Organometallic additions to β-substituted N-Boc-β-aminoaldehydes: A new synthesis of enantiomerically pure 1,3-disubstituted N-Boc-1,3- aminoalcohols

Article abstract of DOI:10.1016/S0040-4020(00)00155-1

1,2-addition of organolithium and organomagnesium derivatives to β- substituted (N-Boc)-β-aminoaldehydes gave access to enantiomerically pure, 1,3-disubstituted, 1,3-aminoalcohols. A diastereoselective version of this addition was also investigated and Gi

Full text of DOI:10.1016/S0040-4020(00)00155-1

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2665±2672
Organometallic Additions to b-substituted
N-Boc-b-aminoaldehydes: a New Synthesis of Enantiomerically
Pure 1,3-disubstituted N-Boc-1,3-aminoalcohols
a
Jean-Louis Toujas, Loõc Toupet and Michel Vaultier
b
a,
*
È
a
Á Â Á Ã Â Â Â
Synthese et electrosynthese organiques, UMR CNRS 6510, bat. 10, Universite de Rennes 1, Avenue du General Leclerc,
F-35042 Rennes Cedex, France
Â
G.M.C.M., UMR 6626, Universite de Rennes, Campus de Beaulieu, F-35042 Rennes Cedex, France
b
Received 15 December 1999; accepted 9 February 2000
AbstractÐ1,2-addition of organolithium and organomagnesium derivatives to b-substituted (N-Boc)-b-aminoaldehydes gave access to
enantiomerically pure, 1,3-disubstituted, 1,3-aminoalcohols. A diastereoselective version of this addition was also investigated and Gilman
cuprates were found to add onto aldehydes 1a±b with notable diastereoselectivity (up to 70% de) in favour of the anti isomer. The absolute
con®guration of each obtained 1,3-aminoalcohol was determined. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
these methodologies have also been used relevantly in
non-racemic synthesis.1a,1b,2,5,8
Chiral 1,3-aminoalcohol sequences are found in compounds
of biological interest such as nucleoside antibiotics1
(sperabilines A±D, negamicine) or in alkaloids.2 Various
methodologies are already available to design such chiral
sequences. Among them, the cycloaddition of ole®ns to
nitrones3 and nitrile oxides,2,3a,4 the addition reaction to
b-alkoxyimines5 or the more speci®c intramolecular
rearrangement of b-silyloxyiminium salts,6 the reduction
of b-hydroxyoximes1b,7 and b-aminoketones,8 the double
reduction of enaminones,9 the addition of azaenolates to
aldehydes,10 and ®nally the cyclofunctionalisation of
homoallylic alcohols11 or amines1a bearing, respectively,
at the oxygen a carbamid group or at the nitrogen a
carboxyl group, are the most well known. Some of
Surprisingly, the simple addition of an organometallic
reagent to the b-aminoaldehydes 1, which would lead to
the N-protected b-aminoalcohols 2 has been scarcely
examined. Only recently, Evans et al. mentioned the non-
diastereoselective addition of vinylmagnesium bromide to
the racemic (N-Boc)-3-aminopropanal.12 Since non-race-
mic N-Boc protected b-aminoaldehydes of type 1 are
readily obtained from the corresponding a-aminoacids,
either through an Arndt±Eistert homologation step
followed by the reduction to the aldehyde13 or by a
chain elongation via a nitrile and subsequent partial
reduction14, we decided to investigate this reaction
(Scheme 1).
Scheme 1.
Keywords: organolithium; organomagnesium; b-aminoaldehydes; diastereoselective addition; cuprates; 1,3-aminoalcohols; enantiomers.
* Corresponding author. Tel.: 133-02-99-28-62-74; fax: 133-02-99-28-69-55; e-mail: michel.vaultier@univ-rennes1.fr
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00155-1

2666
J.-L. Toujas et al. / Tetrahedron 56 (2000) 2665±2672
Optically pure N-Boc protected b-aminoaldehydes 1 (ee up
to 99% depending on the starting a-aminoacid) used in this
study were prepared according to this latter methodology. In
this paper, we wish to describe the synthesis of non-racemic
N-Boc protected b-amino alcohols 2 from b-amino-
aldehydes of type 1 through the addition of various organo-
metallic reagents.
All diastereoisomeric alcohols 2 were readily separated and
puri®ed by ¯ash chromatography. Most of the compounds
obtained are solids and they appeared stable toward usual
puri®cation methods (low-pressure distillation, or silica gel
chromatography).
After these preliminary results, the diastereoselective synth-
esis of one or the other of the two possible diastereoisomeric
alcohols 2 was investigated. A literature survey shows that
cases of good 1,3 inductions in organometallic addition
reactions to b-chiral, b-hetero-substituted aldehydes or
ketones are observed only when using particularly chelating
organometallics, such as methyl titanium chloride reagents,
leading to chelation controlled additions.16 In this regard,
the low diastereoselectivity that we observed with organo-
lithium and Grignard reagents was expected. These latter
reagents have been proved in general to be inef®cient in
chelation controlled additions with substrates bearing
heterosubstituent in b or further positions. Unfortunately,
in our hands, the utilisation of (Me)nTiCl(42n) in reaction
with aldehyde 1a was not satisfactory as we encountered
unsolvable dif®culties in reproducibility and completion of
the reaction which may be due to the presence of the Boc
group. Gilman cuprates are another important class of
reagents used for chelation controlled additions to hetero-
substituted carbonyl compounds.16 Particularly they have
shown good 1,2 inductions in chelation controlled additions
(formation of the Anti-Cram product) to a-chiral b-alkoxy-
aldehydes17 and, noteworthy, to N-Boc-a-aminoalde-
hydes.18 We were curious about the stereochemical
outcome of the addition of Gilman cuprates to the aldehydes
1. We therefore examined the addition of methyl and butyl
cuprates (4 mol equiv.), prepared from copper iodide (I) and
a solution of methyl and butyllithium, respectively, to the
aldehydes 1a and 1b, in diethyl ether at 2908C. After
15 min at this temperature the aldehydes were fully
consumed (GC analysis) and the hydrolysis gave a mixture
of the expected diastereoisomeric alcohols 2a±d. Diastereo-
selectivities were determined by GC analysis. Results are
reported in the Table 2.
