A new approach to non racemic saturated and unsaturated 5-aminoalkyl methyl ketones

Article abstract of DOI:10.1016/S0957-4166(00)00335-9

Non racemic t-Boc protected aminoalkyl ketones have been obtained starting from γ-stannylated (E)-allylamines through a high yielding two step procedure consisting of a Stille coupling and a subsequent Wacker oxidation. These compounds are useful intermed

Full text of DOI:10.1016/S0957-4166(00)00335-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 3759–3768
A new approach to non racemic saturated and unsaturated
5-aminoalkyl methyl ketones
Gianna Reginato,* Alessandro Mordini, Marinella Verrucci, Alessandro Degl’Innocenti and
Antonella Capperucci
Centro CNR Composti Eterociclici, Dipartimento di Chimica Organica ‘U. Schiff’, via G. Capponi 9,
I-50121 Florence, Italy
Received 28 July 2000; accepted 23 August 2000
Abstract
Non racemic t-Boc protected aminoalkyl ketones have been obtained starting from g-stannylated
(E)-allylamines through a high yielding two step procedure consisting of a Stille coupling and a
subsequent Wacker oxidation. These compounds are useful intermediates for obtaining 2,6-disubstituted
piperidines. © 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
The construction of versatile non racemic building blocks provides us with powerful tools for
efficient syntheses of biological compounds. We have already shown in previous works our
efforts in this area1–5 and in particular we have recently reported a procedure for preparing non
racemic stannylated allylamines 4,6 which were obtained with high enantiomeric purity starting
from amino aldehydes 1, easily derived from naturally occurring amino acids (Scheme 1).
Scheme 1.
* Corresponding author. Tel: +39 55 2757609; fax: +39 55 2476964; e-mail: reginato@cesce.fi.cnr.it
0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00335-9

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These compounds have proved to be useful three-carbon homologating reagents, the vinyl-tin
moiety being able to react with electrophiles via palladium-catalyzed coupling (Scheme 2)7,8 and
have been employed for obtaining enantiomerically enriched allylamines6 or aminoalcohols.3
Scheme 2.
In consideration of these premises we envisaged that non racemic vinylstannanes 4 could be
also exploited for developing a general method for the preparation of enantiomerically enriched
aminoketones of type 5. These are a very interesting class of compounds, being, for instance,
useful precursors of the corresponding tetrahydropyridines 6, which have been shown9 to be an
efficient entry to piperidines 7 or 8.
The piperidine ring is a common structural feature of many synthetic pharmaceuticals.
Alkaloids containing 2,6-disubstituted piperidines are abundant in nature and many of them,
having a methyl substituent in the 6 position, exhibit significant biological activity.10,11 They
have been found for example in the skin secretion of tropical frogs of the family of
Dendrobatidae12 and in some species of pines13 and fire ants.14 For this reason this kind of
compound has been the object of intensive synthetic efforts, resulting in a variety of racemic
and asymmetric synthesis.15–17 In many instances aminoalkyl ketones 5 have been employed as
key intermediates for the synthesis of some of these naturally occurring compounds18–20,21,22 such
as solenopsin A23 or some indolizidine alkaloids.24,25
Despite these features no general methods to prepare this class of compounds has been
reported, therefore we reasoned that easily achievable allylation of 4 and subsequent oxidation
would provide a simple and mild method for obtaining a new family of enantiomerically
enriched unsaturated amino ketones 10, in which the R lateral chain and the absolute
configuration of the C2 stereocenter are derived from the starting amino acid. Reduction of
compounds 10 would give the target compounds 5 (Scheme 3).
Scheme 3.
Herein we wish to report our results on the stereoselective synthesis of a new range of non
racemic unsaturated (10) and saturated (5) 5-aminoalkyl methyl ketones. Both the enantiomeric
forms could be selectively obtained, as they are derived from easily available
D
- or -amino acids.
L

G. Reginato et al. / Tetrahedron: Asymmetry 11 (2000) 3759–3768
3761
2. Results and discussions
The transformation of naturally occurring amino acids to the corresponding aldehydes is a
very well known procedure, and these compounds are useful intermediates in organic synthe-
sis.26,27 In particular they have been efficiently used for preparing the corresponding
propargylamines28,6 2a,b,c or the corresponding oxazolidine derivative 2d.29,3 In addition,
stannylallyl derivatives 4 have been efficiently prepared using alkynes 2 through the addition of
a mixed stannylcuprate 3.
