Addition of allylzinc to a-amino acid-derived imines: Synthesis of diamino alcohols by Hydroboration

Article abstract of DOI:10.1007/s00706-009-0239-y

Imines obtained by condensation of Z-pro- tected or Boc-protected α-amino aldehydes with α-amino tert-butyl esters or with O-silyl-protected amino alcohols were reacted with preformed allyl zinc yielding homoal- lylamines with yields around 50% and selectivities ranging from 50:50 to 90:10. Hydroboration of the terminal double bond furnished diamino alcohols with yields up to 97%. The configuration of the substrates was determined by X-ray-crystallographic analysis of a hydroboration product and comparison of physical data. Springer-Verlag 2010.

Full text of DOI:10.1007/s00706-009-0239-y

Monatsh Chem (2010) 141:177–198
DOI 10.1007/s00706-009-0239-y
ORIGINAL PAPER
Addition of allylzinc to a-amino acid-derived imines:
synthesis of diamino alcohols by hydroboration
•
Mickael Virlouvet Helmut Goesmann
•
•
Claus Feldmann Joachim Podlech
Received: 6 October 2009 / Accepted: 12 December 2009 / Published online: 4 February 2010
Ó Springer-Verlag 2010
Abstract Imines obtained by condensation of Z-pro-
tected or Boc-protected a-amino aldehydes with a-amino
tert-butyl esters or with O-silyl-protected amino alcohols
were reacted with preformed allyl zinc yielding homoal-
lylamines with yields around 50% and selectivities ranging
from 50:50 to 90:10. Hydroboration of the terminal double
bond furnished diamino alcohols with yields up to 97%.
The configuration of the substrates was determined by
X-ray-crystallographic analysis of a hydroboration product
and comparison of physical data.
occasionally in the addition of C-nucleophiles. The addi-
tion of cyanide to a-amino imines has been reported once
[10].
In the course of our studies on the synthesis of pepti-
domimetics [11–17] we needed allyl adducts to a-amino
imines and the resulting alcohols obtained by subsequent
hydroboration. Here we report the synthesis of these
compounds, which should be useful starting materials in
organic synthesis.
Keywords Amino acids ꢀ Schiff bases ꢀ Allyl addition ꢀ
Nucleophilic additions ꢀ Amino alcohols
Results and discussion
Preparation of a-amino acid-derived imines
Introduction
We decided to use N-Boc (tert-butyloxycarbonyl)-pro-
tected and N-Z (benzyloxycarbonyl)-protected a-amino
acids as starting materials to enable deprotection of the
compounds obtained by standard procedures [18]. N-Pro-
tected amino aldehydes used for the preparation of imines
were obtained via two routes (Scheme 2). Route A was
used for the preparation of Z-protected products [18] and
included protection, esterification [19], and reduction of
thus obtained Z-protected amino esters with lithium alu-
minum hydride [20]. In route B we started with reduction
of an a-amino acid yielding an amino alcohol [21] and
subsequent N-protection with Boc [22] or Z [23]. Route A
proved to be more effective, because fewer by-products
were obtained during this three-step procedure and chro-
matographic purification of the protected amino alcohols
was often dispensable. In both routes a final oxidation with
either Dess–Martin periodinane [24] or with sodium
hypochlorite and catalytic amounts of 2,2,6,6-tetramethyl-
piperidine-N-oxide (TEMPO) [25] furnished N-protected
amino aldehydes with yields ranging from 50 to 80%.
Amino acids have widely been used as starting materials in
stereoselective synthesis [1]. Astonishingly, this pool of
chiral substances [2, 3] has never been used for addition of
C-nucleophiles to amino acid-derived a-amino imines
(Scheme 1), most probably because of the rather poor
reactivity of imines as compared with, e.g., aldehydes [4].
Similarly reactive a-amino hydrazones [5, 6] and a-amino
nitrones [7–9, and references cited therein] have been used
M. Virlouvet ꢀ J. Podlech (&)
Karlsruher Institut fu¨r Technologie (KIT),
Institut fu¨r Organische Chemie, Fritz-Haber-Weg 6,
76131 Karlsruhe, Germany
e-mail: joachim.podlech@kit.edu
H. Goesmann ꢀ C. Feldmann
Karlsruher Institut fu¨r Technologie (KIT),
Institut fu¨r Anorganische Chemie,
Engesserstraße 15, 76131 Karlsruhe, Germany
123

178
M. Virlouvet et al.
R
R
R
R
BuOAc, HClO
t
R
4
PG
PG
R''
R'
R''M
H2N
H2N
CO Bu
H2N
H2N
CO2H
OH
2t
N
α
-amino
acid
N
H
H
N
HN
R'
R
TBSCl or TBDPSCl
Imidazole
OPG
Scheme 1
R: Me, Pr, Bu, Bn
i
i
PG: TBS, TBDPS
Route A
1) ZCl, NaOH
2) SOCl2, MeOH
3) LiAlH4
Scheme 3
R
R
PG
OH
R1
R1
N
N
H
H2N
CO2H
Route B
1) LiAlH4
2) ZCl, NaHCO3
or Boc2O, Et3N
MS 4 Å or Na2SO4
PG
N
PG
R = Me, iPr, iBu, Bn
PG: Boc, Z
R2
quant.
H
H
N
O
R2
X
OR3
H2N
R1, R2: Me, iPr, iBu, Bn
3 = tBu, TBS, TBDPS
X: O or H,H
R3O
Dess-Martin periodinane
or
X
R
PG
R
N
NaOCl, TEMPO
H
O
Scheme 4
Scheme 2
Amino components used for the preparation of imines
were similarly prepared from a-amino acids (Scheme 3).
Amino acid tert-butyl esters were obtained by transesteri-
fication with tert-butyl acetate [26] and O-silyl-protected
amino alcohols were obtained by silylation of amino
alcohols with tert-butyldimethylsilyl chloride (TBSCl) or
tert-butyldiphenylsilyl chloride (TBDPSCl) [27].
Boc
N
Boc
Boc
Zn, CeCl3·7 H2O
N
H
H
N
Br
HN
1
2
51%
CO2Me
CO2Me
1) 9-BBN
2) H2O2, KOAc
N
OH
H
HN
Imines were obtained by mixing stoichiometric amounts
3
of an aldehyde and an amine component together with
˚
either molecular sieves (4 A) or with anhydrous sodium
CO2Me
Scheme 5
sulfate (Scheme 4).
Addition of organozinc compounds to amino acid-
derived imines
To obtain compounds suitable for a hydroboration by an
oxidative workup in the presence of sodium hydroxide we
used either tert-butyl ester derivatives or silyl-protected
amino alcohol-derived imines 4–19 in further experiments.
Allyl addition under conditions as applied to the methyl
ester 1 gave homoallylamines 20–35 (Table 1) as mixtures
of isomers, which could be separated by conventional
chromatography except for product 35. The allyl adducts
were obtained in yields up to 66%, where differing
amounts of side products were observed. Small amounts
(up to 30%) of homoallylalcohols 36 resulted from allyl
addition to amino aldehydes present, because of partial
imine hydrolysis during the reaction. Degradation products
were observed after imine formation in up to 10% yield.
Products 37 and 38 given in Fig. 1 resulted after
attempted condensation of Z-leucinal and valine tert-
butyl ester. These compounds were unambiguously
identified by comparison with published spectra [30]. A
similar reaction has previously been reported by Lethinen
and Brunow [31]; no explanation or mechanism was
When we applied a method reported by Bocoum et al. [28],
in which a mixture of imine 1 and allyl bromide was added
to a suspension of zinc and cerium chloride (CeCl3ꢀ7H2O)
in tetrahydrofuran at 0 °C, no consumption of the zinc
and no reaction was observed. But when we added imine
1 at 0 °C to a preformed organozinc compound obtained
by reaction of allyl bromide with zinc and cerium chlo-
ride, a 51% yield of the homoallylamine was obtained
(Scheme 5). In this variation it was mandatory to keep the
reaction temperature for the formation of the organozinc
compound below 20 °C to prevent decomposition of the
reagent. Oxidative work-up in the subsequent hydrobora-
tion of alkene 2 had to be performed without sodium
hydroxide, to prevent saponification of the methyl ester.
Nevertheless, utilization of potassium acetate as base [29]
did not prove reactive enough to achieve formation of the
terminal alcohol 3.
123

Addition of allylzinc to a-amino acid-derived imines
Table 1 Allyl addition to a-amino acid-derived imines
179
36
37
38
R
O
R1
R1
R1
PG
OtBu
N
N
Zn
Z
PG
PG
PG
H
H
N
O
CeCl3·7H2O
N
H
N
N
OH
O
+
H
H
H
N
R2
X
HN
R3O
R2
X
HN
R2
X
Br
Fig. 1 Side products observed during allyl addition and imine
formation
R3O
R3O
20b 35b
−
−
−
4 19
20a 35a
No. Imine PG R1 R2
X
R3
Producta Yield d.r.b
(%)
chromatography), in optical rotation, and in NMR spec-
troscopic data (Table 2). Generally, the isomer eluting first
has a significantly lower optical rotation, generally a
smaller vicinal coupling constant (3J) between hydrogen
atoms 40-H and 50-H, and a somewhat lower shift for C-40.
The relative configuration of the isomers was assigned with
the help of these data and because of unambiguous
assignment of the configuration in isomer 24a obtained after
X-ray crystallographic analysis of its derivative 44a (vide
infra) suggesting a 40S configuration for isomers 20–34a.
The best results in the allyl additions were obtained at
0 °C. Selectivities in the allyl addition to aldimine 14 (c.f.
Table 1, entry 11) dropped from 80:20 at 0 °C to 60:40
at -78 °C, whereas yields were essentially the same. The
effect of Lewis acids and other additives on the outcome of
the reaction was tested (Table 3). Allyl addition to imine
17 gave a poor 47:53 selectivity without Lewis acid.
Selectivities and yields did not improve significantly in the
presence of CeCl3ꢀ7H2O, Sm(OTf)3, or ZnCl2. Addition of
Schreiner’s catalyst 39 (Fig. 2) [32–34, and references
cited therein] as a hydrogen bond donor led to a compa-
rable 50:50 selectivity and a slightly improved 56% yield.
Nevertheless, the reactions were performed in the presence
of cerium chloride despite the reduced yields, because the
allylzinc reagent was preferentially obtained with this salt
present.
1
2
3
4
5
6
7
8
9
4
Boc iPr Me H,H TBS
20a, 20b 48
iBu Me H,H TBDPS 21a, 21b 27
iPr Me H,H TBDPS 22a, 22b 59
70:30c
60:40d
90:10d
43:57c
53:47d,e
n.d.f
5
Z
Z
6
7
Boc iPr iPr H,H TBDPS 23a, 23b 57
8
Boc iPr Bn H,H TBS
24a, 24b 44
25a, 25b 55
26a, 26b 32
27a, 27b 36
28a, 28b 50
29a, 29b 38
30a, 30b 66
31a, 31b 40
32a, 32b 49
33a, 33b 31
34a, 34b 64
35a, 35b 33
9
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
iBu Bn H,H TBS
iBu Me H,H TBS
iPr Me H,H TBS
iPr iBu H,H TBS
10
11
12
66:34
n.d.f
65:35c
37:63c
80:20d
37:63d
47:53d
49:51d
87:13d
67:33c,g
10 13
11 14
12 15
13 16
14 17
15 18
16 19
a
iBu iPr
iPr Me
O
O
tBu
tBu
tBu
tBu
tBu
tBu
tBu
iPr iBu O
iBu Bn
iPr iPr
iPr Bn
O
O
O
Me iBu O
Conditions: Zn (2 eq.), CeCl3ꢀ7H2O (0.1 eq.), allyl bromide
(1.9 eq.), THF, 0 °C to r.t., overnight
b
Assignment of the stereoisomers was made on the basis of retention
times, optical rotation, and NMR spectroscopic data
c
Determination of diastereomeric ratio by NMR spectroscopy
d
Determination of diastereomeric ratio by HPLC
e
Configuration unambiguously determined by X-ray crystallographic
analysis of subsequent product 44a (53:47 S:R)
f
Diastereomeric ratio could not be determined
Permutation of both amino acid moieties’ configurations
revealed an insignificant match–mismatch interaction
(Scheme 6). The selectivities, if any, seem to be ruled by
the stereogenic centres in the amino ester-based moiety.
g
Not separable by chromatography. Assignment of configuration
was not possible
given for this reaction. To prevent this side reaction
several dehydrating agents (sodium sulfate, alumina,
molecular sieves) were tested and the reaction was per-
formed with strict exclusion of oxygen and light, but its
appearance could not be prevented.
Hydroboration of homoallylamines
Hydroboration of homoallylamines 20–35 with 9-borabi-
cyclo[3.3.1]nonane (9-BBN) and subsequent oxidative
work-up [35] furnished terminal alcohols 42–52 with high
regioselectivities [36] and with good yields (Scheme 7,
Table 4).
Diastereoselectivities in the allyl addition ranged from
50:50 to 90:10. In the reactions of amino alcohol deriva-
tives 4–12 the best selectivities were obtained for alanine-
derived substrates (entries 1–3 and 7), whereas bulkier side
chains led to reduced selectivities. No general trend was
observed for tert-butyl ester derivatives 13–19.
Compound 35 was carried on as a mixture of isomers,
although only one isomer of the alcohol 52a was isolated
after transformation and chromatography (entry 14). The
structure of diamino alcohol 44a was determined by X-ray-
crystallographic analysis (Fig. 3, Table 5) giving further
unambiguous evidence for the structure of alkene 24a.
Assignment of the isomers was accomplished on the
basis of tendencies in the retention times (thin-layer
123

180
M. Virlouvet et al.
Table 2 Assignment of isomers according to physical data
Table 3 Allyl addition in the presence of additives
R
R
No.
Additive
Yield (%)
d.r.a
4'S
4'R
PG
4'
PG
4'
5'
3'
1'
5'
3'
1'
N
H
N
H
1
2
3
4
5
–
49
31
53
51
56
47:53
49:51
48:52
50:50
50:50
2'
2'
HN
HN
CeCl3ꢀ7H2O
Sm(OTf)3
ZnCl2
R'
R'
Compound Config. [a]D20
Rfa
1H NMR
J4 –5 (Hz) d (C-40)
(ppm)
13C NMR
39
3
C-40
(10-1 deg
cm2 g-1
0
0
Allyl addition to imine 17; Further conditions as given in Table 1
a
Determination of diastereomeric ratio by HPLC
)
20a
20b
21a
21b
22a
22b
23a
23b
24a
24b
25a
25b
26a
26b
27a
27b
28a
28b
29a
29b
30a
30b
31a
31b
32a
32b
33a
33b
34a
34b
35a
35b
S
–3.8
?16.1
–6.5
0.44 1.7
0.35 2.1
0.41 1.8
0.36 2.0
0.37 1.6
0.30 1.7
0.52 1.6
0.52 2.4
0.44 1.7
0.35 n.d.
0.53 1.7–2.2
0.43 3.2
0.45 1.8
0.35 n.d.
0.26 2.0
0.15 n.d.
0.51 1.5
0.37 n.d.
0.44 1.9
0.40 3.1
0.33 1.5
0.15 4.2
0.43 1.4
0.30 4.3
0.41 1.6
0.34 3.3
0.47 1.5
0.38 4.3
0.33 1.5
0.15 5.7
0.41 n.d.
0.41 n.d.
54.3
54.7
n.d.
R
S
H
H
F3C
N
N
CF3
R
S
?18.5
–7.8
n.d.
S
n.d.
CF3
CF3
R
S
?20.0
–17.3
–1.9
n.d.
n.d.
Fig. 2 Schreiner’s catalyst 39 used as hydrogen bond donor
R
Sb
R
S
54.7
54.6
55.7
57.6
58.2
57.4
57.5
54.5
55.7
54.2
55.7
58.9
60.1
55.4
55.7
55.6
56.1
58.7
59.8
55.9
56.6
55.6
57.3
n.d.
–40.6
?4.0
–18.0
?17.6
–4.6
iBu
iBu
Z
Z
Zn, CeCl3·7H2O
Br
N
H
N
H
N
iPr
HN
iPr
*
*
R
S
29a, 29b,
41a,41b
13,40
CO2tBu
CO2tBu
R
S
?37.9
–1.1
S: 13
R: 40
29: 38%, 37:63
41: 39%, 59:41
R
S
?19.7
–10.9
?14.3
–31.6
0.0
Scheme 6
R
S
R1
R1
9-BBN
then H2O2, NaOH
PG
PG
N
*
*
N
OH
R2
R
S
H
H
R2
X
HN
HN
–27.8
–1.0
R
S
R3O
X
R3O
–31.9
–8.8.
–15.6
?8.5
–28.5
–7.0
R
S
Scheme 7
R
S
before, has been achieved with reasonable yields and selec-
tivities up to 90:10. The thus obtained homoallylamines were
transformed, by hydroboration, to diamino alcohols bearing a
terminal hydroxy function. These highly functionalized sub-
strates have been used in the preparation of peptidomimetics.
These investigations will be reported elsewhere.
R
S
–43.2
–21.3
n.d.
R
S
R
n.d.
n.d.
Numbering differs in the respective compounds
n.d., not determined
Experimental
a
Retention factor: Eluent n-hexane–AcOEt, 6:1
b
Tetrahydrofuran (THF) and Et2O were distilled from
sodium benzophenone ketyl radical; CH2Cl2 was distilled
from CaH2. Abbreviations: TBS, tert-butyldimethylsilyl;
TBDPS, tert-butyldiphenylsilyl; 9-BBN, 9-borabicyclo[3.3.1]
nonane; TEMPO, tetramethylpiperidine-N-oxide. All mois-
ture-sensitive reactions were carried out under oxygen-free
argon or N2 using oven-dried glassware and a vacuum line.
Unambiguously assigned by X-ray-crystallographic analysis of
derivative 44a
Conclusion
Allyl addition to a-amino acid-derived imines using or-
ganozinc compounds, a type of reaction not published
123

Addition of allylzinc to a-amino acid-derived imines
Table 4 Synthesis of diamino alcohols by hydroboration
181
spectra were recorded with broadband proton decou-
pling and were assigned using DEPT 135 and DEPT 90
experiments. Melting points were measured on a Bu¨chi
apparatus. IR spectra were recorded on a Bruker IFS-88
spectrometer. Elemental analyses were performed on a
Heraeus CHN–O-rapid or on an elementar vario MICRO
and were in good agreement with calculated values. Elec-
tron-impact high-resolution mass spectra were recorded on
a Finnigan MAT-90. Optical rotations were recorded on a
Perkin Elmer 241 polarimeter (using the sodium D line,
589 nm) and specific optical rotations [a] are given in units
No. Alkene PG R1 R2
X
R3
Product
Yield (%)
1
2
3
4
5
6
7
8
9
20a
22a
24a
25a
25b
27a
30b
31a
31b
Boc iPr Me H,H TBS
42a
87
97
83
79
81
89
62
94
84
Z
iPr Me H,H TBDPS 43a
Boc iPr Bn H,H TBS
44a
45a
45a
46a
47b
48a
48b
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
iBu Bn H,H TBS
iBu Bn H,H TBS
iPr Me H,H TBS
iPr Me
O
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
iPr iBu O
iPr iBu O
of 10-1 deg cm2 g-1
.
10 32a/32ba
11 33b
12 34a
13 34b
14 35a
a
iBu Bn
iPr iPr
iPr Bn
iPr Bn
O
O
O
O
49a, 49bb 52
50b
51a
51b
52ac
71
73
94
64
Allyl additions
General procedure (GP 1) for preparation of amino
alcohols
Me iBu O
The amino acid (1.00 mmol) was added in portions at 0 °C
to a suspension of 57 mg LiAlH4 (1.50 mmol) in 10 cm3
anhydrous Et2O and the mixture was heated to reflux for
3 h. The reaction was stopped by careful addition of
1.50 cm3 H2O, 1.50 cm3 aqueous NaOH (3 M), and
4.50 cm3 H2O at 0 °C with vigorous stirring. The obtained
suspension was stirred for 1 h and filtered. The filtrate was
dried (Na2SO4), concentrated, and purified by distillation
or recrystallization.
As a mixture of isomers
b
c
Isomers could be separated
Only one isomer was obtained after purification by chromatography
Si
O
General procedure (GP 2) for preparation of N-Z-protected
amino alcohols
HN
NH
Benzyl chloroformate (148 mm3, 1.05 mmol) was added at
0 °C to a mixture of amino alcohol (1.00 mmol), 5 cm3
CH2Cl2, and 5 cm3 aqueous saturated NaHCO3 solution.
The mixture was stirred for 3 h at room temperature and the
aqueous layer was extracted with CH2Cl2 (2 9 10 cm3).
The combined organic layers were dried (Na2SO4), con-
centrated, and purified by distillation or recrystallization.
O
OH
O
44a
Fig. 3 Structure of 44a in the crystal
General procedure (GP 3) for preparation
of N-Boc-protected amino alcohols
Flash column chromatography [37] was carried out using
Merck silica gel 60 (230–400 mesh), and thin-layer chro-
matography (TLC) was carried out using commercially
available Merck F254 pre-coated sheets. Medium-pressure
liquid chromatography (MPLC): Pump (Labomatic MD-50),
detection by UV absorption (Latek UVIS 200); Merck
LiChroprep Si 60 (15–25 lm). HPLC: Analyses of diaste-
reoisomer distributions were carried out with a Merck-
Hitachi LaChrom D7000 apparatus with a L7100 mixer and
diode-array detection (L7455) on a Merck LiChrospher Si 60
chromatographic column (5 lm, flow: 1–1.5 cm3 min-1).
1H and 13C NMR spectra were recorded on a Bruker Cryo-
spek WM-250, an AM-400, or a DRX 500. Chemical shifts
are given in ppm downfield of tetramethylsilane. 13C NMR
Boc2O (229 mg, 1.05 mmol) was added at 0 °C to a
solution of amino alcohol (1.00 mmol) and 153 mm3 Et3N
(1.10 mmol) in 10 cm3 THF. The mixture was stirred for
18 h at room temperature and the solvent was removed.
The residue was diluted in 50 cm3 EtOAc and the solution
was washed with 25 cm3 H2O and 25 cm3 brine, dried
(Na2SO4), concentrated, and purified by column chroma-
tography (silica gel).
General procedure (GP 4) for preparation of O-TBS-
protected or O-TBDPS-protected amino alcohols
TBSCl (301 mg, 2.00 mmol) or TBDPSCl (550 mg,
2.00 mmol) was added portionwise at 0 °C to a mixture
123

