One-pot highly stereoselective reduction of β-keto amides to syn-γ-aminols

Article abstract of DOI:10.1016/S0040-4039(01)01904-9

In the presence of titanium tetrachloride, the borane/tetrahydrofuran complex can reduce 2-methyl-3-oxoamides into the corresponding syn-aminols in good yields and high diastereoselectivity. The use of borane/dimethyl sulfide instead of BH₃/THF

Full text of DOI:10.1016/S0040-4039(01)01904-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8811–8815
One-pot highly stereoselective reduction of b-keto amides to
syn-g-aminols
Giuseppe Bartoli,a,* Marcella Bosco,a Renato Dalpozzo,b Enrico Marcantoni,c Massimo Massaccesi,a
Samuele Rinaldia and Letizia Sambria
aDipartimento di Chimica Organica ‘A. Mangini’, Universita` di Bologna, v.le Risorgimento 4, 40136 Bologna, Italy
bDipartimento di Chimica, Universita` della Calabria, Ponte Bucci, I-87030 Arcavacata di Rende (CS), Italy
cDipartimento di Scienze Chimiche, Universita` di Camerino, v. S. Agostino 1, 62032 Camerino (MC), Italy
Received 10 October 2001
Abstract—In the presence of titanium tetrachloride, the borane/tetrahydrofuran complex can reduce 2-methyl-3-oxoamides into
the corresponding syn-aminols in good yields and high diastereoselectivity. The use of borane/dimethyl sulfide instead of
BH3/THF allows a partial reduction to syn-b-hydroxyamides. © 2001 Elsevier Science Ltd. All rights reserved.
to obtain syn-g-amino-b-alkylalcohols 2 (Scheme 1).
We report here how such a conversion can be accom-
plished according to a one-pot procedure by using an
excess of the BH3–THF complex in the presence of
TiCl4.8
The structural unit of 1,3-aminoalcohol is present with
a stereodefined geometry in many compounds having a
biological interest.1 In addition, aminols are useful
building blocks in the synthesis of many natural
products.2
It is well established that the reduction of carbonyl
bidentate compounds with BH3–complexes in the pres-
ence of TiCl4 proceeds via chelate complex intermedi-
ates.9 It can be reasonably assumed that amide 1 forms
a cyclic complex like 3, by treatment with TiCl4 in
dichloromethane–THF at low temperature (see Scheme
2). 1,2-Strain interaction between the methyl and R1
group favours conformation 3A. Addition of an excess
of the BH3–THF complex produces the stereoselective
reduction of the carbonyl function as the result of an
attack of the hydride ion source to the less hindered
face of 3A: very likely this would give a titanium or
boron alkoxy amide of type 4. In order to have a
complete reduction of 1 to 4 and in order to promote
the further reduction of the amide to the amino func-
tion, the mixture was allowed to reach room tempera-
In recent years several procedures for the construction
of this functionality, configurationally defined at the
1,3,3 2,34 and 1,2,35 positions, have been proposed.
Surprisingly, a simple, general, and efficient solution to
the problem of 1,2-stereocontrol is not available. In
particular, the only methods reported in the literature
for the synthesis of 1,2-syn-3-aminols are the regio- and
stereoselective ring-opening of epoxy-amines with
alanes6 and the acidic hydrolysis of certain 3,6-dihydro-
2H-1,3-oxazines.7 These procedures show good
stereoselectivity, but they are rather complex being
based on multistep reactions.
We assumed that the diastereoselective double reduc-
tion of b-ketoamides could be a very simple approach
OH
OH
O
O
1) TiCl4,CH2Cl2-THF,-78°C
2) BH3-THF, -78°C-rt
+
R1
R1
R1
NMe2
NMe2
NMe2
3) HCl 4%
4) HClconc/MeOH, 60°C
syn-2
anti-2
1
Scheme 1.
Keywords: diastereoselection; aminoalcohols; hydroxy amides; TiCl4; boranes.
