Highly diastereoselective addition of allyltitanocenes to ketones

Article abstract of DOI:10.1002/chem.200802340

The reaction of allyltitanocenes, generated by the reductive titanation of allylic sulfides or allylic alcohol derivatives with a titanocene(II) species, with phenyl and sterically hindered alkyl methyl ketones produced and tertiary homoallylic alcohols w

Full text of DOI:10.1002/chem.200802340

DOI: 10.1002/chem.200802340
Highly Diastereoselective Addition of Allyltitanocenes to Ketones
Yasutaka Yatsumonji,[a] Takuya Nishimura,[a] Akira Tsubouchi,[a] Keiichi Noguchi,[b] and
Takeshi Takeda*[a]
Abstract: The reaction of allyltitano-
cenes, generated by the reductive tita-
nation of allylic sulfides or allylic alco-
hol derivatives with a titanocene(II)
species, with phenyl and sterically hin-
dered alkyl methyl ketones produced
anti tertiary homoallylic alcohols with
complete diastereoselectivity. Even
when sterically less congested methyl
ethyl ketone and methyl vinyl ketone
were employed, the anti homoallylic al-
cohols were obtained with unprece-
dented high diastereoselectivity. The
observed anti selectivity suggests that
the reaction proceeds by the addition
of primary (E)-s-allyltitanocenes to ke-
tones through chairlike cyclic transition
states.
Keywords: allylation
·
allylic
compounds · diastereoselectivity ·
ketones · titanium
Introduction
tween the two alkyl groups of the ketones is of crucial im-
portance for the conventional diastereoselective addition of
allyl metals. Recently, we reported that tertiary homopro-
pargyl alcohols were produced with high diastereoselectivity
by a titanocene(II)-promoted one-pot multistep reaction in-
volving thioacetals, alkynyl sulfones, and carbonyl com-
pounds, in which allenyltitanocenes were produced as the
active species.[6] The results prompted us to investigate the
preparation of tertiary homoallylic alcohols by using allylti-
tanocenes 1, generated by the reductive titanation of allylic
substrates 2–4. Herein, we describe the preparation of anti
tertiary homoallylic alcohols 5 with high diastereoselectivity
by the reaction of 1 with a variety of ketones 6 (Scheme 1).
The stereocontrolled construction of two adjacent stereo-
genic centers is one of the most important processes in or-
ganic synthesis. The addition of allyl metal species to car-
bonyl compounds has been extensively studied as a useful
tool for such processes.[1] It is well known that reactions of
allyl metals with aldehydes generally produce secondary ho-
moallylic alcohols with high diastereoselectivity, but the se-
lectivity seriously decreases when ketones are employed. In
this context, much attention has recently been paid to the
diastereoselective addition of allyl metals to ketones.[2,3] Al-
though the reactions of g-substituted allylzinc[2a,b] and allyl-
tin[2c] reagents with aryl and sterically hindered alkyl methyl
ketones produce tertiary homoallylic alcohols with high dia-
stereoselectivity in certain cases, only moderate or low dia-
stereoselectivity is observed in the reactions with sterically
less congested alkyl methyl ketones, such as methyl ethyl ke-
tone.[2a,g,4,5] Thus, a significant difference in bulkiness be-
Results and Discussion
Reductive titanation of allylic substrates: Previously, we re-
ported the diastereoselective preparation of anti secondary
homoallylic alcohols by the reaction of aldehydes with allyl-
titanocenes 1, generated by the desulfurizative titanation of
allylic sulfides 2 with titanocene-1-butene complex (7).[7] On
the basis of these results, we first examined the reaction con-
ditions for the reductive titanation of allylic sulfides and al-
lylic alcohol derivatives with 7. After treatment of sulfide
2a with 7 at À788C for 15 min and then at 08C for 45 min,
the reaction mixture was treated with 1m NaOH to produce
a quantitative mixture of alkenes 8 and 8’ (Scheme 2;
Table 1, entry 1). Upon quenching of the reaction with D2O,
deuterated alkenes 9 and 9’ were produced (87%, 9/9’=
79:21, E/Z ratio of 9’=94:6). These results indicate that the
[a] Y. Yatsumonji, T. Nishimura, Dr. A. Tsubouchi, Prof. T. Takeda
Department of Applied Chemistry, Graduate School of Engineering
Tokyo University of Agriculture and Technology
Koganei, Tokyo 184-8588 (Japan)
Fax : (+81)42-388-7034
E-mail: takeda-t@cc.tuat.ac.jp
[b] Prof. K. Noguchi
Instrumentation Analysis Center
Tokyo University of Agriculture and Technology
Koganei, Tokyo 184-8588 (Japan)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200802340.
2680
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 2680 – 2686

FULL PAPER
the same reaction conditions to produce alkenes 8 and 8’
with a comparable combined yield (Table 1, entry 4).
Reaction of cinnamyltitanocenes 1 with ketones 6: After the
reductive titanation of cinnamyl phenyl sulfide (2b) with the
titanocene(II) reagent 7 (2.0 equiv) at 08C for 45 min, the
resulting cinnamyltitanocene 1 was treated with acetophe-
none (6a; 1.2 equiv) in tetrahydrofuran (THF) at 08C for
1 h to produce homoallylic alcohol 5a as a single diastereo-
mer in 88% yield (Table 2, entry 1). Unlike the syn-selective
addition of allenyltitanocenes to 6a,[6] the reaction of the al-
lyltitanocene proceeded with complete anti selectivity. Simi-
larly, the reaction of the allyltitanocene generated from 2b
with tert-butyl methyl ketone (6b) and isopropyl methyl
ketone (6c) at À788C for 18 h gave the single isomers 5b
and 5c in good to high yields (Table 2, entries 3 and 4).
What is striking is that high anti selectivity was observed
even in the reaction of 2b with methyl ethyl ketone (6 f;
Table 2. anti-Selective preparation of homoallylic alcohols 5 by the reac-
tion of cinnamyltitanocenes 1 with ketones 6.
Entry Substrate Ketone Procedure[a] Product
Yield anti/syn[c]
[%][b]
1
2
3
2b
3b
2b
6a
6a
6b
A[d]
B
88
79
72
100:0
100:0
100:0
Scheme 1. Diastereoselective addition of allyltitanocenes 1 to ketones 6.
Cp: cyclopentadienyl.
5a
A
4
2b
2b
2b
6c
6e
6 f
A
A
A
85
68
88
100:0
96:4
Scheme 2. Reduction of allylic substrates with the titanocene(II) reagent
7.
5
Table 1. Reduction of allylic substrates with the titanocene(II) reagent 7.
