Highly Enantioselective Addition of Mixed Diorganozincs to Aldehydes

Full text of DOI:10.1021/jo971488y

J . Org. Chem. 1997, 62, 7895-7898
7895
catalysis induced by the addition of Ti(Oi-Pr)4 becomes
more important. Thus, the addition of Pent(TMSM)Zn
to benzaldehyde gives a moderate enantioselectivity (48%
ee) in the presence of a large amount of Ti(Oi-Pr)4 (2.0
equiv). An improvement is obtained by reducing the
quantity of Ti(Oi-Pr)4 to 1.6 equiv (88% ee) and further
to 1.2 equiv (95% ee). In the general case, optimum
enantioselectivities are obtained with 0.6 equiv of Ti(Oi-
Pr)4 and 8 mol % of the chiral catalyst 1 (Scheme 1). The
additions to aldehydes 5 are complete in ether at -20
°C after a reaction time of 14-26 h, and the alcohols 6
are obtained in 74-98% yield and 86-98% ee (Table 1).
Aromatic aldehydes such as benzaldehyde (entries
1-6) readily undergo the asymmetric addition leading
to the benzylic alcohols 6a -f in 74-93% yield. Unsatur-
ated aldehydes such as cinnamaldehyde (entries 7 and
8) afford the corresponding allylic alcohols 6e,f with 86-
89% enantiomeric excess. Similarly, the addition to the
functionalized unsaturated aldehyde (E)-4-(triisopropyl-
siloxy)-2-butenal10 furnishes the desired selectively pro-
tected 1,4-diol 6i (entry 9) in 95% ee. Compared to the
previous procedure involving the use of an excess of the
symmetrical diorganozinc reagent 3 similar yields and
enantioselectivities are obtained (compare the yields and
% ee in parentheses in Table 1). Aliphatic aldehydes
require longer reaction times and lead to the secondary
alcohols 6j-l in good yields but somewhat lower enan-
tiomeric excess (74-95% ee) compared to the reactions
with functionalized diorganozincs (entries 10-12).
Interestingly, highly functionalized zinc reagents can
be added to aldehydes by this method. Thus the hy-
droboration, boron-zinc exchange and addition of
(TMSM)2Zn of the dienic ethyl ester 7 furnishes the
mixed zinc reagent 2. Its reaction with benzaldehyde
under typical reaction conditions (Ti(O-i-Pr)4 (0.6 equiv),
ether, -20 °C, 26 h) gives the chiral hydroxy ester 6m
in 81% yield and 93% ee (Scheme 2). We have also
investigated the enantioselective transfer of the methyl
group11 and have prepared the mixed reagent Me-
(TMSM)Zn. Due to the small size of the methyl group,
low enantioselectivity is usually observed with this
diorganozinc reagent. Under regular reaction conditions
(S)-phenylethanol 6n is obtained with only 23% ee by the
direct addition of Me2Zn. Replacing Ti(Oi-Pr)4 by the
more bulky titanium alkoxide12 Ti(Ot-Bu)4 now affords
6n , with 87% ee. By using the mixed reagent Me-
(TMSM)Zn with Ti(Oi-Pr)4 comparable enantioselectivi-
ties are obtained (95% yield, 84% ee) showing that the
CH2SiMe3 group is involved in the stereo-determining
step of the addition.
