Enantioselective alkynylation of aldehydes catalyzed by a camphor sulfonylated amino alcohols titanium(IV) catalyst system

Article abstract of DOI:10.1002/aoc.1622

A new titanium(IV) complex has been developed for the effective enantioselective alkynylation of phenylacetylene addition to aldehydes. The titanium(IV) complex was readily prepared in situ from (R)-C-(7,7-dimethyl-2- oxo-bicyclo[2.2.1]hept-1- yl)-(1R,2S)

Full text of DOI:10.1002/aoc.1622

Full Paper
Received: 4 August 2009
Revised: 26 November 2009
Accepted: 3 January 2009
Published online in Wiley Interscience: 5 February 2010
(www.interscience.com) DOI 10.1002/aoc.1622
Enantioselective alkynylation of aldehydes
catalyzed by a camphor sulfonylated amino
alcohols titanium(IV) catalyst system
Shaohua Goua∗, Zhongbin Yea,b, Zhiyu Huanga and Xiping Maa
A new titanium(IV) complex has been developed for the effective enantioselective alkynylation of phenylacetylene addition
to aldehydes. The titanium(IV) complex was readily prepared in situ from (R)-C-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-
yl)-(1R,2S)-N-(2-hydroxy-1,2-diphenyl-ethyl)-methanesulfonamide (1h) and tetraisopropyl titanate [Ti(i-OPr)4]. A variety of
aromatic aldehydes and α,β-unsaturated aldehydes were found to be suitable substrates in the presence of the camphor
sulfonylated amino alcohol titanium(IV) complex [10 mol% 1h, 40 mol% Ti(i-OPr)4]. The desired propargylic alcohols were
afforded with high isolated yields (up to 90%) and moderate enantioselectivities (up to 65% ee) under mild conditions.
c
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Keywords: aldehydes; amino alcohols; camphor; phenylacetylene; zinc
Introduction
alcohol as start materials (Scheme 1).[9] Initially, we investigated
the alkynylation of phenylacetylene addition to benzaldehyde in
the presence of 10 mol% ligand 1 and 40 mol% tetraisopropyl
titanate [Ti(i-OPr)4] in dry dichloromethane (CH2Cl2) at 22 ◦C
under nitrogen atmosphere. The results in Table 1 showed that
the ligands 1a, 1b and 1c, which derive from (R)-camphor-
10-sulfonic acid and hydrazine hydrate, gave 12, 17 and 14%
ee with good yields (Table 1, entries 1–3). Ligand 1h, which
derives from (R)-camphor-10-sulfonic acid and (1R, 2S)-2-amino-
1,2-diphenyl-ethanol, gavethehighesteewithgoodyield(Table 1,
entry 8); however, other camphor sulfonylated amino alcohols,
which derive from (1S, 2R)-, (1S, 2S)- or (1R, 2R)-2-amino-1,2-
diphenylethanol, gave lower ee with high yield (Table 1, entries
9–11), which might be attributed to the match pair or mismatch
pairoftheconfigurationbetweencamphor-10-sulfonicacidand2-
amino-1,2-diphenyl-ethanol. Othercamphor-sulfonylatedamides,
1d–j, which derive from benzylamine, 2-methoxyphenylamine,
tert-butylamine or (S)-1-phenylethylamine, gave lower ee with
good to excellent yield (Table 1, entries 4–7).
