Diastereoselective alkylation of chiral 2-imidazolidinone glycolates: Asymmetric synthesis of α-hydroxy carboxylic acids

Article abstract of DOI:10.1016/j.tetasy.2005.07.036

Sodium enolates of chiral 2-imidazolidinone glycolates reacted with alkyl halides to produce α-alkylated products with high diastereoselectivities, which were readily removed by simple alkaline hydrolysis and were converted to the protected α-hydroxy carboxylic acids. The new stereogenic center was assigned the (R)-configuration by comparison with known compounds.

Full text of DOI:10.1016/j.tetasy.2005.07.036

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 2989–2992
Diastereoselective alkylation of chiral 2-imidazolidinone
glycolates: asymmetric synthesis of a-hydroxy carboxylic acids
Chong Chul Chun,a Gue-Jae Lee,a Jae Nyoung Kimb and Taek Hyeon Kima,*
aDepartment of Applied Chemistry, Chonnam National University, Gwangju 500-757, South Korea
bDepartment of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, South Korea
Received 29 April 2005; revised 21 July 2005; accepted 22 July 2005
Abstract—Sodium enolates of chiral 2-imidazolidinone glycolates reacted with alkyl halides to produce a-alkylated products with
high diastereoselectivities, which were readily removed by simple alkaline hydrolysis and were converted to the protected a-hydroxy
carboxylic acids. The new stereogenic center was assigned the (R)-configuration by comparison with known compounds.
Ó 2005 Published by Elsevier Ltd.
1. Introduction
agent lithium hydroperoxide has been used instead of
the hydroxide.7a,b
Chiral auxiliary-derived asymmetric alkylations have
been studied extensively and are now important and
general methods for asymmetric carbon–carbon bond
formation.1 The enantioselective synthesis of chiral a-
hydroxy acids has been extensively studied because of
their importance as synthetic building blocks.2 Various
methods including asymmetric dihydroxylations,3 asym-
metric enolate hydroxylation,4 and asymmetric glycolate
alkylation5 have been used to prepare a-hydroxy acids.
During our efforts to prepare various 2-imidazolidi-
nones, we previously developed 2a and 2b from L-valine
and L-phenylalanine, respectively,8,9 which contain the
structural features of similar oxazolidinones. We now
report on the utility and generality of the asymmetric
alkylation of metal enolates of 2-imidazolidinone glyco-
lates with high stereoselectivity for the preparation of a-
hydroxy carboxylic acids as oxazolidinone glycolates.
The auxiliaries are easily removed by simple alkaline
hydrolysis (NaOH), without the need for lithium hydro-
peroxide to suppress the endocyclic cleavage.
Asymmetric glycolate alkylation is a straightforward
approach because of the relative ease of changing the
alkyl groupand the protecting groupof the glycolate
hydroxyl. Chiral auxiliaries attached to the carbonyl
group, the hydroxyl group, or to both have been used
for the diastereoselective alkylation of chiral glyco-
lates. The most notable of these reports employed a
trans-2,5-disubstituted pyrrolidine,5e menthone,5g or
camphorsulfonamide,5i D-fructose,5l,m or EvansÕs
oxazolidinone5k as chiral auxiliaries. In particular, metal
enolates of N-acyl oxazolidinones, as developed by
Evans, are highly effective at controlling facial selectivity
for the preparation of homochiral a-substituted carbox-
ylic acids and their derivatives.6 However, this auxiliary
undergoes troublesome endocyclic cleavage rather than
the required exocyclic cleavage during its removal of
the auxiliary by alkaline hydrolysis.7 Moreover, to sup-
press the undesired endocyclic cleavage, the hazardous
2. Results and discussion
The 2-imidazolidinones 2a and 2b were easily prepared
in two simple steps (addition to isocyanate, and cycliza-
tion)8a starting from readily available L-valinol and L-
phenylalaninol, respectively (Scheme 1). The acylation of
2-imidazolidinones 2 with 1.0 equiv of benzyloxyacetyl
O
O
H2N
OH
TsCl, t-BuOK
THF
rt, 30 min
PhNCO
THF
rt, 5 min
PhHN
HO
NH
PhN
NH
R
2a, 61%
2b, 57%
R
R
1a, R = i -Pr 99%
1b, R = Bn 99%
*
Scheme 1.
