Diastereoconvergent Dehydrative Nucleophilic Substitutions of Diastereomeric Diarylmethanols with 1,3-Dicarbonyls Catalyzed by SnBr4

Article abstract of DOI:10.1002/ejoc.201901377

Diastereoconvergent direct dehydrative nucleophilic substitutions of diastereomeric mixtures of diarylmethanols with 1,3-dicarbonyls in the presence of SnBr₄ as a Lewis acid catalyst are reported. Excellent diastereoselectivities and high yields were achieved by using a chiral auxiliary. The reaction proved applicable to a wide range of substrates, irrespective of aromatic ring substituents tested, and several 1,3-diketones, and β-keto esters were utilized as nucleophilic partners. Efficient transformation of selected alkylated products to pyrazoles was achieved by treatment with NH₂NH₂·H₂O. A plausible reaction pathway for the nucleophilic substitution was proposed.

Full text of DOI:10.1002/ejoc.201901377

A Journal of
Accepted Article
Title: Chiral-Auxiliary-Controlled Diastereoconvergent Dehydrative
Nucleophilic Substitutions of Diarylmethanol Diastereomixtures
with 1,3-Dicarbonyls Catalyzed by SnBr4
Authors: Rikiya Kubo, Hiroshi Yamamoto, and Kenya Nakata
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201901377
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10.1002/ejoc.201901377
European Journal of Organic Chemistry
COMMUNICATION
Chiral-Auxiliary-Controlled Diastereoconvergent Dehydrative
Nucleophilic Substitutions of Diarylmethanol Diastereomixtures
with 1,3-Dicarbonyls Catalyzed by SnBr4
Rikiya Kubo, Hiroshi Yamamoto, and Kenya Nakata*[a]
Abstract: Diastereoconvergent direct dehydrative nucleophilic
substitutions of diastereomixtures of diarylmethanols with 1,3-
dicarbonyls in the presence of SnBr4 as a Lewis acid catalyst are
reported. Excellent diastereoselectivities and high yields were
achieved by a chiral-auxiliary-controlled process. The reaction
proved applicable to a wide range of substrates, irrespective of
aromatic ring substituents tested, and several 1,3-diketones, and
b-ketoesters were utilized as nucleophilic partners. Efficient
transformation of selected alkylated products to pyrazoles was
achieved by treatment with NH2NH2·H2O. A plausible reaction
pathway for the nucleophilic substitution was proposed.
sulfonamides 8a and 8b (Scheme 1 (b)). Thus, we hypothesized
that 1,3-dicarbonyl compounds could be applied to our chiral
inductive methodology and thus extended this to the
development of
methodology (Scheme 1 (c)).
Herein, we describe
diastereoconvergent dehydrative nucleophilic substitution of
a
new asymmetric C–C bond forming
an
auxiliary-controlled
direct
diarylmethanol
diastereomixtures
with
1,3-dicarbonyl
compounds, catalyzed by Lewis acids.
(a) Related previous study[ref 2]
Ar1
R1
Ar2
R2
Lewis acid
or
Brønsted acid
Ar1
R1
R2
OH
Introduction
+
Ar2
O
O
O
O
1
2
In recent years, direct dehydrative nucleophilic substitution
reactions of alcohols have drawn considerable attention in
organic synthesis.[1] The reaction proceeds without the need to
convert the hydroxyl group into a leaving group, making it an
atom-efficient process. Furthermore, ideally, the only reaction
by-product is water, another desirable aspect in terms of
environmental considerations. Within this class of reaction, the
use of 1,3-dicarbonyl compounds as nucleophiles is a well-
known successful methodology for C–C bond formation.
Numerous characteristic reactions using Lewis acids and
Brønsted acids as catalysts have been reported to date
(Scheme 1 (a)).[2] However, almost all previously reported
methods deliver products as racemates, and extension to an
asymmetric version remains a difficult task. On the other hand,
many related organocatalytic enantioselective syntheses utilizing
quinone methides[3] have been developed, but they are often
restricted to substrates containing electron donating groups.
