Asymmetric syntheses of chiral allylic alcohols

Article abstract of DOI:10.1055/s-1998-6103

Chiral allylic alcohols 2 can easily be obtained by elimination from iodo ketals 10. These are available from natural sources, or by application of the asymmetric Sharpless dihydroxylation to vinylogous esters 6, subsequent reduction, halogenation and elimination. This protocol allows the synthesis of highly functionalized allylic alcohols, which can be used in asymmetric Claisen rearrangements.

Full text of DOI:10.1055/s-1998-6103

SYNTHESIS
Papers
1314
Asymmetric Syntheses of Chiral Allylic Alcohols
Christiane Schneider, Uli Kazmaier*
Organisch-Chemisches Institut der Universität, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany
Fax +49(6221)544205; E-mail: ck1@ix.urz.uni-heidelberg.de
Received 10 February 1998; revised 24 February 1998
Abstract: Chiral allylic alcohols 2 can easily be obtained by elim-
epimeric allylic alcohols were obtained by vinylmagne-
sium chloride addition to the corresponding aldehyde.
Starting from achiral aldehydes 1 racemic alcohols 2 are
obtained, while chiral aldehydes provide an epimeric mix-
ture of anti- and syn-configurated alcohols (Scheme 1, Ta-
ble 1).
ination from iodo ketals 10. These are available from natural
sources, or by application of the asymmetric Sharpless dihydroxy-
lation to vinylogous esters 6, subsequent reduction, halogenation
and elimination. This protocol allows the synthesis of highly func-
tionalized allylic alcohols, which can be used in asymmetric
Claisen rearrangements.
Key words: asymmetric dihydroxylation, chiral allylic alcohol,
diols, elimination, vinylogous esters
For several years, highly functionalized γ,δ-unsaturated
amino acids have been of great interest because of their
biological activity.1 Many of them show antibiotic prop-
erties,2 whereas they are also intermediates for the synthe-
sis of complex amino acids and peptides.3
Scheme 1
Table 1. Synthesis of Racemic and Epimeric Allylic Alcohols
Aldehyde
R
Yield
(%)
Ratio
Product
Besides electrophilic and nucleophilic allylations,4 [3.3]-
sigmatropic rearrangements are especially suited for the
introduction of allylic side chains.5 If the reaction is car-
ried out with derivatives of chiral allylic alcohols or
amines, the Claisen rearrangement yields optically active
amino acids.6 Therefore chiral allylic alcohols are highly
interesting synthetic targets. Besides kinetic resolution
procedures, e.g. via asymmetric Sharpless epoxidation,7
or via enzymatic techniques,8 the de novo syntheses of
chiral allylic centers are of special interest. For this pur-
pose also the Sharpless epoxidation of achiral alcohols
can be used,9 but other approaches, like the stereoselec-
tive reductions of vinylogous ketones,10 or the addition of
organometallics to aldehydes in the presence of chiral
ligands,11 are becoming more and more important.
anti/syna
1a
1b
Ph
BnOCH2
63
42
–
–
2a
2b
1c
54
60
60:40
60:40
2c
1d
2d
1e
67
65:35
2e
Recently, we have developed a new variation of the ester
enolate Claisen rearrangement proceeding via chelated al-
lylic ester enolates.12 This procedure is especially suitable
for the generation of various types of γ,δ-unsaturated ami-
no acids.13 Because of our interest in the synthesis of poly-
hydroxylated amino acids and alkaloids,14 we were look-
ing for a general synthetic route especially to oxygenated
allylic alcohols. Herein and in the following paper we de-
scribe the synthesis of functionalized chiral allylic alco-
hols and subsequent ester enolate Claisen rearrangement
of the corresponding chiral allylic amino acid esters,
which gives rise to the respective chiral amino acids in a
highly enantio- as well as diastereoselective fashion.
a
Determined by HPLC and NMR.
The stereochemical outcome of the Grignard addition to
2,3-O-isopropylidene glyceraldehyde was investigated
by Mulzer et al.16 An anti/syn relationship of around 6:4
was observed in most cases. Similar results were also ob-
tained in the vinylmagnesium chloride addition to vari-
ous oxygenated chiral aldehydes (Table 1, entries 3–5).
The trans-configurated substituted allylic alcohol 2f was
obtained from 2,3-O-isopropylidene-D-glyceraldehyde
(1c) by addition of lithium acetylide 3 (anti/syn 6:4) and
The optically active allylic alcohols required for the prep- subsequent reduction of the propargylic alcohol 4 with
aration of the allylic esters were obtained in a few steps LiAlH4 (Scheme 2).
from chiral pool materials or via a dihydroxylation route,
Highly oxygenated natural products like tartaric acid or
using the Sharpless protocol.15
sugars are especially suitable for the stereoselective syn-
For analytical purposes, especially the determination of thesis of these functionalized allylic alcohols, and enanti-
the optical purity of the allylic alcohols and the amino omerically pure 2b and 2c were obtained by this approach
acids obtained by Claisen rearrangement, racemic and (Scheme 3).