Catalytic asymmetric carbon–carbon bond formation is a very
important reaction in the field of organic chemistry.[1] Amongst
these reactions, the enantioselective alkynylation of aldehydes
has attracted much attention in asymmetric synthesis because
of its simplicity and utility for the preparation of propargylic al-
cohols which are key building blocks used in the fine chemical
and pharmaceutical industries.[2] Recently, numerous examples
of using various chiral ligands such as (−)-N-methyl ephedrine,[3]
BINOLs,[4] proline,[5] oxazolidine[6] and others[7] have been re-
ported by different research groups. Despite the achievements
made in this field of organometal (zinc) chemistry, the alkynyla-
tionofaldehydeshasnotyetreachedthelevelofpracticabilitythat
is required for a synthetically useful catalytic system. Thus, it is still
necessary to develop new types of chiral ligands which are greatly
needed to probe how the chiral catalysts work on the reaction and
how to develop new types of chiral ligands. On the other hand,
β-amino alcohols and camphor sulfonic acid and their derivatives
have been used in many asymmetric reactions, and good to ex-
cellent results have been obtained.[8] Inspired by these works, we
continuedtosearchforanewhighlyefficientcatalystsystemusing
camphor sulfonic acid derivatives and amine or β-amino alcohols
to achieve structural diversity. Therefore, a set of camphor sul-
fonic acid derivatives based on amine or β-amino alcohols were
investigated (synthesis for the chiral ligands 1a–k: see Experi-
mental section for details). Herein, we wish to report a camphor
sulfonylated amide or sulfonylated amino alcohols titanium com-
plex that engenders a more effective catalyst for the asymmetric
alkynylation of phenylacetylene addition to aldehydes (Fig. 1).
Optimization of the Catalyst System
Having realized the most promising complex in the enantioselec-
tive alkynylaltion of benzaldehyde, the effect of several reaction
parameters, such as catalyst loading and reaction solvent, were
studied with the aim of optimizing the reaction conditions and
developing a more efficient catalytic system.
∗
Correspondence to: Shaohua Gou, Southwest Petroleum University, School
of Chemistry and Chemical Engineering, Chengdu, Sichuan 610500, China.
E-mail: shaohuagou@swpu.edu.cn
Results and Discussion
a
School of Chemistry and Chemical Engineering, Southwest Petroleum
University, Chengdu 610500, People’s Republic of China
Chiral Catalyst System Screening
Chiral ligands 1a–k were synthesized in good to excellent yields
using (R)-camphor sulfonic acid and different amine or amine
b
State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation,
Southwest Petroleum University, Chengdu 610500, People’s Republic of China
c
Appl. Organometal. Chem. 2010, 24, 374–379
Copyright ꢀ 2010 John Wiley & Sons, Ltd.

Camphor sulfonylated amino alcohols titanium(IV) catalyst system
Figure 1. The structures of the ligands screened in the reaction.
O
O
O
NH
S
O
NH
S
N
NH
NaCNBH3
O
S
1b
O
1a
Cl
Br
O
Ph
O
O
O
O
I
NH
S
S
NHR
O
NH
1c
1d-k
1d: RNH2 = Benzylamine
1h: RNH2 = (1R, 2S)-2-Amino-1,2-diphenylethanol
1i: RNH2 = (1S, 2S)-2-Amino-1,2-diphenylethanol
1j: RNH2 = (1S, 2R)-2-Amino-1,2-diphenylethanol
1k: RNH2 = (1R, 2R)-2-Amino-1,2-diphenylethanol
1e: RNH2 = 2-Methoxyphenylamine
1f: RNH2 = tert-Butylamine
1g: RNH2 = (S)-1-Phenylethylamine
Scheme 1. The synthesis of chiral ligands 1a–k.
First, we investigated the effect of different reaction solvents
(toluene, CH2Cl2, THF, Et2O and hexane) using the best 1h–Ti(IV)
complex (Table 2, entries 1–5). It was found that THF and Et2O
gave very low ee and yield with longer reaction time than
toluene (Table 2, entries 2 and 3). Hexane gave moderate ees
with moderate yield (Table 2, entry 4). The highest ee of 56 with
90% yield was obtained in toluene (Table 2, entry 1).
The optimum loading of 1h and Ti(i-OPr)4 was investigated
under the best conditions (Table 3). It was found that the best
loading was 10 mol% 1h and 40 mol% Ti(i-OPr)4, respectively.
