Neighboring lithium-assisted [1,2]-wittig rearrangement: Practical access to diarylmethanol-based 1,4-diols and optically active binol derivatives with axial and sp3-central chirality

Article abstract of DOI:10.1002/chem.201003111

A facile and practical methodology for the synthesis of synthetically useful diarylmethanol-based 1,4-diols and enantiomerically pure BINOL-derived diols with axial and sp³-central chirality has been developed through neighboring lithium-promot

Full text of DOI:10.1002/chem.201003111

DOI: 10.1002/chem.201003111
Neighboring Lithium-Assisted [1,2]-Wittig Rearrangement: Practical Access
to Diarylmethanol-Based 1,4-Diols and Optically Active BINOL Derivatives
with Axial and sp3-Central Chirality
Guang Gao,[a] Feng-Lei Gu,[a] Jian-Xiong Jiang,[a] Kezhi Jiang,[a] Chun-Qi Sheng,[a]
Guo-Qiao Lai,*[a] and Li-Wen Xu*[a, b]
Abstract: A facile and practical meth-
odology for the synthesis of syntheti-
cally useful diarylmethanol-based 1,4-
diols and enantiomerically pure
BINOL-derived diols with axial and
sp3-central chirality has been developed
through neighboring lithium-promoted
[1,2]-Wittig rearrangement. The chirali-
ty transfer process shows a broad sub-
strate scope in terms of the aromatic
ether substituent, which allows access
to a broad of range of chiral 1,1’-bi-
naphthalene-2-a-arylmethanol-2’-ols
with excellent enantioselectivities
(>99% enantiomeric excess) and
yields (84–96%). This should be con-
sidered as an available and attractACHTUNGTRENNUNGive
chiral source to design and prepare
privileged ligands or catalysts.
AHCTUNGTRENNUNG
Keywords: asymmetric synthesis ·
chirality · chirality transfer · diols ·
Wittig rearrangement
Introduction
acetal compounds, with retention of configuration at the mi-
grating carbon atom.[5] Thus, it would be highly desirable to
develop an enantioselective [1,2]-Wittig rearrangement that
could be used in the preparation of synthetically useful
chiral products. Herein, we report the [1,2]-Wittig rearrange-
ment of two different types of phenol benzyl ethers, based
on a neighboring lithium-promoted process, which results in
synthetically useful diarylmethanol-based 1,4-diols and
enantiomerically pure BINOL-derived diols with axial and
sp3-central chirality.
The facile preparation of unsymmetrical diols is an impor-
tant and challenging goal in synthetic chemistry, because
they are versatile building blocks for complex natural mole-
cules.[6] In particular, 1,4-diols (including diarylmethanol-
based 1,4-diols) are widely used for the preparation of im-
portant heterocycles, such as g-lactones, pyrroles, and tetra-
hydrofurans, and therapeutically relevant compounds, for
example, the antidepressant drug escitalopram.[7] Despite
the proposal of various modified methods for the synthesis
of 1,4-diols in the last decade, some of these still suffer from
drawbacks in the key step, such as low yields, employment
of expensive chemicals, tedious procedures, or multiple
steps. Hence, development of new methodology to simulta-
neously address these issues was desirable.
The [1,2]-Wittig rearrangement is a classic rearrangement
through a 1,2-alkyl shift onto an a-oxycarbanion terminus,
which proceeds by a radical dissociation–recombination
mechanism.[1] The first example of Wittig rearrangement
was reported in 1942[2] and since then the transformation
has attracted much interest from both a mechanistic and
synthetic point of view.[3] Unfortunately, although the [1,2]-
Wittig rearrangement is recognized as a powerful method
for carbon–carbon bond-forming reactions and there are
many reports on mechanistic or stereochemical studies, the
utility of the [1,2]-Wittig rearrangement in organic synthesis
has been limited by low yields, the restricted range of suit-
ACHTUNGTRENNUNG
able substrates, and the lack of good stereocontrol.[4] Few
successes have been reported in the area of asymmetric syn-
thesis; however, the enantioselective [1,2]-Wittig rearrange-
ment was shown to be of particular value for the construc-
tion of chiral alcohols and their analogues from ethers or
[a] G. Gao,+ F.-L. Gu,+ Prof. J.-X. Jiang, Dr. K. Jiang, Dr. C.-Q. Sheng,
Prof. G.-Q. Lai, Prof. Dr. L.-W. Xu
Key Laboratory of Organosilicon Chemistry and
Material Technology of Ministry of Education
Hangzhou Normal University, Hangzhou 310012 (P. R. China)
Fax : (+86)571-28865135
E-mail: liwenxu@hznu.edu.cn
licpxulw@yahoo.com
Results and Discussion
[b] Prof. Dr. L.-W. Xu
State Key Laboratory for Oxo Synthesis and Selective Oxidation
Lanzhou Institute of Chemical Physics
Chinese Academy of Sciences
Our interest in the use of 2-benzyloxyphenylmethanol (3a)
as a scaffold originates from salicylaldehyde (1) alkylation
and reduction.[8] We are particularly attracted to the ability
of the terminal alcohol moiety to induce an aggregate lithi-
um ion around the a-carbon center of the benzyl moiety,
which is beneficent to the lithiation and subsequent [1,2]-
Lanzhou, 730000 (P. R. China)
[+] These authors contributed equally to this work.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201003111.
