Synthesis of unsymmetrically substituted 2,2′-dihydroxy-1,1′- biaryl derivatives using organic-base-catalyzed Ferrier-type rearrangement as the key step

Article abstract of DOI:10.1039/c2cc31594g

A strong organic base, TBD, functioned as a unique catalyst for the intramolecular multi-step transformation of lactols using the Ferrier-type rearrangement as the key step to provide unsymmetrically substituted 2,2′-dihydroxy biaryl compounds having four ortho substituents about the biaryl axis without the need for a metal catalyst.

Full text of DOI:10.1039/c2cc31594g

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COMMUNICATION
Synthesis of unsymmetrically substituted 2,20-dihydroxy-1,10-biaryl
derivatives using organic-base-catalyzed Ferrier-type rearrangement as
the key stepw
Masahiro Terada*ab and Katsunori Dana
Received 2nd March 2012, Accepted 16th April 2012
DOI: 10.1039/c2cc31594g
A strong organic base, TBD, functioned as a unique catalyst
for the intramolecular multi-step transformation of lactols using
the Ferrier-type rearrangement as the key step to provide
unsymmetrically substituted 2,20-dihydroxy biaryl compounds
having four ortho substituents about the biaryl axis without the
need for a metal catalyst.
Axially chiral 2,20-dihydroxy-1,10-biaryl skeletons are widely
utilized as versatile chiral sources for ligands and auxiliaries in
asymmetric synthesis.1,2 Notably, C2-symmetric binaphthol
derivatives, which are a very important class of structural
motifs, have been extensively applied to the design of enantio-
selective catalysts and a number of methodologies have been
established to introduce substituents at the 3,30- and other
positions of the binaphthyl frameworks. Unsymmetrically
substituted C1-symmetric biaryl compounds have received much
Scheme 1 Intramolecular multi-step transformation for the preparation
attention in recent years. Indeed, the tremendous progress in the
development of enantioselective catalysts using C1-symmetric
biaryls has underscored their potential as efficient chiral ligands.2
However, in most cases, these unsymmetrically substituted biaryl
compounds have been prepared through the desymmetrization
of symmetrical biaryl compounds by the introduction of a
substituent to one of two reaction sites. Although a few
examples of oxidative cross-coupling reactions with two different
2-naphthols3 and transition-metal-catalyzed cross-coupling
reactions to give unsymmetrical biaryls have been brilliantly
demonstrated,4 their substrate scopes have had limited success
because of the strong dependence on the redox potential of the
reactants and the limitation on the introduction of substituents
at the three ortho positions about the biaryl axis, respectively. In
order to develop a novel method for the synthesis of unsym-
metrically substituted 2,20-dihydroxy-1,10-biaryl derivatives,
we envisioned an unprecedented intramolecular multi-step
of unsymmetrically substituted biaryl compounds.
transformation of lactols 1 catalyzed by an organic base using
the Ferrier-type rearrangement as the key step (Scheme 1).5
Herein we report that the strong organic base, TBD (1,5,7-
triazabicyclo[4.4.0]dec-5-ene), functioned as an efficient catalyst
for the proposed multi-step transformation that involved
(i) ring opening of lactol 1 catalyzed by TBD to generate an
intermediate keto aldehyde through keto–enol tautomerization;
(ii) subsequent intramolecular aldol reaction [from (i) to
(ii): Ferrier-type rearrangement] to afford a hydroxyl ketone;
(iii) dehydration of the aldol product; and (iv) termination by
aromatization, giving rise to biaryl products 2. The method enabled
efficient access to unsymmetrically substituted 2,20-dihydroxy-
1,10-biaryl derivatives 2 having four ortho substituents about
the biaryl axis without the need for a metal catalyst.
We began by investigating the multi-step transformation of
lactol 1a catalyzed by 10 mol% of an organic base in DMSO
at 100 1C for 12 h. As shown in Table 1, catalytic efficiency was
mostly dependent on the basicity of the organic base employed
(entries 1–6)6 in the exception of TBD (entry 4). Among the
organic bases tested, the strongest base, P4-tBu phosphazene
base, accelerated the reaction efficiently (entry 6). It is note-
worthy that TBD functioned as an adequate catalyst, giving
rise to desired biaryl product 2a in good yield (entry 4), and
the yield was comparable to that of much stronger base,
P4-tBu. In contrast, the reaction catalyzed by MTBD
a Department of Chemistry, Graduate School of Science,
Tohoku University, Aoba-ku, Sendai 980-8578, Japan.
E-mail: mterada@m.tohoku.ac.jp; Fax: +81-22-795-6602;
Tel: +81-22-795-6602
b Research and Analytical Center for Giant Molecules,
Graduate School of Science, Tohoku University, Aoba-ku,
Sendai 980-8578, Japan
w Electronic supplementary information (ESI) available: Representa-
tive experimental procedure, spectroscopic data for lactols 1, biaryl
products 2, and binaphthol derivative 4. See DOI: 10.1039/c2cc31594g
c
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Chem. Commun., 2012, 48, 5781–5783 5781