With increased or decreased loading of Ti(i-OPr)4, dissatisfactory
resultswereafforded(Table 3,entries2–4).Theaboveresultsshow
thegeneralfeatureof excessTi(i-OPr)4 requiredtoachievethebest
enantioselectivities and reactivities in asymmetric alkynylation of
aldehydes. With increasing or decreasing the loading of 1h from
10 to 20 or 5 mol% under same conditions, unfavourable ee was
obtained (Table 3, entries 5–6 entry 1).
electron-donating group (Me or OMe) led to a slight increase in
the ees of the products 3b and c (Table 4, entries 2 and 3 vs entry
1). Electron-withdrawing groups (F, Cl or Br, Table 4, entries 4–6)
showed moderate yields and similar ees with benzaldehyde. The
reaction of β- and α-naphthaldehydes 2g and 2h, respectively,
resulted in good yields and moderate ees (Table 4, entries 7 and
8). Furan-2-carbaldehyde gave lower yield and ee than benzalde-
hyde (Table 4, entry 9 vs entry 1). The reaction of α,β-unsaturated
aldehyde (trans-cinnamaldehyde) only gave 42% ee after 48 h
(Table 4, entry 10). In general, good yields and moderate enan-
tioselectivities of the propargylic alcohols 4a–j were obtained
(Table 4).
Conclusion
In summary, we have developed a Ti(IV) catalyst system based on
(R)-camphor sulfonic acid, (1R,2S)-2-amino-1,2-diphenylethanol
and tetraisopropyl titanate [Ti(i-OPr)4], which was readily prepared
in one simple step from commercially available starting materials
for the asymmetric alkynylation of phenylacetylene addition to
aldehyde. The corresponding titanium(IV) complex, which was
prepared using 10 mol% 1h and 40 mol% Ti(i-OPr)4 in situ, showed
excellent catalytic activities and moderate enantioselectivities (up
to 65% ee) in the asymmetric alkynylation of phenylacetylene
Substrate Generality
To study the generality of the complex 1h–Ti(IV) for the enantios-
elective alkynylation to various aldehydes, a number of aromatic
aldehydes having electron-donating and electron-withdrawing
groups were examined under the optimized conditions reported
in Table 4. In comparison to the results obtained with 2a, the
c
Appl. Organometal. Chem. 2010, 24, 374–379
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
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S. Gou et al.
Table 1. Enantioselective alkynylation of phenylacetylene addition
to benzaldehyde catalyzed by 1–Ti(IV) complex
Table 3. Optimization the ratio of 1h to Ti(i-OPr)4 in the alkynylation
of phenylacetylene addition to benzaldehyde
Entrya
1h (mol%)
Ti(i-Opr)4 (mol%)
Yield (%)b
Ee(%)c
10 mol% 1
40 mol% Ti(i-OPr)4
3.0 equiv. ZnEt2
OH
O
1
2
2
3
4
5
6
10
10
10
10
10
20
5
40
50
30
20
0
90
94
90
99
19
91
70
56
46
10
7
+
H
Ph
Ph
Ph
2a
H
CH2Cl2, 22 °C
3.0 equiv.
Ph
3
4a
Entrya
Ligand
Time (h)
Yield (%)b
Ee(%)c
4
40
20
38
31
1
2
1a
1b
1c
1d
1e
1f
24
24
24
24
24
24
24
40
40
24
24
91
87
90
93
98
87
76
84
85
96
91
12
17
14
7
a Concentration of benzaldehyde: 2.0 M in PhCH3; ZnEt2: 3.0 equiv. in
hexene; the reactions were performed at 22 ◦C.
b Isolated yields.
3
4
c Determined by chiral HPLC (Chiralcel OD-H); the configuration is S of
the major enantiomer of the product.[4g]
5
3
6
10
15
49
10
7
7
1g
1h
1i
8
9
10
11
1j
Table 4. Enantioselective alkynylation of phenylacetylene addition
to different aldehydes in the presence of 1h–Ti(IV) complex
1k
37
a Concentrationofbenzaldehyde:2.0M intoluene;theloadingofligand
1: 10 mol%, 40 mol% Ti(i-OPr)4 in toluene; ZnEt2: 3.0 equiv. in hexene;
the reactions were performed for 24–40 h at 22 ◦C.
b Isolated yields.
10 mol% 1h
40 mol% Ti(i-OPr)4
3.0 equiv. ZnEt2
OH
O
+
H
Ph
R
R
H
c Determined by chiral HPLC (Chiralcel OD-H); the configuration is S of
the major enantiomer of the product.[4g]
Toluene, 22 °C
3.0 equiv.