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FULL PAPER
Table 1. Scope of the [1,2]-Wittig rearrangement of 3 to diarylmethanol-
based diols 4.[a]
Entry
R1
R2
Product
Yield [%][b]
1
2
3
4
5
6
7
8
9
H
5-Cl
H
H
H
4-OMe
5-OMe
4-OMe
4-OMe
H
H
4-Me
4-tBu
2-Me
H
H
4-Me
4-tBu
4a
4b
4c
4d
4e
4 f
4g
4h
4i
91
64
74
85
81
72
31
76
58
[a] Reagents and conditions: A solution of iBuLi (1.23m in hexane,
2.5 equiv) was added to 3 (5 mmol) in anhydrous THF (30 mL) at ꢀ788C
under N2; stirred at RT for 1 h. [b] Isolated yield.
was shifted to the development of a highly efficient enantio-
selective [1,2]-Wittig rearrangement through chirality trans-
fer from C2-axial 1,1’-binaphthalene-2,2’-diol (BINOL) to
BINOL-derived alcohols that contained a stereogenic tetra-
hedral carbon center. Specifically, we were interested in the
application of a modified [1,2]-Wittig rearrangement in the
synthesis of novel BINOL-derived enantiomerically pure lig-
Scheme 1. ACHTUNGTRENNUNG[1,2]-Wittig rearrangement of 2-benzyloxy-phenylmethanol
(3a).
Wittig rearrangement (Scheme 1). We envisioned that an in-
tramolecular neighboring lithium atom would be a useful
linker for the subsequent intramolecular-like radical dissoci-
ation–recombination. The results of this preliminary study
were instructive. Initial experiments demonstrated that the
clean reaction of 3a with iBuLi or nBuLi in THF afforded,
as expected, the diphenylmethanol-based 1,4-diol 4a with a
high yield (Scheme 1, 91%).
With these observations in hand, attention was turned to
the key question of reaction scope. The requisite starting
materials 3 were readily prepared by benzylation, followed
by reduction. Eight further substrates were examined in the
[1,2]-Wittig rearrangement under the optimized conditions
and the results are summarized in Table 1. The intra-
ACHTUNGTRENNUNG
from simple and readily available starting materials is an im-
portant goal and challenge in organic chemistry.[10] Hence,
over the past three decades, the synthesis of enantiopure
compounds has emerged as one of the most active fields in
organic synthesis. Numerous well-documented cases high-
light the necessity for the development of asymmetric syn-
thesis and successful stereoselective reactions.[11] In the field
of asymmetric synthesis, BINOL and its derivatives, for
example,
2,2’-bis(diphenylphosphino)-1,1’-binaphthyl
(BINAP), have been arguably the most widely used as a
source of chirality for both stoichiometric and catalytic
asymmetric reactions.[12]
A
Among many successful ligands and organocatalysts, ax-
ially chiral biaryls, with both axial and sp3-central chirality,
comprise a very interesting and attractive area of research.
The presence of an additional chiral center on the biaryl
framework was found to exert significant influences on the
biological activity of axially chiral biaryl natural products[13]
and the enantioselectivity and activity of the catalysts in
asymmetric reactions.[14] However, to the best of our knowl-
edge to date, there are few successful enantioselective syn-
theses of 2,2’-disubstituted-1,1’-binaphthyls that contain two
chiral elements through axial-to-central chirality transfer.
There are only a few reported successes of the asymmetric
synthesis of enantiomerically pure BINOL derivatives with
axial and sp3-central chirality. An axial-to-central chirality
transfer approach is of particular value for the improvement
of the enantioselectivity. Such an approach is highly desira-
ACHTUNGTRENNUNG
on the aromatic ring and, in most cases, the diols were ob-
tained in good yields. Interestingly, the presence of a chlor-
ine substituent was not problematic (Table1, entry 2), which
is significant as it allows for the introduction of a potential
handle for further functionalization of the diols. A 4-meth-
ACHTUNGTRENNUNGoxy substituent was well tolerated (Table 1, entry 6), where-
as the presence of the methoxy group in the 5-position re-
sulted in low yield (Table 1, entry 7). We suspect that this is
due to the restrictive effect of the para-methoxy substituent
on the cleavage of the C O bond and subsequent formation
of the radical intermediate.