Corresponding author. E-mail: thkim@chonnam.ac.kr
0957-4166/$ - see front matter Ó 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2005.07.036

2990
C. C. Chun et al. / Tetrahedron: Asymmetry 16 (2005) 2989–2992
chloride in the presence of 1.0 equiv of n-BuLi at 0 °C
O
O
O
BnOCH2COCl, t-BuOK
furnished the required N-benzyloxyacetyl-2-imidazolidi-
OBn
20
PhN
NH
R
PhN
N
nones in high yield (Scheme 2) {3a: 93%, ½aŠ ¼ þ17:0 (c
THF, rt, 5 min
D
20
D
4.16, CHCl3), 3b: 96%, ½aŠ ¼ þ39:0 (c 4.45, CHCl3)}.10
R
In initial experiments, the deprotonation of 3a at
À78 °C with LiHMDS and the subsequent alkylation
of the lithium enolate with benzyl bromide did not pro-
vide the required product 4a (Table 1, entry 1), instead
deacylation occurred primarily. In nearly all enolate
alkylations, the use of HMPA as an additive is believed
to increase reactivity appreciably at the expense of selec-
tivity.5j,11 To improve the reactivity of 3a with
LiHMDS, 5% HMPA was added, and as expected the
yield of 4a increased by 72%, but HPLC analysis showed
a poor diastereoselectivity of 56% de (Table 1, entry 2).
with 1.5 equiv of LDA, the yield of 4a was increased by
83% with high diastereoselectivity of 96% de (Table 1,
entry 3). Another base NaHMDS provided slightly
higher yields and proved more reactive than LiHMDS
or LDA (Table 1, entry 5). The addition, of LDA or
NaHMDS in 5% HMPA reduced the de values, and
slightly lowered yields. In most cases, reaction rates were
sluggish at À78 °C and warming to À40 to À45 °C
appeared optimal in most cases.
2a, R = i-Pr 61%
2b, R = Bn 57%
3a, 93%
3b, 96%
Scheme 2.
iodide); results are summarized in Table 2.12 a-Alkylated
products with moderate to excellent diastereoselectivity
were formed in good yields. The ratios of diastereomers
were determined by HPLC. Benzyl bromide and allyl
bromide reacted with these enolates to give the respec-
tive alkylated products in excellent yields (entries 1, 2,
4, and 5) and high de values. Alkylation with methyl
iodide, as expected, was slow and mainly afforded the
deacylation product and small amounts of the required
product (10–18%). The addition of HMPA increased
the alkylation yield from 10–18% to 72–75% and the
diastereoselective level was found to be lower (entries
3 and 6). It was of interest to find that the valine-derived
enolates were slightly more reactive and tended to give
somewhat better yields than the phenylalanine derived
auxiliaries (entries 1–3 vs entries 4–6).
The alkylations of the sodium enolates derived from 3a
and 3b with 1.5 equiv of NaHMDS were performed with
alkyl halide (benzyl bromide, allyl iodide, and methyl
The alkylation products (4a, 4b, and 4c) were hydro-
lyzed by 2 M aqueous NaOH13 in dioxane to furnish
Table 1. Diastereoselective benzylations of 2-phenyliminooxazolidine glycolate 3a
Entry
Base (equiv)
Solvent (additive)
Time (h)a
Yield (%)b
drd
1
2
3
4
5
6
LiHMDS
LiHMDS
LDA
LDA
NaHMDS
NaHMDS
THF
THF (5% HMPA)
THF
THF (5% HMPA)
THF
THF (5% HMPA)
24
4
8
4
2
0c
72
83
79
87
78
—
78:22
98:2
89:11
98:2
81:19
2
a After warming to À40 to À45 °C.
b Isolated yield after purification.
c Deacylation mainly occurred.
d Determined by HPLC (Spherisorb ODS column) after purification.
Table 2. Diastereoselective alkylations of N-acyl-2-phenyliminooxazolidines 3
Na
O
O
O
O
O
O
OBn
OBn
R'
NaHMDS
R'-X
OBn
PhN
N
PhN
N
PhN
N
THF
R
R
-78 oC, 1 h
R
3
4
Entry
Substrate
R
R0
PhCH2Br
CH2@CHCH2I
MeI
PhCH2Br
CH2@CHCH2I
MeI
Producta
Yield (%)b
drc
1
2
3d
4
5
6d
3a
3a
3a
3b
3b
3b
i-Pr
i-Pr
i-Pr
PhCH2
PhCH2
PhCH2
4a
4b
4c
4d
4e
4f
87
87
75
85
85
72
>98:2
>98:2
87:13
>98:2
>98:2
82:18
a The configuration was verified by comparison with authentic samples after auxiliary removal.
b Isolated yields after purification.
c Determined by HPLC (Spherisorb ODS column) after purification.
d 5% HMPA was added to THF.