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Table 1 Intramolecular multi-step transformation of lactol 1a catalyzed
by organic basesa
+ b
pKBH
Entry
Base
Solvent
Yield (%)c
1
2
3
4
5
6
7
8
9
TMG
DBU
23.3
24.3
25.5
26.0
27.0d
42.7
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
CH3CNe
THFe
25
36
46
80
43
84
MTBD
TBD
P1-tOct
P4-tBu
TBD
81
Quant. (90)f
Quant. (94)f
TBD
P4-tBu
THFe
a
Unless otherwise noted, all reactions were carried out using 10 mol%
b
Fig. 1 Plausible reaction mechanism using TBD as the base catalyst.
of base at 100 1C for 12 h. pKBH
Remaining mass was recovered as unchanged 1a. pKBH
+
in CH3CN. c 1H NMR yield.
d
+
of P1-tBu.
e
f
The reactions were conducted in a sealed-tube. Isolated yield.
ring-opened enolate B through antiparallel hydrogen-bonding
model A. This consideration is also applicable to the formation
of thermodynamically unfavorable regioisomeric enolate E
from keto aldehyde C, where the acidity at the a0-position of
C would be lower than that at the a-position because of the
a-carbon bearing two aryl groups. This unfavorable process
would be accelerated through the double hydrogen-bonding
interaction between C and TBD, as shown in model D. Thus,
N-methyl TBD (MTBD), having not only similar basicity but
also structural resemblance to TBD, exhibited lower catalytic
activity (Table 1, entry 3 vs. 4). It seems that the formation of
the two antiparallel hydrogen bonds is the key to achieving the
high catalytic performance. Further transformation of inter-
mediary enolate E into biaryl compound 2 would be also
promoted by the formation of the two hydrogen bonds when
TBD was used as the catalyst.
(7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene) and P1-tOct
phosphazene bases, both having similar basicity to TBD,
afforded product 2a in modest yields under the same reaction
conditions (entries 3 and 5). Further screening for other
solvents revealed that MeCN and THF were also useful in
the present intramolecular reaction (entries 7–9). In THF,
both TBD and P4-tBu phosphazene bases acted as excellent
catalysts to give 2a in high yields (entries 8 and 9).
As shown in Table 1, TBD functioned as a unique catalyst
in the present intramolecular multi-step transformation. The
catalytic efficiency of TBD is comparable to that of P4-tBu
despite the fact that TBD is much less basic than P4-tBu. Other
organic bases that possess similar basicity to TBD, such as MTBD
and P1-tOct, exhibited less catalytic activity than TBD. The
observed unique catalysis by TBD would stem from the fact that
TBD has both hydrogen-bond acceptor and donor sites in close
proximity at the 5- and 7-position of nitrogen atoms, respectively.
This characteristic feature is not available in the other organic
bases employed. A plausible mechanism for the unique catalysis
by TBD is depicted in Fig. 1 on the basis of the formation of two
antiparallel hydrogen bonds.7 Although at the initial step, the ring
opening of lactol 1 to generate intermediary enolate B should be
energetically unfavorable, the double hydrogen-bonding inter-
action between 1 and TBD would aid the smooth formation of
Having identified the suitable reaction conditions and the
catalytic potential of TBD, we next investigated the substrate
scope of the present intramolecular multi-step transformation
(Table 2). Both linear and branched alkyl groups were well
tolerated as the substituents (R) at the 3-position of desired
product 2 (entries 1 and 2). In the present TBD-catalyzed
reaction, heteroatoms, such as oxygen and sulfur, could also
be introduced at the 3-position of product 2 (entries 3 and 4).
6- and 7-Methoxy-substituted binaphthyl products 2f and 2g
were also obtained in excellent yields (entries 5 and 6). Furthermore,
the reaction of lactol 1h having a substituted phenyl group,
c
5782 Chem. Commun., 2012, 48, 5781–5783
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Table 2 Substrate scope of TBD-catalyzed intramolecular multi-step
transformation of 1a
of the optically active biaryl compound through the optical
resolution of racemic 2a using chiral diamine.9 After the
deprotection of methyl ether of 2a by BBr3, thus obtained
