Conversion of chiral unsaturated cyanohydrins into chiral carba- and heterocycles via ring-closing metathesis

Article abstract of DOI:10.1016/j.tet.2004.07.103

Aliphatic unsaturated cyanohydrins 1-3 served as starting materials in the synthesis of a set of new chiral unsaturated cyclic 1,2-ethanolamines. Combining a Grignard addition-NaBH₄ reduction sequence with a ring-closing metathesis afforded uns

Full text of DOI:10.1016/j.tet.2004.07.103

Tetrahedron 60 (2004) 10385–10396
Conversion of chiral unsaturated cyanohydrins into chiral
carba- and heterocycles via ring-closing metathesis
Adrianus M. C. H. van den Nieuwendijk, Amar B. T. Ghisaidoobe, Herman S. Overkleeft,
*
Johannes Brussee and Arne van der Gen
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands
Received 21 May 2004; revised 21 July 2004; accepted 28 July 2004
Available online 27 August 2004
Abstract—Aliphatic unsaturated cyanohydrins 1–3 served as starting materials in the synthesis of a set of new chiral unsaturated cyclic 1,2-
ethanolamines. Combining a Grignard addition–NaBH4 reduction sequence with a ring-closing metathesis afforded unsaturated cyclic 1,2-
ethanolamines 7–11 and 22–25 in good yields and high ee (96–99%). The conversion of cyanohydrins 1–3 via a DIBAL reduction–
transimination–NaBH4 reduction sequence, using allylamine, followed by ring-closing metathesis yielded tetrahydropyridines 28,
tetrahydroazepinols 33 and tetrahydroazocinols 34 in high yields and excellent ee (97–99%).
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
ology for the synthesis of chiral unsaturated cyclic 1,2-
ethanolamines (Scheme 1, path a).
Chiral non-racemic cyanohydrinshave proven to be expedient
starting materials for the synthesis of several classes of
compounds.1–6 Over the past twenty years our research has
focussed on the synthesis and application of chiral cyano-
hydrins with high enantiomeric purity, employing the
enzyme hydroxynitrile lyase (PaHNL, E.C. 4.1.2.10) from
almonds. In previous communications we reported on the
synthesis of several aliphatic unsaturated cyanohydrins.7–9
Three particular examples are depicted in Figure 1.
In a similar fashion, a DIBAL reduction–transimination–
NaBH4 reduction12 sequence, using allylamine, would lead
to a bis-olefinic secondary amine after N-protection, an
obvious precursor for a RCM using the now readily
available Grubbs’ catalyst.13,14 In this way, 3-hydroxy-
tetrahydropyridines could be obtained (Scheme 1, path b).
Applying the same chemistry to cyanohydrins 2 and 3
should lead to a set of compounds depicted in Figure 2. This
report presents our results in the exploration of these routes.
It was envisioned that cyanohydrins 1–3, after conversion to
bis-olefinic compounds, would be excellent starting
materials for the ring-closing metathesis (RCM) mediated
synthesis of a unique set of chiral unsaturated carba- and
heterocyclic compounds.10 Conversion of cyanohydrin 1 via
a one-pot Grignard addition–NaBH4 reduction11 sequence,
using an olefinic Grignard reagent, followed by subsequent
N-protection and RCM, would provide an efficient method-
2. Results and discussion
2.1. Cyclic unsaturated 1,2-ethanolamines
Our attention was first focussed on the conversion of
Figure 1. Unsaturated O-protected cyanohydrins 1–3: starting materials for the synthesis of chiral carba- and heterocyclic compounds.
Keywords: Cyanohydrins; Ring-closing metathesis; Cyclic ethanolamines; Heterocycles.
* Corresponding author. Tel.: C31-71-5274537; e-mail: brussee@chem.leidenuniv.nl
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.07.103

10386
A. M. C. H. van den Nieuwendijk et al. / Tetrahedron 60 (2004) 10385–10396
Scheme 3. O-deprotection of compounds 7b and 9 to obtain the previously
described compounds 12 and 13.
bis-olefinic compounds 4–6 in yields of 72–85%. During the
reduction a mixture of two diastereoisomers was formed
with the depicted erythro isomers 4–6 as the predominant
products (Scheme 2). It was not possible to separate the
diastereoisomers at this stage.
Scheme 1. General pathways for the conversion of cyanohydrin 1 into
cyclic derivatives. (a) Grignard addition–NaBH4 reduction. (b) DIBAL
reduction–transimination–NaBH4 reduction; (c) Grubbs catalyst.
RCM reactions were performed in refluxing dichloro-
methane using 4 mol% of Grubbs catalyst.14 For the
5- and 6-membered rings the RCM proceeded with good
yields (78–89%). The diastereoisomers were readily
separated by silicagel column chromatography, affording
pure ethanolamines 7–10. In the case of the 7-membered
ring 11, dimerization at the terminal double bond was the
prominent reaction. Ethanolamine 11 was obtained in 34%
yield as a mixture of two unseparable diastereoisomers. To
be able to determine the enantiomeric excess (ee) of these
compounds, the racemic forms were also synthesized.
Chiral HPLC of compounds 7–10 showed that all these
cyclic ethanolamines were obtained with excellent enantio-
meric purity (ee 96–98%).
Figure 2. Set of compounds (n, mZ1, 2) obtainable from O-protected
cyanohydrins 2 and 3.
protected cyanohydrin 1 into cyclic 1,2-ethanolamines.
Starting from cyanohydrin 1, addition of 1.5 equiv of the
appropriate Grignard reagent led, after quenching with
methanol, to the formation of a primary imine. Subsequent
in situ NaBH4 reduction, followed by N-protection, afforded
Additional proof of the stereochemistry of these ethanol-
amines was obtained by O-deprotection of compounds 7b
and 9 resulting in the formation of the known compounds
1215 and 1316 (Scheme 3). For both compounds spectral and
physical data were in agreement with the literature.
Scheme 2. Conversion of cyanohydrin 1 into O,N-protected unsaturated
cyclic 1,2-ethanolamines. For compounds 4–6 the major diastereoisomer is
depicted. Reagents: (i) H2C]CH(CH2)nMgBr; (ii) MeOH; (iii) NaBH4;
(iv) Cbz-Cl or Boc2O; (v) Grubbs catalyst; (vi) silicagel column separation.
Scheme 4. Conversion of cyanohydrins 2 and 3 into O,N-protected cyclic
1,2-ethanolamines. For compounds 14–25 the major diastereoisomer is
depicted. Reagents: (i) H2C]CH(CH2)mMgBr; (ii) MeOH; (iii) NaBH4;
(iv) Cbz-Cl or Boc2O; (v) Grubbs catalyst (4 mol%).

A. M. C. H. van den Nieuwendijk et al. / Tetrahedron 60 (2004) 10385–10396
10387
Extension of our strategy to cyanohydrins 2 and 3 afforded
O,N-protected ethanolamines 14–17 (Scheme 4). The
Grignard addition–NaBH4 reduction sequence generally
afforded diastereomeric mixtures (dr G2.5:1), with the
depicted compounds as the major diastereoisomers. Sub-
sequent N-protection of the crude amines 14–17, followed
by RCM afforded new cyclic 1,2-ethanolamines 22–25 in
good overall yields (Table 1). Attempts to separate the
obtained diastereomeric mixtures remained without
success.
Employing the previously described12 DIBAL reduction–
transimination–NaBH4 reduction sequence to cyanohydrin
1, using allylamine in the transimination step, afforded the
secondary amine 26 in quantitative yield. Crude 26 was
protected with a Cbz-, Boc- or Bn-group to give N-protected
dienes 27a–c in good yields (77–88%). Tetrahydropyridines
28a–c were obtained in 80–94% (69–72% overall based on
1) yields via a ring- closing metathesis reaction with
Grubbs’ catalyst in refluxing dichloromethane.13,14
The smooth transformation of 27c into 28c is remarkable, as
the Grubbs catalyst is generally ineffective for the conver-
sion of tertiary amines.13 The ee of 28c was determined by
chiral HPLC and found to be 99%. O-TBDPS-protected
tetrahydropyridine 28a was deprotected to afford benzyl
(R)-3-hydroxy-3,6-dihydropyridine-1(2H)-carboxylate, an
earlier described compound.17 The spectroscopic and
physical data were in complete agreement. It should be
noted that the authors assigned the configuration of this
compound incorrectly as S.17 The ee (98%) was determined
by chiral HPLC. Recently the O-MOM-protected analog of
28b served as the starting compound in a synthesis of 5-des-
(hydroxymethyl)-1-deoxynojir-mycin, reportedly a potent
glycosidase inhibitor.18
Table 1. Results for the conversion of cyanohydrins 2 and 3 into O,N-
protected cyclic 1,2-ethanolamines 22–25
Comp.
n
m
P
Yield (%)
18a
18b
19a
19b
20a
20b
21
22a
22b
23a
23b
24a
24b
25
1
1
1
1
2
2
2
1
1
1
1
2
2
2
1
1
2
2
1
1
2
1
1
2
2
1
1
2
Cbz
Boc
Cbz
Boc
Cbz
Boc
Cbz
Cbz
Boc
Cbz
Boc
Cbz
Boc
Cbz
69
89
79
81
68
56
68
87
77
96
66
94
86
66a
Application of the same chemistry to cyanohydrins 2 and 3
led to the synthesis of the new O,N-protected tetrahydro-
azepinols 33a–c and azocinols 34a,b (Scheme 6). In
general, the yields were slightly lower than in the synthesis
of the tetrahydropyridines. Carbamate protected 7- and
8-membered heterocycles 33a,b and 34a,b were obtained in
53–65% and 38–41% overall yields respectively. RCM with
the tertiary amine 31c failed completely. Using the HCl salt
of 31c in a RCM afforded azepinol 33c in 12% yield.
a
Yield based on 55% converted starting material.
2.2. Unsaturated N-heterocycles
Next, our efforts were directed towards the synthesis of O,N-
protected (R)-3-hydroxy-2HK1,2,3,6-tetrahydro-pyridines
28a–c (Scheme 5).
Scheme 5. Synthesis of (R)-N-protected 3-[(t-butyldiphen-ylsilyl)oxy]-2H-
1,2,3,6-tetrahydropyridines. Reagents: (i) DIBAL; (ii) MeOH; (iii)
Allylamine; (iv) NaBH4; (v) Cbz-Cl or Boc2O or BnBr; (vi) Grubbs
catalyst (4 mol%).
Scheme 6. Transformation of cyanohydrins 2 and 3 into O,N-protected
tetrahydroazepinols (33a–c) and tetrahydro-azocinols (34a,b). Reagents: (i)
DIBAL; (ii) MeOH; (iii) allylamine; (iv) NaBH4; (v) Cbz-Cl or Boc2O or
BnBr; (vi) Grubbs catalyst (4 mol%).