SYNTHESIS
September 1998
1315
Starting from easy accessible α,β-unsaturated esters 6,
asymmetric dihydroxylation (AD) leads to chiral diols 7
(Scheme 4).
Both enantiomeric diols 7a and ent-7a can be obtained in
a highly stereoselective fashion (98% ee) from achiral
cinnamoyl esters 6a, depending on the ligand used (Table
2, entries 1, 2). Using chiral α,β-unsaturated esters like
6d22 and 6e,23 AD proceeded via double diastereoselec-
tion with particularly high anti-selectivities (98% ds) in
Scheme 2
Scheme 3
Starting from dimethyl tartrate, alcohol 5b was easily ob-
tained.17 Conversion into the iodide18 and subsequent
elimination using activated zinc19 in ethanol provided
2b20 in overall good yield. According to Mulzer et al. al-
cohol 2c was obtained from mannitol by a similar proto-
col. In this case the iodide was obtained by Finkelstein
reaction from the corresponding tosylate.21
The Sharpless dihydroxylation15 of olefins is especially
suitable for the de novo generation of chirality centers.
Scheme 4
Table 2. Synthesis of Chiral Allylic Alcohols via Sharpless Dihydroxylation
Ester Sharpless Dihydroxylation
Ketalization
Reduction
Iodination
Elimination
R
Ligand
Yield Diol
(%)
Yield Ketal Yield Alco- Yield Iodide Yield Alco-
Config
(%)
97
(%)
92
hol
(%)
81
(%)
89
hol
6a
6a
Ph
Ph
(DHQD)2PHAL 88
(DHQ)2PHAL 85
7a
8a
5a
10a
2a
(S)
ent-7a 96
ent-8a 89
ent-5a 80
ent-10a 86
ent-2a (R)
6d
(DHQD)2PHAL 74
7d
7e
90
88
8d
8e
88
98
5d
5e
86
81
10d
10e
86
93
2d
2e
(2S,3S,4S)
6e
(DHQ)2PHAL
94
(2S,3R,
4S,5R)

SYNTHESIS
Papers
1316
the matched case (entries 3, 4).24 Protection of the diols 7
to the corresponding ketals 8 and reduction of the ester
functionality yielded the alcohols 5. These were treated as
described before. Tosylation of the primary hydroxy
group gave 9 and subsequent iodination resulted in the
formation of the iodide 10. After elimination with zinc in
ethanol, the anti-configurated chiral allylic alcohols 2
were obtained in good yields and in nearly optically pure
form (98% ds).25
Asymmetric Dihydroxylation of α,â-Unsaturated Esters 6; Gen-
eral Procedure:
Following the Sharpless protocol,15 K3[Fe(CN)6] (3 mmol), K2CO3
(3 mmol) and methanesulfonamide (1 mmol) were suspended in wa-
ter (5 mL) and t-BuOH (5 mL). Under vigorous stirring OsO4
(0.01 mmol) and the corresponding ligand [(DHQ)2PHAL or
(DHQD)2PHAL] (0.01 mmol) were added at 0°C. Stirring was con-
tinued for further 5 min, before the vinylogous ester 6 (1 mmol) was
added. The vigorously stirred mixture was allowed to warm to r.t.
overnight. The mixture was cooled to 0°C again, before solid Na2SO3
(12 mmol) was added. After stirring for 1 h, H2O was added slowly,
until all salts were dissolved. The aqueous layer was extracted three
times with EtOAc, the combined organic layers were dried (Na2SO4),
and the solvent was removed in vacuo. The crude product was puri-
fied by flash chromatography (EtOAc/petroleum ether).
The anti-configurated substituted alcohol 2f was synthe-
sized (Scheme 5) from the tosyl hydrazone of protected D-
aldehydo arabinose.26 Reaction with 2 equivalents of
BuLi gave the expected allylic alcohol as an E/Z mixture
(E/Z 2:1).
Ketalization of the Diols 7; General Procedure:
To a solution of diol 7 (1 mmol) in acetone (0.5 mL) and 2,2-
dimethoxypropane (1 mL) p-TsOH (0.05 mmol) was added. After
stirring for 24 h, anhyd Na2CO3 (1 mmol) was added. After filtration,
the solvent was removed in vacuo. The residue obtained was purified
by flash chromatography (EtOAc/petroleum ether).