Ph
2a-j
34
4a-j
Yield
(%)b
Entrya
Aldehyde
Time(h)
Ee(%)c
Table 2. Enantioselective alkynylation of phenylacetylene addition
to benzaldehyde in the presence of 1h–Ti(IV) complex
1
2
3
4
5
6
7
Benzaldehyde (2a)
p-MeOC6H4 (2b)
p-MeC6H4 (2c)
p-FC6H4 (2d)
24
48
40
40
40
40
24
90
73
87
77
71
74
88
56
61
63
56
54
52
65
Entrya
Solvent
Time(h)
Yield (%)b
Ee(%)c
1
2
3
4
5
CH2Cl2
THF
40
24
24
10
24
84
21
19
83
90
49
14
12
37
56
p-ClC6H4 (2e)
p-BrC6H4 (2f)
Et2O
Naphthalene-2-carbaldehyde
(2g)
Hexene
Toluene
8
Naphthalene-1-carbaldehyde
24
83
51
(2h)
a Concentration of benzaldehyde: 2.0 M in PhCH3; the loading of ligand
1i: 10 mol%, 40 mol% Ti(i-OPr)4 in PhCH3; ZnEt2: 3.0 equiv. in hexene;
the reactions were performed at 22 ◦C.
9
Furan-2-carbaldehyde (2i)
(E)-Cinnamaldehyde (2j)
48
48
79
57
45
42
10
b Isolated yields.
a Concentration of benzaldehyde: 2.0 M in toluene; the loading of
ligand 1h: 10 mol%, 40 mol% Ti(i-OPr)4 in toluene; ZnEt2: 3.0 equiv. in
hexene; the reactions were performed at 22 ◦C.
c Determined by chiral HPLC (Chiralcel OD-H); the configuration is S of
the major enantiomer of the product.[4g]
b Isolated yields.
c Determined by chiral HPLC (Chiralcel OD or OD-H); the configuration
is S of the major enantiomer of the product.[4g,h]
addition to various aldehydes under mild conditions. Further
investigation on the applications of these ligands for other
asymmetric reactions is ongoing.
instruments (75 MHz) with complete proton decoupling. Chem-
ical shifts are reported in ppm from the tetramethylsilane with
the solvent resonance as internal standard (CDCl3, δ = 77.0).
Enantiomeric ratios of the products were determined using chi-
ral HPLC (OD-H or OD column) techniques. Optical rotations
were measured on a commercial polarimeter and reported as
Experimental Section
General Remarks
1H NMR spectra were recorded on commercial instruments
(300 MHz). Chemical shifts were reported in ppm from tetram-
ethylsilane with the solvent resonance as the internal standard
(CDCl3, δ = 7.26). Spectra are reported as follows: chemical shift
(δ ppm), multiplicity (s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet), coupling constants (J, Hz), integration
and assignment. 13C NMR spectra were collected on commercial
follows: [a]T (c = g/100 ml, solvent). HRMS was recorded with
D
ESI source (in CH3OH). Elemental analyses were performed using
commercial instruments. Analytical thin layer chromatography
(TLC) was carried out on commercial plates coated with 0.25 mm
ofsilicagel.Preparativeflashsilicachromatographywasperformed
using silica gel 200–400 mesh. All reactions were carried out under
c
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Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2010, 24, 374–379

Camphor sulfonylated amino alcohols titanium(IV) catalyst system
an atmosphere of nitrogen in flame- or oven-dried glassware with
magnetic stirring unless otherwise indicated.
General Experimental Procedure For synthesis of 1d–l
To
solution (R)-(+)-10-camphorsulfonyl chloride (1.50 g,
a
5.5 mmol) in 20 ml dried CH2Cl2 were added NEt3 (0.9 ml, 6 mmol)
and the corresponding amine or amino alcohol (5.0 mmol) at 0 ◦C.
Then the mixture was stirred at 25 ◦C for 5–10 h (using TLC to
check the reaction procedure). The mixture was washed with 1
M aqueous HCl solution (3 × 10 ml), saturated NaHCO3 aqueous
(adjust the pH value to 6–7) and brine after the reaction finished.
The organic phrase was dried over anhydrous Na2SO4, followed
by further purification via column chromatography to give the
corresponding products 1d– l.