Results and Discussion
The addition of organolithium and Grignard reagents was
®rst tested on the aldehydes 1a (eeˆ97%) and 1b±c
(eeˆ99%); 2.5 equiv. of methyl or butyllithium were
added to a diethyl ether solution of the aldehyde at
2808C. After 1 h, during which the reaction temperature
was raised from 280 to 2408C, the reaction mixture was
hydrolysed and then analysed by GC. The results are given
in Table 1. The same procedure was used for the addition of
diethyl ether solutions of methylmagnesium iodide and
butylmagnesium bromide. Only 70±80% of the starting
aldehyde reacted even in the presence of a large excess of
the nucleophilic reagent; 6±10% of the starting aldehyde
was found in each crude reaction mixture. Using 10 equiv.
of methyllithium did not increase the conversion percent-
age. The most likely reason we can foresee to explain this
lack of completion of the addition is a partial enolisation of
the aldehyde, giving back 1 after hydrolysis of the reaction
mixture. The diastereoselectivity was very poor whatever
reagent used, slightly favouring the syn alcohol in the case
of MeLi, BuLi and BuMgBr. Not surprisingly, this selec-
tivity is not explained by the Felkin's derived model for the
addition of nucleophiles to b-chiral carbonyl compounds.15
Indeed this model which predicts the favoured formation of
the anti diastereoisomer does not take into account polar or
Lewis basic substituents such as the Boc group.
The vinylic and allylic magnesium bromides were also
tested with aldehydes 1 since they give access to the syn-
thetically interesting allylic and homoallylic alcohols 2ac,
2cc and 2bd. The additions were conducted in diethyl
ether or in a diethyl ether/THF mixture. Once again, the
corresponding alcohols were obtained without signi®cant
diastereoselectivity in 61±63% combined yields after
chromatographic separation and puri®cation; 3.5 equiv. of
reagents (see Experimental) were found in this case to be the
optimum stoechiometry in order to obtain the best yields.
Moderate to good 1,3 inductions in favour of the anti
isomer, with a maximum of 70% de observed in the case
of the addition of dimethylcuprate on the aldehyde 2a (entry
1) were obtained. The combined yields determined after
puri®cation and separation of the diastereoisomers by
column chromatography were satisfactory, notably better
Table 1. Addition of organolithium and Grignard reagents to aldehydes 1 (reactions were carried out in diethyl ether from 280 to 2208C)
Entry
Aldehyde
R2-M
Amino alcohols
Diastereomeric ratios
(anti/syn)a
Yieldsb
[%]
1
2
3
4
5
6
7
1a
1a
1a
1a
1b
1b
1a
MeLi
BuLi
MeMgI
BuMgBr
MeLi
2aa
2ab
2aa
2ab
2ba
2bb
2ac
48/52
46/54
53/47
44/56
48/52
49/51
52/48
(78)
(72)
66
62
(80)
(74)
63
BuLi
8
9
1c
2cc
56/44
52/48
61
62
1b
2bd
a Diastereomeric ratios were determined by GC analysis and 1H NMR spectroscopy.
b Yields in brackets are conversion percentages measured by GC analysis; others are isolated yields.

J.-L. Toujas et al. / Tetrahedron 56 (2000) 2665±2672
Table 2. Addition of organo copper reagents to the aldehydes 1
2667
Entry
Aldehyde 1
Copper reagent
Solvent
Temperature (8C)
b-Amino alcohol 2
anti/syn (%)a
Yieldsb [%]
1
2
3
4
5
6
7
8
1a
1a
1b
1b
1a
1a
1a
1a
1a
1a
1a
Me2CuLi´LiI
Bu2CuLi´LiI
Me2CuLi´LiI
Bu2CuLi´LiI
Me2CuLi´LiI
Me2CuLi´LiI
Me2CuLi´LiI
MeCu(CN)´Li
Et2O
Et2O
Et2O
Et2O
Heptane
Toluene
THF
Et2O
THF
290
290
290
290
285
285
285 to 0
280
280
2aa
2ab
2ba
2bb
2aa
2aa
2aa
2aa
2aa
2aa
2aa
85/15
75/25
82/18
61/39
70/30
76/24
53/47
83/17
50/50
51/49
52/48
74
59
76
68
±
±
±
(44)
±
(74)
(90)
9
10
11
MeCu(CN)´Li´BF3
MeCu´MgBrl´SMe2
MeCu(CN)ZnI´2LiCl´BF3´OEt2
Et2O/SMe2
THF
280
280
a Diastereomeric ratios were determined by GC analysis and 1H NMR spectroscopy.
b Yields in brackets are obtained from GC analysis; others are isolated yields.
than when organolithium and Grignard reagents were used.
In contrast with the latter, no trace of the starting aldehyde
was observed at the end of the reaction, which indicates that
no enolisation and subsequent side reactions compete with
the expected 1,2 addition. Reaction temperatures between
270 and 2208C and different solvents (heptane, toluene or
THF) were tested in order to optimise this reaction.
However, the addition at 2908C in diethyl ether remained
the best one in terms of diastereoselectivity and yield;
4±5 equiv. of cuprate were necessary to obtain maximum
completion of the reaction and optimum diastereo-
selectivity. This is a well-known drawback of the use of
cuprates. To obviate this, we tested the lower order cyano-
cuprate MeCu(CN)´Li19 which requires only 1 equiv. of
MeLi for its preparation. With this reagent, the selectivity
is still good in favour of the anti isomer (deˆ66%).
However, the addition of 5 equiv. of MeCu(CN)´Li in
diethyl ether at 2908C to the aldehyde 1a led only to ca.
50% completion of the reaction (Table 2, entry 8). The use
of the more economical Grignards and lithium reagents
remains therefore a worthy alternative, particularly if the
two diastereoisomers are needed. Other copper-based
organometallic reagents were tested: MeCu´MgBrI´SMe2
in OEt2/SMe2 solution,20 MeCu(CN)Li´BF3´OEt2,21 and the
Knochel reagent MeCu(CN)ZnI´2LiCl´BF3´OEt2.22 With
these latter reagents only poor diastereoselectivity was
observed (Table 2, entries 9±11).
In the light of the literature data,16±18 a chelation controlled
addition seems the most likely reason for the notable 1,3
induction observed with the cuprates. The existence of a
chelated transition state is also supported by the sharp
contrast with the diastereoselectivities obtained with all
other tested (known as non-chelating) reagents and by the
fact that when using a more Lewis basic solvent like THF,
the diastereoselectivity of the addition of Me2CuLi to 1a
dramatically dropped (Table 2, entry 7).
In order to establish the relative con®guration of the
alcohols 2 (syn or anti), the structure of the alcohol 2ab-
anti was resolved by single crystal X-ray analysis; 2ab-anti
adopts a cyclic conformation in crystalline form due to a
hydrogen bonding between hydrogen of the OH function
Ê
and oxo oxygen of the carbamate moiety (1.9 A) (Fig. 1).