High ly En a n tioselective Ad d ition of Mixed
Dior ga n ozin cs to Ald eh yd es†
Christian Lutz and Paul Knochel*
Fachbereich Chemie der Philipps-Universita¨t Marburg,
Hans-Meerwein-Strasse, D-35032 Marburg, Germany
Received August 11, 1997
In tr od u ction
The enantioselective addition1 of functionalized dior-
ganozincs2 to aldehydes catalyzed by (1R,2R)-bis(trifluo-
romethanesulfonamido)cyclohexane3 1 and titanium(IV)
alkoxides constitutes an excellent method for the prepa-
ration of polyfunctional secondary alcohols.4 A broad
range of aldehydes and functionalized diorganozincs (FG-
R)2Zn can be used in this reaction, but an excess of
diorganozinc (2-3 equiv, corresponding to 4-6 equiv of
the FG-R group) is required in order to obtain high
chemical yields and high enantioselectivities.4 Recently,
we have found that mixed diorganozincs of the type FG-
R-ZnCH2SiMe3 (2) can be readily prepared and charac-
terized by NMR spectroscopic methods.5 The Me3SiCH2
group behaves as a nontransferable ligand6,7 and pre-
liminary results have shown that these new mixed zinc
reagents are useful for Michael-additions to enones in
NMP.5,8
Resu lts a n d Discu ssion
Herein, we wish to report that various mixed diorga-
nozincs of type 2 can be added to aldehydes with high
enantioselectivity without using a large excess of the
transferable FG-R group. Thus, the mixing of a diorga-
nozinc (FG-R)2Zn (3) (0.8-1.2 equiv), prepared either by
a boron-zinc exchange or an iodine-zinc exchange,2,4 and
bis[(trimethylsilyl)methyl]zinc (4)9 (0.9-1.3 equiv) led to
the formation of the mixed diorganozinc reagent FG-R-
ZnCH2SiMe3 (2). Usually, with nonfunctionalized di-
alkylzincs only 0.8 equiv was used, whereas with the less
reactive functionalized dialkylzincs, 1.2 equiv is required.
NMR-experiments show that less than 20% of (FG-R)2Zn
3 remains at the equilibrium which is set up within a
few minutes at rt.5 The mixed diorganozincs 2 are less
reactive than the zinc species 3, decreasing significantly
the addition rate to the aldehyde. The nonasymmetric
† Dedicated to Professor Dieter Seebach on the occasion of his 60th
birthday.
(1) (a) Soai, K.; Niwa, S. Chem. Rev. (Washington, D.C.) 1992, 92,
833-856. (b) Duthaler, R. O.; Hafner, A. Chem. Rev. (Washington, D.C.)
1992, 92, 807-832. (c) Evans, D. A. Science 1989, 240, 420. (d) Noyori,
R.; Kitamura, M. Angew. Chem., Int. Ed. Engl. 1991, 30, 49-69.
(2) (a) Knochel, P.; Singer, R. D. Chem. Rev. (Washington, D.C.)
1993, 93, 2117-2188. (b) Knochel, P. Synlett 1995, 393-403.
(3) Takahashi, H.; Kawakita, T.; Ohno, M.; Yoshioka, M.; Kobayashi,
S. Tetrahedron 1992, 48, 5691-5700.
(4) (a) Knochel, P., Vettel, S.; Eisenberg, C. Applied Organomet.
Chem. 1995, 9, 175-188. (b) Schwink, L.; Knochel, P. Tetrahedron Lett.
1994, 35, 9007-9010.
(5) Berger, S.; Langer, F.; Lutz, C.; Mobley, A.; Knochel, P. Angew.
Chem. 1997, 109, in press
In summary, we have shown that mixed diorganozincs
of the type FG-R-Zn(TMSM) can be advantageously used
for the enantioselective addition to aldehydes. The
method avoids the use of a large excess of valuable
diorganozinc reagents and provides an improvement of
the enantioselectivity for the addition of small dialkylz-
incs such as Me2Zn and Et2Zn.
Exp er im en ta l Section
(6) Bertz, S. H.; Eriksson, M.; Miao, G.; Snyder, J . P. J . Am. Chem.
Soc. 1996, 118, 10906-10907. See also Bolm, C.; Schlingloff, G.; Harms,
K. Chem. Ber. 1992, 125, 1191-1203.
Typ ica l P r oced u r e for th e En a n tioselective Ad d ition of
a Mixed Dia lk ylzin c to a n Ald eh yd e. A dried and argon-
flushed 50 mL Schlenk-flask was charged with (1R,2R)-1,2-bis-
(7) For the preparation of some other mixed diorganozincs: (a)
Srebnik, M. Tetrahedron Lett. 1991, 32, 2449-2452. (b) Oppolzer, W.;
Radinov, R. N. J . Am. Chem. Soc. 1993, 115, 1593-1594. (c) Niwa, S.;
Soai, K. J . Chem. Soc., Perkin Trans. 1 1990, 937-943.