* Corresponding author. Fax: +39 0512093654; e-mail: bartoli@ms.fci.unibo.it
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01904-9

8812
G. Bartoli et al. / Tetrahedron Letters 42 (2001) 8811–8815
Me
1) BH3-THF
2) HCl 4%
OX
O
NMe2
TiCl4
BH3-THF
syn-2
R1
1
O
O
NMe2
H
3) HClconc
MeOH, 60 °C
X=BH2 or TiCl3
,
R1
TiCl4
4
3A
H-
Scheme 2.
ture. Decomposition with diluted HCl gave aminoalco-
hols as cyclic boron complexes. Further treatment of
the crude with methanolic HCl at 60°C for 3 h allows
one to obtain syn-aminoalcohols 2 in a pure form. We
adopted this decomposition procedure since the usual
oxidative method (H2O2, NaOH, MeOH) fails, due to
the presence of a trivalent nitrogen in the substrate.10
Surprisingly, the BH3–Me2S complex15 allows a very
rapid reduction of ketoamides 1 to syn-b-hydroxy-a-
alkylamides 5 (Scheme 3), however, it fails to accom-
plish the further reduction of the amide to the amine
function. As a consequence this reducing agent can be
conveniently employed when the target is the synthesis
of syn-b-hydroxy-a-alkylamides.16 A few examples of
this reduction are reported in Table 2.
The reaction has been applied to a significative series of
a-methyl-b-ketoamides. As shown in Table 1, yields are
generally good and diastereoisomeric ratios vary from
high to excellent.11,12 The reaction works well when R1
is a phenyl, a t-butyl group and a long chain alkyl
framework. Slightly lower selectivities were observed in
the following cases: (i) when the A1,2 strain is low
(R1=Et, Table 1, entry 1); (ii) when R1 is a i-Pr group
(Table 1, entry 2), owing to the occurrence of 1,5-pen-
tane interaction;13 (iii) when a strong electron with-
drawing group such as NO2 is present in the aromatic
ring bound to the carbonyl function (Table 1, entry 7).
In the latter case, in fact, the decrease in the electron
density at the carbonyl function causes a destabilization
of the chelate complex 3.
The results reported here show how the reaction pro-
ceeds with high diastereoselectivity and in almost quan-
titative yields.17,18 It is interesting to note that such a
conversion cannot be accomplished with the BH3–THF
method by quenching the reaction at low temperature.
The reduction reaction of 1f for example was stopped
after 3 h at −78°C: a mixture containing the unreacted
starting material (10%), the monoreduction product
(hydroxy amide 5f, 63%), and the aminol derivative 2f
(11%) was recovered.
Due to the efficiency and the high diastereoselectivity
observed, the TiCl4–BH3–Me2S method represents a
very useful alternative to previously reported
procedures.19
Other borane complexes were also tested. The BH3–
py14 complex works quite well, although the use of this
reagent leads to serious problems in the purification of
final compounds.
In conclusion, a simple and highly diastereoselective
methodology for the synthesis of aminols with a 1,2-
syn-stereoconfiguration is proposed. The method makes
Table 1. Diastereoselective one-pot reduction of a-methyl-b-ketoamides 2 to the corresponding syn-aminoalcohols 2 with
BH3–THF in THF at −78°C to room temperature
Entry
Starting material
R1
Product
Yield (%)
syn/anti
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
Et
i-Pr
C5H11
t-Bu
c-C6H11
Ph
2a
2b
2c
2d
2e
2f
65
60
89
83
72
87
62
69
96/4
90/10
\99/1
98/2
95/5
\99/1
90/10
94/6
1g
1h
p-NO2-Ph
p-Br-Ph
2g
2h
1) TiCl4,CH2Cl2,-78°C
2) BH3-Me2S, -78°C
3) HCl 4%
OH
O
OH O
O
O
+
R1
R1
NMe2
NMe2
R1
NMe2
syn-5
anti-5
1
Scheme 3.

