Asymmetrie dehydrative cyclization of ω-hydroxy allyl alcohols catalyzed by ruthenium complexes

Article abstract of DOI:10.1002/anie.200904671

New axially chiral ligands and their allyl esters have been designed and synthesized. The combination of these ligands with [CpRu(CH3CN)3]PF6 has realized highly efficient intramolecular dehydrative cylization of w-hydroxy allyl alcohols, to give a-alkeny

Full text of DOI:10.1002/anie.200904671

Communications
DOI: 10.1002/anie.200904671
Asymmetric Catalysis
Asymmetric Dehydrative Cyclization of w-Hydroxy Allyl Alcohols
Catalyzed by Ruthenium Complexes**
Shinji Tanaka, Tomoaki Seki, and Masato Kitamura*
Chiral cyclic ethers constitute one of the most important
structural units in biologically active compounds such as
polycyclic ethers, polyether antibiotics, acetogenins, as well as
coumaran- and chromane-related natural products.[1] Among
many key building blocks reported so far, a-alkenyl-substi-
tuted cyclic ethers are widely recognized as the most useful
because the alkenyl moiety can be transformed into a wide
range of functionalities, thereby facilitating further elonga-
tion. The development of an efficient strategy for the
construction of these cyclic ethers has attracted a great deal
of attention over the last two decades. In particular, the focal
point is the creation of catalytic enantioselective protocols,
which have been categorized into three types: 1) Wacker-type
oxidative cyclization of ortho-allyl- or homoallylphenol
derivatives,[2] 2) Tsuji–Trost-type intramolecular allylation
using w-hydroxy allyl esters,[1c,f,3] and 3) hydroalkoxylation
of alkynes[4] and allenes.[5] Herein, we report a new type of
protocol, in which non-activated or non-protected diols 1
dehydratively cyclize into the corresponding cyclic ethers 2
with high regio- and enantioselectivity.
We have developed
a new chiral ligand—R-naph-
pyCOOH 4 [naph = naphthyl, py = pyridine, R = substituent
(see structures)]—based on the knowledge that a catalytic
system combining [CpRu(CH3CN)3]PF6 (3; Cp = cyclopenta-
dienyl)[6] with a pyridine-2-carboxylic acid derivative or the
corresponding cationic CpRuIV–p-allyl carboxylato complex
can convert a 1:1 mixture of alcohols or allyl alcohols into
allyl ethers with the liberation of water.[7] The ligand is
characterized by the sterically flexible axial chirality through
the C6–C1’ bond[8] and the adjustability of electronic and
steric properties of the naphthalene ring by changing the R
substituent at C2’. The allyl esters R-naph-pyCOOallyl
=
(allyl = CH2CH CH2) 5 were also target ligands because of
the convenient formation of the CpRuIV–p-allyl complex
directly from 3. A series of compounds 5a–c were prepared in
44–64% yield from 2-bromo-3-methylpyridine through a
Suzuki–Miyaura coupling between pyridine and naphthalene
moieties, modified Reissert–Henze reaction, hydrolysis, and
an allyl esterification sequence in combination with Murai–
À
Chatani silylation of aromatic C H bonds and chlorination or
phenylation at C2’.[9] The enantiomers were separated by
HPLC on a chiral stationary phase, and the absolute config-
urations were determined by single-crystal X-ray analysis of
the ester of (1R,2S,5R)-menthol or the amide of (R)-1-
phenylethylamine.[9]
[*] Dr. S. Tanaka, T. Seki, Prof. Dr. M. Kitamura
Research Center for Materials Science and
the Department of Chemistry, Nagoya University
Chikusa, Nagoya 464-8602 (Japan)
Fax: (+81)52-789-2958
E-mail: kitamura@os.rcms.nagoya-u.ac.jp
The effectiveness of R-naph-pyCOOH 4 and the allyl
ester 5 in combination with 3 in the asymmetric dehydrative
[**] This work was supported by the Grant-in-Aid for Scientific Research
(no. 25E07B212) from the Ministry of Education, Science, Sports,
and Culture (Japan).
