3,3-Disubstituted allyl alcohols from palladium-catalyzed coupling of hydroaluminated propargyl alcohols with aryl iodides

Article abstract of DOI:10.1021/jo0162235

3,3-Disubstituted prop-2-en-1-ols 4 were synthesized with a high degree of stereoselectivity from 3-substituted prop-2-yn-1-ols 1 via hydroalumination and subsequent Pd-catalyzed coupling with aryl iodides 3.

Full text of DOI:10.1021/jo0162235

J . Org. Chem. 2002, 67, 2125-2130
2125
3,3-Disu bstitu ted Allyl Alcoh ols fr om P a lla d iu m -Ca ta lyzed
Cou p lin g of Hyd r oa lu m in a ted P r op a r gyl Alcoh ols w ith Ar yl
Iod id es
Miroslav Havra´nek and Dalimil Dvorˇa´k*
Department of Organic Chemistry, Prague Institute of Chemical Technology, Technicka´ 5,
166 28 Prague 6, Czech Republic
dalimil.dvorak@vscht.cz
Received October 22, 2001
3,3-Disubstituted prop-2-en-1-ols 4 were synthesized with a high degree of stereoselectivity from
3-substituted prop-2-yn-1-ols 1 via hydroalumination and subsequent Pd-catalyzed coupling with
aryl iodides 3.
Sch em e 1a
Trisubstituted alkenes are common motifs in nature,
and their preparation remains a challenging problem in
synthetic organic chemistry.1-3 Substituted allyl alcohols
are useful intermediates in synthesis3-7 and can, for
example, be hydrogenated6 or isomerized to aldehydes7
enantioselectively. Preparation of substituted allyl alco-
hols is usually based on Reformatsky reaction of the
corresponding ketone8 or Horner-Wadsworth-Emmons
reaction but often gives a mixture of isomers.7,9,10
a
Reagents: (i) LiAlH4; (ii) (1) AcOEt, (2) Bu3SnOMe.
Sch em e 2a
Palladium-catalyzed coupling of 3-tributylstannyl allyl
alcohols with aryl or alkenyl halides can also be used for
this purpose.11 The preparation of 3-tributylstannyl allyl
alcohols is usually accomplished by regio- and stereo-
specific hydroalumination of 2-propyn-1-ols 1 and sub-
sequent transmetalation from aluminum to tin12 (Scheme
1). The stereo- and regioselectivity of this reaction are
believed to result from the formation of cyclic intermedi-
ate 2. Since a handful of reports on the transition metal
catalyzed coupling reactions using organoalanes have
been reported,13 it is somewhat surprising that hydro-
aluminated intermediates such as 2 have not yet been
a
Reagents: (i) (1) LiAlH4, (2) (MeO)2CO; (ii) PdCl2(PPh3)2,
methyl-4-iodobenzoate (3a ).
used for this type of reaction. Herein, we report our
results on the direct Pd-catalyzed coupling of cyclic
organoalanes 2 with aromatic halides in which 3,3-
disubstituted allyl alcohols are formed.
Hydroaluminated 3-trimethylsilylprop-2-en-1-ol 2e was
used to optimize the coupling reaction. Starting 3-tri-
methylsilylprop-2-en-1-ol 1e was hydroaluminated with
LiAlH4 in the presence of NaOMe, which suppresses
isomerization.12b Excess hydride was then quenched by
addition of dimethyl carbonate, and the resulting alu-
minate was subjected to the reaction with methyl 4-
iodobenzoate 3a in the presence of PdCl2(PPh3)2 (Scheme
2). However, only a low yield (Table 1, entry 1) of the
* To whom correspondence should be addressed. Fax: ++-420-2-
2435 4288.
(1) Yu, S.; Li, N.-S.; Kabalka G. W. J . Org. Chem. 1999, 64, 5822
and references therein.
(2) (a) Shen, W.; Wang, L. J . Org. Chem. 1999, 64, 8873. (b) Hinkle,
R. J .; Leri, A. C.; David, G. A.; Ervin, W. M. Org. Lett. 2000, 2, 1521.
(c) Barbero, A.; Blanco, Y.; Garc´ıa, C.; Pulido, F. J . Synthesis 2000,
1223. (d) Shadakshari, U.; Nayak, S. K. Tetrahedron 2001, 57, 4599.
(e) Fu¨rstner, A.; Thiel, O. R.; Ackermann, L. Org. Lett. 2001, 3, 449.
(f) Yamanoi, S.; Seki, K.; Matsumoto, T.; Suzuki, K. J . Organomet.
Chem. 2001, 624, 143. (g) Marko´, I. E.; Murphy, F.; Kumps, L.; Ates,
A.; Touillaux, R.; Craig, D.; Carballares, S.; Dolan, S. Tetrahedron
2001, 57, 2609.
(3) Tago, K.; Kogen, H. Org. Lett. 2000, 2, 1975 and references
therein.
(4) Cho, C.-G.; Lim, Y.-K.; Lee, K.-S.; J ung, I.-H.; Yoon, M.-Y. Synth.
Commun. 2000, 30, 1643.
(5) Singh, C. Tetrahedron Lett. 1990, 31, 6901.
(6) Broene, R. D.; Buchwald, S. L. J . Am. Chem. Soc. 1993, 115,
12569.
(7) Tanaka, K.; Qiao, S.; Tobisu, M.; Lo, M. M.-C.; Fu, G. Cu. J .
Am. Chem. Soc. 2000, 122, 9870.
desired coupled product 4i was obtained. Addition of
13b
ZnCl2
increased the yield considerably. The optimal
amount of ZnCl2 was found to be 60 mol % (Table 1, entry
4). Among the catalysts screened, PdCl2(PPh3)2 gave the
best results in this case. NiCl2(PPh3)2 was also an active
catalyst; however, the yield was lower than that achieved
with PdCl2(PPh3)2 (Table 1, entry 7). Methyl 4-bromo-
(8) Murphy, J . A.; Patterson, C. W. J . Chem. Soc., Perkin Trans. 1
1993, 405.
