Chirality Exchange from sp3 Central Chirality to Axial Chirality: Benzannulation of Optically Active Diaryl-2,2-dichlorocyclopropylmethanols to Axially Chiral α -Arylnaphthalenes

Article abstract of DOI:10.1021/ja0319442

Chirality exchange benzannulation of optically active (1S)-aryl(aryl′)-2,2-dichlorocyclopropylmethanols (>99% ee) using TiCl₄ successfully proceeded to give axially chiral (M)-α-arylnaphthalenes with excellent levels of stereo induction (′99% e

Full text of DOI:10.1021/ja0319442

Published on Web 04/13/2004
Chirality Exchange from sp3 Central Chirality to Axial Chirality:
Benzannulation of Optically Active Diaryl-2,2-dichlorocyclopropylmethanols
to Axially Chiral r-Arylnaphthalenes
Yoshinori Nishii,* Kazunori Wakasugi,† Keisuke Koga,† and Yoo Tanabe*,†
Department of Chemistry, Faculty of Textile Science and Technology, Shinshu UniVersity, Ueda,
Nagano 386-8567, Japan, and Department of Chemistry, School of Science and Technology,
Kwansei Gakuin UniVersity, Sanda, Hyogo 669-1337, Japan
Received December 25, 2003; E-mail: nishii@giptc.shinshu-u.ac.jp
Axially chiral biaryls are well recognized as a characteristic
chemical class in organic synthesis due to their utility as efficient
chiral ligands and key intermediates of biologically active com-
pounds.1 Various synthetic methods have been exploited to produce
chiral biaryls.2 Chirality transfer protocols from stereogenic axes
to the sp3 centers have also attracted much attention for studies of
asymmetric reactions.3 In addition, opposite methodologies for
chirality transfer from a stereogenic sp3 center to axial chirality
have moved into the spotlight.2c-h,4,5 This transformation requires
more than two steps to obtain atropenantiomers: the initial chirality
transfer to construct chiral atropdiastereomers, followed by removal
of the sp3 central chirality to produce atropenantiomers. Recently,
Shair and co-workers achieved an elegant biomimetic synthesis of
(-)-longithorone A using a chirality transfer as the key step.5
Here we disclose a novel efficient chirality exchange, single-
step chirality transformation from sp3 central to axial; benzannu-
lation of optically active aryl(aryl′)-2,2-dichlorocyclopropylmeth-
anols (AACMs) 1 afforded chiral biaryls 2 with excellent level of
stereo induction (eq 1).
SnCl4 were employed for the reaction of AACM 1a and silyl
triflates for diastereomer 1a′ to obtain the chiral biaryl product 2a.
Table 1 lists the results of the chirality exchange. The benzan-
nulation of AACM 1a using TiCl4 at 0 °C gave the chiral
naphthalene 2a (55% yield, 97% ee) along with 20% of the achiral
R-phenylnaphthalene 3a (entry 1). The reaction at -78 °C suc-
cessfully proceeded in excellent yield (96%) and with both excellent
regio- (>99:1) and enantioselectivities (>99% ee) (entry 2).
Excellent selectivities were also achieved by the use of SnCl4 (entry
3). In the case of AACM 1a′, the use of TiCl4 resulted in a switch
of the regioselectivity to give achiral naphthalene 3a exclusively
(entry 4). This finding is consistent with the reported benzannulation.6d
In contrast to the reaction of 1a′ with TiCl4, the use of silyl triflates
gave mainly 2a, and the yield and enantiomeric excess were
moderate (entries 5-7). Absolute configurations of 1a and 2a were
unambiguously determined by X-ray crystallographic analysis.8
The excellent result using TiCl4 encouraged us to investigate
the chirality exchange of other AACMs 1b-1f (Table 2). Similar
to 1a, Cl (R1) analogue AACM 1b also exhibited an excellent result
(entry 1). A notable aspect of the present method lies in its
generality; when R2 substituents were introduced into AACMs
1c-1f, an excellent level of chirality exchange (>99% ee’s) was
achieved in every case examined to give the desired (M)-R-
naphthalenes 2c-2f (entries 2-5). The absolute configurations of
naphthalenes 2b-2f were determined by analogy with 2a.
The proposed mechanism of the chirality transfer mediated by
TiCl4 is as follows (Scheme 1). First, TiCl4 chelates with the oxygen
and chlorine of AACMs 1 to give a rigid intermediate A. Due to
steric repulsion, the ortho substituent (R1) orients itself at the
backside of the chelation face. Successive TiCl4-promoted elimina-
tion of the OH group gives the cationic intermediate pre-(M)-2 while
sufficiently maintaining the conformation by freezing the free
rotation of bonds a and b. The conjugation between the cyclopro-
pylmethyl cation and benzene ring system should contribute to
prevent the free rotation of bond b bearing an accessory R1-phenyl
in pre-(M)-2.9 Then, highly regioselective ring-opening of bond c
and Friedel-Crafts-type cyclization sequentially occur to give
R-arylnaphthalene (M)-2 exclusively. In contrast, because silyl tri-