Inspired by this success, the previous examples of enantio-
selective [1,2]-Wittig rearrangement,[9] and on the basis of
the unique structure of binaphthyl compounds, our focus
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L.-W. Xu, G.-Q. Lai et al.
Table 2. Scope of the enantioselective [1,2]-Wittig rearrangement of 6 to
Ar-BINMOLs 7.[a]
ble and is not trivial. With knowledge of the mechanism of
the [1,2]-Wittig rearrangement, we assumed that the exis-
tence of a lithium salt in the same molecule could promote
the one-pot enantioselective [1,2]-Wittig rearrangement
through a well-known radical dissociation-recombination
mechanism. As shown in Scheme 2, the intramolecularly as-
Entry
R
Product
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
H
H
7b
7a
7c
7d
7e
7 f
7g
7h
7i
95
96
88
94
84
93
94
93
87
93
88
89
99.1
>99.9[d]
98.9
99.6
99.7
3,5-(tBu)2
p-CH3
p-F
o-CH3
o-OCH3
m-OCH3
p-OCH3
2-Np
99.4
>99.9
>99.9
99.5
99.9
>99.9
99.6
9
10
11
12
7k
7l
7m
p-SiMe3
p-tBu
Scheme 2. Hypothesis of neighboring lithium-assisted [1,2]-Wittig rear-
rangement of monobenzyl BINOL derivative 6a.
[a] Reaction conditions: (S)-BINOL derivative 6 (2 mmol), iBuLi or n-
BuLi (5 mmol, 1.23m in pentane, 2.5 equiv), THF (20 mL); ꢀ788C; 1.5 h.
[b] Isolated yield. [c] Enantiomeric excess was determined by chiral
HPLC analysis. [d] Reaction with the monosubstituted aryl ether of (R)-
BINOL; see Scheme 2 for stereochemistry of the product 7a.
sembled dimeric lithium intermediate (II-1!II-2!II-3) in-
duces the radical to generate an enantiomerically pure
BINOL derivative with axial and sp3-central chirality via a
five-membered transition state, with the aid of hydrogen
bonding and the aggregation of a lithium moiety. Compara-
bly, when a solution of 2,2’-di(2-benzyloxy)-1,1’-binaphthyl
(8) in tetrahydrofuran was treated under the optimized con-
ditions described above, the desired diol, 1,1-(1,1’-binaphth-
2,2’-diyl)-bis(2-phenylmethanol) (9), was isolated in a very
low yield (<10%, Scheme 3), but as a single isomer in ex-
cellent (>99%) enantiomeric excess (ee). In agreement
with the mechanism proposed in Scheme 2, the rearrange-
ment must be slow without the activation by the intra-
had only a small impact on the axial-to-central chirality
transfer and, in all cases, almost complete asymmetric induc-
tion (eeꢁ99%) was obtained. It is worth noting that all of
the 1,1’-binaphthalene-2-a-arylmethan-2’-ol (Ar-BINMOL)
products 7 could be prepared on a multigram scale without
loss of enantioselectivity, which would be beneficial to the
preparation and application of novel ligands and catalysts
based on this scaffold. Consistent with this conclusion, the
reaction of racemic starting materials under the optimized
conditions resulted in the almost quantitative formation of
only two isomers, (SA,RC)-7 and (RA,SC)-7. Thus, it is inter-
esting to study the subsequent formation of (SA,SC)-7 or
(RA,RC)-7 through simple transformations. However, at-
tempts to prepare (SA,SC)-11 from (SA,RC)-7b led to a mix-
ture of two stereoisomers in enantiomeric ratios between
ACHTUNGTRENNUNG
67:33 and 92:8 (SA,RC)-7b/ACHTNUTGRENUNG(SA,SC)-11, dependent on the re-
ducing agent. These reductions of ketone derivative 10 re-
vealed it is difficult to convert (SA,RC)-7b to (SA,SC)-11 by
an oxidation/reduction procedure (Scheme 4).
Scheme 3. ACHTUNGTRENNUNG[1,2]-Wittig rearrangement of 2,2’-di(2-benzyloxy)-1,1’-bi-
naphthyl (8).
