jiménez-Vazquez , Pedro Joseph-Nathan , L. Gerardo Zepeda
a
Centro de Nanociencias y Micro y Nanotecnologías, Instituto Politécnico Nacional, Prol. de Carpio y Plan de Ayala, México City 11340, Mexico
Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. de Carpio y Plan de Ayala, México City 11340, Mexico
Departamento de Química, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara, Jal. 44430, Mexico
Centro de Investigaciones Biomédicas, Universidad Veracruzana, Xalapa, Ver. 91190, Mexico
b
c
d
e
Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado 14-740, México City 07000, Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of acetyldioxanes 4 and 9a starting from (ꢀ)-(1R)-myrtenal is described. The products were
Received 10 July 2017
Accepted 20 July 2017
Available online xxxx
4 4
treated with a representative series of nucleophilic reagents (RMgX, RLi, NaBH and LiAlH ) to assess the
effect of the substituent at C-3 on the stereochemical outcome. It was observed that the nucleophiles pre-
ferred the re-face of the C@O group when the equatorial substituent at C-3 was a methyl group, whereas a
phenyl group at the same position induced the addition through the si-face, thus allowing access to either
desired stereochemistry of a final product. This behavior suggests that the formation of the expected
Cram-chelated coordination complex takes a coplanar orientation with the C-3 equatorial substituent.
Moreover, Grignard reagents were the most stereoselective nucleophiles. The stereochemistry of the
addition was established by X-ray diffraction and chemical correlation.
Dedicated to the memory of Dr. Howard
Flack
Ó 2017 Elsevier Ltd. All rights reserved.
1
. Introduction
Despite the great progress that organocatalysis has shown in
carbinols 6a:6b and 5a:5b, respectively. In turn, acyldioxanes 3
and 4, both bearing an equatorial methyl group at C-3, gave
adducts 7a:7b and 8a:8b, respectively, thus displaying lower
diastereoselectivity than that shown by acyldioxanes 1 and 2
1
–3
recent years,
chiral auxiliaries are still a very effective and
4
,5
6d
widely used tool to prepare non-racemic chiral compounds. In
(Scheme 1). These results clearly showed that an equatorial
this context, we have already described the synthesis of several
substituent at C-3 plays a crucial role in the diastereofacial
nucleophilic additions. It should be noted that in both
acyldioxanes, the nucleophilic additions took place mainly onto
the re-face of the carbonyl group.
Encouraged by these results, we herein extend the assessment
of diastereoselective additions of organometallic reagents on
acetyldioxanes 4 and 9a. Acetyldioxane 9a bears an equatorial phe-
nyl group at C-3 instead of the equatorial methyl group found in
acyldioxanes 3 and 4, and thus allows insight into the influence
of the substituent at this position on the stereochemical control
of the nucleophilic additions.
chiral auxiliary derivatives of (–)-(1R)-myrtenal,6
a–d
which have
proven to be particularly useful for the preparation of chiral
a-
hydroxycarbonyl and 1,2-diol derivatives in high diastereomeric
ratios. Among these, 3-substituted-5-acyl-4,6-dioxanes 1–4 are
noteworthy since they showed a clear dependence of both the
nature and position of the substituent at C-3 on their ability to
induce diastereoselective nucleophilic additions when using
6
d
organometallic reagents (Scheme 1).
It was demonstrated6 that an axial substituent at C-3 in
acyldioxane 2 does not affect the stereochemical course of the
nucleophilic addition, thus yielding practically the same
diastereomeric ratio (dr) as when using acyldioxane 1,
unsubstituted at the C-3 position, as can be observed through
d
2
. Results and discussion
The synthesis of 4 was achieved according to the procedure
6
d
described by Becerra et al., while preparation of acetyldioxane
a was done following a similar procedure (Scheme 2).
⇑
Corresponding author.
E-mail address: lzepeda@woodward.encb.ipn.mx (L.G. Zepeda).
9
https://doi.org/10.1016/j.tetasy.2017.07.008
957-4166/Ó 2017 Elsevier Ltd. All rights reserved.
0
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2
E. Becerra-Martínez et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
R1
R1
R1
5
8
O
PhMgBr
O
+
O
3
O
O
O
1
R2
Ph OH
HO Ph
O
R2
R2
1
1
: R = R2 = H
5a:5b (89:11)
6a:6b (88:12)
7a:7b (67:33)
1
2
2
3
4
: R = Me, R = H
1
2
: R = H, R = Me
8a:8b (77:23)
1
2
: R = R = Me
Scheme 1.
1
2
) PhMgBr
) BH /H
R1
OH
R1
1) column chromatog.
3
2
O
2
O
O
H
OH
2)
O
R2
O
R2
O
MeO
1
9a:
R
1
= H, R2 = Ph (74%)
= Ph, R = H (not formed)
1
1
0a: R = H, R2 = Ph
(1R)-(-)-myrtenal
1
2
OMe
9b: R
1
2
0b: R = Ph, R = H
0a:10b (1:2)
91%)
1
(
Scheme 2.
Thus, treatment of (ꢀ)-(1R)-myrtenal with PhMgBr in THF gave
an epimeric mixture of 10-phenylmyrtenols in 98% yield, which
without further purification was immediately treated with BH
to afford an epimeric mixture of 3,10-pinanediols 10a:10b
1:2, 91%). This mixture was separated by column chromatography
to yield the corresponding epimeric diols 10a and 10b. Pinanediol
0a was reacted with piruvaldehyde dimethyl acetal in benzene,
using p-TsOH as the catalyst at ꢀ78 °C for 8 h, to afford acetyldiox-
ane 9a in 74% yield. In contrast, pinanediol 10b did not yield
acetyldioxane 9b when treated under the protocol used for the
preparation of 9a, most likely due to the strong 1,3-diaxial interac-
tion between the phenyl group at C-3 and the hydrogen atoms at
C-5 and C-7, which would be present in the latter acetyldioxane.
The single crystal X-ray diffraction PLUTO projection of pinanediol
mation on the key factors controlling the stereochemical course of
the reaction; the results obtained with acetyldioxane 4 are sum-
marized in Table 1. As can be observed, nucleophilic additions pro-
ceeded in good to excellent chemical yields. Regarding the
stereoselectivity, the additions of EtMgBr and PhMgBr exhibited
the best diastereoisomeric ratios (entries 1 and 4), followed by
3
/
2 2
H O
(
1
the additions of H
respectively). In contrast, the addition of CH
showed the same behavior as that observed in the reactions with
LiAlH , NaBH and PhLi (entries 7, 8 and 9) where no stereoselec-
2
C@CHMgBr and i-PrMgBr (entries 5 and 2,
3
C„CMgBr (entry 6)
4
4
tivity was observed. The absence of stereoselectivity in entry 6 is
likely due to the minimal steric interactions between the nucle-
ophile possessing a rod-like geometry and the methyl group at
C-3. Under these circumstances, coordination could occur between
1
0b is shown in Figure 1.
3
CH C„CMgBr, the carbonyl group and either oxygen of the diox-
ane ring, and therefore the incoming nucleophile could attack
either from the re- or the si-face of the carbonyl group.
The nucleophilic additions using acyldioxane 9a are summa-
rized in Table 2. As can be observed, the preparation of carbinol
series 13 and 14 generally proceeded very well. Regarding the
stereoselectivity, the obtained carbinols showed inverse diastere-
omeric ratios as compared to the acyldioxanes previously
6
d
described,
since the nucheophilic attack mainly proceeded
through the si-face of the C@O group, thus clearly showing
strong evidence that in this case, the phenyl group at C-3
modulates the stereochemical course of the nucleophiles. The
stereoselectivity order is very similar to those shown by
acyloxathianes and acyldioxanes, in which Grignard reagents are
the most stereoselective, followed by lithium alkyls, with
6
a–c
hydrides being the least stereoselective ones.
Thus, the
aliphatic Grignard reagents (entries 1 and 2) furnished only one
diastereoisomer, whereas the remaining Grignard reagents
showed good stereoselectivity (entries 3–6). Furthermore, the
diastereoselectivities of organolithium reagents, such as PhLi and
EtLi (entries 7 and 8), were significantly lower in comparison to
those of their Grignard reagent counterparts (entries 6 and 1,
respectively), but higher than the adduct obtained after addition
of PhLi to acyldioxane 4 (entry 9, Table 1). In cases where the
Figure 1. Single crystal X-ray PLUTO plot of pinanediol 10b.
The stereochemical arrangement of acetyldioxane 9a was cor-
roborated by nOe difference experiments, in which the acetyl and
phenyl groups were shown to have the equatorial configuration,
1
since the respective H NMR signals H-3ax (5.4%) and H-7
4 4
reduction was carried out using LiAlH and NaBH (entry 9–10),
(
10.2%) were enhanced upon irradiation of the H-5 acetal
hydrogen.
With acetyldioxanes 4 and 9a in hand, they were then subjected
to a representative series of nucleophilic additions to gather infor-
the reactions showed lack of diastereoselectivity, similar to that
observed in acyloxathianes and acyldioxanes.