10388
A. M. C. H. van den Nieuwendijk et al. / Tetrahedron 60 (2004) 10385–10396
3. Conclusion
atmosphere the appropriate O-TBDPS-protected cyanohydrin
(3.0 mmol) was dissolved in dry DEE (30 mL). At K78 8C
DIBAL(4.5 mL, 4.5 mmol, 1.0 Minhexanes)was added. The
reaction was allowed to warm up slowly to 0 8C. After
recooling to K90 8C anhydrous methanol (5.0 mL) was added
at once followed after 5 min, by allyl amine (1.20 mL,
16 mmol). Thecoolingbathwasremovedandthereactionwas
stirred for 2 h at room temperature. The resulting suspension
was cooled to K20 8C and NaBH4 (0.28 g, 7.4 mmol) was
added in three portions. After stirring for 2 h at room
temperature the suspension was poured into an aqueous
0.4 M NaOH (40 mL) solution. The layers were separated and
the water layer was extracted with DEE (2!20 mL). After
washing the combined organic layers with brine (20 mL),
drying (MgSO4), filtration and evaporation of the solvent in
vacuo the crude amines were obtained as colorless oils in
quantitative yield.
Cyanohydrins 1–3 were found to be excellent starting
materials for the enantioselective synthesis of a number of
new chiral N-heterocycles and cyclic 1,2-ethanolamines.
The combination of either a DIBAL reduction–transimina-
tion–NaBH4 reduction or a Grignard addition–NaBH4
reduction sequence with ring-closing metathesis employing
the Grubbs’ catalyst, proved to be a powerful methodology
for the preparation of these compounds in only three steps
and high yields.
4. Experimental
4.1. General procedures and remarks
Reactions were carried out in an inert nitrogen or argon
atmosphere. For reactions involving DIBAL or Grignard
reagents flame dried equipment was used. All compounds
were synthesized in both racemic and non-racemic form. ees
were determined by comparing racemic with non-racemic
General procedure for carbobenzyloxy (Cbz) protections.
The crude amine (1.0 mmol) was dissolved in an ice cold
mixture of CH2Cl2 (5.0 mL) and saturated aqueous
NaHCO3 solution (10 mL). Benzyl chloroformate
(0.30 mL, 2.0 mmol) was added dropwise and the reaction
stirred vigorously overnight while warming to room
temperature. The layers were separated and the water
layer was extracted with CH2Cl2 (2!5 mL). The combined
organic layers were dried (MgSO4), filtered and concen-
trated in vacuo to afford the crude N-Cbz-protected product.
compounds on chiral HPLC employing
a Daicel
CHIRALCEL OD or ODH column, using hexane (HEX)
2-propanol (IPA) mixtures as the eluent, and UV detection
at 254 nm. Eluents are specified in each case. TLC-analyses
were performed on Merck plastic silica gel 60 F254 plates.
Detection by UV (254 nm); ammonium molybdate
(50 g LK1) and cerium(IV) sulfate (1 g LK1) in aqueous
10% H2SO4, followed by heating to 150 8C; or 5% (w/v)
aqueous KMnO4. Column chromatography was performed on
Fluka silica gel (0.063–0.200 mm). Solvents for chromato-
graphy were distilled before use (PEZpetroleum ether 40–60;
DEEZdiethyl ether; EtOAcZethyl acetate). Other solvents
General procedure for butyloxycarbonyl (Boc) protections.
The crude amine (1.0 mmol) was dissolved in CH2Cl2
(5.0 mL). Triethylamine (TEA, 0.16 mL, 1.1 mmol) and di-
t-butyl dicarbonate (654 mg, 3.0 mmol) were added. After
stirring overnight at room temperature the solvent was
evaporated at reduced pressure to obtain the crude N-Boc-
protected product.
˚
were of p.a. quality and stored over molecular sieves (3 A).
Commercial chemicals were used as received. 1H NMR
(200 MHz) and 13C NMR (50 MHz) spectra were recorded on
a Bruker AC-200 instrument. Samples were measured in
CDCl3, using TMS as an internal standard for 1H NMR, and
CDCl3 as internal standard for 13C NMR. Optical rotations
were measured on a Propol automatic polarimeter (Sodium D
line, lZ589 nm). ESI-MS was performed on a Perkin Elmer
SCIEX API 165 instrument. ESI-HRMS was performed on a
Finnigan LTQ FTMS instrument.
General procedure for benzyl (Bn) protections. The amine
(1.0 mmol) was dissolved in CH2Cl2 (4.0 mL) and Na2-
CO3$10H2O (0.60 g, 2.1 mmol), water (2.0 mL) and benzyl
bromide (0.16 mL, 1.3 mmol) were added. The reaction was
stirred vigorously overnight. After separation of the layers
the water layer was extracted with CH2Cl2 (2!2 mL). All
organic layers were combined, dried (MgSO4), filtered and
concentrated in vacuo to afford the crude benzylated
product.
General procedure for the one-pot Grignard addition–
NaBH4 reduction reactions. Under an argon atmosphere the
appropriate O-TBDPS-protected cyanohydrin (3.0 mmol)
was dissolved in dry DEE (30 mL). At room temperature a
solution of Grignard reagent (4.5 mmol) was added
dropwise. The reaction was stirred at room temperature
for 1 h, cooled to K20 8C and quenched with dry MeOH
(5.0 mL). After a few minutes the mixture was cooled to
K80 8C and NaBH4 (0.29 g, 7.5 mmol) added. The mixture
was slowly warmed to room temperature at which it was
stirred for 2 h. Then the reaction was poured into water
(50 mL) and extracted with DEE (3!30 mL). The com-
bined DEE layers were washed with brine, dried (MgSO4),
filtered and concentrated in vacuo to afford the crude amines
as colorless oils in quantitative yield.
General procedure for ring closing metathesis reactions.
The appropriate diene was dissolved in CH2Cl2
(1 mmol/10 mL) and argon was bubbled through the
solution for 3 min. Grubbs’ catalyst (4 mol%) was added
and the mixture refluxed (maximum 24 h). Progress of
reaction was monitored by TLC with the new cyclic
products running slightly lower. Upon completion, the
solvent was evaporated to obtain the crude product.
For 8-membered rings the RCM reactions were performed
at 0.005 M concentration of diene in toluene at 60 8C.
4.1.1. (2R,3E)-2-[(t-Butyldiphenylsilyl)oxy]pent-3-ene
nitrile (1). Prepared as described earlier,7 [a]D20ZK4.2
(cZ1, CHCl3). ee 99%, Chiralcel OD, HEX/IPAZ
99.75:0.25, 1.0 mL/min, RT 7.3 min (R-enantiomer), RT
General procedure for the one-pot DIBAL reduction–
transimination–NaBH4 reductions. Under an argon

A. M. C. H. van den Nieuwendijk et al. / Tetrahedron 60 (2004) 10385–10396
10389
11.0 min (S-enantiomer). 1H NMR (CDCl3): d 1.09 (s, 9H,
t-Bu); 1.68 (d, 3H, JZ5.9 Hz, CH3); 4.75 (d, 1H, JZ
5.8 Hz, CHO); 5.50 (m, 1H, ]CH); 5.72 (m, 1H, ]CH);
7.35 (m, 6H, SiPh); 7.66 (m, 4H, SiPh). 13C NMR
(CDCl3): d 17.3, 19.1, 26.5, 63.3, 118.4, 125.8, 127.7,
127.8, 130.1, 130.2, 131.3, 131.5, 131.9, 135.6.
ylmagnesium bromide as a mixture of two diastereoisomers
in a 3:1Z(6S,7R)–(6R,7R) ratio as determined by 1H NMR.
1H NMR (CDCl3): d 1.06 (s, 9H, t-Bu); 1.16–1.66 (m, 7H,
CH3 and CH2); 1.80–2.05 (m, 2H, CH2); 2.54–2.72 (m, 1H,
CHN); 3.96 (dd, 1H, JZ5.1, 10.2 Hz, CHO); 4.92 (m, 2H,
]CH2); 5.15–5.41 (m, 2H, CH]CH); 5.62–5.79 (m, 1H,
]CH); 7.39 (m, 6H, Ph); 7.66 (m, 4H, Ph). Observed for
minor isomer: 3.86 (dd, 1H, JZ5.1, 8.0 Hz). 13C NMR
(CDCl3): d 17.6, 19.2, 25.3, 27.0, 32.3, 33.6, 55.9, 77.7,
114.4, 127.3, 127.5, 127.8, 128.5, 128.7, 128.8, 129.4,
129.6, 131.0, 134.0, 134.9, 135.1, 135.7, 135.9, 138.4,
138.5. Observed for minor isomer: 17.4, 25.7, 32.4, 33.8,
56.4, 79.2.
4.1.2.
(2R)-2-[(t-Butyldiphenylsilyl)oxy]pent-4-ene
nitrile (2). Prepared as described earlier,8 [a]D25ZC30.3
(cZ1.2, CH2Cl2). ee 97%, Chiralcel ODH, HEX/IPAZ
99.75:0.25, 1.0 mL/min, RT 5.9 min (R-enantiomer), RT
1
8.6 min (S-enantiomer). H NMR (CDCl3): d 1.10 (s, 9H,
t-Bu); 2.35–2.61 (m, 2H, CH2); 4.35 (dd, 1H, JZ5.5,
7.0 Hz, CHO); 5.16 (m, 2H, ]CH2); 5.77 (m, 1H, ]CH);
7.42 (m, 6H, SiPh); 7.64 (m, 4H, SiPh). 13C NMR
(CDCl3): d 18.6, 26.4, 40.1, 62.4, 118.6, 119.9, 127.7,
130.1, 130.3, 131.2, 131.6, 135.4, 135.5.
4.2.4. Benzyl [(2R,3E)-1-allyl-2-(t-butyldiphenylsilyl)-
oxy-pent-3-en-1-yl]carbamate (4a). Obtained as a mixture
of two diastereoisomers in a 3:1Z(1S,2R)–(1R,2R) ratio as
1
determined by H NMR. Yield 71% (colorless oil, purified
by silicagel column chromatography, eluent PE/EtOAcZ
4.1.3. (2R)-2-[(t-Butyldiphenylsilyl)oxy]hex-5-ene nitrile
(3). Prepared as described earlier,9 [a]D20ZC29.0 (cZ1,
CHCl3). ee 97%, Chiralcel ODH, HEX/IPAZ99.75:0.25,
1.0 mL/min, RT 5.4 min (R-enantiomer), RT 7.3 min
(S-enantiomer). 1H NMR (CDCl3): d 1.10 (s, 9H, t-Bu); 1.84
(m, 2H, CH2); 2.21 (m, 2H, CH2); 4.35 (t, 1H, JZ6.2 Hz,
CHO); 4.97 (m, 2H, ]CH2); 5.63 (m, 1H, ]CH); 7.42 (m,
6H, Ph); 7.68 (m, 4H, Ph). 13C NMR (CDCl3): d 19.1, 26.5,
28.2, 35.0, 62.2, 115.9, 119.7, 127.5, 127.8, 129.3, 129.9,
130.2, 131.6, 134.7, 135.1, 135.5.
1
95:5). ESI-MS m/z 514.3 [MCH]C; 536.2 [MCNa]C. H
NMR (CDCl3): d 1.05 (s, 9H, t-Bu); 1.42 (d, 3H, JZ7.7 Hz,
CH3, minor isomer); 1.48 (d, 3H, JZ4.6 Hz, CH3 major
isomer); 2.02–2.44 (m, 2H, CH2); 2.64 (m, 1H, CHN); 4.18
(m, 1H, CHO); 4.63 (m, 1H, NH); 4.90–5.08 (m, 5H,
CH]CH2, CH2Ph); 5.35 (m, 1H, ]CH); 5.61 (m, 1H,
]CH); 7.30 (m, 11H, SiPh, Ph); 7.62 (m, 4H, SiPh). 13C
NMR (CDCl3): d 17.5, 19.3, 27.0, 34.4, 55.6, 66.3, 76.4,
117.2, 127.4, 127.5, 127.8, 128.3, 128.8, 129.0, 129.3,
129.4, 129.6, 133.6, 134.7, 135.5, 135.8, 135.9, 136.6,
155.9. Observed for minor isomer: 18.9, 26.5, 36.2, 66.5,
76.1, 118.5, 156.1.
4.2. Preparation of cyclic unsaturated 1,2-ethanolamines
4.2.1. (5R,6E)-5-(t-Butyldiphenylsilyl)oxyocta-1,6-diene-
4-amine. Prepared from cyanohydrin 1 and allylmagnesium
bromide as a mixture of two diastereoisomers in a 3:1Z
4.2.5. t-Butyl [(2R,3E)-1-allyl-2-(t-butyldiphenylsilyl)-
oxypent-3-en-1-yl]carbamate (4b). Obtained as a mixture
of two diastereoisomers in a 3:1Z(1S,2R)–(1R,2R) ratio as
1
(4S,5R)–(4R,5R) ratio as determined by H NMR. ESI-MS
1
m/z 380.0 [MCH]C. H NMR (CDCl3): d 1.06 (s, 9H,
1
determined by H NMR. Yield 71% (colorless oil, purified
by silicagel column chromatography, eluent PE/EtOAcZ
t-Bu); 1.44 (d, 3H, JZ6.2 Hz, CH3, minor isomer); 1.52 (d,
3H, JZ5.2 Hz, CH3 major isomer); 1.93–2.17 (m, 2H,
CH2); 2.73–2.84 (m, 1H, CHN); 3.54–3.68 (m, 2H, NH2);
3.96 (m, 1H, CHO); 4.94–5.74 (m, 5H, CH]CHC
CH]CH2); 7.37 (m, 6H, Ph); 7.67 (m, 4H, Ph). 13C NMR
(CDCl3): d 17.4, 19.0, 26.8, 37.1, 55.3, 77.3, 116.7, 127.0,
127.2, 127.4, 128.7, 128.9, 129.2, 129.3, 129.8, 130.3,
133.7, 133.9, 134.7, 135.2, 135.5, 135.7, 136.2. Observed
for minor isomer: 18.7, 26.5, 55.7, 78.4, 117.8.
1
97:3). ESI-MS m/z 480.1 [MCH]C; 502.4 [MCNa]C. H
NMR (CDCl3): d 1.06 (s, 9H, t-Bu); 1.40 (s, 9H, t-Bu); 1.48
(d, 3H, JZ4.4 Hz, CH3); 2.24 (m, 2H, CH2); 3.63 (m, 1H,
CHN); 4.12 (m, 1H, CHO); 4.51 (m, 1H, NH); 5.00 (m, 2H,
]CH2); 5.32 (m, 2H, ]CH); 5.59–5.76 (m, 1H, ]CH);
7.40 (m, 6H, SiPh); 7.65 (m, 4H, SiPh). 13C NMR (CDCl3):
d 17.4, 19.2, 26.9, 28.2, 34.5, 54.9, 76.0, 78.5, 116.8, 127.2,
127.4, 128.4, 128.6, 129.3, 129.5, 129.7, 130.1, 133.5,
133.6, 133.8, 134.9, 135.7, 155.3. Observed for minor
isomer: 36.2, 75.5, 155.4.
4.2.2. (6R,7E)-6-(t-Butyldiphenylsilyl)oxynona-1,7-
diene-5-amine. Prepared from cyanohydrin 1 and but-3-
en-1-ylmagnesium bromide as a mixture of two diastereo-
isomers in a 3:1Z(5S,6R)–(5R,6R) ratio as determined by
1H NMR. 1H NMR (CDCl3): d 1.06 (s, 9H, t-Bu); 1.19–1.69
(m, 5H, CH3 and CH2); 1.87–2.21 (m, 2H, CH2); 2.66–2.75
(m, 1H, CHN); 3.97 (dd, 1H, JZ4.4, 7.3 Hz CHO); 4.86–
5.10 (m, 3H, CH]CH2); 5.36 (m, 1H, ]CH); 5.62–5.83
(m, 1H, ]CH); 7.38 (m, 6H, Ph); 7.66 (m, 4H, Ph).
Observed for minor isomer: 3.86 (dd, 1H, JZ5.2, 7.3 Hz,
CHO). 13C NMR (CDCl3): d 17.6, 19.3, 27.1, 30.3, 32.1,
55.6, 77.7, 114.4, 127.3, 127.5, 127.6, 128.8, 129.4, 129.5,
129.6, 134.0, 135.4, 135.7, 135.9, 138.2. Observed for
minor isomer: 26.7, 30.0, 55.9, 79.1, 115.5.
4.2.6. Benzyl [(2R,3E)-1-(but-3-enyl)-2-(t-butyl-di-
phenylsilyl)oxypent-3-en-1-yl]carbamate (5). Obtained
as a mixture of two diastereoisomers in a 3:1Z(1S,2R)–
(1R,2R) ratio as determined by 1H NMR. Yield 58%
(colorless oil, purified by silicagel column chromatography,
eluent PE/EtOAcZ95:5). 1H NMR (CDCl3): d 1.04 (s, 9H,
t-Bu); 1.41–1.61 (m, 5H, CH3 and CH2); 1.81–2.25 (m, 2H,
CH2); 3.65 (m, 1H, CHN); 4.12 (m, 1H, CHO); 4.66 (d, 1H,
JZ9.5 Hz, NH); 4.90–5.10 (m, 5H, PhCH2, CH]CH2);
5.34 (m, 1H, ]CH); 5.75–5.92 (m, 1H, ]CH); 7.34 (m,
11H, Ph); 7.63 (m, 4H, Ph). 13C NMR (CDCl3): d 17.7, 19.4,
27.1, 29.5, 30.3, 56.0, 66.4, 76.6, 114.7, 127.4, 127.6, 127.9,
128.3, 128.4, 128.7, 129.6, 129.8, 133.9, 134.9, 135.9,
136.0, 138.0, 156.2.
4.2.3. (7R,8E)-7-(t-Butyldiphenylsilyl)oxydeca-1,8-diene-
6-amine. Prepared from cyanohydrin 1 and pent-4-en-1-