The relative con®guration of all compounds 2 were
established according to an early work by Jacques et al.8d
by IR-spectral data analysis of the two diastereoisomers. All
IR spectra of the alcohols 2, recorded in a non-protic solvent
(dichloromethane), showed two characteristic absorption
Figure 1. View of 2ab-anti in crystalline form; for more convenience, C±H hydrogens are not represented.

2668
J.-L. Toujas et al. / Tetrahedron 56 (2000) 2665±2672
Table 3. Free and associated OH frequencies of 2-anti and 2-syn in CH2Cl2
1,3-Aminoalcohols
Relative con®guration
TLC Rfa
Infrared
O±H (free) n (cm2)
O±H (associated) n (cm21
)
(eOH ass.1eNH)/eOH free
2aa
2ab
2ba
2bb
2ac
2cc
2bd
anti
syn
anti
syn
anti
syn
anti
syn
anti
syn
anti
syn
anti
syn
0.40
0.19
0.50
0.33
0.59
0.49
0.58
0.40
0.50
0.34
0.31
0.19
0.75
0.62
3603
3609
3621
3610
3607
3607
3608
3610
3602
3602
3601
3609
3600
3596
3455
3435
3433
3436
3439
3440
3439
3440
3433
3435
3436
3440
3439
3440
33
4.0
14
3.4
16
4.4
25
4.8
7.0
1.2
7.8
2.4
18
3.5
a Thin layer chromatography: AcOEt/Heptaneˆ1/2; except for alcohol 2bd (AcOEt/Heptaneˆ1/1).
peaks. The ®rst peak at ca. 3600 cm21 corresponded to a
free O±H bond absorption and the second at ca. 3430 cm21
corresponded to an associated O±H, this latter sometimes
overlapping with the N±H absorption (Table 3).
for synthetic purposes. Relative, then absolute con®gura-
tions of all synthesised alcohols were determined. In our
attempts to ®nd a reagent for the diastereoselective addition
to aldehydes 1, we discovered that Gilman cuprates give the
1,3-aminoalcohols 2 with moderate to good diastereoselec-
tivity (up to 70% de) in favour of the anti diastereoisomer.
The absorption around 3440 cm21 has been attributed to the
associated O±H bond since no variation of its intensity
could be observed when varying the concentration of the
samples. Assuming that all anti diastereoisomers behave
similarly to 2b anti, the anti con®guration was attributed
to all diastereoisomers which display the highest ratio
(eOH ass1eNH)/eOH free) and the lowest polarity, and there-
fore highest Rf in TLC analysis. The X-ray structure of 2ab-
anti showed that the chelated conformer of the alcohols 2
are 8-membered rings which formally possess the 6,8-di-
substituted cyclooct-1-en-3-one structure. Further examina-
tion of this model indicates that the pseudo-equatorial
position of the two substituents R1 and R2 is much more
favourable for the 2-anti than for the 2-syn alcohols. This
is in agreement with the IR observations mentioned above.
The systematic down®eld chemical shift of the OH proton in
the anti diastereoisomers (3.60±4.20 ppm), as compared to
the syn ones (2.17±2.97 ppm), con®rmed the favoured
intramolecular chelation in the former.12
Experimental
General
Melting points were determined with an Electrothermal
IA9300 apparatus and are uncorrected. Thin layer chroma-
tography analysis was performed on aluminum precoated
plates (silica gel 60, 0.2 mm) purchased from Merck; eluant:
ethyl acetate/heptaneˆ1/2 unless other solvent mixture was
speci®ed). For preparative ¯ash-chromatography, Geduran
SI 60 (Merck, 0.040±0.063 mm) silica gel was used. Gas
Chromatography analysis was conducted on a Fisons 8000
instrument equipped with a DB-17 Megabore column from J
& W Scienti®c; oven program for all products: 1008C
during 2 min, then 100±240 at a rate of 108C/min. Optical
rotation measurements were performed on a Perkin±Elmer
241C polarimeter (concentrations in g/100 mL). IR spectra
were recorded on a Fourrier transform apparatus BioRad
All alcohols, 2, were synthesised from optically active
aldehydes 1 of known absolute con®guration (chiral carbon
a to the nitrogen). Hence, having established the relative
con®guration of the two asymmetric centres, it was possible
to determine the absolute con®guration of all the diastereo-
isomeric alcohols.
1
FTS 175C. H and 13C NMR spectra were recorded at 300
and 75 MHz, respectively, on a Bruker AC-300 in CDCl3
with TMS as internal standard. High resolution mass spectra
were obtained on a Varian MAT 311 (CRMPO, University
of Rennes 1). Microanalysis was performed at the Central
Laboratory for Analysis, CNRS, Lyon (France). Single-
crystal X-ray determination of the structure of 2ab-anti
Á
È
was resolved by Dr Loõc Toupet of the `Groupe de Matiere
Conclusion
Â
Condensee et Materiaux', University of Rennes 1, Rennes
(France).
Â
In summary, synthesis of optically active, N-Boc protected,
1,3-disubstituted 1,3-aminoalcohols 2, by addition of
various organometallic reagents to b-aminoaldehydes 1,
has been studied. It has been observed that organolithium
and Grignards reagents led to the 3-alkyl, allyl or homoallyl
alcohols 2 in satisfactory yields but without diastereo-
selectivity. The ease of separation of each diastereoisomer
by column chromatography made this synthesis convenient
All reaction solvents were dried before use using standard
procedures and reactions requiring inert atmosphere were
carried out under nitrogen atmosphere in ¯ame dried glass-
ware. Enantiomerically enriched aldehydes 1a±c were
prepared according to a previously published procedure:14
1a, R con®guration eeˆ97%, 1b, R con®guration, eeˆ99%,

J.-L. Toujas et al. / Tetrahedron 56 (2000) 2665±2672
2669
1
and 1c, S con®guration, eeˆ99%. Copper(I) iodide and cya-
nide were purchased from Aldrich. They were dried in situ
before use by repeated heating with a heat gun (,2008C)
under vacuum (0.1 mmHg). Methyl and butyllithium, 1.6 M
in hexane solution, were purchased from Acros and contain
LiCl residues. All Grignard reagents used, MeMgI (1.65 M
in diethyl ether), BuMgBr, (1.4 M in diethyl ether),
vinylMgBr (0.95 M in THF) and allylMgBr (0.34 M in
THF) were prepared according to classical procedures.
mixtures were analysed by GC and H NMR spectroscopy
after hydrolysis and work-up.