Following this protocol,6 non racemic stannylated amines 4a,b,c and oxazolidine 4d were
prepared starting from the corresponding
L
-amino acids and from
D
-serine, respectively.
According to the well known Stille procedure,30 compounds 4 were reacted with an excess of
allyl bromide in the presence of Pd(PPh3)(CH2Ph)Cl2 complex as catalyst and the corresponding
coupled compounds 9a–d were obtained in good yields after washing of the reaction mixture
with aqueous NaOH solution and filtration through silica gel31 (Scheme 4). As expected, in all
the cases we examined, the reaction proceeded with retention of configuration with respect to the
vinylꢀtin bond, as it was confirmed by 1H NMR analysis. Therefore, as Stille coupling
conditions have already been proved6,32 not to alter the enantiomeric excesses in non racemic
compounds, we could conclude that this can be an efficient and mild method for obtaining non
racemic dienamines 9a–d with a predictable (E)-geometry.
Scheme 4.
The next step was the oxidation of the terminal double bond to the corresponding carbonyl
compounds. This transformation can be easily achieved using PdCl2 in the presence of a
cooxidant, and O2 and we decided to attempt the PdCl2/CuCl system under oxygen atmosphere,
using DMF as solvent (Scheme 5).33
Scheme 5.

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The reaction proceeded smoothly and unsaturated amino ketones 10a–d were obtained in high
yields and purified by flash chromatography. Experimental details are shown in Table 1.
Table 1
Yields and [h]D values determined for compounds 9a–d and 10a–d
Starting materials
9a
Exp. details
[h]D
10a
[h]D
4a
9a 60% (\95%) 72 h
[h]2D1=−4.4
10a
[h]2D1=−20.2
45°C
c=1.16, CHCl3
60% (\95%) c=1.06, CHCl3
CHCl3
9b 77% (\95%) 72 h
4b
4c
4d
[h]2D1=−11.4
10b
[h]2D0=−13.6
45°C
CHCl3
9c 74% (\95%) 48 h
45°C
CHCl3
9d 84% (\95%) 72 h
c=1.26, CHCl3
57% (\95%) c=1.16, CHCl3
[h]2D2=+6.2
[h]2D4=+3.9
c=1.04, CHCl3
10c
49% (\95%)c c=0.90, CHCl3
+9.0
10d
+25.3
45°C
c=1.53, CHCl3
82% (\95%) c=1.12, CHCl3
CHCl3
a Yield of isolated compounds. Conversions (calculated on the crude by 1H NMR analysis) are reported in
parenthesis.
This is a new family of non racemic compounds with interesting features. The presence of the
double bond should allow further functionalizations of positions 2 and 3 of the molecular
backbone, which are currently under investigation. Remarkably, double bond migration to the
corresponding a,b-unsaturated ketones has never been observed under our reaction conditions.
Finally, pure compounds 10a–c were hydrogenated with Pd catalysis to quantitatively obtain the
target compounds 5a–c (Scheme 6).
Scheme 6.
Unfortunately, hydrogenation of compound 10d was found to be more difficult, as an
inseparable mixture of at least three different compounds was recovered after treatment with H2
under Pd/C catalysis. Such behavior has been observed previously in similar compounds,34 and
to circumvent this problem we decided to hydrolyze the acetonide and protect the hydroxyl group
as its tosylate derivative, prior to performing the reduction. TFA/MeOH reagent was used for
the oxazolidine ring opening. As we have already observed in the case of other substrates,5 t-Boc
protecting group was not removed in these conditions. Crude 11 was then reacted with PTSA-Cl
and Et3N/imidazole in order to obtain the corresponding tosylate 12a, a useful precursor for
introducing different lateral chains by nucleophilic substitution. In this case the result was also
not straightforward, as a variable amount of the conjugated isomer 12b was recovered in the
reaction mixture. Purification by chromatography did not allow recovery of pure 12a. Although

G. Reginato et al. / Tetrahedron: Asymmetry 11 (2000) 3759–3768
3763
hydrogenation of the mixture under usual conditions afforded the reduced compound 13, it was
not isolated leading to a rapid decomposition. We concluded therefore, that introduction of
different lateral chains on the backbone of 5-aminoalkyl methyl ketones must be performed at
an earlier stage of the reaction sequence (Scheme 7).