Reduction of the Esters 8; General Procedure:
A solution of 8 (1 mmol) in Et2O (2 mL) was added slowly to a stirred
suspension of LiAlH4 (1.1 mmol) in abs Et2O at 0°C under argon. The
mixture was allowed to warm to r.t. during 12 h. After repeated cool-
ing to 0°C water (0.05 mL), 15% NaOH (0.05 mL) and water
(0.15 mL) were successively added. The precipitate formed (after
stirring for 1 h) was removed by filtration and the solvent was evapo-
rated in vacuo. The residue obtained was purified by flash chromato-
graphy (EtOAc/petroleum ether).
Scheme 5
Tosylation of the Alcohols 5; General Procedure:
p-TsCl (1.5 mmol) in abs pyridine (0.5 mL) was added to a solution
of alcohol 5 (1 mmol) in abs pyridine (1 mL) at 0 ˚C. After removal
of the ice bath, the mixture was stirred for 24 h, before water and Et2O
(10 mL each) were added, and the layers were separated. The aqueous
layer was extracted with Et2O (2 × 10 mL). The combined organic
layers were subsequently washed with 1 N KHSO4 and brine, and
dried (Na2SO4). After evaporation of the solvent in vacuo, the residue
obtained was crystallized from CH2Cl2/petroleum ether.
This mixture was converted into the pure E-alcohol by
photochemical isomerization. Therefore the mixture was
irradiated in cyclohexane with a 150-W UV lamp for 12
hours in the presence of bis(3-cyano-4,6-dimethyl-2-
pyridyl) disulfide27 until no Z-isomer could be detected by
GC.
In conclusion, we have described a general applicable
procedure for the synthesis of highly functionalized chiral
allylic alcohols. These alcohols can be converted into the
corresponding allylic esters, which are suitable substrates
for asymmetric Claisen rearrangements (see following pa-
per).
Finkelstein Reaction with Tosylates 9; General Procedure:
A suspension of tosylate 9 (1 mmol) and NaI (50 mmol) in a mixture
of acetone (20 mL) and MeCN (8 mL) was refluxed for 24 h. If the
reaction was complete (TLC control), water and Et2O were added,
until two layers were formed. After separation of the organic layer,
the aqueous layer was extracted twice with Et2O. The combined or-
ganic layers were dried (Na2SO4), and the solvent was removed in
vacuo. The crude product was purified by flash chromatography
(EtOAc/petroleum ether).
Most reactions were carried out in oven-dried glassware (100°C) un-
der argon. All solvents were dried before use. THF was distilled from
sodium benzophenone, CH2Cl2 and i-Pr2NH from CaH2. The starting
materials and the products were purified by flash chromatography on
silica gel (32–63 µm). Mixtures of EtOAc and petroleum ether (40–
60°C) were generally used as eluents. TLC: commercially precoated
Polygram SIL-G/UV 254 plates (Macherey–Nagel). Visualization
Synthesis of Allylic Alcohols 2; General Procedure:
Zinc dust (8.5 mmol) was added to a solution of iodide 10 (1 mmol)
in abs EtOH (25 mL), and the suspension was refluxed for 4 h. After
filtration through Celite, the solvent was removed in vacuo. The crude
product was purified by flash chromatography (EtOAc/petroleum
ether).
1
was accomplished with UV light, I2, and KMnO4 soln. H and 13C
NMR: Bruker AC-300 spectrometer. Enantiomeric and diastereomer-
ic ratios were determined by analytical HPLC using a Knauer Euro-
sphere column (250 × 4 mm, Si80, 5 µm, flow: 2 mL/min), as well as
a Chiracel-OD-H column (Daicel) (0.5 mL/min) and a Knauer UV
detector. Optical rotations were measured on a Perkin–Elmer pola-
rimeter PE 241.
