Totally selective reaction of CO2 with enantiopure amino epoxides under mild reaction conditions. Synthesis and synthetic applications of enantiopure (4R, 1′S)- or (4S,1′S)-4-(1-aminoalkyl)-2-oxo-1,3- dioxolanes

Article abstract of DOI:10.1021/jo070829x

(Chemical Equation Presented) The reaction of chiral (2R,1′S)- or (25,1′S)-2-(1-aminoalkyl)epoxides 1 or 2 with CO₂, generated from acidic treatment of an aqueous solution of NaHCO₃ at room temperature, efficiently afforded enantiopu

Full text of DOI:10.1021/jo070829x

Totally Selective Reaction of CO2 with Enantiopure Amino Epoxides
under Mild Reaction Conditions. Synthesis and Synthetic
Applications of Enantiopure (4R,1′S)- or
(4S,1′S)-4-(1-Aminoalkyl)-2-oxo-1,3-dioxolanes
Jose´ M. Concello´n* and Virginia del Solar
Departamento de Qu´ımica Orga´nica e Inorga´nica, Facultad de Qu´ımica, UniVersidad de OViedo,
Julia´n ClaVer´ıa, 8, 33071 OViedo, Spain
Santiago Garc´ıa-Granda and M. Rosario D´ıaz
Departamento de Qu´ımica F´ısica y Anal´ıtica, Facultad de Qu´ımica, UniVersidad de OViedo,
Julia´n ClaVer´ıa, 8, 33071 OViedo, Spain
jmcg@unioVi.es
ReceiVed May 18, 2007
The reaction of chiral (2R,1′S)- or (2S,1′S)-2-(1-aminoalkyl)epoxides 1 or 2 with CO2, generated from
acidic treatment of an aqueous solution of NaHCO3 at room temperature, efficiently afforded enantiopure
cyclic carbonates 3 or 4, respectively, with total selectivity. Compounds 3 and 4 were readily transformed
into the corresponding diols 7 and 8 by reaction with LiAlH4 or by basic hydrolysis. When compounds
3 or 4 were allowed to react with methyllithium at -78 °C, O1-acetylalkane-1,2-diols 9 and 10 were
obtained with total or high selectivity.
Introduction
are incorporated in one step with total atom efficiency, and
second, carbon dioxide is an attractive C-1 building block in
organic synthesis since it is highly functional, abundant,
inexpensive, nontoxic, and nonflammable.
Cyclic carbonates or dioxolanones offer important practical
applications.3 Hence, they are used in the manufacture of various
polymers2a,4 and cosmetic products2a and as key additives in
solvent compositions to enhance cleaning power.5 Some of them
also offer biomedical applications,6 and from a synthetic view-
point, dioxolanones are useful intermediates, as for example in
the stereoselective synthesis of vicinal diols through hydrolysis.7
In recent years, the reaction of CO2 with different organic
compounds and catalyzed by transition metal has received much
attention.1 One of the most promising methodologies in this area
has been the synthesis of five-membered cyclic carbonates by
reaction of CO2 with epoxides in the presence of a transition
metal catalyst.2 Two aspects of the CO2 reaction with epoxides
are noteworthy. First, one carbon atom and two oxygen atoms
(1) (a) Behr, A. In Catalysis in C1 Chemistry; Keim, W., Ed.; Reidel:
Dordrecht, 1983. (b) Leitner, W. Coord. Chem. Rev. 1996, 155, 257-284.
(c) Behr, A. Carbon Dioxide ActiVation by Metal Complexes; VCH
Publishers: New York, 1988. (d) Green Chemistry: Frontiers in Benign
Chemical Syntheses and Processes; Anastas, P. T., Williamson, T. C., Eds.;
Oxford University Press: New York, 1998. (e) Inoue, S.; Yamazaki, Y.
Organic and Bio-organic Chemistry of Carbon Dioxide; Kodansha, Ltd.:
Tokyo, 1982. (f) Behr, A. Carbon Dioxide ActiVation by Metal Complexes;
VCH: Weinheim, Germany, 1988. (g) Gibson, D. H. Chem. ReV. 1996,
96, 2063-2096. (h) Casadei, M. A.; Inesi, A.; Rossi, L. Tetrahedron Lett.
1997, 38, 3565-3568.
In recent decades, numerous catalyst systems have been
developed for the former’s synthesis,8 and the advances for the
(2) (a) Shaikh, A. A. G.; Sivaram, S. Chem. ReV. 1996, 96, 951-976.
(b) Darensbourg, D. J.; Holtcamp, M. W. Coord. Chem. ReV. 1996, 153,
155-174. (c) Ochiai, B.; Endo, T. Prog. Polym. Sci. 2005, 30, 183-215.
(3) To see a review of the synthetic applications of cyclic carbonates:
Clements, J. H. Ind. Eng. Chem. Res. 2003, 42, 663-674.
10.1021/jo070829x CCC: $37.00 © 2007 American Chemical Society
Published on Web 08/24/2007
J. Org. Chem. 2007, 72, 7567-7573
7567

Concello´n et al.
yieldb (%)
reaction of carbon dioxide promoted by transition metal9 have
been significant. However, unfortunately all described methods
present some of the following drawbacks: low stability,
reactivity, and air sensitivity of the catalyst, whose structure is
generally complex, the need for a cosolvent, and the requirement
for high pressures and/or high temperatures. Thus, an efficient
method to react CO2 with epoxides at room temperature and
without external pressure by using a simple and more readily
available catalyst would be desirable.
TABLE 1. Synthesis of
(4R,1′S)-4-(1-Aminoalkyl)-2-oxo-1,3-dioxolanes 3
entry
3a
R
t (min)
1
2
3
4
3a
3b
3c
3d
Me
i-Bu
Bn
BnOCH2
5
20
10
20
85
91
88
78
a Diastereoisomeric excess (1H NMR of the crude products) of all
compounds 3 > 98%. b Isolated yield after column chromatography based
on the starting amino epoxide 1.
Previously, we reported the synthesis of both diastereoisomers
(2R,1′S)- or (2S,1′S)-2-(1-aminoalkyl)epoxides 1 or 2 in enan-
tiopure form.10 Thus, syn-amino epoxides 1 were prepared by
total stereoselective reduction with LiAlH4 of the readily
available R-amino-R′-chloro ketones, derived from natural
R-amino acids. The anti diastereoisomers 2 were obtained by
highly stereoselective addition of in situ generated iodometh-
yllithium (from diiodomethane and methyllithium) to R-amino
aldehydes. Recently, we reported the ring opening of these
epoxides 1 and 2 at C-3 by ketones,11 nitriles,12 carboxylic
acids,13 and organolithium compounds14 with total regioselec-
tivity.