The course of the addition of nucleophiles to acyldioxanes can
be explained by considering a Cram-type chelated transition state
6
a–d
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E. Becerra-Martínez et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
3
Table 1
Chemical yields and diastereomeric ratios of carbinols 11:12 obtained by the addition of organometallic reagents to acetyldioxane 4
O
RM
O
+
O
O
O
R
OH
O
HO
R
O
4
11
12
Entry
RM
R
Yield (%)a
Ratiob (11:12)
1
2
3
4
5
6
7
8
9
EtMgBr
Et
75
80
89
90
96
93
94
95
92
84:16 (11a:12a)
62:38 (11b:12b)
60:40 (11c:12c)
77:23 (11d:12d)
65:35 (11e:12e)
50:50 (11f:12f)
50:50 (11g:12g)
50:50 (11g:12g)
50:50 (11d:12d)
i-PrMgBr
i-BuMgBr
PhMgBr
i-Pr
i-Bu
Ph
H
2
C@CHMgBr
CH C„CMgBr
LiAlH
H
H
H
H
2
C@CH
CC„C
3
3
4
NaBH
PhLi
4
Ph
a
Estimated, after column chromatography purification, as a 11 and 12 mixture.
b
Determined by 1H NMR integration of H-5 in the crude reaction mixture.
Table 2
Chemical yields and diastereomeric ratios of carbinols 13:14 obtained by the addition of organometallic reagents to acetyldioxane 9a
O
RM
O
O
+
O
O
O
HO
O
R
OH
R
Ph
Ph
Ph
9a
13
14
Entry
RM
R
Yield (%)a
Ratiob (13:14)
1
2
3
4
5
6
7
8
9
EtMgBr
BuMgBr
i-PrMgBr
Et
Bu
i-Pr
95
90
88
96
89
84
78
95
98
96
01:>99 (13a:14a)
01:>99 (13b:14b)
17:83 (13c:14c)
13:87 (13d:14d)
15:85 (13e:14e)
07:93 (13f:14f)
30:70 (13f:14f)
38:62 (13a:14a)
50:50 (13g:14g)
50:50 (13g:14g)
H
2
C@CHMgBr
H
H
2
C@CH
CC„C
CH C„CMgBr
3
3
PhMgBr
PhLi
EtLi
Ph
Ph
Et
H
LiAlH
NaBH
4
1
0
4
H
a
Estimated after column chromatography purification of the 13 and 14 mixture.
b
Determined by 1H NMR integration of H-5 of the crude reaction mixture.
TS),7 as proposed for acyldioxane 4 through TS-A(Me)6 d and by
tiomer}, and (ꢀ)-(R)-16b [
a
]
23
= ꢀ5.0 (c 1.02, EtOH), {literature
10
(
8
23
Bailey et al. In acetyldioxane 9a, the metal prefers to be coordi-
nated with the carbonyl group and O-6 (TS-B) away from the phe-
nyl group (Fig. 2), avoiding coordination with O-4 due to the steric
hindrance as is shown in TS-A(Ph). With this feature in hand, it is
possible to argue that the methyl or hydrogen at C-3 does not exert
a significant steric factor, as compared to the phenyl group, to
avoid coordination between the metal and O-4, TS-A(Me), particu-
larly with Grignard reagents. The lack of diastereoselectivity
[a
]
D
= ꢀ5.8 (c 0.12, EtOH)} as the major enantiomers.
Additional evidence for the stereochemical outcome of the
nucleophilic additions was obtained from the X-ray structure of
the major diastereoisomer formed by the addition of EtMgBr to
acyldioxane 9a, in which the (S) configuration at the new carbinol
center can be observed, thus revealing that the nucleophile was
added from the si-face of the carbonyl group (Fig. 3).
4 4
shown by RLi, LiAlH and NaBH is in agreement with the well-
known low affinity to form chelated complexes.
3
. Conclusion
The diastereofacial preference of the nucleophile was confirmed
by hydrolyzing the epimeric mixtures of carbinols 13b:14b and
The already known series of carbinol derivatives 11:12 pre-
pared from acyldioxane 4 has been expanded. Furthermore, the
preparation of the new 3-phenyl-5-acetyldioxane 9a allowed us
to gain insight on the reactivity of acyldioxane systems derived
from (ꢀ)-(1R)-myrtenal, thus providing new alternatives to control
the stereochemical outcome. In comparison with acetyldioxane 4,
nucleophilic additions carried out on 9a using Grignard reagents
showed higher diastereoselectivity, even when organolithium
reagents were used. Based on diols obtained by hydrolysis of
1
3f:14f, obtained by the addition of BuMgBr and PhMgBr, respec-
tively (Table 2; entries 1 and 6), with p-TsOH. The hydrolysis pro-
vided the corresponding -hydroxyaldehydes 15a and 15b, which
were easily reduced to the more stable 1,2-diols (Scheme 3) using
NaBH . Subsequently, the crude reaction outcome was separated
by column chromatography to give (ꢀ)-(S)-16a [
a
4
2
3
a]
D
= ꢀ3.1 (c
9
23
1
.27, CHCl ), {literature [a] = +4.4 (c 1.0, CHCl ) for the (R)-enan-
3 D 3
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4
E. Becerra-Martínez et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
3
3
Me
3
R
R
O
O
6
R
6
O
O
4
O
O
Mg
Me
Mg
Mg
O
Me
O
Me
TS-B
O
X
X
X
TS-A(Me)
TS-A(Ph)
Figure 2. Cram-type chelated transition states, TS-A(Me), TS-A(Ph) and TS-B showing coordination sites of Grignard reagents on acetyldioxanes 4 and 9a. It can be observed
that while TS-A(Me) is favored for acetyldioxane 4ß the similar arrangement TS-A(Ph) is disfavored for 9a. TS-B shows the favored si face attack on the carbonyl group for
acetyldioxane 9a.
Spectrum 2000 spectrophotometer. H and 13C NMR spectra were
1
O
TsOH
3
LiAlH
4
3
recorded on a Varian Mercury 300 spectrometer using CDCl solu-
O
H
HO
O
CH CN/
tions with TMS as the internal standard. Chemical shifts are
anh. Et
2
O
HO
R
R
Ph
HO
R
reported in parts per million (d) downfield from TMS for 1H and
2
H O
HO
3
relative to the central line of the triplet of CDCl at 77.00 ppm for
1
4b: R = Bu
4f: R = Ph
15a: R = Bu
15b: R = Ph
(-)-16a : R = Bu
(-)-16b : R = Ph
13
C. The low-resolution mass spectra (LRMS) were recorded on a
Varian Saturn 2000 GC/Ion Trap Detector, using either EI (70 eV)
or CI, as specified. The high-resolution electron impact mass spec-
tra (HREIMS) were recorded on a VG 7070 high-resolution mass
spectrometer at the UCR Mass Spectrometry Facility, University
of California, Riverside, CA. Thin-layer chromatograms were done
on precoated TLC sheets of silica gel 60 F254 (E. Merck). Flash chro-
matography was carried out using Merck silica gel (230–400
mesh). THF used in the nucleophilic addition reactions was dis-
tilled from Na immediately prior to use, while all other reagents
were used as received.
1
Scheme 3. Hydrolysis of the epimeric mixtures of carbinols 13b:14b and 13f:14f to
be correlated with 1,2-diols (ꢀ)-(S)-16a and (ꢀ)-(S)-16b, respectively, of known
absolute configuration (For simplicity, only the major stereoisomers are shown).
carbinols 13:14 and X-ray data of diastereoisomer 14a, nucle-
ophilic attacks on 9a took place on the si-face of the carbonyl
group, giving the opposite absolute configuration at the carbinol
center as compared with the same center formed in the 11:12 ser-
ies. It is noteworthy that hydrolysis of carbinolic dioxanes 11–14
proceeds under milder reaction conditions than the structural ana-
logues carbinolic oxathianes.6
a–d
Thus, the present results provide
4
.2. General procedure for the addition of Grignard reagents to
acyldioxanes 4 and 9a
the possibility to obtain either enantiomers of chiral 1,2-diols with
good to excellent stereoselectivities via a chiral auxiliary protocol,
using either acyldioxanes 1 or 9a, according to the desired
stereochemistry at the carbinol center. In some cases, it also
avoids the use of odourous sulfur molecules required for the
preparation of oxathianes.
4
.2.1. Method 1
To a solution of acetyldioxanes 4 or 9a (1 equiv) in anhydrous
THF, the Grignard reagent (3 equiv) was added at ꢀ78 °C under
an N atmosphere. After stirring for 3 h at the same temperature,
2
the reaction mixture was allowed to warm up to the room temper-
ature and then stirred for 1 h. The reaction mixture was quenched
with 10 mL of a saturated solution of ammonium chloride; the THF
was eliminated by evaporation under reduced pressure, and the
remaining emulsion was extracted with ethyl ether. The organic
layer was washed with a saturated solution of ammonium chlo-
ride, dried over anhydrous Na SO , filtered, and evaporated to dry-
2 4
ness to give the corresponding mixture of carbinols as colorless
oils. Column chromatography separation was unsuccessful due to
f
the very similar R of the diastereoisomers in the mixture and
therefore specific rotations are not reported. Only the spectro-
scopic data of the major diastereoisomers 11a-g and 14a-g,
obtained from the spectra of the corresponding mixture, are
described.
4
.2.2. Method 2
Into an oven-dried two-necked 100 mL round-bottom flask
equipped with a magnetic stirring bar were added magnesium
3 equiv) and the alkyl halide (3 equiv) in 10 mL of anhydrous
THF. The resulting mixture was stirred at room temperature for
0 min. The mixture was then cooled to ꢀ78 °C and a solution of
(
Figure 3. Single crystal X-ray PLUTO plot of 14a.