(9) Walton, R.; Fraser-Reid, B. J . Am. Chem. Soc. 1991, 113, 5791.
(10) Srikrishna, A.; Kumar, P. P.; Viswajanani, R. Tetrahedron Lett.
1996, 37, 1683.
(11) Havra´nek, M.; Dvorˇa´k, D. Collect. Czech. Chem. Commun. 2000,
65, 434.
(12) (a) Corey, E. J .; Eckrich, T. M. Tetrahedron Lett. 1984, 23, 2415.
(b) Havra´nek, M.; Dvorˇa´k, D. Synthesis 1998, 1264.
(13) (a) Negishi, E.; Luo, F.-T.; Frisbee, R.; Matsushita, H. Hetero-
cycles 1982, 18, 117. (b) Negishi, E.; Takahashi, T.; Baba, S. Org. Synth.
1988, 66, 60. (c) Hutzinger, H. W.; Oehlschlager, A. C. J . Org. Chem.
1995, 60, 4595. (d) Mangalagiu, I.; Benneche, T.; Undheim, K.
Tetrahedron Lett. 1996, 37, 1309. (e) Lipshutz, B. H.; Kim S.-K.;
Mollard, P.; Blomgren, P. A.; Stevens, K. L. Tetrahedron 1998, 54,
6999.
10.1021/jo0162235 CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/08/2002

2126 J . Org. Chem., Vol. 67, No. 7, 2002
Havra´nek and Dvorˇa´k
Ta ble 1. In flu en ce of th e Ca ta lytic System on th e Yield
of Cou p lin g Rea ction s
overcome by addition of methanol to the reaction mixture
before workup.
Substitution at the 1-position of the starting propargyl
alcohol decreases the yield of disubstituted allyl alcohol
considerably. Thus, reaction of 4-(2-thienyl)but-3-yn-2-
ol (1g) and 4-methoxyiodobenzene (3i) afforded the
desired product 4o in 27% yield (Table 2, entry 15), while
with 1,1-disubstituted propargyl alcohol 2-methyl-4-(2-
thienyl)but-3-yn-2-ol an inseparable mixture of products
was obtained. Propargyl alcohol itself gave, after hydro-
alumination and reaction with 4-iodoanisole (3i), only a
low yield (27%) of the desired 4-methoxycinnamyl alcohol
(4n ) as an approximately 1:1 mixture of E and Z isomers
accompanied with 3-(4-methoxyphenyl)prop-2-yn-1-ol
(Table 2, entry 14). The reaction of vinyl iodide (E)-1-
iodohept-1-yn (3j) and but-2-yn-1-ol (1a ) afforded the
desired coupled product 4p in 45% yield (Table 2, entry
16).
In conclusion, a new convenient and highly stereo-
selective one-pot synthesis of 3,3-disubstituted allyl al-
cohols starting from substituted propargyl alcohols and
aryl iodides was developed. The procedure eliminates
preparation, purification, and use of toxic stannanes
necessary for the commonly used Stille reaction16 and
tolerates amide, ester, ether, and nitro groups, giving
moderate to high yields of allyl alcohols with good regio-
and stereoselectivity.
amount of ZnCl2
(mol %)
yield
(%)
entry
catalyst
1
2
3
4
5
6
7
8b
0
5
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
Pd2dba3, AsPh3 (PdL2)
NiCl2(PPh3)2
11
44
51
90a
71
82a
56
23
20
60
100
60
60
60
Pd2dba3, AsPh3 (PdL2)
a
Starting iodide was not detected in the reaction mixture.
Methyl-4-bromobenzoate was used instead of methyl-4-iodo-
b
benzoate.
Sch em e 3a
Exp er im en ta l Section
a
Reagents: (i) (1) LiAlH4, (2) EtOAc or (MeO)2CO; (ii) Pd-
catalysis, ZnCl2, Arl (3).
All reactions were performed under a dry argon atmosphere.
THF was distilled from benzophenone ketyl under an Ar
atmosphere prior to use. Petroleum ether refers to the fraction
boiling at 40-60 °C. 4-Methylpent-2-yn-1-ol (1b),17 5-meth-
oxypent-2-yn-1-ol (1c),12b 3-phenylprop-2-yn-1-ol (1d ),18 N,N-
dimethyl-4-iodobenzamide (3g),19 4-iodoacetanilide (3h ),20 and
1-iodohept-1-yne (3j)22 were prepared according to the reported
procedures. Methyl esters of corresponding iodobenzoic acids
were prepared by esterification of commercially available acids
in refluxing methanol with H2SO4 as a catalyst. NMR spectra
were measured on either a Varian Gemini 300 (1H, 300.07
MHz), Bruker AMX3 400 (1H, 400.13 MHz; 13C, 100.6 MHz),
or Bruker DRX 500 Avance (1H, 500.13 MHz; 13C, 125.77 MHz)
spectrometer at 298 K. HPLC analysis (LiChrosfer 100 RP-
18, methanol/water 85:15) with 2-methyl naphthalene as an
internal standard was used for the optimization of the coupling
reactions.