C. C. Chun et al. / Tetrahedron: Asymmetry 16 (2005) 2989–2992
2991
H.; Ballard, C. E.; Boyle, P. D.; Wang, B. Tetrahedron
2002, 58, 7663–7679.
O
O
O
O
2M NaOH, dioxane
reflux, 30 min
OBn
PhN
NH
R
+
OBn
6. (a) Evans, D. A. Aldrichim. Acta 1982, 15, 23; (b) Evans,
D. A. In Asymmetric Synthesis; Morrison, J. D., Ed.;
Academic Press: New York, 1984; Vol. 3; (c) Ager, D. J.;
Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96, 835; (d)
Ager, D. J.; Prakash, I.; Schadd, D. R. Aldrichim. Acta
1997, 30, 3.
HO
PhN
N
R'
R'
R
R' = Bn, Me, Allyl
Scheme 3.
7. (a) Evans, D. A.; Britton, T. C.; Ellman, J. A. Tetrahedron
Lett. 1987, 28, 6141; (b) Evans, D. A.; Chapman, K. T.;
Bisaha, J. J. Am. Chem. Soc. 1988, 110, 1238; (c) Davies,
S. G.; Doisneau, G. J.-M.; Prodger, J. C.; Sanganee, H. J.
Tetrahedron Lett. 1994, 35, 2369; (d) Gibson, C. L.;
Gillon, K.; Cook, S. Tetrahedron Lett. 1998, 39, 6733; (e)
Bull, S. D.; Davies, S. G.; Jones, S.; Sanganee, H. J. J.
Chem. Soc., Perkin Trans. 1 1999, 387; (f) Davies, S. G.;
Sanganee, H. J.; Szolcsanyi, P. Tetrahedron 1999, 55, 3337.
8. (a) Kim, T. H.; Lee, G.-J. J. Org. Chem. 1999, 64, 2941–
2943; (b) Kim, T. H.; Lee, G.-J.; Cha, M.-H. Synth.
Commun. 1999, 29, 2753–2758.
the corresponding benzyl protected a-hydroxyl carbox-
ylic acids in yields of 87%, 95%, and 95%, respectively.14
The absolute configurations of these acids were assigned
(R) by comparing specific rotations with those previ-
ously reported (Scheme 3).15
3. Conclusion
In summary, the asymmetric alkylation of 2-phenyl-
iminooxazolidine glycolates can be used for the enantio-
selective synthesis of highly useful protected a-hydroxy
carboxylic acids by auxiliary removal. In addition the
2-imidazolidineone auxiliaries can be easily removed
by aqueous base, without the need for hydroperoxide,
and can be readily recovered.
9. Kim, T. H.; Lee, G.-J. Tetrahedron Lett 2000, 41, 1505–
1508.
10. General procedure for the preparation of 2-imidazolidinone
glycolates: To a stirred solution of n-BuLi (0.16 g,
1.43 mmol) and 2 (10 mmol) in anhydrous THF (20 mL)
under nitrogen at 0 °C, benzyloxyacetyl chloride (1.84 g,
10 mmol) was added dropwise. The solution was stirred
for 60 min, and then quenched with saturated ammonium
chloride, and extracted with dichloromethane. Combined
extracts were dried over magnesium sulfate, filtered, and
concentrated. Purification by flash chromatography afforded
Acknowledgement
This study was financially supported by the special
research fund of Chonnam National University in 2004.
the desired compounds 3 in good yield.
20
Compound 3a: Yield 93%; oil; ½aŠ ¼ þ17:0 (c 4.16,
D
1
CHCl3); Rf = 0.33 (n-hexane/ethyl acetate 7/3); H NMR
(CDCl3, 300 MHz) d 7.51–7.15 (m, 10H), 4.85–4.71 (m,
2H), 4.68 (s, 2H), 4.46–4.41 (m, 1H), 3.94 (t, 1H,
J = 9.5 Hz), 3.58 (dd, 1H J = 9.7, 2.6 Hz), 2.52–2.47 (m,
1H), 0.97 (d, 3H, J = 7.0), 0.84 (d, 3H, J = 7.0 Hz); 13C
NMR (CDCl3, 75 MHz) d 171.0, 153.4, 138.7, 137.5,
129.5, 128.9, 128.5, 128.3, 125.1, 119.6, 73.8, 70.5, 54.9,
44.3, 28.2, 18.5, 15.0; HRMS calcd for C21H24N2O3:
References
1. (a) Seyden-Penne, J. Chiral Auxiliaries and Ligands for
Asymmetric Synthesis; Wiley: New York, 1995; (b) Gaw-
ley, R. E.; Aube, J. Principles of Asymmetric Synthesis. In
Baldwin, J. E., Magnus, P. D., Eds.; Tetrahedron Organic
Chemistry Series; Elsevier Press: Oxford, 1996; Vol. 14.