Materials
(R)-(+)-10-Camphorsulfonyl chloride I,[9b] chiral ligands 1a–c,[9b]
1d,[9c,e] 1f,[9d] 1g[9e] and 1h–k[9a] were synthesized according
to the literature procedures. These known compounds were
characterized by comparing the 1H, 13C NMR spectra with
those published in the literature. All liquid aldehydes were used
after distilled; phenylacetylene, diethylzinc, Ti(i-OPr)4 and other
chemical reagents are commercially available, and were used
directly without further purification. Anhydrous solvents such as
THF, CH2Cl2, toluene, hexene and Et2O were treated by standard
methods.
(R)-C-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-yl)-N-benzyl-
methanesulfonamide (1d)
Yield: 89%. [a]25 = −6.91 (c = 1.0, CH2Cl2). {Lit.[9c,e] [a]20
=
D
D
+6.68 (c = 1.0, CHCl3) for (S)-C-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]
hept-1-yl)-N-benzyl-methanesulfonamide}.
Synthesis for Chiral Ligands 1a–c
(R)-Cyclic camphor sulfonyl hydrazone (1a)
(R)-C-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-yl)-N-(2-methoxy-
phenyl)-methanesulfonamide (1e)
To a solution of (R)-(+)-10-camphorsulfonyl chloride I (1.25 g,
5.0 mmol) in 20 ml of methanol were added hydrazine monohy-
drate (0.5 ml, 10 mmol) and acetic acid (0.15 ml, 2.5 mmol). The
mixture was stirred under reflux condition for 4 h. Then the re-
action mixture was cooled down. The mixture was dissolved in
small amount of water and extracted with ethyl acetate for three
times (3×20 ml). The pH value of the aqueous phase was adjusted
to 9–10 by K2CO3 and extracted with ethyl acetate (3 × 20 ml).
The combined extracting organic layer was washed with brine
and dried with anhydrous Na2SO4, followed by filtration and
concentration to obtain white solid of cyclic camphor sulfonyl hy-
Yield: 92%. M.p. 90–92 ◦C, [a]25 = −27.56 (c = 1.0, CH2Cl2).
D
1H NMR (300 MHz, CDCl3) δ = 0.95 (s, 3H, OCH3), 1.06 (s, 6H,
2CH3), 1.59–1.65 (m, 2H, CH2 of camphor), 1.79–1.90 (m, 2H,
CH2 of camphor), 2.43–2.51 (m, 1H, CH of camphor), 3.78 (s, 2H,
CH2-SO2), 3.79–4.43 (dd, J1 = 6.3 Hz, J2 = 12.3 Hz, 2H, CH2 of
camphor), 5.10 (br, 1H, NH), 6.79–6.87 (m, 2H, Ar –H), 7.18–7.24
(m, 2H, Ar –H) ppm. 13C NMR (75 MHz, CDCl3) δ = 16.4, 16.8
(2CH3), 29.1, 30.2, 30.6, 39.2, 53.9, 54.9 (C-camphor), 55.3 (OCH3),
56.1 (C-camphor), 91.0, 91.6, 110.4, 120.6, 125.3, 129.2, 129.9,
157.6 (C–Ar), 210.0 (C O) ppm. HRMS: (ESI, CH3OH) calcd for
C17H23NO4S(M+): requires 337.1348, found 337.1331. Anal. calcd
for C17H23NO4S: C, 60.51; H, 6.87; N, 4.15%; found: C, 60.42; H, 6.76;
N, 4.08%.
drazone 1a in 89% yield. [a]25 = +12.5 (c = 1.0, CH2Cl2) {Lit.[9b]
D
[a]20 = −13.1 (c = 1.03, CHCl3) for S-enantiomer}.