(8) Reddy, C. K.; Devasagayaraj, A.; Knochel, P. Tetrahedron Lett.
1996, 37, 4495-4498.
(10) Vettel, S.; Knochel, P. Tetrahedron Lett. 1994, 35, 5849-5852.
(11) For the use of mixed methyl(alkyl)zincs in synthesis, see ref
7a.
(9) Moorhouse, W.; Wilkinson, G. J . Chem. Soc., Dalton Trans. 1974,
2187-2190.
(12) Nowotny, S.; Vettel, S.; Knochel, P. Tetrahedron Lett.1994, 35,
4539-4549.
S0022-3263(97)01488-6 CCC: $14.00 © 1997 American Chemical Society

7896 J . Org. Chem., Vol. 62, No. 22, 1997
Notes
Ta ble 1. Secon d a r y Alcoh ols 6 Obta in ed by th e
Ca ta lytic Asym m etr ic Ad d ition of th e Mixed
Dior ga n ozin cs F G-RZn CH2TMS (2) to Ald eh yd es (5) in
th e P r esen ce of th e Ch ir a l Ca ta lyst
Sch em e 1
(trifluoromethanesulfonamido)cyclohexane (1) (61 mg, 0.16 mmol,
8 mol %), Ti(O-iPr)4 (0.36 mL, 1.2 mmol, 0.6 equiv), and ether
(3 mL). This catalyst solution was cooled to -20 °C. Meanwhile
the dialkylzinc 3 (1.6 mmol, 0.8 equiv) and (TMSCH2)2Zn 4 (0.43
g, 1.8 mmol, 0.9 equiv) were mixed at 25 °C in another Schlenk-
flask. In the case of a functionalized dialkylzinc 1.2 equiv of
(FG-R)2Zn and 1.3 equiv of (TMSCH2)2Zn were used. The
resulting mixed zinc reagent FG-R-(TMSCH2)Zn was slowly
added to the catalyst solution. After 10 min, the aldehyde (2.0
mmol, 1.0 equiv) was added. The reaction mixture was stirred
at -20 °C for 14-26 h and worked up as usual. The crude
product was purified by chromatography (hexanes:ether).
An a lytica l Da ta of P r od u cts of Ta ble 1. (S)-1-P h en yl-
p r op a n ol (6a ). Yield (295 mg, 92%, 98% ee) using diethylzinc
(0.22 mL, 1.6 mmol), 4 (0.43 g, 1.9 mmol), and benzaldehyde
(250 mg, 2.36 mmol). Purified by chromatrography (hexanes/
ether ) 4:1). The enantiomeric excess was determined by chiral
gas chromatographic analysis; Chirasil CD; 120 °C isotherm; 100
kPa (H2); 7.23 min minor, 7.43 min major isomer. [R]25D ) -48.4
(c 2.31, CHCl3). IR (neat): 3360 (s), 2930 (s), 2870 (m), 1475
(m), 1031 (m). 1H NMR (200 MHz, CDCl3): δ 7.35 (m, 5H), 4.75
(t, J ) 6.0 Hz, 1H), 2.48 (s, 1H), 1.81 (m, 2H), 0.93 (t, J ) 7.2
Hz, 3H). 13C NMR (50 MHz, CDCl3): δ 145.0, 128.8, 127.9,
126.4, 76.4, 32.2, 10.6. The obtained analytical data is compa-
rable to the literature.13,14
(S)-1-P h en ylh exa n ol (6b). Yield (401 mg, 92%, 97% ee)