10390
A. M. C. H. van den Nieuwendijk et al. / Tetrahedron 60 (2004) 10385–10396
4.2.7. Benzyl [(2R,3E)-1-(pent-4-enyl)-2-(t-butyl-di-
phenylsilyl)oxypent-3-en-1-yl]carbamate (6). Obtained
as a mixture of two diastereoisomers in a 2.5:1Z(1S,2R)–
(1R,2R) ratio as determined by 1H NMR. Yield 74%
(colorless oil, purified by silicagel column chromatography,
eluent PE/EtOAcZ95:5). 1H NMR (CDCl3): d 1.04 (s, 9H,
t-Bu); 1.26–1.56 (m, 7H, CH3 and CH2); 1.96 (m, 2H, CH2);
3.60 (m, 1H, CHN); 4.07–4.16 (m, 1H, CHO); 4.63 (d, 1H,
JZ9.5 Hz, NH); 4.79–5.18 (m, 4H, PhCH2, ]CH2); 5.34
(m, 2H, CH]CH); 5.72 (m, 1H, ]CH); 7.36 (m, 11H, Ph);
7.62 (m, 4H, Ph). 13C NMR (CDCl3): d 17.6, 19.4, 25.2,
27.1, 29.6, 33.5, 56.2, 66.3, 76.5, 114.7, 126.6, 127.4, 127.6,
127.9, 128.4, 128.6, 128.8, 129.3, 129.7, 130.4, 133.7,
133.9, 134.9, 135.9, 136.0, 136.9, 138.5, 156.3. Observed
for minor isomer: 25.4, 26.7, 31.2, 66.5, 76.1.
NH); 4.61 (m, 1H, CHO); 5.02 (d, 1H, JZ12.5 Hz, CH2Ph);
5.08 (d, 1H, JZ12.5 Hz, CH2Ph); 5.54 (m, 1H, ]CH); 5.78
(m, 1H, ]CH); 7.38 (m, 11H, Ph, SiPh); 7.64 (m, 4H,
SiPh). 13C NMR (CDCl3): d 19.0, 26.8, 37.9, 60.1, 66.4,
83.2, 127.5, 127.9, 128.3, 129.6, 131.5, 132.5, 133.5, 133.9,
135.7, 136.5, 155.7. HRMS calculated for [MCH]C
472.23025, found: 472.23062.
4.2.11. t-Butyl (1R,2R)-(2-[t-butyldiphenylsilyl]-oxy-
cyclo-pent-3-en-1-yl)carbamate (8b). Minor isomer,
obtained from diastereomeric mixture 4b. Yield 19%
(colorless oil, purified by silicagel column chromatography,
second fraction, eluent PE/EtOAcZ95:5). [a]2D0ZK17.4
(cZ0.94, CH2Cl2). ESI-MS m/z 460.1 [MCNa]C; HPLC
Chiralcel ODH, HEX/IPAZ99.75:0.25, 1.0 mL/min, RT
8.7 min (1S,2S-enantiomer), RT 9.3 min (1R,2R-enantio-
mer), no base line separation. 1H NMR (CDCl3): d 1.06 (s,
9H, t-Bu); 1.42 (s, 9H, t-Bu); 2.03 (m, 1H, CH2); 2.84 (dd,
1H, JZ6.6, 16.8 Hz, CH2); 4.11 (m, 1H, CHN); 4.28 (m,
1H, NH); 4.59 (m, 1H, CHO); 5.50 (m, 1H, ]CH); 5.75 (m,
1H, ]CH); 7.41 (m, 6H, SiPh); 7.68 (m, 4H, SiPh). 13C
NMR (CDCl3): d 19.0, 26.9, 28.4, 38.3, 59.8, 79.0, 83.4,
127.6, 129.6, 131.7, 131.9, 132.5, 133.4, 133.6, 134.1,
135.7, 135.9, 155.3. HRMS calculated for [MCH]C
438.24590, found: 438.24640.
4.2.8. Benzyl (1S,2R)-(2-[t-butyldiphenylsilyl]oxycyclo-
pent-3-en-1-yl)carbamate (7a). Major isomer, obtained
from diastereomeric mixture 4a. Yield 60% (colorless oil,
purified by silicagel column chromatography, first fraction,
eluent PE/EtOAcZ96:4). [a]2D5ZK19.6 (cZ0.53,
CH2Cl2). ESI-MS m/z 472.2 [MCH]C; 494.2 [MCNa]C;
965.3 [M2CNa]C; 1437.0 [M3CNa]C; ee 96%, Chiralcel
OD, HEX/IPAZ99:1, 1.0 mL/min, RT 9.4 min (1S,2R-
enantiomer), RT 10.4 min (1R,2S-enantiomer). 1H NMR
(CDCl3): d 1.06 (s, 9H, t-Bu); 2.33 (m, 1H, CH2); 2.62 (m,
1H, CH2); 4.17 (m, 1H, CHN); 4.66 (m, 1H, CHO); 5.12 (s,
2H, CH2Ph); 5.46 (m, 1H, ]CH); 5.64 (d, 1H, JZ10.1 Hz,
NH); 5.82 (m, 1H, ]CH); 7.39 (m, 11H, Ph, SiPh); 7.66 (m,
4H, SiPh). 13C NMR (CDCl3): d 19.0, 26.8, 37.8, 52.4, 66.1,
75.7, 127.4, 127.5, 127.6, 128.2, 129.6, 131.7, 132.9, 133.0,
133.5, 135.4, 135.5, 136.6, 155.8. HRMS calculated for
[MCH]C 472.23025, found: 472.23090.
4.2.12. Benzyl (1S,2R)-(2-[-t-butyldiphenylsilyl]-oxy-
cyclo-hex-3-en-1-yl)carbamate (9). Major isomer,
obtained from diastereomeric mixture 5. Yield 73% (color-
less oil, purified by silicagel column chromatography, first
fraction, eluent PE/EtOAcZ95:5). [a]2D5ZK71.4 (cZ1.0,
CH2Cl2). ee 97%, Chiralcel OD, HEX/IPAZ99:1, 1.0 mL/
min, RT 7.7 min (1R,2S-enantiomer), RT 10.3 min (1S,2R-
enantiomer). 1H NMR (CDCl3): d 1.06 (s, 9H, t-Bu); 1.85–
2.35 (m, 4H, CH2); 3.73 (m, 1H, CHN); 4.21 (m, 1H, CHO);
5.06 (d, 1H, JZ12.4 Hz, CH2Ph); 5.13 (d, 1H, JZ12.4 Hz,
CH2Ph); 5.32 (m, 2H, ]CH and NH); 5.66 (m, 1H, ]CH);
7.15–7.45 (m, 11H, Ph, SiPh); 7.69 (m, 4H, SiPh). 13C NMR
(CDCl3): d 19.4, 24.1 (C5 and C6), 27.1, 50.8, 66.4, 67.1,
127.6, 127.8, 127.9, 128.5, 129.3, 129.8, 129.9, 130.3,
133.4, 133.9, 134.9, 135.8, 135.9, 136.9, 155.9. HRMS
calculated for [MCH]C 486.24590, found: 486.24658.
4.2.9. t-Butyl (1S,2R)-(2-[t-butyldiphenylsilyl]oxycyclo-
pent-3-en-1-yl)carbamate (7b). Major isomer, obtained
from diastereomeric mixture 4b. Yield 70% (colorless oil,
purified by silicagel column chromatography, first fraction,
eluent PE/EtOAcZ95:5). [a]2D0ZK27.0 (cZ1.0, CH2Cl2).
ESI-MS m/z 438.1 [MCH]C; 460.0 [MCNa]C; 875.5
[M2CH]C; 897.6 [M2CNa]C; ee 98%, Chiralcel ODH,
HEX/IPAZ99.75:0.25, 1.0 mL/min, RT 7.0 min (1S,2R-
enantiomer), RT 8.8 min (1R,2S-enantiomer). 1H NMR
(CDCl3): d 1.08 (s, 9H, t-Bu); 1.46 (s, 9H, t-Bu); 2.30 (m,
1H, CH2); 2.60 (dd, 1H, JZ7.3, 16.8 Hz, CH2); 4.11 (m,
1H, CHN); 4.65 (d, 1H, JZ6.6 Hz, CHO); 5.40 (m, 2H,
]CH, NH); 5.82 (m, 1H, ]CH); 7.41 (m, 6H, SiPh); 7.67
(m, 4H, SiPh). 13C NMR (CDCl3): d 19.2, 26.9, 28.3, 38.1,
51.9, 75.8, 78.8, 127.5, 127.7, 129.7, 131.6, 131.9, 132.5,
133.1, 133.4, 133.9, 135.7, 155.6. HRMS calculated for
[MCH]C 438.24590, found: 438.24622.
4.2.13. Benzyl (1R,2R)-(2-[-t-butyldiphenylsilyl]-oxy-
cyclo-hex-3-en-1-yl)carbamate (10). Minor isomer,
obtained from diastereomeric mixture 5. Yield 15% (color-
less solid, purified by silicagel column chromatography, first
fraction, eluent PE/EtOAcZ95:5). [a]2D0ZK23.0 (cZ1.0,
CH2Cl2). ee 97%, Chiralcel OD, HEX/IPAZ99:1, 1.0 mL/
min, RT 9.8 min (1R,2R-enantiomer), RT 14.8 min (1S,2S-
1
enantiomer). H NMR (CDCl3): d 1.04 (s, 9H, t-Bu); 2.10
(m, 4H, CH2); 3.85 (m, 1H, CHN); 3.95 (broad s, 1H, NH);
4.39 (d, 1H, JZ8.0 Hz, CHO); 4.96 (d, 1H, JZ11.7 Hz,
CH2Ph); 5.07 (d, 1H, JZ11.7 Hz, CH2Ph); 5.47 (d, 1H, JZ
10.2 Hz, ]CH); 5.68 (d, 1H, JZ9.5 Hz, ]CH); 7.31–7.45
(m, 11H, Ph, SiPh); 7.66 (m, 4H, SiPh). 13C NMR (CDCl3):
d 19.2, 23.1, 25.5, 26.8, 52.9, 66.4, 70.4, 126.6 127.5, 127.6,
127.9, 128.4, 129.2, 129.6, 133.4, 135.8, 135.9, 136.5,
155.6. HRMS calculated for [MCH]C 486.24590, found:
486.24649.
4.2.10. Benzyl (1R,2R)-(2-[t-butyldiphenylsilyl]-oxy-
cyclo-pent-3-en-1-yl)carbamate (8a). Minor isomer,
obtained from diastereomeric mixture 4a. Yield 18%
(colorless solid, purified by silicagel column chromato-
graphy, second fraction, eluent PE/EtOAcZ96:4).
[a]2D5ZK16.5 (cZ0.51, CH2Cl2). ESI-MS m/z 494.2
[MCNa]C; 965.2 [M2CNa]C; 1436.5 [M3CNa]C; ee
98%, Chiralcel OD, HEX/IPAZ97:3, 1.0 mL/min, RT
8.0 min (1R,2R-enantiomer), RT 17.6 min (1S,2S-enantio-
mer). 1H NMR (CDCl3): d 1.05 (s, 9H, t-Bu); 2.04 (m, 1H,
CH2); 2.88 (m, 1H, CH2); 4.17 (m, 1H, CHN); 4.52 (m, 1H,
4.2.14. Benzyl (2R)-(2-[-t-butyldiphenylsilyl]-oxycyclo-
hept-3-en-1-yl)carbamate (11). Obtained as
a