SCHEME 1. Synthesis of
(4R,1′S)-4-(1-Aminoalkyl)-2-oxo-1,3-dioxolanes 3
(1-aminoalkyl)epoxides 1 or 2 with CO2, generated from acidic
treatment of an aqueous solution of NaHCO3, at room temper-
ature and without external pressure. So, enantiopure cyclic
carbonates 3 or 4 were obtained efficiently. In addition,
compounds 3 or 4 were readily transformed into diols 7 and 8
by reaction with LiAlH4 or by basic hydrolysis and into O1-
acetylalkane-1,2-diols 9 and 10 by reaction with methyllithium
at -78 °C.
In the course of our quest to develop new synthetic applica-
tions of the enantiopure aminoepoxides 1 and 2, we now report
herein the selective reaction of chiral (2R,1′S)- or (2S,1′S)-2-
(4) (a) Peppel, W. J. Ind. Eng. Chem. 1958, 50, 767-770. (b) Ratzen-
hofer, M.; Kisch, H. Angew. Chem., Int. Ed. Engl. 1980, 19, 317-318. (c)
Rakicki, G.; Kuran, W.; Marciniak, B. P. Monatsch. Chem. 1984, 115, 205.
(d) Kihara, N.; Hara, N.; Endo, T. J. Org. Chem. 1993, 58, 6198-6202.
(e) Yano, T.; Matsui, H.; Koike, T.; Ishiguro, H.; Fujihara, H.; Yoshihara,
M.; Maeshima, T. Chem. Commun. 1997, 1129-1130. (f) Yoshira, M.;
Ihara, M. Chem. Eur. J. 2004, 10, 2886-2893.
(5) (a) Duscher, P. A.; Whash, K. U.S. Pat 5.098.594, 1992; Chem. Abstr.
1992, 112, 121161t. (b) Duscher, P. A.; Whash, K. U.S. Pat 5.007.969,
1991; Chem. Abstr. 1992, 112, 121161t. (c) Duscher, P. A. U.S. Pat
5.204.026, 1993; Chem. Abstr. 1993, 119, 98532y.
(6) (a) Biggadike, K.; Angell, R. M.; Burgess, C. M.; Farrell, R. M.;
Hancock, A. P.; Harker, A. J.; Irving, A. J.; Irving, W. R.; Ioannou, C.;
Procopiou, P. A.; Shaw, R. E.; Solanke, Y. E.; Singh, O. M. P.; Snowden,
M. A.; Stubbs, R.; Walton, S.; Weston, H. E. J. Med. Chem. 2000, 43,
19-21. (b) Shaikh, A. A. G.; Sivaram, S. Chem. Rev. 1996, 96, 951-976.
(7) Trost, B. M.; Angle, S. R. J. Am. Chem. Soc. 1985, 107, 6123-
6124.
(8) (a) Yamaguchi, K.; Ebitani, K.; Yoshida, T.; Yoshida, H.; Kaneda,
K. J. Am. Chem. Soc. 1999, 121, 4526-4527. (b) Kawanami, H.; Ikushima,
Y. Chem. Commun. 2000, 2089-2090. (c) Kim, H. S.; Kim, J.; Kimee, J.;
Lee, B. G.; Jung, O. S.; Jang, H. G.; Kang, S. Angew. Chem., Int. Ed. 2000,
39, 4096-4098. (d) Paddock, R. L.; Nguyen, S. T. J. Am. Chem. Soc. 2001,
123, 11498-11499. (e) Tu, M.; Davis, R. J. J. Catal. 2001, 199, 85-91.
(f) George, M.; Weiss, R. G. J. Am. Chem. Soc. 2001, 123, 10393-10394
and references cited therein. (g) Kim, H. S.; Kim, J. J.; Kwon, H. N.; Chung,
M. J.; Lee, B. G.; Jang, H. G. J. Catal. 2002, 205, 226-229. (h) Yasuda,
H.; He, L. N.; Sakakura, T. J. Catal. 2002, 209, 547-550. (i) Shen, Y. M.;
Duan, W. L.; Shi, M. J. Org. Chem. 2003, 68, 1559-1562. (j) Kim, H. S.;
Kim, J. J.; Lee, S. D.; Lah, M. S.; Moon, D.; Jang, H. G. O. Chem. Eur. J.
2003, 9, 678-686. (k) Aresta, M.; Dibenedetto, A.; Gianfrate, L.; Pastore,
C. Appl. Catal. A: General 2003, 255, 5-11. (l) Paddock, R. L.; Hiyama,
Y.; McKay, J. M.; Nguyen, S. T. Tetrahedron Lett. 2004, 45, 2023-2026.
(m) Tanaka, H.; Kitaichi, Y.; Sato, M.; Ikeno, T.; Yamada, T. Chem. Lett.
2004, 33, 676-677. (n) Mori, K.; Mitani, Y. Hara, T.; Mizugati, T.; Ebitami,
K.; Kaneda, K. Chem. Commun. 2005, 3331-3333. (o) Doskocil, E. J. J.
Phys. Chem. B. 2005, 109, 2315-2320. (p) Berkessel, A.; Brandenburg,
M. Org. Lett. 2006, 8, 4401-4401.
(9) To see recent examples of the reaction of CO2 with epoxides without
the use of a metal catalyst: (a) Jagtap, S. R.; Raje, V. P.; Samant, S. D.;
Bhanage, B. M. J. Mol. Catal. A: Chem. 2007, 266, 69-74. (b) Zhao, Y.;
Tian, J.-S.; Qi, X.-H.; Han, Z.-N.; Zhuang, Y.-Y.; He, L.-N. J. Mol. Catal.
A: Chem. 2007, 271, 284-289. (c) Chaorong, Q.; Huanfeng, J.; Zhaoyang,
W.; Bo, Z.; Shaorong, Y. Synlett 2007, 255-258. (d) Jiang, J.-L.; Hua, R.
Synth. Commun. 2006, 36, 3141-3148.
(10) (a) Barluenga, J.; Baragan˜a, B.; Alonso, A; Concello´n, J. M. J. Chem.
Soc., Chem. Commun. 1994, 969-970. (b) Barluenga, J.; Baragan˜a, B.;
Concello´n, J. M. J. Org. Chem. 1995, 60, 6696-6699.
