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DOI: 10.1055/s-0030-1260325
Enantioselective Alkynylation of Aromatic Aldehydes: Pyridyl Phenylene Terpeneol Catalysts with Flexible Biaryl Axes
Publikationsverlauf
Publikationsdatum:
22. September 2011 (online)
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Abstract
Free rotating biaryl axes of pyridyl phenylene terpenols are fixed by zinc cations to give conformationally pure zinc complexes. These zinc alkoxide catalysts provide yields up to 99% and ee values up to 86% in the enantioselective addition of phenylacetylene to aromatic aldehydes.
Key words
enantioselectivity - biaryls - organometallic reagents - zinc - alkynes
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References and Notes
All reactions were carried out under
an argon atmosphere using Schlenk techniques. Solvents used in chemical conversions
were dried by standard methods and distilled under argon prior to
use. The enantiomeric excesses of the chiral propargylic alcohols
were determined by chiral HPLC. A La Chrome elite unit from Hitachi
was employed together with a 25 cm Chiracel OD-H chiral
column (flow: 0.8 mL/min; pressure: 32 bar; detection λ = 240 nm;
eluent: 90% n-hexanes and 10% i-propanol). The enantiomers of the alcohols
were identified by comparison to reference spectra.¹¹
NMR spectroscopy. Deuterated solvents where
purchased from Acros Organics. Toluene-d
8 was
stored over sodium-lead alloy. NMR spectra for characterization
of compounds where recorded with a Bruker DPX 300 spectrometer (¹H frequency
300.13 MHz). 2D NMR and one-dimensional high resolution spectra
for analysis of the catalytically active system were recorded with
a Bruker AVANCE II 600 spectrometer (¹H frequency
600.20 MHz) using a triple resonance Z gradient probe and processed
using TopSpin 2.1 software (Bruker inc.). The temperature was calibrated
with a 100% MeOH sample. 600 MHz 1D and 2D NMR experiments
were carried out according to the following procedures.
Characterization of the methyl zinc alkoxide
based on ligand 1: Ligand 1 (0.026
mmol, 10 mg) was charged into
a NMR tube and degassed
in vacuo for 10 min. absolute toluene-d
8 (0.30
mL) was added prior to addition of dimethyl zinc (2 M in
toluene, 0.8 mL, 0.156 mmol). The constitution of the formed methyl
zinc complex was confirmed by H,C-HMQC, H,N-HMQC and H,H-NOESY spectroscopic analysis
at a temperature of 295 K. The conformation of the chiral
biaryl axis was determined by characteristic NOE contacts.
In situ study of the reaction of the methyl
zinc alkoxide based on 1 with phenylacetylene: A sample was
prepared as described above. The mixture was equilibrated over a period
of 30 min and phenylacetylene (0.02 mL, 0.156 mmol) was added. The
mixture was equilibrated for 1 h
prior to use
for measurements. The methylzinc alkoxide derivative of 1 was shown to be almost completely converted into
a new species, which was analyzed by H,C-HMQC, H,C-HMBC, H,N-HMQC,
and H,H-NOESY spectroscopy at a temperature of 295 K.
Procedure A: Pyridyl phenylene terpenol
(0.074 mmol;
5 mol%; 1:
28 mg; 2: 29 mg; 3:
28 mg) was degassed in vacuum for 10 min, then dissolved
in toluene (6 mL) and a solution of dimethyl zinc (2.0 M in toluene,
1.80 mL 3.6 mmol) was added at 0 ˚C. The ice bath
was removed and the catalyst was equilibrated for 30 min at r.t.
Phenylacetylene (3 mmol, 0.33 mL) was added at r.t. and the mixture
was further stirred for 45 min. The mixture was cooled on the ice bath
again and aldehyde (1.0 mmol) was added. The colorless solution
was kept at 0 ˚C for 3 days and the reaction was
subsequently quenched with saturated NaHSO4 (5 mL). The
organic phase was separated, the aqueous phase was extracted with
MTBE (3 × 5 mL), and the combined organic
phases were evaporated. The resulting oil was purified by column
chromatography (n-hexanes-ethyl acetate,
4:1; 70 g SiO2) to give the pure product.
Procedure B: See procedure A, with 5 min
reaction time after adding phenylacetylene.