A. M. C. H. van den Nieuwendijk et al. / Tetrahedron 60 (2004) 10385–10396
10391
diastereomeric mixture, (1S,2R)–(1R,2R)Z2.5:1, from dia-
stereomeric mixture 6 in 34% yield as a colorless oil,
purified by silicagel column chromatography, eluent PE/
EtOAcZ95:5. 1H NMR (CDCl3): d 1.06 (s, 9H, t-Bu); 1.25–
1.62 (m, 2H, CH2); 1.78–2.42 (m, 4H, CH2); 3.60–3.95 (m,
1H, CHN); 4.44 (m, 1H, CHO); 4.84–5.11 (m, 2H, CH2Ph);
5.38 (m, 1H, NH); 5.56 (m, 1H, ]CH); 5.83 (m, 1H,
]CH); 7.15–7.45 (m, 11H, Ph, SiPh); 7.69 (m, 4H, SiPh).
13C NMR (CDCl3): d 19.2, 21.7, 26.9, 28.1, 32.3, 53.9, 66.4,
73.7, 125.9, 127.5, 127.6, 127.9, 128.4, 129.6, 129.7, 129.9,
133.4, 135.8, 136.0, 156.0. Observed for minor isomer:
27.0, 28.0, 52.8.
5-amine (15). Obtained as a mixture of two diastereo-
isomers in a (4R,5S)–(4R,5R)Z2:1 ratio as determined by
1H NMR. ESI-MS m/z 394.2 [MCH]C, 787.6 [M2CH]C.
1H NMR (CDCl3): d 1.07 (s, 9H, t-Bu); 1.16–1.61 (m, 2H,
CH2); 1.86–2.51 (m, 4H, CH2); 2.60–2.76 (m, 1H, CHN);
3.61–3.74 (m, 1H, CHO); 4.82–4.99 (m, 4H, ]CH2); 5.44–
5.82 (m, 2H, ]CH); 7.40 (m, 6H, SiPh); 7.66 (m, 4H, SiPh).
13C NMR (CDCl3): d 18.9, 26.7, 31.3, 33.3, 36.1, 54.2, 76.5,
114.1, 116.2, 127.0, 127.1, 129.1, 129.3, 129.9, 130.9,
132.8, 133.2, 133.6, 134.7, 134.9, 135.4. Observed for
minor isomer: 18.6, 26.1, 35.1, 37.7, 52.6, 75.7, 113.9,
116.5.
4.2.15. t-Butyl (1S,2R)-(2-hydroxycyclopent-3-en-1-yl)-
carbamate (12). Compound 7b (172 mg, 0.394 mmol) was
dissolved in THF (6 mL) and excess TBAF (3 equiv) was
added. After 2 h the reaction was completed as monitored
by TLC. The solvent was evaporated and the residue
purified by column chromatography. Yield 77 mg (98%).
(colorless oil, purified by silicagel column chromatography,
eluent PE/EtOAcZ95:5/1:1). [a]2D0ZK41.4 (cZ1.0,
CH2Cl2). Enantiomers could not be separated by chiral
HPLC on Daicel Chiralcel ODH, OJ and Chiralpak AD
columns. 1H NMR (CDCl3) lit15b: d 1.46 (s, 9H, t-Bu); 2.01
(broad s, 1H, OH); 2.23 (m, 1H, CH2); 2.70 (m, 1H, CH2);
4.12 (m, 1H, CHN); 4.58 (broad d, 1H, CHO); 5.17 (broad s,
1H, NH); 5.88 (m, 1H, CH]CH); 6.00 (m, 1H, CH]CH).
13C NMR (CDCl3) lit15b: d 28.3, 37.4, 52.2, 74.2, 79.3,
131.7, 134.5, 156.1.
4.2.19. (5R)-5-(t-Butyldiphenylsilyl)oxynona-1,8-diene-
4-amine (16). Obtained as a mixture of two diastereo-
isomers in a (4S,5R)–(4R,5R)Z2.4:1 ratio as determined by
1H NMR. ESI-MS m/z 394.3 [MCH]C. 1H NMR (CDCl3):
d 1.07 (s, 9H, t-Bu); 1.26–2.27 (m, 6H, CH2); 2.79 (m, 1H,
CHN); 3.66 (m, 1H, CHO); 4.77–4.96 (m, 2H, ]CH2);
5.02–5.18 (m, 2H, ]CH2); 5.47–5.70 (m, 2H, ]CH); 7.41
(m, 6H, SiPh); 7.67 (m, 4H, SiPh). 13C NMR (CDCl3): d
19.1, 26.8, 29.5, 30.6, 37.1, 54.3, 76.2, 114.1, 116.6, 127.2,
127.3, 128.8, 129.3, 129.4, 133.5, 133.8, 134.6, 135.6 135.8,
137.6, 137.9. Observed for minor isomer: 26.4, 29.4, 31.3,
38.7, 53.1, 75.6, 117.9.
4.2.20. (6R)-6-(t-Butyldiphenylsilyl)oxydeca-1,9-diene-5-
amine (17). Obtained as a mixture of two diastereoisomers
in a (5S,6R)–(5R,6R)Z2:1 ratio as determined by 1H NMR.
1H NMR (CDCl3): d 1.07 (s, 9H, t-Bu); 1.10–2.27 (m, 8H,
CH2); 2.61–2.79 (m, 1H, CHN); 3.42–3.66 (m, 1H, CHO);
4.77–4.99 (m, 4H, ]CH2); 5.42–5.83 (m, 2H, ]CH); 7.40
(m, 6H, SiPh); 7.67 (m, 4H, SiPh). 13C NMR (CDCl3): d
18.9, 26.6, 29.1, 30.1, 31.4, 33.0, 54.2, 76.4, 113.8, 114.1,
126.9, 127.0, 129.1, 133.1, 133.5, 133.8, 134.4, 135.3 137.3,
137.7, 137.9. Observed for minor isomer: 29.5, 30.4, 31.7,
52.6, 75.6, 113.5.
4.2.16. Benzyl (1S,2R)-(2-hydroxycyclohex-3-en-1-yl)-
carbamate (13). Silyl ether 9 (422 mg, 0.866 mmol) was
dissolved in THF (8 mL) and excess TBAF (3 equiv) was
added. TLC showed complete conversion after 1 h. The
solvent was evaporated and the residue purified by silicagel
column chromatography, eluent PE/EtOAcZ95:5/3:1/
2:3 to afford the title compound (188 mg, 87%) as a
colorless oil. [a]D20ZK100.6 (cZ1.0, CH2Cl2, [lit.16,
[a]2D0ZK55.6 (cZ1.0, CH2Cl2 for eeZ58%]). ee 98%,
Chiralcel ODH, HEX/IPAZ90:10, 1.0 mL/min, RT
10.9 min (1S,2R-enantiomer), RT 19.0 min (1R,2S-enantio-
mer). 1H NMR (CDCl3) lit16: d 1.62 (d, 1H, JZ5.1 Hz, OH);
1.57–1.69 (m, 1H, CH2); 1.73–1.84 (m, 1H, CH2); 2.15 (m,
2H, CH2); 3.79 (m, 1H, CHN); 4.14 (m, 1H, CHO); 5.11 (s,
2H, CH2Ph); 5.31 (m, 1H, NH); 5.77–5.95 (m, 2H,
CH]CH); 7.35 (m, 5H, Ph). 13C NMR (CDCl3) lit16: d
23.1, 24.4, 50.4, 64.5, 66.4, 127.0, 127.8, 128.2, 129.1,
131.0, 136.2, 155.9.
4.2.21. Benzyl [(2R)-1-allyl-2-(t-butyldiphenylsilyl)oxy-
pent-4-en-1-yl]carbamate (18a). Obtained as a mixture of
two diastereoisomers in a (1S,2R)–(1R,2R)Z2.5:1 ratio as
1
determined by H NMR. Yield 69% (colorless oil, purified
by silicagel column chromatography, eluent PE/EtOAcZ
1
95:5). ESI-MS m/z 514.3 [MCH]C. H NMR (CDCl3): d
1.06 (s, 9H, t-Bu); 2.04–2.35 (m, 4H, CH2); 3.70 (m, 1H,
CHN); 3.90 (m, 1H, CHO); 4.71–5.09 (m, 6H, ]CH2,
PhCH2); 5.49–5.78 (m, 2H, ]CH); 7.38 (m, 11H, SiPh,
PhCH2); 7.63 (m, 4H, SiPh). 13C NMR (CDCl3): d 19.3,
27.0, 32.8, 38.8, 53.5, 66.2, 75.0, 117.1, 117.5. 127.5, 127.9,
128.3, 129.6, 129.7, 133.5, 134.6, 135.0, 135.8, 155.6.
Observed for minor isomer: 37.5, 52.4, 66.5, 74.1, 118.1,
156.0.
4.2.17. (5R)-5-(t-Butyldiphenylsilyl)oxyocta-1,7-diene-4-
amine (14). Obtained as a mixture of two diastereoisomers
in a (4S,5R)–(4S,5R)Z2.5:1 ratio as determined by 1H
1
NMR. ESI-MS m/z 380.0 [MCH]C. H NMR (CDCl3): d
1.07 (s, 9H, t-Bu); 1.91–2.41 (m, 4H, CH2); 2.79 (m, 1H,
CHN); 3.73 (m, 1H, CHO); 4.77–5.09 (m, 4H, ]CH2);
5.49–5.72 (m, 2H, ]CH); 7.39 (m, 6H, SiPh); 7.70 (m, 4H,
SiPh). 13C NMR (CDCl3): d 19.0, 26.8, 36.6, 36.8, 54.0,
76.0, 116.4, 116.8, 127.1, 127.2, 127.6, 128.7, 129.0, 129.2,
129.3, 133.3, 133.5, 134.1, 134.6, 135.5. Observed for
minor isomer: 18.6, 26.4, 37.2, 37.8, 52.8, 75.4, 115.7,
117.7.
4.2.22. t-Butyl [(2R)-(1-allyl-t-butyldiphenylsilyl)-oxy-
pent-4-en-1-yl]carbamate (18b). Obtained as a mixture
of two diastereoisomers in a (1S,2R)–(1R,2R)Z2.5:1 ratio
as determined by 1H NMR. Yield 89% (colorless oil,
purified by silicagel column chromatography, eluent PE/
EtOAcZ95:5). ESI-MS m/z 480.2 [MCH]C. 1H NMR
(CDCl3): d 1.06 (s, 9H, t-Bu); 1.37 (s, 9H, t-Bu); 1.95–2.45
(m, 4H, CH2); 3.64 (m, 1H, CHN); 3.91 (m, 1H, CHO); 4.59
(br d, 1H, NH); 4.83–5.09 (m, 4H, ]CH2); 5.43–5.61 (m,
1H, ]CH); 5.67–5.79 (m, 1H, ]CH); 7.40 (m, 6H, SiPh);
4.2.18. (4R)-4-(t-Butyldiphenylsilyl)oxynona-1,8-diene-