Gen er a l P r oced u r e. Sodium methoxide (5 mg, 0.09 mmol)
was added to a 1 M solution of LiAlH4 in THF (1-1.5 mL,
1-1.5 mmol). The mixture was cooled to 0 °C, and a solution
of the appropriate alkynol 1 (1-1.5 mmol) in THF (1 mL) was
slowly added. The temperature and reaction time of hydro-
alumination step for individual compounds are listed sepa-
rately below. After hydroalumination was completed, the
reaction mixture was cooled to 0 °C; ethyl acetate (0.25 mL,
2.5 mmol) was added, and the mixture was stirred for 10 min
without cooling. Dimethyl carbonate (0.15 mL, 1.7 mmol) was
used instead of ethyl acetate when the starting aryl iodide
benzoate was less reactive compared to iodide 3a giving
only 23% of the coupled product 4i (Table 1, entry 8).
The scope of the reaction was examined using a variety
of propargyl alcohols and aryl iodides (Table 2, Scheme
3). The reaction tolerates an array of functionalities on
both substrates, although aryl iodides with electron-
withdrawing groups usually gave higher yields than
those substituted with donors. Vinyl iodides can also be
subjected to the coupling reaction with 2. As for the
catalyst, Pd(PPh3)2Cl2 is generally the most effective, but
Pd2dba3/AsPh3 or Pd(PPh3)4 gave better results with some
substrates (Table 2). The stereochemistry of the reaction
is determined by the hydroalumination step.14 A single
isomer is formed with high selectivity when 3-alkyl-
substituted propargyl alcohols are used, while trimethyl-
silyl- and arylpropargyl alcohols gave products with 90-
95% isomeric purity.
In some cases, unreacted aryl iodide remains in the
reaction mixture and addition of more catalyst does not
increase the yield. In these reactions, the larger excess
of aluminate (ca. 2 equiv) increased the yield (Table 2,
entries 2, 13, and 14). In most cases, it is convenient to
use ethyl acetate for quenching of the remaining hy-
dride.15 However, if the starting aryl iodide contains a
methyl ester group, it is necessary to use dimethyl
carbonate to avoid transesterification by ethoxide formed
in the reduction of ethyl acetate. Excess ethyl acetate (or
dimethyl carbonate) in the reaction mixture can also
acylate the substituted allyl alcohol. This problem was
(16) For other methods minimizing the amount of toxic tin com-
pounds used in cross-coupling reactions, see: (a) Maleczka, R. E., J r.;
Gallagher, W. P.; Terstiege I. J . Am. Chem. Soc. 2000, 122, 384. (b)
Maleczka, R. E., J r.; Lavis, J . M.; Clark, D. H.; Gallagher, W. P. Org.
Lett. 2000, 2, 3655.
(17) Kim, S.; Kim, K. H. Tetrahedron Lett. 1995, 36, 3725.
(18) Denis, J .-N.; Greene, A. E.; Serra, A. A.; Luche, M.-J . J . Org.
Chem. 1986, 51, 46
(19) J ackman, L. M.; Kavanagh, T. E.; Haddon, R. C. Org. Magn.
Reson. 1969, 1, 109.
(20) Bjo¨rnestedt, R.; Zhong, G.; Lerner, R. A.; Barbas, C. F., III. J .
Am. Chem. Soc. 1996, 118, 11720.
(14) This was confirmed by a coupled 13C NMR spectrum of the
product 4a , in which the 3J (CH3, H) of the methyl group and the
hydrogen of the double bond is 6.9 Hz. This coupling constant value
corresponds to a cis relationship.
(15) Hatakeyama, S.; Irie, H.; Shintani, T.; Noguchi, Y.; Yamada,
H.; Nishizawa, M. Tetrahedron 1994, 50, 13369.
(21) J effery, T. Synth. Commun. 1988, 18, 77.
(22) Wang, Z.-X.; Shi, Y. J . Org. Chem. 1998, 63, 3099.

Pd-Catalyzed Coupling of Hydroaluminated Propynols
J . Org. Chem., Vol. 67, No. 7, 2002 2127
Ta ble 2. Cou p lin g Rea ction of Hyd r oa lu m in a ted P r op a r gyl Alcoh ols 1 w ith Iod od er iva tives (Sch em e 3)

2128 J . Org. Chem., Vol. 67, No. 7, 2002
Havra´nek and Dvorˇa´k
Ta ble 2 (Con tin u ed )
a
b
Isolated yield. Determined by 1H NMR spectroscopy.
contained a methyl ester group. (Alcoholate transesterifies the
product in the reaction mixture.) Aryl iodide (1 mmol), pal-
ladium catalyst (Table 1, 5 mol %), and zinc(II) chloride (82
mg, 60 mol %) were then added to the reaction mixture under
an argon atmosphere. When PdCl2(PPh3)2 is used as a catalyst,
it should be added to the reaction mixture before quenching
of hydrides with ethyl acetate. Reaction time and temperature
for each coupling reaction are listed individually below.
Methanol (1 mL) was then added, and after 2 h at room
temperature, the reaction mixture was poured into brine/water
(1:1), acidified with 5% hydrochloric acid to become slightly
acidic (pH ) 5-6), and extracted with ether (three times). The
combined ethereal extracts were dried over MgSO4; the solvent
was evaporated under vacuum, and the crude product was
purified by chromatography on silica gel. In some cases, the
product contained a small amount of colored impurities, which
were not separable by chromatography or detectable by NMR
or elemental analysis. It was possible to remove them by
boiling a methanolic solution of the product with charcoal and
filtering.
(Z)-3-(4-Meth oxyca r bon ylp h en yl)bu t-2-en -1-ol (4a ). So-
dium methoxide (40 mg, 0.75 mmol), but-2-yn-1-ol (1a ) (0.75
mL, 10 mmol), LiAlH4 (10 mmol), dimethyl carbonate (1 mL,
11 mmol), methyl 4-iodobenzoate (3a ) (1.834 g, 7 mmol),

Pd-Catalyzed Coupling of Hydroaluminated Propynols
J . Org. Chem., Vol. 67, No. 7, 2002 2129
Pd2dba3‚CHCl3 (0.169 g, 2.5 mol %), AsPh3 (0.214 g, 10 mol
%), and ZnCl2 (0.574 g, 60 mol %) were used in the procedure.