1
2
À
cyclization was investigated by use of 1a (C C = (CH2)3;
R1 = R2 = H) under a standard set of reaction conditions
([1a] = 100 mm; [(R)-4 or (R)-5] = [[CpRu(CH3CN)3]PF6
(3)] = 1 mm; DMA; 1008C; 1 h). The results are listed in
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200904671.
8948
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Chemie
Table 1. The ligand (R)-Cl-naph-pyCOOH (R)-4a quantita-
tively afforded 2-vinyltetrahydro-2H-pyran (2a) with an
S/R enantiomeric ratio (e.r.) of 97:3 with 6-exo-trig selectivity
(Table 1, entry 1). The reaction was completed within
10 minutes. The enantiomeric ligand (S)-4a gave a mixture
(S/R = 3:97; Table 1, entry 2). (R)-Cl-naph-pyCOOallyl (R)-
5a gave the same result as (R)-4a (Table 1, entry 3). Increas-
ing the substrate concentration to 1m had no effect on either
the enantioselectivity or the reactivity (Table 1, entry 4). The
substrate/catalyst (S/C) ratio was increased to 1000 without
any adverse effects on the reaction outcome (Table 1,
entries 5 and 6). The reaction proceeded even with an
S/C ratio of 10000 or at lower temperatures, although more
slowly (Table 1, entries 7–9). Aprotic solvents, such as DMF,
THF, and CPME, were also tested and had no significant
effect on the reaction outcome (Table 1, entries 10, 13, and
14). However, enantioselectivity decreased to some extent in
acetone, dioxane, or dichloromethane (Table 1, entries 12, 15,
and 16). The reactivity was appreciably decreased in toluene
(Table 1, entry 17), and acetonitrile almost stopped the
reaction (Table 1, entry 11). tert-Butyl alcohol or isopropyl
alcohol were found to be the solvents of choice, although the
e.r. was marginally decreased (Table 1, entries 18–20). In
other protic solvents, such as ethanol, methanol, water, and
acetic acid, the reaction proceeded but not with as high
efficiency as tert-butyl alcohol (Table 1, entries 21–24).
Replacement of the chloro group with a methyl group at
C2’ of the ligand, however, resulted in a decrease in reactivity
by two orders of magnitude (compare Table 1, entries 5 and
26). Moreover, there was also a reversal in the enantiofacial
selectivity of the reaction when using (R)-Cl-naph-
pyCOOallyl (5a; compare Table 1, entries 3 and 25).[10]
Introduction of a phenyl group at C2’ (5c) further decreased
the reactivity compared to 5b (compare Table 1, entries 25
and 27). Use of a catalyst consisting of (R)-5a and [Cp*Ru-
(CH3CN)3]PF6 (Cp* = pentamethylcyclopentadienyl) instead
of 3 afforded little product 2a under the standard reaction
condition (0.1% after 10 min; 0.5% after 60 min).
Table 2 shows the generality of the present asymmetric
catalysis using a variety of E-configured w-hydroxy allyl
Table 1: Enantioselective intramolecular dehydrative cyclization of (E)-
hept-2-ene-1,7-diol ((E)-1a) to 2-vinyltetrahydro-2H-pyran (2a) using a
catalytic system consisting of R-naph-pyCOOH 4 or its allyl ester 5 and
[CpRu(CH3CN)3]PF6 (3).[a]
1
À
alcohols 1a–m. Removal of one methylene unit from 1a (C
2
1
2
À
C = (CH2)3) to 1b (C C = (CH2)2) gave 2-vinyltetrahydro-
furan (2b) with an e.r. of S/R = 94:6, while an extra methylene
Entry Conc. of
substr. [mm]
Ligand (mm) Solvent
Conv.
[%][b]
e.r.