(2R,3S,4E)-1,2-(Isopropylidenedioxy)non-4-en-3-ol (2f):
2f was obtained by photochemical isomerization of the corresponding
(E/Z)-mixture, which was obtained according to the literature.26

SYNTHESIS
September 1998
1317
Table 3. Analytical and Spectroscopic Data of Compounds 2, 5 and 7–10
continued
Com-
pound
[α]D20
(c, Solvent)
1H NMR (300 MHz, CDCl3)
δ, J (Hz)
13C NMR (75 MHz, CDCl3)
δ
2a28
+ 5.2
(0.3, CHCl3)
2.03 (sbr, 1H, OH), 5.17–5.24 (m, 1H, CHOH), 5.20 (d, J = 75.38 (d, C–OH), 115.13 (t, C=CH2), 126.34,
9.9, 1H, CHCH=CHHt), 5.36 (ddd, J = 17.3, 1.1, 1.1, 1H, 127.77, 128.58 (3d, ArC), 140.27 (d, CH=CH2),
CHCH=CHHc), 6.06 (ddd, J = 16.5, 9.9, 6.1, 1H, 142.62 (s, quart. ArC)
CHCH=CH2), 7.28–7.39 (m, 5H, ArH)
ent-2a29
–5.2
(0.3, CHCl3)
2.03 (sbr, 1H, OH), 5.17–5.25 (m, 1H, CHOH), 5.20 (d, J = 75.39 (d, CHOH), 115.13 (t, C=CH2), 126.36,
9.9, 1H, CH=CHHt), 5.35 (ddd, J = 17.3, 1.1, 1.1, 1H, 127.78, 128.59 (3d, ArC), 140.28 (d, CH=CH2),
CH=CHHc), 6.06 (ddd, J = 16.5, 9.9, 6.1, 1H, CH=CH2), 142.64 (s, quart. ArC)
7.26–7.40 (m, 5H, ArH)
2b20
+ 5.4
2.58 (sbr, 1H, OH), 3.39 (dd, J = 9.6, 8.1, 1H, BnOCH2), 3.55 71.53 (t, PhCH2), 73.41 (t, BnOCH2), 74.09 (d,
(0.36, CHCl3) (dd, J = 9.6, 3.4, 1H, BnOCH2), 4.33–4.38 (m, 1H, CHOH), CHOH), 116.41 (t, C=CH2), 127.80, 127.84,
4.58 (s, 2H, PhCH2), 5.20 (dd, J = 10.6, 1.4, 1H, CH=CHHt), 128.49 (3d, ArC), 136.70 (d, CH=CH2), 137.89
5.37 (dd, J = 17.3, 1.5, 1H, CH=CHHc), 5.85 (ddd, J = 17.2, (s, quart. ArC)
10.6, 5.5, 1H, CH=CH2), 7.26–7.42 (m, 5H, ArH)
2c21
+ 1.7
(1.2, CHCl3)
1.36 (s, 3H, CH3), 1.44 (s, 3H, CH3), 2.19 (sbr, 1H, OH), 3.90 25.12 (q, CH3), 26.43 (q, CH3), 64.72 (t, CH2O),
(dd, J = 8.3, 6.8, 1H, CH2O), 3.96 (dd, J = 8.3, 6.5, 1H, 71.89 (d, CHOC), 78.11 (d, CHOH), 109.44 [s,
CH2O), 4.12 (mc, 1H, CHOC), 4.29 (mc, 1H, CHOH), 5.24 C(CH3)2], 116.92 (t, C=CH2), 135.77 (d,
(ddd, J = 10.6, 1.5, 1H, CH=CHHt), 5.38 (ddd, J = 17.3, 1.5, CH=CH2)
1.5, 1H, CH=CHHc), 5.83 (ddd, J = 17.2, 10.6, 5.5, 1H,
CH=CH2)
2d
–21.6
(1.1, CHCl3)
1.43 (s, 3H, CH3), 1.44 (s, 3H, CH3), 2.71 (d, J = 2.6, 1H, 26.94 (q, CH3), 70.70 (t, PhCH2), 72.29 (d,
OH), 3.61 (dd, J = 12.9, 4.8, 1H, CH2OBn), 3.64 (dd, J = 12.9, CHOH), 73.61 (t, CH2O), 76.96 (d, CHOC),
5.2, 1H, CH2OBn), 3.84 (dd, J = 8.1, 5.5, 1H, CHOC), 4.14 80.91 (d, CHOC), 109.37 [s, C(CH3)2], 116.68
(ddd, J = 7.7, 5.2, 4.8, 1H, CHOC), 4.25 (mc, 1H, CHOH), (t, C=CH2), 127.79, 127.85, 128.44, (3d, ArC),
4.58 (d, J = 12.1, 1H, PhCH2), 4.63 (d, J = 12.1, 1H, PhCH2), 136.02 (s, quart. ArC), 136.06 (d, CH=CH2)