Scheme 7.
Amino alcohol 11 has also been transformed to prove that the enantiomeric purity of the
starting material was maintained through the whole reaction sequence. Diastereomeric Mosher
esters were prepared by reaction with both (S)- and (R)-a-methoxy-a-(trifluoromethyl)-
1
phenylacetyl chloride (MTPACl). H NMR analysis of the two diastereomers were found to be
clearly distinguishable and showed no contamination from racemized material.
3. Experimental
3.1. General methods and materials
All reactions were carried out under a positive pressure of dry nitrogen. Ether extracts were
dried with Na2SO4. Reactions were monitored by TLC on SiO2; detection was carried out using
a KMnO4 basic solution. Flash column chromatography35 was performed using glass columns
1
(10–50 mm wide) and SiO2 230–400 mesh. H NMR spectra of hydrogen nuclei were recorded
at 200 or 300 MHz. 13C NMR spectra were recorded at 50.3 MHz. Chemical shifts were
1
determined relative to the residual solvent peak (CHCl3 l 7.26 for H NMR; CHCl3 l 77.0 for
13C NMR). Coupling constants (J) are reported in hertz (Hz). Multiplicities are indicated as s
(singlet), d (doublet), t (triplet), q (quartet), dd (doublet of doublet), m (multiplet) and bs (broad
singlet). Mass spectra were obtained at a 70 eV ionization potential and are reported in the form
m/z (intensity relative to base=100). Polarimetric measurements were performed in CHCl3
solution at u=589 nm, and the temperature is specified case by case.
Stannylated amines 4a–c and oxazolidine 4d were prepared according to the literature.6 THF
was dried by distillation over sodium benzophenone ketyl. CH2Cl2 was purified by the standard
,
procedure, dried over CaCl2 and stored over 4 A molecular sieves. DMF was distilled over
,
calcium hydride and stored over 4 A molecular sieves. Petroleum ether, unless specified, is the
40–70°C boiling fraction.
3.2. Coupling with allylbromide. General procedure
Stannylamines 4 were dissolved in CHCl3 together with allylbromide (2 equiv.) and
Pd(CH2Ph)(PPh3)Cl2 (10%). The reaction was stirred for 24 h or more depending on the

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substrate, then more allylbromide (1–1.5 equiv.) was added and allowed to react for a further 24
h. After completion the solvent was evaporated, the residue was diluted with ether, treated with
a 1 M NaOH solution and stirred for 1 h. After extraction with ether the organic phase was
washed with brine and dried. Evaporation afforded a crude mixture that, after filtration on SiO2,
yielded pure compounds 9.
3.2.1. N-[(2E),(1S)-1-(Methylethyl)hexa-2,5-dienyl](tert-butoxy)carboxamide 9a
Amine 4a (1200 mg, 2.5 mmol) was reacted according to the general procedure. After
1
purification (eluent: petroleum ether/ethyl acetate=8/1) 360 mg of 9a (60%) were obtained: H
NMR (200 MHz) l: 5.81 [ddt, 1H, Japp=17.2, 10.2 Hz, 7.0 Hz]; 5.57 [m, 1H, ABX2, JAB=15.4,
JAx=7.7 Hz]; 5.34 [m, 1H, ABY, JAB=15.4, JBY=6.2 Hz]; 5.09–4.97 [m, 2H]; 4.46 [bs, 1H]; 3.91
[m, 1H]; 2.77 [m, 1H]; 1.82–1.63 [m, 1H]; 1.43 [s, 9H]; 0.88 [d, 3H, J=7.0 Hz]; 0.87 [d, 3H,
J=7.0 Hz]. 13C NMR (50.3 MHz) l: 155.58; 136.73; 130.22; 129.12; 115.32; 79.13; 57.52; 36.33;
32.50; 28.39; 18.59; 18.19. MS m/e: 196 (4); 57 (100). [h]2D3 =−4.4 (c=1.16, CHCl3). Anal. calcd
for C14H25NO2: C, 70.25; H, 10.53; N, 5.85. Found: C, 70.46; H, 10.62; N, 5.88.