3
acetyldioxane 4 or 9a (1 equiv) in 5 mL of anhydrous ether was
added and stirring was continued at the same temperature for a
further 3 h. The reaction mixture was quenched with 10 mL of a
saturated solution of ammonium chloride, the THF was eliminated
by evaporation under reduced pressure, and the remaining emul-
sion was extracted with ethyl ether. The organic layer was washed
with a saturated solution of ammonium chloride, dried over anhy-
4
4
. Experimental
.1. General
Melting points were determined on an Electrothermal capillary
melting point apparatus and are uncorrected. Optical rotations
were measured at 589 nm using a 1 dm cell on a JASCO DIP-370
polarimeter. Infrared spectra were recorded on a Perkin–Elmer
2 4
drous Na SO , filtered, and evaporated to give the corresponding
mixture of carbinols as colorless oils.
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E. Becerra-Martínez et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
5
0
0
0
0
0
0
4
.3. (1S,2R,5R,7S,9R,1 R)-5-(2 -Hydroxybut-2 -yl)-3,3,10,10-tetra-
25.6 (C-12), 25.2 (C-6 ), 24.5 (C-5 ), 23.3 (C-4 ), 21.5 (C-14), 19.4
2,7
ꢀ1
methyl-4,6-dioxatricyclo[7.1.1.0 ]undecane 11a
(C-15). IR (CHCl3): 3587, 2952, 1464, 1369, 1095, 964 cm . MS
+
m/z (rel. int.): 309 (M ꢀ1, 3), 209 (41), 163 (100), 135 (41), 121
4
.3.1. Obtained using method 2
(48), 110 (76), 108 (39), 98 (13), 85 (10), 71 (13).
Compound 4 (80 mg, 0.31 mmol) in anhydrous ethyl ether
0
0
0
0
(
(
10 mL) was treated with 0.07 mL (1 mmol) of EtBr and 24 mg
1 mmol) of magnesium. After work-up, 67 mg (75%) of
4.6. (1S,2R,5R,7S,9R,1 R)-5-(1 -Hydroxy-1 -phenyleth-1 -yl)-3,3,
2
,7
a
10,10-tetramethyl-4,6-dioxatricyclo[7.1.1.0 ]undecane 11d
diastereoisomeric mixture of carbinols 11a:12a (84:16) were
1
obtained as a colorless syrup. (R
NMR (CDCl ): d 4.69 (1H, s, H-5), 4.49 (1H, dd, J = 8.7 Hz, H-7),
.64 (1H, m, H-11eq), 2.34 (1H, m, H-8eq), 2.24 (1H, bs, OH), 2.09
2H, m, H-2, H-9), 1.94 (1H, t, J = 6 Hz, H-1), 1.70 (1H, m, H-8ax),
f
0.48, hexanes-AcOEt 9:1).
H
4.6.1. Method 3
3
A well-stirred cooled (ꢀ78 °C) solution of 84 mg (0.33 mmol) of
acetyldioxane 4 in 10 mL of anhydrous THF was treated with
0.55 mL (0.99 mmol) of 1.8 M PhLi in cyclohexane and stirred
2
(
0
0
1
.56 (2H, m, H-3 ), 1.26 (3H, s, Me-1 ), 1.24 (3H, s, Me-15), 1.20
2
under an N atmosphere for 3 h. The mixture was quenched with
(
3H, s, Me-13), 1.13 (3H, s, Me-14), 1.08 (3H, s, Me-12), 1.05 (1H,
1.5 mL of a saturated solution of ammonium chloride and allowed
to warm up to room temperature. The THF was evaporated and the
residue was extracted with 50 mL of ethyl ether. The organic layer
was washed with 5% aq HCl (3 ꢁ 10 mL), dried over anhydrous
0
13
d, J = 9.6 Hz, H-11ax), 0.92 (3H, t, J = 7.6 Hz, Me-4 ). C NMR (CDCl
d 100.1 (C-5), 76.7 (C-3), 73.4 (C-2 ), 70.8 (C-7), 58.1 (C-2), 43.5 (C-1),
4
1
3
):
0
0
3.3 (C-9), 41.5 (C-11), 39.5 (C-10), 33.1 (C-8), 30.2 (C-1 ), 29.5 (C-
0
0
3), 29.3 (C-3 ), 25.7 (C-12), 21.5 (C-14), 19.4 (C-15), 7.5 (C-4 ). IR
2 4
Na SO , filtered, and evaporated to dryness. The residue was puri-
ꢀ
1
(
CHCl
3
): 3586, 2975, 1457, 1379, 1155, 1095 cm . MS m/z (rel.
fied by column chromatography using silica gel and a mixture of
hexanes-AcOEt as eluent to give 101 mg (92%) of carbinols
11d:12d (50:50) as a colorless syrup.
+
int.): 281 (M ꢀ1, 0.3), 163 (15), 121 (22), 107 (34), 91 (22), 79
(
100), 67 (66), 55 (29), 43 (53), 41 (48), 39 (25).
0
0
0
4
.4. (1S,2R,5R,7S,9R,1 R)-5-(2 -Hydroxybut-3-en-2 -yl)-3,3,10,10-
4.6.2. Obtained using method 1
2,7
tetramethyl-4,6-dioxatricyclo[7.1.1.0 ]undecane 11b
Compound 4 (72 mg, 0.28 mmol) in anhydrous THF (10 mL) was
treated with 1 M PhMgBr (0.86 mL, 86 mmol) in ether. After work-
up, 85 mg (90%) of a diastereoisomeric mixture of carbinols
4
.4.1. Obtained using method 1
Obtained using method 1: Compound 4 (90 mg, 0.35 mmol) in
11d:12d (77:23) was obtained as a colorless syrup. (R
f
0.34, hex-
1
anhydrous THF (10 mL) was treated with 1.0 M i-PrMgBr
0.90 mL, 0.90 mmol) in ether. After work-up, 85 mg (80%) of a
diastereoisomeric mixture of carbinols 11b:12b (62:38) were
anes-AcOEt 98:2). H NMR (CDCl ): d 7.54 (2H, d, J = 8.5 Hz, H-
3
(
ortho), 7.31 (2H, dd, J = 7.2, 8.5 Hz, H-meta), 7.24 (1H, d,
J = 7.2 Hz, H-para), 4.92 (1H, s, H-5), 4.47 (1H, bt, J = 8.7 Hz, H-7),
3.07 (1H, bs, OH), 2.62 (1H, m, H-11eq), 2.30 (1H, m, H-8eq), 2.09
(2H, m, H-2, H-9), 1.92 (1H, t, J = 6.9 Hz, H-1), 1.78 (1H, m, H-
1
obtained as a colorless syrup. (R
NMR (CDCl ): d 4.67 (1H, s, H-5), 4.48 (1H, dd, J = 8.7 Hz, H-7),
.63 (1H, m, H-11eq), 2.35 (1H, m, H-8eq), 2.22 (1H, s, –OH),
f
0.45, hexanes-AcOEt 98:2). H
3
0
2
2
8ax), 1.52 (3H, s, Me-2 ), 1.24 (3H, s, Me-15), 1.19 (6H, s, Me-
0
13
.10 (2H, m, H-2, H-9), 1.97 (1H, c, J = 6.9 Hz, H-3 ), 1.95 (1H, t,
13,14), 1.05 (1H, d, J = 9.5 Hz, H-11ax), 1.04 (3H, s, Me-12).
C
0
J = 6.0 Hz, H-1), 1.71 (1H, m, H-8ax), 1.25 (3H, s, Me-1 ), 1.22
NMR (CDCl ): d 145.2 (C-ipso), 127.9 (C-meta), 126.8 (C-para),
3
0
(
(
3H, s, Me-15), 1.18 (3H, s, Me-13), 1,11 (3H, s, Me-14), 1.08
3H, s, Me-12), 1.05 (1H, d, J = 9.6 Hz, H-11ax), 0.95 (3H, d,
126.2 (C-ortho), 100.5 (C-5), 77.5 (C-3), 74.9 (C-1 ), 71.1 (C-7),
58.1 (C-2), 43.6 (C-1), 43.5 (C-9), 41.7 (C-11), 39.6 (C-10), 33.2
(C-8), 30.3 (C-15), 29.6 (C-13), 25.9 (C-12), 24.6 (C-2 ), 19.6 (C-
0
0
13
0
J = 6.6 Hz, Me-5 ), 0.92 (3H, d, J = 6.9 Hz, Me-4 ). C NMR (CDCl
3
):
0
ꢀ1
d 100.2 (C-5), 76.5 (C-3), 73.3 (C-2 ), 70.9 (C-7), 58.3 (C-2), 43.2
C-1), 43.4 (C-9), 41.5 (C-11), 39.4 (C-10), 33.4 (C-3 ), 33.6 (C-8),
0.2 (C-1 ), 29.5 (C-13), 25.5 (C-12), 21.4 (C-14), 19.4 (C-15),
3
7.7 (C-4 ), 17.1 (C-5 ). IR (CHCl ): 2953, 1457, 1356, 1150,
14). IR (CHCl
3
): 3566, 2976, 1493, 1447, 1379, 1153, 1093 cm
.
0
+
(
MS m/z (rel. int.): 330 (M , 0.3), 163 (146), 135 (16), 121 (51),
0
3
1
1
2
107 (72), 91 (68), 79 (100), 67 (48).