Preceding this research, we developed a chiral auxiliary and
applied it to Lewis acid-catalyzed chiral inductive
(b) Our previous study[refs 4–8]
Ph
Ph
H
MeO
MeO
O
O
N
R
Ar
Ar
6
O
5
Allylation
Amidation
Ph
MeO
O
Ph
Ph
MeO
Friedel–Crafts
Alkylation
MeO
Sulfonylation
Ar
O
O
OH
OH
SO2R
R
Ar
Ar
7
3
4
Sulfonamidation
Ph
Ph
MeO
MeO
O
O
NHTs
NHTs
diastereoconvergent
couplings
of
diarylmethanol
Ar
8a
Ar
8b
diastereomixtures 3, employing nucleophiles such as 2-
naphthols,[4] allyltrimethylsilane,[5] benzamides,[6] and sodium
sulfinates.[7] It was revealed that these reactions were applicable
to a variety of substrates to give products 4, 5, 6, and 7,
respectively (Scheme 1 (b)). In addition, by using different Lewis
Ph
Ar
O
(c) This study
MeO
Ph
O
MeO
O
R1
O
R2
Lewis acid (n mol-%)
+
O
Solvent (0.1 M)
Temp., Time
OH
R1
R2
(1.5 equiv)
acid
catalysts,
chiral
inductive
diastereodivergent
Ar
sulfonamidation[8] of 3 was developed to produce diastereomeric
O
3
9
Scheme 1. (a) Related previous study; direct substitution of diarylmethanols
with 1,3-dicarbonyl compounds, (b) our previous study, and (c) this study;
diastereoconvergent asymmetric substitution of alcohols.
[a]
R. Kubo, H. Yamamoto, Prof. Dr. K. Nakata
Department of Chemistry, Graduate School of Natural Science and
Technology, Shimane University
1060 Nishikawatsu, Matsue, Shimane 690-8504 (Japan)
E-mail: nakata@riko.shimane-u.ac.jp
Homepage: http://www.ipc.shimane-u.ac.jp/yuuki_lab/
Results and Discussion
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/ejoc.201901377
European Journal of Organic Chemistry
COMMUNICATION
To find optimal reaction conditions, we commenced by exploring
9
SnBr2
SnBr2
SnCl4
SnBr4
11
11
11
11
1
72[b] (13)
93[c] (13)
89[c] (13)
89[c] (13)
89: 11
89:11
88:12
89:11
different Lewis acids (Table 1). As
a
model reaction,
diarylmethanol diastereomers 3a[4] [diastereomeric ratio (dr) =
approximately 60:40] were chosen as substrates for nucleophilic
substitution with 1,3-dicarbonyls 10 or 11 using FeCl3 as the
Lewis acid. FeCl3 is an efficient Lewis acid catalyst for
10
11
12
24
1
1
dehydrative nucleophilic substitutions,[9] and
a number of
[a] Diastereomeric ratio (dr) was determined by 1H NMR analysis. [b]
Determined by 1H NMR analysis of the crude reaction mixture using 2-
acetylnaphthalene as an internal standard. [c] Yield of isolated mixtures of
diastereomers.
coupling reactions of benzhydrol derivatives with 1,3-dicarbonyls
using FeCl3 as a catalyst have been reported to date.[2g,2h,2l,2u,2v]
The FeCl3-calalyzed reaction of 3a with 10 was initially carried
out in MeNO2 at 0 °C. The reaction was complete within 1 h, and
the desired product 12a was obtained in 83% yield and with a
97:3 dr (entry 1). We have already reported on the applicability
of tin salts as Lewis acids for the diastereoconvergent coupling
reactions of 3a with several nucleophiles.[4–8] Thus, the same
reaction was conducted in the presence of several tin salts,
namely, SnCl2, SnBr2, SnCl4, and SnBr4. Good results were
obtained in all cases (entries 2–5), and it was found that the
reaction afforded high yields and selectivities, regardless of the
type of Lewis acid used (entries 1–5). However, when the
reaction was carried out using 11 as the nucleophile, reactivity
was found to be influenced by the choice of Lewis acid catalyst.
Reactions using FeCl3, SnCl4, and SnBr4 were complete within 1
h, and good diastereoselectivities were achieved (entries 6, 11,
and 12). On the contrary, prolonged reaction times were
required in the case of SnCl2 and SnBr2 in order to consume the
starting material, although comparable diastereoselectivities
were obtained (entries 7 versus 8, and 9 versus 10). On the
basis of thin-layer chromatography (TLC) analysis and
diastereoselectivity results, reaction conditions shown in entry
12 were selected for further studies, where SnBr4 was selected
as the Lewis acid catalyst.