D
(R)-Cyclic camphor sulfonyl hydrazine (1b)
To a solution of cyclic camphor sulfonyl hydrazone (1a) (460 mg,
2 mmol) in 5 ml of methanol was added 3.0 ml of acetic acid,
followed by adding NaCNBH3 dropwise. Then the reaction mixture
was stirred at 25 ◦C for 12 h. The excess NaCNBH3 was quenched
by 1 M aqueous HCl solution. The pH value of the aqueous
phase was adjusted to 9–10 by K2CO3 and extracted with ethyl
acetate (3 × 20 ml). The combined organic layer was washed
with brine and dried with anhydrous Na2SO4, followed by further
purification via column chromatography to give white solid of
(R)-C-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-yl)-N-tert-butyl-
methanesulfonamide (1f)
Yield: 95%. [a]25 = −6.95 (c = 1.0, CH2Cl2).
D
(R)-C-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-yl)-N-(S)-(1-phenyl-
ethyl)-methanesulfonamide (1g)
Yield: 65%%. [a]25 = −17.3 (c = 1.5, CH2Cl2). {Lit.[9e] [a]20
=
D
D
−16.7 (c = 1.0, CH2Cl2)}.
cyclic camphor sulfonyl hydrazine 1b in 95% yield. [a]25 = +88.6
D
(c = 1.0, CH2Cl2) {Lit.[9b] [a]20 = −89.0 (c = 1.04, CHCl3) for
D
C-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-yl)-N-(2-hydroxy-1,
2-diphenyl-ethyl)-methanesulfonamide (1h–k)
S-enantiomer}.
Yields: 77-84% for 1h–k. [a]25 = −6.0 (1h),−67.2 (1i), −3.4(1j),
(R)-Nβ -Benzyl cyclic camphor sulfonyl hydrazine (1c)
D
+46.6 (1k) (c = 1.0, CH2Cl2). {Lit.[9a] [a]25 = +5.8 (c = 1.0,
D
To a solution of cyclic camphor sulfonyl hydrazine 1b (460 mg,
2 mmol) in 15 ml of dichloromethane were added K2CO3 (414 mg,
3 mmol) and tetrabutylammonium bromide (32 mg, 0.1 mmol),
followed by benzyl bromide (0.36 ml, 3 mmol). The reaction
was stirred at 22 ◦C for 2 days. Waters was added and the
resulting mixture was extracted by ethyl acetate (3 × 20 ml).
The combined organic layer was washed with brine and dried
with anhydrous Na2SO4 followed by further purification via
column chromatography to give white solid of 1c in 68% yield.
CH2Cl2) for (S)-C-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-yl)-N-
(1S,2R)-(2-hydroxy-1,2-diphenyl-ethyl)-methanesulfonamide}.
General experimental procedure for the alkynylation
of phenylacetylene addition to aldehyde
To a solution of ligand 1h (10.68 mg, 0.25 mmol) and Ti(i-OPr)4
(25 µl in toluene, 0.025 mmol) in dry toluene (0.5 ml) at room
temperature, a solution of Et2Zn (1.0 M in hexene, 0.75 ml) was
added. After the mixture was stirred at the room temperature
for 2.5 h, phenylacetylene (82.4 µl, 0.75 mmol) was added and
[a]25 = +148.7 (c = 1.0, CH2Cl2) {Lit.[9b] [a]20 = −150.6
(c =D1.005, CHCl3) for S-enantiomer}.
D
c
Appl. Organometal. Chem. 2010, 24, 374–379
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/aoc

S. Gou et al.
then stirring continued for 1.0 h. The corresponding aldehyde
(0.25 mmol)wasaddedtothesolutionafter10 minat0 ◦C,thenthe
resultant mixture was allowed to warm up to room temperature
(22 ◦C) and stirred for the indicated time (24–48 h). After the
reaction was completed, it was cooled to 0 ◦C and quenched
by 1.0 M aqueous HCl (2.0 ml). The mixture was extracted with
ethyl acetate (EtOAc) (3 × 20 ml). The organic layer was dried over
Na2SO4 and concentrated under vacuum. The residue was purified
by flash column chromatography (silica gel H, EtOAc : hexene
= 1 : 10, v/v) to give the corresponding pure product. These
compounds (4a–j) were characterized by comparing their 1H,
13C NMR spectra with those published in the literature.[3–5] The
ee were determined by HPLC analysis (Chiralcel OD-H column),
and the absolute configuration of major adducts was assigned by
comparison with literature data.[4g–h]
(S)-1-(2-naphthyl)-3-phenyl-prop-2-yn-1-ol (4g)
Yield88%andee65%determinedbyHPLCanalysis(ChiralcelOD-H
column, 10% iPrOH in hexane at 1.0 ml min−1, 254 nm); retention
times, t1 (major) = 40.5 min, t2 (minor) = 13.5 min; [a]25 = −7.5
D
(c = 0.5, CH2Cl2). {Lit.[4g] [a]27 = +13.7 (c = 1.22, CHCl3) for R
D
enantiomer in 98% ee}.