Entry
Substrate
T
t
Yield
[%][b]
8/8’[c]
E/Z ratio
of 8’[c]
[8C][a]
[min][a]
ACHTUNGTRENNUNG
1
2
3
4
2a
3a
3a
4a
0
0
25
25
45
45
20
20
quant
80
92
90:10
90:10
88:12
81:19
93:7
6[g]
90:10
77:23
85:15
97:3
89
7[g]
8[g]
3b
4b
6 f
6 f
B
B
5e
5e
80
73
90:10
90:10
[a] Reaction conditions after the allylic substrate was treated with 7 at
À788C for 15 min. [b] Yield of isolated product. [c] Determined by GLC
analysis.
9[g]
2b
6h
A
72
88:12
corresponding allyltitanocene 1 is produced by reductive ti-
tanation of 2a. A similar treatment of allylic ether 3a with 7
gave alkenes 8 and 8’ in 80% combined yield, and a small
amount of the starting material was also recovered (Table 1,
entry 2). When the reaction was carried out at 258C, howev-
er, the reductive titanation was almost complete within
20 min and the alkenes were obtained in better combined
yield after hydrolysis (Table 1, entry 3). The allylic pivalate
4a was also reduced with the titanocene(II) species 7 under
10
2b
6i
A
67
77:23[i]
[a] Described in the Experimental Section. [b] Yield of isolated product.
[c] Determined by NMR analysis. [d] The reaction of allyltitanocene with
6a was carried out at 08C for 1 h. [e] See reference [2c]. [f] See referen-
ce [2b]. [g] 3 equiv of 6 were used. [h] See reference [2a]. [i] Determined
by GLC analysis.
Chem. Eur. J. 2009, 15, 2680 – 2686
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2681

T. Takeda et al.
Table 2, entry 6). Despite extensive studies on the reactivity
of allyl metal reagents toward carbonyl compounds, only a
few reactions with enones have been reported so far: for ex-
ample, reactions of allylic Grignard reagents with enones
afford the corresponding homoallylic alcohols with poor dia-
stereoselectivity.[8] By contrast, treatment of the allyltitano-
cene generated from 2b with methyl vinyl ketone (6h) and
3-nonen-2-one (6i) gave alcohols 5 f and 5g, respectively, in
good yields and with satisfactory diastereoselectivity
(Table 2, entries 9 and 10). The similar anti-selective allyla-
tion of ketones also proceeded when the allylic methyl ether
3b and allylic pivalate 4b were employed for the prepara-
tion of the corresponding cinnamyltitanocenes 1 (Table 2,
entries 2, 7, and 8).
sulfides and allylic methyl ethers. Thus, the successive treat-
ment of 2d and 3c with 7 and acetophenone (6a) gave the
tertiary homoallylic alcohol 5l, also with complete diaste-
reoselectivity (Table 3, entries 5 and 6). A variety of a-sub-
stituted allylic sulfides are readily prepared by the regiose-
lective alkylation of allyl sulfide,[10] and allylic ethers are
also easily obtained by the addition of vinylmagnesium bro-
mide to aldehydes[11] followed by methylation. Therefore,
the allylation of ketones with these allylic substrates is a ver-
satile tool for the anti-selective preparation of homoallylic
alcohols.
Determination of stereochemistry of homoallylic alcohols 5:
The anti stereochemistry of the major isomers of the new
compounds 5b, 5d, 5g, 5j, and 5l was determined by X-ray
single-crystal structure analysis or NOESY experiments
after the homoallylic alcohols 5 were transformed into g-bu-
tyrolactones 10. The transformation was performed by the
hydroboration–oxidation of 5 and subsequent oxidation of
the resulting diols 11 with pyridinium chlorochromate
(PCC; Scheme 3 and Table 4).
Reaction of 2-alkenyltitanocenes 1 with ketones 6: It is well
known that the reactions of crotyl metal reagents with car-
bonyl compounds generally afford the homoallylic alcohols
with lower diastereoselectivities than the reactions with cin-
namyl metal reagents.[2c,4,5,9] By contrast, the reaction of cro-
tyltitanocene 1, prepared by the reductive titanation of 2c,
with 6a gave the single isomer anti-5h in high yield
(Table 3, entry 1). Even in the
The structures of the lactones 10a and 10e were unequiv-
case of propiophenone (6j), the
alcohol 5k was obtained with
almost complete diastereoselec-
tivity (Table 3, entry 4).
Allyltitanocenes 1 were also
prepared by the reductive tita-
nation of a-substituted allylic Scheme 3. Transformation of allylic alcohols 5 into g-butyrolactones 10. 9-BBN: 9-borabicyclo
ACHTNUTRGNEUNG[3.3.1]nonane.
ocally confirmed through single-crystal X-ray analysis. The
ORTEP drawings of 10a and 10e are shown in Figure 1 and
Figure 2.
Table 3. anti-Selective preparation of homoallylic alcohols 5 by the reac-
tion of 2-alkenyltitanocenes 1 with ketones 6.
Entry Substrate Ketone Procedure[a] Product
Yield anti/
[%][b] syn[c]
1
The H–1H NOESY spectrum of lactone 10d is shown in
Figure 3. A clear cross-peak between the two methyl pro-
tons of lactone 10d confirms that the two methyl groups are
cis relative to each other. The relative configurations of 10b
and 10c were assigned in a similar manner by NOESY ex-
periments (see the Supporting Information).
The stereochemistry of lactones 10 thus determined clear-
ly indicates the anti selectivity of the addition of allyltitano-
cenes 1, generated by the reductive titanation of the allylic
substrates 2–4, to ketones 6.
1
2
2c
2c
6a
6d
A
A
79
82
100:0
100:0
In addition, the anti stereochemistry of the major isomer
of 5 f was confirmed after the compound was transformed
into the saturated tertiary alcohol 12 by reduction of the
3
4
2c
2c
6g
6j
A
A
85
85
88:12
99:1
1
double bonds. The H NMR spectrum of the major isomer
of 12 thus obtained was completely identical to that of 12
obtained by reduction of the known anti homoallylic alcohol
5e[2a] (Scheme 4).
5
6
2d
3c
6a
6a
A
B
80
70
100:0
100:0
Stereochemical pathway: The observed anti selectivity sug-
gests that the most thermodynamically stable primary (E)-s-
allyltitanocenes 1 are produced by the reductive titanation
of both the primary and secondary allylic substrates 2–4 and
that their reaction with ketones 6 proceeds via the chairlike
5l
[a] Described in the Experimental Section. [b] Yield of isolated product.
[c] Determined by NMR analysis. [d] See reference [5].
2682
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 2680 – 2686

Synthesis of Homoallylic Alcohols
FULL PAPER
Table 4. Transformation of allylic alcohols 5 into g-butyrolactones 10.
hols by utilizing allyltitanocenes
that are readily prepared by the
reductive titanation of a variety
of allylic substrates with the ti-
tanocene(II) species. The addi-
tion of allyltitanium reagents
bearing Et2N,[4] iPrO,[4] and
PhO[5] ligands with acetophe-
Entry
R
RL
RS
Intermediate
Yield [%][a]
Product
Yield [%][a]
1
2
3
4
5
Ph
Ph
Ph
Me
tBu
iBu
Me
Me
Me
Me
Me
11a
11b
11c
11d
11e
61
57
55
69
65
10a
10b
10c
10d
10e
80
50
39
60
74
(E)-C5H11CH=CH
PhCH2CH2
Ph
PhCH2CH2
[a] Yield after isolation.