To explore substrate scope and possible limitations thereof, a
series of diarylmethanols 3a–3l bearing various aromatic ring
substituents were reacted with 1,3-dicarbonyl 10, applying the
above-mentioned conditions (Table 2). Reactions of substrates
containing methyl-substituted aromatic rings 3b–3d proceeded
with high levels of diastereoselectivity, and although good yields
were obtained with 3c and 3d (entries 4 and 5), a moderate yield
was achieved in the case of 3b (entry 2). Because the reaction
of 3b resulted in a complex mixture, in order to control the
reactivity, reaction temperature was decreased from 0 °C to –
10 °C. Pleasingly, both the yield and selectivity were improved
(entry 3 versus 2). A good yield and diastereoselectivity was
achieved for 3f, where the MeO substituent is in the meta-
position (entry 7); however, when the MeO substituents are in
ortho- and para-positions, as in 3e and 3g, respectively, reaction
profiles were again complicated at 0 °C. This is likely a
consequence of these reactions proceeding via the active ortho-
and para-quinone methides, which are stabilized by the electron
donating ability of the MeO moiety. However, both gave good
results when the reaction temperature was decreased to –15 °C
(entries 6 and 8). Low reactivities of Cl-substituted aryls were
anticipated as the electron withdrawing properties of Cl, which
result in the formation of unstabilized cation intermediates.
However, reactions of 3i and 3j with Cl substituents at meta- and
para-positions afforded good results (entries 11 and 12), while
low reactivity was observed for the ortho-isomer, 3h, under the
standard conditions. By prolonging the reaction time to 24 h or
by increasing the catalyst loading to 10 mol%, the reactivity of
3h was satisfactorily improved (entries 9 and 10, respectively).
a- and b-Naphthyl-substituted aryls, 3k and 3l, afforded good
results, irrespective of the substitution pattern (entries 13 and
14).
Table 1. Examination of the effect of Lewis acids on the diastereoconvergent
substitutions of 3a with 1,3-dicarbonyls 10 and 11.
R1
R1
Ph
Ph
O
MeO
Ph
Ph
O
O
O
MeO
(1.5 equiv)
[10; R1 = Ph, 11; R1 = Me]
Lewis acid (5 mol-%)
O
R1
R1
OH
O
MeNO2 (0.1 M)
0 °C, Time [h]
3a
12a; R1 = Ph
13; R1 = Me
Entry
Lewis acid
FeCl3
Reagent
10
Time [h]
Yield [%]
83[b] (12a)
87[b] (12a)
92[b] (12a)
90[b] (12a)
87[b] (12a)
99[c] (13)
51[b] (13)
72[c] (13)
dr[a]
1
2
3
4
5
6
7
8
1
97:3
97:3
97:3
95:5
97:3
88:12
89: 11
89:11
Table 2. Diastereoconvergent nucleophilic substitution of
diarylmethanols 3 with 1,3-dicarbonyl compound 10.
a
series of
SnCl2
SnBr2
SnCl4
SnBr4
FeCl3
10
1
Ph
MeO
10
1
Ph
Ph
Ph
Ar
O
MeO
O
O
10
1
O
Ar
(10; 1.5 equiv)
SnBr4 (5 mol-%)
10
1
Ph
Ph
MeNO2 (0.1 M)
0 °C, Time [h]
11
1
OH
3a–3l
O
O
12a–12l
SnCl2
SnCl2
11
1
Entry
1
Ar
Ph (a)
Time [h]
1
Yield of 12[a] [%]
dr[b]
97:3
11
24
90
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10.1002/ejoc.201901377
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COMMUNICATION
Ph
Ph
2
o-MeC6H4 (b)
o-MeC6H4 (b)
m-MeC6H4 (c)
p-MeC6H4 (d)
o-MeOC6H4 (e)
m-MeOC6H4 (f)
p-MeOC6H4 (g)
o-ClC6H4 (h)
o-ClC6H4 (h)
m-ClC6H4 (i)
p-ClC6H4 (j)
a-Np (k)
1
1
1
1
1
1
1
24
4
2
1
1
1
66
82
83
87
74
89
88
81
88
70
91
89
86
92:8
97:3
95:5
95:5
91:9
97:3
97:3
96:4
95:5
97:3
96:4
94:6
96:4
MeO
MeO
R2
OR3
Ph
Ph
O
O
3[c]
4
MeO
O
O
O
Ph
Ph
(14–17; 1.5 equiv)
NaOH aq.