Hydroalumination was performed by stirring the mixture at
room temperature for 4 h, and the coupling reaction was run
at room temperature for 3 h followed by heating at 50 °C for
1.5 h. Chromatography on silica gel (petroleum ether/ether/
acetone 8:1:1) gave 1.121 g (78%) of isomerically pure product.
Analytical data correspond to those previously reported.11
Coupled 13C NMR (100.6 MHz, CDCl3) δ 167.6 (s, CdO), 146.3
s, 139.9 s, 129.4s (2ArC + ArC(CH3)d), 60.8 (t, J ) 142.7 Hz,
CH2OH), 52.8 (q, J ) 147 Hz, OCH3), 25.7 (dq, 1J (CH) ) 127.3,
3J (CH3,H) ) 6.9 Hz).
(Z)-3-(3-Meth oxyca r bon ylp h en yl)bu t-2-en -1-ol (4b). So-
dium methoxide (5 mg, 0.09 mmol), but-2-yn-1-ol (1a ) (0.192
g, 1.5 mmol), LiAlH4 (1.6 mmol), PdCl2(PPh3)2 (25 mg, 5 mol
%), dimethyl carbonate (0.15 mL, 1.7 mmol), methyl 3-iodo-
benzoate (3b) (0.183 g, 0.7 mmol), and ZnCl2 (57 mg, 60 mol
%) were used in the procedure. Hydroalumination was per-
formed by stirring the mixture at room temperature for 4 h
and the coupling at room temperature overnight. Chromatog-
raphy on silica gel (petroleum ether/acetone 4:1) gave 0.101 g
(70%) of oily, isomerically pure product: 1H NMR (300 MHz,
CDCl3) δ 7.82-8.00 (m, 2H, ArH), 7.34-7.47 (m, 2H, ArH),
5.77 (dt, J t ) 6.9 Hz, J d ) 1.1 Hz, 1H, dCHCH2OH), 4.05 (t,
J ) 6.0 Hz, 2H, CH2OH), 3.92 (s, 3H, OCH3), 2.10 (d, J ) 1.1
Hz, 3H, dCCH3), 1.31 (t, J ) 5.5 Hz, 1H, OH); IR (CHCl3) ν
3612, 3473, 3018, 1954, 1720, 1440, 1286, 1121, 1087, 988
cm-1; HRMS calcd for C12H13O2 [M - OH]+ 189.0915, found
189.0995.
(Z)-3-(5-Meth oxyca r bon yl-2-m eth ylp h en yl)bu t-2-en -1-
ol (4c). Sodium methoxide (5 mg, 0.09 mmol), but-2-yn-1-ol
(1a ) (0.192 g, 1.5 mmol), LiAlH4 (1.6 mmol), dimethyl carbon-
ate (0.15 mL, 1.7 mmol), methyl 3-iodo-4-methylbenzoate (3c)
(0.276 g, 1 mmol), Pd(PPh3)4 (56 mg, 5 mol %), and ZnCl2 (82
mg, 60 mol %) were used in the procedure. Hydroalumination
was performed by stirring the reaction mixture at room
temperature for 4 h, and the coupling reaction was run for 2
h at room temperature followed by heating at 60 °C for 2 h.
Chromatography on silica gel (petroleum ether/acetone 4:1)
gave 0.102 g (46%) of oily, isomerically pure product: 1H NMR
(300 MHz, CDCl3) δ 7.84 (dd, J ) 7.7, 1.7 Hz, 1H, ArH), 7.69
(d, J ) 2.1 Hz, 1H, ArH), 7.27 (d, J ) 8.2 Hz, 1H, ArH), 5.78
(dt, J ) 6.9, 1.6 Hz, 1H, dCHCH2OH), 3.90 (s, 3H, CO2CH3),
3.80 (t, J ) 5.5 Hz, 2H, CH2OH), 2.27 (s, 3H, ArCH3), 1.99 (d,
J ) 1.1 Hz, 3H, dCCH3), 1.13 (t, J ) 5.5 Hz, 1H, -OH); 13C
NMR-APT (125.7 MHz, CDCl3) CH, CH3 δ 19.4, 24.9, 52.0,
127.1, 128.2, 129.0, 130.1; C, CH2 δ 60.25, 127.8, 138.8, 140.5,
141.0, 167.1; IR (CHCl3) ν 3620, 3019, 2973, 2953, 1717, 1609,
1438, 1294, 1262, 1119, 996 cm-1. Anal. Calcd for C13H16O3:
C, 70.89; H, 7.32. Found: C, 70.83; H, 7.64.