General procedure for the addition of the other methyl
copper complexes listed in Table 2
A molar solution of aldehyde 1 in diethyl ether was added to
5 M equiv. of the organometallic reagent in the solvent, or
the mixture of solvents (,0.5 M), and at the temperature
mentioned in Table 2. MeCu(CN)Li in diethyl ether,19
MeCu´MgIBr´SMe2 in a OEt2/SMe2 solvent mixture,20
MeCu(CN)´Li´BF3´OEt2 in THF,21 MeCu(CN)ZnI´2LiCl´
BF3´OEt222 were prepared in situ according to the literature
procedures. Hydrolysis and work-up were conducted as
previously described and crude reaction mixtures analysed
General procedure (A) for the addition of organolithium
or organomagnesium derivatives to the aldehydes 1a±c
To a stirred and cooled to 2808C 0.2 M solution of the
aldehyde 1 in diethyl ether or THF (used in the case of
vinyl and allyl magnesium bromides), were added dropwise,
along the surface of the ¯ask, 2.5 M equiv. of the solution of
the organometallic derivative. The mixture was stirred and
allowed to warm up slowly to 2208C over an approximate
1 h period. The hydrolysis was achieved by cautious addi-
tion of a saturated solution of ammonium chloride. After
returning to ambient temperature, the two phases were sepa-
rated and the aqueous phase was extracted twice with
diethyl ether. The organic phases were combined, washed
twice with brine and dried over magnesium sulphate.
Removal of the solvents under reduced pressure gave a
1
by GC and H NMR spectroscopy.
Synthesis of the syn and anti 4-(N-tertiobutyloxycar-
bonyl)-aminohexan-2-ol (2aa) (Procedure B): Starting
from 2.28 g (12.0 mmol) of copper iodide, 14.2 mL
(22.8 mmol) of methyllithium solution (1.6 M in hexane)
and 603 mg (3.00 mmol) of aldehyde 1a, 407 mg
(1.88 mmol, 63%) of 2aa-anti and 72 mg (0.33 mmol,
11%) of 2aa-syn were obtained after ¯ash chromatography
of the crude oily residue.
1
yellowish oil which was analysed by GC and H NMR
(2S,4R)-4-(N-Tertiobutyloxycarbonyl)-aminohexan-2-ol
(2aa-syn). Colourless solid: mp#408C. Rfˆ0.19.
[a]D25ˆ114.7 (cˆ0.3, CHCl3). IR (CH2Cl2): 1708 cm21
(CvO), 3435 (NH, O±Hassociated), 3609 (O±Hfree). 1H
NMR (CDCl3): dˆ0.92 (t, 3 H, Jˆ7.4 Hz, CH3CH2), 1.22
(d, 3 H, Jˆ6.3 Hz, CH3CHOH), 1.49±1.59 (m, 4 H,
CH3CH2, CHCH2CH), 1.44 (s, 9 H, (CH3)3C), 2.30 (br s,
1 H, OH), 3.55±3.60 (m, 1 H, CHNH), 3.91 (m, 1 H,
CHOH), 4.64 (br d, 1 H, Jˆ8.1 Hz, NH), 13C NMR
(CDCl3) d: (10.2 (CH3CH2), 23.7 (CH3CHOH), 28.4
((CH3)3C), 28.9 (CH3CH2), 44.9 (CHCH2CH), 50.5
(CHNH), 66.4 (CHOH), 79.5 ((CH3)3C), 156.2 (CvO).
HRMS (EI, 70 eV): C11H23NO3 (M1z); calcdˆ217.1678,
foundˆ217.1658.
spectroscopy to determine the diastereoisomeric ratio of
the syn and anti alcohols and to evaluate the completion
of the reaction by comparison with an internal standard.
The two diastereoisomers were eventually separated and
isolated by ¯ash chromatography.
General procedure (B) for the addition of methyl and
butyl cuprates to the aldehydes 1a±b
To a suspension of dry copper (I) iodide in diethyl ether
(0.5 M) cooled at 2208C was slowly added, under stirring,
a 1.6 M solution in hexane of methyllithium (1.9 M equiv.).
The transmetallation reaction was immediately observed
and the yellow solution of Me2CuLi´LiCl was then cooled
at 2908C. A ca. 1 M solution in diethyl ether of the alde-
hyde 1 (0.25 M equiv.) was added dropwise, along the
surface of the ¯ask, over 20 min. After 1 h stirring at this
same temperature, the hydrolysis was done by cautious
addition of methanol (ca. 3 M equiv.). After a few minutes,
the cold mixture was poured in a separatory funnel contain-
ing a solution of saturated ammonium chloride and shaken.
After returning to room temperature, the aqueous phase was
extracted twice with diethyl ether. The combined organic
phases were washed twice with brine and dried over mag-
nesium sulphate. After removal of the solvents under
vacuum, a crude oil was obtained which was analysed by
GC and 1H NMR spectroscopy. Flash chromatography
(ethyl acetate/heptane 1/9±1/2) afforded the analytically
pure syn and anti alcohols 1.
(2R,4R)-4-(N-Tertiobutyloxycarbonyl)-aminohexan-2-ol
(2aa-anti). Colourless solid: mp#408C. Rfˆ0.40. [a]2D5ˆ0.0
(cˆ0.5, CHCl3). IR (CH2Cl2): 1687 cm21 (CvO), 3455
(NH1O±Hassociated), 3603 (O±Hfree). 1H NMR (CDCl3):
dˆ0.95 (t, 3 H, Jˆ7.4 Hz, CH3CH2), 1.19 (d, 3 H,
Jˆ6.3 Hz, CH3CHOH), 1.23±1.58 (m, 4 H, CH3CH2,
CHCH2CH), 1.45 (s, 9 H, (CH3)3C), 3.62±3.73 (m, 1 H,
CHNH), 3.79 (m, 1 H, CHOH), 3.97 (br s, 1 H, OH), 4.39
(d, 1 H, Jˆ8.3 Hz, NH), 13C NMR (CDCl3) d: (10.7
(CH3CH2), 22.6 (CH3CHOH), 28.3 ((CH3)3C), 28.7
(CH3CH2), 46.1 (CHCH2CH), 49.1 (CHNH), 63.5
(CHOH), 79.9 ((CH3)3C), 157.5 (CvO). HRMS (EI,
70 eV): C11H23NO3 (M1z); (m/z) calcdˆ217.1678, foundˆ
217.1672.