G. Bartoli et al. / Tetrahedron Letters 42 (2001) 8811–8815
8813
Table 2. Diastereoselective reduction of a-methyl-b-ketoamides 1 to the corresponding syn-a-methyl-b-hydroxyamides 5 with
BH3–Me2S in CH2Cl2 at −78°C
Entry
Starting material
R1
Product
Yield (%)
syn/anti
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
Et
i-Pr
C5H11
t-Bu
c-C6H11
Ph
5a
5b
5c
5d
5e
5f
\99
\99
\99
\99
\99
\99
87
98/2
95/5
\99/1
98/2
90/10
\99/1
91/9
1g
1h
p-NO2-Ph
p-Br-Ph
5g
5h
\99
\99/1
use of starting materials that are easy available, such as
b-ketoamides20 and very common reducing and chelat-
ing agents, such as borane complexes and titanium
tetrachloride. Yields are generally very good and
diastereoselectivities are either high or excellent. More-
over, the reduction can be limited to the step where
b-hydroxyamides are produced by an appropriate
choice of the borane reducing agent.
1994, 537–543; (h) Harding, K. E.; Marman, T. H.; Nam,
D. Tetrahedron 1988, 44, 5605–5614.
4. (a) Hioki, H.; Okuda, M.; Miyagi, W.; Itoˆ, S. Tetra-
hedron Lett. 1993, 34, 6131–6134; (b) Hioki, H.; Izawa,
T.; Yoshizuka, M.; Kunitaka, R.; Itoˆ, S. Tetrahedron
Lett. 1995, 36, 2289–2292.
5. (a) Barluenga, J.; Toma´s, M.; Ballesteros, A.; Kong, J. S.
Tetrahedron 1996, 52, 3095–3106; (b) Barluenga, J.;
Aguilar, E.; Olano, B.; Fustero, S. Synth. Lett. 1990,
463–465; (c) Hioki, H.; Izawa, T.; Yoshizuka, M.; Kuni-
tate, R.; Itoˆ, S. Tetrahedron Lett. 1995, 36, 2289–2292; (d)
Annunziata, R.; Cinquini, M.; Cozzi, F.; Gilardi, A.;
Restelli, A. J. Chem. Soc., Perkin Trans. 1 1985, 2289–
2297.
Acknowledgements
Work carried out in the framework of the National
Project ‘Stereoselezione in Sintesi Organica. Metodolo-
gie ad Applicazioni’ supported by MURST, Rome, and
by the University of Bologna, in the framework of
‘Progetto di Finanziamento Triennale, Ateneo di
Bologna, 1999–2001’.
6. Liu, C.; Hashimoto, Y.; Saigo, K. Tetrahedron Lett.
1996, 37, 6177–6180.
7. Cherkauskas, J. P.; Klos, S. M.; Borziller, R. M.; Sisko,
J.; Weinreb, S. M. Tetrahedron 1996, 52, 3135–3152.
8. Typical procedure: To a THF (10 ml) solution of b-
ketoamide 1 (1 mmol) TiCl4 (1.5 equiv., solution 1 M in
CH2Cl2) was added at −78°C. After 30 min, BH3–THF
(10 equiv., solution 1 M in THF) was added dropwise.
Then the reaction was left to rise to room temperature.
After 48 h, the reaction was quenched with aqueous HCl
(1 M), left to stir for 1 h and then basified with NaOH
(10%) and extracted with CH2Cl2. The organic layer was
evaporated under reduced pressure. The crude of the
reaction was dissolved in MeOH (5 ml/mmol) and HCl
conc. (1 ml/mmol) and heated at 60°C. After 3 h, the
solvent and the volatile boron derivatives were removed
under reduced pressure; then MeOH was added three
times to the residues and evaporated. The mixture was
basified with NaOH (10%) and extracted with CH2Cl2.
The organic layer was dried over MgSO4, filtered and
evaporated under reduced pressure. The crude products
were purified by flash chromatography on aluminium
oxide (Et2O/petroleum ether=7/3) to give pure aminols
2.