(Z)-3-(4-Nitr op h en yl)-4-m eth ylp en t-2-en -1-ol (4d ). So-
dium methoxide (5 mg, 0.09 mmol), 4-methylpent-2-yn-1-ol
(1b) (0.147 g, 1.5 mmol), LiAlH4 (1.6 mmol), dimethyl carbon-
ate (0.15 mL, 1.7 mmol), 4-iodonitrobenzene (3d ) (0.249 g, 1
mmol), Pd2dba3‚CHCl3 (24 mg, 2.5 mol %), AsPh3 (30 mg, 10
mol %), and ZnCl2 (82 mg, 60 mol %) were used in the
procedure. Hydroalumination was performed by stirring the
mixture at room temperature overnight and the coupling by
heating at 65 °C for 5 min. Chromatography on silica gel
(petroleum ether/ether/acetone 8:1:1) gave 0.160 g (72%) of the
isomerically pure product: 1H NMR (300 MHz, CDCl3) δ 8.21
(d, J ) 8.8 Hz, 2H, ArH), 7.28 (d, J ) 8.8 Hz, 2H, ArH), 5.75
(t, J ) 6.9 Hz, 1H, dCHCH2OH), 3.94 (d, J ) 7.1 Hz, 2H,
CH2OH), 2.61 (septet, J ) 6.7 Hz, 1H, CH(CH3)2), 1.04 (d, J )
6.6 Hz, 6H, CH(CH3)2); 13C NMR-APT (125.7 MHz, CDCl3) CH,
CH3 δ 21.4, 35.4, 123.3, 124.7, 129.4; C, CH2 δ 60.0, 146.9,
147.4, 148.6; IR (CHCl3) ν 3613, 3446, 3014, 2967, 2875, 1598,
1521, 1350, 1109, 1026, 1014, 979, 859 cm-1. Anal. Calcd for
mol %), AsPh3 (30 mg, 10 mol %), and ZnCl2 (82 mg, 60 mol
%) were used in the procedure. Hydroalumination was per-
formed by stirring the mixture at room temperature overnight,
and the coupling reaction was run for 2 h at room temperature
followed by heating at 60 °C for 3 h. Chromatography on silica
gel (petroleum ether/ether/acetone 8:1:1) gave 0.100 g (40%)
of isomerically pure product: 1H NMR (300 MHz, CDCl3) δ
7.98-8.04 (m, 2H, ArH), 7.20-7.26 (m, 2H, ArH), 5.81 (t,
J
) 6.9 Hz, 1H, dCHCH2OH), 4.03 (d, J ) 6.6 Hz, 2H,
CH2OH), 3.92 (s, 3H, CO2CH3), 3.34 (t, J ) 6.6 Hz, 2H,
H3COCH2CH2-), 3.26 (s, 3H, H3COCH2CH2-), 2.67 (t, J ) 6.6
Hz, 2H, H3COCH2CH2-); IR (CHCl3) ν 3020, 2954, 1722, 1438,
1407, 1284, 1194, 1116 cm-1; HRMS calcd for C14H17O3 [M -
OH]+ 233.1330, found 233.1240.
3,3-Dip h en ylp r op -2-en -1-ol (4f). Sodium methoxide (5 mg,
0.09 mmol), 3-phenylprop-2-yn-1-ol (1d ) (0.133 g, 1.0 mmol),
LiAlH4 (1.0 mmol), PdCl2(PPh3)4 (36 mg, 5 mol %), ethyl
acetate (0.35 mL, 3.5 mmol), iodobenzene (3e) (0.307 g, 1.5
mmol), and ZnCl2 (82 mg, 60 mol %) were used in the
procedure. Hydroalumination was performed by stirring the
mixture at 0 °C for 1 h and the coupling by heating of the
mixture at 60 °C overnight. Chromatography on silica gel
(petroleum ether/ether/acetone 8:1:1) gave 0.079 g (38%) of the
pure product. The compound was described previously:22 1H
NMR (300 MHz, CDCl3) δ 7.15-7.41 (m, 10H, ArH), 6.25 (t, J
) 6.9 Hz, 1H, dCHCH2OH), 4.20-4.36 (m, 2H, CH2OH), 1.38
(s, 1H, OH).
(Z)-3-(4-Meth oxyca r bon ylp h en yl)-3-p h en ylp r op -2-en -
1-ol (4 g). Sodium methoxide (10 mg, 0.18 mmol), 3-phenyl-
prop-2-yn-1-ol (1d ) (0.316 g, 2.4 mmol), LiAlH4 (2.4 mmol),
PdCl2(PPh3)4 (72 mg, 5 mol %), dimethyl carbonate (0.2 mL,
2.3 mmol), methyl 4-iodobenzoate (3a ) (0.524 g, 2 mmol), and
ZnCl2 (0.164 g, 60 mol %) were used in the procedure.
Hydroalumination was performed by stirring the mixture at
0 °C for 1 h and the coupling reaction by heating of the mixture
at 60 °C overnight. Chromatography on silica gel (petroleum
ether/acetone 4:1) gave 0.270 g (50%) of the product containing
a trace amount of (Z)-isomer. Analytical data correspond to
those previously reported.11
(Z)-3-(4-Nitr op h en yl)-3-p h en ylp r op -2-en -1-ol (4h ). So-
dium methoxide (5 mg, 0.09 mmol), 3-phenylprop-2-yn-1-ol
(1d ) (0.198 g, 1.5 mmol), LiAlH4 (1.6 mmol), PdCl2(PPh3)4 (36
mg, 5 mol %), dimethyl carbonate (0.15 mL, 1.7 mmol),
4-iodonitrobenzene (3d ) (0.249 g, 1 mmol), and ZnCl2 (82 mg,
60 mol %) were used in the procedure. Hydroalumination was
performed by stirring the mixture at 0 °C for 1 h and the
coupling by stirring the mixture for 3 h at room temperature
followed by heating at 50 °C for 3 h. Chromatography on silica
gel (petroleum ether/ether/acetone 8:1:1) gave 0.183 g (72%)
of the product containing 10% of the (Z)-isomer. Crystals
formed from the oily product are the compound with a higher
isomerical purity: 1H NMR (300 MHz, CDCl3) δ 8.24-8.29 (m,
2H, ArH), 7.13-7.44 (m, 7H, ArH), 6.35 (t, J ) 6.9 Hz, 1H,
dCHCH2OH), 4.20 (d, J ) 6.6 Hz, 2H, CH2OH), 1.48 (s, 1H,
OH); peaks of the (Z)-isomer 8.15, 6.39, 4.27; 13C NMR-APT
(125.7 MHz, CDCl3) CH, CH3 δ 123.4, 127.4, 128.1, 128.4,
129.3, 130.6; C, CH2 δ 60.1, 140.5, 142.1, 146.0, 147.1; IR
(CHCl3) ν 3612, 3443, 3014, 1599, 1520, 1347, 1015, 850. Anal.