racemic binaphthol derivative 4 was recrystallized from toluene
in the presence of (S,S)-1,2-diphenyl-1,2-ethanediamine (5).
(R)-4 having 95% ee was recovered from the crystalline
complex composed of (R)-4 and (S,S)-5 in 22% yield, after
decomposition of the complex with dilute hydrochloric acid.
In conclusion, we have demonstrated an efficient method for
the synthesis of unsymmetrically substituted 2,20-dihydroxy-
1,10-biaryl compounds starting from lactol derivatives through
the intramolecular multi-step transformation. TBD functioned
as an efficient and unique catalyst presumably due to the
formation of the antiparallel hydrogen bonds between TBD
and (intermediary) substrates. Further studies of the design of
reaction systems and chiral organic base catalysts are in progress
with the aim of achieving the enantioselective synthesis of axially
chiral biaryl compounds.
Entry
1
1
Ar
R
2
Yield (%)b
1b
1c
nPr
iPr
2b 96
2c 82
2
3
4
’’
1d ’’
1e
OMe 2d 83
SMe
’’
2e
79
5
6
1f
Me
2f
99
This work was partially supported by a Grant-in-Aid for
Scientific Research on Innovative Areas ‘‘Advanced Molecular
Transformations by Organocatalysts’’ from MEXT, Japan.
We gratefully acknowledge Professors T. Ooi and D. Uraguchi
(Nagoya University) and Dr Y. Nakamura and Mr T. Takeda
(Daiichi Sankyo Co., Ltd.) for HRMS analysis.
1g
1h
Me
Me
2g 98
Notes and references
7
2h 96
z Optically active 4 was racemized in the presence of TBD (10 mol%)
in THF at 100 1C. See ESIw for details.
1 For reviews of enantioselective catalysis with BINOL derivatives,
see: (a) L. Pu, Chem. Rev., 1998, 98, 2405; (b) Y. Chen, S. Yekta and
A. K. Yudin, Chem. Rev., 2003, 103, 3155; (c) J. M. Brunel, Chem.
Rev., 2005, 105, 857; (d) M. Terada, Synthesis, 2010, 1929.
a
Unless otherwise noted, all reactions were carried out using 10 mol%
b
of TBD at 100 1C for 12 h in THF (0.2 M) in a sealed tube. Isolated
yield.
2 For reviews, see: (a) P. Kocovsky´ , S. Vyskocil and M. Smrcina,
Chem. Rev., 2003, 103, 3213; (b) M. Shibasaki and S. Matsunaga,
Chem. Soc. Rev., 2006, 35, 269.
3 H. Egami, K. Matsumoto, T. Oguma, T. Kunisu and T. Katsuki,
J. Am. Chem. Soc., 2010, 132, 13633 and references cited therein.
4 X. Shen, G. O. Jones, D. A. Watson, B. Bhayana and
S. L. Buchwald, J. Am. Chem. Soc., 2010, 132, 11278 and references
cited therein.
5 R. J. Ferrier, J. Chem. Soc., Perkin Trans. 1, 1979, 1455.
6 (a) T. Rodima, I. Kaljurand, A. Pihl, V. Maemets, I. Leito and
¨
I. A. Koppel, J. Org. Chem., 2002, 67, 1873–1881; (b) I. Kaljurand,
A. Kutt, L. Soovali, T. Rodima, V. Maemets, I. Leito and
¨
¨
¨
I. A. Koppel, J. Org. Chem., 2005, 70, 1019; (c) R. Schwesinger,
H. Schlemper, C. Hasenfratz, J. Willaredt, T. Dambacher,
T. Breuer, C. Ottaway, M. Fletschinger, J. Boele, H. Fritz,
D. Putzas, H. W. Rotter, F. G. Bordwell, A. V. Satish, G.-Z. Ji,
E.-M. Peters, K. Peters, H. Georg von Schnering and L. Walz,
Liebigs Ann., 1996, 1055.
Scheme 2 Enantioselective intramolecular multi-step transformation
catalyzed by chiral guanidine 3.
instead of the naphthyl group, was demonstrated to emphasize
the potential utility of the present method (entry 7).
7 For TBD as an efficient catalyst having donor–accepter property of
hydrogen bonds, see: (a) L. Simon and J. M. Goodman, J. Org.
´
Finally, we attempted the enantioselective catalysis of
the present multi-step transformation using chiral bicyclic
guanidine 3.8 The reaction of 1a was investigated in the
presence of 20 mol% of (S,S)-3. As shown in Scheme 2, under
the optimal reaction conditions (THF, 100 1C, 12 h), the
catalytic reaction of 1a was sluggish, affording optically active
product 2a in low yield with low enantioselectivity. Prolonging
the reaction time led to a disappointing result in terms of
enantioselectivity, furnishing racemic product 2a, although the
chemical yield of 2a could be improved. These results imply
that optically active 2a was racemized under the reaction
conditions.z We therefore turned our attention to the synthesis
Chem., 2007, 72, 9656; (b) A. Chuma, H. W. Horn, W. C. Swope,
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c
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Chem. Commun., 2012, 48, 5781–5783 5783