0
0
ꢀ
1
+
0
0
0
0
085 cm . MS m/z (rel. int.): 297 (M +1, 2), 279 (1), 253 (3),
4.7.
(1S,2R,5R,7S,9R,1 R)-5-(2 -Hydroxy-3 -buten-2 -yl)-3,3,10,
2
,7
09 (37), 181 (8), 163 (98), 135 (41), 121 (52), 109 (100), 95
10-tetramethyl-4,6-dioxatricyclo[7.1.1.0 ]undecane 11e
(
22), 43 (25).
4
.7.1. Obtained using method 1
Compound 4 (60 mg, 0.23 mmol) in anhydrous THF (10 mL) was
0
0
0
0
4
1
.5. (1S,2R,5R,7S,9R,1 R)-5-(4 -Methyl-2 -hydroxypent-2 -yl)-3,3,
0,10-tetramethyl-4,6-dioxatricyclo[7.1.1.02,7]undecane 11b
treated with 2 M CH
After work-up, 64 mg (96%) of a diastereoisomeric mixture of car-
binols 11e:12e (65:35) were obtained as a colorless syrup (R 0.4,
): d 6.03 (1H, dd, J = 10.8,
2
@CHMgBr (0.35 mL, 0.71 mmol) in ether.
4
.5.1. Obtained using method 1
Compound 4 (100 mg, 0.39 mmol) in anhydrous THF (10 mL)
was treated with 1.0 M i-BuMgBr (0.96 mL, 0.96 mmol) in ether.
After work-up, 110 mg (89%) of a diastereoisomeric mixture of car-
f
1
hexanes-AcOEt 9:1). H NMR (CDCl
3
0
0
17.4 Hz, H-3 ), 5.36 (1H, dd, J = 1.7, 17.4 Hz, H-4 a), 5.12 (1H, dd,
J = 1.7, 10.8 Hz, H-4 b), 4.70 (1H, s, H-5), 4.49 (1H, dd, J = 8.7 Hz,
0
binols 11c:12c (60:40) were obtained as a colorless syrup. (R
hexanes-AcOEt 98:2). 1H NMR (CDCl
): d 4.69 (1H, s, H-5), 4.49
1H, dd, J = 8.7 Hz, H-7), 2.64 (1H, m, H-11eq), 2.34 (1H, m, H-
f
0.45,
H-7), 2.63 (1H, m, H-11eq), 2.53 (1H, m, H-2), 2.33 (1H, m, H-
3
8eq), 2.08 (1H, m, H-9), 1.93 (1H, t, J = 6.0 Hz, H-1), 1.77 (1H, m,
0
(
H-8ax), 1.26 (3H, s, Me-1 ), 1.25 (3H, s, Me-15), 1.24 (3H, s, Me-
8
eq), 2.24 (1H, bs, –OH), 2.09 (2H, m, H-2, H-9), 1.94 (1H, t,
13), 1.21 (3H, s, Me-14), 1.07 (3H, s, Me-12), 1.06 (1H, d,
0
13
0
0
J = 6.0 Hz, H-1), 1.82 (m, 1H, H-4 ), 1.70 (1H, m, H-8ax), 1.45 (m,
J = 8.4 Hz, H-11ax). C NMR d 141.6 (C-3 ), 113.3 (C-4 ), 100.4 (C-
0
0
0
2
H, H-3 ), 1.26 (3H, s, Me-1 ), 1.24 (3H, s, Me-15), 1.20 (3H, s,
5), 77.2 (C-3), 74.0 (C-2 ), 71.0 (C-7), 58.1 (C-2), 43.6 (C-1), 43.4
Me-13), 1.13 (3H, s, Me-14), 1.08 (3H, s, Me-12), 1.05 (1H, d,
(C-9), 41.5 (C-11), 39.6 (C-10), 33.1 (C-8), 30.3 (C-15), 29.6 (C-
0
0
J = 9.6 Hz, H-11ax), 0.98 (d, 3H, J = 6.6 Hz, CH3-5 ), 0.95 (d, 3H,
13), 25.9 (C-12), 22.7 (C-1 ), 19.6 (C-14). IR (CHCl
3
): 3580, 2976,
0
13
ꢀ1
J = 6.7 Hz, CH3-6 ). C NMR (CDCl
7
9
3
): d 100.3 (C-5), 76.4 (C-3),
1646, 1456, 1379, 1155, 1093 cm . MS m/z (rel. int.): 279
0
0
+
3.1 (C-2 ), 70.7 (C-7), 58.4 (C-2), 44.7 (C-3 ), 43.5 (C-1), 43.1 (C-
), 41.6 (C-11), 39.4 (C-10), 33.0 (C-8), 30.1 (C-1 ), 29.4 (C-13),
(M ꢀ1, 0.2), 181 (15), 163 (100), 121 (13), 107 (28), 79 (54), 67
0
(40), 55 (18), 43 (73), 41 (45), 39 (27).
Please cite this article in press as: Becerra-Martínez, E.; et al. Tetrahedron: Asymmetry (2017), https://doi.org/10.1016/j.tetasy.2017.07.008

6
E. Becerra-Martínez et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
0
0
0
0
4
1
.8. (1S,2R,5R,7S,9R,1 R)-5-(2 -Hydroxy-3 -pentin-2 -yl)-3,3,10,
added and the resulting mixture was stirred at the same tempera-
ture for 5 h under an N atmosphere. The crude reaction mixture
was poured into ice-water and extracted (3 ꢁ 100 mL) with ether,
washed with brine, dried with anhydrous Na SO , filtered, and
2,7
0-tetramethyl-4,6-dioxatricyclo[7.1.1.0 ]undecane 11f
2
4
.8.1. Obtained using method 1
2
4
Compound 4 (85 mg, 0.34 mmol) in anhydrous THF (10 mL) was
evaporated to dryness. The residue was purified by column chro-
treated with 0.5 M C
work-up 92 mg (93%) of a diastereoisomeric mixture of carbinols
1f:12f (50:50) were obtained as a colorless syrup. (R 0.2, hex-
): d 4.76 (1H, s, H-5), 4.55 (1H,
bt, J = 8.9 Hz, H-7), 2.80 (1H, s, OH), 2.64 (1H, m, H-11eq), 2.37
3
H
3
MgBr (0.2 mL, 1 mmol) in ether. After
matography (hexanes-EtOAc 98:2) giving 11.8 g (98%) of 10-epi-
phenylmyrtenol as colorless syrup. (R
f
0.37, hexanes-AcOEt 9:1).
1
1
f
H NMR (CDCl ): d 7.26 (5H, m, H-Ar), 5.56 (1H, m, H-3), 5.05
3
1
anes-AcOEt 98:2). H NMR (CDCl
3
(1H, bs, H-10), 2.29 (3H, m, H-4, H-7eq), 2.18 (1H, s, –OH), 2.05
(2H, m, H-1, H-5), 1.17 (3H, s, Me-9), 1.07 (1H, d, J = 8.5 Hz, H-
1
3
(
1H, m, H-8eq), 2.11 (2H, m, H-2, H-9), 1.95 (1H, t, J = 7 Hz, H-1),
3
7ax), 0.71 (3H, s, Me-8). C NMR (CDCl ): d 149.7 (C-ipso), 141.9
0
0
1
.85 (3H, s, Me-5 ), 1.84 (1H, m, H-8ax), 1.43 (3H, s, Me-1 ), 1.27
(C-2), 128.3 (C-ortho), 126.9 (C-para), 126.6 (C-meta), 119.0 (C-3),
(
3H, s, Me-15), 1.26 (3H, s Me-13), 1.24 (3H, s, Me-14), 1.08 (3H,
76.7 (C-10), 42.5 (C-1), 40.9 (C-5), 37.9 (C-6), 32.1 (C-4), 31.5 (C-
13
s, Me-12), 1.07 (1H, d, J = 9.7 Hz, H-11ax). C NMR (CDCl
3
): d
7), 26.2 (C-9), 21.5 (C-8). IR (CHCl
3
): 3392, 3028, 2989, 2915,
0
0
ꢀ1
9
2
3
9.5 (C-5), 80.7 (C-3 ), 80.6 (C-4 ), 77.5 (C-3), 71.1 (C-7), 69.5 (C-
), 57.9 (C-2), 43.6 (C-1), 43.5 (C-9), 41.6 (C-11), 39.6 (C-10),
3.1 (C-8), 30.3 (C-15), 29.6 (C-14), 25.9 (C-12), 24.4 (C-1 ), 19.6
2831, 1636, 1450, 1365, 1267, 1079, 1047, 1017, 753, 700 cm
.
0
+
MS m/z (rel. int.): 228 (M , 3), 228 (30), 211 (100), 210 (58), 195
0
(12), 184 (12), 168 (15), 167 (32), 155 (11), 141 (11), 107 (12),
0
(
C-13), 4.7 (C-5 ). IR (CHCl
3
): 3565, 2977, 1455, 1379, 1154,
105 (20), 91 (16), 79 (19). HRFABMS calcd for C16
Found 228.1521.
H20O 228.1514.
ꢀ1
+
1
097 cm . MS m/z (rel. int.): 292 (M , 0.1), 121 (12), 107 (32),
9
1 (23), 79 (100), 67 (67), 55 (16), 43 (64), 41 (47), 39 (27).