5.29 (ddd, J = 10.3, 1.5, 1.5, 1H, CH=CHHt), 5.23 (ddd,
J = 17.3, 1.5, 1.5, 1H, CH=CHHc),5.86 (ddd, J = 17.3, 10.3,
5.5, 1H, CH=CH2), 7.28–7.39 (m, 5H, ArH)
2e30
+ 22.9
(3.4, CHCl3)
1.37–1.45 (m, 12H, CH3), 3.34 (d, J = 2.6, 1H, OH), 3.72– 25.12 (q, CH3), 26.42 (q, CH3), 26.88 (q, CH3),
3.84 (m, 2H, CHO), 3.98–4.21 (m, 4H, CHO), 5.26 (ddd, J = 67.87 (t, CH2O), 73.30 (d, CHO), 76.59 (d,
10.5, 1.4, 1.4, 1H, CH=CHHt), 5.43 (ddd, J = 17.2, 1.5, 1.5, CHO), 80.47 (d, CHO), 83.16 (d, CHO), 109.62
1H, CH=CHHc), 6.00 (ddd, J = 17.2, 10.7, 6.1, 1H, CH=CH2) [s, C(CH3)2], 110.17 [s, C(CH3)2], 116.69 (t,
C=CH2), 136.79 (d, CH=CH2)
2f26
+ 29.4
(1.1, CHCl3)
0.89 (t, J = 7.1, 3H, CH2CH3), 1.29–1.35 (m, 4H, CH2), 1.36 13.85 (q, CH2CH3), 22.15 (t, CH2CH3), 25.18 [q,
[s, 3H, C(CH3)2], 1.44 [s, 3H, C(CH3)2], 2.01–2.16 (m, 3H, C(CH3)2], 26.42 [q, C(CH3)2], 31.16 (t, CH2),
C=CHCH2, OH), 3.85–3.98 (m, 2H, CH2O), 4.10 (dt, J = 6.6, 32.01 (t, CH2), 64.67 (t, CH2O), 71.65 (d, CHO),
4.0, 1H, CHOC), 4.25 (mc, 1H, CHOH), 5.39 (ddt, J = 15.4, 78.48 (d, CHO), 109.29 [s, C(CH3)2], 127.18 (d,
6.4, 1.4, 1H, CHOHCH=C), 5.77 (ddt, J = 14.9, 6.9, 1.1, 1H, CHOHCH=C), 134.47 (d, C=CHCH2)
C=CHCH2)
5a31
+ 19.4
1.53 (s, 3H, CH3), 1.59 (s, 3H, CH3), 2.15 (dd, J = 8.2, 4.4, 27.11 (q, CH3), 27.15 (q, CH3), 53.40 (t,
(3.0, CH2Cl2) 1H, OH), 3.64 (ddd, J = 12.6, 8.2, 4.4, 1H, CHOC), 3.84–3.90 CH2OH), 78.69 (d, CHO), 83.61 (d, CHO),
(m, 2H, CH2OH), 4.91 (d, J = 8.5, 1H, PhCHO), 7.29–7.42 109.32 [s, C(CH3)2], 126.54, 128.34, 128.65 (3d,
(m, 5H, ArH)
ArC), 127.75 (s, quart. ArC)
ent-5a32
–19.5
1.53 (s, 3H, CH3), 1.59 (s, 3H, CH3), 2.14 (dd, J = 8.2, 4.3, 27.11 (q, CH3), 27.16 (q, CH3), 53.41 (t,
(3.1, CH2Cl2) 1H, OH), 3.64 (ddd, J = 12.6, 8.2, 4.3, 1H, CHOC), 3.82–3.91 CH2OH), 78.69 (d, CHO), 83.62 (d, CHO),
(m, 2H, CH2OH), 4.91 (d, J = 8.2, 1H, PhCHO), 7.29–7.42 109.32 [s, C(CH3)2], 126.55, 128.35, 128.65 (3d,
(m, 5H, ArH)
ArC), 137.75 (s, quart. ArC)
5d
–14.5
(1.2, CHCl3)
1.31 (s, 3H, CH3), 1.38 (s, 3H, CH3), 1.39 (s, 3H, CH3), 1.43 26.80 (q, CH3), 26.93 (q, CH3), 27.04 (q, CH3),
(s, 3H, CH3), 2.16 (sbr, 1H, OH), 3.59 (dd, J = 10.6, 6.0, 62.62 (t, CH2OH), 70.21 (t, CH2OBn), 73.43 (t,
CHOC), 3.70–3.84 (m, CHOC, CH2OH), 4.03 (ddd, J = 8.1, PhCH2O), 77.87 (d, CHO), 79.18 (d, CHO),
8.1, 4.0, 1H, CHOC), 4.20 (ddd, J = 6.3, 6.3, 4.2, 1H, CHOC), 80.35 (d, CHO), 80.97 (d, CHO), 109.04 [s,
4.59 (d, J = 12.4, 1H, PhCH2), 4.63 (d, J = 12.4, 1H, PhCH2), C(CH3)2], 110.22 [s, C(CH3)2], 127.54, 127.64,
7.27–7.35 (m, 5H, ArH)