10392
A. M. C. H. van den Nieuwendijk et al. / Tetrahedron 60 (2004) 10385–10396
7.65 (m, 4H, SiPh). 13C NMR (CDCl3): d 18.5, 26.4, 26.9,
32.1, 38.1, 52.0, 74.3, 77.9, 115.7, 116.0. 126.7, 126.8,
128.9, 129.0, 131.5, 131.8, 132.6, 132.9, 134.0, 134.4,
135.0, 135.2, 154.3. Observed for minor isomer: 36.8, 51.0,
73.6, 115.4, 116.5, 154.8.
1.30–1.59 (m, 2H, CH2); 1.77–1.92 (m, 2H, CH2); 2.33 (m,
2H, CH2); 3.69 (m, 1H, CHN); 3.86 (m, 1H, CHO); 4.61–
5.12 (m, 4H, ]CH2); 5.46–5.82 (m, 2H, ]CH); 7.42 (m,
6H, SiPh); 7.68 (m, 4H, SiPh). 13C NMR (CDCl3): d 19.4,
27.1, 28.3, 29.5, 33.1, 37.6, 53.2, 75.5, 78.6, 114.5, 116.8,
127.5, 127.6, 129.6, 129.7, 133.5, 133.9, 135.0, 135.3,
135.8, 137.7, 155.2. Observed for minor isomer: 27.3, 33.4,
52.0, 73.8, 78.8.
4.2.23. Benzyl [(2R)-(1-but-3-en-1-yl)-2-(t-butyl-di-
phenylsilyl)oxypent-4-en-1-yl]carbamate (19a). Obtained
as a mixture of two diastereoisomers in a (1S,2R)–
1
(1R,2R)Z2:1 ratio as determined by H NMR. Yield 79%
(colorless oil, purified by silicagel column chromatography,
4.2.27. Benzyl [1-but-3-enyl-(2R)-(t-butyldiphenylsilyl)-
oxyhex-5-en-1-yl]carbamate (21). Obtained as a mixture
of two diastereoisomers in a (1S,2R)–(1R,2R)Z2.5:1 ratio
as determined by 1H NMR. Yield 68% (colorless oil,
purified by silicagel column chromatography, eluent PE/
eluent PE/DEEZ95:5). ESI-MS m/z 528.3 [MCH]C; 550.4
1
[MCNa]C. H NMR (CDCl3): d 1.06 (s, 9H, t-Bu); 1.43–
1.68 (m, 2H, CH2); 1.92–2.22 (m, 4H, CH2); 3.65 (m, 1H,
CHN); 3.86 (m, 1H, CHO); 4.71–5.13 (m, 6H, ]CH2,
CH2Ph); 5.28–5.83 (m, 2H, ]CH); 7.37 (m, 11H, SiPh,
PhCH2); 7.65 (m, 4H, SiPh). 13C NMR (CDCl3): d 19.3,
26.9, 27.5, 30.0, 38.7, 53.6, 66.1, 75.4, 114.6, 117.4. 127.4,
127.6, 127.9, 128.2, 129.6, 129.7, 129.8, 133.5, 135.7,
136.6, 137.7, 137.9, 155.7. Observed for minor isomer:
32.4, 52.4, 66.4, 74.7, 114.4, 118.0, 156.1.
1
EtOAcZ95:5). ESI-MS m/z 564.3 [MCNa]C. H NMR
(CDCl3): d 1.05 (s, 9H, t-Bu); 1.25–2.05 (m, 5H, CH2); 2.31
(m, 1H, CH2); 3.76 (m, 1H, CHN); 3.90 (m, 1H, CHO); 4.70
(m, 2H, ]CH2); 4.83–5.18 (m, 4H, ]CH2, PhCH2); 5.45–
5.82 (m, 2H, ]CH); 7.37 (m, 11H, SiPh, PhCH2); 7.66 (m,
4H, SiPh). 13C NMR (CDCl3): d 19.5, 27.1, 29.6, 30.2, 33.1,
33.4, 53.9, 66.3, 75.9, 114.6, 115.1, 127.5, 127.7, 127.9,
128.0, 128.4, 129.7, 129.8, 129.9, 133.5, 133.8, 135.9,
137.5, 138.0, 155.8. Observed for minor isomer: 18.8, 26.4,
32.4, 52.5, 66.6, 74.1, 156.3.
4.2.24. t-Butyl [(2R)-(1-but-3-en-1-yl)-2-(t-butyl-di-
phenyl-silyl)oxypent-4-en-1-yl]carbamate
(19b).
Obtained as a mixture of two diastereoisomers in a
(1S,2R)–(1R,2R)Z2:1 ratio as determined by 1H NMR.
Yield 81% (colorless oil, purified by silicagel column
chromatography, eluent PE/EtOAcZ95:5). ESI-MS m/z
4.2.28. Benzyl (6R)-6-[(t-butyldiphenylsilyl)-oxycyclo-
hex-3-en-1-yl]carbamate (22a). Obtained as a mixture of
two diastereoisomers in a (1S,6R)–(1R,6R)Z2.5:1 ratio as
determined by HPLC. Yield 87% (colorless oil, purified by
silicagel column chromatography, eluent PE/EtOAcZ
95:5). ESI-MS m/z 486.7 [MCH]C. ee 96%, Chiralcel
OD, HEX/IPAZ99.5:0.5, 1.0 mL/min, major diastereo-
isomer RT 16.4 min (1S,6R-enantiomer), RT 25.6 min
(1R,6S-enantiomer). Minor diastereoisomer RT 33.5 min
(1S,6S-enantiomer), RT 35.3 min (1S,6S-enantiomer) no
baseline separation. 1H NMR (CDCl3): d 1.04 (s, 9H, t-Bu);
2.04–2.24 (m, 4H, CH2); 3.84 (m, 1H, CHN); 4.08 (m, 1H,
CHO); 4.79–5.02 (m, 2H, PhCH2); 5.48 (m, 1H, ]CH);
5.61 (m, 1H, ]CH); 7.35 (m, 11H, SiPh, PhCH2); 7.66 (m,
4H, SiPh). 13C NMR (CDCl3): d 19.2, 26.8, 28.3, 32.3, 50.3,
66.2, 69.0, 123.4, 124.5, 127.4, 127.6, 127.8, 128.2, 129.1,
129.5, 129.6, 133.3, 134.0, 134.6, 135.6, 136.5, 155.7.
Observed for minor isomer: 19.0, 26.4, 30.1, 51.2, 69.5,
124.2. HRMS calculated for [MCH]C 486.24649, found:
486.24590.
1
494.3 [MCH]C; 516.2 [MCNa]C. H NMR (CDCl3): d
1.07 (s, 9H, t-Bu); 1.39 (s, 9H, t-Bu); 1.30–1.60 (m, 2H,
CH2); 1.84–2.19 (m, 4H, CH2); 3.45–3.65 (m, 1H, CHN);
3.86 (m, 1H, CHO); 4.57 (d, 1H, JZ10.2 Hz, NH); 4.66–
5.07 (m, 4H, ]CH2); 5.39–5.60 (m, 1H, ]CH); 5.64–5.92
(m, 1H, ]CH); 7.41 (m, 6H, SiPh); 7.65 (m, 4H, SiPh). 13C
NMR (CDCl3): d 19.3, 26.9, 28.2, 30.1, 32.5, 38.8, 52.8,
76.4, 78.4, 114.7, 117.2, 127.4, 127.5, 129.5, 129.8, 132.7,
133.3, 133.5, 133.7, 134.0, 135.6, 137.8, 138.0, 155.1.
Observed for minor isomer: 27.1, 52.5, 75.5, 78.6, 114.5,
117.8, 155.5.
4.2.25. Benzyl [(2R)-(1-allyl-t-butyldiphenylsilyl)-oxy-
hex-5-en-1-yl]carbamate (20a). Obtained as a mixture of
two diastereoisomers in a (1S,2R)–(1R,2R)Z2.5:1 ratio as
1
determined by H NMR. Yield 68% (colorless oil, purified
by silicagel column chromatography, eluent PE/EtOAcZ
1
95:5). ESI-MS m/z 528.3 [MCH]C; 550.3 [MCNa]C. H
NMR (CDCl3): d 1.06 (s, 9H, t-Bu); 1.37–2.04 (m, 4H,
CH2); 2.18–2.45 (m, 2H, CH2); 3.69–3.85 (m, 2H, CHN,
CHO); 4.70–5.17 (m, 6H, ]CH2, CH2Ph); 5.31–5.84 (m,
2H, ]CH); 7.37 (m,11H, SiPh, CH2Ph); 7.64 (m, 4H,
SiPh). 13C NMR (CDCl3): d 19.2, 26.8, 29.3, 32.9, 37.1,
53.6, 66.0, 75.1, 114.5, 117.0, 127.3, 127.5, 127.7, 128.0,
128.1, 128.9, 129.4, 129.5, 133.2, 133.4, 134.4, 134.6,
134.8, 135.6, 137.1, 137.2, 155.4. Observed for minor
isomer: 18.8, 26.4, 33.1, 52.5, 66.3, 73.5, 118.0, 156.0.
4.2.29. t-Butyl (6R)-6-[(t-butyldiphenylsilyl)-oxycyclo-
hex-3-en-1-yl]carbamate (22b). Obtained as a mixture of
two diastereoisomers in a (1S,6R)–(1R,6R)Z2.5:1 ratio as
determined by HPLC. Yield 77% (colorless oil, purified by
silicagel column chromatography, eluent PE/EtOAcZ
95:5). ESI-MS m/z 474.4 [MCH]C. ee 98%, Chiralcel
OD, HEX/IPAZ99.75:0.25, 1.0 mL/min, major diastereo-
isomer RT 10.4 min (1S,6R-enantiomer), RT 12.3 min
(1R,6S-enantiomer). Minor diastereoisomer RT 8.3 min
1
(1S,6S-enantiomer), RT 13.9 min (1R,6R-enantiomer). H
4.2.26. t-Butyl [(2R)-(1-allyl-t-butyldiphenylsilyl)-oxy-
hex-5-en-1-yl]carbamate (20b). Obtained as a mixture of
two diastereoisomers in a (1S,2R)–(1R,2R)Z2.5:1 ratio as
NMR (CDCl3): d 1.06 (s, 9H, t-Bu); 1.43 (s, 9H, t-Bu);
1.94–2.24 (m, 4H, CH2); 3.76 (m, 1H, CHN); 4.10 (m, 1H,
CHO); 4.77 (br s, 1H, NH); 5.46 (m, 1H, ]CH); 5.63 (m,
1H, ]CH); 7.39 (m, 6H, SiPh); 7.67 (m, 4H, SiPh). 13C
NMR (CDCl3): d 19.4, 26.9, 28.3, 32.5 (C2 and C5), 49.7,
69.2, 78.9, 123.4, 124.8, 127.4, 127.6, 129.6, 129.7, 133.5,
133.6, 134.3, 135.6, 155.3. Observed for minor isomer:
1
determined by H NMR. Yield 56% (colorless oil, purified
by silicagel column chromatography, eluent PE/EtOAcZ
1
95:5). ESI-MS m/z 494.4 [MCH]C; 516.4 [MCNa]C. H
NMR (CDCl3): d 1.10 (s, 9H, t-Bu); 1.41 (s, 9H, t-Bu);