Conclusion
The scope of the [1,2]-Wittig rearrangement under the op-
timized conditions was studied with a set of substituted aryl
ether derivatives of (S)-BINOL (Table 2). As indicated by
the results presented in Table 2, the [1,2]-Wittig rearrange-
ment shows a remarkably wide scope and functional group
tolerance, which allows the reaction to be carried out in the
presence of any functionalities that are compatible with the
organolithium reagent. To our delight, variation of the sub-
stituent R in the monosubstituted aryl ether of BINOL 6
The facile and practical methodology described converts
simple and readily accessible benzyl ethers and axially chiral
monoalkylated BINOLs into synthetically useful diaryl-
AHCTUNGTREGmNNUN ethanol-based 1,4-diols and enantiomerically pure
BINOL-derived diols with axial and sp3-central chirality, re-
spectively, through axial-to-central chiral transfer, respec-
tively. The chirality transfer process shows very broad sub-
strate scope in terms of the aromatic ether, with excellent
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Neighboring Lithium-Assisted [1,2]-Wittig Rearrangement
FULL PAPER
(100 MHz, CDCl3): d=62.6, 73.1, 125.5, 127.7, 128.1, 128.5, 129.5, 129.9,
133.7 ppm; IR (KBr): n˜ =3282, 2909, 1598, 1012, 700 cmꢀ1; MS (ESIꢀ): m/
z: 517 [2M+Naꢀ2H]ꢀ.
Diol 4c: 1H NMR (400 MHz, CDCl3): d=2.38 (s, 3H), 4.40 (d, J=
12.0 Hz, 1H), 4.54 (d, J=12.0 Hz, 1H), 5.83 (s, 1H), 7.11–7.32 ppm (m,
8H); 13C NMR (100 MHz, CDCl3): d=21.2, 63.5, 73.9, 126.5, 127.1,
128.1, 128.3, 128.7, 129.0, 129.3, 130.1, 137.0, 137.9, 139.7, 142.4 ppm; IR
(KBr): n˜ =3250, 1482, 1103, 1052, 1022, 1013, 821 cmꢀ1; MS (ESI+): m/z:
549 [2M+Na]+.
Diol 4d: 1H NMR (400 MHz, CDCl3): d=1.35 (s, 9H), 4.42 (d, J=
12.0 Hz, 1H), 4.56 (d, J=12.0 Hz, 1H), 5.95 (s, 1H), 7.24–7.38 ppm (m,
8H); 13C NMR (100 MHz, CDCl3): d=31.4, 63.6, 125.3, 126.2, 128.1,
128.3, 128.7, 130.1, 138.5, 139.6, 142.3, 150.3 ppm; IR (KBr): n˜ =3270,
2965, 1457, 1103, 1017, 758 cmꢀ1; MS (ESIꢀ): m/z: 561 [2M+Naꢀ2H]ꢀ.
Diol 4e: 1H NMR (400 MHz, CDCl3): d=2.04 (s, 3H), 4.52 (d, J=
10.4 Hz, 1H), 4.87 (d, J=8.4 Hz, 1H), 6.16 (s, 1H), 6.90–7.58 ppm (m,
8H); 13C NMR (100 MHz, CDCl3): d=19.2, 63.9, 70.3, 126.1, 126.2,
127.5, 127.9, 128.2, 128.5, 129.8, 130.4, 135.2, 138.9, 140.1 ppm; IR (KBr):
n˜ =3289, 3066, 2894, 1602, 1460, 1022, 898 cmꢀ1; MS (ESIꢀ): m/z: 477
[2M+Naꢀ2H]ꢀ.
Scheme 4. The enantioselective transformation of 7b by oxidation and re-
duction.
Diol 4 f: 1H NMR (400 MHz, CDCl3): d=3.71 (s, 3H), 4.31 (d, J=
12.0 Hz, 1H), 4.45 (d, J=12.0 Hz, 1H), 5.88 (s, 1H), 6.74–7.32 ppm (m,
8H); 13C NMR (100 MHz, CDCl3): d=55.2, 62.9, 73.8, 112.4, 115.0,
126.5, 127.5, 128.3, 130.7, 131.7, 142.6, 144.0, 159.4 ppm; IR (KBr): n˜ =
3336, 2918, 2850, 1609, 1496, 1457, 1259, 1018 cmꢀ1; MS (ESI+): m/z: 511
[2M+Na]+.
enantioselectivities and yields, which allows access to a
broad range of chiral Ar-BINMOLs. This should be consid-
ered as an available and attractive chiral source for the
design and preparation of privileged ligands or catalysts.
Further studies directed towards the preparation and appli-
cation of new ligands and catalysts based on this scaffold
are currently underway.