1
2
(S/R)[c]
À
unit 1c (C C = (CH2)4) resulted in no production of
oxepane derivative 2c (Table 2, entries 1–3). Introduction of
a methyl group at the b position of the allylic moiety of 1a and
1b exerted no negative influence on the reactivity or
enantioselectivity (Table 2, entries 4 and 5). The b-methyl
group of 1d can be replaced with an ethyl, n-pentyl, or
isobutyl group (Table 2, entries 6–8). g-Disubstituted allyl
alcohol 1i can be also used as a substrate, thus constructing a-
disubstituted cyclic ether 2i with high stereocontrol at the tert-
alkyl stereogenic carbon center having no proton (Table 2,
entry 9). tert-Alkyl alcohol 1j at the w-hydroxy end of the
molecule can be applied to this intramolecular cyclization and
gave 2j with an e.r. = 96:4 (Table 2, entry 10). A phenolic
hydroxy group also quantitatively reacted and gave 2-
propenyl substituted chromane 2k (Table 2, entry 11). Cy-
clization of 1l gave a key synthetic intermediate for vitamin E
(Table 2, entry 12).[1c,3b] A coumaran derivative 2m was
quantitatively obtained with nearly perfect enantioselection
when 1m was used (Table 2, entry 13). This framework will be
of interest in the synthesis of tremetone, fomannoxin,
rotenone, and deoxypsorospermin.[1f]
1
2
3
4
5
6
100
(R)-4a (1)
(S)-4a (1)
(R)-5a (1)
(R)-5a (10)
(R)-5a (0.1)
(S)-5a (1)
(R)-5a (0.1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(R)-5a (1)
(S)-5b (1)
(S)-5b (0.1)
(S)-5c (1)
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
>99[d] 97:3
100
100
1000
100
1000
1000
100
100
100
100
100
100
100
100
100
100
100
1000
100
100
100
100
100
100
100
100
>99[d]
3:97
>99[d] 97:3
>99
>99
>99
30
97:3
97:3
3:97
97:3
7[e]
8[f]
9[h]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
74[g] 97:3
5[i]
>99
DMA
96:4
97:3
73:27
80:20
95:5
95:5
72:28
81:19
87:13
92:8
92:8
91:9
85:15
76:24
77:23
65:35
9:91
–
DMF[j]
CH3CN
acetone
THF
7
>99
>99
>99
>99
>99
78
>99
>99
98
92
95
>99
>99
70
CPME
dioxane
CH2Cl2
toluene
tBuOH
tBuOH
iPrOH
C2H5OH
CH3OH
H2O
The preliminary investigation on the ligand structure/
reactivity/enantioselectivity relationship has clearly indicated
that the existence of electron-withdrawing chloro group on
the naphthalene ring of the ligand, and the sterically less
congested Cp ring (rather than Cp*) on Ru are important for
attaining high reactivity and selectivity. We speculate that a
redox-mediated donor–acceptor bifunctional mechanism is
operating[7,11] and that the chloro group is playing a key role in
stabilizing a favorable transition state probably through a
decrease in the LUMO level—thus facilitating a possible rate-
determining RuIV/RuII step[11a]—and also through a CpH/Cl
hydrogen bond.[12] Elucidation of the detailed mechanism is
now an on-going project in our research group.
CH3COOH
DMA
DMA
3
DMA
3
–
[a] All reactions were carried out at 1008C for 1 h using 1 mol of 3 for
ligand 4 or 5, unless otherwise specified.[9] [b] Determined by GC analysis
(J&W Scientific DB-5).[9] The conversions are nearly identical to the yield
of 2a. [c] Determined by GC analysis on a chiral stationary phase
(CHIRALDEX G-BP).[9] [d] The reaction was completed within 10 min.
[e] 1008C, 24 h. [f] 508C. [g] >99% conversion after 5 h. [h] 308C.
[i] 83% conversion after 80 h. [j] Contamination by dimethylamine
dramatically decreased the reactivity. Careful purification is essential.
CPME=cyclopentyl methyl ether, DMA=N,N-dimethylacetamide,
DMF=N,N-dimethylformamide, THF=tetrahydrofuran.
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Communications
tivity.[13] Both aliphatic and aromatic alcohols can be used as
nucleophiles at the w-hydroxy end of the substrate. The
present results will help facilitate the synthesis of a variety of
chiral a-alkenyl cyclic ethers, which are potentially important
intermediates for natural product synthesis, as well as
assisting in the development of higher-performance ligands.
