Convenient access to sterically hindered C2 chiral 2,2,5,5-tetraphenyltetrahydrofuran-3,4-diols: intramolecular selective 1,4-cyclocondensation of (2R,3R)- and (2S,3S)-1,1,4,4-tetraphenylbutanetetraols

Article abstract of DOI:10.1016/j.tetasy.2009.10.005

Sterically hindered C₂ chiral (3R,4R)- and (3S,4S)-2,2,5,5-tetraphenyltetrahydrofuran-3,4-diols have been conveniently prepared in a very high yield via heterogeneous intramolecular selective 1,4-cyclocondensation of (2R,3R)- and (2S,3S)-1,1,4,

Full text of DOI:10.1016/j.tetasy.2009.10.005

Tetrahedron: Asymmetry 20 (2009) 2474–2478
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Convenient access to sterically hindered C2 chiral 2,2,5,5-tetraphenyltetra-
hydrofuran-3,4-diols: intramolecular selective 1,4-cyclocondensation of
(2R,3R)- and (2S,3S)-1,1,4,4-tetraphenylbutanetetraols
*
Xiaoyun Hu, Zixing Shan , Xitian Peng, Zhen Li
Department of Chemistry, Wuhan University, Wuhan 430072, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 July 2009
Accepted 30 September 2009
Available online 2 November 2009
Sterically hindered C2 chiral (3R,4R)- and (3S,4S)-2,2,5,5-tetraphenyltetrahydrofuran-3,4-diols have been
conveniently prepared in a very high yield via heterogeneous intramolecular selective 1,4-cycloconden-
sation of (2R,3R)- and (2S,3S)-1,1,4,4-tetraphenylbutanetetraol in concentrated hydrohalic acids, respec-
tively. Preliminary examination of additives for the Barbas–List reaction showed that in certain cases, the
hindered C2 chiral tetrahydrofuran-3,4-diols were better chiral auxiliaries than enantiopure (R)- and (S)-
1,10-bi-2-naphthols.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
12 h to furnish a white solid. The solid was recrystallized in ethanol
to give colorless crystals with mp 120–122 °C, ½a D25
¼ ꢁ208 (c 0.87,
ꢀ
The hydroxyl group composition of enantiomerically pure
1,1,4,4-tetrasubstituted butanetetraols determines that they must
have rich reaction chemistry. In order to prepare sterically hindered
C2 chiral 1,1,4,4-tetrasubstituted bifunctional dihydroxy, diamino or
diphosphino compounds, which are considered to be candidates of
highly useful chiral ligands or auxiliaries for asymmetric synthesis,
selective functional group transformation of enantiomerically pure
1,1,4,4-tetrasubstituted butanetetraols was investigated. A short
time ago, we1 reported the selective 1,3-cycloboration of enantio-
merically pure 1,1,4,4-tetraphenylbutanetetraol.2 Herein we report
a convenient procedure for preparing C2 chiral (3R,4R)- and (3S,4S)-
2,2,5,5-tetraphenyltetrahydro-furan-3,4-diols via intramolecular
and selective 1,4-cyclocondensation of (2R,3R)- and (2S,3S)-1,1,4,
4-tetraphenylbutanetetraols under heterogeneous conditions and
preliminary examination of the chiral-inducing action of these steri-
cally hindered chiral vicinal diols.
CHCl3). The 1H NMR spectra shows that there are three sets of aro-
matic proton resonances (the integral intensity for the singlet at
7.11 ppm equals the sum for the other two sets) and two sets of
non-aromatic proton resonances (the one at 1.87 ppm disappeared
after the addition of D2O) in an intensity ratio of 2:3:5:1:1 from 7.7
to 1.8 ppm, meaning that the two benzene rings bound to the same
carbon atom are in different environments; namely, the five pro-
tons in one benzene ring are near equivalent, while the ones in an-
other benzene ring experience in a more complicated coupling; for
the non-aromatic protons, two hydroxyl groups of the tetraol were
reacted via halogenation or dehydration. Furthermore, the 13C
NMR spectra exhibited two kinds of aliphatic carbons bound to
oxygen at 85.2 and 79.5 ppm (the chemical shift of the carbon in
the C–X bond for the sec- or tert-alkyl halides is generally less than
60 ppm3). These spectroscopic characteristics reveal that the prod-
uct must have a symmetric molecular structure. The ESMS (ꢁ) dis-
play an ionic peak of 407 (100%), corresponding to a dehydration
product of (2R,3R)-TBTOL ([M426ꢁ18]+). Based on the above facts,
it may be thought that the compound is (3R,4R)-TTFOL. The X-
ray crystallographic analysis4 is in good agreement with the above
estimation. As seen in Figure 1, recrystallization from ethanol
afforded a solvate of (3R,4R)-TTFOL with ethanol, while in the
molecular system, there is no intramolecular H bonding; both
the hydroxyl groups of the TTFOL were separated in the hydrogen
bonding environment with ethanol and one hydroxyl group of an-
other TTFOL molecule. Based on (3R,4R)-TTFOLꢂEtOH, the yield of
(3R,4R)-TTFOL is over 90%.