Synthesis of the syn and anti 3-(N-tertiobutyloxycar-
bonyl)-aminononan-5-ol (2ab) (Procedure B): Starting
from 762 mg (4.0 mmol) of copper iodide, 4.6 mL
(7.8 mmol) of butyllithium solution (1.7 M in hexane) and
201 mg (1.0 mmol) of aldehyde 1a, 116 mg (0.44 mmol,
44%) of 2ab-anti and 38 mg (0.15 mmol, 15%) of
Tests for the addition of methyl cuprates to aldehyde 1a in
diethyl ether at different temperatures ranging from 270 to
2208C and in toluene, heptane, THF at the temperatures
mentioned in Table 2 were conducted using the same
experimental conditions as described above except for
solvent and reaction temperature. The crude reaction

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J.-L. Toujas et al. / Tetrahedron 56 (2000) 2665±2672
1
1708 (CvO), 3439 (NH, O±Hassociated), 3607 (O±Hfree). H
2ab-syn were obtained after ¯ash chromatography of the
crude oily residue.
NMR (CDCl3): dˆ0.92 (d, 3 H, Jˆ6.2 Hz, (CH3)(CH3)CH),
0.94 (d, 3 H, Jˆ6.5 Hz, (CH3)(CH3)CH), 1.20 (d, 3 H,
Jˆ6.4 Hz, CH3CHOH), 1.31 (ddd, 1 H, Jˆ13.8, 11.9,
2.3 Hz, CHCHHCH), 1.45 (s, 9 H, (CH3)3C), 1.51 (ddd, 1
H, Jˆ13.8, 10.6, 2.9 Hz, CHCHHCH), 1.69 (dhept, 1 H,
Jˆ6.7, 5.5 Hz, (CH3)2CH), 3.62 (dddd, 1 H, Jˆ11.9, 9.7,
5.5, 2.9 Hz, CHNH), 3.78 (m, 1 H, Jˆ2.3 Hz, CHOH), 3.92
(br s, 1 H, OH), 4.47 (d, 1 H, Jˆ9.7 Hz, NH). 13C NMR
(CDCl3) d: (18.2 ((CH3)(CH3)CH), 19.4 ((CH3)(CH3)CH),
22.7 (CH3CHOH), 28.4 ((CH3)3C), 32.2 ((CH3)2CH), 43.1
(CHCH2CH), 52.5 (CHNH), 63.7 (CHOH), 79.8 ((CH3)3C),
157.6 (CvO). HRMS (EI, 70 eV): C9H18NO3
([M2zC3H7]1); calcdˆ188.1287, foundˆ188.1313.
(3R,5S)-3-(N-Tertiobutyloxycarbonyl)-aminononan-5-ol
(2ab-syn). Colourless solid: mpˆ578C (pentane). Rfˆ0.33.
[a]2D5ˆ19.4 (cˆ0.5, CHCl3). IR (CH2Cl2): 1708 (CvO),
3436 (NH, O±Hassociated), 3610 (O±Hfree). 1H NMR
(CDCl3) d: 0.90 (t, 3 H, Jˆ7.5 Hz, CH3CH2CH2), 0.95 (t,
3 H, Jˆ6.9 Hz, CH3CH2CH), 1.23±1.75 (m, 10 H, all CH2),
1.44 (s, 9 H, (CH3)3C), 2.46 (br s, 1 H, OH), 3.53±3.63 (m, 1
H, CHNH), 3.66±3.74 (m, 1 H, CHOH), 4.50 (d, 1 H,
Jˆ7.5 Hz, NH). 13C NMR (CDCl3) d: (10.1 (CH3CH2CH),
14.1 (CH3CH2CH2), 22.7 (CH3CH2CH), 27.8 28.9
(CH3CH2CH2), 28.4 ((CH3)3C), 37.4 (C3H7CH2), 43.1
(CHCH2CH), 50.8 (CHNH), 70.4 (CHOH), 79.4
((CH3)3C), 156.2 (CvO). HRMS (EI, 70 eV): C12H24NO3
([M2zC2H5]1); calcdˆ230.1756, foundˆ230.1754.
Synthesis of the syn and anti 2-methyl-3-(N-tertiobutyl-
oxycarbonyl)-aminononan-5-ol (2bb) (Procedure B):
Starting from 762 mg (4.0 mmol) of copper iodide,
4.6 mL (7.8 mmol) of butyllithium solution (1.7 M in
hexane) and 215 mg (1.0 mmol) of aldehyde 1b, 123 mg
(0.45 mmol, 66%) of 2bb-anti and 63 mg (0.23 mmol,
23%) of 2bb-syn were obtained after ¯ash chromatography
of the crude oily residue.
(3R,5R)-3-(N-Tertiobutyloxycarbonyl)-aminononan-5-ol
(2ab-anti). Colourless solid: mpˆ458C (pentane). Rfˆ0.50
[a]2D5ˆ110.0 (cˆ0.25, CHCl3). IR (CH2Cl2): 1687 (CvO),
3433 (NH, O±Hassociated), 3621 (O±Hfree). 1H NMR (CDCl3)
d: 0.90 (t, 3 H, Jˆ7.5 Hz, CH3CH2CH2), 0.95 (t, 3 H,
Jˆ7.5 Hz, CH3CH2CH), 1.27±1.56 (m, 10 H, all CH2),
1.45 (s, 9 H, (CH3)3C), 3.51±3.59 (m, 1 H, CHOH), 3.62±
3.78 (m, 1 H, CHNH), 3.92 (br s, 1 H, OH), 4.37 (d, 1 H,
Jˆ8.8 Hz, NH). 13C NMR (CDCl3) d: (10.7 (CH3CH2CH),
14.1 (CH3CH2CH2), 22.7 (CH3CH2CH), 28.2 28.7
(CH3CH2CH2), 28.3, (CH3)3C), 36.6 (C3H7CH2), 44.3
(CHCH2CH), 49.1 (CHNH), 67.5 (CHOH), 79.8 (CH3)3C),
157.4 (CvO). HRMS (EI, 70 eV): C12H24NO3
([M2zC2H5]1); calcdˆ230.1756, foundˆ230.1777.