4
.11. (1S,2S,3S,5R)-2-((S)-Hydroxy(phenyl)methyl)-6,6-dimethyl-
0
0
0
4
.9. (1S,2R,5R,7S,9R,1 R)-5-(1 -Hydroxy-eth-1 -yl)-3,3,10,10-
bicyclo[3.1.1]heptan-3-ol 10a and (1S,2S,3S,5R)-2-((R)-hydroxy
(phenyl)methyl)-6,6-dimethylbicyclo[3.1.1]heptan-3-ol 10b
2,7
tetramethyl-4,6-dioxatricyclo[7.1.1.0 ]undecane 11g
4
.9.1. Method 4
A
500-mL oven-dried two-necked round bottom flask,
To a cooled (ꢀ78 °C) suspension of 27 mg (0.713 mmol) of
equipped with a pressure-equalizing addition funnel, was cooled
in an ice-water bath and loaded with 100 mL of anhydrous THF
and 15.4 g (67.47 mmol) of 10-epi-phenylmyrtenol under a nitro-
gen atmosphere. A solution of 26.9 mL (269.9 mmol) of 10–
4 2
LiAlH in 5 mL of anhydrous THF under an N atmosphere, a solu-
tion of 60 mg (0.237 mmol) of dioxane 4 in 5 mL of anhydrous THF
was added. The resulting mixture was stirred at the same temper-
ature for 3 h. Next, 10 mL of a saturated solution of ammonium
chloride were added, after which THF was evaporated and the
crude reaction mixture was extracted (3 ꢁ 30 mL) with ethyl ether.
The organic layer was washed with brine, dried with anhydrous
10.2 M BH.
SMe in 30 ml of THF was then added dropwise
3 2
through the addition funnel for 1 h. The resulting mixture was
stirred at 0–4 °C for 3 h and then for 24 h at room temperature.
The mixture was cooled again in an ice-water bath and 10 mL of
water were added dropwise over 30 min, and stirring was contin-
ued for 1 h at the same temperature. Next, 45 mL of 3 M NaOH
were added at once, followed by the dropwise addition of 30 mL
2 4
Na SO , filtered, and evaporated to dryness. The residue was puri-
fied by column chromatography using alkalinized silica gel and a
mixture of hexanes-AcOEt 95:5 as eluent, yielding 57 mg (94%) of
carbinols 11g:12g (50:50) as colorless syrups.
of 30% H
h. Excess THF was eliminated in a rotary evaporator, and the
residue was extracted with CH Cl
(3 ꢁ 100 mL). The organic layer
was dried over anhydrous Na SO , filtered and evaporated to dry-
ness. The solid residue was washed with hexanes (3 ꢁ 50 mL) and
dissolved in 250 mL of a mixture of hexanes-CH Cl (3:1). The
organic layer was washed with water (5 ꢁ 40 mL), dried with
anhydrous Na SO , and evaporated to dryness yielding an epi-
meric mixture of 10a and 10b. The solid was recrystallized from
hexanes-CHCl
2 2
O over 30 min; the mixture was stirred for an additional
1
4
.9.2. Method 5
2
2
To a cooled (ꢀ78 °C) solution of 93 mg (0.37 mmol) of acetyl-
2
4
dioxane 4 in 10 mL of MeOH were added 42 mg (1.11 mmol) of
NaBH
was quenched with 10 mL of a saturated solution of NH
for 30 min, and then the solvent was evaporated. The crude reac-
tion mixture was extracted with Et
O (3 ꢁ 50 mL) and the solution
washed with water. The organic layer was dried with anhydrous
Na SO , filtered, and evaporated to dryness. The residue was puri-
4
and the resulting mixture was stirred for 3 h. The reaction
2
2
4
Cl, stirred
2
4
2
3
.
2
4
fied by column chromatography using hexanes-AcOEt (99:1) as
4.11.1. (1S,2S,3S,5R)-2-((S)-Hydroxy(phenyl)methyl)-6,6-dimethy-
lbicyclo[3.1.1]heptan-3-ol 10a
eluent, giving 89 mg (95%) of carbinols 11g:12g (50:50) as a color-
less syrup. (R
f
0.14, hexanes-AcOEt 98:2). 1H NMR (CDCl
3
): d 4.71
Obtained in 40% yield after column chromatography from the
epimeric mixture of 10a and 10b as colorless needles, mp 104–
0
(
(
1H, s, H-5), 4.52 (1H, bq, J = 8.3 Hz, H-7), 3.68 (1H, m, H-1 ), 2.53
1H, m, H-11eq), 2.39 (2H, m, OH, H-8eq), 2.13 (2H, m, H-2, H-9),
2
1
108 °C. (R
f
= 014, hexanes-AcOEt 8:2). [
D 3
a] = +14.8 (0.32, CHCl ).
1
1
1
.97 (1H, m, H-1), 1.78 (1H, m, H-8ax), 1.27 (6H, s, Me-15, Me-
H NMR (CDCl ): d 7.32 (5H, m, H-Ar), 4.62 (2H, m, H-3, H-10),
3
0
3), 1.26 (3H, s, Me-14), 1.21 (3H, d, J = 6.3 Hz, Me-2 ), 1.07 (3H,
3.03 (1H, bs, OH), 2.78 (1H, bs, OH), 2.53 (1H, m, H-4eq), 2.24
(1H, m, H-7eq), 2.11 (1H, m, H-2), 1.94 (1H, m, H-5), 1.76 (1H, m,
H-4ax), 1.38 (1H, m, H-1), 1.11 (3H, s, Me-9), 1.04 (3H, s, Me-8),
13
s, Me-12), 1.05 (1H, d, J = 9.6 Hz, H-11ax). C NMR (CDCl
3
): d
0
9
1
2
2
0
9.8 (C-5), 77.5 (C-3), 70.9 (C-7), 69.3 (C-1 ), 58.0 (C-2), 43.8 (C-
1
3
), 43.8 (C-9), 41.9 (C-11), 39.8 (C-10), 33.5 (C-8), 30.2 (C-15),
9.9 (C-13), 26.0 (C-12), 19.9 (C-14), 18.8 (C-2 ). IR (CHCl
924, 1455, 1379, 1154, 1092 cm . MS m/z (rel. int.): 254 (M ,
.1), 181 (10), 163 (59), 107 (29), 91 (16), 79 (88), 67 (66), 55
3
0.98 (1H, d, J = 9.9 Hz, H-7ax). C NMR (CDCl ): d 143.7 (C-ipso),
0
3
): 3736,
128.6 (C-ortho), 128.0 (C-para), 127.2 (C-meta), 79.3 (C-10), 69.0
(C-3), 60.3 (C-2), 42.9 (C-1), 42.0 (C-5), 38.2 (C-6), 37.0 (C-4),
ꢀ
1
+
3
34.5 (C-7), 27.8 (C-9), 24.7 (C-8). IR (CHCl ): 3495, 3308, 2912,
ꢀ1
(
28), 43 (100), 41 (76), 39 (37).
1457, 1384, 1284, 1200, 1116, 1030, 853, 760, 699, 554 cm . MS
+
m/z (rel. int.): 245 (M ꢀ1, 1), 211 (38), 210 (17), 185 (14), 167
4
.10. (1R)-10-epi-Phenylmyrtenol
(11), 159 (16), 143 (35), 131 (36), 130 (31), 129 (31), 128 (16),
1
22 (12), 115 (12), 108 (12), 107 (34), 105 (34), 95 (13), 91 (70),
80 (10), 79 (100), 78 (41), 77 (36), 67 (11), 41 (14). HRFABMS calcd
for C16 +NH 246.1856. Found 246.1862.
To a cooled solution (ꢀ78 °C) of 7.43 g (49.5 mmol) of (1R)-
myrtenal in 50 mL of anhydrous THF, 1.5 equiv of PhMgBr were
H
22
O
2
4
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E. Becerra-Martínez et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
7
4
.11.2. (1S,2S,3S,5R)-2-((R)-Hydroxy(phenyl)methyl)-6,6-dimeth-
4.13.2. Using method 3
ylbicyclo[3.1.1]heptan-3-ol 10b
Obtained in 35% yield after column chromatography from the
epimeric mixture of 10a and 10b as colorless crystals, mp = 90–
Compound 9a (281.4 mg, 0.93 mmol) in anhydrous THF (10 mL)
was treated with 0.5 M EtLi (5.62 mL, 2.8 mmol) in ether. After
work-up, 294.6 mg (95%) of a diastereoisomeric mixture of carbi-
nols 13a:14a (38:62) was obtained as colorless syrup. Data for
major diastereoisomer 14a. Colorless crystals, mp = 115–117 °C.
2
1
9
2 °C. (R
f
= 014, hexane-AcOEt 8:2). [
H NMR (300 MHz, CDCl ): d 7.34 (5H, m) H-Ar; 4.58 (1H, dd,
J = 3 y 10 Hz) H-10; 3.97 (1H, m) H-3; 2.45 (2H, m) H-1, H-7e;
.38 (1H, m) H-4e; 2.22 (1H, m) H-2; 2.14 (1H, s) OH; 1.97 (1H,
m) H-5; 1.65 (1H, m) H-4a; 1.27 (3H, s) Me-9; 1.09 (1H, m) H-
a; 0.96 (3H, s) Me-8; 0.84 (1H, m) –OH. 13C NMR (300 MHz,
CDCl ): d 143.7 (C-ipso); 129.2 (C-ortho); 128.6 (C-para); 127.1
C-meta); 76.8 (C-10); 65.1 (C-3); 60.8 (C-2); 42.7 (C-1); 41.8
C-5); 38.3 (C-6); 37.2 (C-4); 33.5 (C-7); 27.0 (C-9); 23.9, (C-8).
a]
D
= ꢀ27.9 (1.14, CHCl
3
).