Calcd for C15H13NO3: C, 70.58; H, 5.13; N, 5.49. Found: C,
70.45; H, 5.42; N, 5.26.
(E)-3-(4-Meth oxycar bon ylph en yl)-3-tr im eth ylsilylpr op-
2-en -1-ol (4i). Sodium methoxide (5 mg, 0.09 mmol), 3-(tri-
methylsilyl)prop-2-yn-1-ol (1e) (0.176 mL, 1.2 mmol), LiAlH4
(1.2 mmol), PdCl2(PPh3)2 (36 mg, 5 mol %), dimethyl carbonate
(0.15 mL, 1.7 mmol), ZnCl2 (82 mg, 60 mol %), and methyl
4-iodobenzoate (3a ) (0.262 g, 1 mmol) were used in the
procedure. Hydroalumination was performed by stirring the
mixture at room temperature for 2 h, and the coupling reaction
was run for 70 min at 65 °C. Chromatography on silica gel
(petroleum ether/ether/acetone 8:1:1) gave 0.193 g (73%) of
oily material. The product contained 10% of the (Z)-isomer.
Analytical data correspond to those previously reported:11
1H NMR (300 MHz, CDCl3) δ 7.97 (d, J ) 8.2 Hz, 2H, ArH),
7.00 (d, J ) 8.2 Hz, 2H, ArH), 6.15 (t, J ) 6.0 Hz, 1H, dCHCH2-
OH), 3.99 (d, J ) 6.0 Hz, 2H, CH2OH), 3.91 (s, 3H, CO2CH3),
C
12H15O3N: C, 65.14; H, 6.83; N, 6.33. Found: C, 64.95; H,
7.02; N, 6.08.
(Z)-3-(4-Met h oxyca r b on ylp h en yl)-5-m et h oxyp en t -2-
en -1ol (4e). Sodium methoxide (5 mg, 0.09 mmol), 5-meth-
oxypent-3-yn-1-ol (1c) (0.171 g, 1.5 mmol), LiAlH4 (1.6 mmol),
dimethyl carbonate (0.15 mL, 1.7 mmol), methyl 4-iodo-
benzoate (3a ) (0.131 g, 1 mmol), Pd2dba3‚CHCl3 (24 mg, 2.5

2130 J . Org. Chem., Vol. 67, No. 7, 2002
Havra´nek and Dvorˇa´k
0.07 (s, 9H, Si(CH3)3); peaks of (Z)-isomer 7.09 d, 6.25 t, 4.36
d, 0.15 s.
material, containing 10% of the (Z)-isomer: mp 114 °C; 1H
NMR (300 MHz, CDCl3) δ 7.43 (d, J ) 8.2 Hz, 2H, ArH), 7.14
(s, 1H, NH), 6.89 (d, J ) 8.8 Hz, 2H, ArH), 6.13 (t, J ) 6.0 Hz,
1H, dCHCH2OH), 4.03 (t, J ) 5.8 Hz, 1H, CH2OH), 2.18 (s,
3H, CH3CONH), 1.29 (t, J ) 5.8, 1H, OH), 0.07 (s, 9H,
Si(CH3)3); peaks of the (Z)-isomer 6.99 d, 6.22 t, 4.35 t, 0.15 s.
13C NMR-APT (125.7 MHz, CDCl3) CH, CH3 δ -1.8, 24.5,
119.8, 127.8, 139.6; C, CH2 δ 60.7, 135.9, 137.5, 146.6, 168.6;
IR (CHCl3) ν 3437, 3019, 1957, 1719, 1685, 1585, 1512, 1399,
(E)-3-(2-Th ien yl)-3-tr im eth ylsilylp r op -2-en -1-ol (4j). So-
dium methoxide (5 mg, 0.09 mmol), 3-(trimethylsilyl)prop-2-
yn-1-ol (1e) (0.176 mL, 1.2 mmol), LiAlH4 (1.4 mmol), PdCl2-
(PPh3)2 (36 mg, 5 mol %), ethyl acetate (0.4 mL, 4 mmol), ZnCl2
(82 mg, 60 mol %), and 2-iodothiophene (3f) (0.210 g, 1 mmol)
were used in the procedure. Hydroalumination was performed
by stirring the mixture at room temperature for 2 h and the
coupling reaction by heating at 65 °C overnight. Chromatog-
raphy on silica gel (petroleum ether/acetone 4:1) gave 0.115 g
(53%) of oily product. The compound contained 5% of the (Z)-
isomer: 1H NMR (300 MHz, CDCl3) δ 7.22 (dd, J ) 5.0, 1.1
Hz, 1H, ArH), 6.99 (dd, J ) 5.0, 3.3 Hz, 1H, ArH), 6.65 (dd, J
) 1.1, 3.3 Hz, 1H, ArH), 6.22 (t, J ) 5.8 Hz, 1H, dCHCH2OH),
4.06 (t, J ) 5.8 Hz, 2H, CH2OH), 1.42 (t, J ) 5.8 Hz, 2H, OH),
0.13 (s, 9H, Si(CH3)3); peaks of the (Z)-isomer 6.52 t, 4.36 t,
0.23 s; IR (CHCl3) ν 3614, 3458, 3019, 2959, 2898, 1721, 1666,
1435, 1408, 1250, 1037, 1018, 888, 841 cm-1. Anal. Calcd for
1310, 1286, 1250, 1014, 909, 842 cm-1. Anal. Calcd for C14H21
-
NO2Si: C, 63.84; H, 8.04; N, 5.32. Found: C, 63.80; H, 8.07;
N, 4.89.