Results and Discussion
Synthesis of (4R,1′S)- or (4S,1′S)-4-(1-Aminoalkyl)-2-oxo-
1,3-dioxolanes. Initial attempts to obtain carbonates were
performed from syn diastereoisomers 1. Thus, a solution of
amino epoxides (1 equiv) 1 in diethyl ether was successively
treated with BF3‚Et2O (5 equiv) and diisopropylamine (1.5
equiv). After the reaction mixture was stirred for the time shown
in Table 1, it was treated with a saturated aqueous solution of
NaHCO3, and after the flask was sealed the mixture was stirred
for 10 min. Then, the reaction mixture was neutralized with
NaHCO3 and stirred for an additional 10 min. Standard workup
afforded the crude cyclic carbonate 3 (Scheme 1).
Importantly, no use of dry solvents or inert atmosphere was
necessary to carry out the reactions. Moreover, the presence of
both diisopropylamine and BF3‚Et2O is essential to perform the
transformation of 1 into 3. In the absence of amine or BF3‚
Et2O, unchanged amino epoxide 1 was fully recovered, and the
use of an amount less than 5 equiv of BF3‚Et2O produced a
mixture of the starting epoxide 1 and the carbonate 3. In
addition, when no addition of NaHCO3 was performed, as was
expected, no cyclic carbonate was obtained and the unchanged
starting compound 1 or 2 was isolated.
In a similar manner, anti-amino epoxides 2 afforded the
corresponding carbonates 4, under the same reaction conditions
(Scheme 2, Table 2).
The results of the synthesis of carbonates 3 and 4 are listed
in Tables 1 and 2. This process appears to be general, and no
(11) Concello´n, J. M.; Sua´rez, J. R.; Garc´ıa-Granda, S.; D´ıaz, M. R. Org.
Lett. 2005, 7, 247-250.
(12) Concello´n, J. M.; Sua´rez, J. R.; del Solar, V. J. Org. Chem. 2005,
70, 7447-7450.
(13) Concello´n, J. M.; Sua´rez, J. R.; del Solar, V.; Llavona, R. J. Org.
Chem. 2005, 70, 10348-10353.
(14) Concello´n, J. M.; Bernad, P. L.; del Solar, V; Sua´rez, J. R.; Garc´ıa-
Granda, S.; D´ıaz, M. R. J. Org. Chem. 2006, 71, 6420-6426.
7568 J. Org. Chem., Vol. 72, No. 20, 2007

Synthesis of (4R,1′S)- or (4S,1′S)-4-(1-Aminoalkyl)-2-oxo-1,3-dioxolanes
SCHEME 2. Synthesis of
(4S,1′S)-4-(1-Aminoalkyl)-2-oxo-1,3-dioxolanes 4
This transformation and the observed stereochemistry of
products 3 and 4 may be explained by assuming the generation
of CO2 from the reaction of the aqueous solution of NaHCO3
with the BF3‚Et2O, present in the reaction mixture. Support for
this is provided by (a) the observation of CO2 effervescence
and (b) the isolation of unchanged amino epoxide 1 or 2 (instead
of carbonates 3 or 4) when the reaction was carried out in an
open flask.16 In addition, to unambiguously prove the participa-
tion of CO2 in the reaction, two experiments were performed
by bubbling gas CO2 and by using dry CO2 instead of the
aqueous solution of NaHCO3. Thus, the synthesis of cyclic
carbonate 4c was performed by bubbling gas CO2 through a
solution of the amino epoxide 2c, diisopropylamine, and BF3‚
Et2O in diethyl ether for 2 h at room temperature in an open
flask. After usual workup, carbonate 4c (62% yield) and
epoxide 2c (14% yield) were isolated. The lower yield of 4c
could be explained by taking into account that this experiment
was performed in an open flask.16 The reaction with dry CO2
was performed from amino epoxide 1a, and no important
differences were detected. Thus, carbonate 4a was obtained in
80% yield (similar to the shown in Table 1) by treatment of a
solution of amino epoxide 1a, diisopropylamine and 1 equiv of
BF3‚Et2O (instead of 5 equiv)18 in diethyl ether with dry CO2
(4 equiv) for 45 min. Finally, no important differences were
observed when the synthesis of cyclic carbonates was carried
out at higher scale: 78% of 3a was obtained starting from 8
mmol of 1a.
When the described reaction of CO2 was performed, under
the same reaction conditions, from 2-cyclohexyloxirane instead
of the amino epoxides 1 or 2, no chemical fixation of CO2 was
observed. This result suggested the essential participation of
the dibenzylamino group in the reaction. So, presumably, the
ring opening of 1 could proceeds through an effective co-
operation between the BF3‚Et2O and the dibenzylamino group.19
The Lewis acid, which was added in excess (5 equiv), could
activate the oxirane by coordination of the epoxide oxygen to
the Lewis acid.20 Then, an intramolecular ring opening at C-2
by the dibenzylamino group, with inversion of configuration,
would afford the aziridinium salt 5,21 which could be in
TABLE 2. Synthesis of
(4S,1′S)-4-(1-Aminoalkyl)-2-oxo-1,3-dioxolanes 4
entry
4
R
t (min)
dea (%)
yieldb (%)
1
2
3
4a
4b
4c
Me
i-Bu
Bn
10
20
10
>98 (>98)
91 (91)
91 (92)
80
89
82
a Diastereoisomeric excess determined by 1H NMR analysis of the crude
products 4; de of the starting amino epoxides 2 is given in parentheses.
b Isolated yield after column chromatography based on the starting amino
epoxide 2.
important differences in the reaction were observed when the
structure of R or the absolute configuration of the oxirane of
the starting amino epoxide was changed.
The selectivity of the reactions was determined by 1H NMR
spectroscopy (300 MHz) of the crude reaction products. All
carbonates 3 were obtained as single isomers. Carbonates 4 were
obtained as a mixture of diastereoisomers, in the same relation-
ship to that of the starting aminoepoxides 2. The synthesis of
2-oxo-1,3-dioxolanes 4 with the same diastereoisomeric excess
as that of the starting aminoepoxides 2 could be indirect support
of the total selectivity of the ring-opening reaction. After
purification of carbonates 4 by column chromatography, the
major diastereoisomer was isolated as a single enantioisomer.
The structure and the absolute configuration of compound
3c was established unambiguously by single-crystal X-ray
analysis,15 and the structure and absolute configuration of the
other cyclic carbonates 3 or 4, as depicted in Schemes 1 and 2,
were assigned by analogy. The X-ray analysis of 3c showed
that the absolute configurations are the same as the starting
amino epoxide 1c.