Procedure
C: See procedure A, with 5 min reaction time after adding phenylacetylene
and the solvent was replaced by a mixture of toluene and n-hexanes (1:1).
Procedure
D: See procedure A, the precatalyst was stirred with dimethyl
zinc (0.6 mmol) in toluene (3 mL) for 45 min and, separately, a
mixture of dimethyl zinc (3.0 mmol) and phenylacetylene (3.0 mmol)
in toluene (3 mL) was stirred for 30 min, then added to the catalyst
complex at 0 ˚C.
1,3-Diphenylprop-2-yn-1-ol:¹¹b ¹H
NMR (300 MHz, CDCl3): δ = 2.36 (s,
1 H), 5.72 (s, 1 H), 7.34-7.64 (m, 10 H). ¹³C
NMR (75.5 MHz, CDCl3): δ = 42.0, 118.1,
123.0, 128.9, 140.0. HPLC [Daicel Chiracel OD-H; λ = 254
nm; hexane-IPA = 90:10; 0.8
mL/min]: t
R = 10.7
(R), 17.4 (S)
min.
1-(3-Fluorophenyl)-3-phenylprop-2-yn-1-ol:¹¹c ¹H
NMR (300 MHz, CDCl3): δ = 1.28 (s,
1 H), 5.71 (s, 1 H), 7.28-7.50 (m, 9 H). ¹³C
NMR (75.5 MHz, CDCl3): δ = 64.3, 86.6, 88.2,
113.7, 115.3, 122.0, 122.0, 122.3, 128.4, 128.8, 130.2, 131.8, 143.2,
164.5. HPLC [Daicel Chiracel OD-H; λ = 254 nm;
hexane-IPA = 90:10; 0.8 mL/min]: t
R = 9.4,
21.8 min.
(
E
)-1,5-Diphenylpent-1-en-4-yn-3-ol:¹¹a ¹H
NMR (300 MHz, CDCl3): δ = 5.31 (t, J = 6.0 Hz,
1 H), 6.38 (m, 1 H), 6.90 (d, 1 H), 7.28-7.49
(m, 10 H). ¹³C NMR (75.5 MHz, CDCl3): δ = 63.5,
86.5, 87.9, 122.4, 126.8, 128.1, 128.2, 128.4, 128.7, 131.9, 132.1,
136.0. HPLC [Daicel Chiracel OD-H; λ = 254
nm; hexane-IPA = 90:10; 0.8
mL/min]: t
R = 14.1
(R), 39.8 (S)
min.
1-(Naphthalen-1-yl)-3-phenylprop-2-yn-1-ol:¹¹a ¹H
NMR (300 MHz, CDCl3): δ = 2.40 (d, J = 6.0 Hz,
1 H), 6.38 (d, J = 5.9
Hz, 1 H), 7.40-7.80 (m, 8 H), 7.95 (d, J = 10.1 Hz, 1 H),
8.12 (d, J = 8.2
Hz, 1 H), 8.43 (d, J = 8.4
Hz, 1 H), 9.27 (d, J = 8.5
Hz, 1 H). ¹³C NMR (75.5 MHz,
CDCl3): δ = 63.3, 87.2, 89.0, 122.4,
124.9, 127.0, 128.4, 128.8, 130.7, 131.3, 131.8, 134.1, 135.4, 135.5,
138.0. HPLC [Daicel Chiracel OD-H; λ = 254
nm; hexane-IPA = 90:10; 0.8
mL/min]: t
R = 15.2
(R), 28.6 (S)
min.
4,4-Dimethyl-1-phenylpent-1-yn-3-ol:¹¹d ¹H
NMR (300 MHz, CDCl3): δ = 1.09 (s,
9 H), 1.95 (1 H), 4.26 (d, J = 5.9 Hz,
1 H), 7.28-7.46 (m, 5 H). ¹³C
NMR (75.5 MHz, CDCl3): δ = 25.4, 36.0,
71.9, 85.7, 89.0, 122.8, 128.3, 128.6, 131.7. HPLC [Daicel
Chiracel OD-H; λ = 254
nm; hexane-IPA = 90:10; 0.8
mL/min]: t
R = 8.0
(R), 10.7 (S)
min.