3-(4-Meth oxyp h en yl)p r op -2-en -1-ol (4n ). Sodium meth-
oxide (10 mg, 0.18 mmol), propargyl alcohol (1f) (0.112 g, 2
mmol), LiAlH4 (2 mmol), dimethyl carbonate (0.15 mL, 1.7
mmol), 4-iodoanisole (3i) (0.234 g, 1 mmol), Pd2dba3‚CHCl3 (24
mg, 2.5 mol %), AsPh3 (30 mg, 10 mol %), and ZnCl2 (82 mg,
60 mol %) were used in the procedure. Hydroalumination was
performed by mixing the components at -78 °C followed by
stirring at room temperature overnight. The coupling reaction
was run at 60 °C overnight. Chromatography on silica gel
(dichloromethane) gave 0.044 g (27%) of the product as a
mixture of both geometric isomers (∼1:1) and 0.045 g (27%) of
the 3-(4-methoxyphenyl)prop-2-yn-1-ol. Compounds were de-
scribed previously.23 (E)/(Z) 3-(4-Methoxyphenyl)prop-2-en-1-
ol: 1H NMR (300 MHz, CDCl3) δ 7.33 (d, J ) 8.8 Hz, 2H, ArH),
7.17 (d, J ) 8.8 Hz, 2H, ArH), 6.88 (d, J ) 8.8 Hz, 2H, ArH),
6.86 (d, J ) 8.8 Hz, 2H, ArH), 6.56 (d, J ) 16.5 Hz, 1H,
ArCHd), 6.51 (d, J ) 12.1 Hz, 1H, ArCHd), 6.24 (td, J t ) 6.1
C
10H16OSSi: C, 56.55; H, 7.59; S, 15.10. Found: C, 56.24; H,
7.40; S, 15.08.
(E )-3-(4-N ,N -Dim e t h yla m in oca r b on ylp h e n yl)-3-t r i-
m eth ylsilylp r op -2-en -1-ol (4k ). Sodium methoxide (50 mg,
0.9 mmol), 3-(trimethylsilyl)prop-2-yn-1-ol (1e) (1.46 mL, 10
mmol), LiAlH4 (10 mmol), ethyl acetate (2.5 mL, 25 mmol),
Pd(PPh3)4 (575 mg, 5 mol %), ZnCl2 (0.84 g, 60 mol %), and
N,N-dimethyl-4-iodobenzamide (3g) (2.75 g, 10 mmol) were
used in the procedure. Hydroalumination was performed by
stirring the mixture at room temperature for 2 h, and the
coupling reaction was run at 65 °C overnight. Chromatography
on silica gel (heptane/ethyl acetate/ethanol 40:55:5) gave 2.062
g (74%) of oily product. The compound contained 10% of the
(Z)-isomer. Crystallization from petroleum ether/toluene af-
forded isomerically pure product: mp 78 °C; 1H NMR (300
MHz, CDCl3) δ 7.38 (d, J ) 8.2 Hz, 2H, ArH), 6.95 (d, J ) 8.2
Hz, 2H, ArH), 6.15 (t, J ) 6 Hz, 1H, dCHCH2OH), 4.01 (t, J
) 5.22 Hz, 2H, CH2OH), 3.11 (s, 3H, N(CH3)2), 3.01 (s, 3H,
N(CH3)2), 1.27-1.35 (m, 1H, OH), 0.08 (s, 9H, Si(CH3)3); peaks
of the (Z)-isomer 7.04 d, 6.22 t, 4.35 d, 0.14 s; 13C NMR-APT
(125.7 MHz, CDCl3) CH, CH3 δ -1.8, 35.4, 39.7, 127.1, 127.2,
140.2; C, CH2 δ 60.5, 133.4, 143.3, 145.9, 171.7; IR (CHCl3) ν
3615, 3009, 2957, 1823, 1488, 1401, 1250, 1083, 1018, 910, 841
cm-1. Anal. Calcd for C15H23NO2Si: C, 64.94; H, 8.36; N, 5.05.
Found: C, 64.89; H, 8.36; N, 5.01.
(E)-3-(4-Nitr oph en yl)-3-tr im eth ylsilylpr op-2-en -1-ol (4l).
Sodium methoxide (5 mg, 0.09 mmol), 3-(trimethylsilyl)prop-
2-yn-1-ol (1e) (0.176 mL, 1.2 mmol), LiAlH4 (1.2 mmol), PdCl2-
(PPh3)2 (36 mg, 5 mol %), ethyl acetate (0.25 mL, 2.5 mmol),
ZnCl2 (82 mg, 60 mol %), 4-iodonitobenzene (3d ) (0.249 g, 1
mmol) were used in the procedure. Hydroalumination was
performed by stirring the mixture at room temperature for 2
h and the coupling reaction by heating at 65 °C overnight.
Chromatography on silica gel (petroleum ether/ether/acetone
8:1:1) gave 0.140 g (56%) of oily product. The compound
contained 10% of the (Z)-isomer: 1H NMR (300 MHz, CDCl3)
δ 8.18 (d, J ) 8.2 Hz, 2H, ArH), 7.09 (d, J ) 8.2 Hz, 2H, ArH),
6.20 (t, J ) 6.0 Hz, 1H, dCHCH2OH), 3.99 (d, J ) 6.0 Hz, 2H,
CH2OH), 0.10 (s, 9H, Si(CH3)3); peaks of the (Z)-isomer 7.17
d, 6.27 t, 4.49 d, 0.17 s; 13C NMR-APT (125.7 MHz, CDCl3)
CH, CH3 δ -1.9, 123.6, 128.1, 140.3; C, CH2 δ 60.6, 145.7,
146.2, 149.5; IR (CHCl3) ν 3614, 3014, 2959, 1594, 1518, 1345,
1251, 1110, 1014, 913, 858, 841, 828 cm-1. Anal. Calcd for
Hz, J d ) 15.9 Hz, 1H, ArCHdCH), 5.78 (td, J t ) 6.6 Hz, J d
)
11.5 Hz, 1H, ArCHdCH), 4.44 (bs, 2H, CH2OH), 4.30 (bs, 2H,
CH2OH), 3.82 (s, 3H, OCH3), 3.81 (s, 3H, OCH3). 3-(4-
Methoxyphenyl)prop-2-yn-1-ol: 1H NMR (300 MHz, CDCl3) δ
7.38 (d, J ) 8.8 Hz, 2H, ArH), 6.83 (d, J ) 8.8 Hz, 2H, ArH),
4.79 (s, 2H, CH2OH), 3.81 (s, 3H), 1.67 (s, 1H, OH).