using dipentylzinc (0.15 g, 1.6 mmol), 4 (0.43 g, 1.9 mmol), and
benzaldehyde (260 mg, 2.45 mmol). Purified by chromatrogra-
phy (hexanes/ether ) 4:1). The enantiomeric excess was deter-
mined by chiral gas chromatographic analysis; Chirasil CD; 145
°C isotherm; 100 kPa (H2); 7.53 min major, 7.95 min minor
isomer. [R]25D ) -36.8 (c 3.18, CHCl3). IR (neat): 3360 (s), 2930
(s), 2870 (m), 1475 (m), 1031 (m). 1H NMR (200 MHz, CDCl3):
δ 7.33-7.25 (m, 5H), 4.61 (t, J ) 7.1 Hz, 1H), 2.19 (s, 1H), 1.79-
1.66 (m, 2H), 1.42-1.28 (m, 6H), 0.88 (t, J ) 6.8 Hz, 3H). 13C
NMR (50 MHz, CDCl3): δ 145.0, 128.3, 127.4, 125.9, 74.6, 39.0,
31.7, 25.4, 22.5, 13.9. The obtained analytical data is identical
with the literature.15
(S)-5-Ch lor o-1-p h en ylp en ta n ol (6c). Yield (336 mg, 86%,
>94% ee) using bis(4-chlorobutyl)zinc (0.54 g, 2.2 mmol), 4 (0.57
g, 2.4 mmol), and benzaldehyde (209 mg, 1.97 mmol). Purified
by chromatrography (hexanes/ether ) 4:1). The enantiomeric
excess was determined by chiral HPLC analysis; Chiracel OD,
heptane/2-propanol ) 95:5; flow ) 0.6 mL/min; 27.05 min major,
28.42 min minor isomer. [R]25 ) -14.7 (c 2.36, benzene). IR
D
(neat): 3370 (s), 2940 (s), 1454 (s), 1195 (m). 1H NMR (200 MHz,
CDCl3): δ 7.30-7.02 (m, 5H), 4.58 (m, 1H), 3.48 (t, J ) 6.7 Hz,
2H) 2.28 (s, 1H), 1.97-1.35 (m, 6H). 13C NMR (50 MHz,
CDCl3): δ 144.6, 129.1, 127.7, 126.1, 74.5, 44.9, 37.9, 33.5, 23.3.
The obtained analytical data is identical with the literature.16
(S)-4-Hyd r oxy-4-p h en ylbu tyl P iva la te (6d ). Yield (379
mg, 81%, 96% ee) using bis(3-pivaloxypropyl)zinc (0.83 g, 2.2
(13) Takahashi, H.; Kawakita, T.; Ohno, M.; Yoshioka, M.; Koba-
yashi, S. Tetrahedron 1992, 48, 5691-5700.
(14) Kitamura, M.; Suga, D.; Kawai, K.; Noyori, R. J . Am. Chem.
Soc. 1986, 108, 6071-6072.
mmol), 4 (0.43 g, 1.9 mmol), and benzaldehyde (0.199 g ,1.87
mmol). Purified by chromatrography (hexanes/ether ) 2:1). The
enantiomeric excess was determined by chiral HPLC analysis;
Chiracel OD, heptane/2-propanol ) 90:10; flow 0.6 mL/min; 12.6
(15) Lipshutz, B. H.; Wilhelm, R. S.; Kozlowski, J . A.; Parker, D. J .
Org. Chem. 1984, 49, 3928.
min major, 15.3 min minor isomer. [R]25 ) -20.3(c 2.87,
D
(16) Rozema, M. J .; Sidduri, A. R.; Knochel, P. J . Org. Chem 1992,
57, 1956-1958.