Diol 4g: 1H NMR (400 MHz, CDCl3): d=3.78 (s, 3H), 4.42 (d, J=
12.4 Hz, 1H), 4.59 (d, J=12.4 Hz, 1H), 5.96 (s, 1H), 6.75–7.34 ppm (m,
8H); 13C NMR (100 MHz, CDCl3): d=55.3, 63.7, 73.7, 112.8, 115.8,
126.4, 127.3, 128.3, 130.3, 134.4, 140.2, 142.9, 159.2 ppm; IR (KBr): n˜ =
3334, 2918, 2849, 1608, 1496, 1016 cmꢀ1; MS (ESI+): m/z: 511 [2M+Na]+.
1
Diol 4h: H NMR (400 MHz, CDCl3): d=2.34 (s, 3H), 3.74 (s, 3H), 4.36
(d, J=12.0 Hz, 1H), 4.51 (d, J=12.0 Hz, 1H), 5.90 (s, 1H), 6.75–
7.22 ppm (m, 7H); 13C NMR (100 MHz, CDCl3): d=21.1, 55.3, 63.1, 74.0,
112.3, 115.0, 126.4, 129.1, 130.7, 131.7, 137.1, 139.5, 144.1, 159.4 ppm; IR
Experimental Section
Flash column chromatography was performed on silica gel (200–300
mesh). 1H and 13C NMR spectra were recorded at 400 and 100 MHz, re-
spectively, by using a Bruker Avance 400 MHz spectrometer and were
referenced to the internal solvent signals. TLC was performed on silica
gel F254 TLC plates and visualization was performed with ultraviolet
light. HPLC was carried out by using a Waters 2695 Millennium chroma-
tography system equipped with a photodiode array detector. EI and CI
mass spectra were performed with a Trace DSQ GC/MS spectrometer.
Substrate 1, isobutyllithium, and n-butyllithium were commercially avail-
able and used directly. The structures of known [1,2]-Wittig rearrange-
ment products were confirmed by 1H NMR, 13C NMR, and IR spectros-
copy. ESI-MS analysis was performed on an LCQ Advantage mass spec-
trometer (ThermoFisher Company, USA), equipped with an ESI ion
source in the positive ionization mode, with data acquisition using the
Xcalibur software (Version 1.4). UV/Vis absorption and circular dichro-
ism spectra were recorded on MOS-450/AF-CD and Evolution-300 spec-
trometers, respectively.
(KBr): n˜ =3334, 2923, 1611, 1506, 1017 cmꢀ1
;
MS (ESI+): m/z: 539
[2M+Na]+.
Diol 4i: 1H NMR (400 MHz, CDCl3): d=1.32 (s, 9H), 3.76 (s, 3H), 4.39
(d, J=12.0 Hz, 1H), 4.53 (d, J=12.0 Hz, 1H), 5.94 (s, 1H), 6.79–
7.36 ppm (m, 7H); 13C NMR (100 MHz, CDCl3): d=31.4, 34.5, 55.3, 63.2,
74.1, 112.3, 115.1, 125.3, 126.2, 130.7, 131.7, 139.4, 144.0, 150.4,
159.5 ppm; IR (KBr): n˜ =3281, 2956, 1611, 1280, 1043, 1022 cmꢀ1; MS
(ESI+): m/z: 539 [2M+Na]+.
Typical procedure for enantioselective [1,2]-Wittig rearrangement of 6:
iBuLi (1.23m in pentane, 5 mmol) was added by syringe to a solution of
(S)-6 (2 mmol) in THF (20 mL) maintained at ꢀ788C. The reaction mix-
ture was stirred at ꢀ788C for 1.5 h and then treated with saturated aque-
ous NH4Cl solution. The resultant mixture was extracted with diethyl
ether (ꢁ3) and the combined organic layers were washed with brine,
dried over anhydrous Na2SO4, and concentrated in vacuo. The crude
product was purified by chromatography on silica gel (petroleum ether/
EtOAc 10:1) to give the desired product 7 (Table 2).
General procedure for the [1,2]-Wittig rearrangement of 3: iBuLi (1.23m
in hexane, 2.5 equiv) was added to a solution of 3 (5 mmol) in anhydrous
THF (30 mL) under N2 at ꢀ788C. The mixture was allowed to warm
slowly to RT, then the mixture was stirred at RT for 1 h. After the reac-
tion was complete, the reaction was quenched with water and extracted
with EtOAc. The combined organic layers were dried over anhydrous
Na2SO4 and concentrated in vacuo. The crude product was purified by
column chromatography on silica gel (petroleum ether/EtOAc 4:1) to
afford the pure diol 4 (Table 1).