SnBr4 (n mol-%)
(2.0 equiv)
R2
OR3
R2
MeNO2 (0.1 M)
0 °C, Time [h]
14; R2, R3 = Me
MeOH
80 °C
5
OH
O
O
18–21
O
3a
22–24
6[d]
7
15; R2 = Me, R3 = Bn
16; R2 = iPr, R3 = Me
17; R2 = Ph, R3 = Et
8[d]
9
Ph
Ph
Ph
O
Ph
Ph
O
MeO
Me
MeO
MeO
MeO
O
O
O
10[e]
11
12
13
14
Ph
Ph
Ph
OEt
OMe Me
OBn iPr
OMe Ph
O
O
O
O
O
O
O
18; 88%
(n = 20, 4 h)
19; 88%
(n = 10, 4 h)
20; 58%
(n = 10, 4 h)
21; 89%
(n = 20, 1 h)
Decarboxylation Decarboxylation Decarboxylation Decarboxylation
b-Np (l)
Ph
Ph
Ph
Ph
MeO
MeO
MeO
MeO
[a] Isolated yield of major diastereomer. [b] Diastereomeric ratio (dr) was
determined by 1H NMR analysis. [c] Reaction temperature was –10 °C. [d]
Reaction temperature was –15 °C. [e] Using 10 mol% SnBr4.
O
O
O
O
Ph
Ph
Ph
Ph
Me
Me
iPr
Ph
O
O
O
O
22; 88%[a]
88:12 dr
(1 h)
22; 76%[a]
87:13 dr
(2 h)
23; 74%[a]
90:10 dr
(24 h)
24; 77%[a]
90:10 dr
(24 h)
Next, to test the scope and limitations of nucleophiles,
reactions of 3a with b-ketoesters 14–17 were carried out
(Scheme 2). Reactivity was slightly decreased in all cases, when
compared to results obtained with 1,3-dicarbonyl 10. However,
reactions of 14, 15, and 17 afforded the corresponding targets
18, 19, and 21 in high yields when catalyst loading was
increased and/or by prolonging the reaction time. b-Ketoester 16
afforded the desired product 20 in a moderate yield, probably
owing to steric repulsion of the isopropyl group. Since products
18–21 were mixtures of keto-enol tautomers, in order to estimate
diastereoselectivities of the nucleophilic substitution step, they
were decarboxylated by treatment with NaOH. Decarboxylation
of 18 and 19 was complete within 1–2 h, whereas a reaction
time of 24 h was necessary for intermediates 20 and 21. In all
cases, good diastereoselectivities were obtained. Unfortunately,
malonic esters were unreactive, in agreement with our previous
analogous report.[2e]
Scheme 2. Diastereoconvergent nucleophilic substitutions of 3a with various
1,3-ketoesters, followed by decarboxylation. [a] Yield of isolated mixtures of
diastereomers.
Next, we undertook to transform single diastereomer 24 into
the 1-benzopyran derivative 25, a motif frequently present in
biologically active compounds[10] (Scheme 3). When 24 was
treated with BBr3 at –40 °C for 2 h, cleavage of the chiral
auxiliary followed by cyclization afforded the pyran 25 in 72%
yield without erosion of optical purity. The absolute configuration
of 25 was determined by comparison with a previously reported
optical rotation value.[11] In addition, absolute configurations of
other alkylated products 12a–12l, 22, 23 and 24 were assigned
based on the result.
Ph
MeO
O
Ph
O
BBr3 (3.0 equiv)
Ph
CH2Cl2 (0.1 M)
–40 °C, 2 h
Ph
Ph
25 (72%, 99% ee)
O
24 (99:1 dr)
Scheme 3. Transformation of 24 into 1-benzopyran 25, and determination of
the absolute configuration.
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10.1002/ejoc.201901377
European Journal of Organic Chemistry
COMMUNICATION
L* Ph Ph L*
To further transform alkylated products 12a, b, d, g and j, we
attempted to construct the corresponding pyrazoles. The
pyrazole scaffold has versatile applicability in many fields, such
as pharmaceuticals, agricultural chemicals, and functional
materials.[12] To explore the effect of different substituents on the
aromatic rings of the substrates, single diastereomers of above-
mentioned alkylated products 12 were treated with NH2NH2·H2O
in MeOH (Scheme 4).[13] All para-substituted intermediates
afforded corresponding pyrazoles 26 in high yields after 48 h,
irrespective of the electronic nature of substituents. However,
the reaction of 12b bearing a methyl substituent in the ortho
position proceeded slowly, and a prolonged reaction time of 72 h
was required to give 26b in 78% yield. In every case, products
26 were obtained as single diastereomers without epimerization.