182
M. Virlouvet et al.
careful addition of K2CO3. The aqueous layers were
extracted with Et2O (2 9 50 cm3) and the combined
organic layers were washed with brine, dried (Na2SO4),
concentrated, and used without further purification.
Table 5 Crystal data and structure refinement for tert-butyl
(3S,4S,20S)-4-[1-(tert-butyldimethylsilyloxy)-3-phenyl-2-propylamino]-
7-hydroxy-2-methyl-3-heptylcarbamate (44a)
Identification code
Empirical formula
Formula weight
Temperature
pod08 and CCDC-721237
28H52N2O4Si
508.81 g mol-1
C
General procedure (GP 6) for preparation
of N-protected amino aldehydes
203(2) K
˚
0.71073 A
Variation A: 530 mg Dess–Martin periodinane (1.25 mmol)
was added to a solution of the N-protected amino alcohol
(1.00 mmol) in 10 cm3 CH2Cl2. The mixture was stirred
for 2–4 h (monitoring with TLC) and further periodinane
was added if necessary. A solution of 1 g NaHCO3 and 1 g
Na2S2O3 in 15 cm3 H2O was added at room temperature
with vigorous stirring and stirring was continued for
45 min. The aqueous layer was extracted with CH2Cl2
(2 9 10 cm3) and the combined organic layers were
washed with 20 cm3 brine, dried (Na2SO4), concentrated,
and used without purification.
Wavelength
Crystal system
Space group
Monoclinic
P21
˚
Unit cell dimensions
a = 11.433(2) A, a = 908
˚
b = 9.824(2) A, b = 108.80(3)8
˚
c = 15.575(3) A, c = 908
3
1,656.0(6) A , 2
1.020 Mg m-3
0.101 mm-1
560
˚
Volume, Z
Density (calculated)
Absorption coefficient
F(000)
Crystal size
0.4 9 0.06 9 0.08 mm3
Variation B: An aqueous solution of 0.71 cm3 NaOCl
(1.14 mmol) and 252 mg NaHCO3 (3.00 mmol) was added
at 0 °C within 1–2 h to a mixture of the N-protected amino
alcohol (1.00 mmol), 108 mg NaBr (1.00 mmol), and
0.39 mg TEMPO (0.02 mmol) in 3 cm3 toluene, 3 cm3
EtOAc, and 0.5 cm3 H2O. The aqueous layer was extracted
with Et2O (2 9 5 cm3) and the organic layers were washed
successively with 8 mg KI in 2 cm3 10% KHSO4 solution,
with 1 cm3 10% Na2S2O3 solution, and with 2 cm3 brine.
Drying (Na2SO4) and concentration yielded the aldehyde,
which was used without purification.
2Hmax
48.028
Limiting indices
-13 B h B 13, -10 B k B 10,
-17 B l B 17
Reflections collected
Independent reflections
Refinement method
9,579
4,969 [R(int) = 0.0540]
Full-matrix least squares on F2
4,969/1/328
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I [ 2r(I)]
R indices (all data)
0.958
R1 = 0.0468, xR2 = 0.0911
R1 = 0.0933, xR2 = 0.1078
3
˚
Largest diff. peak and hole (e/A ) 0.15 and -0.17
Structure solution SHELXS-97 [38]
General procedure (GP 7) for preparation
Structure refinement SHELXL-97 [38]
of amino acid-derived imines
Details of the crystallographic analysis of tert-butyl (3S,4S,20S)-4-[1-
(tert-butyldimethylsilyloxy)-3-phenyl-2-propylamino]-7-hydroxy-2-
methyl-3-heptylcarbamate (44a) have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publica-
tion number CCDC-721237. Data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax:
?44-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk)
The amino acid-derived amine (1.00 mmol) was added to a
mixture of the N-protected amino aldehyde (1.00 mmol),
3
500 mg molecular sieves (4 A), and 10 cm CH2Cl2. After
˚
stirring for 3 h at room temperature, filtration, and con-
centration, a crude product was obtained, which was used
without purification.
of amino alcohol (1.00 mmol) and 150 mg imidazole
(2.20 mmol) in 20 cm3 CH2Cl2. The mixture was stirred
overnight at room temperature and the reaction was stopped
by addition of 10 cm3 aqueous saturated NaHCO3 solution.
The aqueous layer was extracted with CH2Cl2 (2 9 20 cm3).
The combined organic layers were dried (Na2SO4), concen-
trated, and purified by column chromatography (silica gel).
General procedure (GP 8) for allyl addition
to amino acid-derived imines
Allyl bromide (165 mm3, 1.90 mmol) was added slowly at
0 °C under an argon atmosphere to a suspension of 130 mg
Zn (2.00 mmol) and 37 mg CeCl3ꢀ7H2O (0.10 mmol)
in 3 cm3 anhydrous THF. Stirring was continued for
30–60 min at 0 °C until complete consumption of the zinc
and a solution of the aldimine in 3 cm3 anhydrous THF
was added slowly. The mixture was warmed to room
temperature, stirred for 15 h, and the reaction was stopped
by addition of 904 mg Na4EDTAꢀ4H2O (2.00 mmol) in
10 cm3 H2O. The mixture was extracted with Et2O
(4 9 10 cm3). The combined organic layers were washed
with 25 cm3 brine, dried (Na2SO4), and concentrated, and
General procedure (GP 5) for preparation of amino
acid tert-butyl esters
HClO4 (70%, 3.60 cm3, 15.0 mmol) was added slowly at
0 °C to a suspension of the amino acid (10.0 mmol) in
24 cm3 AcOtBu. The mixture was stirred for 24 h at room
temperature, diluted with H2O, and brought to pH 12 by
123

Addition of allylzinc to a-amino acid-derived imines
183
(m, 2H, 7-H2), 5.81 (ddt, 3J = 17.7 Hz, 3J = 9.6 Hz,
3J = 7.3 Hz, 1H, 6-H) ppm; 13C NMR (100 MHz, CDCl3):
d = -5.4 (q, Si(CH3)2), 18.4 (s, SiC(CH3)3), 18.8 (q, C-
30), 19.5 (q, CH(CH3)a(CH3)b), 20.1 (q, CH(CH3)a(CH3)b),
25.9 (q, SiC(CH3)3), 28.5 (q, OC(CH3)3), 30.7 (d, C-2),
38.6 (t, C-5), 53.3 (d, C-20), 54.7 (d, C-4), 58.9 (d, C-3),
67.4 (t, C-10), 78.5 (s, OC(CH3)3), 117.5 (t, C-7), 135.6 (d,
C-6), 156.4 (s, NHCO) ppm; IR (KBr): v = 3,438, 3,353
(N–H), 1,718 (C=O) cm-1; MS (FAB pos.): m/z (%) = 415
(100) [(M ? H)?]; HRMS (C22H47N2O3Si): calcd.
415.3356, found 415.3352.
the residue was separated and purified by chromatography
(silica gel).
tert-Butyl (3S,4S,20S) and (3S,4R,20S)-4-[1-(tert-butyldi-
methylsilyloxy)-2-propylamino]-2-methylhept-6-en-3-
ylcarbamate (20a, 20b, C22H46N2O3Si)
Aldimine 4 (1.49 g, 4.00 mmol), 524 mg Zn (8.00 mmol),
149 mg CeCl3ꢀ7H2O (0.40 mmol), and 662 mm3 allyl
bromide (7.60 mmol) were reacted according to GP 8 in
5 cm3 THF within 16 h. Chromatography (hexanes–Et2O
8:1 ? 6:1) yielded 561 mg adduct 20a (1.35 mmol, 34%)
and 238 mg adduct 20b (0.57 mmol, 14%) as colourless
oils.
Benzyl (4S,5S,20S) and (4S,5R,20S)-5-[1-(tert-butyldiphe-
nylsilyloxy)-2-propylamino]-2-methyloct-7-en-4-ylcarba-
mate (21a, 21b, C36H50N2O3Si)
20a: Rf = 0.44 (hexanes–EtOAc 6:1); [a]2D0 = -3.8 9
10-1 deg cm2 g-1 (c = 1.17, CHCl3); 1H NMR (400 MHz,
CDCl3): d = 0.06 (s, 3H, SiCH3), 0.06 (s, 3H, SiCH3), 0.90
(s, 9H, SiC(CH3)3), 0.89–0.93 (m, 6H, 30-H3, CH(CH3)a
(CH3)b), 0.92 (d, 3J = 6.8 Hz, 3H, CH(CH3)a(CH3)b),
1.20–1.50 (bs, 1H, CHNHCH), 1.44 (s, 9H, OC(CH3)3),
Aldimine 5 (1.09 g, 2.00 mmol), 262 mg Zn (4.00 mmol),
76 mg CeCl3ꢀ7H2O (0.20 mmol), and 331 mm3 allyl
bromide (3.80 mmol) were reacted according to GP 8 in
5 cm3 THF within 16 h. Chromatography (hexanes–EtOAc
6:1) yielded 180 mg adduct 21a (0.31 mmol, 15%) and
135 mg adduct 21b (0.23 mmol, 12%) as colourless oils.
21a: Rf = 0.41 (hexanes–EtOAc 6:1); [a]2D0 = -6.5 9
10-1 deg cm2 g-1 (c = 0.79, CHCl3); 1H NMR (400 MHz,
3
3
1.66 (dsept, J = 9.3 Hz, J = 6.9 Hz, 1H, 2-H), 2.05 (dt,
3
2J = 13.8 Hz, J = 7.9 Hz, 1H, 5-Ha), 2.15–2.23 (m, 1H,
3
3
5-Hb), 2.71 (ddd, J = 8.2 Hz, J = 4.8 Hz, J = 1.5 Hz,
3
3
3
1H, 4-H), 2.79 (u-quintd, J = 6.4 Hz, J = 4.2 Hz, 1H,
20-H), 3.21 (ddd, 3J = 10.3 Hz, 3J = 9.3 Hz, 3J = 1.7 Hz,
1H, 3-H), 3.32 (dd, J = 9.8 Hz, J = 7.0 Hz, 1H, 10-Ha),
3.53 (dd, J = 9.8 Hz, J = 4.2 Hz, 1H, 10-Hb), 4.80 (d,
3J = 10.2 Hz, 1H, NHCO), 5.05 (ddt, 3J = 10.2 Hz,
3J = 2.2 Hz, J = 1.0 Hz, 1H, 7-Hcis), 5.06–5.13 (m, 1H,
3
CDCl3): d = 0.90 (d, J = 6.6 Hz, 3H, CHCH3), 0.91 (d,
3J = 6.5 Hz, 3H, CHCH3), 0.92 (d, 3J = 6.4 Hz, 3H,
2
3
2
CHCH3), 1.05 (s, 9H, C(CH3)3), 1.24 (ddd, J = 13.7 Hz,
2
3
3J = 8.7 Hz, 3J = 5.3 Hz, 1H, 3-Ha), 1.37 (ddd, 2J =
3
3
13.8 Hz, J = 9.4 Hz, J = 5.5 Hz, 1H, 3-Hb), 1.45 (bs,
3
3
3
7-Htrans), 5.84 (ddt, 3J = 17.2 Hz, 3J = 10.1 Hz, 3J =
7.3 Hz, 1H, 2-H) ppm; 13C NMR (100 MHz, CDCl3):
d = -5.4 (q, SiCH3), -5.3 (q, SiCH3), 17.7 (q, C-30),
18.3 (s, SiC(CH3)3), 19.4 (q, CH(CH3)a(CH3)b), 20.1
(q, CH(CH3)a(CH3)b), 25.9 (q, SiC(CH3)3), 28.4 (q,
OC(CH3)3), 30.3 (d, C-2), 37.7 (t, C-5), 52.4 (d, C-20),
54.3 (d, C-4), 58.1 (d, C-3), 67.4 (t, C-10), 78.4
(s, OC(CH3)3), 117.4 (t, C-7), 135.5 (d, C-6), 156.3
(s, NHCO) ppm; IR (KBr): v = 3,446 (N–H), 1,719
(C=O) cm-1; MS (FAB pos.): m/z (%) = 415 (100)
[(M ? H)?]; HRMS (C22H47N2O3Si): calcd. 415.3356,
found 415.3360.
1H, CHNHCH), 1.60 (u-doct, J = 8.2 Hz, J = 6.2 Hz,
1H, 2-H), 2.12 (u-t, 3J = 7.0 Hz, 2H, 6-H2), 2.52 (td,
3J = 6.9 Hz, 3J = 1.9 Hz, 1H, 5-H), 2.82 (u-quintd,
3
3J = 6.4 Hz, J = 4.0 Hz, 1H, 20-H), 3.40 (dd, 2J =
3
2
10.0 Hz, J = 6.5 Hz, 1H, 10-Ha), 3.57 (dd, J = 9.9 Hz,
3J = 4.2 Hz, 1H, 10-Hb), 3.75 (tdd, 3J = 9.5 Hz,
3J = 5.2 Hz, 3J = 1.7 Hz, 1H, 4-H), 4.93 (d, 3J = 9.7
Hz, 1H, NHCO), 5.03 (dd, 3J = 10.2 Hz, 2J = 2.1 Hz, 1H,
8-Hcis), 5.07 (dd, 3J = 17.0 Hz, 2J = 1.8 Hz, 1H, 8-Htrans),
5.08 (d, 2J = 12.3 Hz, 1H, CHaHbPh), 5.11 (d,
2J = 12.3 Hz, 1H, CHaHbPh), 5.81 (ddt, 3J = 17.2 Hz,
3
3J = 10.1 Hz, J = 7.2 Hz, 1H, 7-H), 7.26–7.45 (m, 11H,
3 Ph), 7.62–7.67 (m, 4H, 3 Ph) ppm; 13C NMR (100 MHz,
CDCl3): d = 18.0 (q), 19.2 (s), 22.3 (q), 23.2 (q), 24.9 (d),
26.9 (q), 37.4 (t), 42.4 (t), 51.3 (d), 53.0 (d), 57.3 (d), 66.5
(t), 67.9 (t), 117.6 (t), 127.7 (d, 4 C), 128.0 (d), 128.0 (d,
2C), 128.5 (d), 129.6 (d), 129.7 (d), 133.5 (s), 133.6 (s),
134.8 (d), 135.2 (s), 135.5 (d), 135.6 (d, 2C), 135.6 (d, 2C),
156.3 (s) ppm; IR (KBr): v = 3,418, 3,336 (N–H), 1,721
(C=O) cm-1; MS (FAB pos.): m/z (%) = 587 (97)
[(M ? H)?]; HRMS (C36H51N2O3Si): calcd. 587.3669,
found 587.3666.
20b: Rf = 0.35 (hexanes–EtOAc 6:1); [a]2D0 = ?16.1 9
10-1 deg cm2 g-1 (c = 0.50, CHCl3); 1H NMR (400
MHz, CDCl3): d = 0.05 (s, 6H, Si(CH3)2), 0.70–0.90
(bs, 1H, CHNHCH), 0.90 (s, 9H, SiC(CH3)3), 0.92 (d,
3
3J = 6.7 Hz, 3H, CH(CH3)a(CH3)b), 0.93 (d, J = 6.7 Hz,
3
3H, CH(CH3)a(CH3)b), 1.02 (d, J = 6.4 Hz, 3H, 30-H3),
1.44 (s, 9H, OC(CH3)3), 1.67 (dsept, 3J = 9.3 Hz,
3J = 6.7 Hz, 1H, 2-H), 2.09–2.17 (m, 2H, 5-H2), 2.70
3
3
3
(qt, J = 6.4 Hz, J = 5.1 Hz, 1H, 20-H), 2.83 (td, J =
6.6 Hz, 3J = 2.1 Hz, 1H, 4-H), 3.17 (td, 3J = 9.7 Hz,
3J = 2.1 Hz, 1H, 3-H), 3.40 (dd, 2J = 9.8 Hz, 3J =
21b: Rf = 0.36 (hexanes–EtOAc 6:1); [a]2D0 = ?18.5 9
10-1 deg cm2 g-1 (c = 0.74, CHCl3); 1H NMR (400 MHz,
2
3
5.4 Hz, 1H, 10-Ha), 3.45 (dd, J = 9.8 Hz, J = 4.7 Hz,
1H, 10-Hb), 4.97 (d, J = 10.0 Hz, 1H, NHCO), 5.03–5.10
3
3
CDCl3): d = 0.85 (d, J = 6.6 Hz, 3H, CH(CH3)a(CH3)b),
123

184
M. Virlouvet et al.
3
0.86 (d, J = 6.5 Hz, 3H, CH(CH3)a(CH3)b), 1.05 (s, 9H,
(100 MHz, CDCl3): d = 17.7 (q), 19.2 (s), 19.5 (q), 20.0
(q), 26.9 (q), 30.9 (d), 37.7 (t), 52.5 (d), 54.1 (d), 58.9 (d),
66.5 (t), 68.2 (t), 117.6 (t), 127.7 (d, 4 C), 128.0 (d), 128.0
(d, 2C), 128.5 (d, 2C),129.6 (d), 129.7 (d), 133.5 (s), 133.5
(s), 135.5 (d), 135.6 (d, 2C), 135.7 (2d), 137.0 (s), 156.8 (s)
ppm; IR (KBr): v = 3,423, 3,300 (N–H), 1,726 (C=O)
cm-1; MS (FAB pos.): m/z (%) = 573 (100) [(M ? H)?];
HRMS (C35H49N2O3Si): calcd. 573.3512, found 573.3515.
22b: Rf = 0.30 (hexanes–EtOAc 6:1); [a]2D0 = ?20.0 9
10-1 deg cm2 g-1 (c = 0.80, CHCl3); 1H NMR (400
MHz, CDCl3): d = 0.84 (d, 3J = 6.7 Hz, 3H, H(CH3)a
(CH3)b), 0.87 (d, 3J = 6.7 Hz, 3H, CH(CH3)a(CH3)b), 1.05
3
C(CH3)3), 1.06 (d, J = 6.5 Hz, 3H, 30-H3), 1.19 (ddd,
3
3
2J = 13.3 Hz, J = 9.4 Hz, J = 4.8 Hz, 1H, 3-Ha), 1.30
2
3
3
(ddd, J = 13.6 Hz, J = 9.6 Hz, J = 5.5 Hz, 1H, 3-Hb),
1.15–1.45 (m, 1H, CHNHCH), 1.47–1.61 (m, 1H, 2-H),
2.00 (dtt, 2J = 13.8 Hz, 3J = 7.6 Hz, 4J = 1.1 Hz, 1H,
2
3
4
6-Ha), 2.16 (dtt, J = 13.6 Hz, J = 6.2 Hz, J = 1.2 Hz,
1H, 6-Hb), 2.61 (ddd, 3J = 7.9 Hz, 3J = 6.1 Hz,
3J = 2.0 Hz, 1H, 5-H), 2.72–2.82 (m, 1H, 2-H), 3.45 (dd,
3
2J = 9.8 Hz, J = 5.4 Hz, 1H, 10-Ha), 3.51 (dd, 2J =
3
3
9.8 Hz, J = 4.7 Hz, 1H, 10-Hb), 3.70 (tdd, J = 9.6 Hz,
3J = 4.8 Hz, J = 2.0 Hz, 1H, 4-H), 4.99–5.08 (m, 3H,
3
8-H2, NHCO), 5.07 (d, 2J = 12.6 Hz, 1H, CHaHbPh), 5.10
(d, 2J = 12.6 Hz, 1H, CHaHbPh), 5.77 (dddd, 3J =
16.8 Hz, 3J = 10.5 Hz, 3J = 7.9 Hz, 3J = 6.5 Hz, 1H,
7-H), 7.28–7.45 (m, 11H, 3 Ph), 7.63–7.70 (m, 4H, 3 Ph)
ppm; 13C NMR (100 MHz, CDCl3): d = 18.1 (q), 19.3 (s),
22.2 (q), 23.3 (q), 24.9 (d), 26.9 (q), 37.9 (t), 42.2 (t), 51.6
(d), 53.3 (d), 57.1 (d), 66.5 (t), 68.6 (t), 117.6 (t), 127.8 (d,
4 C), 128.0 (d), 128.1 (d, 2C), 128.5 (d, 2C), 129.6 (d),
129.7 (d), 133.7 (s, 2C), 135.6 (d, 4 C), 135.7 (d), 136.9 (s),
156.3 (s) ppm; IR (KBr): v = 3,412, 3,339 (N–H), 1,720
(C=O) cm-1; MS (FAB pos.): m/z (%) = 587 (100)
[(M ? H)?]; HRMS (C36H51N2O3Si): calcd. 587.3669,
found 587.3666.
(s, 9H, C(CH3)3), 1.07 (d, J = 6.4 Hz, 3H, 30-H3), 1.26
3
(bs, 1H, CHNHCH), 1.59 (dsept, 3J = 9.6 Hz, 3J =
6.7 Hz, 1H, 2-H), 2.00–2.18 (m, 2H, 5-H2), 2.69 (qdd,
3
3J = 6.4 Hz, 3J = 5.7 Hz, J = 4.3 Hz, 1H, 20-H), 2.78
(td, 3J = 6.7 Hz, 3J = 1.7 Hz, 1H, 4-H), 3.17 (td,
3J = 9.8 Hz, 3J = 1.7 Hz, 1H, 3-H), 3.43 (dd, 2J =
3
2
9.9 Hz, J = 5.7 Hz, 1H, 10-Ha), 3.50 (dd, J = 9.9 Hz,
3J = 4.4 Hz, 1H, 10-Hb), 5.00–5.08 (m, 2H, 7-H2), 5.08 (d,
2J = 12.4 Hz, 1H, CHaHbPh), 5.12 (d, J = 12.2 Hz, 1H,
2
CHaHbPh), 5.23 (d, 3J = 10.0 Hz, 1H, NHCO), 5.75
(dddd, 3J = 17.0 Hz, 3J = 10.2 Hz, 3J = 7.8 Hz, 3J =
6.7 Hz, 1H, 6-H), 7.28–7.44 (m, 11H, 3 Ph), 7.63–7.69 (m,
4H, 3 Ph) ppm; 13C NMR (100 MHz, CDCl3): d = 18.6
(q), 19.3 (s), 19.7 (q), 20.0 (q), 26.9 (q), 30.7 (d), 38.9 (t),
53.7 (d), 54.3 (d), 59.9 (d), 66.5 (t), 68.4 (t), 117.8 (t), 127.7
(d, 4 C), 128.0 (d), 128.1 (d, 2C), 128.5 (d, 2C), 129.7 (2d),
133.7 (s, 2C), 135.3 (d), 135.6 (4d), 137.0 (s), 156.8 (s) ppm;
IR (KBr): v = 3,418, 3,341 (N–H), 1,726 (C=O) cm-1; MS
(FAB pos.): m/z (%) = 573 (99) [(M ? H)?]; HRMS
(C35H49N2O3Si): calcd. 573.3512, found 573.3510.
Benzyl (3S,4S,20S) and (3S,4R,20S)-4-[1-(tert-butyldiphe-
nylsilyloxy)-2-propylamino]-2-methylhept-6-en-3-ylcarba-
mate (22a, 22b, C35H48N2O3Si)
Aldimine 6 (5.55 g, 10.5 mmol), 1.37 g Zn (20.9 mmol),
398 mg CeCl3ꢀ7H2O (1.05 mmol), and 1.73 cm3 allyl
bromide (19.9 mmol) were reacted according to GP 8 in
20 cm3 THF within 16 h. Chromatography (hexanes–Et2O
5:1) yielded 3.07 g adduct 22a (5.36 mmol, 51%) and
493 mg adduct 22b (0.86 mmol, 8%) as colourless oils.
22a: Rf = 0.37 (hexanes–EtOAc 6:1); [a]2D0 = -7.8 9
10-1 deg cm2 g-1 (c = 0.77, CHCl3); 1H NMR (400
tert-Butyl (3S,4S,20S) and (3S,4R,20S)-4-[1-(tert-butyldi-
phenylsilyloxy)-3-methyl-2-butylamino]-2-methylhept-6-
en-3-ylcarbamate (23a, 23b, C34H54N2O3Si)
Aldimine 7 (1.57 g, 3.00 mmol), 392 mg Zn (6.00 mmol),
114 mg CeCl3ꢀ7H2O (0.30 mmol), and 496 mm3 allyl
bromide (5.70 mmol) were reacted according to GP 8 in
5 cm3 THF within 16 h. Chromatography (hexanes–Et2O
8:1 ? 5:1) yielded 416 mg adduct 23a (0.73 mmol, 24%)
and 552 mg adduct 23b (0.97 mmol, 32%) as colourless oils.
23a: Rf = 0.52 (hexanes–EtOAc 6:1); [a]2D0 = -17.3 9
10-1 deg cm2 g-1 (c = 0.82, CHCl3); 1H NMR (400 MHz,
CDCl3): d = 0.79 (d, 3J = 6.9 Hz, 3H, CHCH3), 0.82
3
MHz, CDCl3): d = 0.90 (d, J = 6.4 Hz, 3H, 30-H3),
0.91 (d, 3J = 6.7 Hz, 3H, CH(CH3)a(CH3)b), 0.91 (d,
3J = 6.7 Hz, 3H, H(CH3)a(CH3)b), 1.04 (s, 9H, C(CH3)3),
3
1.15–1.60 (bs, 1H, CHNHCH), 1.70 (dsept, J = 9.6 Hz,
3J = 6.7 Hz, 1H, 2-H), 2.05 (dddt, 2J = 13.6 Hz,
3
4
3J = 8.3 Hz, J = 7.3 Hz, J = 1.2 Hz, 1H, 5-Ha), 2.15–
3
3
2.24 (m, 1H, 5-Hb), 2.73 (ddd, J = 8.4 Hz, J = 4.9 Hz,
3J = 1.6 Hz, 1H, 4-H), 2.83 (u-quintd, 3J = 6.4 Hz,
3J = 4.2 Hz, 1H, 20-H), 3.28 (ddd, 3J = 10.2 Hz, 3J =
9.6 Hz, 3J = 1.6 Hz, 1H, 3-H), 3.40 (dd, 2J = 9.9 Hz,
3J = 6.7 Hz, 1H, 10-Ha), 3.56 (dd, 2J = 9.9 Hz,
3J = 4.3 Hz, 1H, 10-Hb), 5.00–5.11 (m, 3H, 7-H, NHCO),
5.09 (d, 2J = 12.3 Hz, 1H, CHaHbPh), 5.13 (d, 2J =
12.2 Hz, 1H, CHaHbPh), 5.79 (ddt, 3J = 17.2 Hz,
3J = 10.1 Hz, 3J = 7.2 Hz, 1H, 6-H), 7.27–7.44 (m,
11H, 3 Ph), 7.62–7.67 (m, 4H, 3 Ph) ppm; 13C NMR
3
3
(d, J = 7.0 Hz, 3H, CHCH3), 0.87 (d, J = 6.6 Hz, 3H,
CHCH3), 0.91 (d, 3J = 6.7 Hz, 3H, CHCH3), 1.06 (s,
9H, SiC(CH3)3), 1.10–1.40 (bs, 1H, CHNHCH), 1.45 (s, 9H,
OC(CH3)3), 1.72 (dsept, 3J = 9.3 Hz, 3J = 6.7 Hz, 1H,
2-H), 1.80 (septd, 3J = 7.0 Hz, 3J = 4.3 Hz, 1H, 30-H), 2.02
2
3
3
(ddd, J = 13.6 Hz, J = 8.4 Hz, J = 7.6 Hz, 1H, 5-Ha),
2
2.16 (ddd, J = 13.3 Hz, J = 6.8 Hz, J = 4.8 Hz, 1H,
5-Hb), 2.47 (dt, J = 6.5 Hz, J = 4.5 Hz, 1H, 20-H), 2.68
3
3
3
3
123