2. Results and discussion
2.1. Preparation of (3R,4R)- and (3S,4S)-2,2,5,5-tetraphenyltetra-
hydrofuran-3,4-diols (TTFOL)
The reaction behavior of (2R,3R)- and (2S,3S)-1,1,4,4-tetra-
phenylbutanetetraols (TBTOL) in hydrohalic acids was examined.
Solid (2R,3R)-TBTOL was allowed to stir in concentrated hydro-
chloric acid or 48% hydrobromic acid at room temperature for
A similar reaction of (2S,3S)-1,1,4,4-tetraphenylbutanetetraol
afforded (3S,4S)-2,2,5,5-tetraphenyltetrahydrofuran-3,4-diol; after
* Corresponding author. Tel.: +86 27 68764768; fax: +86 27 68754067.
E-mail address: zxshan@whu.edu.cn (Z. Shan).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.10.005

X. Hu et al. / Tetrahedron: Asymmetry 20 (2009) 2474–2478
2475
Figure 2. Molecular structure of 5,5-diphenyl-2-diphenylmethyl-4-hydroxy-1,3-
dioxolane (DDHDA).
Hydrogen bonding: O6 H6A O3 0.82 1.96 2.776(3) 178.4
O7 H7A O2 0.82 2.03 2.725(4) 142.8
catalysis of hydrohalic acids, there is competition between the for-
mation reactions of DDHDA and TTFOL.
The reaction of (2R,3R)- and (2S,3S)-1,1,4,4-tetraphenylbutane-
tetraols in hydrohalic acids is summarized in Scheme 1.
The above facts reveal that (2R,3R)- and (2S,3S)-1,1,4,4-tetra-
phenylbutanetetraol cannot be halogenated by dilute or concen-
trated hydrohalic acids HX (X = Cl, Br or I) under the experimental
conditions.
Figure 1. ORTEP of (3R,4R)-2,2,5,5-tetraphenyltetrahydrofuran-3,4-diol (TTFOL)
bearing one ethanol molecule.
recrystallization in ethanol, a solvate of (3S,4S)-TTFOL with ethanol
was obtained, mp 119–121 °C; ½a D25
¼ þ207:5 (c 0.5, CHCl3).
ꢀ
Compound (3R,4R)-TTFOL has previously been reported by See-
bach et al.5 as a by-product of chlorination of 4,5-bis(diph-
enylhydroxymethyl)-2,2-dimethyl-1,3-dioxolane with CH3SO2Cl
in the presence of triethylamine, but with a yield of only 17%.
The synthesis and electron spectra of racemic TTFOL have also
been reported.6
2.3. Mechanism of the formation of TTFOL and DDHDA
As aforementioned, (3R,4R)- and (3S,4S)-TTFOLs as well as
DDHDA are isomers possessing the same composition. How is
DDHDA generated from (2R,3R)- or (2S,2S)-TBTOL, via the isomeri-
zation of (3R,4R)- or (2S,3S)-TTFOL or via other routes? To under-
stand the reactions of (2R,3R)- and (2S,3S)-TBTOLs in the
hydrohalic acids, some experiments were performed. The results
indicated that when solid (2R,3R)- and (2S,3S)-TBTOLs were
worked-up in dilute hydrochloric acid or hydrobromic acid (ca.