A. M. C. H. van den Nieuwendijk et al. / Tetrahedron 60 (2004) 10385–10396
10393
27.3, 50.8, 69.5, 124.2. HRMS calculated for [MCH]C
452.26155, found: 452.26230.
136.6, 155.3. Observed for minor isomer: 19.0, 21.6, 26.5,
29.6, 32.1, 52.5, 66.4 HRMS calculated for [MCH]C
500.26155, found: 500.26215.
4.2.30. Benzyl (2R)-[(t-butyldiphenylsilyl)oxycyclohept-
4-en-1-yl]carbamate (23a). Obtained as a mixture of two
diastereoisomers in a (1S,2R)–(1R,2R)Z2.8:1 ratio as
determined by HPLC. Yield 96% (colorless oil, purified
by silicagel column chromatography, eluent PE/DEEZ
92:8). ESI-MS m/z 500.3 [MCH]C; 522.6 [MCNa]C.
Chiral HPLC, ee 98%, Chiralcel OD, HEX/IPAZ99.5:0.5,
1.0 mL/min, major diastereoisomer RT 16.8 min (1R,2S-
enantiomer); RT 26.1 min (1S,2R-enantiomer). Minor
diastereoisomer RT 15.4 min (1R,2R-enantiomer), RT
4.2.33. t-Butyl (7R)-[(t-butyldiphenylsilyl)oxycyclohept-
3-en-1-yl]carbamate (24b). Obtained as a mixture of two
diastereoisomers in a (1S,7R)–(1R,7R)Z2.5:1 ratio as
1
determined by H NMR. Yield 86% (colorless oil, purified
by silicagel column chromatography, eluent PE/DEEZ
95:5). ESI-MS m/z 466.2 [MCH]C; 488.2 [MCNa]C.
Chiral HPLC, ee 98%, Chiralcel OD, HEX/IPAZ
99.75:0.25, 0.6 mL/min, Major diastereoisomer RT
10.8 min (1S,7R-enantiomer); RT 14.4 min (1R,7S-enantio-
mer). Minor diastereoisomer RT 8.1 min (1S,7S-enantio-
mer), RT 8.6 min (1R,7R-enantiomer). 1H NMR (CDCl3): d
1.09 (s, 9H, t-Bu); 1.39 (s, 9H, t-Bu); 1.46–1.65 (m, 2H,
CH2); 1.70–2.17 (m, 2H, CH2); 2.22–2.40 (m, 1H, CH2);
2.65–2.84 (m, 1H, CH2); 3.66–3.85 (m, 1H, CHN); 3.93–
4.08 (m, 1H, CHO); 4.85 (d, 1H, JZ9.5 Hz, NH); 5.60–5.95
(m, 2H, ]CH); 7.41 (m, 6H, SiPh); 7.69 (m, 4H, SiPh). 13C
NMR (CDCl3): d 19.4, 21.7, 27.1, 28.3, 29.0, 32.3, 52.6,
75.5, 78.6, 127.5, 127.7, 128.0, 129.7, 130.6, 130.7, 133.1,
133.7, 135.8, 154.9. HRMS calculated for [MCH]C
466.27720, found: 466.27728.
1
27.4 min (1S,2S-enantiomer). H NMR (CDCl3): d 1.06 (s,
9H, t-Bu); 1.51–1.88 (m, 2H, CH2); 1.95–2.38 (m, 4H,
CH2); 3.71 (m, 1H, CHN); 4.02 (m, 1H, CHO); 4.52 (d, 1H,
JZ8.0 Hz, NH); 5.02 (s, 2H, PhCH2); 5.39 (m, 1H, ]CH);
5.68–5.91 (m, 1H, ]CH); 7.36 (m, 11H, SiPh, PhCH2);
7.66 (m, 4H, SiPh). Observed for minor isomer: 3.52 (m,
CHN); 3.89 (m, CHO). 13C NMR (CDCl3): d 19.1, 24.5,
26.9, 27.7, 31.9, 58.0, 66.2, 71.1, 126.0, 127.4, 127.6, 127.7,
128.0, 128.3, 129.6, 132.3, 133.1, 133.5, 133.6, 134.1,
135.6, 135.8, 136.6, 155.3. Observed for minor isomer:
23.5, 30.2, 59.0, 66.4, 73.7, 155.5. HRMS calculated for
[MCH]C 500.26155, found: 500.26172.
4.2.34. Benzyl (8R)-[(t-butyldiphenylsilyl)oxycycloocta-
4-en-1-yl]carbamate (25). Obtained as a mixture of two
diastereoisomers in a (1S,8R)–(1R,8R)Z2.2:1 ratio as
determined by HPLC. Yield 66% at 55% conversion.
(Colorless oil, purified by silicagel column chromatography,
eluent PE/EtOAcZ95:5). ESI-MS m/z 514.2 [MCH]C;
536.6 [MCNa]C. Chiral HPLC, Chiralcel OD, HEX/IPAZ
99.5:0.5, 1.0 mL/min, major diastereoisomer RT 24.2 min
(1S,8R-enantiomer and 1R,8S-enantiomer). Minor dia-
stereoisomer RT 10.6 min (1S,8S-enantiomer and 1R,8R-
enantiomer). 1H NMR (CDCl3): d 1.10 (s, 9H, t-Bu); 1.41–
1.63 (m, 2H, CH2); 1.77–2.04 (m, 4H, CH2); 2.28–2.65 (m,
1H, CH2); 2.75–2.86 (m, 1H, CH2); 3.77–3.89 (m, 1H,
CHN); 4.06 (m, 1H, CHO); 4.32 (d, 1H, JZ8.8 Hz, NH);
4.93 (s, 2H, PhCH2); 5.51–5.78 (m, 2H, ]CH); 7.33 (m,
11H, SiPh, PhCH2); 7.67 (m, 4H, SiPh). 13C NMR (CDCl3):
d 19.4, 21.8, 22.8, 27.1, 31.0, 34.3, 53.4, 66.1, 77.5, 127.5,
127.7, 127.8, 128.3, 128.5, 129.7, 129.9, 131.2, 134.0,
134.7, 135.8, 135.9, 136.7, 155.2. HRMS calculated for
[MCH]C 514.27720, found: 514.27783.
4.2.31. t-Butyl (2R)-2-[(t-butyldiphenylsilyl)-oxycyclo-
hept-4-en-1-yl]carbamate (23b). Obtained as a mixture
of two diastereoisomers in a (1S,2R)–(1R,2R)Z2.5:1 ratio
as determined by HPLC. Yield 66% (colorless oil, purified
by silicagel column chromatography, eluent PE/EtOAcZ
95:5). ESI-MS m/z 466.2 [MCH]C; 488.2 [MCNa]C.
Chiral HPLC, Chiralcel OD, HEX/IPAZ99.75:0.25,
1.0 mL/min, major diastereoisomer, RT 7.9 min (1S,2R-
and 1R,2S-enantiomers), minor diastereoisomer RT 9.3 min
1
(1S,2S- and 1R,2R-enantiomers). H NMR (CDCl3): d 1.08
(s, 9H, t-Bu); 1.40 (s, 9H, t-Bu); 1.72–2.27 (m, 6H, CH2);
3.45–3.76 (m, 1H, CHN); 3.83–4.05 (m, 1H, CHO); 4.84 (br
s, 1H, NH); 5.36 (m, 1H, ]CH); 5.71–90 (m, 1H, ]CH);
7.40 (m, 6H, SiPh); 7.68 (m, 4H, SiPh). 13C NMR (CDCl3):
d 19.4, 26.9, 27.0, 27.8, 28.3, 32.0, 58.9, 71.5, 78.7, 125.9,
126.2, 127.5, 127.6, 129.6, 132.4, 133.3, 133.7, 133.9,
134.3, 135.7, 135.9, 154.9. Observed for minor isomer:
19.2, 30.5, 34.0, 57.6, 73.8, HRMS calculated for [MCH]C
466.27720, found: 466.27753.
4.3. Preparation of N-heterocycles
4.2.32. Benzyl (7R)-[(t-butyldiphenylsilyl)oxycyclohept-
3-en-1-yl]carbamate (24a). Obtained as a mixture of two
diastereoisomers in a (1S,7R)–(1R,7R)Z2.8:1 ratio as
determined by HPLC. Yield 94% (colorless oil, purified
by silicagel column chromatography, eluent PE/DEEZ
95:5). ESI-MS m/z 500.2 [MCH]C; 522.4 [MCNa]C. ee
98%, Chiralcel OD, HEX/IPAZ99.5:0.5, 1.0 mL/min, RT
10.3 min (1R,7R-enantiomer), RT 11.4 min (1R,7S-enantio-
4.3.1. (2R,3E)-1-Allylamino-2-[(t-butyldiphenylsilyl)-
oxy]-pent-3-ene-2-ol (26). [a]2D0ZK14.2 (cZ1.0,
CH2Cl2). ESI-MS m/zZ380.2 [MCH]C. 1H NMR
(CDCl3): d 1.05 (s, 9H, t-Bu); 1.50 (d, 3H, JZ5.9 Hz,
CH3); 2.51–2.73 (m, 2H, CH2); 3.12 (d, 2H, JZ5.8 Hz,
CH2); 4.23 (m, 1H, CHO); 5.07 (m, 2H, ]CH2); 5.19–5.45
(m, 2H, ]CH); 5.72–5.91 (m, 1H, ]CH); 7.35 (m, 6H,
SiPh); 7.66 (m, 4H, SiPh). 13C NMR (CDCl3); d 17.3, 19.1,
26.9, 51.8, 55.3, 73.7, 115.6, 127.1, 127.3, 127.5, 129.3,
129.4, 132.0, 134.0, 135.6, 135.8, 136.5.
1
mer), RT 16.1 (1S,7R- and 1S,7S-enantiomers). H NMR
(CDCl3): d 1.10 (s, 9H, t-Bu); 1.38–1.58 (m, 2H, CH2);
1.65–2.17 (m, 2H, CH2); 2.26–2.45 (m, 1H, CH2); 2.50–
2.88 (m, 1H, CH2); 3.77 (m, 1H, CHN); 4.01 (m, 1H, CHO);
4.79 (d, 1H, JZ8.8 Hz, NH); 5.00 (s, 2H, PhCH2); 5.68 (m,
1H, ]CH); 5.81 (m, 1H, ]CH); 7.35 (m, 11H, SiPh,
PhCH2); 7.69 (m, 4H, SiPh). 13C NMR (CDCl3): d 19.3,
21.8, 27.0, 28.8, 32.3, 53.1, 66.1, 75.3, 127.5, 127.7, 128.3,
129.3, 129.7, 133.3, 133.6, 133.7, 134.7, 135.7, 135.8,
4.3.2. Benzyl 1-allyl[(2R,3E)-2-(t-butyldiphenylsilyl)-
oxy-pent-3-en-1-yl]carbamate (27a). Yield 88% (colorless
oil, purified by silicagel column chromatography, eluent
PE/DEEZ95:5). [a]D25ZK14.8 (cZ1.0, CH2Cl2). ESI-MS