To the best of our knowledge, no previous synthesis of cyclic
carbonates by reaction of epoxides with CO2 has been described
at room temperature and without to use a metal catalyst9 or
external pressure.16 In addition, from a preparative viewpoint
it is the first time in which two diastereoisomers of cyclic
carbonates are obtained in enantiopure form.17
(18) A minor amount of BF3‚Et2O was used in this reaction because the
Lewis acid was not necessary to generate CO2 from NaHCO3.
(19) To explain the ring opening of amino epoxides 1 or 2 by other
nucleophiles (refs 11-14), a direct attack of the nucleophiles to the oxirane
ring, without participation of the dibenzylamino group, was proposed
because the reaction took place (under the same reaction conditions) on
epoxides without a dibenzylamino group.
(20) The selective coordination of the Lewis acid with the epoxide instead
of the nitrogen of dibenzylamino group is proposed on the basis of previous
results. Thus, the treatment of dibenzylamino aziridines with BF3 and
further treatment with lithium aluminium hydride afforded the corres-
ponding complex aziridine-borane with total selectivity, and no complex
of dibenzylamino-borane was detected on the crude reactions. The aziridine-
borane complex was isolated, and its structure was established by single-
crystal X-ray diffraction analysis: Concello´n, J. M.; Sua´rez, J. R.;
Garc´ıa-Granda, S.; D´ıaz, M. R. Angew. Chem., Int. Ed. 2004, 43, 4333-
4336.
(21) The same participation of the dibenzylamino group in ring-opening
of amino epoxides by ketones was previously proposed: (a) Concello´n, J.
M.; Sua´rez, J. R.; Garc´ıa-Granda, S.; D´ıaz, M. R. Org. Lett. 2005, 7, 247-
250. A similar participation of the dibenzylamino group to justify the ring-
opening of amino aziridines by various nucleophiles was also proposed:
(b) Concello´n, J. M.; Riego, E. J. Org. Chem. 2003, 68, 6407-6410. (c)
Concello´n, J. M.; Riego, E.; Su´arez, J. R. J. Org. Chem. 2003, 68, 9242-
9246. (d) Concello´n, J. M.; Sua´rez, J. R.; Garc´ıa-Granda, S.; D´ıaz, M. R.
Angew. Chem., Int. Ed. 2004, 43, 4333-4336. (e) Concello´n, J. M.; Sua´rez,
J. R.; Garc´ıa-Granda, S.; D´ıaz, M. R. Org. Lett. 2004, 6, 4499-4501. (f)
Concello´n, J. M.; Bernad, P. L.; Sua´rez, J. R.; Garc´ıa-Granda, S.; D´ıaz, M.
R. J. Org. Chem. 2005, 70, 9411-9416.
(15) Crystallographic Data for 3c. A colorless, prismatic crystal, 0.20
× 0.15 × 0.10 mm3 was selected for the experiment. Cu KR was used on
a Nonius Kappa-CCD (λ ) 1.54184 Å) single-crystal diffractometer: T )
293(2) K. Unit cell dimensions: a ) 11.0013(8), b ) 9.2305(6), c )
21.6130(2), b ) 91.697(7). Space group P21. Absolute structure was checked
using Friedel pairs and chemical information. CCDC-630533 (3c) contains
the supplementary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc-.cam.ac.uk/conts/retrieving.html (or
the Cambridge Data Center, 12 Union Road, Cambridge CB21EZ, UK;
fax (+44)1223-336.033; or deposit@ccdc.cam.ac.uk).
(16) When CO2 is generated, pressure builds up in the flask. So, an
experiment was carried out to determinate the generated pressure after
addition of the aqueous solution of NaHCO3. The reaction was performed
starting from 0.43 mmol of epoxide 1a and by using a 38 mL flask. When
the flask was sealed (after addition of the solution of NaHCO3), the pressure
measured inside the flask was 1.15 bar.
(17) A catalytic resolution of racemic epoxides by reaction with CO2 by
using chiral Salen Co(III)/quaternary ammonium halide as the catalyst
system is described in: Lu, X. B.; Liang, B.; Tian, Y.-J.; Wang, Y. M.;
Bai, C. X.; Wang, H.; Zhang, R. J. Am. Chem. Soc. 2004, 126, 3732-
3733.
J. Org. Chem, Vol. 72, No. 20, 2007 7569

Concello´n et al.
TABLE 3. Synthesis of (2S,3S)- or (2R,3S)-3-Aminoalkan-1,2-diols
7 or 8
SCHEME 3. Proposed Mechanism
yielda (%)
entry
compd
R
LiAlH4
KOH 50%
1
2
3
7a
7b
8b
Me
i-Bu
i-Bu
82
88
84
84
87
83
equilibrium with the salt derived of the amine and BF3. The
generated CO2 could be activated by diisopropylamine22 and
would attack at C-2 the aziridinium salt 5 with a second
inversion of configuration to afford the intermediate 6, which
could cycle to give the corresponding cyclic carbonate 3
(Scheme 3).
An attack at C-3 of the aziridinium salt by the activated CO2
would be also possible. The complete regioselectivity observed
could be explained as consequence of an interaction between
the +NHiPr2 and the -OBF3 groups. A similar explanation has
been used to justify the observed regioselectivity on the
nucleophilic ring opening of similar compounds such as amino
aziridines.23 The same mechanism would justify the synthesis
of 4.
a Isolated yield after column chromatography based on the starting cyclic
carbonates 3 and 4.
SCHEME 4. Synthesis of (2S,3S)- or
(2R,3S)-O1-Acetyl-3-aminoalkane-1,2-diol 9 or 10
Preparation of (2S,3S)- or (2R,3S)-3-Aminoalkan-1,2-diols
7 or 8 Using LiAlH4 or KOH 50%. To prove the synthetic
applications of these cyclic carbonates 3 and 4, they were
transformed into the corresponding 3-dibenzylaminoalkane-1,2-
diols 7 or 8. Thus, treatment of a solution of cyclic carbonates
3a,b or 4b in methanol with KOH (1 mL of a 50% aqueous
solution) at room temperature for 1 h afforded enantiopure diols
7a,b or 8b in high yield (Table 3).
TABLE 4. Synthesis of (2S,3S)- or
(2R,3S)-O1-Acetyl-3-aminoalkane-1,2-diol 9 or 10
entry
compd
R
yielda (%)
1
2
3
4
9a
9b
10a
10b
Me
i-Bu
Me
66
Alternatively, diols 7a,b and 8b were also obtained by
reduction of cyclic carbonates with LiAlH4 (Table 3) in very
similar yields.