benzene). IR (neat): 3540 (s), 2970 (m), 2930 (s), 1720 (s), 2480

Notes
J . Org. Chem., Vol. 62, No. 22, 1997 7897
129.0, 128.1, 126.9, 74.9, 34.0, 30.6, 10.2. The obtained analyti-
cal data is comparable to the literature.13,17
Sch em e 2
(E)-(S)-1-P h en yloct-1-en -3-ol (6h ). Yield (315 mg, 89%,
86% ee) using dipenthylzinc (0.15 g, 1.6 mmol), 4 (0.43 g, 1.9
mmol), and cinnamaldehyde (230 mg, 1.74 mmol). Purified by
chromatrography (hexanes/ether ) 2:1). The enantiomeric
excess was determined by chiral HPLC analysis; Chiracel OD;
heptane/2-propanol ) 90:10; flow 0.6 mL/min; 13.09 min minor,
21.23 min major isomer. [R]25 ) +1.6 (c 6.3, benzene). IR
D
(neat): 3400 (s), 2920 (s), 2860 (s), 1700 (m). 1H NMR (200 MHz,
CDCl3): δ 7.27-7.11 (m, 5H), 6.43 (d, J ) 16 Hz, 1H), 6.09 (dd,
J ) 16.0 Hz, 6.8 Hz, 1H), 4.20-4.05 (m, 1H), 2.24 (s, 1H), 1.54-
1.44 (m, 2H), 1.33-1.20 (m, 6H), 0.79 (t, J ) 6.3 Hz, 3H) . 13C
NMR (50 MHz, CDCl3): δ 137.1, 132.9, 130.7, 128.9, 128.0, 126.9,
73.6, 37.7, 32.2, 25.6, 23.0, 14.5. The analytical data obtained
is identical with the literature.18
(E)-(S)-1-[(Tr iisop r op ylsilyl)oxy]h ex-2-en -4-ol (6i). Yield
(244 mg, 95%, 95% ee) using diethylzinc (0.15 g, 1.6 mmol), 4
(0.43 g, 1.9 mmol), and 3-(triisopropylsiloxy)propanal (274 mg,
1.03 mmol). Purified by chromatrography (hexanes/ether ) 4:1).
The enantiomeric excess was determined by chiral gas chro-
matographic analysis; Chirasil CD; 120 °C isotherm; 100 kPa
Sch em e 3
(H2); 21.40 min minor, 21.65 min major isomer. [R]25 ) +2.3
D
(c 4.01, CHCl3). IR (neat): 3370 (s), 2940 (s), 2870 (s), 1460 (s),
1130 (s), 1010 (m). 1H NMR (200 MHz, CDCl3): δ 5.73 (m, 2H),
4.23 (m, 2GH), 4.08-3.98 (m, 1H), 3.87 (m, 1H), 1.80 (s, 1H),
1.63 (s, 1H), 1.58-1.48 (m, 21H), 0.86 (t, J ) 7.3 Hz, 3H). 13C
NMR (50 MHz, CDCl3): δ 131.31, 129.6, 73.0, 62.4, 29.23, 16.8,
10.6, 8.8. MS (EI): 272 (0.5), 254 (1), 229 (36), 131 (94), 103
(100), 89 (20), 75 (88), 61 (55). Anal. Calcd for C15H32O2Si: C,
66.11; H, 11.84. Found: C, 66.06; H 11.81.