Table 2: Catalytic asymmetric cyclization of w-hydroxy allyl alcohols 1 to
give a-alkenyl cyclic ethers 2 using (R)-Cl-naph-pyCOOallyl [(R)-5a] and
[CpRu(CH3CN)3]PF6 (3).[a]
Entry
1
Product
Yield [%][b]
90[d]
e.r.[c]
97:3 (S/R)
2a
[e]
2
2b
2c
–
94:6 (S/R)
Experimental Section
[CpRu(CH3CN)3]PF6 (3; 32.0 mg, 73.8 mmol) and (R)-5a (10.0 mm in
CH2Cl2, 7.38 mL, 73.8 mmol) were added to a 500 mL Schlenk tube.
The resulting pale yellow solution was carefully concentrated
in vacuo and to this residue was added (E)-1a (1000 mm in DMA,
73.8 mL, 73.8 mmol) at RT. After stirring for 1 h at 1008C the mixture
was cooled to RT and the mixture was partitioned between pentane/
diethyl ether (3:1, 30 mL) and water (20 mL). The aqueous layer was
extracted with pentane/diethyl ether (3:1, 30 mL ꢀ 5), and the
combined organic extracts were passed through a pad of silica gel
(2 cm ꢀ 2 cm). The filtrate was concentrated to a volume of about
10 mL, which was distilled at 1508C and 760 mmHg by using a
Kugelrohr apparatus to give (S)-2a (7.41 g, 90% yield).
3[f]
–
–
4
5
2d
2e
87
98:2
[e]
–
97:3 (S/R)
Details of the synthetic methods used for the preparation of chiral
ligands, general procedure for asymmetric cyclization, and the NMR
spectroscopic data of the substrates and products are available in the
Supporting Information.
6
2 f
2g
2h
R=C2H5
R=C5H11
R=iBu
93[g]
98
94
98:2
98:2
98:2
7
8[h]
9[i]
10
2i
92[g]
92[g]
96:4
Received: August 22, 2009
Published online: October 19, 2009
2j
96:4
Keywords: asymmetric catalysis · chiral cyclic ethers ·
.
cyclization · homogeneous catalysis · ruthenium
11[j,k]
2k
98
97:3
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12[j,l]
2l
97
98
97:3 (S/R)
13[j,k]
2m
>99:1 (S/R)
[a] All reactions were carried out under the standard reaction conditions
(1 mmol scale, [1]=100 mm; [3]=[(R)-5a]=1 mm; DMA; 1008C; 1 h)
unless otherwise specified. In all cases, the conversions were >99%.
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2m.[9] [b] Yield of isolated product. Extraction carried out using pentane/
diethyl ether. [c] Determined by GC analysis using a chiral stationary
phase.[9] [d] 10 g reaction scale (73.8 mmol, [1a]=1000 mm; [3]=[(R)-
5a]=1 mm; DMA). Yield of isolated product after distillation.
[e] 1H NMR experiment in [D7]DMF. The conversion was >99%.
[f] Undetermined products such as oligomers were formed, but not
2c. [g] Yield after taking into consideration of the amount of the
contaminated pentane/diethyl ether. [h] 3 h. [i] 708C, 10 h. The diene-like
products were produced at 1008C for 1 h. [j] A 10:1 tC4H9OH/DMA
mixture was used as the solvent. [k] The diene-like products were
produced only in DMA. [l] 24 h. Bn=benzyl.
In summary, we have developed a novel axially chiral
ligand R-naph-pyCOOH 4 and its corresponding allyl esters
(5), and have shown that the combination of Cl-naph-
pyCOOH or Cl-naph-pyCOOallyl with a Trost-type CpRu
complex achieves dehydrative intramolecular cyclization of
w-hydroxy allyl alcohols with excellent reactivity and selec-
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Chemie
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[10] The R/S absolute configuration of 5a and 5b are reversed
because of the priority rule.
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