(3R,5R)-2-Methyl-3-(N-Tertiobutyloxycarbonyl)-amino-
nonan-5-ol (2bb-syn). Colourless oil: Rfˆ0.40. IR
(CH2Cl2): 1709 (CvO), 3440 (NH, O±Hassociated), 3610
1
(O±Hfree). H NMR (CDCl3) d: 0.87 (d, 3 H, Jˆ6.6 Hz,
(CH3)(CH3)CH), 0.90 (t, 3 H, Jˆ7.0 Hz, CH3CH2), 0.91
(d, 3 H, Jˆ6.7 Hz, (CH3)(CH3)CH), 1.28±1.52 (m, 7 H,
CHCHHCH, CH3CH2CH2CH2), 1.44 (s, 9 H, (CH3)3C),),
1.64 (dt-like, 1 H, Jˆ14.0, 4.1 Hz, CHCHHCH), 1.78
(dhept, 1 H, Jˆ6.6, 5.0 Hz, (CH3)2CH), 2.76 (br s, 1 H,
OH), 3.49±3.58 (m, 1 H, CHNH), 3.63±75 (m, 1 H,
CHOH), 4.55 (d, 1 H, Jˆ9.8 Hz, NH). 13C NMR (CDCl3)
d: (14.1 (CH3CH2), 17.5 ((CH3)(CH3)CH), 18.8
((CH3)(CH3)CH), 22.7 (CH3CH2), 27.8 (CH3CH2CH2),
28.4 ((CH3)3C), 32.5 ((CH3)2CH), 37.2 (C3H7CH2), 40.5
(CHCH2CH), 54.1 (CHNH), 70.8 (CHOH), 79.4
((CH3)3C), 156.4 (CvO). HRMS (EI, 70 eV): C12H24NO3
([M2zC3H7]1); calcdˆ230.1756, foundˆ230.1777.
Synthesis of the syn and anti 5-methyl-4-(N-tertiobutyl-
oxycarbonyl)-aminohexan-2-ol (2ba) (Procedure B):
Starting from 2.28 g (12.0 mmol) of copper iodide,
14.2 mL (22.7 mmol) of methyllithium solution (1.6 M in
hexane) and 646 mg (3.00 mmol) of aldehyde 1b, 440 mg
(1.90 mmol, 63%) of 2ba-anti and 60 mg (0.26 mmol, 9%)
of 2ba-syn were obtained after ¯ash chromatography of the
crude oily residue.
(2R,4R)-5-Methyl-4-(N-tertiobutyloxycarbonyl)-amino-
hexan-2-ol (2ba-syn). Colourless solid: mp#408C.
Rfˆ0.49. [a]2D5ˆ29.4 (cˆ0.8, CHCl3). IR (CH2Cl2): 1709
(CvO), 3440 (NH, O±Hassociated), 3607 (O±Hfree). 1H NMR
(CDCl3): 0.88 (d, 3 H, Jˆ7.0 Hz, (CH3)(CH3)CH), 0.91 (d, 3
H, Jˆ6.8 Hz, (CH3)(CH3)CH), 1.27 (d, 3 H, Jˆ6.2 Hz,
CH3CHOH), 1.45 (s, 9 H, (CH3)3C), 1.48 (ddd, 1 H,
Jˆ14.3, 9.0, 7.0 Hz, CHCHHCH), 1.58 (dt-like, 1 H,
Jˆ14.3, 4.5 Hz, CHCHHCH), 1.76 (dhept, 1 H, Jˆ6.7,
5.0 Hz, (CH3)2CH), 2.42 (br s, 1 H, OH), 3.47±3.55 (m, 1
H, CHNH), 3.90 (sext-like, 1 H, Jˆ6.3 Hz, CHOH), 4.56 (d,
1 H, Jˆ8.5 Hz, NH). 13C NMR (CDCl3) d: (17.5
((CH3)(CH3)CH), 18.8 ((CH3)(CH3)CH), 23.6 (CH3CHOH),
28.4 ((CH3)3C), 32.7 ((CH3)2CH), 42.3 (CHCH2CH), 54.0
(CHNH), 66.9 (CHOH), 79.4 ((CH3)3C), 156.3 (CvO).
HRMS (EI, 70 eV): C9H18NO3 ([M2zC3H7]1); calcdˆ
188.1287, foundˆ188.1294.
(3R,5S)-2-Methyl-3-(N-tertiobutyloxycarbonyl)-amino-
nonan-5-ol (2bb-anti). Colourless solid: mpˆ628C.
Rfˆ0.58. [a]2D5ˆ29.2 (cˆ0.8, CHCl3) IR (CH2Cl2): 1687
(CvO), 3439 (NH, O±Hassociated), 3608 (O±Hfree). 1H
NMR (CDCl3) d: 0.90 (t, 3 H, Jˆ7.3 Hz, CH3CH2), 0.92
(d, 3 H, Jˆ6.2 Hz, (CH3)(CH3)CH), 0.94 (d, 3 H, Jˆ6.2 Hz,
(CH3)(CH3)CH), 1.24±1.54 (m, 8 H, all CH2), 1.45 (s, 9 H,
(CH3)3C), 1.69 (dhept, 1 H, Jˆ6.2, 5.6 Hz, (CH3)2CH),
3.50±3.59 (m, 1 H, CHOH), 3.65 (dddd, 1 H, Jˆ12.0, 9.8,
5.6, 2.9 Hz, CHNH), 3.86 (s, 1 H, OH), 4.43 (d, 1 H,
Jˆ9.8 Hz, NH). 13C NMR (CDCl3) d: (14.1 (CH3CH2),
18.3 ((CH3)(CH3)CH), 19.4 ((CH3)(CH3)CH), 22.7
(CH3CH2), 28.3 (CH3CH2CH2), 28.4 ((CH3)3C), 32.3
((CH3)2CH), 36.7 (C3H7CH2), 41.4 (CHCH2CH), 52.4
(CHNH), 67.6 (CHOH), 79.8 ((CH3)3C), 157.6 (CvO).
HRMS (EI, 70 eV): C12H24NO3 ([M2zC3H7]1); calcdˆ
230.1756, foundˆ230.1754.
(2S,4R)-5-Methyl-4-(N-tertiobutyloxycarbonyl)-amino-
hexan-2-ol (2ba-anti). Colourless oil: Rfˆ0.59.
[a]2D5ˆ24.4 (cˆ0.7, CHCl3). IR (CH2Cl2): 1688 (CvO),
Synthesis of the syn and anti 5-(N-tertiobutyloxycar-
bonyl)-aminohept-1-en-3-ol (2ac) (Procedure A): Starting
from 1.51 g (7.50 mmol) of 1a and 27.5 mL (26.1 mmol,

J.-L. Toujas et al. / Tetrahedron 56 (2000) 2665±2672
2671
3.3 equiv.) of vinyl magnesium bromide solution (0.95 M in
THF), 558 mg (2.43 mmol, 33%) of 2ac-anti and 532 mg
(2.32 mmol, 30%) of 2ac-syn were obtained after ¯ash
chromatography of the crude oily residue.
pent-1-en-3-ol (2cc-anti). Colourless solid: mp#408C.