3.2.2. N-[(2E),(1S)-1-(3-Methylpropyl)hexa-2,5-dienyl](tert-butoxy)carboxamide 9b
Amine 4b (905 mg, 1.8 mmol) was reacted according to the general procedure. After
1
purification (eluent: petroleum ether/ethyl acetate=10/1) 345 mg of 9b (77%) were obtained: H
NMR (200 MHz) l: 5.80 [ddt, 1H, J=16.9 Hz, 10.3 Hz, 6.4 Hz]; 5.59 [m, 1H, ABX2, JAB=15.4,
JBX=6.4 Hz]; 5.33 [m, 1H, ABY, JAB=15.4, JAY=6.2 Hz]; 5.07–4.97 [m, 2H]; 4.33 [bs, 1H]; 4.09
[m, 1H]; 2.75 [m, 2H]; 1.74–1.50 [m, 1H]; 1.43 [s, 9H]; 1.35–1.25 [m, 2H]; 0.91 [d, 3H, J=6.6 Hz];
0.89 [d, 3H, 6.6 Hz]. 13C NMR (50.3 MHz) l: 155.20; 136.59; 132.37; 128.11; 115.27; 79.11;
50.69; 44.97; 36.29; 28.48; 24.78; 22.63. MS m/e: 196 (6); 57 (100). [h]2D3=−11.4 (c=1.26,
CHCl3). Anal. calcd for C15H27NO2: C, 71.10; H, 10.74; N, 5.53; Found: C, 71.12; H, 10.72; N,
5.58.
3.2.3. N-[(2E),(1S)-1-Benzylhexa-2,5-dienyl](tert-butoxy)carboxamide 9c
Amine 4c (410 mg, 0.75 mmol) was reacted according to the general procedure. After
1
purification (eluent: petroleum ether/ethyl acetate=10/1) 166 mg of 9c (74%) were obtained: H
NMR (200 MHz) l: 7.32–7.09 [m, 5H]; 5.75 [ddt, 1H, J=18.3 Hz, 9.1 Hz, 6.4 Hz]; 5.52 [m, 1H,
ABX2, JAB=15.6, JBX=5.9 Hz]; 5.39 [m, 1H, ABY, JAB=15.6, JAY=5.2 Hz]; 5.05–4.90[m, 2H];
4.54–4.24 [m, 1H+1H]; 2.86–2.76 [m, 2H]; 2.72 [m, 2H]; 1.39 [s, 9H]. 13C NMR (50.3 MHz) l:
155.07; 137.60; 136.36; 130.95; 129.58; 128.78; 128.20; 126.32; 115.38; 79.33; 53.24; 41.97; 36.27;
28.42. MS m/e: 196 (4); 91 (27); 57 (100). [h]2D0=+3.9 (c=1.04, CHCl3). Anal. calcd for
C18H25NO2: C, 75.22; H, 8.77; N, 4.87. Found: C, 75.43; H, 8.72; N, 4.88.
3.2.4. tert-Butyl 4-[(1E)-penta-1,4-dienyl](4S)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate 9d
Oxazolidine 4d (3.6 g, 7.0 mmol) was reacted according to the general procedure. After
1
purification (eluent: petroleum ether/ethyl acetate=10/1) 1.56 mg of 9d (84%) were obtained: H
NMR (200 MHz) l: 5.79 [ddt, 1H, J=16.9 Hz, 10.3 Hz, 6.6 Hz]; 5.56 [m, 1H]; 5.43 [m, 1H,
ABY, JAB=15.4 Hz, JAY=7.4 Hz]; 5.08–4.96 [m, 2H]; 4.38–4.14 [m, 1H]; 3.99 [dd, 1H, J=8.8,
5.8 Hz]; 3.69 [dd, 1H, J=8.8, 2.2 Hz]; 2.77 [m, 2H]; 1.57 [bs, 6H]; 1.48–1.42 [m, 9H]. 13C NMR
(50.3 MHz) l: 151.97; 136.41; 130.16; 129.96; 115.50; 93.73; 79.53; 68.39; 59.05; 36.14; 28.39;
26.12; 23.22. MS m/e: 252 (2); 196 (29); 57 (100). [h]2D4=+9.0 (c=1.53, CHCl3). Anal. calcd for
C15H25NO3: C, 67.38; H, 9.42; N, 5.24. Found: C, 67.53; H, 9.36; N, 5.28.