128.28 (3d, ArC), 138.10 (s, quart. ArC)
5e
+ 7.2
(3.6, CHCl3)
1.33–1.43 (m, 18H, CH3), 2.23 (dd, J = 8.2, 4.7, 1H, OH), 25.34, 26.40, 26.57, 26.88, 27.07, 27.51 (6q,
3.71 (ddd, J = 12.2, 8.2, 4.3, 1H, CH2OH), 3.79–4.13 (m, 7H, CH3), 62.69 (t, CH2OH), 65.98 (t, CH2OC),
1-Hb, CHOC, CH2OH, CH2OC), 4.23 (dd, J = 11.9, 5.0, 1H, 76.06, 78.98, 79.45, 79.97, 90.07 (5d, CHO),
CH2OC)
109.55, 109.65, 110.52 [3s, C(CH3)2]

SYNTHESIS
Papers
Table 3. continued
1318
Com-
pound
[α]D20
(c, Solvent)
1H NMR (300 MHz, CDCl3)
δ, J (Hz)
13C NMR (75 MHz, CDCl3)
δ
7d
+ 8.8
(1.0, CHCl3)
1.30 (t, J = 7.1, 3H, CH2CH3), 1.39 (s, 3H, CH3), 1.40 (s, 3H, 14.17 (q, CH2CH3), 26.23 (q, CH3), 26.92 (q,
CH3), 3.11 (d, J = 6.9, 1H, 2-OH), 3.37 (d, J = 4.3, 1H, 3-OH), CH3), 61.97 (t, CH2CH3), 70.53 (t, CH2OBn),
3.54 (dd, J = 9.3, 7.0, 1H, CHOH), 3.73 (dd, J = 9.3, 4.8, 1H, 70.83 (d, CHOC), 73.76 (d, CHOC), 73.82 (t,
CHOH), 3.90 (dd, J = 15.1, 9.8, 2H, CH2OBn), 4.11 (mc, 1H, PhCH2O), 78.50 (d, CHOH), 78.64 (d, CHOH),
CHOC), 4.28 (dq, J = 7.1, 1.5, 2H, CH2CH3), 4.39 (d, J = 6.6, 109.68 [s, C(CH3)2], 127.98, 128.07, 128.54 (3d,
1H, CHOC), 4.56 (d, J = 12.1, 1H, PhCH2O), 4.62 (d, J = ArC), 136.99 (s, quart. ArC), 173.24 (s, C=O)
12.1, 1H, PhCH2O), 7.28–7.37 (m, 5H, ArH)
7e23
–9.9
(1.3, CHCl3)
1.31 (t, J = 7.1, 3H, CH2CH3), 1.34 (s, 3H, CH3), 1.38 (s, 3H, 14.18 (q, CH2CH3), 25.04 (q, CH3), 26.31 (q,
CH3), 1.39 (s, 3H, CH3), 1.43 (s, 3H, CH3), 3.02 (d, J = 8.0, CH3), 26.91 (q, CH3), 61.82 (t, CH2CH3),
1H, OH), 3.05 (d, J = 7.9, 1H, OH), 3.75–3.80 (m, 2H, 67.96 (t, CH2OC), 70.89 (d, CHOC), 73.66 (d,
CHOH), 3.88 (d, J = 9.0, 1H, CHOC), 3.97–4.09 (m, 3H, CHOC), 76.40 (d, CHOC), 78.96 (d, CHOH),
CHOC), 4.20 (dd, J = 8.2, 5.7, 1H, CHOC), 4.25–4.30 (m, 81.19 (d, CHOH), 109.93 [s, C(CH3)2], 110.37
CH2CH3)
[s, C(CH3)2], 173.21 (s, C=O)
8d
+ 7.6
(1.1, CHCl3)
1.28 (t, J = 7.1, CH2CH3), 1.41 (2s, 6H, CH3), 1.43 (2s, 6H, 14.08 (q, CH2CH3), 26.02, 26.97, 27.12, 27.23
CH3), 3.61 (dd, J = 10.4, 5.5, 1H, CH2OBn), 3.69 (dd, J = (4q, CH3), 61.44 (t, CH2CH3), 70.56 (t,
10.4, 3.8, 1H, CH2OBn), 3.99 (dd, J = 7.4, 6.4, 1H, CHOC), CH2OBn), 73.51 (t, PhCH2O), 77.04, 78.11,
4.20–4.27 (m, 3H, CHOC, CH2CH3), 4.35 (dd, J = 6.1, 6.1, 78.42, 79.92 (4d, CHOC), 110.14 [s, C(CH3)2],
1H, CHOC), 4.53 (d, J = 5.8, 1H, CHOC), 4.60 (sbr, 2H, 112.01 [s, C(CH3)2], 127.61, 127.65, 128.33 (3d,
PhCH2O), 7.27–7.34 (m, 5H, ArH)
ArC), 138.06 (s, quart. ArC), 170.95 (s, C=O)
8e
9a
+ 3.7
(0.6, CHCl3)
1.29 (t, J = 7.2, 3H, CH2CH3), 1.33–1.42 (m, 18H, CH3), 14.12 (q, CH2CH3), 15.23, 25.92, 26.47, 26.98,