67
65b
64c
i-Bu
a Isolated yield after column chromatography based on the starting cyclic
carbonates 3 and 4. b As a 5/1 mixture of regioisomers of 10a (major) and
the corresponding O2-acetyl regioisomer (minor). b As a 7/1 mixture of
regioisomers of 10b (major) and the corresponding O2-acetyl regioisomer
(minor).
The structure of diols 7b and 8b, as depicted in Table 3, was
unambiguously established by comparison of the NMR spec-
troscopic data of 7b and 8b with the 1H and 13C NMR spectra
of authentic samples, previously described in the literature.11
The structure and absolute configuration of 7a was assigned
by analogy.
Preparation of (2S,3S)- or (2R,3S)-O1-Acetyl-3-aminoal-
kane-1,2-diol 9 or 10 Using MeLi. When the reaction with
MeLi was carried out at room or -10 °C a complex mixture of
products was obtained. However, the reaction of a solution of
cyclic carbonates 3a,b and 4a in THF at -78 °C with 1.1 equiv
of MeLi for 30 min afforded, after standard workup, the
corresponding enantiopure O1-acetyl alkane-1,2-diols 9a,b and
10a,b in good yield and with high (10a,b) or total (9a,b)
regioselectivity (Scheme 4 and Table 4).
the presence of a single regioisomer in the synthesis of 9a,b.
On the contrary, 10a,b were obtained as a mixture of the two
possible regioisomers (1,2-diols O1-acetylated or O2-acetylated)
in a relationship of 5/1 and 7/1, respectively. No separation of
regioisomers by conventional column chromatography was
possible. The regiochemistry of the ester group in compounds
9 and 10 (major regioisomer) was determined by the HMBC
2D-NMR experiment performed on 9b, which showed correla-
tion between the methylene hydrogens of CH2OCOMe and the
carbonyl compound CH2OCOMe, and no interaction between
the hydrogens of CHOH and the carbonyl carbon. Consequently,
the acetylated hydroxyl group of 9b would be the primary
alcohol function. In addition, the structure of compounds 9b
and 10b was also established by comparison of their NMR
1
The selectivity of the reaction was determined by H NMR
spectroscopy (300 MHz) of the crude mixture products, showing
(22) The activation of CO2 by a base has been previously proposed by
other authors to explain the reaction of CO2 with epoxides: refs 7a and 7l
and references cited therein.
(23) Concello´n, J. M.; Riego, E.; Su´arez, J. R. J. Org. Chem. 2003, 68,
9242-9246.
1
spectroscopic data with the H and 13C NMR spectra of the
same compound previously described in the literature.13
7570 J. Org. Chem., Vol. 72, No. 20, 2007

Synthesis of (4R,1′S)- or (4S,1′S)-4-(1-Aminoalkyl)-2-oxo-1,3-dioxolanes
SCHEME 5. Proposed Mechanism
To explain the transformation of cyclic carbonates 3 or 4 into
O1-acetylalkane-1,2-diols 9 and 10, we propose the mechanism
depicted in Scheme 5. Thus, the addition of MeLi to the cyclic
carbonate 3 would afford the cyclic intermediate 11, which could
undergo two different opening of the oxirane to give the
regioisomers 9 or 12. A possible explanation of the selective
ring-opening, to afford the 1,2-diols O1-acetylated 9 as single
regioisomer could be based on steric hindrance between the
bulkiest groups O-acetyl and dibenzylamino. Thus, regioisomer
9 (the former groups are in a relative 1,3-position) is favored
versus 12 (1,2-position). Further studies to justify the selectivity
of this transformation are currently under investigation.
The lower regioselectivity observed in the synthesis of 10a,
b could be also explained based on steric hindrance. So, the
steric hindrance is higher in the O2-acetylated syn-diol 12 than
in the O2 acetylated anti-diol 13, as is shown in their Newman
projections (Scheme 5). Thus, formation of 13 is more favored
than formation of 12. Therefore, 9 would be the only regioi-
somer obtained from 3 and a mixture of the O1 and O2 acetylated
regioisomers could be obtained from 4.
Experimental Section
General Procedure of the Synthesis of 3 and 4. BF3‚OEt2 (5
equiv, 1 mmol, 0.15 mL) and diisopropylamine (1.5 equiv, 0.3
mmol, 0.040 mL) were added to a stirred solution of the corre-
sponding amino epoxide 1 or 210 (0.2 mmol) in Et2O (2 mL) at
room temperature. After the mixture was stirred for the time
indicated in Tables 1 and 2, an aqueous saturated solution of
NaHCO3 (2 mL) was added, and after the flask was sealed, the
mixture was stirred for 10 min. Then, the reaction was neutralized
by adding an aqueous saturated solution of NaHCO3 (5 mL), and
the mixture was stirred for 10 min. The resulting mixture was
extracted with diethyl ether (3 × 5 mL), and the combined organic
layers were dried over anhydrous Na2SO4, filtered, and concentrated
in vacuo. Flash column chromatography on silica gel (hexane/
EtOAc 20:1) provided pure compounds 3 or 4.
When the synthesis of 3a was performed at higher scale from 8
mmol of 1a, the reaction was carried out in a flask of 500 mL. So,
a solution of 6 mL of BF3‚OEt2 (40 mmol) and 1.6 mL of
diisopropylamine (12 mmol) in 75 mL of Et2O was stirred for 15
min, and 1a10 (8 mmol, 2.024 g) and an aqueous saturated solution
of NaHCO3 (80 mL) were added successively at room temperature.
After the flask was sealed, the mixture was stirred for 30 min.
Synthesis of 3a Using dry CO2. BF3‚OEt2 (1,1 equiv, 0.44
mmol, 0.066 mL) and diisopropylamine (1.5 equiv, 0.6 mmol, 0.080
mL) were added to a stirred solution of the amino epoxide 1a10
(0.4 mmol, 0.101 g) in Et2O (3 mL) at room temperature. After
the mixture was stirred for 5 min, 12.5 equiv of dry CO2 (5 mmol,
240 mg) was added, and after the flask was sealed, the mixture
was stirred for 75 min. Then, the reaction was neutralized by adding
an aqueous saturated solution of NaHCO3 (3 mL), and the mixture
was stirred for 10 min. The resulting mixture was extracted with
diethyl ether (3 × 5 mL), and the combined organic layers were
dried over anhydrous Na2SO4, filtered, and concentrated in vacuo.
Flash column chromatography on silica gel (hexane/EtOAc 20:1)
provided pure compounds 3a.