1
3
2
1
1
(R
f
0.25, hexanes-AcOEt 9:1). [
a
]
D
= ꢀ10.2 (c 1.08, CHCl
3
).
H
2
NMR (CDCl
3
): d 7.30 (5H, m, H-Ar), 4.78 (1H, s, H-5), 4.62 (1H, d,
J = 10.2 Hz, H-3), 4.53 (1H, bq, J = 9.2 Hz, H-7), 2.41 (2H, m, H-
7
8eq, H-11eq), 3.30 (1H, bs, OH), 2.82 (2H, m, H-2, H-9), 1.86 (1H,
0
0
3
m, H-8ax), 1.61 (3H, m, H-1, H-3 ), 1.24 (3H, s, Me-1 ), 1.21 (3H,
0
(
s, Me-13), 0.99 (3H, s, Me-12), 0.94 (3H, t, J = 7 Hz, H-4 ), 0.88
(1H, d, J = 9 Hz, 11ax). C NMR (CDCl ): d 139.7 (C-ipso), 128.4
3
1
3
(
ꢀ1
IR (
m
, cm ); 3561; 3421; 2923; 2886; 1457; 1361; 1287; 1047;
(C-ortho), 128.1 (C-para), 127.2 (C-meta), 106.4 (C-5), 84.9 (C-3),
0
1
019; 765; 707; 641; 552. EM (70 eV) m/z (rel. int.): 244
76.9 (C-7), 73.8 (C-2 ), 55.8 (C-2), 43.3 (C-9), 42.8 (C-1), 40.2 (C-
+
0
0
(
M ꢀ2, 1); 211 (30); 210 (14); 185 (13); 184 (12); 169 (15);
67 (18); 159 (10); 143 (14); 131 (14); 130 (14); 129 (14); 122
13); 108 (24); 107 (44); 105 (29); 95 (13); 91 (33); 79 (100);
11), 39.1 (C-10), 33.4 (C-8), 30.1 (C-1 ), 29.6 (C-3 ) 25.6 (C-13),
0
1
(
21.6 (C-12), 7.7 (C-4 ). IR (CHCl
3
): 3529, 2927, 1456, 1376, 1175,
ꢀ
1
+
1095, 1017, 909, 761, 702 cm . MS m/z (rel. int.): 331 (M +1)
(3), 229 (30), 211 (88), 185 (17), 169 (18), 155 (18), 141 (20),
130 (25), 122 (42), 107 (34), 91 (68), 79 (98), 78 (100), 77 (9).
7
2
8 (34). HRFABMS calcd for C16
45.1522.
22 2
H O – H 245.1542. Found
HRFABMS calcd for C21
30 3
H O +H 331.2272. Found 331.2262.
4
.12. (1S,2R,3S,5R,7S,9R)-5-Acetyl-10,10-dimethyl-3-phenyl-4,6-
2
,7
0
0
0
dioxatricyclo[7.1.1.0 ]undecane 9a
4.14. (1S,2R,3S,5R,7S,9R,1 S)-5-(2 -Hydroxy-hex-2 -yl)-10,10-dime-
2
,7
thyl-3-phenyl-4,6-dioxatricyclo[7.1.1.0 ]undecane 14b
A 100 mL oven-dried two-necked round-bottom flask equipped
with a Dean Stark trap and a magnetic stirring bar, containing a
solution of 208 mg (0.84 mmol) of diol 10a and 20 mg of p-TsOH
in 50 mL of anhydrous benzene, was placed in an oil bath and
4.14.1. Obtained using method 2
Compound 9a (270 mg, 0.89 mmol) in anhydrous ethyl ether
(10 mL) was treated with 0.27 mL (2.52 mmol) of BuBr and
63.1 mg (2.52 mmol) of magnesium. After work-up, 289.1 mg
(90%) of a diastereoisomeric mixture of carbinols 13b:14b (1:
warmed to 78 °C. Then 0.40 mL (3.38 mmol) of a,a-dialkoxyacetal
was added dropwise, and the resulting mixture was stirred at the
same temperature under a nitrogen atmosphere for 8 h. The reac-
tion mixture was allowed to reach the room temperature and
>99) was obtained as colorless syrup. (R
f
0.42, hexanes-AcOEt
2
1
1
9:1). [
a
]
D
= ꢀ12.4 (c 0.58, CHCl
3
). H NMR (CDCl ): d 7.31 (5H,
3
5
1
Na
0 mL of hexanes were added. The organic layer was washed with
0 mL of a 5% aqueous solution of NaHCO , dried with anhydrous
SO , filtered, and evaporated at 40–45 °C under a reduced pres-
sure. The oil residue was purified by column chromatography
using silica gel alkalinized with Et N and a mixture of hexanes-
AcOEt (98:2) to give 186.7 mg (74%) of acetyldioxane 9a as a color-
m, H-Ar), 4.76 (1H, s, H-5), 4.62 (1H, d, J = 10 Hz, H-3), 4.53 (1H,
bq, J = 9.2 Hz, H-7), 2.41 (2H, m, H-8eq, H-11eq), 2.28 (1H, bs,
OH), 2.08 (2H, m, H-2, H-9), 1.86 (1H, m, H-8ax), 1.59 (3H, m, H-
3
2
4
0
0
0
1, H-3 ), 1.35 (4H, m, H-4 , H-5 ), 1.25 (3H, s, Me-13), 1.21 (6H, s,
0
13
3
3
Me-12, Me-13), 0.88 (4H, m, 11ax, Me-6 ). C NMR (CDCl ): d
139.7 (C-ipso), 128.4 (C-ortho), 128.0 (C-para), 127.2 (C-meta),
100.5 (C-5), 84.9 (C-3), 76.9 (C-7), 73.7 (C-2 ), 55.8 (C-2), 43.3 (C-
9), 42.8 (C-1), 40.2 (C-11), 39.1 (C-10), 36.8 (C-3 ), 33.4 (C-8),
21
0
less syrup (R
CHCl
f
= 0.42, hexanes-AcOEt 9:1). [
a
]
D
= ꢀ28.2 (c 0.97,
1
0
3
). H NMR (CDCl ): d 7.34 (5H, m, H-Ar), 5.18 (1H, s, H-5),
3
0
0
0
4
.72 (1H, d, J = 10.4 Hz, H-3), 4.62 (1H, c, J = 9, 18.3 Hz, H-7), 2.47
30.1 (C-13) 25.6 (C-12), 25.4 (C-5 ), 23.6 (C-4 ), 22.1 (C-1 ), 14.4
0
0
(
2H, m, H-8eq, H-11eq), 2.32 (3H, s, Me-2 ), 2.27 (1H, t, J = 9.8 Hz,
(C-6 ). IR (CHCl
3
): 3584, 2928, 2878, 1455, 1380, 1136, 1094,
ꢀ1
+
H-2), 2.12 (1H, c, J = 5.7, 10.8 Hz, H-9), 1.94 (1H, dd, J = 9.6,
2.7 Hz, H-8ax), 1.60 (1H, t, J = 6 Hz, H-1), 1.21 (6H, s, Me-12,
1078, 1015, 758, 699 cm . MS m/z (rel. int.): 257 (M ꢀ1, 2), 229
1
(73), 212 (27), 211 (100), 185 (15), 122 (19), 91 (15), 79 (12), 78
13
Me-13), 0.96 (1H, d, J = 9.6 Hz, H-11ax). C NMR (CDCl
3
): d 202.1
34 3
(12). HRFABMS calcd for C23H O +H 359.2586. Found 359.2572.
0
(
C-1 ), 138.7 (C-ipso), 128.6 (C-ortho), 128.5 (C-para), 127.3 (C-
0
0
0
0
meta), 102.4 (C-5), 85.8 (C-3), 77.5 (C-7), 55.5 (C-2), 43.3 (C-9),
4.15. (1S,2R,3S,5R,7S,9R,1 S)-5-(3 -Methyl-2 -hydroxybut-2 -yl)-
0
2,7
4
2.9 (C-1), 40.2 (C-11), 39.1 (C-10), 33.3 (C-8), 30.0 (C-2 ), 25.6
10,10-dimethyl-3-phenyl-4,6-dioxatricyclo[7.1.1.0 ]undecane
(
1
C-13), 25.4 (C-12). IR (CHCl
420, 1366, 1315, 1268, 1178, 1114, 1026, 861, 784, 718 cm .