Figure 1. Molecular structure of compound 10a.
Figure 3. 1H–1H NOESY spectrum of 10d.
Scheme 4. Transformation of 5e and 5 f into the tertiary alcohol 12.
Figure 2. Molecular structure of compound 10e.
six-membered transition state 13 (Scheme 5).[1a] The high
degree of diastereoselectivity in the present reaction would
be attributable to the Cp ligands of 1: it is assumed that the
unfavorable steric repulsion between the bulky Cp ring on
the titanium atom and the larger alkyl group (RL) of the
ketone in transition state 13b suppresses the formation of
the syn isomer (Scheme 5).
Scheme 5. Stereochemical pathway for the addition of allyltitanocenes 1
to ketones 6.
none and isopropyl methyl ketone tends to produce the anti
tertiary homoallylic alcohols with high diastereoselectivity.
The reactions of these allylic titanium reagents with alkyl
methyl ketones such as 2-octanone and 2-heptanone, howev-
er, show only moderate selectivity. Therefore, allyltitano-
cene species 1, generated by the reductive titanation of allyl-
Conclusion
We have established a practical method for the highly dia-
stereoselective preparation of anti tertiary homoallylic alco-
Chem. Eur. J. 2009, 15, 2680 – 2686
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2683

T. Takeda et al.
CDCl3): d=21.6, 26.6, 39.2, 58.0, 77.8, 116.6, 126.3, 128.4, 129.0, 140.7,
143.3 ppm; IR (neat): n˜ =3568, 3062, 3026, 2959, 2875, 1632, 1601, 1483,
1454, 1395, 1374, 1329, 1211, 1099, 1004, 906, 728, 703 cmÀ1; elemental
analysis: calcd (%) for C15H22O: C 82.52, H 10.16; found: C 82.50, H
9.96.
ic substrates, are the reagents of choice for the preparation
of a variety of anti homoallylic alcohols. Further studies on
the stereoselective reactions of these organotitanium species
are currently underway.
The following homoallylic alcohols 5 were obtained in a similar fashion.
In the case of the preparation of 5a, the reaction of allyltitanocene 1,
generated from 2b, with 6a was carried out at 08C for 1 h.
AHCTUNGTRENNUNG
(2S*,3R*)-2,3-diphenylpent-4-en-2-ol (5a):[2c] The reaction was carried
Experimental Section
out by using 2b (453 mg, 2.0 mmol) and 6a (288 mg, 2.4 mmol) to pro-
duce 5a (420 mg, 88%): 1H NMR (300 MHz, CDCl3): d=1.45 (s, 3H),
2.02 (s, 1H), 3.64 (d, J=8.6 Hz, 1H), 4.94 (d, J=17.0 Hz, 1H), 5.06 (d,
J=10.3 Hz, 1H), 6.13 (ddd, J=17.0, 10.3, 8.6 Hz, 1H), 7.10–7.37 ppm (m,
10H); 13C NMR (75 MHz, CDCl3): d=28.5, 61.8, 76.3, 118.0, 125.5, 126.5,
126.8, 127.7, 128.1, 129.6, 137.3, 140.1, 146.3 ppm; IR (neat): n˜ =3562,
3470, 3060, 3027, 2977, 1494, 1446, 1374, 1066, 1029, 917, 759, 737,
General: THF was distilled from sodium and benzophenone. Preparative
thin-layer chromatography (PTLC) was carried out by using Wakogel B-
5F. 1H (300 MHz) and 13C (75 MHz) NMR spectra were recorded in
CDCl3, and chemical shifts (d) are quoted in parts per million relative to
tetramethylsilane (TMS) for 1H NMR spectroscopy and relative to
CDCl3 for 13C NMR spectroscopy. IR absorptions are reported in cmÀ1
GC analysis was carried out with nitrogen as the carrier gas on a TC-
FFAP column (GL Science, 0.32 mmꢁ30 m).
.
700 cmÀ1
AHCTUNGTRENNUNG
(3S*,4S*)-2,3-Dimethyl-4-phenylhex-5-en-3-ol (5c):[2b] The reaction was
.
Reduction of the allylic sulfide 2a: A 1.59m hexane solution of BuLi
(1.3 mL, 2.0 mmol) was added to a THF (3 mL) suspension of Cp2TiCl2
(249 mg, 1.0 mmol) at À788C under argon. After 1 h, a THF (2 mL) solu-
tion of 2a (138 mg, 0.5 mmol) was added to the mixture dropwise over a
period of 5 min. Stirring was continued for 15 min at the same tempera-
ture and then at 08C for 45 min. The reaction was quenched by addition
of 1m NaOH, and insoluble materials were filtered off through celite and
washed with diethyl ether. The organic materials were extracted with di-
ethyl ether and dried over Na2SO4. After removal of the solvent, the resi-
due was purified by PTLC (hexane) to give a mixture of 2-allylnaphtha-
lene (8) and 2-(prop-1-enyl)naphthalene (8’;[12] combined yield=84 mg,
quantitative, 8/8’=90:10, E/Z ratio of 8’=93:7): 1H NMR (300 MHz,
CDCl3): d=1.90–2.00 (m, 0.3H), 3.54 (d, J=6.6 Hz, 1.8H), 5.08–5.18 (m,
1.8H), 6.04 (ddt, J=16.9, 10.3, 6.6 Hz, 0.9H), 6.35 (dq, J=15.8, 6.6 Hz,
0.1H), 6.55 (d, J=16.2 Hz, 0.1H), 7.21–7.82 ppm (m, 7H); 13C NMR
(75 MHz, CDCl3; major isomer): d=40.3, 116.0, 125.2, 125.9, 126.6, 127.4,
127.5, 127.6, 127.9, 132.1, 133.6, 137.3, 137.5 ppm; IR (neat): n˜ =3054,
carried out by using 2b (453 mg, 2.0 mmol) and 6c (176 mg, 2.4 mmol) to
produce 5c (347 mg, 85%): H NMR (300 MHz, CDCl3): d=0.87 (s, 3H),
1
0.91 (d, J=6.8 Hz, 3H), 0.98 (d, J=6.8 Hz, 3H), 1.37 (s, 1H), 1.96
(septet, J=6.8 Hz, 1H), 3.42 (d, J=9.7 Hz, 1H), 5.09 (ddd, J=17.2, 1.9,
0.7 Hz, 1H), 5.14 (dd, J=10.3, 2.0 Hz, 1H), 6.35 (dt, J=17.2, 10.0 Hz,
1H), 7.18–7.34 ppm (m, 5H); 13C NMR (75 MHz, CDCl3): d=16.8, 17.5,
20.1, 34.0, 57.6, 76.1, 116.8, 126.4, 128.2, 129.3, 137.9, 141.8 ppm; IR
(neat): n˜ =3483, 3074, 3027, 2961, 2876, 1635, 1601, 1491, 1470, 1454,
1387, 1156, 1081, 1005, 917, 736, 702 cmÀ1
.