G. Reginato et al. / Tetrahedron: Asymmetry 11 (2000) 3759–3768
3765
3.3. Oxidation to methylketones. General procedure
CuCl (1 equiv.) and PdCl2 (0.2 equiv.) were dissolved into a 10/1 DMF/H2O solution and
stirred under O2 atmosphere at room temperature for 2 h. Dienamines 9 (1 equiv.) were then
added and left to react overnight. After this time the mixture was diluted with ether and treated
with an NH4Cl saturated solution. The organic layer was washed with water (three times) and
with brine and then dried. After evaporation of the solvent pure compounds 10 were obtained
after column chromatography.
3.3.1. N-[(2E)(1S)-1-(Methylethyl)-5-oxohex-2-enyl](tert-butoxy)carboxamide 10a
Amine 9a (308 mg, 1.29 mmol) was reacted according to the general procedure. After
1
purification (eluent: petroleum ether/ethyl acetate=2/1) 200 mg of 10a (60%) were obtained: H
NMR (200 MHz) l: 5.67 [m, 1H; ABMXX%, JAB=15.5 Hz, JBX=7.3 Hz, JBM=1.2 Hz]; 5.45 [m,
1H, ABM, JAB=15.5, JAM=5.9 Hz]; 4.51 [bs, 1H]; 4.01–3.84 [m, 1H]; 3.15 [d, 2H, J=6.6 Hz];
2.14 [s, 3H]; 1.71 [sest, 1H, J=7.0 Hz]; 1.43 [s, 9H]; 0.88 [d, 3H, J=7.0 Hz]; 0.87 [d, 3H, J=7.0
Hz]. 13C NMR (50.3 MHz) l: 206.87; 155.54; 133.78; 123.12; 79.27; 57.32; 47.23; 32.37; 29.66;
28.37; 18.66; 18.14. MS m/e: 212 (2); 83 (29); 57 (100). [h]2D7=−20.2 (c=1.06, CHCl3). Anal.
calcd for C14H25NO3: C, 65.85; H, 9.87; N, 5.49. Found: C, 65.79; H, 9.82; N, 5.44.
3.3.2. N-[(2E)(1S)-1-(2-Methylpropyl)-5-oxohex-2-enyl](tert-butoxy)carboxamide 10b
Amine 9b (350 mg, 1.4 mmol) was reacted according to the general procedure. After
1
purification (eluent: petroleum ether/ethyl acetate=3/1) 215 mg of 10b (57%) were obtained: H
NMR (200 MHz) l: 5.70 [dt, 1H, Japp=15.6, 7.6 Hz]; 5.45 [dd, 1H, Japp=15.6, 6.0 Hz]; 4.36
[bs, 1H]; 4.12 [m, 1H]; 3.13 [d, 2H, Japp=7.0 Hz]; 2.14 [s, 3H]; 1.76–1.51 [m, 1H]; 1.37–1.24 [m,
2H]; 1.43 [s, 9H]; 0.91 [d, 2H, Japp=6.2 Hz]. 13C NMR (50.3 MHz) l: 206.85; 155.17; 135.80;
122.16; 79.25; 50.34; 47.15; 44.57; 29.39, 28.40; 24.73; 22.64; 22.42. MS m/e: 186 (2); 57 (100).
[h]2D3=−13.6 (c=1.16, CHCl3). Anal. calcd for C15H27NO3: C, 66.88; H, 10.10; N, 5.20. Found:
C, 66.75; H, 9.98; N, 4.98.
3.3.3. N-[(2E)(1S)-5-Oxo-1-benzylhex-2-enyl](tert-butoxy)carboxamide 10c
Amine 9c (135 mg, 0.5 mmol) was reacted according to the general procedure. After
1
purification (eluent: petroleum ether/ethyl acetate=2/1) 70 mg of 10c (49%) was obtained: H
NMR (200 MHz) l: 7.35–7.10 [m, 5H]; 5.72–5.45 [m, 2H]; 4.48 [bs, 1H]; 4.38 [m, 1H]; 3.11 [d,
2H, J=6.2 Hz]; 2.82 [m, 2H]; 2.07 [s, 3H]; 1.40 [s, 9H]. 13C NMR (50.3 MHz) l: 206.46; 155.04;
137.32; 134.26; 129.47; 128.33; 126.47; 122.85; 79.51; 65.86; 47.14; 41.70; 29.75; 28.40. MS m/e:
212 (6); 156 (37); 57 (100). [h]D22=+6.2 (c=0.90, CHCl3). Anal. calcd for C18H25NO3: C, 71.26;
H, 8.31; N, 4.62. Found: C, 71.35; H, 8.18; N, 4.68.