3
): 3365, 2935, 1642, 1577, 1446,
14c
ꢀ1
MS m/z (rel. int.): 212 (40), 169 (27), 151 (19), 143 (22), 141
17), 131 (13), 130 (23), 129 (21), 128 (16), 122 (43), 121 (13),
4.15.1. Obtained using method 2
(
Compound 9a (306.0 mg, 1.01 mmol) in anhydrous ethyl ether
(10 mL) was treated with 0.4 mL (5.08 mol) of 2-bromopropane
and 123.5 mg (5.08 mmol) of magnesium. After work-up,
1
8
C
19 (11), 115 (23), 107 (43), 105 (23), 93 (13), 91 (78), 83 (30),
0 (12), 79 (95), 78 (100), 77 (40), 67 (17). HRFABMS calcd for
19
H
24
O
3
+NH
4
318.2069. Found 318.2067.
308.7 mg (89%) of
1
a
diastereoisomeric mixture of carbinols
3c:14c (17:83) were obtained as colorless syrup. (R 0.34, hex-
). H NMR (CDCl ): d
f
0
0
0
21
1
4
.13. (1S,2R,3S,5R,7S,9R,1 S)-5-(2 -Hydroxybut-2 -yl)-10,10-dime-
anes-AcOEt 9:1). [
a]
D
= +31.0 (c 0.78, CHCl
3
3
2,7
thyl-3-phenyl-4,6-dioxatricyclo[7.1.1.0 ]undecane 14a
7.31 (5H, m, H-Ar), 4.87 (1H, s, H-5), 4.63 (1H, d, J = 9.9 Hz, H-3),
4
.53 (1H, m, H-7), 2.41 (2H, m, H-8eq, H-11eq), 2.30 (1H, bs, OH),
0
4
.13.1. Using method 2
2.09 (2H, m, H-2, H-9), 1.99 (1H, c, J = 6.9 Hz, H-3 ), 1.88 (1H, dd,
J = 10.2, 12.9 Hz, H-8ax), 1.59 (1H, m, J = 6 Hz, H-1), 1.21 (6H, s,
Me-12, Me-13), 1.19 (3H, s, Me-1 ), 0.96 (3H, d, J = 6.6 Hz, Me-5 ),
0.93 (3H, d, J = 6.9 Hz, Me-4 ), 0.92 (1H, d, J = 9.6 Hz, H-11ax).
NMR (CDCl ): d 139.7 (C-ipso), 128.4 (C-ortho), 128.0 (C-para),
127.1 (C-meta), 105.3 (C-5), 85.0 (C-3), 76.9 (C-7), 75.5 (C-2 ), 55.8
Compound 9a (270 mg, 0.89 mmol) in anhydrous ethyl ether
0
0
(
6
(
10 mL) was treated with 0.2 mL (2.68 mmol) of EtBr and
5.1 mg (2.68 mmol) of magnesium. After work-up, 282.2 mg
95%) of a diastereoisomeric mixture of carbinols 13a:14a (1:>99)
were obtained as a colorless syrup.
0
13
C
3
0
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8
E. Becerra-Martínez et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
(
(
(
C-2), 43.3 (C-9), 42.8 (C-1), 40.2 (C-11), 39.1 (C-10), 33.4 (C-8), 33.1
103.3 mg (4.30 mmol) of magnesium. After work-up, 454.7 mg
(84%) of a diastereoisomeric mixture of carbinols 13e:14e (07:93)
0
0
0
0
C-3 ), 30.1 (C-13), 25.6 (C-12), 19.1 (C-1 ), 17.7 (C-4 ), 17.1 (C-5 ). IR
CHCl ): 3583, 3497, 2928, 1456, 1366, 1213, 1180, 1140, 1091,
001, 926, 870, 837 cm . MS m/z (rel. int.): 229 (9), 212 (19), 211
3
were obtained as a colorless syrup. (R
f
0.28, hexanes-AcOEt 9:1).
ꢀ1
21
1
1
[a]
D
3
= ꢀ23.4 (c 0.69, CHCl ). H NMR (CDCl ): d 7.38 (10H, m, H-
3
(
(
(
(
80), 185 (17), 169 (43),155 (22), 143 (30), 141 (23), 131 (16), 130
38), 129 (26), 128 (25), 122 (53), 121 (16), 119 (11), 117 (19), 115
25), 108 (16), 107 (51), 105 (28), 95 (15) 93 (14), 87 (15), 79
100), 78 (97), 77 (31), 69 (19), 45 (11), 43 (26), 41 (35), 39 (27).
Ar), 4.97 (1H, s, H-5), 4.59 (1H, d, J = 10.2 Hz, H-3), 4.52 (1H, bq,
J = 9.1 Hz, H-7), 3.03 (1H, bs, OH), 2.38 (2H, m, H-8eq, H-11eq),
0
2.05 (2H, m, H-2, H-9), 1.84 (1H, m, H-8ax), 1.65 (3H, s, Me-2 ),
1.57 (1H, t, J = 6.3 Hz, H-1), 1.19 (3H, s, Me-13), 1.17 (3H, s, Me-
1
3
HRFABMS calcd for C22
H
32
O
3
+Na 367.2249. Found 367.2247.
12), 0.88 (1H, d, J = 9.6 Hz, H-11ax). C NMR (CDCl
3
): d 144.4 (C-
0
ipso), 139.0 (C-ipso ), 106.3 (C-5), 84.5 (C-3), 76.8 (C-7), 74.9 (C-
1 ), 55.8 (C-2), 43.3 (C-9), 42.8 (C-1), 40.2 (C-11), 39.1 (C-10),
33.4 (C-8), 30.1 (C-13), 25.5 (C-12), 24.8 (C-2 ). IR (CHCl
0
0
0
0
4
.16. (1S,2R,3S,5R,7S,9R,1 S)-5-(2 -Hydroxybut-3-en-2 -yl)-10,10-
2,7
0
dimethyl-3-phenyl-4,6-dioxatricyclo[7.1.1.0 ]undecane 14d
3
): 3391,
3
028, 2915, 2831, 1492, 1450, 1365, 1264, 1047, 1015, 966, 883,
ꢀ1
4
.16.1. Obtained using method 1
785, 753 cm . MS m/z (rel. int.): 229 (4), 212 (46), 211 (53), 170
(12), 169 (78), 155 (30), 143 (25), 141 (29), 130 (21), 129 (18),
128 (22), 122 (17), 121 (99), 117 (11), 115 (21),108 (30), 107
(33), 105 (43), 103 (10), 95 (27), 93 (20), 91 (98), 79 (75), 78
(46), 77 (48), 51 (18), 43 (100), 41 (15), 39 (18). HRFABMS calcd
Compound 9a (237 mg, 0.79 mmol) in anhydrous THF (10 mL)
was treated with 0.5 M C H MgBr (3.65 mL, 1.83 mmol) in ether.
2 3
After work-up 249 mg (96%) of a diastereoisomeric mixture of carbi-
nols 13d:14d (13:83) was obtained as a colorless syrup (Rf 0.44, hex-
1
ane-AcOEt 9:1). H NMR (CDCl3): d 7.36 (5H, m, H-Ar), 6.03 (1H, dd,
30 3
for C25H O +Na 401.2093. Found 401.2094.
0
0
J = 10.8, 17.4 Hz, H-3 ), 5.36 (1H, dd, J = 1.6, 17.4 Hz, H-4 ), 5.12 (1H,
dd, J = 1.8, 10.8 Hz, H-4 ), 4.83 (1H, s, H-5), 4.67 (1H, d, J = 9.9 Hz, H-
0
4.18.2. Obtained using method 3
3
), 4.54 (1H, c, J = 9.3 Hz, H-7), 2.80 (1H, s, –OH), 2.45 (2H, m, H-8eq,
Compound 9a (315 mg, 1.04 mmol) in 10 mL of anh. THF was
treated with 0.49 mL (0.89 mmol) of 1.8 M PhLi in cyclohexane
H-11eq), 2.11 (2H, m, H-2, H-9), 1.90 (1H, m, H-8ax), 1.57 (1H, t,
0
J = 6 Hz, H-1), 1.50 (3H, s, Me-1 ), 1.22 (6H, s, Me-12, Me-13), 0.95
and was stirred at ꢀ78 °C under an N
2
atmosphere for 3 h. After
usual work-up, 310 mg (78%) of a diastereoisomeric mixture of car-
1H, d, J = 9.6 Hz, H-11ax). 13C NMR (CDCl3): d 141.4 (C-3 ), 139.3
0
(
(
4
C-ipso), 128.1 (C-ortho), 128.0 (C-para), 127.5 (C-meta), 113.4 (C-
binols 13e:14e (30:70) was obtained as colorless syrup.
0
), 105.1 (C-5), 84.8 (C-3), 55.6 (C-2), 43.3 (C-9), 42.6 (C-1), 40.2
0
0
0
0
(
C-11), 39.3 (C-10), 33.2 (C-8), 30.0 (C-13), 25.3 (C-12), 24.9 (C-1 ).
4.19.
(1S,2R,3S,5R,7S,9R,1 S)-5-(1 -Hydroxyeth-2 -yl)-10,10-
2
,7
IR (CHCl
1
3
): 3500, 2920, 2869, 3501, 2930, 1456, 1368, 1140,
091 cm . MS m/z (rel. Int.): 328 (M , 1), 210 (1), 257 (11), 212
dimethyl-3-phenyl-4,6-dioxatricyclo[7.1.1.0 ]undecane 14f
ꢀ
1
+
(
(
12), 211 (100), 183 (73), 151 (75), 166 (90), 143 (86), 131 (35), 43
55), 41 (40), 39 (39).
4.19.1. Obtained using method 4
Compound 9a (150 mg, 0.50 mmol) in anhydrous THF (10 mL)
was treated with LiAlH
4
(56.9 mg, 1.5 mmol). After work-up,
0
0
0
4
.17. (1S,2R,3S,5R,7S,9R,1 S)-5-(2 -Hydroxy-3-penten-2 -yl)-10,10-
147.9 mg (98%) of diastereoisomeric mixture of carbinols
a
2,7
dimethyl-3-phenyl-4,6-dioxatricyclo[7.1.1.0 ]undecane 14d
13f:14f (50:50) were obtained as a colorless syrup.