2 mol Lꢁ1) for 12 h, no cyclization product (3R,4R)-TTFOL, (3S,4S)-
TTFOL or DDHDA could be separated, and (2R,3R)- or (2S,3S)-TBTOL
was recovered almost quantitatively; (3R,4R)- and (3S,4S)-TTFOLs,
whether they were solids or in solution, were sufficiently stable
to the hydrohalic acids, and were not isomerized to DDHDA at
ambient temperatures. These facts reveal that (3R,4R)- or (3S,4S)-
TTFOL was not an intermediate for DDHDA, that is, DDHDA must
be generated from (2R,3R)- or (2S,3S)-TBTOL via a complicated
process under the catalysis of the appropriate concentration of
hydrohalic acids.
For the reaction system, it may be thought that the dehydration
reaction of (2R,3R)- or (2S,3S)-TBTOL is essential and sequentially
competition between the cyclization and rearrangement reaction
takes place. Under heterogeneous condition, the intermediate gen-
erated by dehydration was quickly cyclized into stable (3R,4R)- or
(3S,4S)-TTFOL and isolated out of the reaction system. However,
under homogeneous conditions, the intermediate is readily at-
tacked in situ by the hydrohalic acids to form DDHDA via a compli-
cated process involving C–C bond cleavage.
2.2. Influence of the reaction system on the formation of
(3R,4R)- and (3S,4S)-TTFOL
The formation of (3R,4R)- and (3S,4S)-TTFOL is in close relation-
ship with the reaction system. In the aforementioned two concen-
trated hydrohalic acids, the heterogeneous reactions of solid
(2R,3R)- or (2S,3S)-TBTOL afforded nearly quantitatively (3R,4R)-
or (3S,4S)-TTFOL. While a similar reaction in hydriodic acid gave
some floccule, except (3R,4R)- or (3S,4S)-TTFOL. The floccue was
recrystallized from ethyl acetate to afford a colorless crystal with
mp 164–166 °C. The 1H and 13C NMR spectra, and mass spectra
as well as single crystal X-ray diffraction analysis7 showed the
compound to be 5,5-diphenyl-2-diphenylmethyl-4-hydroxy-1,3-
dioxolane (DDHDA, Fig. 2). The specific rotation indicates that
DDHDA is a racemate. This result may be attributed to its compli-
cated formation process (see Section 2.3).
Solid (2R,3R)-TBTOL was stirred in hydriodic acid at room tem-
perate for 48 h to offer (3R,4R)-TTFOL in 47% yield and DDHDA in
42% yield. It seems that the reaction of (2R,3R)-TBTOL in hydriodic
acid is more complicated than in concentrated hydrochloric acid or
hydrobromic acid.
It has been observed that the homogeneous reaction product of
(2R,3R)- or (2S,3S)-TBTOL in the hydrohalic acids is dependent on
the reaction time. When a homogeneous mixture of a dilute THF
or MeOH solution of (2R,3R)- or (2S,3S)-TBTOL with hydrohalic
acid was stirred for several hours, most of the (2R,3R)- or (2S,3S)-
TBTOL was recovered; however, if it was stirred overnight (more
than 12 h), DDHDA was obtained in very high yield, and little
(3R,4R)- or (3S,4S)-TTFOL was isolated. It appears that under the
A
possible mechanism for the formation of (3R,4R)- or
(3S,4S)-TTFOL and DDHDA from (2R,3R)- or (2S,3S)-TBTOL is
shown in Scheme 2. As can be seen in Scheme 2, (2R,3R)-
TBTOL (A) is dehydrated under catalysis of hydrohalic acids
to generate a tertiary carbonium ion C (C1 or C2) via dehydra-
tion. The carbonium ion undergoes deprotonation to form

2476
X. Hu et al. / Tetrahedron: Asymmetry 20 (2009) 2474–2478
Ph
Ph
Ph
Ph
Ph
O
Ph
Ph
Ph
Ph
Ph
O
Ph
HO
HO
Ph
Ph
Ph
Ph
O
O
HX-H2O
r.t. 12 h
OH
OH
or
+
OH
(3S,4S)-TTFOL
HO
OH
HO
HO
DDHDA
(3R,4R)-TTFOL
Ph
or
trace
over 90%
Ph
HX/MeOH-H2O
or THF-H2O
Ph
Ph
Ph
O
Ph
Ph
OH
OH
HO
HO
Ph
.
r.t. overnight
O
HO
DDHDA
over 90%
Ph
TBTOL
HX = HCl, HBr
Scheme 1. Reaction of (2R,3R)- or (2S,3S)-1,1,4,4-tetraphenylbutanetetraol in hydrohalic acid.
