Modular synthesis of axially chiral 3,3′-disilyl dicarboxylic acids by silalactones

Article abstract of DOI:10.1002/asia.201100172

A modular strategy for the synthesis of a variety of axially chiral dicarboxylic acids bearing 3,3′-disilyl groups has been developed. Dehydrogenative silalactonization and subsequent Grignard addition offered a straightforward way towards axially chiral

Full text of DOI:10.1002/asia.201100172

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DOI: 10.1002/asia.201100172
Modular Synthesis of Axially Chiral 3,3’-Disilyl Dicarboxylic Acids by
Silalactones
Takuya Hashimoto, Toshiki Takagaki, Hidenori Kimura, and Keiji Maruoka*[a]
Dedicated to Professor Eun Lee on the occasion of his retirement and 65th birthday
In asymmetric reactions facilitated by catalysts bearing a
binaphthyl unit as a source of chirality, modification of the
substituents at the 3,3’-position has been regarded as an ef-
fective method to achieve high enantioselectivities.[1] Among
the various options to be adapted, incorporation of sterically
demanding trialkylsilyl groups was known to be one of the
most effective strategies.[2]
As a novel class of chiral Brønsted acids having a bi-
naphthyl moiety, we have developed the synthesis of axially
chiral dicarboxylic acids and proven their promising catalyt-
ic activity in various reaction systems.[3] Introduction of the
silyl group at the 3,3’-positions of axially chiral dicarboxylic
acid was initally reported by Yang and co-workers by build-
ing on the direct ortho-lithiation and silylation of (R)-1,1’-bi-
naphthyl-2,2’-dicarboxylic acid (R)-1 (Scheme 1).[4] Howev-
er, in the course of our study, we faced difficulties to apply
Scheme 1. Synthesis of axially chiral 3,3’-disilyl dicarboxylic acids.
this procedure for the introduction of silyl groups other than
the trimethylsilyl group, presumably owing to the steric con-
straints. To circumvent this issue, we set out to investigate
an alternative procedure, which would allow us to access a
variety of axially chiral 3,3’-disilyl dicarboxylic acids in a
modular manner.
Our strategy to achieve this goal was the initial attach-
ment of a silyl group, which has one hydride atom at the
3,3’-positions of axially chiral dicarboxylic acid (R)-1, by
using directed ortho-lilthiation and addition of dialkylchlor-
osilane (Scheme 1). Introduction of hydrosilane was expect-
ed to be far more feasible compared to that of trialkylsilyl
groups owing to the minimization of the steric constraints.
As a key transformation, we then planned to convert the
thus obtained 3,3’-bis(dialkylhydrosilyl) dicarboxylic acid
(R)-2 into disilalactone (R)-3 by dehydrogenation. In the re-
ported example to synthesize silalactones, Shindo and co-
workers synthesized similar five-membered silalactones by
À
the oxidative cleavage of the silicon carbon bond by treat-
ment with iodine or N-iodosuccinimide (NIS) and demon-
strated that addition of a Grignard reagent to silalactones
occurs at the silicon center to give trialkylsilyl carboxylic
acid (Scheme 2).[5,6] Based on this inspiring report, we ini-
tially anticipated that disilalactones (R)-3 might be formed
by oxidative dehydrogenation. However, it turned out that
no oxidative treatment was actually required, as hydrogen
gas evolved spontaneously from this intermediate to give
disilalactones.[7] As a variety of Grignard reagents are readi-
ly available, this synthetic plan is expected to provide a di-
verse array of novel 3,3’-disilyl dicarboxylic acids (R)-4 from
a common intermediate (R)-3.
[a] Dr. T. Hashimoto, T. Takagaki, H. Kimura, Prof. Dr. K. Maruoka
Department of Chemistry
Graduate School of Science
Kyoto University
Sakyo, Kyoto, 606-8502 (Japan)
Fax : (+81)75-753-4041
E-mail: maruoka@kuchem.kyoto-u.ac.jp
Following the established method for the ortho-lithiation
of benzoic acids with lithium 2,2,6,6-tetramethylpiperidide
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201100172.
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Chem. Asian J. 2011, 6, 1936 – 1938