A mixture of (3S*,4S*)- and (3S*,4R*)-4,6-dimethyl-3-phenylhept-1-en-4-
ol (5d): The reaction was carried out by using 2b (453 mg, 2.0 mmol) and
6e (240 mg, 2.4 mmol) to produce 5d (297 mg, 68%; 3S*,4S*/3S*,4R*=
96:4): 1H NMR (300 MHz, CDCl3): d=0.92 (d, J=6.6 Hz, 3H), 0.96 (d,
J=6.6 Hz, 3H), 1.11 (s, 2.88H), 1.18 (s, 0.12H), 1.36–1.40 (m, 2H), 1.45
(s, 1H), 1.72–1.94 (m, 1H), 3.27 (d, J=9.7 Hz, 0.96H), 3.31 (d, J=9.7 Hz,
0.04H), 5.07–5.21 (m, 2H), 6.20–6.38 (m, 1H), 7.17–7.34 ppm (m, 5H);
13C NMR (75 MHz, CDCl3; major isomer): d=24.0, 24.3, 24.9, 25.1, 48.2,
61.8, 74.5, 117.7, 126.5, 128.2, 129.2, 137.8, 141.1 ppm; IR (neat): n˜ =3569,
3482, 3077, 3028, 2954, 2870, 1493, 1453, 1376, 1157, 1082, 918, 746,
703 cmÀ1; elemental analysis: calcd (%) for C15H22O: C 82.52, H 10.16;
found: C 82.72, H 9.93.
2977, 2908, 1636, 1600, 1508, 1432, 994, 960, 914, 851, 815, 752, 606 cmÀ1
.
Reduction of the allylic ether 3a: A 1.59m hexane solution of BuLi
(5.0 mL, 8.0 mmol) was added to a THF (12 mL) suspension of Cp2TiCl2
(996 mg, 4.0 mmol) at À788C under argon. After 1 h, a THF (8 mL) solu-
tion of 3a (536 mg, 2.0 mmol) was added to the mixture dropwise over a
period of 5 min. Stirring was continued for 15 min at the same tempera-
ture and then at 258C for 20 min. The reaction was quenched by addition
of 1m NaOH, and insoluble materials were filtered off through celite and
washed with diethyl ether. The organic materials were extracted with di-
ethyl ether and dried over Na2SO4. After removal of the solvent, the resi-
due was purified by PTLC (hexane) to give a mixture of 8 and 8’
(311 mg, 92%, 8/8’=90:10, E/Z ratio of 8’=77:23).
A mixture of (3S*,4S*)- and (3S*,4R*)-3-methyl-4-phenylhex-5-en-3-ol
(5e):[2a] The reaction was carried out by using 2b (453 mg, 2.0 mmol) and
6 f (433 mg, 6.0 mmol) to produce 5e (384 mg, 88%; 3S*,4S*/3S*,4R*=
1
90:10): H NMR (300 MHz, CDCl3): d=0.91 (t, J=7.3 Hz, 0.3H), 0.93 (t,
J=7.5 Hz, 2.7H), 1.06 (s, 2.7H), 1.15 (s, 0.3H), 1.45 (s, 1H), 1.53 (q, J=
7.5 Hz, 2H), 3.30 (d, J=9.5 Hz, 0.9H), 3.31 (d, J=9.5 Hz, 0.1H), 5.06–
5.22 (m, 2H), 6.33 (dt, J=16.9, 9.9 Hz, 1H), 7.19–7.34 ppm (m, 5H);
13C NMR (75 MHz, CDCl3; major isomer): d=7.9, 24.2, 32.5, 60.0, 74.1,
117.5, 126.5, 128.2, 129.2, 137.8, 141.2 ppm; IR (neat): n˜ =3464, 3076,
3028, 2972, 2937, 2881, 1636, 1601, 1492, 1453, 1416, 1377, 1282, 1157,
Reduction of the allylic pivalate 4a: The reduction of 4a (536 mg,
2.0 mmol) under the above conditions produced a mixture of 8 and 8’
(299 mg, 89%, 8/8’=81:19, E/Z ratio of 8’=97:3).
1114, 1072, 1048, 1032, 997, 916, 741, 702 cmÀ1
.
Preparation of anti-homoallylic alcohols 5
A mixture of (3S*,4S*)- and (3S*,4R*)-3-methyl-4-phenylhexa-1,5-dien-
3-ol (5 f): The reaction was carried out by using 2b (453 mg, 2.0 mmol)
and 6h (421 mg, 6.0 mmol) to produce 5 f (271 mg, 72%; 3S*,4S*/
3S*,4R*=88:12): 1H NMR (300 MHz, CDCl3): d=1.25 (s, 3H), 1.61 (s,
0.88H), 1.84 (s, 0.12H), 3.36 (d, J=8.8 Hz, 1H), 5.04–5.25 (m, 4H), 5.93
(dd, J=17.2, 10.8 Hz, 0.12H), 5.97 (dd, J=17.3, 10.7 Hz, 0.88H), 6.22
(ddd, J=17.0, 10.3, 9.0 Hz, 0.88H), 6.18–6.30 (m, 0.12H), 7.20–7.34 ppm
(m, 5H); 13C NMR (75 MHz, CDCl3; major isomer): d=26.5, 61.0, 74.8,
112.8, 117.8, 126.8, 128.1, 129.5, 137.4, 139.9, 143.3 ppm; IR (neat): n˜ =
Typical procedure A: ACTHUNRGTNEUNG(3S*,4R*)-2,2,3-trimethyl-4-phenylhex-5-en-3-ol
(5b): A 1.54m hexane solution of BuLi (5.2 mL, 8.0 mmol) was added to
a THF (12 mL) suspension of Cp2TiCl2 (996 mg, 4.0 mmol) at À788C
under argon. After 1 h, a THF (8 mL) solution of 2b (453 mg, 2.0 mmol)
was added to the mixture dropwise over a period of 5 min. Stirring was
continued for 15 min at the same temperature and then at 08C for
45 min. After the reaction mixture had been stirred at À788C for 15 min,
6b (240 mg, 2.4 mmol) in THF (4 mL) was added dropwise over a period
of 10 min; the reaction mixture was then stirred for a further 18 h. The
reaction was quenched by addition of 1m NaOH, and insoluble materials
were filtered off through celite and washed with diethyl ether. The organ-
ic materials were extracted with diethyl ether and dried over Na2SO4.
After removal of the solvent, the residue was purified by PTLC (hexane/
AcOEt 95:5) to give (3S*,4R*)-2,2,3-trimethyl-4-phenylhex-5-en-3-ol
3567, 3462, 3083, 3028, 2979, 2930, 1454, 1372, 1173, 995, 921, 702 cmÀ1
;
elemental analysis: calcd (%) for C13H16O: C 82.94, H 8.57; found: C
83.01, H 8.78.