Ph
Ph
Ph
Ph
H
O
Ph
Ph
HO
HO
Ph
Ph
H2+O
HO
Ph
Ph
H+
OH
OH
OH
OH
OH
-H2O
+
+
O
H
HO
Ph
OH
OH
Ph
Ph
Ph
Ph
Ph
A
B
C1
C2
I
-H+
O
II
-H+
Ph
Ph
Ph
O
Ph
O
Ph
O
Ph
Ph
O
Ph
Ph
Ph
Ph
OH
Ph
HO
+
cyclization
H2O
-H+
O
O
O
Ph
Ph
Ph
Ph
Ph
H
+
HO
TTFOL
Ph
Ph
O
HO
Ph
I
J
DDHDA
D
hemiacetal
formation
reaction
proton
shifting
+
OH
OH2
Ph
Ph
Ph
Ph
HO
Ph
+
Ph
Ph
HO
H+
-H2O
O
Ph
Ph
O
Ph
Ph
enolization
O
Ph
Ph
O
Ph
HO
+
Ph
Ph
H
O
H
F
E
G
Scheme 2. A possible mechanism for the formation of (3R,4R)-TTFOL and DDHDA from (2R,3R)-1,1,4,4-tetraphenylbutanetetraol.
(3R,4R)-TTFOL from C1 via Route I or a dihydroxyaldehyde D
from C2 via Route II. It can be anticipated, that D would un-
dergo intramolecular hemiacetal formation reaction to produce
a 2,4-dihydroxytetrahydrofuran E. Compound E is not stable
under acidic conditions, and would undergo further dehydra-
tion, enolization, rearrangement, cyclization and hydration to
give DDHDA.
It is well known that the C–C bond of a vicinal diol is readily
broken by periodic acid8 or lead tetreacetate9 via oxidation. The
cleavage reaction of the C–C bond by a hydrohalic acid seems to
have been seldom observed.
2.4. Preliminary examination on the chiral induction activity of
(3R,4R)- and (3S,4S)-TTFOLs
Compounds (3R,4R)- and (3S,4S)-TTFOLs are sterically hindered,
C2 chiral diols and can be conveniently transformed into diamine,
diphosphine, and cyclophosphoric ester. according to similar pro-
cedures for transformation of hydroxyl group to other functional
groups reported previously. However, the chemistry of the steri-
cally hindered C2 chiral diols has been seldom investigated before,
although unsubstituted optically active cis- and trans-tetrahydro-
furan-3,4-diols have been synthesized via a variety of routes10

X. Hu et al. / Tetrahedron: Asymmetry 20 (2009) 2474–2478
2477
and their derivatives applied in asymmetric epoxidations,11 asym-
metric hydrogenation10f, etc.12 Considering that chiral diols13 are
highly effective chiral induction auxiliary agents for the (S)-pro-
line-catalyzed asymmetric direct aldol reaction, we decided to
examine the action of (3R,4R)- and (3S,4S)-TTFOLs in this type of
reaction; we found that they displayed an excellent chiral assistant
function. The addition of 1 mol % (3R,4R)- or (3S,4S)-TTFOL, in the
direct (S)-proline-catalyzed addition of acetone to 4-chlorobenzal-
dehyde, 4-bromobenzaldehyde, or 2,6-dichlorobenaldehyde, in-
creased the enantiomeric purity of the desired products up to 9%,
11%, and 26%, respectively, and in the cases of the reactions with
4-chlorobenaldehyde and 2,6-dichlorobenzaldehyde, (3R,4R)- and
(3S,4S)-TTFOLs were stronger asymmetric induction auxiliary
agents than enantiopure (R)- and (S)-1,10-bi-2-naphthols (Table 1).
and PhMgBr in THF in a conventional Grignard reaction procedure.
-Proline was purchased from commercial suppliers, and oven-
dried at ca. 120 °C and ground finely prior to use. Acetone was
dried over anhydrous K2CO3 and redistilled from KMnO4. Other
commercially available starting materials were used without fur-
ther purification unless specified.