Table 1. Addition of Grignard reagents to disilalactones.[a]
Entry
R1
R2
R3 MgX
Yield [%][b]
1
2
3
4
5
6
7
8
Me
Me
Me
Me
Me
Me
Me
Ph
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
3a
3a
3a
3a
3a
3b
3b
3c
3c
3c
3c
MeMgI
EtMgI
78 (4a)
74
55
ACHTUNGTRENNUNG
Scheme 2. Formation of silalactones and their ring opening by Grignard
reagents.
BnMgBr
iPrMgI
PhMgI
MeMgI
PhMgI
MeMgI
EtMgI
ACHTUNGTRENNUNG
trace (4d)
70 (4e)
66 (4e)
46 (4 f)
39 (4 f)
36 (4g)
37 (4h)
38 (4i)
(LiTMP),[8] we performed the functionalization of (R)-1 by
using Me2Si(H)Cl as a source of the silyl moiety in anticipa-
tion of providing the 3,3’-bis(dimethylhydrosilyl) dicarboxyl-
ic acid. Contrary to our expectation, an acidic work-up led
to the spontaneous evolution of hydrogen gas, and disilalac-
tone (R)-3a was obtained directly without a need for any
additional reaction step. In addition to chlorodimethylsilane,
other silyl groups possessing phenyl groups could also be ob-
tained by using the same procedure to give (R)-3b and 3c,
respectively, though some decrease in yields was found to be
unavoidable despite some attempts for optimizations. It
should be noted that (R)-3b was isolated as a mixture of
diastereomers (ca. 1:2:1), arising from the stereogenic center
at the silicon atom (Scheme 3).
9
10
11
Ph
Ph
Ph
BnMgBr
PhMgI
Ph
[a] Reactions were performed with (R)-2 (1 equiv) and an ethereal solu-
tion of Grignard reagent (4–8 equiv) in THF at room temperature.
[b] Isolated yield.
demanding silyl groups in moderate yields (entries 6–11).
Although our attempt to create additional stereocenters at
the silicon atom using (R)-3b with a Grignard reagent such
as ethylmagnesium iodide led to the formation of a mixture
of diastereomers (data not shown), their separation would
allow further elaboration of the catalyst structure in the
future.
In conclusion, we have developed herein a modular ap-
proach for the synthesis of a variety of axially chiral 3,3’-dis-
ilyl dicarboxylic acids. The fundamental parts for the suc-
cessful implementation of this strategy are 1) the feasibility
of chlorosilanes bearing hydrogen to be incorporated into
the binaphthyl scaffold; 2) novel spontaneous silalactoniza-
tion of hydrosilyl carboxylic acid by evolution of hydrogen
gas; 3) generation of a variety of axially chiral 3,3’-disilyl di-
carboxylic acids by treatment with Grignard reagents. Re-
search is currently underway to explore the advantages of
these axially chiral dicarboxylic acids in asymmetric cataly-
sis.
Scheme 3. Preparation of silalactones from (R)-1,1’-binaphthyl-2,2’-dicar-
boxylic acid.
With the simple one-pot procedure for the synthesis of
desired disilalactones in hand, we set out to examine the ad-
dition of Grignard reagents to these key intermediates as a
means to deliver structurally diverse axially chiral 3,3’-disilyl
dicarboxylic acids (Table 1). By the addition of methyl-,
ethyl-, and benzyl Grignard reagents, respectively, in tetra-
hydrofuran (THF) at room temperature, (R)-3a could be
successfully converted into the corresponding axially chiral
3,3’-disilyl dicarboxylic acids in good yields (Table 1, en-
tries 1–3). Whereas a secondary alkyl Grignard reagent was
found to be unreactive (entry 4), an aromatic group was in-
corporated into the catalyst without difficulty (entry 5).
Other disilalactones, which have phenyl groups (R)-3b and
3c could be utilized as well, thereby giving the correspond-
ing axially chiral dicarboxylic acids (R)-4 bearing sterically
Experimental Section
Preparation of (R)-3a
A hexane solution (1.6m) of butyllithium (12.0 mmol, 7.50 mL) was
added to a solution of 2,2,6,6-tetramethylpiperidine (2.02 mL 12.0 mmol)
in THF (6.0 mL) at 08C and the solution was stirred for 15 min. This so-
lution was then transferred to the flask containing (R)-1,1’-binaphthyl-