O
Ph
MeO
L* =
L*
AA
O
Ph
Ph
O
A
MeO
Ph
O
L*
L*
(c)
SnBr4
Ph
Ph
Ph
(a)
(b)
SnBr4
Ph
HO
OH
A (= 3a)
int-1
int-2
+
O
12a
HO-SnBr4
Ph
H
Ph
Ph
Ph
SnBr4
(d)
Ph
Ph
O
O
O
O
(e)
O
O
SnBr4
int-4
10
SnBr4
int-3
H2O, SnBr4
Ph
Ph
MeO
Ph
MeO
Scheme 5. Plausible reaction mechanism of the nucleophilic substitution.
O
O
NH2NH2·H2O (5.0 equiv)
R
R
MeOH (0.05 M)
RT, Time [h]
Ph
Ph
Ph
Ph
Ph
Ph
MeO
O
O
O
N NH
O
Ph Ph
O
O
SnBr4 (5 mol-%)
MeO
OMe
12a; R = H (>99:1 dr)
26a; 92%, >99:1 dr (48 h)
26b; 78%, >99:1 dr (72 h)
26d; 91%, >99:1 dr (48 h)
26g; 95%, >99:1 dr (48 h)
26j; 98%, >99:1 dr (48 h)
Ph
MeNO2 (0.1 M)
0 °C, 10 min
12b; R = o-Me (>99:1 dr)
12d; R = p-Me (>99:1 dr)
12g; R = p-MeO (>99:1 dr)
12j; R = p-Cl (>99:1 dr)
OH
A (= 3a)
AA; 85% (dl, meso = 55:28:17)
Ph
MeO
Ph
Ph
Scheme 4. Transformation of the alkylated 12 into the pyrazoles 26.
O
O
O
Ph
(10; 3.0 equiv)
SnBr4 (10 mol-%)
A plausible reaction mechanism for the Lewis acid-catalyzed
dehydrative nucleophilic substitution of diarylmethanol A (= 3a)
with 1,3-dicarbonyl compound 10 is depicted in Scheme 5.
Diarylmethyl cation int-2 is generated by activation of the
hydroxy group on the diarylmethanol A with SnBr4, as shown in
step (a), followed by subsequent elimination of the hydroxy
group in step (b). It is expected that int-2 is stabilized by
chelation of the oxygen atom of the MeO group on the chiral
auxiliary, and its conformation is controlled to form a seven-
membered ring transition state.[4,5] TLC analysis shows that
there is a partial equilibrium between int-2 and homoether AA,
Ph
Ph
AA
MeNO2 (0.1 M)
0 °C, 1 h
O
O
12a; 81%, 97:3 dr
Scheme 6. Synthesis of homoether AA, and the reaction of AA with 1,3-
dicarbonyl 10, catalyzed by SnBr4.
Conclusions
We have developed a diastereoconvergent methodology for
derived from
2
equivalents of A.[2c,14] In step (d), SnBr4
dehydrative
substitutions
of
diastereomixtures
of
coordinates to the two oxygen atoms of 1,3-dicarbonyl 10 to
generate int-3. The activated int-3 is subsequently enolized by
deprotonation with hydroxy tetrabromostannate to generate int-4,
along with the release of H2O and the regeneration of SnBr4 in
step (e). In the final step, step (c), int-4 attacks int-2 to afford
desired 12a.
To confirm the above described reaction mechanism, we
carried out the reaction of isolated homoether AA with 1,3-
dicarbonyl compound 10 under the optimal reaction conditions
(Scheme 6). Treatment of diarylmethanol A (= 3a) with SnBr4 as
a catalyst without a nucleophile gave homoether AA in 85%
yield (dl, meso = 55:28:17, stereochemistries not assigned).
When homoether AA was reacted with 10 in the presence of
SnBr4 as a catalyst, the results were almost identical to those of
the reaction of diarylmethanol 3a (see Table 2, entry 1). These
results indicate that alcohol A (= 3a) is partially in equilibrium
with homoether AA.
diarylmethanols bearing a chiral auxiliary, carried out with 1,3-
dicarbonyls and catalyzed by SnBr4 as a Lewis acid. It was
revealed that the efficacy of the reaction is dependent on the
stability of carbocation intermediates. Where optimization was
necessary, desired products were obtained in high yields with
high diastereoselectivities in the case of substrates bearing an
electron donating group, by lowering the temperature; in the
case of substrates bearing an electron withdrawing group, by
increasing the catalyst loading or prolonging the reaction time.