A mixture of (E)-(3S*,4S*)- and (E)-(3S*,4R*)-4-methyl-3-phenylunde-
ca-1,5-dien-4-ol (5g): The reaction was carried out by using 2b (543 mg,
2.4 mmol) and 6i (280 mg, 2.0 mmol) to produce 5g (345 mg, 67%;
3S*,4S*/3S*,4R*=77:23): 1H NMR (300 MHz, CDCl3): d=0.85–0.93 (m,
1H), 1.17–1.42 (m, 9H), 1.58 (s, 0.77H), 1.80 (s, 0.23H), 1.97–2.07 (m,
2H), 3.30–3.37 (m, 1H), 5.05–5.23 (m, 2H), 5.46–5.60 (m, 2H), 6.15–6.31
1
(5b; 314 mg, 72%): H NMR (300 MHz, CDCl3): d=0.93 (s, 9H), 1.16 (s,
3H), 1.70 (s, 1H), 3.62 (d, J=9.5 Hz, 1H), 5.02–5.13 (m, 2H), 6.37 (ddd,
J=16.9, 9.9, 9.9 Hz, 1H), 7.15–7.32 ppm (m, 5H); 13C NMR (75 MHz,
2684
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 2680 – 2686

Synthesis of Homoallylic Alcohols
FULL PAPER
(m, 1H), 7.18–7.33 ppm (m, 5H); 13C NMR (75 MHz, CDCl3; major
isomer): d=14.0, 22.5, 29.0, 31.3, 32.3, 61.6, 74.3, 117.7, 126.7, 128.1,
129.3, 129.6, 134.8, 137.7, 140.3 ppm; IR (neat): n˜ =3463, 3062, 3028,
2926, 2856, 1454, 1373, 975, 917, 702 cmÀ1; elemental analysis: calcd (%)
for C18H26O: C 83.67, H 10.14; found: C 84.09, H 10.48.
2.4 mmol), respectively. The homoallylic alcohol 5e (377 mg, 73%) was
also obtained by using 4b (437 mg, 2.0 mmol) and 6 f (433 mg, 6.0 mmol).
Transformation of homoallylic alcohols 5 into g-butyrolactones 10
Transformation of 5 into 10 by using BH3·Me2S: Typical procedure: A
2m diethyl ether solution of BH3·Me2S (0.6 mL, 1.2 mmol) was added to
a THF (5.6 mL) solution of the homoallylic alcohol 5j (isomeric ratio=
88:12; 377 mg, 1.85 mmol) at room temperature under argon. The mix-
ture was stirred for 4 h, and the reaction was then quenched by addition
of water at 08C. Sodium perborate (2.6 g, 17 mmol) and NaOH (67 mg,
17 mmol) were subsequently added at 08C, and the mixture was heated
at 508C for 4 h. After the mixture had cooled to room temperature, the
organic materials were extracted with diethyl ether and dried over
Na2SO4. After removal of the solvent under reduced pressure, the residue
was purified by PTLC (hexane/AcOEt 2:1) to give 11d (284 mg, 69%).
A CH2Cl2 (3 mL) solution of 11d (267 mg, 1.2 mmol) was added to PCC
(1.13 g, 4.5 mmol) in CH2Cl2 (15 mL), and the mixture was stirred for
18 h at room temperature under argon. Purification of the reaction mix-
ture by column chromatography (Kanto silica gel 60N, eluted with
AcOEt) gave the crude product, which was further purified by PTLC
(hexane/AcOEt 2:1) to give a mixture of (3S*,4R*)- and (3S*,4S*)-3,4-di-
methyl-4-(phenylethyl)butyrolactone (10d; 157 mg, 60%; 3S*,4R*/
3S*,4S*=91:9): 1H NMR (300 MHz, CDCl3): d=1.04–1.12 (m, 3H), 1.30
(s, 2.73H), 1.48 (s, 0.27H), 1.68–2.07 (m, 2H), 2.18–2.51 (m, 2H), 2.60–
2.85 (m, 3H), 7.16–7.33 ppm (m, 5H); 13C NMR (75 MHz, CDCl3; major
isomer): d=14.4, 19.6, 30.0, 36.5, 38.3, 42.1, 88.5, 126.0, 128.2, 128.5,
141.4, 175.8 ppm; IR (neat): n˜ =3027, 2974, 2937, 2879, 1766, 1496, 1455,
1422, 1385, 1244, 1198, 1171, 1122, 1081, 1052, 962, 945, 924, 754, 701,
634 cmÀ1; elemental analysis: calcd (%) for C14H18O2: C 77.03, H 8.31;
found: C 77.02, H 8.63.
ACHTUNGTRENNUNG
(2S*,3S*)-3-Methyl-2-phenylpent-4-en-2-ol (5h):[5] The reaction was car-
ried out by using 2c (329 mg, 2.0 mmol) and 6a (288 mg, 2.4 mmol) to
produce 5h (278 mg, 79%): 1H NMR (300 MHz, CDCl3): d=0.97 (d, J=
6.9 Hz, 3H), 1.53 (s, 3H), 1.95 (s, 1H), 2.60 (dq, J=6.9, 7.1 Hz, 1H),
5.06–5.22 (m, 2H), 5.65–5.77 (m, 1H), 7.19–7.34 ppm (m, 5H); 13C NMR
(75 MHz, CDCl3): d=14.1, 25.8, 48.7, 75.6, 116.6, 125.4, 126.6, 127.8,
139.9, 147.0 ppm; IR (neat): n˜ =3458, 3061, 3026, 2977, 2934, 2877, 1446,
1373, 1071, 1028, 912, 701 cmÀ1
ACHTUNGTRENNUNG
(2S*,3R*)-2-Cyclohexyl-3-methylpent-4-en-2-ol (5i):[5] The reaction was
.
carried out by using 2c (329 mg, 2.0 mmol) and 6d (303 mg, 2.4 mmol) to
produce 5i (299 mg, 82%): 1H NMR (300 MHz, CDCl3): d=1.00 (d, J=
7.0 Hz, 3H), 1.03 (s, 3H), 1.05–1.25 (m, 4H), 1.26 (s, 1H), 1.35–1.47 (m,
1H), 1.60–1.87 (m, 6H), 2.42 (dq, J=7.1, 7.2 Hz, 1H), 5.06 (d, J=
15.4 Hz, 1H), 5.10 (d, J=9.9 Hz, 1H), 5.90 (ddd, J=17.2, 10.3, 8.4 Hz,
2H), 7.19–7.34 ppm (m, 5H); 13C NMR (75 MHz, CDCl3): d=14.6, 20.1,
26.2, 26.6, 26.7, 26.8, 27.3, 44.2, 45.0, 75.2, 115.8, 140.6 ppm; IR (neat):
n˜ =3482, 3073, 2926, 2853, 1636, 1450, 1378, 1120, 1074, 909 cmÀ1
.