Addition of allylzinc to a-amino acid-derived imines
185
3
(ddd, J = 8.7 Hz, J = 4.7 Hz, J = 1.6 Hz, 1H, 4-H),
3
3
and 60 mg adduct 24b (0.12 mmol, 22%) as colourless
oils.
3
3
3.18 (td, J = 10.0 Hz, J = 1.6 Hz, 1H, 3-H), 3.50 (dd,
3
2J = 10.3 Hz, J = 6.5 Hz, 1H, 10-Ha), 3.62 (dd, 2J =
24a: Rf = 0.44 (hexanes–EtOAc 6:1); [a]2D0 = -40.6 9
10-1 deg cm2 g-1 (c = 0.61, CHCl3); 1H NMR (400 MHz,
CDCl3): d = 0.03 (s, 3H, SiCH3), 0.03 (s, 3H, SiCH3), 0.78
(d, 3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.83 (d, 3J =
6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.91 (s, 9H, SiC(CH3)3),
1.26 (bs, 1H, CHNHCH), 1.36–1.45 (m, 1H, 2-H), 1.44
(s, 9H, OC(CH3)3), 2.03–2.19 (m, 2H, 5-H2), 2.60
3
3
10.3 Hz, J = 4.6 Hz, 1H, 10-Hb), 4.83 (d, J = 10.2 Hz,
1H, NHCO), 5.00 (dd, 3J = 10.2 Hz, 2J = 2.2 Hz, 1H,
7-Hcis), 5.02 (dd, 3J = 17.1 Hz, 2J = 1.8 Hz, 1H, 7-Htrans),
3
3
3
5.75 (ddt, J = 17.3 Hz, J = 10.2 Hz, J = 7.2 Hz, 1H,
6-H), 7.36–7.47 (m, 6H, 2 Ph), 7.63–7.69 (m, 4H, 2 Ph)
ppm; 13C NMR (100 MHz, CDCl3): d = 18.0 (q), 18.8 (q),
19.2 (s), 19.6 (q), 20.2 (q), 26.9 (q), 28.5 (d), 28.9 (q), 30.3
(d), 38.0 (t), 54.7 (d), 58.7 (d), 62.5 (d), 63.3 (t), 78.5 (s),
117.4 (t), 127.7 (d, 4 C), 129.7 (d), 129.7 (d), 133.5 (2s),
135.6 (d), 135.7 (2d), 135.7 (d, 2C), 156.3 (s) ppm; IR
(KBr): v = 3,437 (N–H), 1,719 (C=O) cm-1; MS (FAB
pos.): m/z (%) = 567 (100) [(M ? H)?]; HRMS
(C34H55N2O3Si): calcd. 567.3982, found 567.3979.
3
(dd, 2J = 13.4 Hz, J = 7.4 Hz, 1H, 30-Ha), 2.65 (dd,
3
2J = 13.6 Hz, J = 6.6 Hz, 1H, 30-Hb), 2.75–2.81 (m, 2H,
3
3
20-H, 4-H), 3.09 (td, J = 9.9 Hz, J = 1.7 Hz, 1H, 3-H),
2
3
3.40 (dd, J = 9.9 Hz, J = 4.7 Hz, 1H, 10-Ha), 3.52 (dd,
2J = 9.9 Hz, J = 4.1 Hz, 1H, 10-Hb), 4.77 (d, 3J =
10.1 Hz, 1H, NHCO), 5.03–5.11 (m, 2H, 7-H2), 5.82
3
3
3
3
(ddt, J = 17.3 Hz, J = 10.1 Hz, J = 7.2 Hz, 1H, 6-H)
7.14–7.35 (m, 5H, Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = -5.5 (q, SiCH3), -5.4 (q, SiCH3), 18.2 (s, SiC
(CH3)3), 19.5 (q, CHCH3), 20.0 (q, CHCH3), 25.9 (q,
SiC(CH3)3), 28.5 (q, OC(CH3)3), 30.5 (d, C-2), 38.2 (t,
C-5), 39.1 (t, C-30), 54.6 (d, C-4), 59.8 (d, C-20), 58.6 (d,
C-3), 64.2 (t, C-10), 78.3 (s, OC(CH3)3), 117.5 (t, C-7),
126.0 (d, Ph), 128.2 (d, 2C, Ph), 129.3 (d, 2C, Ph), 135.5
(d, C-6), 139.8 (s, Ph), 156.2 (s, NHCO) ppm; IR (KBr):
v = 3,426 (N–H), 1,718 (C=O) cm-1; MS (FAB pos.): m/z
(%) = 491 (43) [(M ? H)?]; HRMS (C28H51N2O3Si):
calcd. 491.3669, found 491.3665.
23b: Rf = 0.52 (hexanes–EtOAc 6:1); [a]2D0 = -1.9 9
10-1 deg cm2 g-1 (c = 0.84, CHCl3); 1H NMR
(400 MHz, CDCl3): d = 0.78 (d, 3J = 6.6 Hz, 3H,
CHCH3), 0.82 (d, 3J = 6.7 Hz, 3H, CHCH3), 0.85 (d,
3J = 7.5 Hz, 3H, CHCH3), 0.87 (d, 3J = 6.9 Hz, 3H,
CHCH3), 1.05 (s, 9H, SiC(CH3)3), 1.42 (s, 9H, OC(CH3)3),
1.63 (dsept, 3J = 9.1 Hz, 3J = 6.7 Hz, 1H, 2-H), 1.92
(septd, 3J = 6.9 Hz, 3J = 4.3 Hz, 1H, 30-H), 2.00–2.15 (m,
3
3
3H, 5-H2, CHNHCH), 2.45 (dt, J = 5.6 Hz, J = 4.6 Hz,
1H, 20-H), 2.73 (ddd, 3J = 7.6 Hz, 3J = 5.3 Hz,
3J = 2.4 Hz, 1H, 4-H), 3.15 (ddd, 3J = 9.8 Hz, 3J =
9.0 Hz, 3J = 2.3 Hz, 1H, 3-H), 3.50 (dd, 2J = 10.5
Hz, 3J = 4.9 Hz, 1H, 1-Ha), 3.55 (dd, 2J = 10.5 Hz,
3J = 5.8 Hz, 1H, 1-Hb), 4.87 (d, 3J = 10.0 Hz, 1H,
NHCO), 5.01–5.08 (m, 2H, 7-H2), 5.77 (ddt, 3J =
24b: Rf = 0.35 (hexanes–EtOAc 6:1); [a]2D0 = ?4.0 9
10-1 deg cm2 g-1 (c = 0.91, CHCl3); 1H NMR (400
MHz, CDCl3): d = 0.02 (s, 3H, SiCH3), 0.02 (s, 3H,
3
SiCH3), 0.86 (d, J = 6.7 Hz, 3H, CH(CH3)a(CH3)b), 0.90
(d, 3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.91 (s, 9H,
SiC(CH3)3), 1.47 (s, 9H, OC(CH3)3), 1.60 (bs, 1H,
3
3
16.7 Hz, J = 9.4 Hz, J = 7.2 Hz, 1H, 6-H), 7.36–7.46
(m, 6H, 2 Ph), 7.64–7.69 (m, 4H, 2 Ph) ppm; 13C NMR
(100 MHz, CDCl3): d = 18.3 (s, SiC(CH3)3), 19.0 (q,
CHCH3), 19.2 (q, CHCH3), 19.3 (q, CHCH3), 20.1 (q,
CHCH3), 26.9 (q, SiC(CH3)3), 28.4 (q, OC(CH3)3), 29.3
(d, C-30), 30.3 (d, C-2), 37.7 (t, C-5), 54.7 (d, C-4), 58.4 (d,
C-20), 61.8 (d, C-3), 64.3 (t, C-10), 78.5 (s, OC(CH3)3),
117.5 (t, C-7), 127.7 (d, 4C, Ph), 129.6 (d, Ph), 129.7
(d, Ph), 133.6 (2s, Ph), 135.4 (d, C-20), 135.6 (4d, Ph),
156.4 (s, NHCO) ppm; IR (KBr): v = 3,437 (N–H), 1,718
(C=O) cm-1; MS (FAB pos.): m/z (%) = 567 (94)
[(M ? H)?]; HRMS (C34H55N2O3Si): calcd. 567.3982,
found 567.3985.
3
CHNHCH), 1.86 (u-oct, J = 6.6 Hz, 1H, 2-H), 2.13 (dt,
2J = 13.9 Hz, 3J = 7.0 Hz, 1H, 5-Ha), 2.26 (ddd,
3
3
2J = 13.6 Hz, J = 6.6 Hz, J = 5.4 Hz, 1H, 5-Hb), 2.60
(dd, 2J = 13.3 Hz, J = 8.6 Hz, 1H, 30-Ha), 2.73 (dd,
3
3
2J = 13.3 Hz, J = 5.3 Hz, 1H, 30-Hb), 2.77–2.84 (m, 1H,
2
4-H), 2.92–3.01 (m, 1H, 20-H), 3.34 (dd, J = 10.0 Hz,
3J = 5.2 Hz, 1H, 10-Ha), 3.50 (dd, 2J = 10.0 Hz,
3J = 3.9 Hz, 1H, 10-Hb), 3.44–3.51 (m, 1H, 3-H), 4.55
3
3
(d, J = 10.5 Hz, 1H, NHCO), 5.09 (ddd, J = 10.1 Hz,
2J = 2.1 Hz, 4J = 1.1 Hz, 1H, 7-Hcis), 5.14 (ddd,
3J = 17.1 Hz, 2J = 2.0 Hz, 4J = 1.5 Hz, 1H, 7-Htrans),
3
3
3
5.88 (ddt, J = 17.2 Hz, J = 10.1 Hz, J = 7.1 Hz, 1H,
6-H), 7.17–7.32 (m, 5H, Ph) ppm; 13C NMR (100 MHz,
CDCl3): d = -5.5 (q, SiCH3), -5.4 (q, SiCH3), 18.2 (q,
CH(CH3)a(CH3)b), 18.2 (s, SiC(CH3)3), 20.7 (q, CH(CH3)a
(CH3)b), 25.9 (q, SiC(CH3)3), 28.5 (q, OC(CH3)3), 28.8 (d,
C-2), 35.4 (t, C-5), 38.9 (t, C-30), 55.7 (d, C-4), 57.2 (d,
C-3), 58.4 (d, C-20), 63.4 (t, C-10), 78.8 (s, OC(CH3)3),
117.4 (t, C-7), 126.0 (d, Ph), 128.2 (d, 2C, Ph), 129.4 (d,
2C, Ph), 135.8 (d, C-6), 139.7 (s, Ph), 156.3 (s, NHCO)
tert-Butyl (3S,4S,20S) and (3S,4R,20S)-4-[1-(tert-butyldi-
methylsilyloxy)-3-phenyl-2-propylamino]-2-methylhept-6-
en-3-ylcarbamate (24a, 24b, C28H50N2O3Si)
Aldimine 8 (247 mg, 0.55 mmol), 72 mg Zn (1.10 mmol),
21 mg CeCl3ꢀ7H2O (0.06 mmol), and 91 mm3 allyl
bromide (1.05 mmol) were reacted according to GP 8 in
3 cm3 THF within 16 h. Chromatography (hexanes–Et2O
8:1 ? 6:1) yielded 60 mg adduct 24a (0.12 mmol, 22%)
123

186
M. Virlouvet et al.
ppm; IR (KBr): v = 3,357 (N–H), 1,702 (C=O) cm-1; MS
(FAB pos.): m/z (%) = 491 (74) [(M ? H)?]; HRMS
(C28H51N2O3Si): calcd. 491.3669, found 491.3672.
1.48 (bs, 1H, CHNHCH), 1.50–1.60 (m, 1H, 2-H), 1.97–
2
2.08 (m, 1H, 6-Ha), 2.24 (dtt, J = 13.9 Hz, J = 6.8 Hz,
3
2
3
3J = 1.5 Hz, 1H, 6-Hb), 2.53 (dd, J = 13.5 Hz, J = 7.3
2
3
Hz, 1H, 30-Ha), 2.62 (dd, J = 13.5 Hz, J = 6.4 Hz, 1H,
30-Hb), 2.73 (td, 3J = 7.1 Hz, 3J = 3.2 Hz, 1H, 5-H),
2.83–2.91 (m, 1H, 20-H), 3.35 (dd, 2J = 10.0 Hz,
Benzyl (4S,5S,20S) and (4S,5R,20S)-5-[1-(tert-butyldi-
methylsilyloxy)-3-phenyl-2-propylamino]-2-methyloct-7-
en-4-ylcarbamate (25a, 25b, C32H50N2O3Si)
2
3
3J = 6.2 Hz, 1H, 10-Ha), 3.49 (dd, J = 10.0 Hz, J = 4.2
Hz, 1H, 10-Hb), 3.70 (tt, 3J = 10.0 Hz, 3J = 3.2 Hz, 1H, 4-
H), 4.76 (d, 3J = 9.3 Hz, 1H, NHCO), 4.91 (dd, 3J =
Aldimine 9 (6.21 g, 12.5 mmol), 1.63 g Zn (25.0 mmol),
473 mg CeCl3ꢀ7H2O (1.25 mmol), and 1.79 cm3 allyl
bromide (23.8 mmol) were reacted according to GP 8 in 10
cm3 THF within 16 h. Chromatography (hexanes–EtOAc
10:1) yielded 1.86 g adduct 25a (3.46 mmol, 28%) and
1.16 g adduct 25b (2.16 mmol, 17%) as colourless oils.
25a: Rf = 0.53 (hexanes–EtOAc 6:1); [a]2D0 = -18.0 9
10-1 deg cm2 g-1 (c = 1.00, CHCl3); 1H NMR (500 MHz,
CDCl3): d = 0.03 (2s, 6H, Si(CH3)2), 0.82 (d, 3J = 6.6 Hz,
3H, CH(CH3)a(CH3)b), 0.84 (d, 3J = 6.6 Hz, 3H,
CH(CH3)a(CH3)b), 0.91 (s, 9H, C(CH3)3), 1.05 (ddd,
2
3
17.2 Hz, J = 1.6 Hz, 1H, 8-Htrans), 4.96 (dd, J = 10.2
2
2
Hz, J = 1.9 Hz, 1H, 8-Hcis), 5.05 (d, J = 12.2 Hz, 1H,
OCHaHbPh), 5.09 (d, 2J = 11.7 Hz, 1H, OCHaHbPh), 5.79
3
3
3
(ddt, J = 17.2 Hz, J = 9.9 Hz, J = 7.3 Hz, 1H, 7-H),
7.11–7.37 (m, 10H, 2 Ph) ppm; 13C NMR (100 MHz,
CDCl3): d = -5.5 (q, Si(CH3)a(CH3)b), -5.4 (q, Si(CH3)a
(CH3)b), 18.2 (s, C(CH3)3), 21.6 (q, CH(CH3)a(CH3)b),
24.0 (q, CH(CH3)a(CH3)b), 24.5 (d, C-2), 25.9 (q,
C(CH3)3), 37.2 (t, C-6), 37.6 (t, C-3), 39.3 (t, C-30), 51.3
(d, C-4), 58.2 (d, C-5), 59.9 (d, C-20), 64.6 (t, C-10), 66.4 (t,
OCH2Ph), 117.2 (t, C-8), 126.0 (d, Ph), 127.9 (d, 3C, Ph),
128.3 (d, 2C, Ph), 128.4 (d, 2C, Ph), 129.4 (2d, Ph), 135.4
(d, C-7), 136.9 (s, Ph), 139.7 (s, Ph), 156.1 (s, NHCO)
ppm; IR (KBr): v = 3,402, 3,337 (N–H), 1,722 (C=O)
cm-1; MS (FAB pos.): m/z (%) = 539 (76) [(M ? H)?];
HRMS (C32H51N2O3Si): calcd. 539.3669, found 539.3666.
3
3
2J = 13.7 Hz, J = 9.1 Hz, J = 5.2 Hz, 1H, 3-Ha), 1.10
2
3
3
(ddd, J = 13.4 Hz, J = 9.4 Hz, J = 5.5 Hz, 1H, 3-Hb),
3
3
1.31 (bs, 1H, CHNHCH), 1.47 (dsext, J = 8.7 Hz, J =
6.7 Hz, 1H, 2-H), 2.06 (dt, 2J = 14.1 Hz, 3J = 7.4 Hz, 1H,
6-Ha), 2.13 (dt, 2J = 13.7 Hz, 3J = 6.8 Hz, 1H, 6-Hb), 2.60
3
3
3
(ddd, J = 7.2 Hz, J = 5.6 Hz, J = 2.2 Hz, 1H, 5-H),
2.63 (dd, 2J = 12.9 Hz, 3J = 7.0 Hz, 1H, 30-Ha), 2.66 (dd,
2J = 13.3 Hz, 3J = 6.8 Hz, 1H, 30-Hb), 2.77 (tt,
3J = 7.1 Hz, J = 3.9 Hz, 1H, 20-H), 3.40 (dd, J = 10.0
Benzyl (4S,5S,20S) and (4S,5R,20S)-5-[1-(tert-butyldi-
methylsilyloxy)-2-propylamino]-2-methyloct-7-en-4-ylcar-
bamate (26a, 26b, C26H46N2O3Si)
3
2
Hz, J = 4.0 Hz, 1H, 10-Ha), 3.52 (dd, 2J = 10.0 Hz,
3
3J = 4.1 Hz, 1H, 10-Hb), 3.64 (tdd, J = 9.6 Hz, J = 5.1
Hz, 3J = 1.7 Hz, 1H, 4-H), 4.92 (d, 3J = 9.5 Hz, 1H,
NHCO), 5.05 (dd, 3J = 10.3 Hz, 2J = 1.6 Hz, 1H, 8-Hcis),
5.06 (d, 2J = 12.5 Hz, 1H, OCHaHbPh), 5.08 (dd,
3J = 17.3 Hz, 2J = 1.6 Hz, 1H, 8-Htrans), 5.09 (d,
3
3
Aldimine 10 (2.88 g, 6.86 mmol), 897 mg Zn (13.7 mmol),
256 mg CeCl3ꢀ7H2O (0.69 mmol), and 0.98 cm3 allyl
bromide (13.0 mmol) were reacted according to GP 8 in
10 cm3 THF within 16 h. Chromatography (hexanes–Et2O
9:1 ? 5:1) yielded 619 mg adduct 26a (1.34 mmol, 19%)
and 428 mg adduct 26b (0.92 mmol, 13%) as colourless
oils.
26a: Rf = 0.45 (hexanes–EtOAc 6:1); [a]2D0 = -4.6 9
10-1 deg cm2 g-1 (c = 0.62, CHCl3); 1H NMR (400 MHz,
CDCl3): d = 0.04 (2s, 6H, Si(CH3)2), 0.89 (s, 9H, C(CH3)3),
2J = 12.5 Hz, 1H, OCHaHbPh), 5.80 (ddt, J = 17.2 Hz,
3
3
3J = 10.1 Hz, J = 7.2 Hz, 1H, 7-H), 7.11–7.46 (m, 10H,
2 Ph) ppm; 13C NMR (125 MHz, CDCl3): d = -5.4
(q, Si(CH3)a(CH3)b), -5.4 (q, Si(CH3)a(CH3)b), 18.3 (s,
C(CH3)3), 22.2 (q, CH(CH3)a(CH3)b), 23.2 (q, CH(CH3)a
(CH3)b), 24.9 (d, C-2), 26.0 (q, C(CH3)3), 37.7 (t, C-6), 39.4
(t, C-30), 42.2 (t, C-3), 51.5 (d, C-4), 57.6 (d, C-5), 60.2 (d,
C-20), 63.5 (t, C-10), 66.4 (t, OCH2Ph), 117.2 (t, C-8), 126.1
(d, Ph), 128.0 (d, 3C, Ph), 128.3 (d, 2C, Ph), 128.5 (d, 2C, Ph),
129.5 (2d, Ph), 135.6 (d, C-7), 137.0 (s, Ph), 140.0 (s, Ph),
156.3 (s, NHCO) ppm; IR (DRIFT): v = 3,412, 3,338
(N–H), 1,721 (C=O) cm-1; MS (FAB pos.): m/z (%) = 539
(76) [(M ? H)?]; HRMS (C32H51N2O3Si): calcd. 539.3669,
found 539.3671.
3
3
0.89 (d, J = 6.5 Hz, 3H, CHCH3), 0.91 (d, J = 7.0 Hz,
3H, CHCH3), 0.93 (d, 3J = 6.6 Hz, 3H, CHCH3), 1.28 (ddd,
2J = 13.7 Hz, J = 8.5 Hz, J = 5.0 Hz, 1H, 3-Ha), 1.28
3
3
2
3
3
(ddd, J = 13.6 Hz, J = 9.4 Hz, J = 5.5 Hz, 1H, 3-Hb),
1.44 (bs, 1H, CHNHCH), 1.57 (u-doct, 3J = 8.8 Hz,
3J = 6.5 Hz, 1H, 2-H), 2.11 (u-t, J = 7.0 Hz, 2H, 6-H2),
3
2.55 (td, 3J = 6.7 Hz, 3J = 1.9 Hz, 1H, 5-H), 2.77
3
3
(u-quintd, J = 6.4 Hz, J = 3.9 Hz, 1H, 20-H), 3.32 (dd,
3
2
25b: Rf = 0.43 (hexanes–EtOAc 6:1); [a]2D0 = ?
17.6 9 10-1 deg cm2 g-1 (c = 0.65, CHCl3); 1H NMR
(400 MHz, CDCl3): d = 0.01 (s, 3H, Si(CH3)a(CH3)b),
2J = 9.8 Hz, J = 6.4 Hz, 1H, 10-Ha), 3.53 (dd, J = 9.8
Hz, J = 4.1 Hz, 1H, 10-Hb), 3.75 (tdd, 2J = 9.4 Hz,
3
3J = 5.1 Hz, 3J = 1.8 Hz, 1H, 4-H), 4.97 (d, 3J = 9.5 Hz,
3
2
1H, NHCO), 5.05 (ddv, J = 1.8 Hz, 1H, 8-Hcis), 5.07 (d,
0.02 (s, 3H, Si(CH3)a(CH3)b), 0.87 (d, J = 6.6 Hz, 3H,
CH(CH3)a(CH3)b), 0.87 (d, 3J = 6.6 Hz, 3H, Si(CH3)a
(CH3)b), 0.89 (s, 9H, C(CH3)3), 1.03–1.25 (m, 2H, 3-H2),
2J = 12.2 Hz, 1H, CHaHbPh), 5.05 (dd, 3J = 17.2 Hz,
2J = 1.8 Hz, 1H, 8-Htrans), 5.11 (d, 2J = 12.3 Hz, 1H,
123