Conclusions
In conclusion, we have described the reaction of chiral anti-
or syn-amino epoxides 1 or 2 with CO2 (generated by reaction
of aqueous solution of NaHCO3 with BF3‚Et2O) in the presence
of diisopropylamine, affording the corresponding enantiopure
carbonates 3 or 4. The structure of the cyclic carbonate was
established on the basis of the results of the X-ray analysis of
3c. A mechanism has been proposed to explain this transforma-
tion. Basic hydrolysis or reduction with LiAlH4 of carbonates
3 or 4 afforded the corresponding enantiopure diols 7 or 8,
respectively, in high yields. The treatment of cyclic carbonates
3 or 4 with MeLi at low temperature (-78 °C) gave the optically
active 1,2-diol O1-acetylated 9 or 10, respectively, in good yield
and with complete or high regioselectivity. A possible explana-
tion to justify the regioselectivity of this transformation is given.
The synthetic applications of the obtained cyclic carbonates and
studies directed toward fully delineating the factors involved
in these transformations are currently under investigation in our
laboratory.
(4R)-4-[(S)-1-(Dibenzylamino)ethyl]-1,3-dioxolan-2-one (3a):
white solid; mp ) 79 °C; [R]20 ) -17.2 (c 1.27, CHCl3); H
1
D
NMR (300 MHz, CDCl3) δ 7.37-7.21 (m, 10 H), 4.63 (dt, J )
7.8, 5.2 Hz, 1 H), 4.24 (apparent t, J ) 8.3 Hz, 1 H), 4.17 (apparent
t, J ) 7.8 Hz, 1 H), 3.88 (d, J ) 13.4 Hz, 2 H), 3.46 (d, J ) 13.4
Hz, 2 H), 2.93-2.84 (m, 1 H), 1.20 (d, J ) 6.8 Hz, 3 H); 13C
NMR (75 MHz, CDCl3): δ 155.0 (C), 139.2 (2 × C), 128.8 (4 ×
CH), 128.3 (4 × CH), 127.1 (2 × CH), 79.7 (CH), 66.7 (CH2),
54.9 (2 × CH2), 53.9 (CH), 9.9 (CH3); MS (70 eV, EI) m/z (%)
J. Org. Chem, Vol. 72, No. 20, 2007 7571

Concello´n et al.
i
311 (M+, <1), 224 (20), 181 (17), 91 (100; HRMS (70 eV) calcd
for C19H21NO3 (M+) 311.1521, found 311.1550; IR (neat) 3397,
3061, 2972, 2834, 1795, 1602, 1494, 1453, 1377 cm-1; Rf ) 0.11
(hexane/EtOAc 10:1).
EI) m/z 310 (M+ - Pr, <1), 266 (100), 91 (90); HRMS (70 eV)
calcd for C19H20NO3 (M+ - Pr) 310.1443, found 310.1405; IR
i
(neat) 3381, 3029, 2960, 1807, 1494, 1454, 1369 cm-1; Rf ) 0.14
(hexane/EtOAc 10:1).
(4R)-4-[(S)-1-(Dibenzylamino)-3-methylbutyl]-1,3-dioxolan-2-
one (3b): white solid; mp ) 99 °C; [R]20D ) -35.6 (c 1.36, CHCl3);
1H NMR (400 MHz, CDCl3) δ 7.25-7.12 (m, 10 H), 4.66 (dt, J )
7.9, 5.7 Hz, 1 H), 4.17 (apparent t, J ) 8.1 Hz, 1 H), 4.05 (apparent
t, J ) 7.9 Hz, 1 H), 3.73 (d, J ) 13.1 Hz, 2 H), 3.49 (d, J ) 13.1
Hz, 2 H), 2.63 (apparent q, J ) 6.5 Hz, 1 H), 1.72-1.63 (m, 1 H),
1.49-1.40 (m, 1 H), 1.16-1.04 (m, 1 H), 0.79 (d, J ) 6.6 Hz, 3
H), 0.62 (d, J ) 6.5 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ 154.9
(C), 139.3 (2 × C), 129.1 (4 × CH), 128.3 (4 × CH), 127.1 (2 ×
CH), 78.1 (CH), 67.0 (CH2), 55.9 (CH), 55.0 (2 × CH2), 34.8 (CH2),
24.4 (CH), 22.7 (CH3), 22.4 (CH3); MS (70 eV, EI) m/z 353 (M+,
3), 267 (88), 266 (100), 210 (33), 181 (67), 131 (29); HRMS (70
eV) calcd for C22H27NO3 (M+) 353.1991, found 353.2065; IR (neat)
3408, 3028, 2957, 2868, 1798, 1495, 1454, 1376 cm-1; Rf ) 0.13
(hexane/EtOAc 10:1).
(4S)-4-[(S)-1-(Dibenzylamino)-2-phenylethyl]-1,3-dioxolan-2-
one (4c): white solid; mp ) 98 °C; [R]20D ) +22.9 (c 1.64, CHCl3);
1H NMR (300 MHz, CDCl3) δ 7.45-7.24 (m, 11 H), 7.16-7.11
(m, 4 H), 4.70 (apparent q, J ) 7.7 Hz, 1 H), 4.44 (apparent t, J )
8.4 Hz, 1 H), 3.93 (apparent t, J ) 8.2 Hz, 1 H), 3.73 (d, J ) 13.7
Hz, 2 H), 3.57 (d, J ) 13.7 Hz, 2 H), 3.21-2.99 (m, 2 H); 13C
NMR (75 MHz, CDCl3) δ 154.8 (C), 139.1 (C), 138.6 (2 × C),
129.5 (2 × CH), 128.7 (4 × CH), 128.6 (2 × CH), 128.4 (4 ×
CH), 127.4 (2 × CH), 126.6 (CH), 77.0 (CH), 68.8 (CH2), 62.2
(CH), 54.8 (2 × CH2), 32.9 (CH2); HRMS (70 eV) calcd for C25H25-
NO3 (M+) 387.1834, found 387.1819; IR (neat) 3492, 3028, 2852,
1806, 1602, 1495, 1454, 1370 cm-1; Rf ) 0.13 (hexane/EtOAc 10:
1).
General Procedure for the Synthesis of Compounds 7 and 8.
LiAlH4 (1.1 equiv, 0.2 mmol, 0.2 mL, 1 M in THF) was added to
a stirred solution of the corresponding cyclic carbonate 3 or 4 (0.2
mmol) in THF (2 mL) at -50 °C. After the mixture was stirred at
this temperature for 30 min, an aqueous saturated solution of NH4-
Cl (5 mL) was added, and the mixture was stirred for 5 min at
room temperature. Then, the aqueous phase was extracted with
diethyl ether (3 × 5 mL), and the combined organic layers were
dried over anhydrous Na2SO4, filtered, and concentrated in vacuo.