2,2’-dicarboxylic acid (682 mg, 2.0 mmol) in THF (2.0 mL) at À788C.
Chlorodimethylsilane (666 mL, 6.0 mmol) was added to the resultant solu-
tion, and the reaction solution was then gradually warmed to room tem-
perature within 3 h. An aqueous solution of 1N HCl was added carefully
to this mixture until the aqueous phase became sufficiently acidic and
evolution of hydrogen gas ceased. Organic layers were extracted with
ethyl acetate, dried over Na2SO4, and evaporated to give reasonably pure
(R)-3a as a white solid in 96% yield (877 mg, 1.93 mmol). 1H NMR
Chem. Asian J. 2011, 6, 1936 – 1938
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K. Maruoka et al.
COMMUNICATION
(400 MHz, CDCl3): d=8.33 (2H, s), 8.03 (2H, d, J=8.2 Hz), 7.60–7.56
(2H, m), 7.34–7.30 (2H, m), 7.18 (2H, d, J=8.5 Hz), 0.66 ppm (12H, s);
13C NMR (100 MHz, CDCl3): d=167.5, 139.8, 136.8, 136.1, 135.1, 133.5,
131.4, 129.5, 129.1, 128.6, 128.1, 0.01, 0.00 ppm; IR (neat): n˜ =1742, 1387,
1256, 1215, 1117, 1069 cmÀ1; HRMS (ESI): m/z: calcd for C26H22O4Si2:
517.1497 [M+2CH3OHÀHÀ]; found: 517.1490; [a]D =+25.0 (c=1.0,
CHCl3).
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[2] For pioneering works, see: a) K. Maruoka, T. Itoh, T. Shirasaka, H.
Yamamoto, J. Am. Chem. Soc. 1988, 110, 310–312; b) K. Maruoka, T.
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1988, 61, 2975–2976.
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10055; b) T. Hashimoto, K. Maruoka, Synthesis 2008, 3703–3706;
c) T. Hashimoto, N. Uchiyama, K. Maruoka, J. Am. Chem. Soc. 2008,
130, 14380–14381; d) T. Hashimoto, M. Hirose, K. Maruoka, J. Am.
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Maruoka, Tetrahedron: Asymmetry 2010, 21, 1187–1188; f) T. Hashi-
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106–108; Angew. Chem. Int. Ed. 2004, 43, 104–106.
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Christensen, Tetrahedron Lett. 1995, 36, 6213–6216; c) S. A. Calad,
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Preparation of (R)-3,3’-bis(dimethylphenylsilyl)-1,1’-binaphthyl-2,2’-
dicarboxylic acid (R)-4e (Table 1, entry 5)
An ethereal solution (1m) of phenylmagnesium iodide (0.80 mL,
0.80 mmol) was added to a THF (2.0 mL) solution of (R)-3a (90.9 mg,
0.20 mmol), which was azeotroped in toluene prior to use, and the reac-
tion was stirred for 15 min at room temperature. The reaction mixture
was then poured into 1N HCl. Organic layers were extracted with ethyl
acetate, dried over Na2SO4, and evaporated. The residue was purified by
column chromatography on silica gel eluting with hexane/ethyl acetate=
3:1 (0.5% acetic acid) to give (R)-4e as a white solid in 70% yield
(85.5 mg, 0.140 mmol). 1H NMR (400 MHz, CDCl3): d=8.12 (2H, s),
7.82 (2H, d, J=8.2 Hz), 7.53 (4H, d, J=6.0 Hz), 7.47 (2H, apparent t,
J=7.5 Hz), 7.39–7.28 (8H, m), 6.99 (2H, d, J=8.5 Hz), 0.69 (6H, s)
0.67 ppm (6H, s); 13C NMR (100 MHz, CDCl3): d=173.2, 138.3, 137.9,
135.9, 134.3, 133.1, 133.0, 132.8, 132.5, 129.1, 128.3, 128.1, 127.7, 127.5,
126.5, À1.1, À1.5 ppm; IR (neat): n˜ =2955, 1682, 1425, 1252, 1113 cmÀ1
;
HRMS (ESI): m/z: calcd for C38H34O4Si2: 609.1912 [MÀHÀ]; found:
609.1909; [a]D =+130.3 (c=1.0, CHCl3).
[7] For the transition-metal-catalyzed dehydrogenative synthesis of silyl
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Chem. 2008, 4, DOI:10.3762/bjoc.4.27, and references therein.
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Mortier, Org. Lett. 2005, 7, 2445–2448; b) T.-H. Nguyen, A.-S. Casta-
net, J. Mortier, Org. Lett. 2006, 8, 765–768.
Acknowledgements
This work was partially supported by a Grant-in-Aid for Scientific Re-
search from the MEXT, Japan.
Keywords: dehydrogenation
nucleophilic addition · synthesis design
·
lactones
·
lithiation
·
Received: February 19, 2011
Published online: May 12, 2011
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