(S)-1-P h en ylp en ta n -3-ol (6j). Yield (293 mg, 87%, >95%
ee) using diethylzinc (0.15 g, 1.6 mmol), 4 (0.43 g, 1.9 mmol),
and hydrocinnamaldehyde (277 mg, 2.06 mmol). Purified by
chromatrography (hexanes/ether ) 2:1). The enantiomeric
excess was determined by chiral gas chromatographic analysis;
Chirasil CD; 120 °C isotherm; 100 kPa (H2); 14.70 min major,
(m). 1H NMR (200 MHz, CDCl3): δ 7.36-7.28 (m, 5H), 4.72-
4.70 (m, 1H), 4.10-4.06 (t, J ) 6.0 Hz, 2H) 1.89-1.31 (m, 5H),
1.20 (s, 3H). 13C NMR (50 MHz, CDCl3): δ 179.1, 144.9, 128.9,
128.0, 126.2, 74.4, 64.5, 39.1, 35.7, 27.6, 25.5. The obtained
analytical data is identical with the literature.16
15.12 min minor isomer. [R]25 ) +24.1 (c 1.08, EtOH). IR
(S)-5-Hyd r oxy-5-p h en ylp en tyl P iva la te (6e). Yield (438
mg, 81%, 97% ee) using bis(4-pivaloxybutyl)zinc (0.61 g, 1.6
mmol), 4 (0.43 g, 1.9 mmol), and benzaldehyde (223 mg, 2.10
mmol). Purified by chromatrography (hexanes/ether ) 2:1). The
enantiomeric excess was determined by chiral HPLC analysis;
Chiracel OD, heptane/2-propanol ) 95:5, flow 0.6 mL/min; 23.95
D
(neat): 3360 (s), 2930 (s), 2870 (m), 1475 (m). 1H NMR (200
MHz, CDCl3): δ 7.33-7.20 (m, 5H), 3.58 (m, 1H), 2.86-2.66 (m,
2H), 2.32 (s, 1H), 1.84-1.76 (m, 2H), 1.59-1.24 (m, 2H), 1.00 (t,
J ) 7.4 Hz, 3H). 13C NMR (50 MHz, CDCl3): δ 142.5, 128.6,
128.5, 125.9, 72.8, 38.7, 33.8, 30.4, 10.0. The obtained analytical
data is comparable to the literature.13,17
min major, 26.41 min minor isomer. [R]25 ) -25.3 (c 1.50,
D
CHCl3). IR (neat): 3440 (s), 3090 (w), 3060 (s), 2940 (m), 1880
(s), 1550 (s). 1H NMR (200 MHz, CDCl3): δ 7.35-7.27 (m, 5H),
4.65 (m, 1H), 4.03 (t, J ) 6.5 Hz, 2H), 2.20 (br s, 1H), 1.82-1.22
(m, 6H), 1.75 (s, 9H). 13C NMR (50 MHz, CDCl3): δ 177.9, 143.9,
127.6, 126.7, 125.1, 73.6, 63.4, 37.9, 37.8, 27.7, 26.4, 21.4. MS
(EI): 264 (0.6), 129 (25), 144 (26), 101 (100), 79 (25), 57 (75), 41
(25). Anal. Calcd for C16H24O3: C, 72.69; H, 9.15. Found: C,
72.53; H 9.07.
(S)-7-P h en yl-5-h yd r oxyh ep tyl P iva la te (6k ). Yield (446
mg, 76%, 74% ee) using bis(4-pivaloxybutyl)zinc (0.83 g, 2.2
mmol), 4 (0.57 g, 2.4 mmol), and hydrocinnamaldehyde (271 mg,
2.01 mmol). Purified by chromatrography (hexanes/ether ) 4:1).
The enantiomeric excess was determined by chiral HPLC
analysis; Chiracel OD; heptane/2-propanol ) 95:5; flow 0.6 mL/
min; 17.57 min minor, 19.14 min major isomer. [R]25 ) +10.7
D
(c 1.59, CHCl3). IR (neat): 3680 (s), 3030 (w), 2940 (s), 1880
(s), 1540 (s), 1230 (s). 1H NMR (300 MHz, CDCl3): δ 7.28-7.10
(m, 5H), 4.05 (t, J ) 6.6 Hz, 2H), 3.59 (m, 1H), 2.78-2.64 (m,
4H), 1.77-1.48 (m, 7H), 1.45 (s, 9H). 13C NMR (75 MHz,
CDCl3): δ 178.6, 142.0, 128.9, 126.0, 71.1, 64.2, 39.1, 38.7, 37.0,
32.3, 27.2, 22,0. MS (EI): 103 (43), 85 (16), 57 (100), 41 (23).
Anal. Calcd for C18H28O3: C, 73.93; H, 9.65. Found: C, 73.84;
H 9.53.