Flash column chromatography on silica gel (hexane/EtOAc 10:1)
provided pure compounds 7 or 8.
(4R)-4-[(S)-1-(Dibenzylamino)-2-phenylethyl]-1,3-dioxolan-2-
one (3c): white solid; mp ) 150 °C; [R]20 ) +17.6 (c 1.89,
D
CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.37-7.19 (m, 15 H), 4.56
(ddd, J ) 8.6, 7.1, 3.2 Hz, 1 H), 4.24 (apparent t, J ) 7.5 Hz, 1
H), 4.06 (d, J ) 13.5 Hz, 2 H), 4.02 (apparent t, J ) 8.3 Hz, 1 H),
3.56 (d, J ) 13.5 Hz, 2 H), 3.26 (dd, J ) 13.2, 3.9 Hz, 1 H), 2.97
(apparent t, J ) 12.0 Hz, 1 H), 2.81 (dt, J ) 10.8, 3.9 Hz, 1 H);
13C NMR (75 MHz, CDCl3) δ 154.9 (C), 138.8 (2 × C), 138.2
(C), 129.2 (2 × CH), 129.0 (4 × CH), 128.8 (2 × CH), 128.4 (4
× CH), 127.3 (2 × CH), 126.6 (CH), 76.8 (CH), 66.2 (CH2), 60.1
(CH), 55.7 (2 × CH2), 30.9 (CH2); MS (70 eV, EI) m/z 296 (M+
An aqueous solution of KOH (50%, 1 mL) was added to a stirred
solution of the corresponding cyclic carbonate 3 or 4 (0.2 mmol)
in MeOH (2 mL) at room temperature. The reaction was stirred
for 1 h, and H2O (5 mL) was added to the mixture, which was
stirred for additional 5 min. Then, the aqueous phase was extracted
with diethyl ether (3 × 5 mL), and the combined organic layers
were dried over anhydrous Na2SO4, filtered, and concentrated in
vacuo. Flash column chromatography on silica gel (hexane/EtOAc
10:1) provided pure compounds 7 or 8.
- Bn, 60), 91 (100); HRMS (70 eV) calcd for C18H18NO3 (M+
-
Bn) 296.1287, found 296.1300; IR (neat) 3423, 3063, 3028, 2816,
1797, 1601, 1494, 1454, 1398 cm-1; Rf ) 0.10 (hexane/EtOAc 10:
1).
(4R)-4-[(S)-2-(Benzyloxy)-1-(dibenzylamino)ethyl]-1,3-dioxolan-
2-one (3d): white solid; mp) 170 °C; [R]20 ) +15.1 (c 1.08,
CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.42-D7.23 (m, 15 H), 4.94
(dt, J ) 7.9, 5.4 Hz, 1 H), 4.53 (s, 2 H), 4.24 (apparent t, J ) 8.4
Hz, 1 H), 4.14 (apparent t, J ) 8.0 Hz, 1 H), 3.96 (d, J ) 13.4 Hz,
2 H); 3.88 (dd, J ) 9.4, 5.4 Hz, 1 H), 3.75 (dd, J ) 9.4, 7.7 Hz,
1 H), 3.61 (d, J ) 13.4 Hz, 2 H), 2.99 (dt, J ) 7.7, 5.4 Hz, 1 H);
13C NMR (75 MHz, CDCl3) δ 155.0 (C), 139.1 (2 × C), 137.4
(C), 128.9 (4 × CH), 128.5 (2 × CH), 128.4 (4 × CH), 128.0
(CH), 127.6 (2 × C), 127.3 (2 × C), 77.2 (CH), 73.6 (CH2), 67.0
(2 × CH2), 57.9 (CH); 55.6 (2 × CH2); HRMS (70 eV) calcd for
C26H27NO4 (M+) 417.1940, found 417.1931; IR (neat) 3442, 3019,
2865, 1793, 1520, 1496, 1454, 1363 cm-1; Rf ) 0.10 (hexane/
EtOAc 10:1).
(2R,3S)-3-(Dibenzylamino)butane-1,2-diol (7a): colorless oil;
1
[R]20 ) +46.7 (c 1.49, CHCl3); H NMR (300 MHz, CDCl3) δ
D
7.24-7.12 (m, 10 H), 3.72 (d, J ) 13.3 Hz, 2 H), 3.64 (dd, J )
11.7, 2.8 Hz, 1 H), 3.42 (ddd, J ) 9.6, 4.2, 2.8 Hz, 1 H), 3.27 (dd,
J ) 11.7, 4.2 Hz, 1 H), 3.23 (d, J ) 13.3 Hz, 2 H), 2.76 (dq, J )
9.6, 6.6 Hz, 1 H), 0.95 (d, J ) 6.6 Hz, 3 H); 13C NMR (75 MHz,
CDCl3) δ 138.6 (2 × C), 128.9 (4 × CH), 128.3 (4 × CH), 127.1
(2 × CH), 71.5 (CH), 63.2 (CH2), 54.1 (CH), 53.2 (2 × CH2), 8.0
(CH3); HRMS (70 eV) calcd for C17H20NO (M+ - CH2OH)
254.1545, found 254.1543; IR (neat) 3406, 3028, 2932, 1602, 1495,
1453, 1378 cm-1; Rf ) 0.27 (hexane/EtOAc 3:1).
(2R,3S)-3-(dibenzylamino)-5-methylhexane-1,2-diol (7b). See
ref 11.
(2S,3S)-3-(dibenzylamino)-5-methylhexane-1,2-diol (8b). See
ref 11.
(4S)-4-[(S)-1-(Dibenzylamino)ethyl]-1,3-dioxolan-2-one (4a):
1
white solid; mp ) 87 °C; [R]20 ) +38.9 (c 1.24, CHCl3); H
D
NMR (300 MHz, CDCl3) δ 7.26-7.14 (m, 10 H), 4.37-4.27 (m,
2 H), 3.95-3.88 (m, 1 H), 3.60 (d, J ) 13.4 Hz, 2 H), 3.35 (d, J
) 13.4 Hz, 2 H), 2.980-2.71 (m, 1 H); 1.15 (d, J ) 6.6 Hz, 3 H);
13C NMR (75 MHz, CDCl3) δ 154.9 (C), 138.7 (2 × C), 128.7 (4
× CH), 128.5 (4 × CH), 127.5 (2 × CH), 77.8 (CH), 68.9 (CH2),
56.4 (CH), 54.6 (2 × CH2), 8.7 (CH3); MS (70 eV, EI) m/z 311
(M+, <1), 91 (100); HRMS (70 eV) calcd for C19H21NO3 (M+)
311.1521, found 311.1584; IR (neat) 3453, 3028, 2976, 2841, 1085,
1494, 1453, 1380 cm-1; Rf ) 0.11 (hexane/EtOAc 10:1).