10394
A. M. C. H. van den Nieuwendijk et al. / Tetrahedron 60 (2004) 10385–10396
1
m/zZ414.3 [MCH]C. H NMR (CDCl3): d 1.03 (s, 9H,
t-Bu); 1.43 (d, 3H, JZ5.9 Hz, CH3); 3.14–3.40 (m, 2H,
CH2); 3.78 (m, 2H, CH2); 4.19–4.39 (m, 1H, CHO); 4.91–
5.13 (m, 5H, PhCH2, CH]CH2); 5.26 (m, 1H, ]CH);
5.59–5.76 (m, 1H, ]CH); 7.28 (m, 11H, SiPh, PhCH2);
7.60 (m, 4H, SiPh). 13C NMR (CDCl3): d 17.4, 19.1, 26.9,
50.7, 52.6, 66.9, 73.0, 116.3, 127.2, 127.4, 127.7, 128.0,
128.3, 129.4, 131.3, 133.4, 133.6, 133.9, 135.8, 136.0,
156.0.
(m, 1H, CHO); 5.65 (m, 2H, CH]CH); 7.38 (m, 6H, SiPh);
7.65 (m, 4H, SiPh). 13C NMR (CDCl3): d 19.1, 26.9, 28.3,
42.9, 48.7, 65.2, 79.3, 125.8, 127.4, 127.5, 127.7, 129.4,
129.5, 129.6, 133.9, 134.1, 135.6, 154.4. HRMS calculated
for [MCNa]C 460.22812, found: 460.22784.
4.3.7.
(3R)-1-Benzyl-3-[(t-butyldiphenylsilyl)oxy]-
1,2,3,6-tetrahydropyridin-3-ol (28c). Yield 94% (colorless
oil, purified by silicagel column chromatography, eluent
PE/DEEZ95:5). [a]D25ZK18.2 (cZ1.0, CH2Cl2). ESI-MS
m/zZ428.0 [MCH]C. ee O99%, Chiralcel OD, HEX/
IPAZ99.75:0.25, 1.0 mL/min, RT 9.8 min (R-enantiomer),
4.3.3. t-Butyl 1-allyl[(2R,3E)-2-(t-butyldiphenylsilyl)-
oxy-pent-3-en-1-yl]carbamate (27b). Yield 86% (color-
less oil, purified by silicagel column chromatography,
eluent PE/DEEZ95:5). [a]2D5ZK17.0 (cZ1.0, CH2Cl2).
1
RT 12.2 min (S-enantiomer). H NMR (CDCl3): d 1.05 (s,
9H, t-Bu); 2.36 (dd, 1H, JZ6.6, 11.0 Hz, CH2); 2.68 (dd,
1H, JZ5.1, 11.0 Hz, CH2); 2.90 (m, 2H, CH2); 3.53 (m, 2H,
CH2); 4.36 (m, 1H, CHO); 5.69 (m, 2H, CH]CH); 7.23–
7.41 (m, 11H, Ph, SiPh); 7.64 (m, 4H, SiPh). 13C NMR
(CDCl3): d 19.1, 26.9, 52.4, 57.2, 62.1, 66.9, 127.0, 127.5,
128.2, 128.9, 129.3, 129.6, 134.1, 135.7, 135.8, 138.0.
HRMS calculated for [MCH]C 428.24042, found:
428.24097.
ESI-MS m/zZ480.2 [MCH]C. H NMR (CDCl3): d 1.05
1
(s, 9H, t-Bu); 1.38 (d, 3H, JZ5.9 Hz, CH3); 1.41 (s, 9H,
t-Bu); 3.07–3.40 (m, 2H, CH2); 3.63–3.84 (m, 2H, CH2);
4.25 (m, 1H, CHO); 5.00 (m, 2H, ]CH2); 5.12–5.37 (m,
2H, ]CH); 5.58–5.75 (m, 1H, ]CH); 7.35 (m, 6H, SiPh);
7.64 (m, 4H, SiPh). 13C NMR (CDCl3): d 17.4, 19.0, 26.9,
28.1, 50.4, 52.4, 73.3, 79.1, 115.6, 127.1, 127.3, 129.3,
131.6, 133.8, 135.6, 135.8, 155.0.
4.3.8. Benzyl (3R)-3-hydroxy-3,6-dihydropyridine-
(132 mg,
4.3.4.
(2R,3E)-1-[Allyl(benzyl)amino-2-(t-butyl-di-
1(2H)-carboxylate.
Compound
28a
phenylsilyl)oxypent-3-en-2-ol (27c). Yield 77% (colorless
oil, purified by silicagel column chromatography, eluent PE/
DEEZ100:0/90:10). [a]2D5ZC15.2 (cZ1.0, CH2Cl2).
0.280 mmol) was dissolved in THF (5.0 mL) and an excess
of tetrabutylammonium fluoride (3 equiv) was added. After
2 h TLC showed complete conversion of 28a. The solvent
was evaporated in vacuo and the residue purified by
silicagel column chromatography, eluent PE/EtOAcZ
3:1/1:3, to give the title compound (56 mg) in 99%
yield as a colorless oil. [a]2D1ZK65.4 (cZ1.0, CHCl3, lit.17,
[a]3D0ZK67.0 (cZ0.96, CHCl3)). ee 98%, Chiralcel ODH,
HEX/IPAZ85:15, 1.0 mL/min, RT 8.3 min (R-enantio-
1
ESI-MS m/zZ470.2 [MCH]C. H NMR (CDCl3): d 1.03
(s, 9H, t-Bu); 1.52 (d, 3H, JZ6.6 Hz, CH3); 2.50 (m, 2H,
CH2); 2.92 (d, 2H, JZ6.6 Hz, C]CCH2); 3.43 (s, 2H,
PhCH2); 4.14 (m, 1H, CHO); 5.04 (m, 2H, ]CH2); 5.20–
5.47 (m, 2H, ]CH2); 5.62–5.79 (m, 1H, ]CH); 7.21 (s,
5H, PhCH2); 7.37 (m, 6H, SiPh); 7.66 (m, 4H, SiPh). 13C
NMR (CDCl3): d 17.6, 19.2, 27.1, 57.3, 58.8, 60.4, 73.1,
116.9, 126.2, 126.6, 127.2, 127.4, 127.9, 128.1, 128.3,
128.7, 128.9, 129.3, 129.4, 133.3, 134.3, 134.4, 135.9,
136.0, 139.7.
1
mer), 10.5 min (S-enantiomer). H NMR (CDCl3): d 2.19
(broad s, 1H, OH); 3.63 (m, 2H, CH2); 3.92 (m, 2H, CH2);
4,21 (m, 1H, CHO); 5.15 (s, 2H, PhCH2); 5.90 (m, 2H,
CH]CH); 7.35 (s, 5H, Ph). 13C NMR (CDCl3): d 43.1,
47.4, 63.1, 67.2, 125.9, 126.8, 127.8, 127.9, 128.4, 136.3,
155.6.
4.3.5. Benzyl (3R)-3-[(t-butyldiphenylsilyl)oxy]-3,6-di-
hydropyridine-1(2H)-carboxylate (28a). Yield 82%
(colorless oil, purified by silicagel column chromatography,
eluent PE/EtOAcZ95:5). [a]2D5ZK18.8 (cZ1.0, CH2Cl2).
ESI-MS m/zZ472.5 [MCH]C, 943.5 [M2CH]C. Chiralcel
OD, HEX/IPAZ99.8:0.2, 1.0 mL/min, RT 16.7 min (R-
enantiomer) and 18.3 min (S-enantiomer) no baseline
4.3.9. (2R)-1-Allylamino-2-[(t-butyldiphenylsilyl)-oxy]-
pent-4-en-2-ol (29). [a]2D0ZK9.4 (cZ1.0, CH2Cl2). ESI-
MS m/zZ380.1 [MCH]C. 1H NMR (CDCl3): d 1.06 (s, 9H,
t-Bu); 2.26 (m, 2H, CH2); 2.61 (d, 2H, JZ5.1 Hz, CH2);
3.08 (d, 2H, JZ5.8 Hz, CH2); 3.89 (m, 1H, CHO); 4.96 (m,
4H, ]CH2); 5.57–5.85 (m, 2H, ]CH); 7.40 (m, 6H, SiPh);
7.66 (m, 4H, SiPh). 13C NMR (CDCl3): d 19.2, 26.9, 39.9,
52.1, 53.9, 72.4, 115.3, 117.0, 125.2, 127.5, 128.1, 128.9,
129.6, 134.0, 134.4, 135.8, 136.8.
1
separation. H NMR (CDCl3): d 1.06 (s, 9H, t-Bu); 3.29
(m, 1H, CH2); 3.67 (m, 1H, CH2); 3.96 (m, 2H, CH2); 4.23
(m, 1H. CHO); 5.06 (m, 2H, PhCH2); 5.71 (m, 2H,
CH]CH); 7.32 (m, 11H, Ph, SiPh); 7.64 (m, 4H, SiPh).
13C NMR (CDCl3): d 19.1, 26.9, 43.2, 47.4, 64.9, 67.0,
124.9, 125.9, 127.6, 127.9, 128.4, 129.2, 129.8, 132.3,
133.7, 135.7, 136.6, 155.1. HRMS calculated for [MCNa]C
494.21219, found: 494.21271.
4.3.10. (2R)-1-Allylamino-2-[(t-butyldiphenylsilyl)-oxy]-
hex-5-en-2-ol (30). [a]2D0ZK3.0 (cZ1.0, CH2Cl2). ESI-
MS m/zZ394.0 [MCH]C. 1H NMR (CDCl3): d 1.06 (s, 9H,
t-Bu); 1.43–1.64 (m, 2H, CH2); 1.77–2.03 (m, 2H, CH2);
2.60 (d, 2H, JZ5.1 Hz, CH2); 3.07 (d, 2H, JZ5.8 Hz, CH2);
3.84–3.93 (m, 1H, CHO); 4.80–4.91 (m, 2H, ]CH2); 4.99–
5.11 (m, 2H, ]CH2); 5.50–5.88 (m, 2H, 2!ZCH); 7.38
(m, 6H, SiPh); 7.69 (m, 4H, SiPh). 13C NMR (CDCl3): d
19.3, 27.0, 29.4, 34.4, 52.2, 54.2, 72.4, 114.3, 115.4, 127.5,
129.5, 129.6, 134.1, 135.7, 135.8, 136.8, 138.2.
4.3.6. t-Butyl (3R)-3-[(t-butyldiphenylsilyl)oxy]-3,6-di-
hydropyridine-1(2H)-carboxylate (28b). Yield 80%
(colorless oil, purified by silicagel column chromatography,
eluent PE/DEEZ95:5). [a]2D5ZK25.4 (cZ1.0, CH2Cl2).
ESI-MS m/zZ438.0 [MCH]C. Chiralcel OD, HEX/IPAZ
99.8:0.2, 1.0 mL/min, RT 10.0 min (R-enantiomer) and
1
10.6 min (S-enantiomer) no baseline separation. H NMR
(CDCl3): d 1.07 (s, 9H, t-Bu); 1.41 (s, 9H, t-Bu); 3.21 (dd,
1H, JZ7.2, 12.9 Hz, CH2); 3.68–3.93 (m, 3H, CH2); 4.27
4.3.11. Benzyl 1-allyl[(2R)-2-(t-butyldiphenylsilyl)-oxy-
pent-4-en-1-yl]carbamate (31a). Yield 72% (colorless oil,