3.3.4. tert-Butyl 4-((1E)-4-oxopent-1-enyl)(4S)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate 10d
Oxazolidine 9d (1.30 g, 4.9 mmol) was reacted according to the general procedure. After
workup 1.14 g of pure 10d (82%) were obtained. 88 mg of the crude were purified (eluent:
1
petroleum ether/ethyl acetate=3/1) to afford 50 mg of analytically pure 10d: H NMR (200
MHz) l: 5.69 [m, 1H]; 5.53 [m, 1H, JAB=15.2 Hz, JBX=7.0 Hz]; 4.28 [m, 1H]; 4.02 [dd, 1H,
J=9.0, 6.0 Hz]; 3.72 [dd, 1H, J=9.0, 2.0 Hz]; 3.15 [d, 2H, J=7.0 Hz]; 2.14 [s, 3H]; 1.58 [bs, 6H];
1.48–1.43 [bs, 9H]. 13C NMR (50.3 MHz) l: 206.36; 151.85; 133.26; 124.16; 93.77; 79.80; 68.17;
58.88; 46.98; 29.48; 28.46; 26.59; 23.69. MS m/e: 268 (1); 168 (30); 57(100). [h]2D3=+25.3

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G. Reginato et al. / Tetrahedron: Asymmetry 11 (2000) 3759–3768
(c=1.12, CHCl3). Anal. calcd for C15H25NO4: C, 63.58; H, 8.89; N, 4,94. Found: C, 63.87; H,
8.82; N, 4.88.
3.4. Hydrogenation of unsaturated amino ketones
Compounds 10a–d were dissolved in 95% ethanol, and hydrogenated (H2, 1 atm) over a
catalytic amount of Pd on carbon. The reaction was monitored by GC; after completion, the
solution was filtered over Celite. Evaporation of the solvent afforded pure compounds 5a–d.
3.4.1. N-[(1R)-1-(Methylethyl)-5-oxohexyl](tert-butoxy)carboxamide 5a
Compound 10a (200 mg, 0.8 mmol) was reacted according to the general procedure. After
1
workup 186 mg of pure 5a (93%) were obtained: H NMR (200 MHz) l: 4.26 [bs, 1H]; 3.41 [m,
1H]; 2.50–2.40 [m, 2H]; 2.13 [s, 3H]; 1.76–1.15 [m, 1H+4H] 1.43 [s, 9H]; 0.88 [d, 3H, J=6.8 Hz];
0.85 [d, 3H, J=6.8 Hz]. 13C NMR (50.3 MHz) l: 208.81; 155.94; 78.89; 55.05; 43.26; 32.11;
31.79; 29.71; 28.44; 20.37; 19.17; 17.62. MS m/e: 214 (2); 158 (68); 114 (100); 57(100). [h]2D1=+9.6
(c=0.93, CHCl3).
3.4.2. N-[(1R)-1-(2-Methylpropyl)-5-oxohexyl](tert-butoxy)carboxamide 5b
Compound 10b (215 mg, 0.8 mmol) was reacted according to the general procedure. After
1
workup 185 mg of pure 5b (85%) were obtained: H NMR (200 MHz) l: 4.36 [bs, 1H]; 3.60 [m,
1H]; 2.41 [m, 2H]; 2.12 [s, 3H]; 1.70–1.05 [m, 1H+2H+4H]; 1.42 [s, 9H]; 0.89 [d, 3H, J=6.6 Hz];
0.88 [d, 3H, J=6.6 Hz]. 13C NMR (50.3 MHz) l: 208.71; 155.60; 78.89; 48.38; 44.97; 43.33;
35.49; 29.90; 28.44; 24.93; 23.16; 22.25; 19.96. MS m/e: 214 (5); 85 (86); 57 (100). [h]2D1 =−9.6
(c=0.96, CHCl3].