Rfˆ0.31. IR (CH2Cl2): 1712 (CvO), 3436 (NH,
1
O±Hassociated), 3601 (O±Hfree). H NMR (CDCl3) d: 1.38
(s, 9 H, (CH3)3C), 1.82 (dd, 2 H, Jˆ6.9, 6.6 Hz, CHCH2CH),
3.62 (br s, 1 H, OH), 4.13 (dt-like, 1 H, Jˆ6.3 Hz, CHOH),
4,88 (q-like, 1 H, Jˆ7.5 Hz, CHNH), 5.04 (dt-like, 1 H,
Jˆ10.3, 1.4 Hz, CHCHvCHH), 5.10 (broad s, 1 H, NH),
5.20 (d, 1 H, Jˆ17.4 Hz, CHvCHH), 5.84 (ddd, 1 H,
Jˆ17.0, 10.6, 5.7 Hz, CHCHvCH2), 7.16±7.33 (m, 5 H,
H arom.). 13C NMR (CDCl3) d: (29.7 ((CH3)3C), 44.3
(CH2), 51.7 (CHNH), 68.9 (CHOH), 80.1 ((CH3)3C),
114.4 (CHvCH2), 126.4, 127.5, 128.8 (Carom.), 140.1
(CHvCH2), 141.8 (Carom., quat.), 156.5 (CvO). HRMS (EI,
70 eV): C16H23NO3 (M1z); calcdˆ277.1678, foundˆ
277.1686.
(3R,5R)-5-(N-Tertiobutyloxycarbonyl)-aminohept-1-en-
3-ol (2ac-syn). Colourless oil. Rfˆ0.34. [a]2D5ˆ18.6
(cˆ0.9, CHCl3). IR (CH2Cl2): 1710 (CvO), 3435 (NH,
1
O±Hassociated), 3602 (O±Hfree). H NMR (CDCl3): 0.92 (t, 3
H, Jˆ7.4 Hz, CH3CH2), 1.44 (s, 9 H, (CH3)3C), 1.17±1.74
(m, 4 H, all CH2), 2.97 (br s, 1 H, OH), 3.37±3.73 (m, 1 H,
CHNH), 4.22 (dt-like, 1 H, Jˆ6.2 Hz, CHOH), 4.57 (d, 1 H,
Jˆ8.0 Hz, NH), 5.10 (d, 1 H, Jˆ10.3 Hz, CHvCHH), 5.25
(dt-like, 1 H, Jˆ16.5, 1.3 Hz, CHvCHH), 5.89 (ddd, 1 H,
Jˆ17.0, 10.6, 5.7 Hz, CHvCH2). 13C NMR (CDCl3) d:
(10.1 (CH3CH2), 28.4 ((CH3)3C), 28.8 (CH3CH2), 42.6
(CHCH2CH), 49.8 (CHNH), 71.0 CHOH), 79.3 ((CH3)3C),
114.5 (CHvCH2), 140.9 (CHvCH2), 156.1 (CvO).
Elemental analysis: C12H23NO3 (229.32): calcd C 62.85 H
10.10; found C 62.32 H 10.13.
Synthesis of the syn and anti 2-methyl-3-(N-tertiobutyl-
oxycarbonyl)-aminooct-7-en-5-ol (2bd) (Procedure A):
Starting from 215 mg (1.00 mmol) of 1b and 12 mL
(4.0 mmol, 4.0 equiv.) of allyl magnesium bromide solution
(0.34 M in THF), 77 mg (0.30 mmol, 30%) of 2bd-anti and
83 mg (0.32 mmol, 32%) of 2bd-syn were obtained after
¯ash chromatography of the crude oily residue.
(3S,5R)-5-(N-Tertiobutyloxycarbonyl)-aminohept-1-en-
3-ol (2ac-anti). Colourless solid: mpˆ698C. Rfˆ0.50,
[a]2D5ˆ123.2 (cˆ0.8, CHCl3). IR (CH2Cl2): 1688 (CvO),
3433 (NH, O±Hassociated), 3602 (O±Hfree). 1H NMR (CDCl3)
d: 0.96 (t, 3 H, Jˆ7.4 Hz, CH3CH2), 1.45 (s, 9 H, (CH3)3C),
1.26±1.77 (m, 4 H, all CH2), 3.61±3.81 (m, 1 H, CHNH),
4.09±4.21 (m, 1 H, CHOH), 4.11 (s, 1 H, OH), 4.84 (d, 1 H,
Jˆ8.8 Hz, NH), 5.09 (dt-like, 1 H, Jˆ10.4, 1.6 Hz,
(3R,5R)-2-Methyl-3-(N-tertiobutyloxycarbonyl)-aminooct-
7-en-5-ol (2bd-syn). Colourless oil: Rfˆ0.62 (ethyl acetate/
Heptaneˆ1/1). [a]D25ˆ28.6 (cˆ0.4, CHCl3). IR (CH2Cl2):
1
1709 (CvO), 3440 (NH, O±Hassociated), 3596 (O±Hfree). H
NMR (CDCl3): 0.87 (d, 3 H, Jˆ7.0 Hz, (CH3)(CH3)CH),
0.91 (d, 3 H, Jˆ6.7 Hz, (CH3)(CH3)CH), 1.47 (ddd, 1 H,
Jˆ14.0, 9.4, 7.0 Hz, NHCHCHHCH), 1.65 (dt-like, 1 H,
Jˆ14.0, 4.6 Hz, NHCHCHHCH), 1.44 (s, 9 H, (CH3)3C),),
1.77 (oct-like, 1 H, Jˆ6.9 Hz, (CH3)2CHCH), 2.19 (dt-like,
1 H, Jˆ13.8, 7.3 Hz, CHHCHvCH2), 2.35 (dt-like, 1 H,
Jˆ13.8, 6.8 Hz, CHHCHvCH2), 2.79 (br s, 1 H, OH),
3.49±3.56 (m, 1 H, CHNH), 3.71±3.79 (m, 1 H, CHOH),
4.60 (d, 1 H, Jˆ8.9 Hz, NH), 5.12 (d, 1 H, Jˆ11.1 Hz,
CHvCHH), 5.13 (d, 1 H, Jˆ16.1 Hz, CHvCHH), 5.75±
5.89 (m, 1 H, CHvCH2). 13C NMR (CDCl3) d: (17.6
((CH3)(CH3)CH),), 18.8 ((CH3)(CH3)CH), 28.4 ((CH3)3C),
CHvCHH), 5.27 (dt-like,
1
H, Jˆ17.2, 1.6 Hz,
CHvCHH), 5.89 (ddd, 1 H, Jˆ17.2, 10.4, 5.3 Hz,
CHCHvCH2). 13C NMR (CDCl3) d: (10.7 (CH3CH2),
28.4 ((CH3)3C), 28.5 (CH3CH2), 43.8 (CHCH2CH),), 49.1
(CHNH), 68.6 (CHOH), 79.8 ((CH3)3C), 113.7 (CHvCH2),
140.4 (CHvCH2), 157.3 (CvO). Elemental analysis:
C12H23NO3 (229.32): calcd C 62.85 H 10.11; found C
62.62 H 9.93.
Synthesis of the syn and anti 5-phenyl-5-(N-tertiobutyl-
oxycarbonyl)-aminopent-1-en-3-ol (2cc) (Procedure A):
Starting from 1.07 g (4.29 mmol) of 1c and 15.8 mL
(15.0 mmol, 3.5 equiv.) of vinyl magnesium bromide solu-
tion (0.95 M in THF), 404 mg (1.46 mmol, 34%) of 2cc-anti
and 321 mg (1.16 mmol, 27%) of 2cc-syn were obtained
after ¯ash chromatography of the crude oily residue.
32.5
((CH3)2CH),
39.6
(CH2CHvCH2),
41.8
(NHCHCH2CH), 53.7 (CHNH), 69.5 (CHOH), 79.4
((CH3)3C), 117.9 (CHvCH2), 134.8 (CHvCH2), 156.3
(CvO). HRMS (EI, 70 eV): C11H20NO3 ([M2zC3H7]1);
calcdˆ214.1443, foundˆ214.1452.
(3R,5S)-5-Phenyl-5-(N-tertiobutyloxycarbonyl)-amino-
pent-1-en-3-ol (2cc-syn). Colourless oil: Rfˆ0.19. IR
(CH2Cl2): 1712 (CvO), 3440 (NH, O±Hassociated), 3609
(3R,5S)-2-Methyl-3-(N-tertiobutyloxycarbonyl)-aminooct-
7-en-5-ol (2bd-anti). Colourless solid: mpˆ598C (pentane).
Rfˆ0.75 (ethyl acetate/Heptaneˆ1/1). [a]2D5ˆ213.3
(cˆ0.7, CHCl3). IR (CH2Cl2): 1687 (CvO), 3439 (NH,
1
(O±Hfree). H NMR (CDCl3) d: 1.33 (s, 9 H, (CH3)3C),
1
1.87±2.09 (m, 3 H, CH2, OH), 4.11 (q-like, 1 H,
Jˆ5.9 Hz, CHOH), 4.71±4.89 (m, 1 H, CHNH), 5.05±
5.11 (m, 1 H, NH), 5.04 (dt-like, 1 H, Jˆ10.3, 1.4 Hz,
CHvCHH), 5.16 (dt-like, 1 H, Jˆ17.2, 1.3 Hz, vCHH),
5.88 (ddd, 1 H, Jˆ17.2, 10.4, 5.8 Hz, CHCHvCH2), 7.19±
7.31 (m, 5 H, H arom.). 13C NMR (CDCl3) d: (28.3
((CH3)3C), 44.0 (CH2), 52.9 (CHNH), 70.8 (CHOH), 79.7
((CH3)3C), 114.8 (CHvCH2), 126.4 127.4 128.7 (Carom.),
140.7 (CHvCH2), 142.6 (Carom., quat.), 155.4 (CvO).
HRMS (EI, 70 eV): C12H15NO3 ([M2CH2vC(CH3)2]1z);
calcdˆ221.1051, foundˆ221.1045.
O±Hassociated), 3600 (O±Hfree). H NMR (CDCl3): 0.92 (d,
3 H, Jˆ6.7 Hz, (CH3)(CH3)CH), 0.94 (d, 3 H, Jˆ6.2 Hz,
(CH3)(CH3)CH), 1.30±1.56 (m, 2 H, NHCHCH2CH), 1.45
(s, 9 H, (CH3)3C), 1.70 (oct-like, 1 H, Jˆ6.6 Hz,
(CH3)2CHCH), 2.21 (dddt-like, 1 H, Jˆ13.8, 7.0, 1.5,
1.2 Hz, CH2vCHCHHCH), 2.30 (dt-like-t-like, 1 H,
Jˆ13.8, 7.0, 1.2 Hz, CH2vCHCHHCH), 3.60±3.70 (m, 2
H, CHOH, CHNH), 3.77 (br s, 1 H, OH), 4.45 (d, 1 H,
Jˆ10.0 Hz, NH), 5.06 (ddt, 1 H, Jˆ10.3, 2.0, 1.2 Hz,
CH2CHvCHH), 5.09 (ddt, 1 H, Jˆ17.3, 2.0, 1.5 Hz,
CH2CHvCHH), 5.87 (ddt, 1 H, Jˆ17.2, 10.2, 7.0 Hz,
CH2CHvCH2).
13C
NMR
(CDCl3)
d:
(18.2
(3S,5S)-5-Phenyl-5-(N-tertiobutyloxycarbonyl)-amino-
((CH3)(CH3)CH), 19.4 ((CH3)(CH3)CH), 28.4 ((CH3)3C),

2672
J.-L. Toujas et al. / Tetrahedron 56 (2000) 2665±2672
9. (a) Maroni, P.; Cazaux, L.; Tisnes, P.; Zambeti, M. Bull. Soc.
32.3
((CH3)2CH),
40.7
(CH2CHvCH2),
41.5
Chim. Fr. 1980, 117, 179±186. (b) Matsumura, Y.; Fujiwara, J.;
Maruoka, K.; Yamamoto, H. J. Am. Chem. Soc. 1983, 105, 6312±
6314.
(NHCHCH2CH), 52.4 (CHNH), 67.2 (CHOH), 79.8
((CH3)3C), 116.8 (CHvCH2), 135.5 (CHvCH2), 157.5
(CvO). HRMS (EI, 70 eV): C11H20NO3 ([M2zC3H7]1);
calcdˆ214.1443, foundˆ214.1438.
10. Tirel, P.-J.; Vaultier, M.; Carrie, R. Tetrahedron Lett. 1989, 30
(15), 1947±1950.
Ã
11. Hirama, M.; Shigemoto, T.; Yamazaki, Y.; Ito, S. J. Am.
Chem. Soc. 1985, 107, 1797±1798.
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