(S)-8-P h en yl-6-h yd r oxyoctyl P iva la te (6l). Yield (475 mg,
79%, 82% ee) using bis(5-pivaloxypentyl)zinc (0.89 g, 2.2 mmol),
4 (0.57 g, 2.4 mmol), and hydrocinnamaldehyde (263 mg, 1.96
mmol). Purified by chromatrography (hexanes/ether ) 4:1). The
enantiomeric excess was determined by chiral HPLC analysis;
Chiracel OD; heptane/2-propanol ) 90:10; flow 0.6 mL/min;
14.04 min minor, 22.24 min major isomer. [R]25D ) +41.8 (c 0.98,
CHCl3). IR (neat): 3680 (s), 3030 (w), 2940 (s), 1880 (s), 1540
(s), 1230 (s). 1H NMR (300 MHz, CDCl3): δ 7.28-7.10 (m, 5H),
4.02 (t, J ) 6.6 Hz, 2H), 3.60 (m, 1H), 2.79-2.63 (m, 4H), 1.78-
1.34 (m, 9H), 1.30 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 178.5,
142.0, 128.6, 125.7, 71.1, 64.2, 39.0, 38.6, 37.3, 31.9, 28.5, 27.1,
25.9, 25.1. MS (EI): 288 (5), 186 (12), 117 (20), 104 (64), 91
(S)-6-Hyd r oxy-6-p h en ylh exen yl Aceta te (6f). Yield (388
mg, 74%, 90% ee) using bis(5-acetoxypentyl)zinc (0.65 g, 1.6
mmol), 4 (0.43 g, 1.9 mmol), and benzaldehyde (236 mg, 2.22
mmol). Purified by chromatrography (hexanes/ether ) 2:1). The
enantiomeric excess was determined by chiral HPLC analysis;
Chiracel OD; heptane/2-propanol ) 90:10; flow 0.6 mL/min;
17.50 min major, 19.42 min minor isomer. [R]25D ) -22.1 (c 1.94,
benzene). IR (neat): 3450 (s), 2940 (s), 1737 (s), 1464 (m), 1039
(m). 1H NMR (300 MHz, CDCl3): δ 7.27-7.18 (m, 5H), 4.56 (m,
1H), 3.95 (t, J ) 6.7 Hz, 2H), 2.42 (s, 1H), 1.94 (s, 3H), 1.73-
1.23 (m, 8H). 13C NMR (75 MHz, CDCl3): δ 171.3, 144.9, 128.5,
127.5, 125.9, 74.4, 64.5, 38.9, 28.6, 25.5, 25.2, 20.9. The obtained
analytical data is identical with the literature.16
(E)-(S)-5-P h en ylp en t-4-en -3-ol (6g). Yield (311 mg, 95%,
89% ee) using diethylzinc (0.22 mL, 1.6 mmol), 4 (0.43 g, 1.9
mmol), and cinnamaldehyde (267 mg, 2.02 mmol). Purified by
chromatrography (hexanes/ether ) 2:1). The enantiomeric
excess was determined by chiral gas chromatography analysis;
Chirasil CD; 140 °C isotherm; 100 kPa (H2); 8.57 min major,
8.67 min minor isomer. [R]25 ) -5.6 (c 3.71, CHCl3). IR
D
(neat): 3360 (s), 2965 (s), 2930 (s), 1455 (m), 965 (s). 1H NMR
(200 MHz, CDCl3): δ 7.24-7.09 (m, 5H), 6.40 (d, J ) 16 Hz),
1H), 5.98 (dd, J ) 16 Hz, J ) 6.8 Hz, 1H), 4.05 ((dt, J ) 6.8, J
) 0.8 Hz, 1H), 1.83 (s, 1H), 1.57-1.45 (m, 2H), 0.79 (t, J ) 7.4
Hz, 3 H). 13C NMR (50 MHz, CDCl3): δ 137.2, 132.6, 130.9,
(17) Soai, K.; Ookawa, A.; Kaba, T.; Ogawa, K. J . Am. Chem. Soc.
1987, 109, 7111-7115.
(18) Vettel, S.; Lutz, C.; Diefenbach, A.; Haderlein, G.; Hammer-
schmidt, S.; Ku¨hling, K.; Mofid, M.-R.; Zimmermann, T.; Knochel, P.