IR spectra were recorded on a Nicolet 170 SX FT-IR spectropho-
tometer, in KBr, in cmꢁ1. NMR spectra were recorded at 300 or
400 MHz for 1H, and 75 MHz for 13C on a Varian Mercury VS 300
or Bruker AV 400; d in (ppm) relative to TMS. Optical rotations
were measured on a Perkin–Elmer 341 Mc polarimeter. Mp: VEB
Wägetechnik Rapido PHMK 05; uncorrected.
L
The single crystal X-ray diffraction analysis was performed on
Bruker SMART 1 K CCD diffractometer using graphite-monochro-
0
mated Mo K
a radiation (k = 0.71073 ÅA). The structure was solved
by direct methods (SHELXS-97)16 and refined17 on F2 values by full-
3. Conclusion
matrix least squares for all unique data.
In conclusion, a convenient access to sterically hindered C2
chiral (3R,4R)- and (3S,4S)-TTFOLs has been developed. Solid
(2R,3R)- or (2S,3S)-TBTOL have been worked-up in concentrated
hydrochloric acid or 48% hydrobrominic acid at ambient tempera-
ture for 12 h under heterogeneous condition to form nearly quan-
titatively (3R,4R)- or (3S,4S)-TTFOL. However, under homogeneous
condition (such as in a THF–H2O or MeOH–H2O solution), the
1,1,4,4-tetraphenylbutanetetraols reacted with the hydrohalic
acids overnight to offer 5,5-diphenyl-2-diphenylmethyl-4-hydro-
xy-1,3-dioxolane in high yield. Preliminary examination of their
asymmetric induction ability shows that (3R,4R)- or (3S,4S)-TTFOL
is a promising chiral auxiliary agent for asymmetric synthesis.
4.2. Preparation of (3R,4R)- and (3S,4S)-2,2,5,5-tetraphenyltetra-
hydrofuran-3,4-diols (TTFOL)
A representative procedure: A mixture of 0.396 g (0.93 mmol) of
(2R,3R)-1,1,4,4-tetraphenyl- butanetetraol and 12 mL concentrated
hydrochloric acid was stirred at ambient temperature for 12 h,
filtered, and a white solid was collected. The solid was crystallized
in ethanol to afford 0.361 g of colorless needle crystals of (3R,4R)-
2,2,5,5-tetraphenyltetrahydrofuran-3,4-diol bearing one ethanol
molecule, mp: 120–122 °C, 95% yield. ½a D25
¼ ꢁ208 (c 0.87, CHCl3).
ꢀ
IR (KBr, cmꢁ1):
m
3414 s br, 1637 s, 1618 s, 1017 ms. 1H NMR
(CDCl3, 300 MHz): d 7.68 (d, J = 6.9 Hz, 4H, Ph-H), 7.45–7.33 (m,
6H, Ph-H), 7.11 (s, 10H, Ph-H), 4.51 (d, J = 6.9 Hz, 1H, C(3)–H or
C(4)–H), 4.50 (d, J = 7.8 Hz, 1H, C(4)–H or C(3)–H), 3.71
(q, J = 6.9 Hz, 2H, CH2 of EtOH); 1.87 (s, 2H, OH, disappeared after
adding D2O), 1.23 (t, J = 6.9 Hz, 3H, Me of EtOH). 13C NMR (CDCl3,
75 MHz): d 145.9, 142.1, 128.5, 128.0, 127.8, 127.6, 127.3, 126.6,
85.1, 79.3, 58.7, 18.6. ES-MS (MeOH, ES+): 431(100, [M408+Na]+).
4. Experimental
4.1. General
Enantiopure (2R,3R)- and (2S,3S)-1,1,4,4-tetraphenylbutanetet-
raols were synthesized from diethyl (2R,3R)- and (2S,3S)-tartrate
According to
a
similar procedure, (3S,4S)-2,2,5,5-tetra-
phenyltetrahydrofuran-3,4-diol was obtained via intramolecular
Table 1
Comparison of (3R,4R)- and (3S,4S)-TTFOLs with enantiopure BINOLs in chiral assistant activity in asymmetric aldol additions catalyzed by a (S)-proline-diol systema
0.5-1 mol% diol
30 mol% (S)-proline
O
O
Ο
OH
+
acetone / DMSO (3:1)
R
H
R
a 2D0
a 2D7
a 2D5
a 2D0
a 2D0
a 2D5
a 2D7
a 2D5
a 2D7
a 2D7
a 2D0
a 2D7
a 2D5
a 2D7
a 2D7
a 2D0
ꢀ
ꢀ (in CHCl3)
Entry
R in aldehyde
Chiral diol additive
Yield (%)
ee (%)
Config.