(E)-4-(4-Met h oxyp h en yl)-4-(t h iop h en -2-yl)b u t -3-en -2-
ol (4o). Sodium methoxide (5 mg, 0.09 mmol), 4-(thiophen-2-
yl)but-4-yn-2-ol (1g) (0.152 g, 1.0 mmol), LiAlH4 (1.1 mmol),
PdCl2(PPh3)4 (36 mg, 5 mol %), ethyl acetate (0.35 mL, 3.5
mmol), 4-iodoanisole (3i) (0.234 g, 1 mmol), and ZnCl2 (82 mg,
60 mol %) were used in the procedure. Hydroalumination was
performed by stirring the mixture at 0 °C for 4h and the
coupling reaction by heating at 45 °C for 2 days. Chromatog-
raphy on silica gel (petroleum ether/ether/acetone 8:1:1) gave
0.070 g (27%) of the pure product: 1H NMR (300 MHz, CDCl3)
δ 7,15-7.23 (m, 3H, ArH), 6.88-6.97 (m, 3H, ArH), 6.68 (dd,
J ) 3.3, 1.1 Hz, 1H, ArH), 6.09 (d, J ) 9.3 Hz, 1H, dCHCH2-
OH), 4.32 (dq, J d ) 9.3 Hz, J q) 6.2 Hz, 1H, CH(OH)CH3), 3.85
(s, 3H, OCH3), 1.46 (s, 1H, OH), 1.31 (d, J ) 6.1 Hz, 3H,
CH(OH)CH3); IR (CHCl3) ν 3805, 3011, 2974, 2992, 2838, 1608,
1510, 1462, 1376, 1289, 1247, 1176, 1035 cm-1. Anal. Calcd
for C15H16O2S: C, 69.20; H, 6.19; S, 12.31. Found: C, 69.11;
H, 6.24; S, 12.14.
(2Z,4E)-3-Meth yld eca -2,4-d ien -1-ol (4p ). Sodium meth-
oxide (5 mg, 0.09 mmol), but-2-yn-1-ol (1a ) (0.192 g, 1.5 mmol),
LiAlH4 (1.6 mmol), ethyl acetate (0.35 mL, 3.5 mmol), 1-iodo-
hept-1-ene (3j) (0.224 g, 1 mmol), Pd2dba3‚CHCl3 (24 mg, 2.5
mol %), triphenyl arsine (30 mg, 10 mol %), and ZnCl2 (82 mg,
60 mol %) were used in the procedure. Hydroalumination was
performed by stirring the mixture at room temperature for 4
h and the coupling reaction by heating at 50 °C overnight and
then at 60 °C for 4 h. Chromatography on silica gel (petroleum
ether/ether/acetone 8:1:1) gave 0.075 g (45%) of product: 1H
NMR (500 MHz, CDCl3) δ 6.44 (d, J ) 15.5 Hz, 1H), 5.81 (dt,
J d ) 15.5 Hz, J t ) 7.2 Hz, 1H), 5.50 (t, J ) 7.1 Hz, 1H), 4.30
(d, J ) 7.2 Hz, 2H), 2.16 (q, J ) 7.2 Hz, 2H), 1.88 (s, 3H), 1.44
(quintet, J ) 7.2 Hz, 2H), 1.27-1.40 (m, 4H), 1.23 (bs, 1H),
0.92 (t, J ) 6.9 Hz, 3H); IR (CHCl3) ν 3609, 3016, 2959, 2930,
2859, 1083, 1456, 1379, 990, 986. Anal. Calcd for C11H20O: C,
78.51; H, 11.98. Found: C, 78.26; H, 11.57.
C
12H17NO3Si: C, 57.36; H, 6.82; N, 5.57. Found: C, 57.37; H,
6.83; N, 5.32.
(E)-3-(4-Aceta m id op h en yl)-3-tr im eth ylsilylp r op -2-en -
1-ol (4m ). Sodium methoxide (5 mg, 0.09 mmol), 3-(trimeth-
ylsilyl)prop-2-yn-1-ol (1e) (0.192 mL, 1.5 mmol), LiAlH4 (1.6
mmol), dimethyl carbonate (0.15 mL, 1.7 mmol), 4-iodoacet-
anilide (3h ) (0.183 g, 0.7 mmol), Pd2dba3‚CHCl3 (17 mg, 2.5
mol %), triphenyl arsine (21 mg, 10 mol %), and ZnCl2 (57 mg,
60 mol %) were used in the procedure. Hydroalumination was
performed by stirring the mixture at room temperature for 2
h and the coupling reaction by heating at 65 °C overnight.
Chromatography on silica gel (petroleum ether/ether/acetone/
methanol 50:30:17:3) gave 0.085 g (46%) of the crystalline
J O0162235
(23) Salih, R. G.; Shandala, M. Y. Collect. Czech. Chem. Commun.
1976, 41, 262.