Addition of allylzinc to a-amino acid-derived imines
187
3
CHaHbPh), 5.82 (ddt, 3J = 17.3 Hz, 3J = 10.1 Hz,
3J = 7.2 Hz, 1H, 7-H), 7.26–7.37 (m, 5H, Ph) ppm; 13C
NMR (100 MHz, CDCl3): d = -5.4 (q, Si(CH3)a(CH3)b), -5.3
(q, Si(CH3)a(CH3)b), 18.6 (q, C-30), 18.3 (s, C(CH3)3), 22.3
(q, CH(CH3)a(CH3)b), 23.3 (q, CH(CH3)a(CH3)b), 24.9 (d,
C-2), 25.9 (q, C(CH3)3), 37.3 (t, C-6), 42.3 (t, C-3), 51.3 (d,
C-4), 53.1 (d, C-20), 57.4 (d, C-5), 66.4 (t, CH2Ph), 66.8 (t,
C-10), 117.5 (t, C-8), 128.0 (d, 3C, Ph), 128.5 (2d, Ph), 135.5
(d, C-7), 136.9 (s, Ph), 156.3 (s, NHCO) ppm; IR (KBr):
v = 3,436, 3,335 (N–H), 1,723 (C=O) cm-1; MS (FAB
pos.): m/z (%) = 463 (100) [(M ? H)?]; HRMS
(C26H47N2O3Si): calcd. 463.3356, found 463.3354.
3J = 9.5 Hz, J = 6.7 Hz, 1H, 2-H), 2.05–2.19 (m, 2H, 5-
3
3
H2), 2.69 (qt, J = 6.5 Hz, J = 4.9 Hz, 1H, 20-H), 2.87
3
3
3
(td, J = 6.7 Hz, J = 2.0 Hz, 1H, 4-H), 3.23 (td, J =
9.6 Hz, 3J = 2.0 Hz, 1H, 3-H), 3.39 (dd, 2J = 9.8 Hz,
3J = 5.2 Hz, 1H, 10-Ha), 3.43 (dd, 2J = 9.8 Hz,
3J = 4.7 Hz, 1H, 10-Hb), 4.97–5.07 (m, 2H, 7-H), 5.05
2
2
(d, J = 12.3 Hz, 1H, CHaHbPh), 5.09 (d, J = 12.3 Hz,
3
1H, CHaHbPh), 5.29 (d, J = 9.9 Hz, 1H, NHCO), 5.75
3
3
3
(ddt, J = 16.8 Hz, J = 10.8 Hz, J = 7.3 Hz, 1H, 6-H),
7.24–7.36 (m, 5H, Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = -5.4 (q, Si(CH3)a(CH3)b), -5.3 (q, Si(CH3)a(CH3)b),
18.3 (s, C(CH3)3), 18.6 (q, C-30), 19.6 (q, CH(CH3)a
(CH3)b), 20.0 (q, CH(CH3)a(CH3)b), 25.9 (q, C(CH3)3),
30.7 (d, C-2), 38.6 (t, C-5), 53.3 (d, C-20), 54.5 (d, C-4),
59.7 (d, C-3), 66.4 (t, CH2Ph), 67.4 (t, C-10), 117.7 (t, C-7),
127.9 (d, Ph), 128.0 (d, 2C, Ph), 128.5 (2d, Ph), 135.3 (d,
C-6), 137.0 (s, Ph), 156.8 (s, NHCO) ppm; IR (DRIFT):
v = 3,341 (N–H), 1,726 (C=O) cm-1; MS (FAB pos.): m/z
(%) = 449 (100) [(M ? H)?]; HRMS (C25H45N2O3Si):
calcd. 449.3199, found 449.3195.
26b: Rf = 0.35 (hexanes–EtOAc 6:1); [a]2D0 = ?37.9 9
10-1 deg cm2 g-1 (c = 0.87, CHCl3); 1H NMR
(400 MHz, CDCl3): d = 0.04 (s, 3H, Si(CH3)a(CH3)b),
3
0.04 (s, 3H, Si(CH3)a(CH3)b), 0.83 (d, J = 6.2 Hz, 3H,
CH(CH3)a(CH3)b), 0.89 (s, 9H, C(CH3)3), 0.88–0.94 (m,
6H, CH(CH3)a(CH3)b, 30-H3), 1.15–1.22 (m, 2H, 3-H2),
1.54 (bs, 1H, CHNHCH), 1.59–1.72 (m, 1H, 2-H), 1.95–
2
3
2.09 (m, 1H, 6-Ha), 2.33 (dtt, J = 13.9 Hz, J = 6.2 Hz,
3J = 1.5 Hz, 1H, 6-Hb), 2.68–2.76 (m, 1H, 5-H), 2.78–2.88
(m, 1H, 20-H), 3.40 (dd, 2J = 9.8 Hz, 3J = 5.3 Hz, 1H, 10-
Ha), 3.46 (dd, 2J = 9.7 Hz, 3J = 4.9 Hz, 1H, 10-Hb), 3.72–
3.82 (m, 1H, 4-H), 5.02–5.14 (m, 4H, 8-H2, CH2Ph), 5.28
(d, 3J = 9.1 Hz, 1H, NHCO), 5.73–5.86 (m, 1H, 7-H),
7.27–7.40 (m, 5H, Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = -5.4 (q, Si(CH3)a(CH3)b), -5.4 (q, Si(CH3)a(CH3)b),
17.2 (q, C-30), 18.2 (s, C(CH3)3), 21.6 (q, CH(CH3)a
(CH3)b), 24.0 (q, CH(CH3)a(CH3)b), 24.6 (d, C-2), 25.9 (q,
C(CH3)3), 37.6 (t, C-3 or C-6), 37.8 (t, C-3 or C-6), 50.5 (d,
C-4), 52.1 (d, C-20), 57.2 (d, C-5), 66.3 (t, CH2Ph), 67.5 (t,
C-10), 117.2 (t, C-8), 127.9 (d, 3C, Ph), 128.4 (d, 2C, Ph),
135.3 (d, C-7), 137.0 (s, Ph), 156.3 (s, NHCO) ppm; IR
(KBr): v = 3,417, 3,332 (N–H), 1,723 (C=O) cm-1; MS
(FAB pos.): m/z (%) = 463 (100) [(M ? H)?]; HRMS
(C26H47N2O3Si): calcd. 463.3356, found 463.3354.
27b: Rf = 0.15 (hexanes–EtOAc 6:1); [a]2D0 = ?18.0 9
10-1 deg cm2 g-1 (c = 0.73, CHCl3); m.p.: 48–50 °C; H
1
NMR (400 MHz, CDCl3): d = 0.04 (s, 6H, Si(CH3)2), 0.85
3
3
(d, J = 6.8 Hz, 3H, CH(CH3)a(CH3)b), 0.94 (d, J = 6.8
Hz, 3H, CH(CH3)a(CH3)b), 0.89 (s, 9H, C(CH3)3), 0.89 (d,
3J = 6.6 Hz, 3H, 30-H3), 1.50 (bs, 1H, CHNHCH), 1.99
(septd, 3J = 6.9 Hz, 3J = 5.2 Hz, 1H, 2-H), 2.10–2.27 (m,
2H, 5-H2), 2.73 (q, 3J = 6.0 Hz, 1H, 4-H), 2.84 (dqd,
3J = 7.3 Hz, 3J = 6.6 Hz, J = 4.3 Hz, 1H, 20-H), 3.31
3
(dd, 2J = 9.7 Hz, J = 7.3 Hz, 1H, 10-Ha), 3.49 (dd,
3
3
3
2J = 9.7 Hz, J = 4.4 Hz, 1H, 10-Hb), 3.55 (dt, J = 10.3
Hz, 3J = 5.6 Hz, 1H, 3-H), 4.93 (d, 3J = 10.4 Hz, 1H,
2
NHCO), 5.03–5.12 (m, 2H, 7-H2), 5.08 (d, J = 12.1 Hz,
1H, CHaHbPh), 5.12 (d, 2J = 12.1 Hz, 1H, CHaHbPh), 5.85
3
3
3
(ddt, J = 17.3 Hz, J = 10.1 Hz, J = 7.1 Hz, 1H, 6-H),
7.25–7.38 (m, 5H, Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = -5.4 (q, Si(CH3)a(CH3)b), -5.4 (q, Si(CH3)a(CH3)b),
17.4 (q, C-30), 17.7 (q, CH(CH3)a(CH3)b), 18.3 (q,
CH(CH3)a(CH3)b), 18.3 (s, C(CH3)3), 25.9 (q, C(CH3)3),
28.5 (d, C-2), 35.2 (t, C-5), 51.8 (d, C-20), 55.7 (d, C-4),
57.8 (d, C-3), 66.6 (t, CH2Ph), 67.6 (t, C-10), 117.5 (t, C-7),
128.0 (d, 3C, Ph), 128.5 (2d, Ph), 135.4 (d, C-20), 136.9 (s,
Ph), 156.8 (s, NHCO) ppm; IR (DRIFT): v = 3,326 (N–H),
1,712, 1,691 (C=O) cm-1; MS (FAB pos.): m/z (%) = 449
(100) [(M ? H)?]; HRMS (C25H45N2O3Si): calcd.
449.3199, found 449.3202.
Benzyl (3S,4S,20S) and (3S,4S,20S)-4-[1-(tert-butyldi-
methylsilyloxy)-2-propylamino]-2-methylhept-6-en-3-
ylcarbamate (27a, 27b, C25H44N2O3Si)
Aldimine 11 (5.10 g, 14.3 mmol), 1.87 g Zn (28.6 mmol),
533 mg CeCl3ꢀ7H2O (1.43 mmol), and 2.36 cm3 allyl
bromide (27.2 mmol) were reacted according to GP 8 in
20 cm3 THF within 16 h. Chromatography (hexanes–Et2O
8:1 ? 3:1) yielded 1.85 g adduct 27a (4.12 mmol, 29%)
as colourless oil and 440 mg adduct 27b (0.98 mmol, 7%)
as a colourless solid.
27a: Rf = 0.26 (hexanes–EtOAc 6:1); [a]2D0 = ?19.7 9
10-1 deg cm2 g-1 (c = 1.00, CHCl3); 1H NMR (400 MHz,
CDCl3): d = 0.04 (s, 6H, Si(CH3)2), 0.88 (s, 9H, C(CH3)3),
0.93 (d, 3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.95 (d,
Benzyl (3S,4S,20S) and (3S,4R,20S)-4-[1-(tert-butyldi-
methylsilyloxy)-4-methyl-2-pentylamino]-2-methylhept-6-
en-3-ylcarbamate (28a, 28b, C28H50N2O3Si)
Aldimine 12 (3.42 g, 7.62 mmol), 994 mg Zn (15.2 mmol),
288 mg CeCl3ꢀ7H2O (0.76 mmol), and 1.09 cm3 allyl
bromide (14.5 mmol) were reacted according to GP 8 in
3
3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 1.00 (d, J = 6.4 Hz,
3H, 30-H3), 0.50–1.50 (bs, 1H, CHNHCH), 1.72 (dsept,
123

188
M. Virlouvet et al.
15 cm3 THF within 16 h. Chromatography (hexanes–Et2O
8:1 ? 5:1) yielded 1.42 g adduct 28a (2.89 mmol, 38%) as a
colourless oil and 466 mg adduct 28b (0.95 mmol, 12%) as a
colourless solid.
CH2CH(CH3)a(CH3)b), 23.5 (q, CH2CH(CH3)a(CH3)b),
24.5 (d, C-1), 24.9 (d, C-40), 25.9 (q, C(CH3)3), 28.7 (d,
C-2), 35.6 (t, C-5), 41.9 (t, C-30), 54.6 (d, C-20), 55.7 (d,
C-4), 57.7 (d, C-3), 65.2 (t, C-10), 66.5 (t, CH2Ph), 117.4
(t, C-7), 128.0 (d, 3C, Ph), 128.5, (2d, Ph), 135.6 (d, C-6),
136.9 (s, Ph), 156.7 (s, NHCO) ppm; IR (DRIFT):
v = 3,301 (N–H), 1,721, 1,692 (C=O) cm-1; MS (FAB
pos.): m/z (%) = 491 (100) [(M ? H)?]; HRMS
(C28H51N2O3Si): calcd. 491.3669, found 491.3666.
28a: Rf = 0.51 (hexanes–EtOAc 6:1); [a]2D0 = -10.9 9
10-1 deg cm2 g-1 (c = 0.89, CHCl3); 1H NMR (400 MHz,
CDCl3): d = 0.03 (s, 3H, Si(CH3)a(CH3)b), 0.04 (s, 3H,
Si(CH3)a(CH3)b), 0.86 (d, 3J = 6.6 Hz, 3H, CH2CH(CH3)a
(CH3)b), 0.86–0.90 (m, 3H, CH2CH(CH3)a(CH3)b), 0.88
(s, 9H, C(CH3)3), 0.94 (d, 3J = 6.7 Hz, 3H, CH(CH3)a
(CH3)b), 0.94 (d, 3J = 6.7 Hz, 3H, CH(CH3)a(CH3)b), 1.15
(u-t, 3J = 6.7 Hz, 2H, 30-H2), 1.05–1.40 (bs, 1H,
CHNHCH), 1.64 (u-oct, 3J = 6.7 Hz, 1H, 2-H), 1.65–
1.76 (m, 1H, 40-H), 2.07 (u-dt, 2J = 14.2 Hz, 3J = 7.1 Hz,
1H, 5-Ha), 2.15 (dddt, 2J = 13.7 Hz, 3J = 7.0 Hz,
tert-Butyl (2S,40S,50S) and (2S,40R,50S)-2-[5-(benzyloxy-
carbonylamino)-7-methyloct-1-en-4-ylamino]-3-methylbut-
anoate (29a, 29b, C26H42N2O4)
Aldimine 13 (404 mg, 1.00 mmol), 131 mg Zn
(2.00 mmol), 37 mg CeCl3ꢀ7H2O (0.10 mmol), and
170 mm3 allyl bromide (1.90 mmol) were reacted accord-
ing to GP 8 in 4 cm3 THF within 16 h. Chromatography
(hexanes–Et2O 10:1 ? 8:1) yielded 98 mg adduct 29a
(0.22 mmol, 22%) as a colourless solid and 72 mg adduct
29b (0.16 mmol, 16%) as a colourless oil.
4
3J = 5.5 Hz, J = 1.3 Hz, 1H, 5-Hb), 2.53–2.64 (m, 1H,
3
3
3
20-H), 2.81 (ddd, J = 7.9 Hz, J = 5.4 Hz, J = 1.5 Hz,
3
3
1H, 4-H), 3.23 (td, J = 9.8 Hz, J = 1.5 Hz, 1H, 3-H),
3.36 (dd, 2J = 10.0 Hz, 3J = 4.9 Hz, 1H, 10-Ha), 3.62 (dd,
2J = 10.0 Hz, J = 3.7 Hz, 1H, 10-Hb), 5.00–5.15 (m, 4H,
3
29a: Rf = 0.44 (hexanes–EtOAc 6:1); [a]2D0 = -31.6 9
3
7-H2, CH2Ph), 5.26 (d, J = 10.1 Hz, 1H, NHCO), 5.81
1
10-1 deg cm2 g-1 (c = 1.20, CHCl3); m.p.: 48–50 °C; H
3
3
3
(dtt, J = 17.2 Hz, J = 10.1 Hz, J = 7.2 Hz, 1H, 6-H),
7.27–7.40 (m, 5H, Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = -5.5 (q, Si(CH3)a(CH3)b), -5.4 (q, Si(CH3)a(CH3)b),
18.2 (s, C(CH3)3), 19.7 (q, CH(CH3)a(CH3)b), 20.0 (q,
CH(CH3)a(CH3)b), 22.8 (q, CH2CH(CH3)a(CH3)b), 23.2 (q,
CH2CH(CH3)a(CH3)b), 24.9 (d, C-40), 25.9 (q, C(CH3)3),
30.6 (d, C-2), 38.4 (t, C-5), 42.3 (t, C-30), 54.2 (d, C-4),
56.0 (d, C-20), 59.3 (d, C-3), 64.9 (t, C-10), 66.4 (t, CH2Ph),
117.5 (t, C-7), 128.0 (d, Ph), 128.0 (d, 2C, Ph), 128.5 (2d,
Ph), 135.3 (d, C-6), 137.0 (s, Ph), 156.8 (s, NHCO) ppm;
IR (KBr): v = 3,430, 3,343 (N–H), 1,727 (C=O) cm-1; MS
(FAB pos.): m/z (%) = 491 (100) [(M ? H)?]; HRMS
(C28H51N2O3Si): calcd. 491.3669, found 491.3671.
3
NMR (400 MHz, CDCl3): d = 0.91 (d, J = 6.3 Hz, 3H,
CHCH3), 0.92 (d, 3J = 6.5 Hz, 3H, CHCH3), 0.93
(d, 3J = 6.5 Hz, 3H, CHCH3), 0.93 (d, 3J = 6.8 Hz,
3H, CHCH3), 1.26 (bs, 1H, CHNHCH), 1.32 (ddd,
3
2J = 13.7 Hz, 3J = 8.2 Hz, J = 5.6 Hz, 1H, 60-Ha),
2
1.37 (ddd, J = 14.0 Hz, J = 8.6 Hz, J = 5.5 Hz, 1H,
3
3
3
60-Hb), 1.47 (s, 9H, C(CH3)3), 1.64 (dsept, J = 7.9 Hz,
3
3J = 6.5 Hz, 1H, 70-H), 1.77 (u-oct, J = 6.7 Hz, 1H, 3-
H), 2.03–2.12 (m, 1H, 30-Ha), 2.16 (dtt, 2J = 13.9 Hz,
3
3
3J = 6.9 Hz, J = 1.9 Hz, 1H, 30-Hb), 2.48 (td, J = 7.0
3
3
Hz, J = 1.9 Hz, 1H, 40-H), 2.89 (d, J = 6.6 Hz, 1H, 2-
H), 3.72 (tdd, 3J = 9.2 Hz, 3J = 5.6 Hz, 3J = 1.9 Hz, 1H,
3
28b: Rf = 0.37 (hexanes–EtOAc 6:1); [a]2D0 = ?14.3 9
50-H), 5.03 (d, J = 9.5 Hz, 1H, NHCO), 5.04–5.11 (m,
2
1
10-1 deg cm2 g-1 (c = 0.75, CHCl3); m.p.: \45 °C; H
2H, 10-H), 5.07 (d, J = 12.2 Hz, 1H, OCHaHb), 5.11 (d,
2J = 12.2 Hz, 1H, OCHaHb), 5.78 (dddd, J = 17.0 Hz,
3
NMR (400 MHz, CDCl3): d = 0.04 (s, 6H, Si(CH3)2), 0.87
(d, 3J = 6.6 Hz, 3H, CHCH3), 0.86–0.91 (m, 3H, CHCH3),
0.89 (d, 3J = 6.6 Hz, 3H, CHCH3), 0.89 (s, 9H, C(CH3)3),
0.94 (d, 3J = 6.8 Hz, 3H, CHCH3), 1.15 (u-t, 3J = 6.7 Hz,
2H, 30-H2), 1.40 (bs, 1H, CHNHCH), 1.60 (u-nonet,
3J = 6.6 Hz, 3J = 6.6 Hz, 1H, 40-H), 1.96 (septd,
3
3
3J = 9.5 Hz, J = 7.6 Hz, J = 6.8 Hz, 1H, 20-H), 7.27–
7.40 (m, 5H, Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = 18.9 (q, CH(CH3)a(CH3)b), 19.5 (q, CH(CH3)a(CH3)b),
22.3 (q, CH2CH(CH3)a(CH3)b), 23.3 (q, CH2CH(CH3)a
(CH3)b), 24.9 (d, C-70), 28.2 (q, C(CH3)3), 32.2 (d, C-3),
37.7 (t, C-30), 42.4 (t, C-60), 51.2 (d, C-50), 58.9 (d, C-40),
66.5 (t, OCH2), 68.0 (d, C-2), 81.0 (s, C(CH3)3), 117.8 (t,
C-10), 128.1 (d, Ph), 128.1 (d, 2C, Ph), 128.5 (d, 2C, Ph),
135.3 (d, C-20), 136.9 (s, Ph), 156.2 (s, NHCO), 174.9 (s,
C-1) ppm; IR (KBr): v = 3,346 (N–H), 1,721, 1,704 (C=O)
cm-1; MS (FAB pos.): m/z (%) = 447 (86) [(M ? H)?];
HRMS (C26H43N2O4): calcd. 447.3223, found 447.3226.
3
3J = 6.7 Hz, J = 5.5 Hz, 1H, 2-H), 2.10–2.26 (m, 2H,
5-H2), 2.70 (qd, 3J = 6.7 Hz, 3J = 4.2 Hz, 1H, 20-H), 2.75
(q, 3J = 6.0 Hz, 1H, 4-H), 3.32 (dd, 2J = 10.0 Hz,
3
3
3J = 6.2 Hz, 1H, 10-Ha), 3.54 (dt, J = 10.2 Hz, J = 5.6
2
3
Hz, 1H, 3-H), 3.61 (dd, J = 9.9 Hz, J = 3.8 Hz, 1H, 10-
Hb), 4.97 (d, 3J = 10.2 Hz, 1H, NHCO), 5.03–5.13 (m, 4H,
7-H2, CH2Ph), 5.84 (ddt, 3J = 17.2 Hz, 3J = 10.2 Hz,
3J = 7.2 Hz, 1H, 6-H), 7.25–7.38 (m, 5H, Ph) ppm; 13C
NMR (100 MHz, CDCl3): d = -5.5 (q, Si(CH3)a(CH3)b),
-5.4 (q, Si(CH3)a(CH3)b), 18.0 (q, CH(CH3)a(CH3)b),
20.9 (q, CH(CH3)a(CH3)b), 18.3 (s, C(CH3)3), 22.8 (q,
29b: Rf = 0.40 (hexanes–EtOAc 6:1); [a]D20
=
0.0 9
10-1 deg cm2 g-1 (c = 0.84, CHCl3); 1H NMR (400 MHz,
CDCl3): d = 0.89 (d, 3J = 6.3 Hz, 3H, CHCH3), 0.90
(d, J = 6.5 Hz, 3H, CHCH3), 0.91 (d, J = 6.5 Hz, 3H,
3
3
123