3.92–4.02 (m, 2H, CH2CH3), 4.04–4.14 (m, 2H, CH2OC), 27.25, 27.57 (6q, CH3), 61.45 (t, CH2CH3),
4.18–4.31 (m, 3H, CHOC), 4.46 (dd, J = 6.0, 4.4, 1H, 67.18 (t, CH2OC), 75.74, 76.76, 78.43, 79.35,
CHOC), 4.63 (d, J = 6.1, CHOC)
79.56 (5d, CHOC), 109.77, 110.40, 111.88 [3s,
C(CH3)2], 171.34 (s, C=O)
–0.3
(3.9, CHCl3)
1.45 (2s, 3H, CH3), 1.52 (2s, 3H, CH3), 2.45 (s, 3H, ArCH3), 21.63 (q, ArCH3), 26.73 (q, CH3), 27.04 (q,
3.90 (ddd, J = 8.4, 4.1, 3.3, 1H, CHOC), 4.11 (dd, J = 11.0, CH3), 67.37 (t, CH2OTos), 79.05 (d, CHOC),
4.2, 1H, CH2OC), 4.24 (dd, J = 11.0, 3.2, 1H, CH2OC), 4.83 80.63 (d, CHOC), 110.01 [s, C(CH3)2], 126.51,
(d, J = 8.5, 1H, PhCHOC), 7.26–7.38 (m, 7H, ArH), 7.77 (d, 128.03, 128.59, 128.73, 129.85 (5d, ArC),
J = 8.3, 2H, ArH)
132.88 (s, ArCCH3), 136.97 (s, quart. ArC),
144.94 (s, quart. ArC)
ent-9a
+ 0.3
(3.2, CHCl3)
1.45 (s, 3H, CH3), 1.52 (s, 3H, CH3), 2.45 (s, 3H, ArCH3), 21.63 (q, ArCH3), 26.74 (q, CH3), 27.04 (q,
3.91 (ddd, J = 8.2, 4.1, 3.4, 1H, CHOC), 4.11 (dd, J = 11.0, CH3), 67.38 (t, CH2OTos), 79.06 (d, CHOC),
4.2, 1H, CH2OTos), 4.24 (dd, J = 11.0, 3.2, 1H, CH2OTos), 80.63 (d, CHOC), 110.01 [s, C(CH3)2], 126.52,
4.83 (d, J = 8.5, 1H, PhCHOC), 7.24–7.37 (m, 7H, ArH), 7.77 128.03, 128.60, 128.73, 129.85 (5d, ArC),
(d, J = 8.3, 2H, ArH)
132.89 (s, ArCCH3), 136.98 (s, quart. ArC),
144.94 (s, quart. ArC)
9d
+ 3.8
(3.3, CHCl3)
1.27 (s, 3H, CH3), 1.30 (s, 3H, CH3), 1.31 (s, 3H, CH3), 1.38 21.61 (q, ArCH3), 26.76, 26.94, 27.03 (3q,
(s, 3H, CH3), 2.44 (s, 3H, ArCH3), 3.40 (d, J = 10.9, 1H, CH3), 69.23 (t, CH2OTos), 70.22 (t, CH2OBn),
CH2OBn), 3.56 (dd, J = 10.6, 5.9, 1H, CH2OBn), 3.69–3.78 73.48 (t, PhCH2O), 77.71, 78.07, 78.19, 80.20
(m, 2H, CHOC), 4.06–4.13 (m, 3H, CHOC, CH2OTos), 4.29 (4d, CHOC), 110.21 [s, C(CH3)2], 110.64 [s,
(dd, J = 12.4, 4.2, 1H, CH2OTos), 4.57 (d, J = 12.2, 1H, C(CH3)2], 127.62, 127.66, 128.08, 128.32,
PhCH2O), 4.62 (d, J = 12.2, 1H, PhCH2O), 7.26–7.34 (m, 7H, 129.76 (5d, ArC), 133.04 (s, ArCCH3), 138.12
ArH), 7.80 (d, J = 7.8, 2H, ArH)
(s, quart. ArC) 144.79 (s, quart. ArC)
9e
–7.3
(0.5, MeOH)
1.31–1.40 (m, 18H, CH3), 2.44 (s, 3H, ArCH3), 3.86–4.20 (m, 21.61 (q, ArCH3), 25.31, 26.41, 26.86, 26.97,
8H, CHOC, CH2OTos), 4.27 (dd, J = 10.5, 2.5, 1H, 27.41, 27.45 (6q, CH3), 66.19 (t, CH2OC),
CH2OTos), 7.33 (d, J = 8.1, 2H, ArH), 7.80 (d, J = 8.3, 2H, 69.29 (t, CH2OTos), 76.07, 77.12, 77.27,
ArH)
79.54, 79.84 (5d, CHOC), 109.68, 110.48,
110.52 [3s, C(CH3)2], 128.06, 129.78 (2d,
ArC), 133.00 (s, ArCCH3), 144.84 (s, quart.