Thus, the reaction is applicable to a broad range of substrates,
and several 1,3-dicarbonyl compounds and b-ketoesters can be
utilized. Further studies are currently underway in our laboratory
to discover other nucleophiles and establish a more general
utility of the present method.
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10.1002/ejoc.201901377
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Experimental Section
Typical Procedure for the Diastereoconvergent Nucleophilic
Substitutions of Diarylmethanols Diastereomixtures with 1,3-
Dicarbonyl Compounds (Table 2, entry 1): To a solution of SnBr4 (4.2
mg, 9.58 μmol) in MeNO2 (0.4 mL) at 0 °C were successively added
diarylmethanol 3a[4] (63.9 mg, 0.191 mmol) in MeNO2 (0.5 mL + 0.5 mL +
0.5 mL rinse) and (PhCO)2CH2 (64.7 mg, 0.289 mmol). The reaction
mixture was stirred for 1 h at 0 °C and then it was quenched with
saturated aqueous NaHCO3 at 0 °C and the mixture diluted with CH2Cl2.
The organic layer was separated and the aqueous layer was extracted
with EtOAc. The combined organic layer was dried over Na2SO4. After
filtration of the mixture and evaporation of the solvent, the crude product
was semi-purified by thin-layer chromatography on silica (hexane/EtOAc
= 4:1 x2) to afford the diastereomer mixtures 12a, whose ratio was
determined by 1H NMR analysis (dr = 97:3). The both diastereomers
were separated by thin-layer chromatography on silica (toluene/EtOAc =
20:1 x2) to afford the major diastereomer 12a (93.2 mg, 90% yield) as a
white solid.
The 1 mmol-scale Synthesis of 12a: To a solution of SnBr4 (23.0 mg,
52.5 μmol) in MeNO2 (6.5 mL) at 0 °C were successively added
diarylmethanol 3a[4] (352.0 mg, 1.05 mmol) in MeNO2 (2 mL + 1 mL + 1
mL rinse) and (PhCO)2CH2 (353.1 mg, 1.57 mmol). The reaction mixture
was stirred for 1 h at 0 °C and then it was quenched with saturated
aqueous NaHCO3 at 0 °C and the mixture diluted with CH2Cl2. The
organic layer was separated and the aqueous layer was extracted with
EtOAc. The combined organic layer was dried over Na2SO4. After
filtration of the mixture and evaporation of the solvent, the crude product
was semi-purified by column chromatography on silica (hexane/EtOAc =
4:1 x2) to afford the diastereomer mixtures 12a, whose ratio was
determined by 1H NMR analysis (dr = 97:3). The both diastereomers
were separated by thin-layer chromatography on silica (toluene/EtOAc =
20:1 x2) to afford the major diastereomer 12a (517.8 mg, 91% yield) as a
white solid.
Acknowledgments
This study was supported by a Research Grant from The
Takahashi Industrial and Economic Research Foundation,
Japan.
Keywords: Benzylation • Carbocations • Chiral auxiliaries •
Diastereoselectivity • Tin
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10.1002/ejoc.201901377
European Journal of Organic Chemistry
COMMUNICATION
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10.1002/ejoc.201901377
European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 2:
COMMUNICATION
Synthetic Methods*
Ph
MeO
Ph
MeO
O
R. Kubo, H. Yamamoto, Prof. Dr. K.
Nakata*
R1
R2
SnBr4 (cat.)
O
+
Ar
O
O
MeNO2 (0.1 M)
0 °C, ca. 1 h
Ar
OH
R1
R2
(1.5 equiv)
Page No. – Page No.
up to 97:3 dr
O
O
Chiral-Auxiliary-Controlled
Diastereoconvergent Dehydrative
Nucleophilic Substitutions of
Diarylmethanol Diastereomixtures
with 1,3-Dicarbonyls Catalyzed by
SnBr4
SnBr4-catalyzed direct dehydrative substitutions of diastereomixtures of
diarylmethanols with 1,3-dicarbonyls was achieved in high yields and
diastereoselectivities in a chiral inductive diastereoconvergent fashion.
*one or two words that highlight the emphasis of the paper or the field of the study
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