A mixture of (3S*,4R*)- and (3S*,4S*)-3,4-dimethyl-1-phenylhex-5-en-3-
ol (5j):[2g] The reaction was carried out by using 2c (329 mg, 2.0 mmol)
and 6g (356 mg, 2.4 mmol) to produce 5j (347 mg, 85%; 3S*,4R*/
3S*,4S*=88:12): 1H NMR (300 MHz, CDCl3): d=1.05 (d, J=7.0 Hz,
3H), 1.17 (s, 2.64H), 1.21 (s, 0.36H), 1.43 (s, 0.12H), 1.56 (s, 0.88H),
1.68–1.89 (m, 2H), 2.34 (dq, J=7.0, 7.3 Hz, 1H), 2.59–2.83 (m, 2H),
5.06–5.21 (m, 2H), 5.72–5.95 (m, 2H), 7.13–7.34 ppm (m, 5H); 13C NMR
(75 MHz, CDCl3; major isomer): d=15.0, 23.5, 29.8, 42.1, 47.5, 73.6,
116.7, 125.7, 128.4, 140.1, 142.8 ppm; IR (neat): n˜ =3447, 3063, 3026,
In a similar fashion, the following g-butyrolactones 10 were obtained.
AHCTUNGTERG(NNUN 3S*,4R*)-4-tert-Butyl-4-methyl-3-phenylbutyrolactone (10a): The hydro-
2974, 2874, 1455, 1375, 1059, 911, 699 cmÀ1
.
boration–oxidation of 5b (283 mg, 1.3 mmol) was carried out by using
BH3·Me2S (2m in diethyl ether, 0.40 mL, 0.80 mmol), sodium perborate
(2.0 g, 13 mmol), and NaOH (50 mg, 13 mmol) to produce 11a (189 mg,
61%). The oxidation of 11a (186 mg, 0.80 mmol) was carried out by
using PCC (755 mg, 3.0 mmol) to produce 10a (146 mg, 80%): m.p.=
126–1278C; 1H NMR (300 MHz, CDCl3): d=1.06 (s, 9H), 1.07 (s, 3H),
2.87 (dd, J=18.7, 6.4 Hz, 1H), 3.09 (dd, J=18.7, 10.3 Hz, 1H), 3.82 (dd,
J=10.3, 6.4 Hz, 1H), 7.17–7.38 ppm (m, 5H); 13C NMR (75 MHz,
CDCl3): d=19.7, 25.4, 38.3, 39.1, 44.4, 94.1, 127.3, 128.5, 128.8, 140.5,
176.2 ppm; IR (KBr): n˜ =3005, 2976, 2880, 1746, 1499, 1484, 1458, 1418,
1397, 1377, 1298, 1268, 1203, 1153, 1124, 1087, 960, 943, 750, 706 cmÀ1; el-
emental analysis: calcd (%) for C15H20O2: C 77.55, H 8.68; found: C
77.21, H 8.66.
A mixture of (3S*,4S*)- and (3S*,4R*)-4-methyl-3-phenylhex-5-en-3-ol
(5k):[5] The reaction was carried out by using 2c (329 mg, 2.0 mmol) and
6j (322 mg, 2.4 mmol) to produce 5k (323 mg, 85%; 3S*,4S*/3S*,4R*=
99:1): 1H NMR (300 MHz, CDCl3): d=0.72 (t, J=7.4 Hz, 3H), 0.81 (d,
J=6.8 Hz, 0.01H), 1.02 (d, J=6.8 Hz, 0.99H), 1.81 (s, 1H), 1.83 (dq, J=
14.3, 7.2 Hz, 1H), 1.97 (dq, J=14.5, 7.3 Hz, 1H), 2.65 (dq, J=14.1,
6.9 Hz, 1H), 5.03 (d, J=11.2 Hz, 1H), 5.05 (d, J=17.6 Hz, 1H), 5.55–5.69
(m, 1H), 7.18–7.41 ppm (m, 5H); 13C NMR (75 MHz, CDCl3; major
isomer): d=7.8, 13.4, 31.4, 47.6, 78.2, 116.2, 126.1, 126.3, 127.7, 140.0,
144.6 ppm; IR (neat): n˜ =3488, 3061, 3026, 2974, 2937, 2879, 1494, 1446,
1376, 1139, 1058, 1005, 969, 913, 759, 702 cmÀ1
ACHTUNGTRENNUNG(2S*,3S*)-3-Phenylethyl-2-phenylpent-4-en-2-ol (5l): The reaction was
.
carried out by using 2d (509 mg, 2.0 mmol) and 6a (288 mg, 2.4 mmol) to
produce 5l (426 mg, 80%): 1H NMR (300 MHz, CDCl3): d=1.35 (dddd,
J=13.3, 11.0, 9.6, 4.8 Hz, 1H), 1.54 (s, 3H), 1.78 (dddd, J=13.1, 8.6, 7.3,
2.6 Hz, 1H), 2.01 (s, 1H), 2.24–2.36 (m, 2H), 2.60 (ddd, J=14.0, 10.0,
4.3 Hz, 1H), 5.17 (dd, J=17.1, 2.1 Hz, 1H), 5.27 (dd, J=10.3, 2.0 Hz,
1H), 5.63 (ddd, J=17.0, 8.5, 8.5 Hz, 1H), 6.98–7.05 (m, 2H), 7.09–
7.42 ppm (m, 8H); 13C NMR (75 MHz, CDCl3): d=25.7, 30.4, 33.9, 56.0,
75.4, 119.4, 125.6, 125.9, 126.7, 127.8, 128.2, 128.3, 138.5, 142.2,
146.1 ppm; IR (neat): n˜ =3456, 3061, 3026, 2976, 2926, 1495, 1446, 1063,
1029, 918, 754, 700 cmÀ1; elemental analysis: calcd (%) for C19H22O: C
85.67, H 8.32; found: C 85.78, H 8.52.