(S)-1-(1-naphthyl)-3-phenyl-prop-2-yn-1-ol (4h)
Yield 83% and ee 51% determined by HPLC analysis (Chiralcel
OD-H column, 10% iPrOH in hexane at 1.0 ml min−1, 254 nm);
retention times, t1 (major) = 29.5 min and t2 (minor) = 12.4 min.
[a]25 = 12.0 (c = 0.5, CH2Cl2). {Lit.[4h] [a]25 = −27.8 (c = 1.25,
D
D
CHCl3) for R enantiomer in 94.6% ee}.
(S)-1-(2-Furyl)-3-phenyl-prop-2-yn-1-ol (4i)
(S)-1,3-diphenyl-prop-2-yn-l-ol (4a)
Yield79%andee45%determinedbyHPLCanalysis(ChiralcelOD-H
Yield 90% and ee 56% determined by HPLC analysis (Chiralcel OD-
column, 10% iPrOH in hexane at 1.0 ml min−1, 254 nm); retention
Hcolumn, 10%iPrOHinhexaneat1.0 mlmin−1, 254 nm);retention
times, t1 (major) = 18.6 min, t2 (minor) = 9.5 min; [a]25 = −1.9
times, t1 (major) = 17.5 min, t2 (minor) = 11.8 min; [a]25 = −2.4
D
D
(c = 0.5, CH2Cl2). {Lit.[4h] [a]22 = +4.4 (c = 0.81, CHCl3) for R
(c = 0.5, CH2Cl2). {Lit.[4g] [a]27 = +9.3 (c = 0.6, CHCl3) for R
D
D
enantiomer in 87.5% ee}.
enantiomer in 96% ee}.
(S)-(E)-1,5-diphenyl-pent-1-en-4-yn-3-ol (4j)
(S)-1-(4-methoxyphenyl)-3-phenyl-prop-2-yn-1-ol(4b)
Yield73%andee61%determinedbyHPLCanalysis(ChiralcelOD-H
Yield 61% and ee 46% determined by HPLC analysis (Chiralcel OD
column, 10% iPrOH in hexane at 1.0 ml min−1, 254 nm); retention
column, 10% iPrOH in hexane at 1.0 ml min−1, 254 nm); retention
times t1 (major) = 26.4 min, t2 (min) = 15.1 min; [a]25 = −4.3
times, t1 (major) = 72.5 min, t2 (minor) = 24.2 min; [a]25 = −2.1
D
D
(c = 0.5, CH2Cl2). {Lit.[4h] [a]22 = +7.8 (c = 1.0, CHCl3) for R
(c = 0.5, CH2Cl2). {Lit.[4h] [a]25 = +6.2 (c = 0.85, CHCl3) for R
D
D
enantiomer in 93% ee}.
enantiomer in 91.7% ee}.
(S)-1-(4-methylphenyl)-3-phenyl-prop-2-yn-1-ol(4c)
Acknowledgments
Yield87%andee63%determinedbyHPLCanalysis(ChiralcelOD-H
The authors gratefully acknowledge the Open Fund (no. PLN0908)
of the Key Laboratory of Oil and Gas Reservoir Geology
and Exploitation (Southwest Petroleum University) for financial
support and Professor Chen Jinyu for helpful discussions.
column, 10% iPrOH in hexane at 1.0 ml min−1, 254 nm); retention
times t1 (major) = 17.6 min, t2 (minor) = 9.4 min; [a]25 = −1.7
D
(c = 0.5, CH2Cl2). {Lit.[4g] [a]25 = +2.99 (c = 0.93, CHCl3) for R
D
enantiomer in 92.5% ee}.
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