General Procedure for the Synthesis of Compounds 9 and
10. MeLi (1.1 equiv, 0.2 mmol, 0.15 mL) was added to a stirred
solution of the corresponding cyclic carbonate 3 or 4 (0.2 mmol)
in THF (2 mL) at -78 °C. After the mixture was stirred at this
temperature for 30 min, an aqueous saturated solution of NH4Cl
(5 mL) was added, and the resulting mixture was stirred at room
temperature for 5 min. Then, the aqueous phase was extracted with
diethyl ether (3 × 5 mL), and the combined organic layers were
dried over anhydrous Na2SO4, filtered, and concentrated in vacuo.
Flash column chromatography on silica gel (hexane/EtOAc 10:1)
provided pure compounds 9 or 10.
(4S)-4-[(S)-1-(Dibenzylamino)-3-methylbutyl]-1,3-dioxolan-2-
1
one (4b): colorless oil; [R]20 ) -3.1 (c 1.02, CHCl3); H NMR
D
(300 MHz, CDCl3) δ 7.35-7.25 (m, 10 H), 4.64 (apparent q, J )
7.8 Hz, 1 H), 4.45 (t, J ) 8.4 Hz, 1 H), 3.96 (t, J ) 8.4 Hz, 1 H),
3.64 (s, 4 H), 2.78 (apparent q, J ) 6.6 Hz, 1 H), 2.02-1.89 (m,
1 H), 1.80-1.71 (m, 1 H), 1.42-1.33 (m, 1 H), 0.95 (d, J ) 6.5
Hz, 3 H), 0.86 (d, J ) 6.5 Hz, 3 H); 13C NMR (50 MHz, CDCl3)
δ 155.0 (C), 138.9 (2 × C), 128.8 (4 × CH), 128.5 (4 × CH),
127.4 (2 × CH), 77.4 (CH), 68.9 (CH2), 58.1 (CH), 54.7 (2 ×
CH2), 35.7 (CH2), 24.9 (CH), 22.9 (CH3), 22.8 (CH3); MS (70 eV,
(2R,3S)-O1-Acetyl-3-(dibenzylamino)butane-1,2-diol (9a): col-
1
orless oil; [R]20 ) +45.9 (c 1.54, CHCl3); H NMR (300 MHz,
D
CDCl3) δ 7.35-7.22 (m, 10 H), 4.60 (br s, 1 H), 4.22 (dd, J )
11.7, 2.6 Hz, 1 H), 3.88 (dd, J ) 11.7, 5.4 Hz, 1 H), 3.83 (d, J )
13.1 Hz, 2 H), 3.69 (ddd, J ) 9.7, 5.4, 2.6 Hz, 1 H), 3.33 (d, J )
13.1 Hz, 2 H), 2.73 (dq, J ) 9.7, 6.8 Hz, 1 H), 1.94 (s, 3 H), 1.08
7572 J. Org. Chem., Vol. 72, No. 20, 2007

Synthesis of (4R,1′S)- or (4S,1′S)-4-(1-Aminoalkyl)-2-oxo-1,3-dioxolanes
(d, J ) 6.8 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ 171.0 (C),
138.4 (2 × C), 129.0 (4 × CH), 128.5 (4 × CH), 127.3 (2 × CH),
69.4 (CH), 65.6 (CH2), 54.2 (CH), 53.1 (2 × CH2), 20.6 (CH3),
8.2 (CH3); MS (70 eV, EI) m/z 310 (M+ - OH, 26), 231 (49), 219
(41), 132 (44), 69 (100); HRMS (70 eV) calcd for C20H24NO2 (M+
- OH) 310.1807, found 310.1775; IR (neat) 3407, 3028, 2968,
2840, 1806, 1738, 1495, 1453, 1378 cm-1; Rf ) 0.16 (hexane/
EtOAc 5:1).
327 (M+, 2), 224 (100), 181 (37); HRMS (70 eV) calcd for C20H25-
NO3 (M+) 327.1834, found 327.1824; IR (neat) 3452, 3028, 2933,
2805, 1738,1494, 1453, 1378 cm-1; Rf ) 0.11 (hexane/EtOAc 5:1).
(2S,3S)-O1-Acetyl-3-dibenzylamino-5-methylhexane-1,2-diol
(10b). See ref 13.
Acknowledgment. We thank the Ministerio de Ciencia y
Tecnolog´ıa (CTQ2004-1191/BQU) for financial support and
Euan C. Goddard for his revision of the English. J.M.C. thanks
Carmen Ferna´ndez-Flo´rez for her time. V.d.S. acknowledges
the Principado de Asturias for a contract investigation.
(2R,3S)-O1-Acetyl-3-(dibenzylamino)-5-methylhexane-1,2-
diol (9b). See ref 13.
(2S,3S)-O1-Acetyl-3-(dibenzylamino)butane-1,2-diol (10a): col-
1
orless oil; [R]20 ) +33.8 (c 1.03, CHCl3); H NMR (300 MHz,
D
CDCl3) δ 7.37-7.20 (m, 10 H), 4.42 (dd, J ) 11.4, 2.9 Hz, 1 H),
4.03 (dd, J ) 11.4, 6.6 Hz, 1 H), 3.86-3.79 (m, 1 H), 3.60 (d, J
) 13.5 Hz, 2 H), 3.40 (d, J ) 13.5 Hz, 2 H), 2.80 (apparent qt, J
) 6.8 Hz, 1 H), 1.94 (s, 3 H), 1.18 (d, J ) 6.7 Hz, 3 H); 13C NMR
(75 MHz, CDCl3) δ 171.2 (C), 138.9 (2 × C), 128.8 (4 × CH),
128.3 (4 × CH), 127.0 (2 × CH), 67.7 (CH), 65.8 (CH2), 55.9
(CH), 54.1 (2 × CH2), 25.4 (CH3), 8.3 (CH3); MS (70 eV, EI) m/z
Supporting Information Available: Full experimental proce-
dures, characterization data, and 1H and 13C NMR spectra of 3, 4,
7, 9, and 10 and X-ray crystallographic information of 3c (CIF).
This material is available free of charge via the Internet at
http://pubs.acs.org.
JO070829X
J. Org. Chem, Vol. 72, No. 20, 2007 7573