Tetrahedron Asymmetry 1997, 8, 779-800.

7898 J . Org. Chem., Vol. 62, No. 22, 1997
Notes
(62), 57 (100). Anal. Calcd for C19H30O3: C, 74.47; H, 9.87.
Found: C, 74.38; H 9.69.
(d, J ) 15.6 Hz, 3H). 13C NMR (50 MHz, CDCl3): δ 146.2, 128.9,
127.8, 125.8, 70.8, 25.6. The obtained analytical data is identical
with the literature.19,20
An a lytica l Da ta of P r od u cts 6m a n d 6n . (S)-Eth yl
7-P h en yl-7-h yd r oxy-2-m eth ylen eh ep ta n oa te (6m ). Yield
(428 mg, 81%, 93% ee) using 6m (0.15 g, 1.6 mmol), 4 (0.43 g,
1.9 mmol), and benzaldehyde (214 mg, 2.02 mmol). Purified by
chromatrography (hexanes/ether ) 4:1). The enantiomeric
excess was determined by chiral HPLC analysis; Chiracel OD,
heptane/2-propanol ) 95:5; flow 0.6 mL/min; 12.83 min major,
Ack n ow led gm en t. We thank the DFG (SFB 260,
Leibniz Prize, and Graduierten Kolleg) as well as the
Fonds der Chemischen Industrie for generous financial
support. C.L. thanks Chemetall (Frankfurt) and Sipsy
(Avrille´, France) for a fellowship. We thank WITCO AG
(Bergkamen), BASF AG (Ludwigshafen), and BAYER
AG (Leverkusen) for the generous gift of chemicals.
13.74 min minor isomer. [R]25 ) -9.7 (c 1.68, CHCl3). IR
D
(neat): 3480 (s), 2940 (vs), 1720 (vs), 1630 (m). 1H NMR (300
MHz, CDCl3): δ 7.34-7.21 (m, 5H), 6.08 (m, 1H), 5.46 (m, 1H),
4.60 (m, 1H), 4.15 (q, J ) 8.0 Hz, 2H), 2.28 (t, J ) 7.1 Hz, 2H),
1.96 (s, 1H), 1.84-1.42 (m, 6H), 1.26 (t, J ) 7.1 Hz, 3H). 13C
NMR (75 MHz, CDCl3): δ 167.2, 144.8, 140.8, 128.4, 127.4, 125.8,
124.2, 74.4, 60.4, 38.8, 31.6, 28.2, 25.3, 14.1. MS (EI): 244 (7),
156 (100), 115 (43), 91 (40), 79 (54). Anal. Calcd for : C, 73.24;
H, 8.45. Found: C, 73.01; H 8.61.
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and 13C
NMR spectras of compounds 6e, 6i, 6k , 6l, and 6m (10 pages).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any masthead
page for ordering information.
(S)-1-P h en yleth a n ol (6n ). Yield (262 mg, 95%, 84% ee)
using dimethylzinc (0.15 g, 1.6 mmol), 4 (0.43 g, 1.9 mmol), and
benzaldehyde (240 mg, 2.3 mmol). Purified by chromatrography
(hexanes/ether ) 4:1). The enantiomeric excess was determined
by chiral gas chromatographic analysis; Chirasil CD; 120 °C
isotherm; 100 kPa (H2); 4.32 min major, 4.75 min minor isomer.
J O971488Y
(19) Yamaghuchi, S.; Mosher, H. S. J . Org. Chem. 1973, 33, 1870-
1877.
(20) Rinaldi, R. L.; Baldwin, N. J . J . Am. Chem. Soc. 1983, 105,
7523-7527.
[R]25 ) -35.2 (c 1.97, CHCl3). IR (neat): 3360 (s), 2930 (s),
D
2870 (m), 1475 (m), 1031 (m). 1H NMR (200 MHz, CDCl3): δ
7.30-7.32 (m, 5H), 4.78 (q, J ) 8.0 Hz, 1H), 2.39 (s, 1H), 1.43