Enantiomeric diols 7a and b: [a]2D5 (7a, c=1.20 in CH2Cl2)=ꢀ265.82;
1
[a]2D5 (7b, c=1.20 in CH2Cl2)=+254.44; H NMR (400 MHz, CDCl3): d=
3.26 (s, 1H), 5.60 (s, 1H), 6.38 (s, 1H), 6.80 (d, J=8.4 Hz, 2H), 7.01–7.32
(m, 7H), 7.39–7.47 (m, 2H), 7.72–7.82 ppm (m, 3H); 13C NMR
(100 MHz, CDCl3): d=73.4, 117.2, 118.0, 123.6, 125.0, 126.1, 126.5, 126.6,
126.7, 127.1, 128.1, 128.1, 129.6, 130.2, 133.0, 133.4, 134.1, 141.4, 142.5,
151.3 ppm; IR (KBr): n˜ =3379, 3056, 2954, 1944, 1619, 1595, 1507, 1341,
1268, 1237, 1143, 1012 cmꢀ1
.
Diol 4a: 1H NMR (400 MHz, CDCl3): d=4.26 (d, J=12.0 Hz, 1H), 4.43
(d, J=12.0 Hz, 1H), 5.91 (s, 1H), 7.19–7.36 ppm (m, 9H); 13C NMR
(100 MHz, CDCl3): d=63.4, 73.9, 126.5, 127.3, 128.2, 128.3, 128.3, 128.8,
130.1, 138.4, 142.3, 142.6 ppm; IR (KBr): n˜ =3249, 2951, 1493, 1442,
999 cmꢀ1; MS (ESIꢀ): m/z: 449 [2M+Naꢀ2H]ꢀ.
Diol 7c: [a]2D5 (c=1.36 in CH2Cl2)=+195.24; 1H NMR (400 MHz,
CDCl3): d=1.14 (s, 18H), 2.74 (s, 1H), 5.67 (s, 1H), 5.76 (d, J=4.4 Hz,
1H), 6.78 (d, J=8.4 Hz, 1H), 6.85 (d, J=1.2 Hz, 2H), 7.05 (t, J=7.2 Hz,
1H), 7.13 (t, J=8.8 Hz, 2H), 7.24 (m, 3H), 7.44 (t, J=6.8 Hz, 1H), 7.66
(d, J=8.8 Hz, 1H), 7.82 ppm (m, 4H); 13C NMR (100 MHz, CDCl3):
31.4, 34.8, 73.8, 117.0, 117.9, 120.4, 121.2, 123.4, 125.1, 125.2, 126.4, 126.6,
126.7, 126.8, 128.07, 128.14, 129.1, 129.5, 129.7, 130.1, 133.0, 134.1, 141.8,
Diol 4b: 1H NMR (400 MHz, CDCl3): d=4.28 (d, J=12.8 Hz, 1H), 4.43
(d, J=12.8 Hz, 1H), 5.83 (s, 1H), 7.11–7.32 ppm (m, 8H); 13C NMR
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L.-W. Xu, G.-Q. Lai et al.
142.0, 150.5, 151.2 ppm; IR (KBr): n˜ =3500, 3058, 2962, 2902, 1621, 1596,
1508, 1433, 1362, 1344 cmꢀ1
Diol 7m: [a]2D5 (c=1.63 in CH2Cl2)=+267.48; 1H NMR (400 MHz,
CDCl3): d=1.24 (s, 9H), 2.91 (s, 1H), 5.31 (s, CH2Cl2), 5.54 (s, 1H), 5.76
(s, 1H), 6.25 (d, J=8.4 Hz, 1H), 6.83 (d, J=8.4 Hz, 2H), 7.06 (t, J=
8.0 Hz, 3H), 7.19 (d, J=8.4 Hz, 1H), 7.26–7.31 (m, 3H), 7.49 (t, J=
8.0 Hz, 1H), 7.70 (d, J=8.4 Hz, 1H), 7.88 ppm (q, J=8.8, 16.0 Hz, 4H);
13C NMR (100 MHz, CDCl3): d=31.3, 34.4, 53.5 (CH2Cl2), 73.3, 117.1,
117.9, 123.5, 124.9, 124.97, 125.05, 125.9, 126.38, 126.44, 126.8, 127.9,
128.1, 129.0, 129.5, 129.7, 130.1, 133.1, 133.4, 134.0, 139.4, 141.7, 149.99,
151.1 ppm; IR (KBr): n˜ =3404, 3058, 2960, 1618, 1595, 1507, 1459, 1383,
.