Addition of allylzinc to a-amino acid-derived imines
189
3
CHCH3), 0.92 (d, J = 6.8 Hz, 3H, CHCH3), 1.15–1.40
3
CDCl3): d = 0.93 (d, J = 6.7 Hz, 3H, CH(CH3)a(CH3)b),
0.93 (d, 3J = 6.7 Hz, 3H, CH(CH3)a(CH3)b), 1.18 (d,
3J = 6.8 Hz, 3H, 3-H3), 1.45 (s, 9H, C(CH3)3), 1.60–1.90
(m, 2H, 60-H), 1.46 (s, 9H, C(CH3)3), 1.55–1.72 (m, 2H,
CHNHCH, 70-H), 1.80 (u-oct, 3J = 6.6 Hz, 1H, 3-H), 2.11
3
3
3
(t, J = 7.1 Hz, 2H, 30-H2), 2.57 (td, 3J = 6.6 Hz,
(bs, 1H, CHNHCH), 1.76 (dsept, J = 7.9 Hz, J = 6.7
Hz, 1H, 60-H), 1.98 (dt, 2J = 14.0 Hz, 3J = 8.6 Hz, 1H, 30-
3
3J = 3.1 Hz, 1H, 40-H), 2.91 (d, J = 7.3 Hz, 1H, 2-H),
2
4
3
3.77–3.86 (m, 1H, 50-H), 5.00–5.13 (m, 5H, 10-H, NHCO,
OCH2), 5.67–5.79 (m, 1H, 20-H), 7.26–7.39 (m, 5H, Ph)
ppm; 13C NMR (100 MHz, CDCl3): d = 18.4 (q,
CH(CH3)a(CH3)b), 19.3 (q, CH(CH3)a(CH3)b), 21.9 (q,
CH2CH(CH3)a(CH3)b), 23.6 (q, CH2CH(CH3)a(CH3)b),
24.7 (d, C-70), 28.1 (q, C(CH3)3), 32.4 (d, C-3), 36.3 (t,
C-30), 38.8 (t, C-60), 50.3 (d, C-50), 60.1 (d, C-40), 66.2 (d,
C-2), 66.4 (t, OCH2), 81.0 (s, C(CH3)3), 117.6 (t, C-10),
127.9 (d, 3C, Ph), 128.4 (2d, Ph), 135.0 (d, C-20), 136.9 (s,
Ph), 156.3 (s, NHCO), 175.1 (s, C-1) ppm; IR (KBr):
v = 3,346 (N–H), 1,725 (bs, C=O) cm-1; MS (FAB pos.):
m/z (%) = 447 (30) [(M ? H)?]; HRMS (C26H43N2O4):
calcd. 447.3223, found 447.3221.
Ha), 2.24 (dddt, J = 14.0 Hz, J = 8.6 Hz, J = 5.6 Hz,
3J = 3.6 Hz, 1H, 30-Hb), 2.72 (dt, 3J = 8.5 Hz, 3J =
4.1 Hz, 1H, 40-H), 3.44 (q, J = 6.9 Hz, 1H, 2-H), 3.55
3
3
3
3
(ddd, J = 10.3 Hz, J = 8.1 Hz, J = 4.3 Hz, 1H, 50-H),
4.66 (d, 3J = 10.9 Hz, 1H, NHCO), 5.06 (d, 2J = 12.3 Hz,
1H, OCHaHb), 5.14 (d, 2J = 12.3 Hz, 1H, OCHaHb),
5.08–5.18 (m, 2H, 10-H), 5.83 (dddd, 3J = 16.7 Hz,
3J = 10.3 Hz, J = 8.4 Hz, 3J = 6.0 Hz, 1H, 20-H), 7.27–
3
7.40 (m, 5H, Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = 19.3 (q, CH(CH3)a(CH3)b), 20.3 (q, CH(CH3)a(CH3)b),
19.5 (q, C-3), 28.1 (q, C(CH3)3), 29.5 (d, C-60), 34.5 (t, C-
30), 54.7 (d, C-2), 55.7 (d, C-40), 57.2 (d, C-50), 66.6 (t,
OCH2), 80.7 (s, C(CH3)3), 118.1 (t, C-10), 128.0 (d, 3C,
Ph), 128.5 (d, 2C, Ph), 135.2 (d, C-20), 136.8 (s, Ph), 156.9
(s, NHCO), 175.4 (s, C-1) ppm; IR (KBr): v = 3,335 (N–
H), 1,726 (C=O) cm-1; MS (FAB pos.): m/z (%) = 405
(100) [(M ? H)?]; HRMS (C23H37N2O4): calcd. 405.2753,
found 407.2751.
tert-Butyl (2S,40S,50S) and (2S,40R,50S)-2-[5-(benzyloxy-
carbonylamino)-6-methylhept-1-en-4-ylamino]propanoate
(30a, 30b, C23H36N2O4)
Aldimine 14 (1.45 g, 4.00 mmol), 523 mg Zn (8.00 mmol),
149 mg CeCl3ꢀ7H2O (0.40 mmol), and 661 mm3 allyl
bromide (7.60 mmol) were reacted according to GP 8 in
5 cm3 THF within 16 h. Chromatography (hexanes–Et2O
8:1 ? 3:1) yielded 860 mg adduct 30a (2.13 mmol, 53%)
and 216 mg adduct 30b (0.53 mmol, 13%) as colourless
oils.
tert-Butyl (2S,40S,50S) and (2S,40R,50S)-2-[5-(benzyloxy-
carbonylamino)-6-methylhept-1-en-4-ylamino]-4-methyl-
pentanoate (31a, 31b, C26H42N2O4)
Aldimine 15 (29.7 g, 73.5 mmol), 9.61 g Zn (147 mmol),
2.74 g CeCl3ꢀ7H2O (7.35 mmol), and 10.5 cm3 allyl bro-
mide (140 mmol) were reacted according to GP 8 in
40 cm3 THF within 16 h. Chromatography (hexanes–Et2O
6:1 ? 3:1) yielded 6.58 g adduct 31a (14.7 mmol, 20%)
and 6.70 g adduct 31b (15.0 mmol, 20%) as colourless
oils.
31a: Rf = 0.43 (hexanes–EtOAc 6:1); [a]2D0 = -31.9 9
10-1 deg cm2 g-1 (c = 0.70, CHCl3); 1H NMR (400 MHz,
CDCl3): d = 0.88 (d, 3J = 6.6 Hz, 3H, CH2CH(CH3)a
30a: Rf = 0.33 (hexanes–EtOAc 6:1); [a]2D0 = -27.8 9
10-1 deg cm2 g-1 (c = 0.82, CHCl3); 1H NMR (400 MHz,
3
CDCl3): d = 0.94 (d, J = 6.7 Hz, 3H, CH(CH3)a(CH3)b),
0.95 (d, 3J = 6.7 Hz, 3H, CH(CH3)a(CH3)b), 1.17 (d,
3J = 6.9 Hz, 3H, 3-H3), 1.46 (s, 9H, C(CH3)3), 1.44–1.50
(m, 1H, CHNHCH), 1.67 (dsept, 3J = 9.8 Hz, 3J =
6.7 Hz, 1H, 60-H), 2.06–2.20 (m, 2H, 30-H2), 2.76 (ddd,
3J = 7.7 Hz, 3J = 6.4 Hz, 3J = 1.5 Hz, 1H, 40-H), 3.22 (q,
3J = 6.9 Hz, 1H, 2-H), 3.17–3.24 (m, 1H, 50-H), 5.03–5.14
(m, 3H, 10-H2, NHCO), 5.08 (d, 2J = 12.3 Hz, 1H,
OCHaHb), 5.13 (d, 2J = 12.2 Hz, 1H, OCHaHb), 5.77
(ddt, 3J = 15.9 Hz, 3J = 11.2 Hz, 3J = 7.2 Hz, 1H, 20-H),
7.28–7.41 (m, 5H, Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = 19.7 (q, CHCH3), 19.8 (q, CHCH3), 19.9 (q, CHCH3),
28.1 (q, C(CH3)3), 31.2 (d, C-60), 38.7 (t, C-30), 55.4 (d, C-
40), 57.4 (d, C-2 or C-50), 59.4 (d, C-2 or C-50), 66.5 (t,
OCH2), 81.0 (s, C(CH3)3), 117.9 (t, C-10), 128.0 (d, Ph),
128.1 (d, 2C, Ph), 128.5 (2d, Ph), 135.0 (d, C-20), 136.9 (s,
Ph), 156.7 (s, NHCO), 175.4 (s, C-1) ppm; IR (KBr):
v = 3,337 (N–H), 1,727 (C=O) cm-1; MS (FAB pos.): m/z
(%) = 405 (100) [(M ? H)?]; HRMS (C23H37N2O4):
calcd. 405.2753, found 407.2751.
3
(CH3)b), 0.90 (d, J = 6.6 Hz, 3H, CH2CH(CH3)a(CH3)b),
0.95 (d, 3J = 6.7 Hz, 3H, CH(CH3)a(CH3)b), 0.96 (d,
3J = 6.7 Hz, 3H, CH(CH3)a(CH3)b), 1.26–1.34 (m, 1H, 3-
2
Ha), 1.30–1.55 (bs, 1H, CHNHCH), 1.35 (dt, J = 14.0
3
Hz, J = 7.0 Hz, 2H, 3-Hb), 1.41 (s, 9H, C(CH3)3), 1.60–
3
4
1.77 (m, 2H, 4-H, 60-H), 2.11 (tt, J = 7.0 Hz, J = 1.3
Hz, 2H, 30-H2), 2.76 (td, 3J = 6.9 Hz, 3J = 1.5 Hz, 1H, 40-
H), 3.13 (dd, 3J = 7.5 Hz, 3J = 7.0 Hz, 1H, 2-H), 3.20 (td,
3J = 9.9 Hz, J = 1.4 Hz, 1H, 50-H), 5.04 (ddt, 3J =
3
10.4 Hz, 2J = 2.0 Hz, J = 1.3 Hz, 1H, 10-Hcis), 5.01–
4
5.09 (m, 1H, 10-Htrans), 5.09 (d, 2J = 12.1 Hz, 1H,
2
OCHaHb), 5.13 (d, J = 12.1 Hz, 1H, OCHaHb), 5.30 (d,
3J = 9.9 Hz, 1H, NHCO), 5.76 (ddt, 3J = 17.6 Hz,
3J = 10.4 Hz, J = 7.2 Hz, 1H, 20-H), 7.14–7.40 (m, 5H,
3
30b: Rf = 0.15 (hexanes–EtOAc 6:1); [a]2D0 = -1.0 9
Ph) ppm; 13C NMR (100 MHz, CDCl3): d = 19.7 (q,
CH(CH3)a(CH3)b), 20.1 (q, CH(CH3)a(CH3)b), 22.5 (q,
10-1 deg cm2 g-1 (c = 1.00, CHCl3); 1H NMR (400 MHz,
123

190
M. Virlouvet et al.
CH2CH(CH3)a(CH3)b), 22.7 (q, CH2CH(CH3)a(CH3)b),
24.8 (d, C-4), 28.1 (q, C(CH3)3), 31.4 (d, C-60), 38.9 (t,
C-30), 43.7 (t, C-3), 55.6 (d, C-40), 59.5 (d, C-50), 61.0 (d,
C-2), 66.5 (t, OCH2), 81.0 (s, C(CH3)3), 118.0 (t, C-10),
128.0 (d, Ph), 128.1 (d, 2C, Ph), 128.5 (2d, Ph), 134.9 (d,
C-20), 137.0 (s, Ph), 156.7 (s, NHCO), 175.7 (s, C-1) ppm;
IR (KBr): v = 3,337 (N–H), 1,727 (C=O) cm-1; MS
(FAB pos.): m/z (%) = 447 (97) [(M ? H)?]; HRMS
(C26H43N2O4): calcd. 447.3223, found 447.3221.
3J = 6.9 Hz, 4J = 1.4 Hz, 1H, 30-Ha), 2.14 (dtt, 2J = 13.6
4
Hz, 3J = 6.8 Hz, J = 1.2 Hz, 1H, 30-Hb), 2.50 (td,
3
2
3J = 7.0 Hz, J = 1.8 Hz, 1H, 40-H), 2.71 (dd, J = 13.4
3
2
3
Hz, J = 8.0 Hz, 1H, 3-Ha), 2.83 (dd, J = 13.4 Hz, J =
6.3 Hz, 1H, 3-Hb), 3.35 (dd, 3J = 8.0 Hz, 3J = 6.3 Hz,
1H, 2-H), 3.62 (tdd, 3J = 9.3 Hz, 3J = 5.7 Hz, 3J =
1.5 Hz, 1H, 50-H), 4.72 (d, 3J = 9.7 Hz, 1H, NHCO),
5.02–5.10 (m, 4H, 10-H2, OCH2), 5.75 (dddd, 3J =
3
3
3
17.5 Hz, J = 9.4 Hz, J = 7.8 Hz, J = 6.5 Hz, 1H, 20-
H), 7.15–7.40 (m, 10H, 2 Ph) ppm; 13C NMR (100 MHz,
CDCl3): d = 22.2 (q, CH(CH3)a(CH3)b), 23.1 (q,
CH(CH3)a(CH3)b), 24.8 (d, C-70), 28.0 (q, C(CH3)3), 37.9
(t, C-30), 40.5 (t, C-3), 42.6 (t, C-60), 51.3 (d, C-50), 58.7 (d,
C-40), 63.9 (d, C-2), 66.4 (t, OCH2), 81.3 (s, C(CH3)3),
118.0 (t, C-10), 126.5 (d, Ph), 128.0 (d, 3C, Ph), 128.2 (d,
2C, Ph), 128.5 (d, 2C, Ph), 129.5 (2d, Ph), 135.2 (d, C-20),
137.0 (s, Ph), 138.0 (s, Ph), 156.2 (s, NHCO), 174.4 (s, C-
31b: Rf = 0.30 (hexanes–EtOAc 6:1); [a]2D0 = -8.8 9
10-1 deg cm2 g-1 (c = 0.63, CHCl3); 1H NMR (400 MHz,
CDCl3): d = 0.87 (d, 3J = 6.7 Hz, 3H, CH2CH
3
(CH3)a(CH3)b), 0.91 (d, J = 6.7 Hz, 3H, CH2CH(CH3)a
(CH3)b), 0.93 (d, 3J = 6.8 Hz, 3H, CH(CH3)a(CH3)b), 0.94
(d, 3J = 6.8 Hz, 3H, CH(CH3)a(CH3)b), 1.30 (dt, 2J =
3
2
13.4 Hz, J = 7.3 Hz, 1H, 3-Ha), 1.39 (dt, J = 13.6 Hz,
3J = 6.9 Hz, 1H, 3-Hb), 1.46 (s, 9H, C(CH3)3), 1.60–1.72
(m, 2H, 4-H, CHNHCH), 1.79 (u-oct, 3J = 6.8 Hz, 1H, 60-
1) ppm; IR (KBr): v = 3,339 (N–H), 1,724 (C=O) cm-1
;
2
H), 1.92–2.03 (m, 1H, 30-Ha), 2.22 (dddt, J = 14.0 Hz,
MS (FAB pos.): m/z (%) = 495 (21) [(M ? H)?]; HRMS
(C30H43N2O4): calcd. 495.3223, found 495.3227.
3
4
3J = 5.9 Hz, J = 4.2 Hz, J = 1.6 Hz, 1H, 30-Hb), 2.69
(dt, 3J = 8.6 Hz, 3J = 4.2 Hz, 1H, 40-H), 3.33 (t, 3J = 7.3
Hz, 1H, 2-H), 3.57 (ddd, 3J = 10.2 Hz, 3J = 8.0 Hz,
3J = 4.4 Hz, 1H, 50-H), 4.68 (d, 3J = 10.0 Hz, 1H,
NHCO), 5.04–5.17 (m, 4H, 10-H, OCH2), 5.79 (dddd,
3J = 16.9 Hz, 3J = 10.9 Hz, 3J = 8.4 Hz, 3J = 6.0 Hz,
1H, 20-H), 7.27–7.39 (m, 5H, Ph) ppm; 13C NMR
(100 MHz, CDCl3): d = 19.3 (q, CH(CH3)a(CH3)b), 20.3
(q, CH(CH3)a(CH3)b), 22.6 (q, CH2CH(CH3)a(CH3)b), 22.8
(q, CH2CH(CH3)a(CH3)b), 24.9 (d, C-4), 28.1 (q, C(CH3)3),
29.6 (d, C-60), 34.7 (t, C-30), 43.5 (t, C-3), 56.1 (d, C-40),
57.2 (d, C-50), 58.4 (d, C-2), 66.6 (t, OCH2), 80.7 (s,
C(CH3)3), 118.1 (t, C-10), 128.0 (d, 3C, Ph), 128.5 (d, 2C,
Ph), 135.2 (d, C-20), 136.9 (s, Ph), 156.8 (s, NHCO), 175.7
(s, C-1) ppm; IR (KBr): v = 3,335 (N–H), 1,726 (C=O)
cm-1; MS (FAB pos.): m/z (%) = 447 (100) [(M ? H)?];
HRMS (C26H43N2O4): calcd. 447.3223, found 447.3221.
32b: Rf = 0.34 (hexanes–EtOAc 6:1); [a]2D0 = ?8.5 9
10-1 deg cm2 g-1 (c = 1.19, CHCl3); 1H NMR (400 MHz,
3
CDCl3): d = 0.86 (d, J = 6.5 Hz, 3H, CH(CH3)a(CH3)b),
0.88 (d, 3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 1.04–1.24
(m, 2H, 60-H2), 1.35 (s, 9H, C(CH3)3), 1.49–1.60 (m, 2H,
70-H, CHNHCH), 2.05–2.15 (m, 2H, 30-H2), 2.56 (td,
3
2
3J = 7.2 Hz, J = 3.3 Hz, 1H, 40-H), 2.73 (dd, J = 13.4
Hz, 3J = 7.8 Hz, 1H, 3-Ha), 2.81 (dd, 2J = 13.4 Hz,
3J = 6.6 Hz, 1H, 3-Hb), 3.43 (dd, 3J = 7.7 Hz, 3J =
6.5 Hz, 1H, 2-H), 3.70–3.80 (m, 1H, 50-H), 4.57 (d,
3J = 9.2 Hz, 1H, NHCO), 5.03–5.14 (m, 4H, 10-H2,
3
3
3
OCH2), 5.71 (ddt, J = 17.4 Hz, J = 10.4 Hz, J = 7.2
Hz, 1H, 20-H), 7.15–7.40 (m, 10H, 2 Ph) ppm; 13C NMR
(100 MHz, CDCl3): d = 21.8 (q, CH(CH3)a(CH3)b), 23.7
(q, CH(CH3)a(CH3)b), 24.6 (d, C-70), 28.0 (q, C(CH3)3),
36.4 (t, C-30), 38.6 (t, C-3), 40.7 (t, C-60), 50.4 (d, C-50),
59.8 (d, C-40), 62.8 (d, C-2), 66.4 (t, OCH2), 81.2 (s,
C(CH3)3), 117.7 (t, C-10), 126.4 (d, Ph), 128.0 (d, 2C, Ph),
128.0 (d, Ph), 128.2 (d, 2C, Ph), 128.4 (d, 2C, Ph), 129.5
(2d, Ph), 134.9 (d, C-20), 136.9, 138.0 (2s, 2 Ph), 156.2 (s,
NHCO), 174.8 (s, C-1) ppm; IR (KBr): v = 3,341 (N–H),
1,722 (C=O) cm-1; MS (FAB pos.): m/z (%) = 495 (45)
[(M ? H)?]; HRMS (C30H43N2O4): calcd. 495.3223,
found 495.3220.
tert-Butyl (2S,40S,50S) and (2S,40R,50S)-2-[5-(benzyloxy-
carbonylamino)-7-methyloct-1-en-4-ylamino]-3-phenyl-
propanoate (32a, 32b, C30H42N2O4)
Aldimine 16 (2.26 g, 5.00 mmol), 654 mg Zn (10.0 mmol),
186 mg CeCl3ꢀ7H2O (0.50 mmol), and 720 mm3 allyl
bromide (9.50 mmol) were reacted according to GP 8 in
15 cm3 THF within 16 h. Chromatography (hexanes–Et2O
8:1 ? 4:1) yielded 537 mg adduct 32a (1.09 mmol, 22%)
and 672 mg adduct 32b (1.36 mmol, 27%) as colourless
oils.
tert-Butyl (2S,40S,50S) and (2S,40R,50S)-2-[5-(benzyloxy-
carbonylamino)-6-methylhept-1-en-4-ylamino]-3-methyl-
butanoate (33a, 33b, C25H40N2O4)
32a: Rf = 0.41 (hexanes–EtOAc 6:1); [a]2D0 = -15.6 9
10-1 deg cm2 g-1 (c = 1.17, CHCl3); 1H NMR (400 MHz,
Aldimine 17 (5.86 g, 15.0 mmol), 1.96 g Zn (30.0 mmol),
559 mg CeCl3ꢀ7H2O (1.50 mmol), and 2.43 cm3 allyl
bromide (28.5 mmol) were reacted according to GP 8 in
30 cm3 THF within 16 h. Chromatography (hexanes–Et2O
8:1 ? 4:1) yielded 878 mg adduct 33a (2.00 mmol, 14%)
3
CDCl3): d = 0.81 (d, J = 6.6 Hz, 3H, CH(CH3)a(CH3)b),
0.83 (d, 3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.95–1.15
(m, 2H, 60-H), 1.38 (s, 9H, C(CH3)3), 1.33–1.52 (m, 2H, 70-
H, CHNHCH), 2.06 (dddt, 2J = 13.7 Hz, 3J = 7.9 Hz,
123

Addition of allylzinc to a-amino acid-derived imines
191
and 1.09 g adduct 33b (2.50 mmol, 17%) as colourless
oils.
tert-Butyl (2S,40S,50S) and (2S,40R,50S)-2-[5-(benzyloxy-
carbonylamino)-6-methylhept-1-en-4-ylamino]-3-phenyl-
propanoate (34a, 34b, C29H40N2O4)
33a: Rf = 0.47 (hexanes–EtOAc 6:1); [a]2D0 = -28.5 9
10-1 deg cm2 g-1 (c = 0.84, CHCl3); 1H NMR (400 MHz,
Aldimine 18 (6.50 g, 14.8 mmol), 1.94 g Zn (29.6 mmol),
552 mg CeCl3ꢀ7H2O (1.48 mmol), and 2.45 cm3 allyl
bromide (28.2 mmol) were reacted according to GP 8 in
20 cm3 THF within 16 h. Chromatography (hexanes–
EtOAc 6:1) yielded 3.74 g adduct 34a (7.79 mmol, 53%)
and 771 mg adduct 34b (1.60 mmol, 11%) as colourless
oils.
3
CDCl3): d = 0.90 (d, J = 6.7 Hz, 3H, CHCH3), 0.94 (d,
3J = 6.7 Hz, 3H, CHCH3), 0.94 (d, 3J = 6.8 Hz, 3H,
CHCH3), 0.95 (d, 3J = 6.8 Hz, 3H, CHCH3), 1.18 (bs, 1H,
CHNHCH), 1.48 (s, 9H, C(CH3)3), 1.71 (dsept, 3J =
10.0 Hz, 3J = 6.7 Hz, 1H, 60-H), 1.74 (u-oct, 3J = 6.8 Hz,
3
3
1H, 3-H), 2.12 (tt, J = 7.0 Hz, J = 1.3 Hz, 2H, 30-H2),
2.72 (td, 3J = 6.9 Hz, J = 1.5 Hz, 1H, 40-H), 2.82
(d, 3J = 6.9 Hz, 1H, 2-H), 3.20 (td, 3J = 10.0 Hz,
3J = 1.5 Hz, 1H, 50-H), 5.02–5.08 (m, 2H, 10-H2), 5.09
34a: Rf = 0.33 (hexanes–EtOAc 6:1); [a]2D0 = -43.2 9
3
10-1 deg cm2 g-1 (c = 0.86, CHCl3); 1H NMR (400 MHz,
3
CDCl3): d = 0.79 (d, J = 6.7 Hz, 3H, CH(CH3)a(CH3)b),
0.84 (d, J = 6.7 Hz, 3H, CH(CH3)a(CH3)b), 1.37 (s, 9H,
2
2
3
(d, J = 12.1 Hz, 1H, OCHaHb), 5.13 (d, J = 12.2 Hz,
1H, OCHaHb), 5.27 (d, 3J = 9.9 Hz, 1H, NHCO), 5.76
(ddt, 3J = 17.8 Hz, 3J = 10.6 Hz, 3J = 7.2 Hz, 1H, 20-H),
7.27–7.41 (m, 5H, Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = 19.1 (q, CHCH3), 19.3 (q, CHCH3), 19.8 (q,
CHCH3), 20.1 (q, CHCH3), 28.2 (q, C(CH3)3), 31.2
(d, C-60), 32.2 (d, C-3), 38.9 (t, C-30), 55.9 (d, C-40), 59.6
(d, C-50), 66.5 (t, OCH2), 68.5 (d, C-2), 81.1 (s, C(CH3)3),
117.9 (t, C-10), 128.0 (d, Ph), 128.1 (d, 2C, Ph), 128.5 (d,
2C, Ph), 135.0 (d, C-20), 137.0 (s, Ph), 156.7 (s, NHCO),
174.9 (s, C-1) ppm; IR (KBr): v = 3,343 (N–H), 1,725
(C=O) cm-1; MS (FAB pos.): m/z (%) = 433 (100)
[(M ? H)?]; HRMS (C25H41N2O4): calcd. 433.3066,
found 433.3072.
C(CH3)3), 1.33–1.43 (m, 1H, 60-H), 1.68 (bs, 1H,
3
CHNHCH), 2.09 (tq, J = 7.2 Hz, J, J = 1.4 Hz, 2H,
4
3
2
3
30-H2), 2.72 (dd, J = 13.3 Hz, J = 8.0 Hz, 1H, 3-Ha),
3
3
2.74 (dt, J = 7.1 Hz, J = 1.6 Hz, 1H, 40-H), 2.81 (dd,
2J = 13.4 Hz, 3J = 6.7 Hz, 1H, 3-Hb), 3.11 (td, 3J =
3
3
10.0 Hz, J = 1.4 Hz, 1H, 50-H), 3.30 (dd, J = 7.9 Hz,
3J = 6.7 Hz, 1H, 2-H), 5.01–5.13 (m, 2H, 10-H, NHCO),
5.06 (d, 2J = 12.5 Hz, 1H, OCHaHb), 5.12 (d, 2J =
12.3 Hz, 1H, OCHaHb), 5.73 (ddt, 3J = 16.3 Hz,
3J = 10.7 Hz, J = 7.2 Hz, 1H, 20-H), 7.14–7.40 (m,
3
10H, 2 Ph) ppm; 13C NMR (100 MHz, CDCl3): d = 19.7
(q, CH(CH3)a(CH3)b), 19.9 (q, CH(CH3)a(CH3)b), 28.0 (q,
C(CH3)3), 31.1 (d, C-60), 38.8 (t, C-30), 40.5 (t, C-3), 55.6
(d, C-40), 59.5 (d, C-50), 64.0 (d, C-2), 66.4 (t, OCH2), 81.3
(s, C(CH3)3), 118.0 (t, C-10), 126.5 (d, Ph), 127.9 (d, 3C,
Ph), 128.2 (d, 2C, Ph), 128.5 (d, 2C, Ph), 129.4 (2d, Ph),
134.9 (d, C-20), 137.1, 137.8 (2s, 2 Ph), 156.6 (s, NHCO),
174.4 (s, C-1) ppm; IR (KBr): v = 3,400, 3,335 (N–H),
1,725 (C=O) cm-1; MS (FAB pos.): m/z (%) = 481 (100)
[(M ? H)?]; HRMS (C29H41N2O4): calcd. 481.3066,
found 481.3071.
33b: Rf = 0.38 (hexanes–EtOAc 6:1); [a]2D0 = -7.0 9
10-1 deg cm2 g-1 (c = 1.00, CHCl3); 1H NMR (400 MHz,
CDCl3): d = 0.89 (d, 3J = 6.5 Hz, 3H, CHCH3), 0.91
3
3
(d, J = 6.3 Hz, 3H, CHCH3), 0.92 (d, J = 6.6 Hz, 3H,
3
CHCH3), 0.93 (d, J = 6.7 Hz, 3H, CHCH3), 1.46 (s, 9H,
C(CH3)3), 1.61 (bs, 1H, CHNHCH), 1.75 (u-oct, 3J =
3
6.8 Hz, 1H, 3-H), 1.81 (u-oct, J = 6.7 Hz, 1H, 60-H),
1.99 (dt, 2J = 13.6 Hz, J = 8.0 Hz, 1H, 30-Ha), 2.22
3
2
(dddt, J = 13.8 Hz, J = 6.1 Hz, J = 4.3 Hz, J = 1.6
3
3
4
34b: Rf = 0.15 (hexanes–EtOAc 6:1); [a]2D0 = -21.3 9
3
3
Hz, 1H, 30-Hb), 2.65 (dt, J = 8.6 Hz, J = 4.4 Hz, 1H,
40-H), 3.00 (d, 3J = 6.6 Hz, 1H, 2-H), 3.55 (ddd,
10-1 deg cm2 g-1 (c = 1.07, CHCl3); 1H NMR (400 MHz,
3
CDCl3): d = 0.85 (d, J = 6.7 Hz, 3H, CH(CH3)a(CH3)b),
0.88 (d, J = 6.7 Hz, 3H, CH(CH3)a(CH3)b), 1.35 (s, 9H,
3J = 10.0 Hz, J = 7.5 Hz, J = 4.3 Hz, 1H, 50-H), 4.74
3
3
3
(d, 3J = 10.3 Hz, 1H, NHCO), 5.06 (d, J = 12.3 Hz, 1H,
2
3
C(CH3)3), 1.56 (bs, 1H, CHNHCH), 1.88 (septd, J = 6.7
OCHaHb), 5.10 (d, 2J = 12.3 Hz, 1H, OCHaHb), 5.09–5.16
(m, 2H, 10-H), 5.73–5.85 (m, 1H, 20-H), 7.27–7.38 (m, 5H,
Ph) ppm; 13C NMR (100 MHz, CDCl3): d = 18.8 (q,
CHCH3), 19.1 (q, CHCH3), 19.2 (q, CHCH3), 20.4 (q,
CHCH3), 28.2 (q, C(CH3)3), 29.4 (d, C-60), 32.1 (d, C-3),
34.9 (t, C-30), 56.6 (d, C-40), 57.1 (d, C-50), 65.7 (d, C-2),
66.6 (t, OCH2), 80.7 (s, C(CH3)3), 118.0 (t, C-10), 128.0
(d, Ph), 128.1 (d, 2C, Ph), 128.5 (2d, Ph), 135.3 (d, C-20),
136.8 (s, Ph), 156.8 (s, NHCO), 175.0 (s, C-1) ppm; IR
(KBr): v = 3,343 (N–H), 1,724 (C=O) cm-1; MS (FAB
pos.): m/z (%) = 433 (93), [(M ? H)?]; HRMS
(C25H40N2O4): calcd. 433.3066, found 433.3064.
Hz, J = 6.2 Hz, 1H, 60-H), 2.03 (dddt, 2J = 14.3 Hz,
3
3
4
3J = 7.2 Hz, J = 5.9 Hz, J = 1.3 Hz, 1H, 30-Ha), 2.12
2
(dddt, J = 14.1 Hz, J = 7.0 Hz, J = 5.3 Hz, J = 1.4
3
3
4
3
Hz, 1H, 30-Hb), 2.59 (q, J = 5.7 Hz, 1H, 40-H), 2.80
(dd, 2J = 13.3 Hz, 3J = 7.5 Hz, 1H, 3-Ha), 2.90 (dd,
2J = 13.4 Hz, 3J = 6.6 Hz, 1H, 3-Hb), 3.51 (dt, 3J =
3
3
10.1 Hz, J = 5.7 Hz, 1H, 50-H), 3.52 (dd, J = 7.6 Hz,
3J = 6.5 Hz, 1H, 2-H), 4.89 (d, 3J = 10.4 Hz, 1H,
3
2
4
NHCO), 4.93 (ddt, J = 17.1 Hz, J = 1.9 Hz, J = 1.3
3
2
Hz, 1H, 10-Htrans), 4.96 (ddt, J = 10.3 Hz, J = 2.0 Hz,
4J = 1.0 Hz, 1H, 10-Hcis), 5.07 (d, 2J = 12.0 Hz, 1H,
OCHaHb), 5.11 (d, 2J = 12.3 Hz, 1H, OCHaHb), 5.73 (ddt,
123