flates cannot coordinate with Cl, nonchelation intermediate B is
presumably produced. Thus, bonds a and b rotate to some extent
to generate pre-(P)-2 in the cation-formation step.
As part of the program of synthetic studies on the transformation
of gem-dihalocyclopropropanes,6 we reported the Lewis acid-
promoted regiocontrolled benzannulation of some racemic AACMs
1 lacking ortho substituents (R1 or R2) to afford achiral R-arylnaph-
thalenes.6d The choice of Lewis acids determined the cyclization
regioselectivity of the benzannulation: TiCl4 and SnCl4 utilized
the chelation pathway, while silyl triflates utilized a nonchelation
one eventually to give regioisomeric R-arylnaphthalenes. The
present plan is based on the hypothesis that the incorporation of
an ortho substituent (R1 and/or R2) into chiral AACMs 1 would
rationally control the orientation of the benzannulation by fixing
the conformation around bonds a and b of the cationic intermediate
pre-(M)-2. Thus, (M)-R-arylnaphthalenes 2 would be produced by
the chirality exchange (a type of memory effect7).
A couple of chiral diastereomeric AACM substrates, 1a and 1a′,
were conveniently prepared to verify our hypothesis (eq 2) (Sup-
porting Information describes the preparation and characterization
of 1a and 1a′). Both (S)- and (R)-cyclopropanecarboxylic acids,
the precursors of chiral AACMs 1, were obtained; in this context
we used the (S)-form. On the basis of previous studies,6d TiCl4 and
† Kwansei Gakuin University.
9
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J. AM. CHEM. SOC. 2004, 126, 5358-5359
10.1021/ja0319442 CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Chirality Exchange Benzannulation of AACM 1a and 1a′
Acknowledgment. We are grateful to Dr. Kazunori Yanagi and
Mr. Suguru Umeki for X-ray crystallographic analysis. This research
was partially supported by Grant-in-Aids for Scientific Research
on Priority Areas (A) “Exploitation of Multi-Element Cyclic
Molecules” and for the 21st Century COE Program from the
Ministry of Education, Culture, Sports, Science and Technology
of Japan.
yield
(%)c
ratiod
(2a:3a)
ee of 2a
Supporting Information Available: Experimental details, analyti-
cal and crystallographic data and characterization for reactions in Tables
1 and 2 (PDF). X-ray crystallographic files in CIF format. This material
is available free of charge via the Internet at http://pubs.acs.org.
entry
substratea
Lewis acidb
TiCl4
TiCl4
SnCl4
T (°C)
(%)e
1
2
3
4
5
6
7
1a
1a
1a
1a′
1a′
1a′
1a′
0
-78
-78
-78
0
0
-78
75
96
72
89
41
54
trace
(74:26)
(>99:1)
(>99:1)
(>1:99)
(97:3)
(77:23)
-
97
>99
>99
-
45
55
TiCl4
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TBDMSOTf
TMSOTf
TBDMSOTf
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Table 2. Chirality Exchange Benzannulation of AACMs 1b-f
a
Using TiCl4
1
2
entry
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R
R
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yield (%)c
ee (%)d
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2
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4
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1b
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1e
1f
Cl
Cl
MeO
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Me
H
Cl
Me
Cl
Cl
2b
2c
2d
2e
2f
97
70
71
65
47
>99
>99
>99
>99
>99
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Scheme 1
(8) The absolute configuration of 1a was deduced as follows. The stereogenic
center of the cyclopropane moiety was determined as (S) using a derivative,
N-(1S)-1-phenylethyldichlorocyclopropylcarboxamide. That of the tertiary
carbon-bearing OH group was determined as (S) using AACM 1a. The
absolute configuration of 2a was determined as (M) using a derivative,
(-)-(P)-2-bromomethyl-1-(2-bromomethylphenyl)-4-chloronaphthalene.
(The reverse stereodescriptor (P) is a consequence of the sequence rule
of the CIP nomenclature.)
(9) Both the σ-orbital of the cyclopropyl group and the π-orbital of the o-R2-
aryl group can stabilize the π-orbital of the adjacent carbocation with a
maximum overlap, in which the bisected conformation of the cyclopro-
pylmethyl cation is the most stable system. For discussion of cyclopro-
pylmethyl cation, see: Smith, M. B.; March, J. March’s AdVanced Organic
Chemistry, 5th ed.; Wiley-Interscience: New York, 2001; pp 222-223,
p 416-418.
In summary, we achieved the first chirality exchange benzan-
nulation from sp3 central chirality to axial chirality using optically
active o-R1-substituted AACMs 1 and obtained axially chiral
R-arylnaphthalenes 2 with excellent enantioselectivity. The present
method is a new avenue for the synthesis of axially chiral biaryls.
JA0319442
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