Diol 7d: [a]2D5 (c=1.20 in CH2Cl2)=+252.92; 1H NMR (400 MHz,
CDCl3): d=2.22 (s, 3H), 2.64 (d, J=1.2 Hz, 1H), 5.59 (s, 1H), 5.64 (s,
1H), 6.80 (d, J=8.4 Hz, 1H), 6.89 (q, J=8.4, 23.6 Hz, 4H), 7.12 (m, 2H),
7.24 (m, 3H), 7.46 (s, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.87 ppm (m, 4H);
13C NMR (100 MHz, CDCl3): d=20.9, 73.2, 117.2, 117.9, 123.4, 125.01,
125.05, 125.9, 126.4, 126.5, 126.8, 127.96, 128.03, 128.7, 129.0, 129.4, 129.6,
129.7, 130.1, 132.9, 133.3, 134.0, 136.7, 139.6, 141.7, 151.2 ppm; IR (KBr):
1362, 1267, 1205, 1169, 1142, 1026, 1011 cmꢀ1
.
n˜ =3422, 3056, 2917, 1909, 1619, 1595, 1509, 1435, 1341, 1205, 1018 cmꢀ1
.
Diol 7e: [a]2D5 (c=1.18 in CH2Cl2)=+197.82; 1H NMR (400 MHz,
CDCl3): d=2.26 (dd, J=2.8, 6.0 Hz, 1H), 5.31 (s, 1H), 5.76 (s, 1H), 6.77
(dd, J=9.6, 18.0 Hz, 3H), 6.96 (q, J=8.4 Hz, 2H), 7.13 (dd, J=0.8,
8.4 Hz, 1H), 7.20 (d, J=8.4 Hz, 1H), 7.32 (m, 2H), 7.51 (dd, J=0.8,
7.6 Hz, 1H), 7.67 (d, J=8.8 Hz, 1H), 7.93 ppm (m, 4H); 13C NMR
(100 MHz, CDCl3): d=72.8, 114.8, 115.0, 117.0, 117.8, 123.7, 124.7, 124.8,
126.4, 126.6, 126.7, 127.0, 127.8, 127.9, 128.09, 128.15, 129.1, 129.5, 129.8,
130.3, 133.0, 133.5, 133.9, 138.3, 141.5, 151.1 ppm; IR (KBr): n˜ =3476,
Acknowledgements
Financial support by the National Natural Science Foundation of China
(NSFC, No. 20973051) and Zhejiang Provincial Natural Science Founda-
tion of China (Y4090139) is appreciated.
3389, 3056, 2955, 1621, 1597, 1508, 1382, 1219, 1182, 1157, 1029 cmꢀ1
.
Diol 7 f: [a]2D5 (c=1.96 in CH2Cl2)=+117.83; 1H NMR (400 MHz,
CDCl3): d=1.56 (s, 3H), 2.94 (d, J=1.2 Hz, 1H), 5.82 (s, 1H), 6.24 (d,
J=1.6 Hz, 1H), 6.80 (d, J=8.4 Hz, 1H), 6.86 (d, J=7.6 Hz, 1H), 7.03–
7.72 (m, 4H), 7.22 (m, 4H), 7.39 (d, J=8.4 Hz, 1H), 7.45 (t, J=7.2 Hz,
1H), 7.54 (d, J=7.6 Hz, 1H), 7.85 ppm (dd, J=8.4, 18.8 Hz, 4H);
13C NMR (100 MHz, CDCl3): d=19.2, 71.4, 118.1, 118.5, 123.6, 124.8,
125.4, 125.9, 126.1, 126.2, 126.4, 126.5, 126.8, 127.2, 127.9, 128.1, 129.2,
129.4, 130.2, 131.5, 133.3, 133.6, 133.7, 135.1, 139.9, 140.1, 151.6 ppm; IR
(KBr): n˜ =3385, 3051, 1623, 1595, 1507, 1435, 1272, 1206, 1180,
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Diol 7g: [a]2D5 (c=0.68 in CH2Cl2)=+136.54; 1H NMR (400 MHz,
CDCl3): d=2.98 (s, 1H), 3.32 (s, 3H), 5.73 (m, 1H), 5.96 (s, 1H), 6.61 (d,
J=8.0 Hz, 1H), 6.88 (t, J=8.8 Hz, 2H), 7.12 (m, 1H), 7.25 (m, 2H), 7.36
(t, J=8.8 Hz, 2H), 7.44 (m, 1H), 7.58 (d, J=8.4 Hz, 1H), 7.89 ppm (m,
4H); 13C NMR (100 MHz, CDCl3): d=19.2, 71.4, 118.1, 118.5, 123.6,
124.8, 125.4, 125.9, 126.1, 126.2, 126.4, 126.5, 126.7, 127.3, 127.9, 128.1,
129.2, 129.3, 130.2, 131.5, 133.3, 133.5, 133.6, 135.1, 139.9, 140.0,
151.6 ppm; IR (KBr): n˜ =3186, 3050, 2992, 2954, 2831, 1896, 1622, 1596,
1490, 1465, 1434, 1342, 1273, 1243, 1031 cmꢀ1
.