½
1
2,6-Cl2C6H3
2,6-Cl2C6H3
2,6-Cl2C6H3
2,6-Cl2C6H3
2,6-Cl2C6H3
4-ClC6H4
(R,R)-TTFOL
(S,S)-TTFOL
(R)-BINOL
(S)-BINOL
0
80
83
89
90
80
78
79
78
79
76
83
87
74
76
82
98
97
96
96
89
86
85
83
83
75
89
91
97
97
65b
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
½
½
½
½
½
½
½
½
½
½
½
½
½
½
½
ꢀ
¼ ꢁ53:3 (c 0.6)
¼ ꢁ52:8 (c 0.7)
¼ ꢁ51 (c 0.9)
2
ꢀ
3
ꢀ
4
ꢀ
¼ ꢁ51:7 (c 1.3)
¼ ꢁ48:4 (c 1.0)
¼ þ55:4 (c 0.8)
¼ þ54:7 (c 0.9)
¼ þ53:5 (c 1.0)
¼ þ52:9 (c 1.3)
¼ þ48:3 (c 1.0)
¼ þ44:3 (c 0.9)
¼ þ45:3 (c 0.9)
¼ þ48:3 (c 0.8)
¼ þ47:1 (c 0.8)
¼ þ35:3 (c 1.0)
5
ꢀ
6
(R,R)-TTFOL
(S,S)-TTFOL
(R)-BINOL
(S)-BINOL
0
ꢀ
7
4-ClC6H4
ꢀ
8
4-ClC6H4
ꢀ
9
4-ClC6H4
ꢀ
10
11
12
13
14
15
4-ClC6H4
ꢀ
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
(R,R)-TTFOL
(S,S)-TTFOL
(R)-BINOL
(S)-BINOL
0
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
a
The reactions were carried out in acetone/DMSO (3:1) at 0 °C for 48 h, where 1 mol % (3R,4R)- or (3S,4S)-TTFOL, 0.5 mol % (R)-BINOL and 1 mol % (S)-BINOL were used as
chiral additives, respectively. Entries 5 and 10 are abstracted from the literature.14 The ee was obtained by comparison with the maximum of specific rotation.
b
Entry 15 is cited from the literature.15

2478
X. Hu et al. / Tetrahedron: Asymmetry 20 (2009) 2474–2478
cyclocondensation of (2S,3S)-1,1,4,4-tetraphenylbutanetetraol.
extracted with ethyl acetate (10 mL ꢃ 3). The combined organic
phase was dried over anhydrous Na2SO4, filtered, concentrated,
and purified through flash column chromatography on a silica gel
(200–300 mesh, eluent: petroleum ether/acetate 2:1) to give the
desired product. The results are summarized in Table 1.
mp: 119–121 °C, 92% yield. ½a D25
ꢀ
¼ ꢁ207:8 (c 0.7, CHCl3). 1H NMR
(CDCl3, 400 MHz): d 7.70 (d, J = 8.0 Hz, 4H, Ph-H), 7.47–7.36 (m,
6H, Ph-H), 7.13–7.09 (s, 10H, Ph-H), 4.49 (s, 2H, C(4)–H and
C(3)–H), 3.69 (q J = 6.8 Hz, 2H, CH2 of EtOH), 2.26 (s, 2H, OH, disap-
peared after adding D2O), 1.40 (s, 1H, OH, disappeared after adding
D2O), 1.24 (t, J = 6.8 Hz, 3H, Me of EtOH). 13C NMR (CDCl3, 75 MHz):
d 145.6, 141.9, 128.3, 127.8, 127.4, 127.1, 126.4, 85.0, 79.2, 58.5,
18.4.
Acknowledgments
We thank the National Natural Science Foundation of China
(20672083 and 20872115) for financial support. We also thank
associate professor Zhongxing Jing for beneficial discussion on
the formation mechanism of 2-diphenylmethyl-4-hydroxy-5,5-di-
phenyl-1,3-dioxolane.