9. (a) Maier, G.; Seipp, U.; Boese, R. Tetrahedron Lett.
1987, 28, 4515–4516; (b) Sarko, C. R.; Collibee, S. E.;
Knorr, A. L.; Di Mare, M. J. Org. Chem. 1996, 61,
868–873; (c) Bartoli, G.; Bosco, M.; Sambri, L.; Marcan-
toni, E.; Dalpozzo, R. Chem. Eur. J. 1997, 3, 1941–1950;
(d) Bartoli, G.; Bosco, M.; Cingolani, S.; Marcantoni, E.;
Sambri, L. J. Org. Chem. 1998, 63, 3624–3630.
10. Smith, K. In Organometallic in Synthesis. A Manual;
Schlosser, M., Ed.; Wiley-Interscience: London, 1994;
Chapter 6, pp. 461–508.
References
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Cimarelli, C.; Palmieri, G. J. Chem. Soc., Perkin Trans. 1

8814
G. Bartoli et al. / Tetrahedron Letters 42 (2001) 8811–8815
11. Compound
(1R*,2S*)-3-(dimethylamino)-2-methyl-1-
(d, 1H, CH, JHH=3.3), 7.10–7.20 (m, 2H, Ph), 7.40–7.50
(m, 2H, Ph); 13C NMR (CDCl3, 75 MHz): l=15.0
(CH3), 34.8 (CH), 45.7 (CH3), 62.3 (CH2), 78.0 (CH),
120.5 (C), 128.7 (CH), 130.6 (CH), 141.1 (C).
phenyl-1-propanol (2f) was recognized by comparison
with literature data: Risch, N.; Esser, A. Liebigs Ann.
Chem. 1992, 233–37.
13. (a) Roush, W. R. J. Org. Chem. 1991, 56, 4151–4157; (b)
Bernardi, A.; Gennari, C.; Goodman, J. M.; Paterson, I.
Tetrahedron: Asymmetry 1995, 6, 2613–2636; (c) Gennari,
C.; Vieth, S.; Comotti, A.; Vulpetti, A.; Goodman, J. M.;
Paterson, I. Tetrahedron 1992, 48, 4439–4458; (d) Esteve,
C.; Ferrero, M.; Romea, P.; Urp`ı, F.; Vilarrasa, J. Tetra-
hedron Lett. 1999, 40, 5079–5082.
14. (a) Bartoli, G.; Bellucci, M. C.; Alessandrini, S.; Mala-
volta, M.; Marcantoni, E.; Sambri, L.; Dalpozzo, R. J.
Org. Chem. 1999, 64, 1986–1992; (b) Bartoli, G.; Bosco,
M.; Bellucci, M. C.; Dalpozzo, R.; Marcantoni, E.; Sam-
bri, L. Org. Lett. 2000, 2, 45–47.
15. (a) Ballini, R.; Bosica, G.; Marcantoni, E.; Vita, P.;
Bartoli, G. J. Org. Chem. 2000, 65, 5854–5857; (b) Bar-
toli, G.; Bosco, M.; Dalpozzo, R.; De Nino, A.; Proco-
pio, A.; Sambri, L.; Tagarelli, A. Eur. J. Org. Chem.
2001, 2971–2976.
16. Typical procedure: To a CH2Cl2 (10 ml) solution of
b-ketoamide 1 (1 mmol) TiCl4 (1.5 equiv., solution 1 M
in CH2Cl2) was added at −78°C. After 30 min, BH3–
Me2S (5 equiv., solution 10 M in Me2S) was added
dropwise. After 3 h at −78°C, the reaction was quenched
with aqueous HCl (1 M) and extracted with CH2Cl2. The
organic layer was dried over MgSO4, filtered and evapo-
rated under reduced pressure. The crude products were
purified by flash chromatography on aluminiumoxide
(Et2O/petroleum ether=8/2) to give pure hydroxyamides
5.