192
M. Virlouvet et al.
3J = 17.3 Hz, 3J = 10.2 Hz, J = 7.1 Hz, 1H, 20-H),
7.17–7.38 (m, 10H, 2 Ph) ppm; 13C NMR (100 MHz,
CDCl3): d = 17.8 (q, CH(CH3)a(CH3)b), 20.6 (q,
CH(CH3)a(CH3)b), 28.0 (q, C(CH3)3), 28.7 (d, C-60), 34.9
(t, C-30), 40.1 (t, C-3), 57.3 (d, C-40), 58.5 (d, C-50), 61.2 (d,
C-2), 66.6 (t, OCH2), 81.0 (s, C(CH3)3), 117.1 (t, C-10),
126.5 (d, Ph), 128.0 (d, Ph), 128.0 (d, 2C, Ph), 128.3 (d,
2C, Ph), 128.5 (d, 2C, Ph), 129.4 (2d, Ph), 135.5 (d, C-20),
136.8, 137.7 (2s, 2 Ph), 156.8 (s, NHCO), 173.8 (s, C-1)
ppm; IR (KBr): v = 3,403, 3,337 (N–H), 1,725 (C=O)
cm-1; MS (FAB pos.): m/z (%) = 481 (35) [(M ? H)?];
HRMS (C29H41N2O4): calcd. 481.3066, found 481.3061.
bromide (1.90 mmol) were reacted according to GP 8 in
4 cm3 THF within 16 h. Chromatography (hexanes–Et2O
10:1 ? 8:1) yielded 95 mg adduct 41a (0.21 mmol, 21%)
and 80 mg adduct 41b (0.18 mmol, 18%) as colourless
oils.
3
41a: Rf = 0.47 (hexanes–EtOAc 6:1); [a]2D0 = ?30.5 9
10-1 deg cm2 g-1 (c = 0.93, CHCl3); 1H NMR (400 MHz,
3
CDCl3): d = 0.91 (d, J = 6.4 Hz, 3H, CHCH3), 0.92 (d,
3J = 6.5 Hz, 3H, CHCH3), 0.93 (d, 3J = 6.0 Hz, 3H,
3
CHCH3), 0.94 (d, J = 6.8 Hz, 3H, CHCH3), 1.32 (ddd,
3
2J = 13.6 Hz, 3J = 8.2 Hz, J = 5.5 Hz, 1H, 60-Ha),
2
1.35–1.50 (bs, 1H, CHNHCH), 1.37 (ddd, J = 14.0 Hz,
3
3J = 8.7 Hz, J = 5.4 Hz, 1H, 60-Hb), 1.47 (s, 9H,
tert-Butyl (2S,40S,50S) and (2S,40S,50S)-2-[2-(benzyloxy-
carbonylamino)hex-5-en-3-ylamino]-4-methylpentanoate
(35a, 35b, C24H38N2O4)
3
3
C(CH3)3), 1.64 (u-dsept, J = 8.1 Hz, J = 6.5 Hz, 1H,
70-H), 1.77 (u-oct, 3J = 6.7 Hz, 1H, 3-H), 2.08 (ddd,
3
3
2J = 13.6 Hz, J = 7.8 Hz, J = 6.8 Hz, 1H, 30-Ha), 2.16
Aldimine 19 (1.07 g, 2.85 mmol), 373 mg Zn (5.70 mmol),
106 mg CeCl3ꢀ7H2O (0.29 mmol), and 470 mm3 allyl
bromide (5.42 mmol) were reacted according to GP 8 in
4 cm3 THF within 16 h. Chromatography (hexanes–EtOAc
6:1) yielded a mixture of isomers 35a/35b (395 mg,
0.94 mmol, 33%) as a colourless oil. Rf = 0.40 (hex-
anes–EtOAc 6:1). Spectroscopic data given for a mixture
of isomers: Major isomer, selected data: 1H NMR
(400 MHz, CDCl3): d = 0.81 (d, 3J = 6.6 Hz, 3H,
CH(CH3)a(CH3)b), 0.86 (d, 3J = 6.7 Hz, 3H, CH(CH3)a
2
3
4
(dtt, J = 13.9 Hz, J = 6.9 Hz, J = 1.4 Hz, 1H, 30-Hb),
2.48 (td, 3J = 7.0 Hz, J = 1.9 Hz, 1H, 40-H), 2.89 (d,
3
3J = 6.4 Hz, 1H, 2-H), 3.72 (tdd, J = 9.2 Hz, J = 5.7
3
3
Hz, J = 1.8 Hz, 1H, 50-H), 5.03 (d, 3J = 9.3 Hz, 1H,
3
2
NHCO), 5.04–5.11 (m, 2H, 10-H2), 5.07 (d, J = 12.3 Hz,
2
1H, OCHaHb), 5.11 (d, J = 12.2 Hz, 1H, OCHaHb), 5.78
(ddt, 3J = 17.4 Hz, 3J = 10.1 Hz, 3J = 7.3 Hz, 1H, 20-H),
7.28–7.40 (m, 5H, Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = 18.9 (q, CH(CH3)a(CH3)b), 19.5 (q, CH(CH3)a(CH3)b),
22.3 (q, CH2CH(CH3)a(CH3)b), 23.3 (q, CH2CH(CH3)a
(CH3)b), 24.9 (d, C-70), 28.2 (q, C(CH3)3), 32.2 (d, C-3),
37.7 (t, C-30), 42.4 (t, C-60), 51.2 (d, C-50), 58.9 (d, C-40),
66.5 (t, OCH2), 68.0 (d, C-2), 81.0 (s, C(CH3)3), 117.8 (t,
C-10), 128.0 (d, Ph), 128.1 (d, 2C, Ph), 128.5 (d, 2C, Ph),
135.3 (d, C-20), 136.9 (s, Ph), 156.2 (s, NHCO), 174.9 (s,
3
(CH3)b), 1.05 (d, J = 6.7 Hz, 3H, 60-H3), 1.48 (s, 9H,
C(CH3)3), 2.54 (td, J = 7.2 Hz, J = 3.7 Hz, 1H, 40-H),
3
3
3.10 (dd, J = 7.7 Hz, J = 6.7 Hz, 1H, 2-H) ppm; 13C
NMR (100 MHz, CDCl3): d = 15.3 (q, C-60), 22.2 (q,
CH(CH3)a(CH3)b), 22.8 (q, CH(CH3)a(CH3)b), 24.9 (d,
C-4), 28.1 (q, C(CH3)3), 36.1 (t, C-30), 43.8 (t, C-3), 47.7
(d, C-50), 59.4 (d, C-40), 60.7 (d, C-2), 66.4 (t, OCH2), 81.0
(s, C(CH3)3), 117.9 (t, C-10), 134.9 (d, C-20), 136.8 (s, Ph),
156.1 (s, NHCO), 175.8 (s, C-1) ppm. Minor isomer,
3
3
C-1) ppm; IR (KBr): v = 3,340 (N–H), 1,725 (C=O) cm-1
;
MS (FAB pos.): m/z (%) = 447 (30) [(M ? H)?]; HRMS
(C26H43N2O4): calcd. 447.3223, found 447.3226.
41b: Rf = 0.43 (hexanes–EtOAc 6:1); [a]2D0 = -0.8 9
1
selected data: H NMR (400 MHz, CDCl3): d = 0.85 (d,
10-1 deg cm2 g-1 (c = 0.88, CHCl3); 1H NMR (400 MHz,
3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.87 (d, J = 6.7 Hz,
3
3
CDCl3): d = 0.89 (d, J = 6.8 Hz, 3H, CHCH3), 0.90 (d,
3H, CH(CH3)a(CH3)b), 1.48 (s, 9H, C(CH3)3), 2.44 (td,
3J = 6.9 Hz, 3J = 2.1 Hz, 1H, 40-H), 3.13–3.20 (m, 1H, 2-
H) ppm; 13C NMR (100 MHz, CDCl3): d = 19.0 (q, C-60),
22.5 (q, CH(CH3)a(CH3)b), 22.8 (q, CH(CH3)a(CH3)b),
24.8 (d, C-4), 28.1 (q, C(CH3)3), 37.6 (t, C-30), 43.7 (t,
C-3), 48.7 (d, C-50), 59.1 (d, C-2), 59.4 (d, C-40), 66.5 (t,
OCH2), 81.0 (s, C(CH3)3), 117.9 (t, C-10), 135.1 (d, C-20),
136.8 (s, Ph), 155.9 (s, NHCO), 175.5 (s, C-1) ppm;
IR (KBr): v = 3,339 (N–H), 1,727 (C=O) cm-1; MS
(FAB pos.): m/z (%) = 419 (100) [(M ? H)?]; HRMS
(C24H39N2O4): calcd. 41.2910, found 419.2908.
3J = 6.9 Hz, 3H, CHCH3), 0.91 (d, 3J = 7.0 Hz, 3H,
3
CHCH3), 0.92 (d, J = 7.1 Hz, 3H, CHCH3), 1.15–1.45
(m, 3H, 60-H2, CHNHCH), 1.46 (s, 9H, C(CH3)3), 1.58–
3
1.71 (m, 1H, 70-H), 1.80 (u-oct, J = 6.8 Hz, 1H, 3-H),
3
3
2.11 (t, J = 7.1 Hz, 2H, 30-H2), 2.57 (td, J = 7.1 Hz,
3J = 3.4 Hz, 1H, 40-H), 2.91 (d, J = 7.0 Hz, 1H, 2-H),
3
3.76–3.86 (m, 1H, 50-H), 5.01–5.13 (m, 5H, 10-H2, NHCO,
OCH2), 5.67–5.80 (m, 1H, 20-H), 7.25–7.38 (m, 5H,
Ph) ppm; 13C NMR (100 MHz, CDCl3): d = 18.4 (q,
CH(CH3)a(CH3)b), 19.3 (q, CH(CH3)a(CH3)b), 21.9 (q,
CH2CH(CH3)a(CH3)b), 23.6 (q, CH2CH(CH3)a(CH3)b),
24.7 (d, C-70), 28.1 (q, C(CH3)3), 32.4 (d, C-3), 36.3 (t,
C-30), 38.8 (t, C-60), 50.3 (d, C-50), 60.1 (d, C-40), 66.2 (d,
C-2), 66.4 (t, OCH2), 81.0 (s, C(CH3)3), 117.6 (t, C-10),
127.9 (d, 3C, Ph), 128.4 (d, 2C, Ph), 135.1 (d, C-20), 136.9
(s, Ph), 156.3 (s, NHCO), 175.1 (s, C-1) ppm; IR (KBr):
tert-Butyl (2R,40S,50S) and (2R,40R,50S)-2-[5-(benzyloxy-
carbonylamino)-7-methyloct-1-en-4-ylamino]-3-methylbut-
anoate (41a, 41b, C26H42N2O4)
Aldimine 40 (404 mg, 1.00 mmol), 131 mg Zn (2.00 mmol),
37 mg CeCl3ꢀ7H2O (0.10 mmol), and 170 mm3 allyl
123

Addition of allylzinc to a-amino acid-derived imines
193
v = 3,345 (N–H), 1,725 (C=O) cm-1; MS (FAB pos.): m/z
(%) = 447 (65) [(M ? H)?]; HRMS (C26H43N2O4): calcd.
447.3223, found 447.3221.
Benzyl (3S,4S,20S)-4-[1-(tert-butyldiphenylsilyloxy)-2-pro-
pylamino]-7-hydroxy-2-methyl-3-heptylcarbamate
(43a, C35H50N2O4Si)
Alkene 22a (1.22 g, 2.13 mmol) and 8.50 cm3 of a solution
of 9-BBN (0.5 M in THF, 4.26 mmol) in 10 cm3 anhydrous
THF were reacted according to GP 9 within 3 h at room
temperature. Purification by chromatography (hexanes–
EtOAc 3:1 ? 2:1) yielded 1.23 g alcohol 43a (2.08 mmol,
97%) as a colourless oil. Rf = 0.50 (hexanes–EtOAc 1:1);
Synthesis of alcohols via hydroboration
General procedure (GP 9) for synthesis of alcohols via
hydroboration
A solution of the alkene (prepared according to GP 8,
1 mmol) in 5 cm3 anhydrous THF was added at 0 °C under
an argon atmosphere to 4 cm3 9-BBN (0.5 M in THF,
2 mmol). The mixture was warmed to room temperature
and stirred for 3 h. NaOH (3 M, 5.50 cm3), 7.80 cm3 H2O2
(30%), and 1 g NaOH were added at 0 °C and the mixture
was extracted with Et2O (3 9 20 cm3). The combined
organic layers were washed with 40 cm3 brine, dried
(Na2SO4), concentrated, and purified by chromatography
(silica gel).
[a]2D0 = -5.0 9 10-1 deg cm2 g-1 (c = 0.67, CHCl3); H
1
3
NMR (400 MHz, CDCl3): d = 0.90 (d, J = 6.3 Hz, 3H,
CHCH3), 0.91 (d, 3J = 6.6 Hz, 3H, CHCH3), 0.92 (d,
3J = 6.7 Hz, 3H, CHCH3), 1.04 (s, 9H, SiC(CH3)3), 1.30–
1.41 (m, 1H, 5-Ha), 1.41–1.77 (m, 5H, 6-H2, 5-Hb, OH,
CHNHCH), 1.77–1.87 (m, 1H, 2-H), 2.65 (ddd,
3J = 8.5 Hz, 3J = 4.2 Hz, 3J = 2.3 Hz, 1H, 4-H), 2.80
3
(td, 3J = 6.4 Hz, J = 4.3 Hz, 1H, 20-H), 3.30 (ddd,
3
3
3J = 10.4 Hz, J = 9.0 Hz, J = 2.3 Hz, 1H, 3-H), 3.42
(dd, 2J = 9.9 Hz, J = 6.6 Hz, 1H, 10-Ha), 3.53 (ddd,
3
tert-Butyl (3S,4S,20S)-4-[1-(tert-butyldimethylsilyloxy)-2-
propylamino]-7-hydroxy-2-methyl-3-heptylcarbamate
(42a, C22H48N2O4Si)
3
3
2J = 10.6 Hz, J = 7.0 Hz, J = 5.4 Hz, 1H, 7-Ha), 3.58
2
3
(dd, J = 9.8 Hz, J = 4.2 Hz, 1H, 10-Hb), 3.54–3.63 (m,
3
1H, 7-Hb), 5.02 (d, J = 10.2 Hz, 1H, NHCO), 5.07 (d,
Alkene 20a (237 mg, 0.57 mmol) and 2.30 cm3 of a
solution of 9-BBN (0.5 M in THF, 1.14 mmol) in 5 cm3
anhydrous THF were reacted according to GP 9 within 3 h
at room temperature. Purification by chromatography
(hexanes–EtOAc 3:1 ? 2:1) yielded 216 mg alcohol 42
(0.50 mmol, 87%) as a colourless oil. Rf = 0.51 (hexanes–
EtOAc 1:1); [a]2D0 = ?0.4 9 10-1 deg cm2 g-1 (c = 1.14,
2J = 12.3 Hz, 1H, CHaHbPh), 5.12 (d, J = 12.3 Hz, 1H,
2
CHaHbPh), 7.26–7.45 (m, 11H, 3 Ph), 7.62–7.66 (m, 4H, 3
Ph) ppm; 13C NMR (100 MHz, CDCl3): d = 17.7 (q, C-
30), 19.3 (q, CH(CH3)a(CH3)b), 20.1 (q, CH(CH3)a(CH3)b),
26.9 (s, C(CH3)3), 29.1 (t, C-30), 29.5 (t, C-6), 29.9 (d, C-
2), 52.5 (d, C-20), 54.2 (d, C-4), 59.0 (d, C-3), 62.8 (t, C-7),
66.7 (t, CH2Ph), 68.2 (t, C-10), 127.7 (d, 4C, Ph), 128.0 (d,
3C, Ph), 128.5 (d, 2C, Ph), 129.7 (d, 2C, Ph), 133.5 (s, Ph),
133.5 (s, Ph), 135.6 (d, 2C, Ph), 135.6 (2d, Ph), 136.8 (s,
Ph), 157.1 (s, NHCO) ppm; IR (KBr): v = 3,420 (N–H, O–
H), 1,708 (C=O) cm-1; MS (FAB pos.): m/z (%) = 591
(100) [(M ? H)?]; HRMS (C35H51N2O4Si): calcd.
591.3618, found 591.3616.
1
CHCl3); H NMR (400 MHz, CDCl3): d = 0.06 (s, 3H,
Si(CH3)a(CH3)b), 0.06 (s, 3H, Si(CH3)a(CH3)b), 0.90 (s,
9H, SiC(CH3)3), 0.91 (d, 3J = 6.3 Hz, 3H, CH(CH3)a
(CH3)b), 0.94 (d, 3J = 6.3 Hz, 3H, CH(CH3)a(CH3)b), 0.92
(d, 3J = 6.3 Hz, 3H, 30-H3), 1.43 (s, 9H, OC(CH3)3), 1.35–
1.87 (m, 7H, 7-H2, 6-H2, 3-H, OH, CHNHCH), 2.64 (ddd,
3J = 8.3 Hz, 3J = 4.0 Hz, 3J = 2.9 Hz, 1H, 5-H), 2.79
(u-dquint, 3J = 6.4 Hz, 3J = 4.3 Hz, 1H, 20-H), 3.27 (ddd,
tert-Butyl (3S,4S,20S)-4-[1-(tert-butyldimethylsilyloxy)-3-
phenyl-2-propylamino]-7-hydroxy-2-methyl-3-heptylcar-
bamate (44a, C28H52N2O4Si)
3
3
3J = 10.4 Hz, J = 8.6 Hz, J = 2.7 Hz, 1H, 4-H), 3.36
(dd, 3J = 9.8 Hz, J = 6.8 Hz, 1H, 10-Ha), 3.53 (dd,
3
2J = 9.8 Hz, 3J = 4.4 Hz, 1H, 10-Hb), 3.53 (ddd,
Alkene 24a (1.18 g, 2.40 mmol) and 9.60 cm3 of a solution
of 9-BBN (0.5 M in THF, 4.80 mmol) in 10 cm3 anhy-
drous THF were reacted according to GP 9 within 3 h at
room temperature. Purification by chromatography (hex-
anes–EtOAc 3:1 ? 2:1) yielded 1.02 g alcohol 44a
(2.00 mmol, 83%) as a colourless solid. Rf = 0.62 (hex-
anes–EtOAc 1:1); [a]2D0 = ?38.5 9 10-1 deg cm2 g-1
(c = 1.03, CHCl3); m.p.: 117–119 °C; 1H NMR
(400 MHz, CDCl3): d = 0.03 (s, 3H, Si(CH3)a(CH3)b),
3
3
2J = 10.9 Hz, J = 7.4 Hz, J = 4.9 Hz, 1H, 1-Ha), 3.66
(dt, 2J = 11.0 Hz, 3J = 5.7 Hz, 1H, 1-Hb), 4.76 (d,
3J = 10.3 Hz, 1H, NHCO) ppm; 13C NMR (100 MHz,
CDCl3): d = -5.4 (q, Si(CH3)a(CH3)b), -5.3 (q, Si(CH3)a
(CH3)b), 17.5 (q, C-30), 18.2 (s, SiC(CH3)3), 19.1 (q,
CH(CH3)a(CH3)b), 20.2 (q, CH(CH3)a(CH3)b), 25.9
(q, SiC(CH3)3), 28.4 (q, OC(CH3)3), 28.8 (t, C-6), 29.4
(t, C-7), 29.6 (d, C-3), 52.3 (d, C-20), 54.4 (d, C-5), 58.2 (d,
C-4), 62.7 (t, C-8), 67.4 (t, C-10), 78.9 (s, SiC(CH3)3),
156.8 (s, NHCO) ppm; IR (KBr): v = 3,341 (N–H, O–H),
1,697 (C=O) cm-1; MS (FAB pos.): m/z (%) = 433 (100)
[(M ? H)?]; HRMS (C22H49N2O4Si): calcd. 433.3462,
found 433.3458.
3
0.04 (s, 3H, Si(CH3)a(CH3)b), 0.79 (d, J = 6.7 Hz, 3H,
CH(CH3)a(CH3)b), 0.85 (d, 3J = 6.6 Hz, 3H, CH(CH3)a
(CH3)b), 0.91 (s, 9H, SiC(CH3)3), 1.43 (s, 9H, OC(CH3)3),
1.38–1.72 (m, 7H, 6-H2, 5-H2, 2-H, OH, CHNHCH), 2.63
3
(u-d, J = 7.0 Hz, 2H, 30-H2), 2.71 (ddd, 3J = 7.5 Hz,
123