ArC)
10a
+ 35.7
(3.9, CHCl3)
1.51 (s, 6H, CH3), 3.17 (dd, J = 11.0, 5.0, 1H, CH2I), 3.33 (dd, 4.56 (t, CH2I), 27.27 (q, CH3), 27.36 (q, CH3),
J = 11.0, 3.7, 1H, CH2I), 3.53 (ddd, J = 8.1, 4.8, 3.5, 1H, 81.36 (d, CHO), 83.27 (d, CHO), 109.52 [s,
CHOC), 4.66 (d, J = 8.0, 1H, PhCHOC), 7.26–7.34 (m, 5H, C(CH3)2], 126.63, 128.61, 128.73 (3d, ArC),
ArH)
137.00 (s, quart. ArC)

SYNTHESIS
September 1998
1319
Table 3. continued
Com-
pound
[α]D20
(c, Solvent)
1H NMR (300 MHz, CDCl3)
δ, J (Hz)
13C NMR (75 MHz, CDCl3)
δ
ent-10a
–35.9
(3.9, CHCl3)
1.51 (s, 6H, CH3), 3.17 (dd, J = 11.2, 5.0, 1H, CH2I), 3.33 (dd, 4.56 (t, CH2I), 27.26 (q, CH3), 27.36 (q, CH3),
J = 11.1, 3.7, 1H, CH2I), 3.53 (ddd, J = 8.1, 4.8, 3.7, 1H, 81.34 (d, CHO), 83.26 (d, CHO), 109.52 [s,
CHOC), 4.66 (d, J = 8.1, 1H, PhCHOC), 7.26–7.34 (m, 5H, C(CH3)2], 126.62, 128.61, 128.72 (3d, ArC),
ArH)
137.00 (s, quart. ArC)
10d
+ 5.7
(0.5, CHCl3)
1.30 (s, 3H, CH3), 1.38 (s, 3H, CH3), 1.41 (s, 3H, CH3), 1.43 7.06 (t, CH2I), 26.84, 26.88, 27.02, 27.17 (4q,
(s, 3H, CH3), 3.36 (dd, J = 10.8, 5.5, 1H, CH2I), 3.49 (dd, J = CH3), 70.08 (t, CH2OBn), 73.24 (t, PhCH2),
10.7, 3.3, 1H, CH2I), 3.56 (dd, J = 10.8, 5.8, 1H, CHOC), 77.65, 78.95, 79.96, 81.62 (4d, CHO), 109.86
3.67–3.80 (m, 4H, CHOC), 4.16–4.19 (m, 1H, CHOC), 4.57 [s, C(CH3)2], 110.01 [s, C(CH3)2], 127.34,
(d, J = 13.6, 1H, PhCH2), 4.62 (d, J = 13.6, 1H, PhCH2), 7.24– 127.44, 128.08 (3d, ArC), 137.91 (s, quart.
7.33 (m, 5H, ArH)
ArC)
10e
–12.4
(1.0, CHCl3)
1.36–1.47 (m, 18H, CH3), 3.32 (dd, J = 10.8, 5.2, 1H, CH2I), 7.51 (t, CH2I), 25.33, 26.49, 27.26, 27.51,
3.50 (dd, J = 10.8, 3.5, 1H, CH2I), 3.83 (dd, J = 14.0, 7.0, 1H, 27.72 (5q, CH3), 66.20 (t, CH2O), 76.16,
CHOC), 3.88–3.93 (m, 1H, CHOC), 3.95–4.00 (m, 2H, 78.15, 79.50, 79.86, 81.24 (5d, CHO), 109.70,
CHOC), 4.05–4.12 (m, 2H, CHOC, CH2OC), 4.20 (dd, J = 109.98, 110.58 [3s, C(CH3)2]
12.1, 6.0, 1H, CH2OC)
Therefore a solution of (E/Z)-2f (1 g, 4.67 mmol, E/Z 7:3) and bis(3-
cyano-4,6-dimethyl-2-pyridyl) disulfide27 (14 mg, 0.05 mmol) in cy-
clohexane (500 mL) was irradiated for 5 h in a photoreactor with a
150-W high pressure lamp At this point an E/Z ratio of 86:14 was
obtained. After addition of further bis(3-cyano-4,6-dimethyl-2-
pyridyl) disulfide (14 mg, 0.05 mmol) and irradiation for 8 h, no
Z-isomer could be detected by GC. Flash chromatography (EtOAc/
petroleum ether 15:85) gave 2f (810 mg, 81%) as a colorless oil.
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