12. Spectroscopic data for unknown products follow:
1
(2S*,3S*)-1-(dimethylamino)-2-methyl-3-pentanol (2a): H
NMR (CDCl3, 300 MHz): l=0.80 (d, 3H, CH3, JHH
=
7.2), 1.00 (t, 3H, CH3, JHH=7.5), 1.30–1.50 (m, 2H,
CH2), 2.05–2.20 (m, 2H, CH and CH2), 2.30 (s, 6H,
2CH3), 2.65 (dd, 1H, CH, JHH=12.5, JHH=10.7), 3.1 (bs,
1H, OH), 3.51 (dt, 1H, CH, JHH=9.0, JHH=3.6); 13C
NMR (CDCl3, 75 MHz): l=11.0 (CH3), 14.0 (CH3), 25.0
(CH2), 34.4 (CH), 45.5 (CH3), 63.0 (CH2), 76.5 (CH);
(2S*,3S*)-1-(dimethylamino)-2,4-dimethyl-3-pentanol (2b):
1H NMR (CDCl3, 300 MHz): l=0.83 (d, 3H, CH3,
J
HH=6.7), 0.89 (d, 3H, CH3, JHH=6.9), 1.00 (d, 3H,
CH3, JHH=6.6), 1.60–1.75 (m, 1H, CH), 1.80–1.95 (m,
1H, CH), 2.26 (s, 6H, 2CH3), 2.29 (dd, 1H, CH, JHH
12.6, JHH=5.4), 2.49 (dd, 1H, CH, JHH=12.6, JHH=7.2),
=
3.0 (bs, 1H, OH), 3.31 (dd, 1H, CH, JHH=2.4, JHH
=
8.4); 13C NMR (CDCl3, 75 MHz): l=11.7 (CH3), 19.2
(CH3), 19.6 (CH3), 30.8 (CH), 33.0 (CH), 46.5 (CH3),
64.6 (CH2), 78.9 (CH); (2S*,3S*)-1-(dimethylamino)-2-
1
methyl-3-octanol (2c): H NMR (CDCl3, 300 MHz): l=
0.77 (d, 3H, CH3,
JHH=6.9), 0.88 (t, 3H, CH3,
JHH=6.8), 1.20–1.40 (m, 7H, 3CH2 and 1H, CH2), 1.50–
1.65 (m, 1H, CH2), 2.00–2.20 (m, 2H, CH and CH2), 2.24
(s, 6H, 2CH3), 2.56 (dd, 1H, CH, JHH=13.2, JHH=11.7),
3.50–3.60 (m, 1H, CH), 3.7 (bs, 1H, OH); 13C NMR
(CDCl3, 75 MHz): l=14.0 (CH3), 14.4 (CH3), 22.7
(CH2), 26.3 (CH2), 32.0 (CH2), 32.1 (CH2), 34.5 (CH),
45.8 (CH3), 63.3 (CH2), 75.7 (CH); (2S*,3R*)-1-(dimethyl-
17. Compounds (2R*,3S*)-3-hydroxy-N,N,2-trimethylpentan-
amide (5a), (2R*,3R*)-3-hydroxy-N,N,2,4,4-pentamethyl-
pentanamide (5d), (2R*,3S*)-3-cyclohexyl-3-hydroxy-N,N,
2-trimethylpropanamide (5e), (2R*,3R*)-3-hydroxy-N,N,2-
trimethyl-3-phenylpropanamide (5f) were recognized by
comparison with literature data (see Ref. 19a).