Diol 7h: [a]2D5 (c=1.0 in CH2Cl2)=+248.22; 1H NMR (400 MHz,
CDCl3): d=2.74–2.80 (m, 1H), 3.55 (s, 1H), 5.23 (s, CH2Cl2), 6.45 (s,
2H), 6.62 (q, J=2.4, 8.0 Hz, 2H), 6.82 (d, J=8.4 Hz, 1H), 7.01 (t, J=
8.0 Hz, 1H), 7.13 (q, J=9.2, 18.0 Hz, 2H), 7.23–7.30 (m, 3H), 7.45 (t, J=
7.2 Hz, 1H), 7.58 (d, J=8.8 Hz, 1H), 7.83–7.89 ppm (m, 4H); 13C NMR
(100 MHz, CDCl3): d=55.0, 73.2, 111.3, 113.1, 117.1, 118.0, 118.3, 123.5,
125.1, 126.47, 126.54, 126.6, 126.8, 128.08, 128.12, 129.1, 129.6, 130.0,
130.2, 133.0, 133.4, 134.2, 141.4, 144.3, 151.3, 159.3 ppm; IR (KBr): n˜ =
3394, 3056, 2927, 1596, 1490, 1434, 1259, 1206, 1144, 1029 cmꢀ1
.
Diol 7k: [a]2D5 (c=0.60 in CH2Cl2)=+263.58; 1H NMR (400 MHz,
CDCl3): d=3.20 (d, J=1.2 Hz, 1H), 5.77 (s, 1H), 5.93 (s, 1H), 6.76 (d,
J=8.8 Hz, 1H), 6.99–7.05 (m, 2H), 7.16 (d, J=8.4 Hz, 1H), 7.21–7.28 (m,
2H), 7.35 (t, J=4.0 Hz, 3H), 7.42 (t, J=8.0 Hz, 1H), 7.49 (t, J=8.4 Hz,
2H), 7.55 (d, J=8.8 Hz, 1H), 7.65 (t, J=3.6 Hz, 1H), 7.78–7.87 ppm (m,
1H); 13C NMR (100 MHz, CDCl3): d=73.4, 117.2, 118.0, 123.6, 124.3,
124.7, 125.0, 125.2, 125.6, 125.9, 126.55, 126.64, 126.9, 127.8, 128.0, 128.08,
128.12, 129.1, 129.6, 130.1, 130.3, 132.6, 132.97, 133.05, 133.4, 134.1, 139.9,
151.3 ppm; IR (KBr): n˜ =3411, 3054, 2922, 1620, 1595, 1507, 1381, 1342,
1269, 1204, 1171, 1143, 1123, 1030 cmꢀ1
.
Diol 7l: [a]2D5 (c=0.50 in CH2Cl2)=+250.21; 1H NMR (400 MHz,
CDCl3): d=0.15 (s, 9H), 3.25 (s, 1H), 5.55 (s, 1H), 6.02 (s, 1H), 6.71 (d,
J=8.4 Hz, 1H), 6.82 (d, J=8.0 Hz, 1H), 7.03 (t, J=6.8 Hz, 1H), 7.11–
7.26 (m, 7H), 7.42 (t, J=6.8 Hz, 1H), 7.52 (d, J=8.4 Hz, 1H), 7.78 ppm
(t, J=8.8 Hz, 4H); 13C NMR (100 MHz, CDCl3): d=1.1, 73.3, 117.1,
118.0, 123.5, 125.1, 125.5, 126.4, 126.5, 126.6, 126.8, 128.0, 128.1, 129.1,
129.6, 130.05, 130.12, 133.0, 133.1, 133.4, 134.1, 139.0, 141.4, 143.9,
151.2 ppm; IR (KBr): n˜ =3405, 3058, 2953, 1620, 1597, 1506, 1383, 1247,
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1204, 1169, 1142, 1127, 1111, 1025 cmꢀ1
.
2702
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ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 2698 – 2703

Neighboring Lithium-Assisted [1,2]-Wittig Rearrangement
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Received: October 28, 2010
Published online: January 24, 2011
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