194
M. Virlouvet et al.
3J = 5.1 Hz, 3J = 2.3 Hz, 1H, 4-H), 2.80 (u-tt, 3J =
(KBr): v = 3,408, 3,340 (N–H, O–H), 1,705 (C=O) cm-1
;
3
3
6.9 Hz, J = 4.6 Hz, 1H, 20-H), 3.14 (ddd, J = 10.1 Hz,
3J = 9.1 Hz, 3J = 2.3 Hz, 1H, 3-H), 3.42 (dd, 3J =
MS (FAB pos.): m/z (%) = 557 (100) [(M ? H)?]; HRMS
(C32H53N2O4Si): calcd. 557.3775, found 557.3771.
3
2
10.0 Hz, J = 4.8 Hz, 1H, 10-Ha), 3.53 (dd, J = 9.9 Hz,
3J = 4.2 Hz, 1H, 10-Hb), 3.59 (ddd, 2J = 10.6 Hz,
Benzyl (4S,5S,20S)-5-[1-(tert-butyldimethylsilyloxy)-3-phe-
nyl-2-propylamino]-8-hydroxy-2-methyloct-4-ylcarbamate
(45b, C32H52N2O4Si)
3J = 7.1 Hz, J = 5.3 Hz, 1H, 7-Ha), 3.64 (u-td, 3J = 5.5
3
3
2
3
Hz, J, J = 11.1 Hz, 1H, 7-Hb), 4.65 (d, J = 10.2 Hz,
1H, NHCO), 7.15–7.33 (m, 5H, Ph) ppm; 13C NMR
(100 MHz, CDCl3): d = -5.5 (q, Si(CH3)a(CH3)b), -5.4
(q, Si(CH3)a(CH3)b), 18.2 (s, SiC(CH3)3), 19.4 (q,
CH(CH3)a(CH3)b), 20.1 (q, CH(CH3)a(CH3)b), 25.9 (q,
SiC(CH3)3), 28.5 (q, OC(CH3)3), 29.5 (t, C-6 or C-5), 29.6
(t, C-6 or C-5), 29.9 (d, C-2), 38.9 (t, C-30), 54.7 (d, C-4),
58.6 (d, C-3), 59.6 (d, C-20), 62.7 (t, C-7), 64.3 (t, C-10),
78.7 (s, OC(CH3)3), 126.1 (d, Ph), 128.3 (d, 2C, Ph) 129.3
(d, 2C, Ph), 139.7 (s, Ph), 156.7 (s, NHCO) ppm; IR (KBr):
v = 3,367, 3,183 (N–H, O–H), 1,709 (C=O) cm-1; MS
(FAB pos.): m/z (%) = 509 (100) [(M ? H)?]; HRMS
(C28H53N2O4Si): calcd. 509.3775, found 509.3777.
Alkene 25a (940 mg, 1.74 mmol) and 7.00 cm3 of a
solution of 9-BBN (0.5 M in THF, 3.48 mmol) in 10 cm3
anhydrous THF were reacted according to GP 9 within 3 h
at room temperature. Purification by chromatography
(hexanes–EtOAc 3:1 ? 2:1) yielded 788 mg alcohol 45b
(1.42 mmol, 81%) as a colourless oil. Rf = 0.54 (hexanes–
EtOAc 1:1); [a]2D0 = ?11.9 9 10-1 deg cm2 g-1 (c = 1.06,
1
CHCl3); H NMR (400 MHz, CDCl3): d = 0.01 (s, 3H,
Si(CH3)a(CH3)b), 0.02 (s, 3H, Si(CH3)a(CH3)b), 0.87 (d,
3
3J = 6.3 Hz, 3H, CH(CH3)a(CH3)b), 0.88 (d, J = 6.3 Hz,
3H, CH(CH3)a(CH3)b), 0.89 (s, 9H, C(CH3)3), 1.04 (ddd,
3
3
2J = 14.5 Hz, J = 9.5 Hz, J = 3.5 Hz, 1H, 3-Ha), 1.14
(ddd, 2J = 13.7 Hz, 3J = 10.7 Hz, 3J = 4.2 Hz, 1H,
3-Hb), 1.23–1.36 (m, 1H, 6-Ha), 1.44–1.74 (m, 4H, 6-Hb,
2-H2, 2-H), 2.45 (bs, 2H, OH, CHNHCH), 2.55 (dd,
Benzyl (4S,5S,20S)-5-[1-(tert-butyldimethylsilyloxy)-3-phe-
nyl-2-propylamino]-8-hydroxy-2-methyl-4-octylcarbamate
(45a, C32H52N2O4Si)
3
2J = 13.4 Hz, J = 7.2 Hz, 1H, 30-Ha), 2.66 (dd, 2J =
3
3
13.4 Hz, J = 6.7 Hz, 1H, 30-Hb), 2.72 (ddd, J = 8.2 Hz,
3J = 5.2 Hz, 3J = 3.2 Hz, 1H, 5-H), 2.96–3.04 (m, 1H, 20-
Alkene 25a (1.50 g, 2.79 mmol) and 11.2 cm3 of a solution
of 9-BBN (0.5 M in THF, 5.58 mmol) in 10 cm3 anhy-
drous THF were reacted according to GP 9 within 3 h at
room temperature. Purification by chromatography (hex-
anes–EtOAc 3:1 ? 2:1) yielded 1.23 g alcohol 45a
(2.21 mmol, 79%) as a colourless oil. Rf = 0.61 (hex-
anes–EtOAc 1:1); [a]2D0 = -57.6 9 10-1 deg cm2 g-1
(c = 0.685, CHCl3); 1H NMR (400 MHz, CDCl3):
d = 0.04 (s, 3H, Si(CH3)a(CH3)b), 0.05 (s, 3H, Si(CH3)a
(CH3)b), 0.80 (d, 3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.82
(d, 3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.91 (s, 9H,
C(CH3)3), 1.09 (ddd, 2J = 13.0 Hz, 3J = 9.7 Hz, 3J = 4.8
Hz, 1H, 3-Ha), 1.34 (ddd, 2J = 13.9 Hz, 3J = 6.9 Hz,
3J = 2.9 Hz, 1H, 3-Hb), 1.39–1.74 (m, 5H, 7-H2, 6-H2, 2-
2
3
H), 3.47 (dd, J = 10.1 Hz, J = 5.6 Hz, 1H, 10-Ha), 3.52
(dd, 2J = 10.1 Hz, J = 4.5 Hz, 1H, 10-Hb), 3.56 (ddd,
3
2J = 10.7 Hz, J = 7.4 Hz, J = 4.9 Hz, 1H, 8-Ha), 3.65
3
3
2
(dt, J = 11.0 Hz, J = 5.5 Hz, 1H, 8-Hb), 3.80 (tt, J =
3
3
3
3
10.1 Hz, J = 3.2 Hz, 1H, 4-H), 4.52 (d, J = 10.1 Hz,
1H, NHCO), 5.03 (d, 2J = 12.4 Hz, 1H, OCHaHbPh), 5.06
2
(d, J = 12.2 Hz, 1H, OCHaHbPh), 7.14–7.37 (m, 10H, 2
Ph) ppm; 13C NMR (100 MHz, CDCl3): d = -5.4
(q, Si(CH3)a(CH3)b), -5.4 (q, Si(CH3)a(CH3)b), 18.2 (s,
C(CH3)3), 21.8 (q, C-1), 23.7 (q, C-1), 24.7 (d, C-2), 25.9
(q, SiC(CH3)3), 29.1 (t, C-7), 30.1 (t, C-6), 39.1 (t, C-3),
39.3 (t, C-30), 50.9 (d, C-4), 58.3 (d, C-5), 59.1 (d, C-20),
62.7 (t, C-8), 65.0 (t, C-10), 66.6 (t, OCH2Ph), 126.2 (d,
Ph), 128.0 (d, 2C, Ph), 128.0 (d, Ph), 128.4 (d, 2C, Ph),
128.5 (d, 2C, Ph), 129.4 (2d, Ph), 136.7 (s, Ph), 139.2 (s,
Ph), 156.2 (s, NHCO) ppm; IR (KBr): v = 3,400, 3,331
(N–H, O–H), 1,718 (C=O) cm-1; MS (FAB pos.): m/z
(%) = 557 (10) [(M ? H)?]; HRMS (C32H53N2O4Si):
calcd. 557.3775, found 557.3770.
3
H), 1.89 (bs, 2H, CHNHCH, OH), 2.55 (td, J = 6.6 Hz,
3J = 2.2 Hz, 1H, 5-H), 2.59 (dd, 2J = 13.3 Hz, 3J =
2
3
7.4 Hz, 1H, 30-Ha), 2.71 (dd, J = 13.3 Hz, J = 6.5 Hz,
3
3
1H, 30-Hb), 2.81 (tt, J = 6.9 Hz, J = 4.2 Hz, 1H, 20-H),
3.47 (dd, 2J = 10.0 Hz, 3J = 4.0 Hz, 1H, 10-Ha), 3.54 (dd,
2J = 10.0 Hz, 3J = 4.4 Hz, 1H, 10-Hb), 3.59 (u-t, 3J = 6.1
Hz, 2H, 8-H2), 3.66 (tdd, 3J = 9.9 Hz, 3J = 4.4 Hz,
3J = 2.0 Hz, 1H, 4-H), 4.83 (d, 3J = 9.6 Hz, 1H, NHCO),
5.05 (d, 2J = 12.3 Hz, 1H, OCHaHbPh), 5.08 (d,
2J = 12.5 Hz, 1H, OCHaHbPh), 7.17–7.39 (m, 10H, 2
Ph) ppm; 13C NMR (100 MHz, CDCl3): d = -5.4 (q,
Si(CH3)2), 18.3 (s, SiC(CH3)3), 22.0 (q, CH(CH3)a(CH3)b),
23.3 (q, CH(CH3)a(CH3)b), 24.8 (d, C-2), 25.9 (q,
SiC(CH3)3), 29.5 (t, C-6), 29.9 (t, C-7), 39.2 (t, C-30),
41.6 (t, C-3), 51.3 (d, C-4), 57.9 (d, C-5), 59.8 (d, C-20),
62.7 (t, C-8), 63.8 (t, C-10), 66.5 (t, OCH2Ph) ppm; IR
Benzyl (3S,4S,20S)-4-[1-(tert-butyldimethylsilyloxy)-2-pro-
pylamino]-7-hydroxy-2-methyl-3-heptylcarbamate
(46b, C25H46N2O4Si)
Alkene 27a (1.85 g, 4.12 mmol) and 16.5 cm3 of a solution
of 9-BBN (0.5 M in THF, 8.24 mmol) in 20 cm3 anhy-
drous THF were reacted according to GP 9 within 3 h
at room temperature. Purification by chromatography
(hexanes–EtOAc 3:1 ? 2:1) yielded 1.71 g alcohol
46b (3.67 mmol, 89%) as a colourless oil. Rf = 0.46
123

Addition of allylzinc to a-amino acid-derived imines
195
(hexanes–EtOAc 1:1); [a]2D0 = ?0.8 9 10-1 deg cm2 g-1
(c = 0.95, CHCl3); 1H NMR (400 MHz, CDCl3): d = 0.04
(s, 6H, Si(CH3)2), 0.88 (s, 9H, C(CH3)3), 0.91 (d,
3J = 6.3 Hz, 3H, CHCH3), 0.92 (d, 3J = 6.8 Hz, 3H,
CH(CH3)a(CH3)b), 27.0 (t, C-30), 28.0 (q, C(CH3)3), 29.8 (t,
C-20), 30.1 (d, C-60), 54.3 (d, C-2), 56.5 (d, C-40), 57.3 (d,
C-50), 62.8 (t, C-10), 66.8 (t, CH2Ph), 80.8 (s, C(CH3)3),
128.1 (d, 2C, Ph), 128.1 (d, Ph), 128.5 (d, 2C, Ph), 136.6 (s,
Ph), 157.1 (s, NCHO), 174.6 (s, C-1) ppm; IR (KBr):
v = 3,331 (N–H, O–H), 1,724 (C=O) cm-1; MS (FAB
pos.): m/z (%) = 423 (100) [(M ? H)?]; HRMS
(C23H39N2O5): calcd. 423.2859, found 423.2863.
3
CHCH3), 0.95 (d, J = 6.6 Hz, 3H, CHCH3), 1.33–1.45
(m, 1H, 5-Ha), 1.47–1.87 (m, 5H, 5-Hb, 6-H2, OH,
CHNHCH), 1.78 (u-dquint, 3J = 8.8 Hz, 3J = 6.7 Hz,
1H, 2-H), 2.69 (ddd, J = 8.0 Hz, J = 4.6 Hz, J = 2.5
3
3
3
3
3
Hz, 1H, 4-H), 2.76 (u-quintd, J = 6.4 Hz, J = 4.2 Hz,
1H, 20-H), 3.30 (ddd, 3J = 10.3 Hz, 3J = 8.7 Hz, 3J =
2.5 Hz, 1H, 3-H), 3.34 (dd, 2J = 9.8 Hz, 3J = 6.4 Hz, 1H,
tert-Butyl (2S,40S,50S)-2-[5-(benzyloxycarbonylamino)-1-
hydroxy-6-methyl-4-heptylamino]-4-methylpentanoate
(48a, C26H44N2O5)
3
10-Ha), 3.52 (dd, 2J = 9.8 Hz, J = 4.2 Hz, 1H, 10-Hb),
Alkene 31a (5.36 g, 12.0 mmol) and 48.0 cm3 of a solution
of 9-BBN (0.5 M in THF, 24.0 mmol) in 50 cm3 anhy-
drous THF were reacted according to GP 9 within 3 h at
room temperature. Purification by chromatography (hex-
anes–EtOAc 2:1 ? 3:2) yielded 5.25 g alcohol 48a
(11.3 mmol, 94%) as a colourless oil. Rf = 0.27 (hex-
anes–EtOAc 2:1); [a]2D0 = -29.7 9 10-1 deg cm2 g-1
(c = 1.32, CHCl3); 1H NMR (400 MHz, CDCl3):
d = 0.88 (d, 3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.91
(d, 3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.92 (d, 3J =
3.56 (ddd, 2J = 10.7 Hz, 3J = 7.1 Hz, 3J = 5.5 Hz, 1H, 7-
2
3
Ha), 3.63 (dt, J = 10.6 Hz, J = 5.9 Hz, 1H, 7-Hb), 5.07
(d, 2J = 12.3 Hz, 1H, CHaHbPh), 5.10 (d, 3J = 9.1 Hz,
2
1H, NHCO), 5.11 (d, J = 12.3 Hz, 1H, CHaHbPh), 7.27–
7.37 (m, 5H, Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = -5.4 (q, Si(CH3)a(CH3)b), -5.3 (q, Si(CH3)a(CH3)b),
17.7 (q, C-30), 18.2 (s, C(CH3)3), 19.2 (q, CH(CH3)a
(CH3)b), 20.2 (q, CH(CH3)a(CH3)b), 25.9 (q, C(CH3)3),
29.3 (t, C-6 or C-5), 29.4 (t, C-6 or C-5), 29.9 (d, C-2), 52.7
(d, C-20), 54.3 (d, C-4), 59.1 (d, C-3), 62.8 (t, C-7), 66.6 (t,
CH2Ph), 67.2 (t, C-10), 128.0 (d, 2C, Ph), 128.0 (d, Ph),
128.5 (2d, Ph), 136.9 (s, Ph), 157.1 (s, NHCO) ppm; IR
(KBr): v = 3,326 (N–H, O–H), 1,703 (C=O) cm-1; MS
(FAB pos.): m/z (%) = 467 (100) [(M ? H)?]; HRMS
(C25H47N2O4Si): calcd. 467.3305, found 467.3308.
3
6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.95 (d, J = 6.6 Hz, 3H,
2
CH2CH(CH3)a(CH3)b), 1.17 (ddt, J = 13.7 Hz, J = 9.7
3
3
Hz, J = 6.7 Hz, 1H, 30-Ha), 1.23–1.31 (m, 1H, 3-Ha),
1.46 (s, 9H, C(CH3)3), 1.44–1.75 (m, 6H, 60-H, 30-Hb, 20-
H2, 4-H, 3-Hb), 2.41 (bs, 2H, OH, CHNHCH), 2.63 (dt,
3J = 9.3 Hz, 3J = 3.2 Hz, 1H, 40-H), 3.45 (t, 3J = 7.1 Hz,
1H, 2-H), 3.54 (dt, 2J = 10.8 Hz, 3J = 5.9 Hz, 1H, 10-Ha),
tert-Butyl (2S,40R,50S)-2-[5-(benzyloxycarbonylamino)-1-
hydroxy-6-methyl-4-heptylamino]propanoate
3
3
3
3.60 (ddd, J = 10.4 Hz, J = 8.5 Hz, J = 3.9 Hz, 1H,
3
50-H), 3.66 (dt, 2J = 10.7 Hz, J = 5.3 Hz, 1H, 10-Hb),
(47b, C23H38N2O5)
4.68 (d, 3J = 10.3 Hz, 1H, NHCO), 5.07 (d, 2J = 13.0 Hz,
1H, CHaHbPh), 5.10 (d, 2J = 12.9 Hz, 1H, CHaHbPh),
7.28–7.39 (m, 5H, Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = 19.5 (q, CH(CH3)a(CH3)b), 20.1 (q, CH(CH3)a(CH3)b),
22.6 (q, CH2CH(CH3)a(CH3)b), 22.8 (q, CH2CH(CH3)a
(CH3)b), 25.0 (d, C-4), 27.1 (t, C-30), 28.1 (q, C(CH3)3),
29.7 (t, C-20), 30.1 (d, C-60), 43.4 (t, C-3), 56.6 (d, C-40),
57.2 (d, C-50), 58.0 (d, C-2), 62.7 (t, C-10), 66.7 (t, CH2Ph),
80.9 (s, C(CH3)3), 128.0 (d, Ph), 128.1 (d, 2C, Ph), 128.5
(d, 2C, Ph), 136.7 (s, Ph), 157.0 (s, NHCO), 174.9 (s, C-1)
ppm; IR (KBr): v = 3,420 (N–H, O–H), 1,725 (C=O)
cm-1; MS (FAB pos.): m/z (%) = 465 (100) [(M ? H)?];
HRMS (C26H45N2O5): calcd. 465.3328, found 465.3325.
Alkene 30b (309 mg, 0.76 mmol) and 3.10 cm3 of a
solution of 9-BBN (0.5 M in THF, 1.52 mmol) in 5 cm3
anhydrous THF were reacted according to GP 9 within 3 h
at room temperature. Purification by chromatography
(hexanes–EtOAc 2:1 ? 1:1) yielded 200 mg alcohol 47b
(0.47 mmol, 62%) as a colourless oil. Rf = 0.30 (hexanes–
EtOAc 2:1); [a]2D0 = -1.4 9 10-1 deg cm2 g-1 (c = 0.74,
CHCl3); 1H NMR (400 MHz, CDCl3): d = 0.91 (d,
3J = 6.7 Hz, 3H, CH(CH3)a(CH3)b), 0.95 (d, 3J = 6.7
3
3
Hz, 3H, CH(CH3)a(CH3)b), 1.16 (ddt, J = 6.7 Hz, J =
2
3
9.8 Hz, J = 13.7 Hz, 1H, 30-Ha), 1.21 (d, J = 6.8 Hz,
3H, 3-H3), 1.46 (s, 9H, C(CH3)3), 1.59 (ddt, 2J = 13.8 Hz,
3J = 7.0 Hz, 3J = 2.7 Hz, 1H, 30-Hb), 1.67 (dsept,
3J = 7.7 Hz, J = 6.7 Hz, 1H, 60-H), 1.67–1.76 (m, 2H,
3
tert-Butyl (2S,40R,50S)-2-[5-(benzyloxycarbonylamino)-1-
hydroxy-6-methyl-4-heptylamino]-4-methylpentanoate
(48b, C26H44N2O5)
Alkene 31b (6.27 g, 14.0 mmol) and 56.2 cm3 of a
solution of 9-BBN (0.5 M in THF, 28.1 mmol) in 50 cm3
anhydrous THF were reacted according to GP 9 within 3 h
at room temperature. Purification by chromatography
(hexanes–EtOAc 2:1 ? 1:1) yielded 5.49 g alcohol 48b
(11.8 mmol, 84%) as a colourless oil. Rf = 0.32 (hexanes–
20-H2), 2.68 (bs, 2H, OH, CHNHCH), 2.68 (dt,
3J = 9.8 Hz, J = 3.1 Hz, 1H, 40-H), 3.45–3.67 (m, 2H,
3
10-Ha, 50-H), 3.53 (q, 3J = 6.8 Hz, 1H, 2-H), 3.69 (dt,
2J = 10.6 Hz, J = 5.2 Hz, 1H, 10-Hb), 4.61 (d, 3J =
3
10.3 Hz, 1H, NHCO), 5.07 (d, 2J = 12.2 Hz, 1H,
2
CHaHbPh), 5.12 (d, J = 12.2 Hz, 1H, CHaHbPh), 7.28–
7.40 (m, 5H, Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = 19.4 (q, C-3), 19.7 (q, CH(CH3)a(CH3)b), 20.0 (q,
123