1
amino)-2,4,4-trimethyl-3-pentanol (2d): H NMR (CDCl3,
300 MHz): l=0.93 (s, 9H, 3CH3), 0.94 (d, 3H, CH3,
J
J
HH=7.0), 1.85–2.00 (m, 1H, CH), 2.18 (dd, 1H, CH2,
HH=12.4, JHH=5.5), 2.22 (s, 6H, 2CH3), 2.34 (dd, 1H,
CH2, JHH=12.4, JHH=7.4), 2.9 (bs, 1H, OH), 3.42 (d,
1H, CH, JHH=2.4); 13C NMR (CDCl3, 75 MHz): l=
13.0 (CH3), 27.0 (CH3), 32.2 (CH), 35.4 (C), 46.1 (CH3),
66.3 (CH2), 78.9 (CH); (1S*,2S*)-1-cyclohexyl-3-
(dimethylamino)-2-methyl-1-propanol (2e): 1H NMR
(CDCl3, 300 MHz): l=0.88 (d, 3H, CH3, JHH=7.0),
0.85–1.00 (m, 2H, CH2), 1.05–1.30 (m, 2H, CH2), 1.30–
1.45 (m, 1H, CH2), 1.50–1.80 (m, 5H, 2CH2 and 1H
CH2), 1.80–1.90 (m, 1H, CH), 2.00–2.10 (m, 1H, CH),
18. Spectroscopic data for unknown products follow:
(2R*,3S*) - 3 - hydroxy - N,N,2,4 - tetramethylpentanamide
1
(5b): H NMR (CDCl3, 300 MHz): l=0.84 (d, 3H, CH3,
JHH=6.8), 1.03 (d, 3H, CH3, JHH=6.6), 1.11 (d, 3H,
CH3, JHH=7.1), 1.65–1.80 (m, 1H, CH), 2.85 (dq, 1H,
CH, JHH=7.1, JHH=2.1), 2.95 (s, 3H, CH3), 3.05 (s, 3H,
CH3), 3.40 (dd, 1H, CH, JHH=9.0, JHH=2.1), 4.7 (bs,
1H, OH); 13C NMR (CDCl3, 75 MHz): l=9.3 (CH3),
18.6 (CH3), 19.2 (CH3), 30.0 (CH), 35.2 (CH3), 35.6
(CH), 37.1 (CH3), 76.6 (CH), 177.6 (C); (2R*,3S*)-3-
hydroxy-N,N,2-trimethyloctanamide (5c): 1H NMR
(CDCl3, 300 MHz): l=0.88 (t, 3H, CH3, JHH=6.8), 1.13
(d, 3H, CH3, JHH=7.1), 1.20–1.35 (m, 6H, 3CH2), 1.40–
2.23 (s, 6H, 2CH3), 2.24 (dd, 1H, CH2, JHH=12.6, JHH
=
5.4), 2.42 (dd, 1H, CH2, JHH=12.6, JHH=7.2), 3.36 (dd,
1H, CH, JHH=2.4, JHH=8.7), 4.0 (bs, 1H, OH); 13C
NMR (CDCl3, 75 MHz): l=11.5 (CH3), 25.9 (CH2), 26.1
(CH2), 26.4 (CH2), 29.1 (CH2), 29.8 (CH2), 32.4 (CH),
40.3 (CH), 46.3 (CH3), 64.5 (CH2), 77.2 (CH); (1R*,2S*)-
3-(dimethylamino)-2-methyl-1-(4-nitrophenyl)-1-propanol
1.60 (m, 2H, CH2), 2.62 (dq, 1H, CH, JHH=7.1, JHH
=
2.1), 2.94 (s, 3H, CH3), 3.04 (s, 3H, CH3), 3.80–3.90 (m,
1H, CH), 4.6 (bs, 1H, OH); 13C NMR (CDCl3, 75 MHz):
l=9.4 (CH3), 13.8 (CH3), 22.4 (CH2), 25.5 (CH2), 31.9
(CH2), 33.6 (CH2), 35.1 (CH3), 37.2 (CH3), 38.5 (CH),
71.0 (CH), 177.8 (C); (2R*,3R*)-3-hydroxy-N,N,2-
trimethyl-3-(4-nitrophenyl)-propanamide (5g): 1H NMR
(CDCl3, 300 MHz): l=0.98 (d, 3H, CH3, JHH=7.2), 2.86
(dq, 1H, CH, JHH=7.2, JHH=2.2), 3.00 (s, 3H, CH3),