4.3. Crystallographic data of (3R,4R)-TTFOL
Empirical formula, C30H30O4 (C28H24O3ꢂC2H5OH); formula weight,
454.54;calculateddensity, 1.149 g/cm3;volume(V), 5257(2) Å3;crystal
system, orthorhombic; Z = 8; space group, P2(1)2(1)2(1); unit cell
References
dimensions, a = 10.120 (3), b = 14.658 (4), c = 35.440 (9);
l, 0.075
mmꢁ1; ꢁ12 < h < 12, ꢁ13 < k < 18, ꢁ43 < l < 37; F(0 0 0): 1936; GOF,
1. Shan, Z. X.; Hu, X. Y.; Zhou, Y.; Peng, X. T.; Yi, J. Tetrahedron: Asymmetry 2009,
20, 1445–1450.
2. Toda, F.; Tanaka, K. Tetrahedron Lett. 1988, 29, 551–554.
1.028; T = 273(2) K; radiation type, Mo Ka; R(reflections) = 0.0558
(7317); wR2 (reflections) = 0.1727 (10296).
3. Larterbur, P. C. Ann. N.Y. Acad. Sci. 1958, 70, 841.
4. Final atomic coordinates of the crystal, along with lists of anisotropic thermal
parameters, hydrogen coordinates, bond lengths, and bond angles, have been
deposited with the Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC 719629. Data can be obtained free of charge, on request,
via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK (fax:
+44 1223 336 033 or e-mail: deposit@ccdc.cam.ac.uk).
5. Seebach, D.; Beck, A. K.; Hayakawa, M.; Jaeschke, G.; Kuhnle, F. N. M.; Nageli, I.;
Pinkerton, A. B.; Rheiner, P. B.; Duthaler, R. O.; Rothe, P. M.; Weigand, W.;
Wunsch, R.; Dick, S.; Nesper, R.; Worle, M.; Gramlich, V. Bull. Soc. Chim. Fr. 1997,
134, . 315–331.
4.4. Formation of 2-diphenylmethyl-4-hydroxy-5,5-diphenyl-
1,3-dioxolane (DDHDA)
In a similar reaction to the above, a THF solution of (2R,3R)-
1,1,4,4-tetraphenylbutanetetraol was allowed to stir with hydro-
chloric or hydrobromic acid under homogeneous conditions over-
night to afford a solid. The solid was recrystallized in AcOEt to
give 2-diphenylmethyl-4-hydroxy-5,5-diphenyl-1,3-dioxolane, 90%
6. Jasiobedzki, W.; Wozniak-Kornacka, J. Bull. Acad. Pol. Sci. Ser. Sci. Chim. 1979, 27,
665–680 (Chem. Abstr. 94:120347).
yield, mp 164–166 °C. ½a D25
ꢀ
¼ 0 (c 1, CHCl3). IR (KBr, cmꢁ1): 2027
w, 1650 br, 1435, 1360, 1102, 1026; 1H NMR (300 MHz, CDCl3): d
7.51–7.45 (m, 8H, Ph-H), 7.38–7.19 (m, 12H, Ph-H), 5.91 (d,
J = 12.6 Hz, 1H, C–H), 5.55 (d, J = 2.1 Hz, 1H, C–H), 4.54 (s, 1H, C–
H), 1.11 (d, J = 11.7 Hz, 1H, OH, disappeared after adding D2O).
13C NMR (75 MHz, CDCl3): d 136.9, 136.8, 127.6, 126.4, 126.0,
125.8, 125.1, 124.8, 124.0, 101.1, 95.3, 88.2, 52.8. ES-MS (MeOH,
ES+): 431 (58, [M408+Na]+).
7. Final atomic coordinates of the crystal, along with lists of anisotropic thermal
parameters, hydrogen coordinates, bond lengths, and bond angles, have been
deposited with the Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC-719628. Data can be obtained free of charge, on request,
from the Director, Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge, CB2 1EZ, UK (fax: (+44) 1223 336 033; e-mail: deposit@ccdc.
cam.ac.uk; web: http//www.ccdc.cam.ac.uk).
8. Morrison, R. T.; Boyd, R. N. Organic Chemistry, 3rd ed.; Allyn and Bacon, 1973.
9. (a) Trahanovsky, W. S.; Young, L. H.; Bierman, M. H. J. Org. Chem. 1969, 34, 869–
871; (b) Criegee, R. In Oxidation in Organic Chemistry; Wiberg, K. B., Ed.;
Academic Press: New York, NY, 1965. Chapter V; (c) Starnea, W. H., Jr. J. Am.