196
M. Virlouvet et al.
EtOAc 1:1); [a]2D0 = -25.7 9 10-1 deg cm2 g-1 (c = 0.81,
CHCl3); 1H NMR (400 MHz, CDCl3): d = 0.88 (d,
3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.90 (d, 3J = 6.6
Hz, 3H, CH(CH3)a(CH3)b), 0.96 (d, 3J = 6.6 Hz, 3H,
CH2CH(CH3)a(CH3)b), 0.97 (d, 3J = 6.6 Hz, 3H,
CH2CH(CH3)a(CH3)b), 1.22–1.38 (m, 2H, 3-H), 1.46 (s,
9H, C(CH3)3), 1.38–1.78 (m, 8H, 60-H, 30-H2, 20-H2, 4-H,
OH, CHNHCH), 2.69 (ddd, 3J = 7.4 Hz, 3J = 5.9 Hz,
42.4 (t, C-60), 51.4 (d, C-50), 59.5 (d, C-40), 62.6 (t, C-10),
64.1 (d, C-2), 66.5 (t, OCH2Ph), 81.5 (s, C(CH3)3), 126.6
(d, Ph), 128.0 (d, 2C, Ph), 128.0 (d, Ph), 128.3 (d, 2C, Ph),
128.5 (d, 2C, Ph), 129.5 (2d, Ph), 136.8 (s, Ph), 137.9 (s,
Ph), 156.4 (s, NHCO), 174.9 (s, C-1) ppm; IR (KBr):
v = 3,344 (N–H, O–H), 1,719 (C=O) cm-1; MS (FAB
pos.): m/z (%) = 513 (100) [(M ? H)?]; HRMS
(C30H45N2O5): calcd. 513.3328, found 513.3331.
3
3
3J = 1.4 Hz, 1H, 40-H), 3.12 (dd, J = 7.6 Hz, J = 6.8
49b: Rf = 0.11 (hexanes–EtOAc 2:1); [a]2D0 = ?4.8 9
Hz, 1H, 2-H), 3.19 (td, 3J = 10.0 Hz, 3J = 1.4 Hz, 1H, 50-
10-1 deg cm2 g-1 (c = 0.83, CHCl3); 1H NMR (400 MHz,
2
3
H), 3.51–3.64 (m, 2H, 10-H2), 5.07 (d, J = 12.2 Hz, 1H,
CDCl3): d = 0.87 (d, J = 6.6 Hz, 6H, CH(CH3)2), 1.05
CHaHbPh), 5.12 (d, 2J = 12.2 Hz, 1H, CHaHbPh), 5.28 (d,
3J = 10.0 Hz, 1H, NHCO), 7.28–7.40 (m, 5H, Ph) ppm;
13C NMR (100 MHz, CDCl3): d = 19.8 (q, CH(CH3)a
(CH3)b), 20.1 (q, CH(CH3)a(CH3)b), 22.5 (q, CH2CH
(CH3)a(CH3)b), 22.7 (q, CH2CH(CH3)a(CH3)b), 24.7 (d,
C-4), 28.1 (q, C(CH3)3), 29.6 (t, C-20), 30.5 (t, C-30), 31.0
(d, C-60), 43.7 (t, C-3), 55.8 (d, C-40), 59.7 (d, C-50), 61.1
(d, C-2), 62.5 (t, C-10), 66.6 (t, CH2Ph), 81.1 (s, C(CH3)3),
128.0 (d, 2C, Ph), 128.1 (d, Ph), 128.6 (d, 2C, Ph), 136.8 (s,
Ph), 157.0 (s, NHCO), 176.1 (s, C-1) ppm; IR (KBr):
v = 3,342 (N–H, O–H), 1,723 (C=O) cm-1; MS (FAB
pos.): m/z (%) = 465 (100) [(M ? H)?]; HRMS
(C26H45N2O5): calcd. 465.3328, found 465.3326.
(ddd, 2J = 13.5 Hz, 3J = 9.2 Hz, 3J = 3.6 Hz, 1H, 60-Ha),
2
3
3
1.20 (ddd, J = 13.9 Hz, J = 11.0 Hz, J = 4.3 Hz, 1H,
60-Hb), 1.37 (s, 9H, C(CH3)3), 1.25–1.65 (m, 5H, 20-H2, 30-
H2, 70-H), 2.10 (bs, 2H, OH, CHNHCH), 2.50 (ddd,
3
3J = 8.4 Hz, 3J = 5.7 Hz, J = 3.1 Hz, 1H, 40-H), 2.71
(dd, 2J = 13.3 Hz, 3J = 8.1 Hz, 1H, 3-Ha), 2.86 (dd,
2J = 13.3 Hz, 3J = 6.4 Hz, 1H, 3-Hb), 3.52 (dd,
3
3J = 8.0 Hz, J = 6.3 Hz, 1H, 2-H), 3.54–3.60 (m, 1H,
2
3
10-Ha), 3.64 (dt, J = 11.0 Hz, J = 5.9 Hz, 1H, 10-Hb),
3.74–3.83 (m, 1H, 50-H), 4.46 (d, 3J = 9.6 Hz, 1H,
NHCO), 5.04 (s, 2H, OCH2Ph), 7.10–7.40 (m, 10H, 2
Ph) ppm; 13C NMR (100 MHz, CDCl3): d = 21.9 (q,
CH(CH3)a(CH3)b), 23.6 (q, CH(CH3)a(CH3)b), 24.7 (d,
C-70), 28.0 (q, C(CH3)3), 28.3 (t, C-30), 29.8 (t, C-20), 39.2
(t, C-3), 40.6 (t, C-60), 50.4 (d, C-50), 60.1 (d, C-40), 62.6 (d,
C-2), 62.7 (t, C-10), 66.5 (t, OCH2Ph), 81.4 (s, C(CH3)3),
126.5 (d, Ph), 128.0 (d, 2C, Ph), 128.0 (d, Ph), 128.3 (d,
2C, Ph), 128.5 (d, 2C, Ph), 129.6 (2d, Ph), 136.7 (s, Ph),
136.8 (s, Ph), 156.2 (s, NHCO), 174.5 (s, C-1) ppm; IR
tert-Butyl (2S,40S,50S) and (2S,40R,50S)-2-[5-(benzyloxy-
carbonylamino)-1-hydroxy-7-methyl-4-octylamino]-3-phe-
nylpropanoate (49a, 49b, C30H44N2O5)
Alkene 32a/32b (2.42 g, 4.89 mmol) and 19.6 cm3 of a
solution of 9-BBN (0.5 M in THF, 9.78 mmol) in 20 cm3
anhydrous THF were reacted according to GP 9 within 3 h
at room temperature. Purification by chromatography
(hexanes–EtOAc 2:1 ? 1:1) yielded 581 mg alcohol 49a
(1.13 mmol, 23%) and 728 mg alcohol 49b (1.42 mmol,
29%) as colourless oils.
(KBr): v = 3,398, 3,341 (N–H, O–H), 1,720 (C=O) cm-1
;
MS (FAB pos.): m/z (%) = 513 (100) [(M ? H)?]; HRMS
(C30H45N2O5): calcd. 513.3328, found 513.3,331.
tert-Butyl (2S,40R,50S)-2-[5-(benzyloxycarbonylamino)-1-
hydroxy-6-methyl-4-heptylamino]-3-methylbutanoate
(50b, C25H42N2O5)
49a: Rf = 0.20 (hexanes–EtOAc 2:1); [a]2D0 = -24.2 9
10-1 deg cm2 g-1 (c = 1.07, CHCl3); 1H NMR (400 MHz,
3
CDCl3): d = 0.80 (d, J = 6.6 Hz, 3H, CH(CH3)a(CH3)b),
Alkene 33b (995 mg, 2.30 mmol) and 9.20 cm3 of a
solution of 9-BBN (0.5 M in THF, 4.60 mmol) in 10 cm3
anhydrous THF were reacted according to GP 9 within 3 h
at room temperature. Purification by chromatography
(hexanes–EtOAc 2:1 ? 1:1) yielded 731 mg alcohol 50b
(1.62 mmol, 71%) as a colourless oil. Rf = 0.45 (hexanes–
EtOAc 1:1); [a]2D0 = -24.9 9 10-1 deg cm2 g-1 (c = 1.11,
CHCl3); 1H NMR (400 MHz, CDCl3): d = 0.91 (d,
3
0.83 (d, J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.97 (ddd,
3
3
2J = 13.5 Hz, J = 8.7 Hz, J = 4.9 Hz, 1H, 60-Ha), 1.05
(ddd, 2J = 13.5 Hz, 3J = 9.8 Hz, 3J = 5.5 Hz, 1H, 60-Hb),
1.39 (s, 9H, C(CH3)3), 1.30–1.70 (m, 7H, 20-H2, 30-H2, 70-
3
3
H, CHNHCH, OH), 2.40 (td, J = 6.8 Hz, J = 1.7 Hz,
1H, 40-H), 2.71 (dd, 2J = 13.4 Hz, 3J = 8.2 Hz, 1H, 3-Ha),
2
3
2.84 (dd, J = 13.4 Hz, J = 6.1 Hz, 1H, 3-Hb), 3.34 (dd,
3J = 8.3 Hz, 3J = 6.1 Hz, 1H, 2-H), 3.53–3.60 (m, 2H, 10-
H2), 3.62 (tdd, 3J = 9.6 Hz, 3J = 4.8 Hz, 3J = 1.6 Hz,
1H, 50-H), 4.89 (d, 3J = 9.7 Hz, 1H, NHCO), 5.05 (d,
2J = 12.6 Hz, 1H, OCHaHbPh), 5.08 (d, 2J = 12.8 Hz,
1H, OCHaHbPh), 7.15–7.40 (m, 10H, 2 Ph) ppm; 13C NMR
(100 MHz, CDCl3): d = 22.1 (q, CH(CH3)a(CH3)b), 23.2
(q, CH(CH3)a(CH3)b), 24.8 (d, C-70), 28.0 (q, C(CH3)3),
29.6 (t, C-20 or C-30), 29.7 (t, C-20 or C-30), 40.5 (t, C-3),
3
3J = 6.8 Hz, 9H, 3 CHCH3), 0.94 (d, J = 6.6 Hz, 3H,
2
CHCH3), 1.20 (ddt, J = 14.8 Hz, J = 9.1 Hz, J = 6.7
3
3
Hz, 1H, 30-Ha), 1.47 (s, 9H, C(CH3)3), 1.59 (dtd,
3
2J = 14.4 Hz, 3J = 7.5 Hz, J = 3.1 Hz, 1H, 30-Hb),
1.64–1.72 (m, 2H, 20-H2), 1.73 (dsept, 3J = 8.3 Hz,
3
3J = 6.8 Hz, 1H, 3-H), 1.82 (u-oct, J = 6.7 Hz, 1H, 60-
H), 2.53 (bs, 2H, OH, CHNHCH), 2.60 (dt, J = 9.2 Hz,
3
3
3J = 3.3 Hz, 1H, 40-H), 3.15 (d, J = 6.6 Hz, 1H, 2-H),
123

Addition of allylzinc to a-amino acid-derived imines
197
3.55 (dt, 2J = 10.8 Hz, 3J = 6.0 Hz, 1H, 10-Ha), 3.54–3.62
(m, 1H, 50-H), 3.67 (dt, 2J = 10.7 Hz, 3J = 5.3 Hz, 1H, 10-
Hb), 4.70 (d, 3J = 10.5 Hz, 1H, NHCO), 5.08 (s, 2H,
CH2Ph), 7.28–7.37 (m, 5H, Ph) ppm; 13C NMR (100 MHz,
CDCl3): d = 18.8 (q, CHCH3), 19.1 (q, CHCH3), 19.5 (q,
CHCH3), 20.1 (q, CHCH3), 27.1 (t, C-30), 28.1 (q,
C(CH3)3), 29.7 (d, C-20), 30.0 (d, C-3), 31.9 (d, C-60),
56.9 (d, C-40 or C-50), 57.0 (d, C-40 or C-50), 62.7 (t, C-10),
65.3 (d, C-2), 66.7 (t, CH2Ph), 80.9 (s, C(CH3)3), 128.1 (d,
Ph), 128.1 (d, 2C, Ph), 128.5 (d, 2C, Ph), 136.7 (s, Ph),
156.9 (s, NHCO), 174.9 (s, C-1) ppm; IR (KBr): v = 3,340
(N–H, O–H), 1,722 (C=O) cm-1; MS (FAB pos.): m/z
(%) = 451 (64) [(M ? H)?]; HRMS (C25H43N2O5): calcd.
451.3172, found 451.3171.
anhydrous THF were reacted according to GP 9 within 3 h
at room temperature. Purification by chromatography
(hexanes–EtOAc 2:1 ? 1:1) yielded 600 mg alcohol 51b
(1.20 mmol, 73%) as a colourless oil. Rf = 0.51 (hexanes–
EtOAc 1:1); [a]2D0 = -21.4 9 10-1 deg cm2 g-1 (c = 1.32,
CHCl3); 1H NMR (400 MHz, CDCl3): d = 0.87 (d,
3J = 6.6 Hz, 3H, CHCH3), 0.90 (d, 3J = 6.6 Hz, 3H,
2
3
3
CHCH3), 1.12 (ddt, J = 13.6 Hz, J = 9.6 Hz, J = 6.6
Hz, 1H, 30-Ha), 1.33 (s, 9H, C(CH3)3), 1.53–1.78 (m, 4H,
20-H2, 30-Hb, 60-H), 2.33 (bs, 2H, OH, CHNHCH), 2.66 (dt,
3
2
3J = 9.4 Hz, J = 3.1 Hz, 1H, 40-H), 2.77 (dd, J = 13.2
Hz, J = 7.1 Hz, 1H, 10-Ha), 2.87 (dd, 2J = 13.1 Hz,
3
3J = 7.6 Hz, 1H, 3-Hb), 3.55 (ddd, 2J = 10.9 Hz, 3J =
3
3
7.4 Hz, J = 4.7 Hz, 1H, 10-Ha), 3.59 (ddd, J = 10.5 Hz,
3
3J = 8.7 Hz, J = 3.4 Hz, 1H, 50-H), 3.68 (ddd, 2J =
tert-Butyl (2S,40S,50S)-2-[5-(benzyloxycarbonylamino)-1-
hydroxy-6-methyl-4-heptylamino]-3-phenylpropanoate
(51a, C29H42N2O5)
3
3
10.7 Hz, J = 5.8 Hz, J = 4.5 Hz, 1H, 10-Hb), 3.74 (dd,
3J = 7.4 Hz, 3J = 6.9 Hz, 1H, 2-H), 4.49 (d, 3J =
10.5 Hz, 1H, NHCO), 5.01 (d, 2J = 12.2 Hz, 1H,
Alkene 34a (3.53 g, 7.34 mmol) and 29.4 cm3 of a solution
of 9-BBN (0.5 M in THF, 14.7 mmol) in 30 cm3 anhy-
drous THF were reacted according to GP 9 within 3 h at
room temperature. Purification by chromatography (hex-
anes–EtOAc 2:1 ? 3:2) yielded 3.44 g alcohol 51a
(6.90 mmol, 94%) as a colourless oil. Rf = 0.22 (hex-
anes–EtOAc 2:1); [a]2D0 = -36.5 9 10-1 deg cm2 g-1
(c = 0.82, CHCl3); 1H NMR (400 MHz, CDCl3):
d = 0.79 (d, 3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 0.83
(d, 3J = 6.6 Hz, 3H, CH(CH3)a(CH3)b), 1.37 (s, 9H,
C(CH3)3), 1.29–1.45 (m, 5H, 30-H2, 60-H, OH, CHNHCH),
1.45–1.69 (m, 2H, 20-H2), 2.66 (td, 3J = 6.7 Hz, 3J =
2
CHaHbPh), 5.09 (d, J = 12.2 Hz, 1H, CHaHbPh), 7.15–
7.38 (m, 10H, 2 Ph) ppm; 13C NMR (100 MHz, CDCl3):
d = 19.6 (q, CHCH3), 20.0 (q, CHCH3), 27.0 (t, C-30), 27.9
(q, C(CH3)3), 29.9 (t, C-20), 30.0 (d, C-60), 40.2 (t, C-3),
56.5 (d, C-40), 57.0 (d, C-50), 60.8 (d, C-2), 62.7 (t, C-10),
66.8 (t, CH2Ph), 81.1 (s, C(CH3)3), 126.5 (d, Ph), 128.1 (d,
2C, Ph), 128.1 (d, Ph), 128.2 (d, 2C, Ph), 128.5 (d, 2C, Ph),
129.6 (2d, Ph), 136.6 (s, Ph), 137.2 (s, Ph), 156.9 (s,
NHCO), 173.6 (s, C-1) ppm; IR (KBr): v = 3,341 (N–H,
O–H), 1,720 (C=O) cm-1; MS (FAB pos.): m/z (%) = 499
(100) [(M ? H)?]; HRMS (C29H43N2O5): calcd. 499.3172,
found 499.3169.
2
3
1.6 Hz, 1H, 40-H), 2.72 (dd, J = 13.3 Hz, J = 7.9 Hz,
2
1H, 3-Ha), 2.82 (dd, J = 13.4 Hz, J = 6.6 Hz, 1H, 3-
3
tert-Butyl (2S,40S,50S)-2-[2-(benzyloxycarbonylamino)-6-
hydroxy-3-hexylamino]-4-methylpentanoate
(52a, C24H40N2O5)
3
3
Hb), 3.11 (td, J = 10.0 Hz, J = 1.6 Hz, 1H, 10-Ha), 3.30
3
(dd, J = 8.0 Hz, J = 6.6 Hz, 1H, 2-H), 3.51–3.62 (m,
3
2
2H, 10-H2), 5.04 (d, J = 12.3 Hz, 1H, OCHaHbPh), 5.10
Alkene 35 as a mixture of isomers (322 mg, 0.77 mmol)
and 3.10 cm3 of a solution of 9-BBN (0.5 M in THF,
1.54 mmol) in 5 cm3 anhydrous THF were reacted accord-
ing to GP 9 within 3 h at room temperature. Purification by
chromatography (CH2Cl2–MeOH 40:1) yielded 215 mg
alcohol 52a as a single isomer (0.49 mmol, 64%) as a
(d, 3J = 10.1 Hz, 1H, NHCO), 5.11 (d, J = 12.3 Hz, 1H,
2
OCHaHbPh), 7.14–7.41 (m, 10H, 2 Ph) ppm; 13C NMR
(100 MHz, CDCl3): d = 19.7 (q, CH(CH3)a(CH3)b), 19.9
(q, CH(CH3)a(CH3)b), 28.0 (q, C(CH3)3), 29.5 (t, C-20),
30.4 (t, C-30), 30.7 (d, C-60), 40.5 (t, C-3), 56.0 (d, C-40),
59.6 (d, C-50), 62.6 (t, C-10), 64.1 (d, C-2), 66.5 (t,
OCH2Ph), 81.5 (s, C(CH3)3), 126.6 (d, Ph), 127.9 (d, 2C,
Ph), 128.0 (d, Ph), 128.3 (d, 2C, Ph), 128.5 (d, 2C, Ph),
129.4 (2d, Ph), 136.9 (s, Ph), 137.7 (s, Ph), 157.0 (s,
NHCO), 174.9 (s, C-1) ppm; IR (KBr): v = 3,399 (N–H,
O–H), 1,722 (C=O) cm-1; MS (FAB pos.): m/z (%) = 499
(100) [(M ? H)?]; HRMS (C29H43N2O5): calcd. 499.3172,
found 499.3170.
colourless oil. Rf = 0.31 (CH2Cl2–MeOH 40:1); [a]D20
=
-13.2 9 10-1 deg cm2 g-1 (c = 0.69, CHCl3); H NMR
(400 MHz, CDCl3): d = 0.90 (d, 3J = 6.5 Hz, 3H,
CH(CH3)a(CH3)b), 0.91 (d, 3J = 6.5 Hz, 3H, CH(CH3)a
1
3
(CH3)b), 1.16 (d, J = 6.8 Hz, 3H, 60-H3), 1.28–1.70 (m,
8H, 3-H2, 20-H2, 30-H2, OH, CHNHCH), 1.46 (s, 9H,
3
C(CH3)3), 1.71–1.80 (m, 1H, 4-H), 2.39 (td, J = 6.6 Hz,
3
3
3J = 2.0 Hz, 1H, 40-H), 3.20 (dd, J = 7.8 Hz, J = 6.6
3
Hz, 1H, 2-H), 3.59 (u-t, J = 6.2 Hz, 2H, 10-H2), 3.75
tert-Butyl (2S,40R,50S)-2-[5-(benzyloxycarbonylamino)-1-
hydroxy-6-methyl-4-heptylamino]-3-phenylbutanoate
(51b, C29H42N2O5)
Alkene 34b (797 mg, 1.66 mmol) and 6.65 cm3 of a
solution of 9-BBN (0.5 M in THF, 3.32 mmol) in 10 cm3
3
3
3
(ddd, J = 9.2 Hz, J = 6.7 Hz, J = 2.0 Hz, 1H, 50-H),
5.06 (d, 2J = 12.2 Hz, 1H, CHaHbPh), 5.10 (d,
2J = 12.2 Hz, 1H, CHaHbPh), 5.17 (d, J = 8.4 Hz, 1H,
3
NHCO), 7.28–7.38 (m, 5H, Ph) ppm; 13C NMR (100 MHz,
123

198
M. Virlouvet et al.
CDCl3): d = 19.0 (q, C-60), 22.4 (q, CH(CH3)a(CH3)b),
22.8 (q, CH(CH3)a(CH3)b), 24.8 (d, C-4), 28.1 (q, 3C,
C(CH3)3), 29.4 (t, C-20 or C-30), 29.5 (t, C-20 or C-30), 43.7
(t, C-3), 48.8 (d, C-40), 60.1 (d, C-50), 61.0 (d, C-2), 62.6 (t,
C-10), 66.6 (t, CH2Ph), 81.1 (s, C(CH3)3), 128.1 (d, Ph),
128.1 (d, 2C, Ph), 128.5 (d, 2C, Ph), 136.7 (s, Ph), 156.2 (s,
NHCO), 176.0 (s, C-1) ppm; IR (KBr): v = 3,342 (N–H,
O–H), 1,724 (bs, C=O) cm-1; MS (FAB pos.): m/z
(%) = 437 (100) [(M ? H)?]; HRMS (C24H41N2O5):
calcd. 437.3015, found 437.3013.
16. Taubinger AA, Fenske D, Podlech J (2008) Synlett 539
17. Taubinger AA, Fenske D, Podlech J (2008) Tetrahedron 64:8659
18. Podlech J, Gurrath M, Mu¨ller G, Lohof E (2002) In: Goodman M,
Felix A, Moroder L, Toniolo C (eds) Houben-Weyl, methods of
organic chemistry. Synthesis of peptides and peptidomimetics,
vol E22a. Georg Thieme Verlag, Stuttgart, p 41
19. Ritter AR, Miller MJ (1994) J Org Chem 59:4602
20. Soai K, Oyamada H, Takase M (1984) Bull Chem Soc Jpn
57:2327
21. Maat L, Wulkan RW (1981) Recl Trav Chim Pays-Bas 100:204
22. Saitoh A, Uda T, Morimoto T (1999) Tetrahedron Asymmetr
10:4501
23. Hsiao Y, Hegedus LS (1997) J Org Chem 62:3586
24. Soucek M, Urban J (1995) Collect Czech Chem Commun 60:693
25. Leanna MR, Sowin TJ, Morton HE (1992) Tetrahedron Lett
33:5029
References
26. Taschner E, Wasielewski C, Biernat JF (1961) Justus Liebigs
Ann Chem 646:119
27. Brickmann K, Yuan Z, Sethson I, Somfai P, Kihlberg J (1999)
Chem Eur J 5:2241
28. Bocoum A, Savoia D, Umani-Ronchi A (1993) J Chem Soc
Chem Comm 1542
1. Coppola GM, Schuster HF (1987) Asymmetric synthesis.
Construction of chiral molecules using amino acids. Wiley, New York
2. Seebach D, Kalinowski H-O (1976) Nachr Chem Tech Lab
24:415
3. Blaser H-U (1992) Chem Rev 92:935
4. Bloch R (1998) Chem Rev 98:1407
5. Manabe K, Oyamada H, Sugita K, Kobayashi S (1999) J Org
Chem 64:8054
6. Hirabayashi R, Ogawa C, Sugiura M, Kobayashi S (2001) J Am
Chem Soc 123:9493
7. Merino P, Delso I, Mannucci V, Tejero T (2006) Tetrahedron
Lett 47:3311
8. Dullin A, Dufrasne F, Gelbcke M, Gust R (2006) ChemMed-
Chem 1:644
9. Fleming JJ, McReynolds MD, Du Bois J (2007) J Am Chem Soc
129:9964
10. Myers AG, Kung DW, Zhong B, Movassaghi M, Kwon S (1999)
J Am Chem Soc 121:8401
29. Ohshima T, Gnanadesikan V, Shibuguchi T, Fukuta Y, Nemoto
T, Shibasaki M (2003) J Am Chem Soc 125:11206
30. Spectral Database for Organic Compounds, SDBS (2009)
National Institute of Advanced Industrial Science and Technol-
ogy (AIST), Japan. http://riodb01.ibase.aist.go.jp/sdbs/cgi-bin/
cre_index.cgi?lang=eng
31. Lethinen C, Brunow G (2000) Org Process Res Dev 4:544
32. Schreiner PR, Wittkopp A (2002) Org Lett 4:217
33. Weil T, Kotke M, Kleiner CM, Schreiner PR (2008) Org Lett
10:1513
34. Doyle AG, Jacobsen EN (2007) Chem Rev 107:5713
35. Alexakis A, Tomassini A, Chouillet C, Roland S, Mangeney P,
Bernardinelli G (2000) Angew Chem Int Ed 39:4093
36. Brown HC, Knights EF, Scouten CG (1974) J Am Chem Soc
96:7765
37. Still WC, Kahn M, Mitra A (1978) J Org Chem 43:2923
38. Sheldrick GM (1997) SHELXS97 and SHELXL97, Release 97-2.
¨ ¨
Universitat Gottingen, Deutschland
11. Linder MR, Podlech J (1999) Org Lett 1:869
12. Steurer S, Podlech J (1999) Org Lett 1:481
13. Steurer S, Podlech J (1999) Eur J Org Chem 1551
14. Steurer S, Podlech J (2002) Eur J Org Chem 899
15. Maier TC, Frey WU, Podlech J (2002) Eur J Org Chem 2686
123