4
.17.1. Obtained using method 1
4.19.2. Using method 5
Compound 9a (301 mg, 1.0 mmol) in anhydrous THF (10 mL)
Compound 9a (199.0 mg, 0.66 mmol) in methanol THF (10 mL)
was treated with 0.5 M C
work-up, 303.6 mg (89%) of a diastereoisomeric mixture of carbi-
nols 13d:14d (15:85) was obtained as colorless syrup (R 0.34, hex-
). H NMR (CDCl ): d
.38 (5H, m, H-Ar), 4.84 (1H, s, H-5), 4.68 (1H, d, J = 9.9 Hz, H-3),
3
H
3
MgBr (6.0 mL, 3 mmol) in ether. After
was treated with NaBH
192 mg (96%) of a diastereoisomeric mixture of carbinols 13f:14f
(50:50) were obtained as a colorless syrup. (R 0.14, hexanes-AcOEt
): d 7.31 (5H, m, H-Ar), 4.78 (1H, d, J = 4.8, H-
5), 4.62 (1H, d, J = 10 Hz, H-3), 4.55 (1H, bq, J = 9.2 Hz, H-7), 3.85
(1H, m, H-1), 2.43 (2H, m, H-8eq, H-11eq), 2.13 SO(CDCl ): d
4
(37.3 mg, 0.98 mmol). After work-up,
f
f
2
1
1
1
anes-AcOEt 9:1). [
a]
D
= ꢀ18.7 (c 0.88, CHCl
3
3
8:2). H NMR (CDCl
3
7
4
2
1
.58 (1H, m, H-7), 2.81 (1H, bs, OH), 2.44 (2H, m, H-8eq, H-11eq),
3
0
.12 (2H, m, H-2, H-9), 1.92 (1H, m, H-8ax), 1.87 (3H, s, Me-5 ),
139.2 (C-ipso), 128.5 (C-ortho), 128.3 (C-para), 127.4 (C-meta),
0
0
.59 (1H, t, J = 6 Hz, H-1), 1.51 (3H, s, Me-1 ), 1.21 (6H, s, Me-12,
105.4 (C-5), 85.1 (C-3), 76.9 (C-7), 69.0 (C-1 ), 55.6 (C-2), 43.3 (C-
13
Me-13), 0.93 (1H, d, J = 9.6 Hz, H-11ax). C NMR (CDCl
3
): d 139.4
9), 42.8 (C-1), 40.2 (C-11), 39.1 (C-10), 33.2 (C-8), 30.1 (C-13),
0
(
5
C-ipso), 128.4 (C-ortho), 128.1 (C-para), 127.3 (C-meta), 105.0 (C-
), 84.9 (C-3), 80.5 (C-4 ), 80.3 (C-3 ), 55.5 (C-2), 43.3 (C-9), 42.7
25.6 (C-12), 17.6 (C-2 ). IR (CHCl
3
): 3467, 2945, 1454, 1366, 1263,
0
0
ꢀ1
1136, 1115, 1093, 1076, 1018, 938, 759, 700 cm . MS m/z (rel.
int.): 301 (25), 169 (10), 155 (15), 130 (20), 122 (30), 107 (32),
91 (51), 79 (93), 78 (100), 77 (10). HRFABMS calcd for
(
2
1
C-1), 40.1 (C-11), 39.1 (C-10), 33.2 (C-8), 30.0 (C-13), 25.5 (C-12),
0
4.9 (C-1 ). IR (CHCl
215, 1140, 1092, 1054, 1008, 963, 872, 839, 727, 669, 530 cm
3
): 3500, 2920, 2869, 1455, 1368, 1329, 1254,
ꢀ1
.
19 26 3
C H O +H 303.1960. Found 303.1945.
+
MS m/z (rel. int.): 340 (M +1, 1), 211 (15), 210 (11), 169 (53), 167
(
(
(
(
12), 156 (13), 155 (78),153 (10), 143 (34), 142 (14), 141 (60), 133
13), 131 (22), 130 (40), 129 (42), 128 (23), 122 (72), 121 (13), 119
30), 117 (22), 115 (21), 113 (12), 108 (25), 107 (81), 105 (30), 95
39), 93 (21), 91 (88), 81 (12), 79 (58), 78 (100), 43(13). HRFABMS
4.20. (ꢀ)-(S)-2-Methyl-1,2- hexanediol 16a
A diastereoisomeric mixture of 391 mg (1.09 mmol) of carbinols
13b:14b (1:>99) in 10 mL of acetonitrile:water (4:1) was treated
with 80 mg of p-TsOH and the resulting mixture was stirred and
28 3
calcd for C22H O +Na 363.1936. Found 363.1936.
3
refluxed by 3 h. After, 5 mL of a NaHCO saturated aq. solution
was poured into the reaction mixture and stirred for 15 min,
extracted with ethyl ether, washed with water, dried with anh.
0
0
0
0
4
1
1
.18. (1S,2R,3S,5R,7S,9R,1 S)-5-(1 -Hydroxy-1 -phenyleth-2 -yl)-
2,7
0,10-dimethyl-3-phenyl-4,6-dioxatricyclo[7.1.1.0 ]undecane
4e
Na
in 5 mL of anh. ethyl ether, cooled at ꢀ78 °C and treated with a sus-
pension of 22 mg (0.59 mmol) of LiAlH in 10 mL of anh. ethyl
ether. The reaction mixture was stirred at room temperature for
1 h and the residual LiAlH was deactivated by slow addition of
2 4
SO and concentrated to dryness. This residue was dissolved
4
.18.1. Obtained using method 2
Compound 9a (431.2 mg, 1.43 mmol) in anhydrous ethyl ether
10 mL) was treated with 0.45 mL (4.30 mol) of PhBr and
4
(
4
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E. Becerra-Martínez et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
9
ice chips and stirred until precipitation of a white solid. The crude
reaction was extracted with ethyl ether, washed with brine, dried
refinement, the non-hydrogen atoms were treated anisotropically,
and the hydrogen atoms, included in the structure factor calcula-
tion, were refined isotropically. The final R indices for 10b were
with anh. Na
was chromatographed (silica gel) using hexane-AcOEt (9:1) as elu-
ent, yielding 105 mg (78%) of diol 16a as colorless oil
= +4.4 for the (R)
)}. The mixture of eluents was changed
2 4
SO and concentrated to dryness. The resulting syrup
[I > 2
r
(I)] R
1
= 4.9% and wR
2
3
= 13.0%, largest difference peak and
(I)]
a
hole, 0.148 and ꢀ0.202 e.Å ., and those for 14a were [I > 2
r
2
3
), literature9
23
{[
a]
D
= ꢀ3.1 (c 1.27, CHCl
3
[
a]
D
1 2
R = 5.8% and wR = 14.4%, largest difference peak and hole, 0.237
3
12
enantiomer (c 1.0, CHCl
3
and ꢀ0.199 e.Å . The Olex2 v1.1.5 software allowed calculating
13 14,15
to hexane:EtOAc (1:1) to recover 230 mg (92%) of the chiral auxil-
the Flack (x) and Hooft (y) parameters.
In the case of 10b
iary 10-phenyl-3,10-pinanediol 10a.
these parameters were x = ꢀ0.4(5) and y = 0.15(16) which for the
inverted structure were x = 1.3(5) and y = 0.85(16), while for 14a
they were x = 0.2(3) and y = 0.1(3) which again for the inverted
structure were x = 0.1(3) and y = 01.02(2). Crystallographic data
(excluding structure factors) have been deposited at the Cambridge
Crystallographic Data Centre, from where copies of the data can be
obtained free of charge on application to the CCDC, Cambridge, UK.
The CCDC deposition numbers for 10b and 14a are 1560035 and
1560037, respectively.
4
.21. (ꢀ)-(S)-2-Phenyl-1,2-propanediol 16b
Following a similar procedure as described for 16a, after hydrol-
ysis of a diastereoisomeric mixture of carbinols 13f:14f (07:93),
successive reduction of the resulting crude reaction and purifica-
tion through column chromatography, was obtained diol 16b
2
3
10
23
(
[
a
]
D
= ꢀ5.0 (c 1.02, EtOH), [literature
[
a]
D
= ꢀ5.8 (c 0.12,
EtOH)).
Acknowledgments
4
.22. Single crystal X-ray analysis of 10b and 14a
This research received financial support from SIP-IPN (Grants
20160607 and 20170808) and from CONACyT, Mexico (239906).
Suitable colorless crystals of 10b and 14a, obtained by slow
evaporation from CH
glass fibers and measurements were carried out at room tempera-
ture with graphite monocromated Cu K radiation (k = 1.54184 Å)
in the /2h scan mode on a Siemens P4 diffractometer equipped
with a scintillation detector. Three standard reflections were mon-
itored periodically, which showed no significant change during
data collection. The unit cell parameters for 10b were obtained
from least-squares refinements of 44 reflections in the
2 2
Cl -hexanes solutions, were mounted on
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5
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2 2
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7
3
3
ꢀ1
V = 1962.9(5) Å , Z = 4,
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= 1.118 mg/mm ,
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1
1
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1
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1
1
Please cite this article in press as: Becerra-Martínez, E.; et al. Tetrahedron: Asymmetry (2017), https://doi.org/10.1016/j.tetasy.2017.07.008