Chem. Soc. 1968, , 90, 1807. and references cited therein; (d) Perlin, A. S.;
Suzuki, S. Can. J. Chem. 1962, 40, 1226–1229.
4.5. Crystallographic data of DDHDA
10. (a) Ohta, T.; Komoriya, S.; Yoshino, T.; Uoto, K.; Nakamoto, Y.; Naito, H.;
Mochizuki, A.; Nagata, T.; Kanno, H.; Haginoya, N.; Yoshikawa, K; Nagamochi,
M.; Kobayashi, S.; Ono, M. U.S. 2005020645, 2005.; (b) Zhao, L. S.; Han, B.;
Huang, Z. L.; Miller, M.; Huang, H. J.; Malashock, D. S.; Zhu, Z. L.; Milan, A.;
Robertson, D. E.; Weiner, D. P.; Burk, M. J. J. Am. Chem. Soc. 2004, 126, 11156–
11157; (c) Lambert, J. B.; Lu, G.; Singer, S. R.; Kolb, V. M. J. Am. Chem. Soc. 2004,
126, 9611–9625; (d) Skarzewski, J.; Gupta, A. Tetrahedron: Asymmetry 1997, 8,
1861–1867; (e) Barili, P. L.; Berti, G.; Mastrorilli, E. Tetrahedron 1993, 49, 6263–
6276; (f) Terfort, A. Synthesis 1992, 951–953; (g) Korolev, A. M.; Eremenko, L.
T.; Berezina, L. I.; Lagodzinskaya, G. V.; Manelis, G. B. Izvestiya Akademii Nauk
SSSR. Seriya Khimicheskaya 1975, 2516–2524.
Empirical formula, C28H24O3; formula weight, 408.47; calculated
density, 1.257 g/cm3; volume (V), 4316 (4) Å3; crystal system, mono-
clinic; Z = 8; space group, C2/c; unit cell dimensions, a = 39.95 (2),
b = 5.622 (3), c = 22.604 (12); b = 121.784 (8);
l
, 0.081 mmꢁ1; ꢁ28 < h
< 50, ꢁ6 < k < 7, ꢁ28 < l < 17; F(0 0 0): 1728; GOF, 1.049. T = 273(2) K,
radiation type, Mo Ka; R (reflections) = 0.0394 (3306); wR2 (reflec-
tions) = 0.1041 (4443).
4.6. Asymmetric direct aldol reaction catalyzed by a (S)-proline-
11. Bell, D.; Miller, D.; Attrill, R. P. WO 9403271, 1994.
12. (a) Recuero, V.; Brieva, R.; Gotor, V. Tetrahedron: Asymmetry 2008, 19, 1684–
1688; (b) Chan, K. F. Diss. Abstr. Int., B 2002, 63, 2386 (Chem. Abstr. 141: 71585).
13. (a) Zhou, Y.; Shan, Z. X. J. Org. Chem. 2006, 71, 9510–9512; (b) Zhou, Y.; Shan, Z.
X. Tetrahedron: Asymmetry 2006, 17, 1671–1677.
14. Zhou, Y. Ph. D. Dissertation, Wuhan University, 2006, (in Chinese).
15. List, B.; Lerner, R. A.; Barbas, C. F., III J. Am. Chem. Soc. 2000, 122, 2395–2396.
16. Sheldrick, G. M. SHELXS-97, Program for Structure Solution. Acta Crystallogr., Sect.
A 1990, 46, 467–473.
enantiopure TTFOL system
A representative procedure: In a test tube fitted with a magnetic
bar, (S)-proline (1.5 mmol) and (3R,4R)-2,2,5,5-tetraphenyltetra-
hydrofuran-3,4-diol (0.05 mmol) were charged, and followed by
injection of acetone (3 mL) and DMSO (1 mL). After stirring for
15 min at 0–5 °C, an aromatic aldehyde (5 mmol) was added and
stirred continuously at the same temperature for 48 h. The reaction
was quenched with saturated aqueous ammonium chloride and
17. Sheldrick, G. M. In shelxl-97, Program for Crystal Structure Refinement;
University of Göttingen: Göttingen, Germany, 1997.