AHCTUNGTERG(NNUN 3S*,4S*)-4-Isobutyl-4-methyl-3-phenylbutyrolactone (10b): The hydro-
boration–oxidation of 5d (148 mg, 0.60 mmol) was carried out by using
BH3·Me2S (2m in diethyl ether, 0.20 mL, 0.40 mmol), sodium perborate
(923 mg, 5.8 mmol), and NaOH (23 mg, 5.8 mmol) to produce 11b
(81 mg, 57%). The oxidation of 11b (71 mg, 0.30 mmol) was carried out
by using PCC (273 mg, 1.1 mmol) to produce 10b (26 mg, 50%):
1H NMR (300 MHz, CDCl3): d=0.97 (d, J=6.6 Hz, 3H), 1.04 (d, J=
6.6 Hz, 3H), 1.04 (s, 3H), 1.63 (dd, J=14.7, 7.5 Hz, 1H), 1.75 (dd, J=
14.7, 5.1 Hz, 1H), 1.80–2.00 (m, 1H), 2.84 (dd, J=17.6, 8.6 Hz, 1H), 3.00
(dd, J=17.6, 10.8 Hz, 1H), 3.53 (dd, J=10.7, 8.7 Hz, 1H), 7.20–7.40 ppm
(m, 5H); 13C NMR (75 MHz, CDCl3): d=21.1, 23.7, 24.2, 24.5, 34.0, 48.4,
50.4, 89.6, 127.7, 128.1, 128.6, 136.5, 175.6 ppm; IR (neat): n˜ =3032, 2955,
2871, 1775, 1498, 1456, 1384, 1367, 1303, 1269, 1223, 1194, 1122, 1052,
1030, 968, 939, 743, 702, 619 cmÀ1; elemental analysis: calcd (%) for
C15H20O2: C 77.55, H 8.68; found: C 77.95, H 8.84.
Typical procedure B:
A 1.54m hexane solution of BuLi (5.2 mL,
8.0 mmol) was added to a THF (12 mL) suspension of Cp2TiCl2 (996 mg,
4.0 mmol) at À788C under argon. After 1 h, a THF (8 mL) solution of
3b (296 mg, 2.0 mmol) was added to the mixture dropwise over a period
of 5 min. Stirring was continued for 15 min at the same temperature and
then at 258C for 20 min. After the reaction mixture had been stirred at
À788C for 15 min, 6a (288 mg, 2.4 mmol) in THF (4 mL) was added
dropwise over a period of 10 min, and the reaction mixture was stirred
for a further 18 h. The workup used in procedure A afforded 5a (377 mg,
79%).
AHCTUNGTERG(NNUN 3S*,4S*)-4-Methyl-3-phenylethyl-4-phenylbutyrolactone (10e): The hy-
droboration–oxidation of 5l (346 mg, 1.3 mmol) was carried out by using
BH3·Me2S (2m in diethyl ether, 0.40 mL, 0.80 mmol), sodium perborate
(2.0 g, 13 mmol), and NaOH (50 mg, 13 mmol) to produce 11e (240 mg,
65%). The oxidation of 11e (228 mg, 0.80 mmol) was carried out by
using PCC (745 mg, 3.0 mmol) to produce 10e (166 mg, 74%): m.p.=
109–1108C; 1H NMR (300 MHz, CDCl3): d=1.59 (s, 3H), 1.64–1.82 (m,
1H), 1.93–2.06 (m, 1H), 2.40 (dd, J=16.1, 9.5 Hz, 1H), 2.45–2.67 (m,
3H), 2.68 (dd, J=16.1, 7.3 Hz, 1H), 7.08–7.38 ppm (m, 10H); 13C NMR
In a similar fashion, the homoallylic alcohols 5e (349 mg, 80%) and 5l
(373 mg, 70%) were obtained by using 3b (296 mg, 2.0 mmol) with 6 f
(433 mg, 6.0 mmol) and 3c (353 mg, 2.0 mmol) with 6a (288 mg,
Chem. Eur. J. 2009, 15, 2680 – 2686
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2685

T. Takeda et al.
(75 MHz, CDCl3): d=21.7, 31.3, 34.1, 34.7, 46.5, 88.7, 124.3, 126.2, 127.7,
128.1, 128.4, 140.7, 143.9, 175.4 ppm; IR (KBr): n˜ =3518, 3086, 3061,
3027, 2979, 2938, 2861, 1769, 1602, 1496, 1447, 1421, 1383, 1317, 1272,
1223, 1191, 1141, 1114, 1090, 1054, 1030, 1010, 970, 936, 767, 700,
661 cmÀ1; elemental analysis: calcd (%) for C19H20O2: C 81.40, H 7.19;
found: C 81.22, H 7.24.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Research
(no. 18350018) and a Grant-in-Aid for Scientific Research on Priority
Areas “Advanced Molecular Transformations of Carbon Resources”
(no. 19020016) from the Ministry of Education, Culture, Sports, Science
and Technology, Japan.
Transformation of 5g into 10c by using 9-BBN: A 0.5m THF solution of
9-BBN (3.0 mL, 1.5 mmol) was added to a THF (1.4 mL) solution of the
homoallylic alcohol 5g (96 mg, 0.37 mmol) at room temperature under
argon. The mixture was stirred for 1.5 h, and the reaction was then
quenched by addition of 3m NaOH (0.4 mL) at 08C. Hydrogen peroxide
(30%, 1.5 mL) was subsequently added at 08C, and the mixture was
stirred at 258C for 30 min. The organic materials were extracted with di-
ethyl ether and dried over Na2SO4. After removal of the solvent under
reduced pressure, the residue was purified by PTLC (hexane/AcOEt 2:1)
to give 11c (57 mg, 55%). A CH2Cl2 (3 mL) solution of 11c (55 mg,
0.2 mmol) was added to PCC (199 mg, 0.8 mmol) in CH2Cl2 (3 mL), and
the mixture was stirred for 18 h at room temperature under argon. The
workup described above afforded (3S*,4S*)-4-((E)-hept-1-enyl)-4-
methyl-3-phenylbutyrolactone (10c; 74 mg, 39%): 1H NMR (300 MHz,
CDCl3): d=0.90 (t, J=6.8 Hz, 3H), 1.08 (s, 3H), 1.23–1.47 (m, 6H),
2.05–2.13 (m, 2H), 2.92 (d, J=8.4 Hz, 1H), 3.56 (d, J=8.4 Hz, 1H), 5.61–
5.77 (m, 2H), 7.15–7.38 ppm (m, 5H); 13C NMR (75 MHz, CDCl3): d=
13.9, 21.4, 22.3, 28.6, 31.2, 32.0, 34.2, 50.3, 87.9, 127.6, 127.7, 128.5, 131.4,
132.2, 136.9, 175.7 ppm; IR (neat): n˜ =3524, 3032, 2927, 1778, 1498, 1455,
1379, 1222, 1061, 971, 700, 619 cmÀ1; elemental analysis: calcd (%) for
C18H24O2: C 79.37, H 8.88; found: C 79.32, H 9.17.
[1] a) S. E. Denmark, N. G. Almstead in Modern Carbonyl Chemistry
(Ed.: J. Otera), Wiley-VCH, Weinheim, 2000, chapter 10; b) S. R.
Chemler, W. R. Roush in Modern Carbonyl Chemistry (Ed.: J.
Otera), Wiley-VCH, Weinheim, 2000, chapter 11; c) N. Risch, M.
Arend in Stereoselective Synthesis, Methods of Organic Chemistry,
Vol. 3 (Eds.: G. Helmchen, R. Hoffmann, J. Mulzer, E. Schaumann),
Thieme, Stuttgart, 1996, pp. 1357–1602; d) J. Szymoniak, C. Moꢃse
in Titanium and Zirconium in Organic Synthesis (Ed.: I. Marek),
Wiley-VCH, Weinheim, 2002, chapter 13; e) S. E. Denmark, J. Fu,
Chem. Rev. 2003, 103, 2763–2793; f) I. Fleming, A. Barbaro, D.