A. M. C. H. van den Nieuwendijk et al. / Tetrahedron 60 (2004) 10385–10396
10395
purified by silicagel column chromatography, eluent PE/
EtOAcZ97:3/95:5). [a]2D0ZK20.2 (cZ1.0, CH2Cl2).
4.3.16. Benzyl (3R)-3-[(t-butyldiphenylsilyl)oxy]-2,3,4,7-
tetrahydro-1H-azepine-1-carboxylate (33a). Yield 74%
(colorless oil, purified by silicagel column chromatography,
eluent PE/EtOAcZ95:5). [a]2D0ZK12.6 (cZ1.0, CH2Cl2).
ESI-MS m/zZ486.3 [MCH]C, 508.3 [MCNa]C. ee 98%,
Chiralcel OD, HEX/IPAZ99.75:0.25, 1.2 mL/min, RT
1
ESI-MS m/zZ514.4 [MCH]C. H NMR (CDCl3): d 1.04
(s, 9H, t-Bu); 2.10 (m, 2H, CH2); 3.16 (m, 1H, CH2); 3.29–
3.61 (m, 1H, CH2); 3.75 (m, 2H, CH2); 4.02 (m, 1H, CHO);
4.77–5.07 (m, 6H, ]CH2, PhCH2); 5.67 (m, 2H, 2!ZCH);
7.35 (m, 11H, SiPh, PhCH2); 7.63 (m, 4H, SiPh). 13C NMR
(CDCl3): d 19.1, 26.9, 39.2, 50.6, 51.5, 66.9, 71.1, 116.3,
117.2, 127.5, 127.7, 127.9, 128.2, 129.6, 130.0, 130.3,
133.3, 133.4, 133.7, 135.7, 135.8, 136.5, 155.9.
1
24.1 min (S-enantiomer); RT 25.8 min (R-enantiomer). H
NMR (CDCl3): d 1.05 (s, 9H, t-Bu); 2.25 (dd, 2H, JZ5.1,
5.9 Hz, CH2); 3.32 (m, 1H, CH2); 3.68–4.24 (m, 4H, CH2,
CHO); 5.06 (m, 2H, PhCH2); 5.55 (m, 1H, ]CH); 5.74 (m,
1H, ]CH); 7.32 (m, 11H, SiPh, PhCH2); 7.64 (m, 4H,
SiPh). 13C NMR (CDCl3): d 19.0, 26.8, 34.8, 46.6, 54.5,
66.7, 69.8, 126.7, 127.2, 127.5, 127.7, 128.2, 129.2, 129.3,
129.6, 133.7, 135.6, 155.5. HRMS calculated for [MCH]C
486.24590, found: 486.24637.
4.3.12. t-Butyl 1-allyl[(2R)-2-(t-butyldiphenylsilyl)-oxy-
pent-4-en-1-yl]carbamate (31b). Yield 86% (colorless oil,
purified by silicagel column chromatography, eluent PE/
EtOAcZ95:5). [a]D20ZK19.6 (cZ1.0, CH2Cl2). ESI-MS
1
m/zZ480.3 [MCH]C. H NMR (CDCl3): d 1.06 (s, 9H,
t-Bu); 1.40 (s, 9H, t-Bu); 2.06 (dd, 2H, JZ6.6, 13.9 Hz,
CH2); 3.00–3.88 (m, 4H, 2!CH2); 4.00 (m, 1H, CHO);
4.83–5.05 (m, 4H, ]CH2); 5.65 (m, 2H, ]CH); 7.40 (m,
6H, SiPh); 7.67 (m, 4H, SiPh). 13C NMR (CDCl3): d 19.0,
26.8, 28.1, 39.3, 50.6, 51.3, 71.4, 79.0, 115.6, 117.0, 127.4,
129.5, 133.7, 133.9, 135.1, 135.6, 155.1.
4.3.17. t-Butyl (3R)-3-[(t-butyldiphenylsilyl)oxy]-2,3,4,7-
tetrahydro-1H-azepine-1-carboxylate (33b). Yield 76%
(colorless oil, purified by silicagel column chromatography,
eluent PE/EtOAcZ95:5). [a]2D0ZK23.4 (cZ1.0, CH2Cl2).
ESI-MS m/zZ452.2 [MCH]C, 474.3 [MCNa]C. ee 97%,
Chiralcel OD, HEX/IPAZ99.8:0.2, 1.0 mL/min, RT
9.3 min (R-enantiomer), 10.9 min (S-enantiomer). 1H
NMR (CDCl3): d 1.06 (s, 9H, t-Bu); 1.37 (s, 9H, t-Bu);
2.25 (m, 2H, CH2); 3.19 (dd, 1H, JZ8.0, 13.9 Hz, CH2);
3.45–4.09 (m, 3H, CH2); 4.24 (m, 1H, CHO); 5.53 (m, 1H,
]CH); 5.68 (m, 1H, ]CH); 7.39 (m, 6H, SiPh), 7.65 (m,
4H, SiPh). 13C NMR (CDCl3): d 19.2, 27.2, 28.3, 34.5, 46.8,
54.3, 70.4, 79.5, 126.2, 126.9, 127.6, 129.6, 129.7, 133.8,
135.7, 154.8. HRMS calculated for [MCH]C 452.26155,
found: 452.26239.
4.3.13. (2R)-1-Allyl-1-benzyl-2-[(t-butyldiphenylsilyl)-
oxy]-1-aminopent-4-ene-2-ol (31c). Yield 67% (colorless
oil, purified by silicagel column chromatography, eluent PE/
EtOAcZ100:0/90:10). [a]2D0ZC30.8 (cZ1.0, CH2Cl2).
1
ESI-MS m/zZ470.3 [MCH]C. H NMR (CDCl3): d 1.04
(s, 9H, t-Bu); 2.18 (m, 1H, CH2); 2.35 (m, 2H, CH2); 2.54
(m, 1H, CH2); 2.83 (m, 2H, CH2); 3.33 (dd, 2H, JZ2.2,
13.9 Hz, PhCH2); 3.85 (m, 1H, CHO); 4.80–5.05 (m, 4H,
]CH2); 5.61–5.85 (m, 2H, ]CH); 7.20–7.43 (m, 11H,
PhCH2, SiPh); 7.67 (m, 4H, SiPh). 13C NMR (CDCl3): d
19.3, 27.1, 33.2, 39.4, 57.4, 58.9, 71.5, 116.9, 117.2, 126.7,
127.5, 128.0, 128.3, 128.7, 128.9, 129.6, 134.2, 134.4,
135.1, 135.7, 136.0, 136.5, 139.6.
4.3.18. (3R)-1-Benzyl-3-[(t-butyldiphenylsilyl)oxy]-
2,3,4,7-tetrahydroazepine (33c). For this reaction diene
31c (184 mg, 0.392 mmol) was dissolved in CH2Cl2
(40 mL) and HCl (4 M in dioxane, 0.11 mL, 0.440 mmol)
was added. Argon was bubbled through the solution for
5 min and the Grubbs catalyst (13 mg, 4 mol%) was added.
The reaction was refluxed for 24 h, cooled, washed with an
aqueous saturated NaHCO3 solution, dried (MgSO4) and
concentrated to afford the crude product. Purification gave
the title compound (20 mg) in 12% yield. (colorless oil,
purified by silicagel column chromatography, eluent PE/
4.3.14. Benzyl 1-allyl[(2R)-2-(t-butyldiphenylsilyl)-oxy-
hex-5-en-1-yl]carbamate (32a). Yield 62% (colorless oil,
purified by silicagel column chromatography, eluent PE/
EtOAcZ95:5). [a]D20ZK12.2 (cZ1.0, CH2Cl2). ESI-MS
1
m/zZ528.2 [MCH]C. H NMR (CDCl3): d 1.04 (s, 9H,
t-Bu); 1.25–1.56 (m, 2H, CH2); 1.84–2.05 (m, 2H, CH2);
3.13 (m, 1H, CH2); 3.31–3.83 (m, 3H, CH2); 3.94 (m, 1H,
CHO); 4.71–5.18 (m, 6H, ]CH2, PhCH2); 5.40–5.71 (m,
2H, ]CH); 7.36 (m, 11H, SiPh, PhCH2); 7.64 (m, 4H,
SiPh). 13C NMR (CDCl3): d 19.0, 26.8, 28.6, 33.6, 50.3,
51.3, 66.8, 70.8, 114.2, 116.1, 127.3, 127.6, 128.1, 129.4,
133.1, 133.7, 135.6, 136.3, 137.8, 155.8.
EtOAcZ95:5). [a]D20ZC161 (cZ0.4, CH2Cl2). H NMR
1
(CDCl3): d 1.02 (s, 9H, t-Bu); 2.42 (m, 2H, CH2); 2.84 (dd,
1H, JZ8.0, 13.2 Hz, CH2); 3.14 (m, 3H, CH2); 3.54 (d, 1H,
JZ13.2 Hz, CH2Ph); 3.62 (d, 1H, JZ13.2 Hz, CH2Ph);
3.94 (m, 1H, CHO); 5.61 (m, 2H, CH]CH); 7.25 (s, 5H,
Ph); 7.39 (m, 6H, SiPh); 7.61 (m, 4H, SiPh). 13C NMR
(CDCl3): 19.2, 26.9, 36.5, 52.4, 56.6, 59.9, 68.2, 127.4,
127.6, 128.3, 128.7, 129.3, 129.7, 135.7, 137.2.
4.3.15. t-Butyl 1-allyl[(2R)-2-(t-butyldiphenylsilyl)-oxy-
hex-5-en-1-yl]carbamate (32b). Yield 47% (colorless oil,
purified by silicagel column chromatography, eluent PE/
DEEZ98:2/95:5). [a]2D0ZK18.6 (cZ1.0, CH2Cl2). ESI-
MS m/zZ494.6 [MCH]C, 516.3 [MCNa]C. 1H NMR
(CDCl3): d 1.05 (s, 9H, t-Bu); 1.40 (s, 9H, t-Bu); 1.25–1.53
(m, 2H, CH2); 2.00 (m, 2H, CH2); 3.02 (m, 1H, CH2); 3.55
(m, 2H, CH2); 3.77 (m, 1H, CH2); 3.92 (m, 1H, CHO); 4.80–
5.03 (m, 4H, 2!ZCH2); 5.47–5.68 (m, 2H, 2!ZCH);
7.40 (m, 6H, SiPh); 7.67 (m, 4H, SiPh). 13C NMR (CDCl3):
d 19.1, 26.9, 28.2, 28.7, 33.7, 50.2, 51.2, 71.2, 79.3, 114.1,
115.6, 127.5, 127.8, 129.5, 133.8, 134.0, 135.7, 136.7,
138.1, 138.3, 155.2.
4.3.19. Benzyl (3R)-3-[(t-butyldiphenylsilyl)oxy]-3,4,5,8-
tetrahydroazocine-1(2H)-carboxylate (34a). Yield 61%,
based on converted starting material, conversion 50% after
24 h. (colorless oil, purified by silicagel column chroma-
tography, eluent PE/DEEZ9:1). [a]2D1ZC20.4 (cZ1,
CH2Cl2). ESI-MS m/zZ500.2 [MCH]C, 522.4 [MC
Na]C. ee 97%, Chiralcel OD, HEX/IPAZ99.75:0.25,
1.0 mL/min, RT 22.6 min (S-enantiomer), 25.1 min (R-
enantiomer). 1H NMR (CDCl3): d 1.04 (s, 9H, t-Bu); 1.55–
2.27 (m, 4H, CH2); 3.30–4.13 (m, 5H, CH2, CHO); 5.01 (s,
2H, PhCH2); 5.11 (s, 2H, PhCH2); 5.30 (m, 1H, ]CH); 5.63

10396
A. M. C. H. van den Nieuwendijk et al. / Tetrahedron 60 (2004) 10385–10396
Biocatalysis; Marcel Dekker: New York; 2000, pp 289–320,
Chapter 11.
(m, 1H, ]CH); 7.15–7.41 (m, 11H, SiPh, PhCH2); 7.64 (m,
4H, SiPh). 13C NMR (CDCl3): d 19.1, 21.5, 26.9, 34.9, 47.4,
52.9, 67.0, 69.7, 125.0, 126.3, 127.5, 127.8, 128.0, 128.3,
129.6, 130.9, 133.9, 134.3, 134.9, 135.7, 136.8, 155.8.
HRMS calculated for [MCH]C 500.26155, found:
500.26251.
6. Effenberger, F. Hydroxynitrile lyases in stereo selective
synthesis. Patel, R. N., Ed.; Stereoselective Biocatalysis;
Marcel Dekker: New York; 2000, pp 321–342, Chapter 12.
7. Warmerdam, E. G. J. C.; Brussee, J.; Kruse, C. G.; van der
Gen, A. Tetrahedron 1993, 49, 1063–1070.
4.3.20. t-Butyl (3R)-3-[(t-butyldiphenylsilyl)oxy]-3,4,5,8-
tetrahydroazocine-1(2H)-carboxylate (34b). Yield 87%,
based on converted starting material, conversion 52% after
24 h. (colorless oil, purified by silicagel column chroma-
tography, eluent PE/DEEZ95:5). [a]2D1ZC23.4 (cZ1,
CH2Cl2). ESI-MS m/zZ466.2 [MCH]C, 488.2 [MC
Na]C, 954.0 [M2CNa]C. Chiral HPLC, Chiralcel OD, no
separation. 1H NMR (CDCl3): d 1.05 (s, 9H, t-Bu); 1.38 (s,
9H, t-Bu); 1.66–1.94 (m, 3H, CH2); 2.21 (m, 1H, CH2);
3.12–3.54 (m, 2H, CH2); 3.70–3.92 (m, 2H, CH2); 4.01–
4.13 (m, 1H, CHO); 5.27 (m, 1H, ]CH); 5.60 (m, 1H,
]CH); 7.40 (m, 6H, SiPh,); 7.67 (m, 4H, SiPh). 13C NMR
(CDCl3): d 19.1, 21.3, 26.9, 28.9, 35.1, 47.5, 53.0, 69.7,
79.4, 125.9, 127.5, 128.4, 129.6, 129.9, 133.9, 134.2, 134.3,
135.7, 155.1. HRMS calculated for [MCH]C 466.27720,
found: 466.27924.
8. Gerrits, P. J.; Marcus, J.; Birikaki, L.; van der Gen, A.
Tetrahedron: Asymmetry 2001, 12, 971–974.
9. Marcus, J.; Brussee, J.; van der Gen, A. Eur. J. Org. Chem.
1998, 2513–2517.
10. For recent reviews see: (a) Trnka, T. M.; Grubbs, R. H. Acc.
Chem. Res. 2001, 34, 18–29. (b) Maier, M. E. Angew. Chem.,
Int. Ed. 2000, 39, 2073–2077. (c) Roy, R.; Das, S. K. Chem.
Commun. 2000, 519–529. (d) Phillips, A. J.; Abell, A. D.
Aldrichim. Acta 1999, 32, 75–89.
11. Brussee, J.; van der Gen, A. Recl. Trav. Chim. Pays-Bas 1991,
110, 25–26.
12. Zandbergen, P.; van den Nieuwendijk, A. M. C. H.; Brussee,
J.; van der Gen, A.; Kruse, C. G. Tetrahedron 1992, 48,
3977–3982.
13. Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc.
1996, 118, 100–110.
14. Bis(tricyclohexylphosphine)benzylidine ruthenium(IV)
dichloride, Grubbs’ catalyst, was obtained from Strem.
15. Compound 12 was described as a racemate. (a) van Benthem,
R. A. T. M.; Hiemstra, H.; Speckamp, W. N. J. Org. Chem.
1992, 57, 6083–6085. van Benthem, R. A. T. M. Palladium
cluster catalyzed oxidative cyclizations in the synthesis of
aminoalkenols and diamines, Chapter 9, PhD Thesis,
University of Amsterdam, The Netherlands, 1995.
16. Compound 13 was prepared in 58% e.e. Bayer, A.; Hansen,
L. K.; Gautun, O. R. Tetrahedron: Asymmetry 2002, 13,
2407–2415.
References and notes
1. North, M. Tetrahedron: Asymmetry 2003, 14, 147–176.
2. Gregory, R. J. H. Chem. Rev. 1999, 99, 3649–3682.
3. Effenberger, F. Angew. Chem., Int. Ed. Engl. 1994, 33,
1555–1563.
4. Schmidt, M.; Griengl, H. Top. Curr. Chem. 1999, 200,
193–226.
5. Brussee, J.; van der Gen, A. Biocatalysis in the enantio-
selective formation of chiral cyanohydrins, valuable building
blocks in organic chemistry. Patel, R. N., Ed.; Stereoselective
17. Sakagami, H.; Ogasawara, K. Synthesis 2000, 521–524.
18. Han, H. Tetrahedron Lett. 2003, 44, 1567–1569.