3.06 (s, 3H, CH3), 5.18 (d, 1H, CH, JHH=2.2), 5.5 (bs,
1H, OH), 7.50–7.60 (m, 2H, Ph), 8.15–8.25 (m, 2H, Ph);
13C NMR (CDCl3, 75 MHz): l=9.2 (CH3), 35.5 (CH3),
37.4 (CH3), 40.9 (CH), 72.5 (CH), 123.4 (CH), 126.9
1
(2g): H NMR (CDCl3, 300 MHz): l=0.69 (d, 3H, CH3,
JHH=6.8), 2.10–2.20 (m, 1H, CH), 2.37 (s, 6H, 2CH3),
2.30–2.60 (m, 2H, CH and CH2), 4.7 (bs, 1H, OH), 4.97
(d, 1H, CH, JHH=3.3), 7.40–7.50 (m, 2H, Ph), 8.15–8.25
(m, 2H, Ph); 13C NMR (CDCl3, 75 MHz): l=14.5
(CH3), 35.0 (CH), 45.6 (CH3), 62.4 (CH2), 77.7 (CH),
122.8 (CH), 127.6 (CH), 146.9 (C), 150.1 (C); (1R*,2S*)-
1-(4-bromophenyl)-3-(dimethylamino)-2-methyl-1-propanol
1
(2h): H NMR (CDCl3, 300 MHz): l=0.67 (d, 3H, CH3,
JHH=6.8), 2.00–2.10 (m, 1H, CH), 2.33 (s, 6H, 2CH3),
2.35–2.50 (m, 2H, CH and CH2), 4.4 (bs, 1H, OH), 4.78

G. Bartoli et al. / Tetrahedron Letters 42 (2001) 8811–8815
8815
(CH), 147.0 (C), 149.2 (C), 176.7 (C); (2R*,3R*)-3-(4-
bromophenyl) - 3 - hydroxy - N,N,2 - trimethylpropanamide
(5h): 1H NMR (CDCl3, 300 MHz): l=0.99 (d, 3H,
Fujita, M.; Hiyama, T. J. Org. Chem. 1988, 53, 5405–
5414; (d) Fujita, M.; Hiyama, T. J. Org. Chem. 1988,
53, 5415–5421; (e) Fujita, M.; Hiyama, T. Org. Synth.
1990, 69, 44–53; (f) Fujii, H.; Oshima, K.; Utimoto, K.
Tetrahedron Lett. 1991, 32, 6147–6150.
CH3, JHH=7.2), 2.79 (dq, 1H, CH, JHH=7.2, JHH
=
2.4), 2.97 (s, 3H, CH3), 3.02 (s, 3H, CH3), 3.5 (bs, 1H,
OH), 5.04 (d, 1H, CH, JHH=2.4), 7.20–7.30 (m, 2H,
Ph), 7.40–7.50 (m, 2H, Ph); 13C NMR (CDCl3, 75
MHz): l=9.6 (CH3), 35.1 (CH3), 37.0 (CH3), 41.1 (CH),
72.5 (CH), 120.5 (C), 127.5 (CH), 130.8 (CH), 140.7 (C),
176.5 (C).
20. b-Ketoamides with no enolizable R1 group (1d, 1f, 1g,
1h) were synthesized in high yields from the a-anion of
N,N-dimethyl propionamide and the appropriate ester
following the same procedure adopted for the synthesis
of b-ketophosphineoxides (see: Bartoli, G.; Bosco, M.;
Sambri, L.; Marcantoni, E. Tetrahedron Lett. 1996, 37,
7421); b-ketoamides with enolizable R1 group (1a, 1b,
1c, 1e) were synthesized according to Ref. 19a.
19. (a) Taniguchi, M.; Fujii, H.; Oshima, K.; Utimoto, K.
Tetrahedron 1993, 49, 11169–11182; (b) Fujita, M.;
Hiyama, T. J. Am. Chem. Soc. 1985, 107, 8294–8296; (c)