3.4.3. N-[(1R)-5-Oxo-1-benzylhexyl](tert-butoxy)carboxamide 5c
Compound 10c (70 mg, 0.23 mmol) was reacted according to the general procedure. After
1
workup 65 mg of pure 5c (94%) was obtained: H NMR (200 MHz) l: 7.30–7.10 [m, 5H]; 4.41
[bd, 1H, J=7.6 Hz]; 3.80 [m, 1H]; 2.74 [m, 2H]; 2.46–2.35 [m, 2H]; 2.08 [s, 3H]; 1.80–1.20 [m,
4H]; 1.38 [s, 9H]. 13C NMR (50.3 MHz) l: 208.54; 155.41; 138.02; 129.31; 128.20; 126.18; 79.06;
51.22; 43.06; 41.39; 33.41; 29.86; 28.33; 20.06. MS m/e: 214 (5); 158 (50); 57(100). [h]2D1=+9.9
(c=0.92, CHCl3).
3.5. (1S)-N-[(2E)-1-(Hydroxymethyl)-5-oxo-esen-2-enyl](tert-butyl)lcarboxamide 11
Compound 10d (630 mg, 2.2 mmol) was dissolved in MeOH (30 mL) and, after cooling at
0°C, 10 mL of CF3COOH were added dropwise. After 1 h the reaction was let to reach rt and
reacted until the starting material was consumed. Volatiles were evaporated and the residue
diluted with ether and washed with a Na2CO3 saturated solution and brine. Pure 11 (530 mg,
1
98%) was obtained after evaporation of the solvent: H NMR (200 MHz) l: 5.79 [m, 1H,
J
AB=15.6 Hz]; 5.52 [m, 1H, JAB=15.6 Hz, JBX=5.7 Hz]; 4.94 [bd, 1H, J=6.6 Hz]; 4.23 [m, 1H];
3.65 [m, 2H]; 3.20 [d, 2H, J=6.8 Hz]; 2.20 [bs, 1H]; 2.16 [s, 3H]; 1.44 [s, 9H]. 13C NMR (50.3
MHz) l: 206.73; 155.77; 131.90; 124.15; 79.74; 64.96; 54.00; 46.86; 29.60; 28.36. MS m/e: 212
(3); 156 (31); 57 (100).

G. Reginato et al. / Tetrahedron: Asymmetry 11 (2000) 3759–3768
3767
3.5.1. (3E)(2S)-2-[(t-butoxy)carbonylamino]-6-oxohepten-3-yl-4-methylbenzensulfonate 12a and
(4E)(2S)-2-[(tert-butoxy)carbonylamino]-6-oxohept-4-enyl-4-methylbenzenesulfonate 12b
Crude 11 (130 mg, 0.5 mmol) was dissolved in anhydrous CH2Cl2 (10 mL) together with TsCl
(125 mg, 0.65 mmol), 0.1 mL of NEt3 and DMAP. After 24 h the reaction mixture was diluted
with CH2Cl2 washed with Na2CO3 saturated solution and brine. After purification (eluent:
petroleum ether/ethyl acetate=3/2) a 1/1 mixture of 12a and 12 b (174 mg, 88%) was obtained.
1
12a: H NMR (200 MHz) l: 7.80–7.79 [m, 2H]; 7.42–7.39 [m, 2H]; 5.87 [m, 1H, JAB=15.8 Hz,
J
BX=6.8 Hz]; 5.50 [m, 1H, JAB=15.8 Hz]; 4.68 [m, 1H]; 4.55 [m, 1H]; 4.39 [m, 2H]; 3.21 [d, 2H,
JbX=6.8 Hz]; 2.48 [s, 3H]; 2.15 [s, 3H]; 1.43 [s, 9H]. 13C NMR (50.3 MHz) l: 206.36; 151.85;
1
133.26; 124.16; 93.77; 79.80; 68.17; 58.88; 46.98; 29.48; 28.46; 26.59; 23.69. 12b: H NMR (200
MHz) l: 7.76–7.75 [m, 2H]; 7.34–7.33 [m, 2H]; 6.62 [m, 1H, JAB=16.0 Hz, JBX=7.2 Hz]; 6.04
[d, 1H, J=16.0 Hz]; 4.68 [m, 1H]; 4.35 [m, 1H]; 4.09 [m, 2H]; 2.45 [s, 3H]; 2.42 [m, 2H]; 2.13
[s, 3H]; 1.40 [s, 9H].
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