Walter, Chem. Rev. 1997, 97, 2063–2192; g) Y. Yamamoto, N. Asao,
Chem. Rev. 1993, 93, 2207–2293.
[2] For recent examples of diastereoselective allylation of ketones, see:
[Zn]: a) G. Dunet, P. Mayer, P. Knochel, Org. Lett. 2008, 10, 117–
120; b) H. Ren, G. Dunet, P. Mayer, P. Knochel, J. Am. Chem. Soc.
2007, 129, 5376–5377; [Sn]: c) M. Yasuda, K. Hirata, M. Nishino, A.
Yamamoto, A. Baba, J. Am. Chem. Soc. 2002, 124, 13442–13447;
[Si]: d) L. F. Tietze, T. Kinzel, S. Schmatz, J. Am. Chem. Soc. 2006,
128, 11483–11495; [In]: e) S. A. Babu, M. Yasuda, A. Baba, J. Org.
Chem. 2007, 72, 10264–10267; f) N. Hayashi, H. Honda, M. Yasuda,
I. Shibata, A. Baba, Org. Lett. 2006, 8, 4553–4556; [V]: g) Y. Katao-
ka, I. Makihara, T. Yamahata, K. Tani, Organometallics 1997, 16,
4788–4795.
Transformation of homoallylic alcohols 5 into the saturated alcohol 12
Reduction of the homoallylic alcohol 5 f: An EtOH (1.7 mL) solution of
5 f (94 mg, 0.50 mmol) was added to a flask charged with 10% Pd/C
(18 mg) under hydrogen at room temperature, and the reaction mixture
was stirred for 3 h. The insoluble materials were filtered off and washed
with diethyl ether. The solvent was evaporated under reduced pressure,
and the residue was purified by PTLC (hexane/AcOEt 95:5) to give a
mixture of (3S*,4S*)- and (3S*,4R*)-3-methyl-4-phenylhexan-3-ol (12;
91 mg, 95%; 3S*,4S*/3S*,4R*=88:12): 1H NMR (300 MHz, CDCl3): d=
0.71 (t, J=7.3 Hz, 3H), 0.90 (t, J=7.4 Hz, 2.64H), 0.92 (t, J=7.3 Hz,
0.36H), 1.06 (s, 2.64H), 1.13 (s, 0.36H), 1.20 (s, 1H), 1.38–1.56 (m, 2H),
1.66–1.82 (m, 1H), 1.82–1.99 (m, 1H), 2.50 (dd, J=11.9, 3.3 Hz, 0.88H),
2.50–2.59 (m, 0.12H), 7.17–7.34 ppm (m, 5H); 13C NMR (75 MHz,
CDCl3; major isomer): d=8.0, 12.9, 21.8, 24.3, 32.5, 57.6, 74.7, 126.4,
128.0, 129.7, 141.3 ppm; IR (neat): n˜ =3446, 3061, 3027, 2967, 2876, 1493,
1454, 1378, 1156, 702 cmÀ1; elemental analysis: calcd (%) for C13H20O: C
81.20, H 10.48; found: C 81.66, H 10.01.
[3] For diastereoselective asymmetric allylation of ketones, see: a) M.
Wadamoto, H. Yamamoto, J. Am. Chem. Soc. 2005, 127, 14556–
14557; b) R. Wada, K. Oisaki, M. Kanai, M. Shibasaki, J. Am.
Chem. Soc. 2004, 126, 8910–8911.
[4] M. T. Reetz, R. Steinbach, J. Westermann, R. Peter, B. Wenderoth,
Chem. Ber. 1985, 118, 1441–1454.
[5] D. Seebach, L. Wildler, Helv. Chim. Acta 1982, 65, 1972–1981.
[6] T. Takeda, M. Ando, T. Sugita, A. Tsubouchi, Org. Lett. 2007, 9,
2875–2878.
[7] T. Takeda, I. Miura, Y. Horikawa, T. Fujiwara, Tetrahedron Lett.
1995, 36, 1495–1498.
[8] a) T. Zair, C. Santelli-Rouvier, M. Santelli, J. Org. Chem. 1993, 58,
2686–2693; b) M. El Idrissi, M. Santelli, J. Org. Chem. 1988, 53,
1010–1016.
[9] a) A. R. Katritzky, C. N. Fali, M. Qi, Tetrahedron Lett. 1998, 39,
363–366; b) H. Maeda, K. Shono, H. Ohmori, Chem. Pharm. Bull.
1994, 42, 1808–1812; c) Y. Rollin, S. Derien, E. DuÇach, C. Gebeh-
enne, J. Pꢄrichon, Tetrahedron 1993, 49, 7723–7732; d) H. Hebri, E.
DuÇach, J. Pꢄrichon, Tetrahedron Lett. 1993, 34, 1475–1478; e) R. E.
Sjçholm, Acta Chem. Scand. 1990, 44, 82–89.
Reduction of the homoallylic alcohol 5e: The homoallylic alcohol 5e
(94 mg, 0.50 mmol) was reduced under the same reaction conditions for
2 h to give 12 (85 mg, 88%).
Crystal data for compounds 10: CCDC 708323 (10a) and CCDC 708322
(10e) contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
10a: C15H20O2, MW =232.31; crystal size 0.60ꢁ0.20ꢁ0.20 mm; monoclin-
ic; space group P21/c; a=11.1678(3), b=11.6635(3), c=10.7369(3) ꢂ; b=
110.922(2)8; V=1306.33(6) ꢂ3; Z=4; T=193 K; Dx =1.181 gcmÀ3
;
mCu-Ka =0.603 mmÀ1; Rint =0.0270; number of measured/independent re-
flections=22817/2385; R=0.0399 and wR(F2)=0.1152 (all data).
[10] E. Negishi, Organometallics in Organic Synthesis, Vol. 1, Wiley, New
York, 1980, pp. 136–178.
10e: C19H20O2, MW =280.35; crystal size 0.60ꢁ0.20ꢁ0.08 mm; monoclin-
ic; space group P21/c; a=10.42773(19), b=12.0634(2), c=12.3870(2) ꢂ;
[11] R. G. Salomon, S. Ghosh, Org. Synth. 1990, Coll. Vol. VII, 177–183.
[12] Y. Kayaki, T. Koda, T. Ikariya, Eur. J. Org. Chem. 2004, 4989–4993.
b=96.5130(10)8; V=1548.14(5) ꢂ3; Z=4; T=193 K; Dx =1.203 gcmÀ3
;
mCu-Ka =0.602 mmÀ1; Rint =0.0349; number of measured/independent re-
flections=27683/2841; R=0.0397 and wR(F2)=0.1037 (all data).
Received: November 11, 2008
Published online: January 29, 2009
2686
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 2680 – 2686