2. (a) Coppola, G. M.; Schuster, H. F. Hydroxy Acids in
Enantioselective Synthesis; Weinheim: VCH, 1997; (b)
Hannession, S. Total Synthesis of Natural Products. The
Chiron Approach; New York: Pergamon Press, 1983;
Chapter 2.
352.1787. Found 352.1784. Compound 3b: Yield 96%; oil;
20
D
½aŠ ¼ þ39:0 (c 4.45, CHCl3); Rf = 0.4 (n-hexane/ethyl
acetate 7/3); 1H NMR (CDCl3, 300 MHz) d 7.42–7.12 (m,
15), 4.86–4.85 (m, 2H), 4.72 (s, 2H), 4.72–4.65 (m, 1H),
3.88 (t, 1H, J = 9.3 Hz), 3.55 (dd, 1H, J = 9.7, 2.1 Hz),
3.33 (dd, 1H, J = 13.3, 3.1 Hz), 2.82 (dd, 1H, J = 13.3,
6.2 Hz); 13C NMR (CDCl3, 75 MHz) 170.4, 152.3, 138.2,
137.5, 135.7, 129.4, 128.9, 128.8, 128.4, 127.9, 127.8, 127.1,
124.6, 119.1, 73.3, 70.0, 51.1, 47.1, 38.4; HRMS calcd for
C25H24N2O3: 400.1787. Found 400.1785.
3. Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B.
Chem. Rev. 1994, 94, 2483–2547.
4. Evans, D. A.; Morrissey, M. M.; Dorow, R. L. J. Am.
Chem. Soc. 1985, 107, 4346–4348.
5. (a) Frater, G. Y.; Muller, U.; Gunther, W. Tetrahedron
Lett. 1981, 22, 4221–4224; (b) dÕAngelo, J.; Pages, O.;
Maddaluno, J.; Dumas, F.; Revial, G. Tetrahedron Lett.
1983, 24, 5869–5872; (c) Helmchen, G.; Wierzchowski, R.
Angew. Chem., Int. Ed. Engl. 1984, 23, 60–61; (d) Kelly, T.
R.; Arvanitis, A. Tetrahedron Lett. 1984, 25, 39–42; (e)
Enomoto, M.; Ito, Y.; Katsuki, T.; Yamaguchi, M.
Tetrahedron Lett. 1985, 25, 1343–1344; (f) Ludwig, J.
W.; Newcomb, M.; Bergbreiter, D. E. Tetrahedron Lett.
1986, 26, 2731–2734; (g) Pearson, W. H.; Cheng, M.-C. J.
Org. Chem. 1986, 51, 3746–3748; (h) Cardillo, G.; Orena,
M.; Romero, M.; Sandri, S. Tetrahedron 1989, 45, 1501–
1508; (i) Chang, J.-W.; Jang, D.-P.; Uang, B.-J.; Liao,
F.-L.; Wang, S.-L. Org. Lett. 1999, 1, 2061–2063; (j) Jung,
J. E.; Ho, H.; Kim, H.-D. Tetrahedron Lett. 2000, 41,
1793–1796; (k) Crimmins, M.; Emmitte, K. A.; Katz, J. D.
Org. Lett. 2000, 2, 2165–2167; (l) Yu, H.; Ballard, E.;
Wang, B. Tetrahedron Lett. 2001, 42, 1835–1838; (m) Yu,
11. Kishida, M.; Eguchi, T.; Kakinuma, K. Tetrahedron Lett.
1996, 37, 2061–2062.
12. Typical procedure for the alkylation of 2-imidazolidinone
glycolates: A solution of 2-imidazolidinone glycolate
(1 mmol) in anhydrous THF (4 mL) was added to a dry
round-bottomed flask under nitrogen and cooled to
À78 °C. A solution of sodium bistrimethylsilylamide
(1.0 M in THF, 1.5 mmol) was then added dropwise over
5 min, stirred at À78 °C for 60 min, and then a solution of
benzyl bromide (3 mmol or 5 mmol) in THF (2 mL) was
added dropwise. This solution was stirred at À78 °C for
60 min, allowed to warm to À40 to À45 °C, and stirred for
a further 2 h. The reaction was monitored by TLC. After
the reaction had gone to completion, saturated aqueous
ammonium chloride was added. It was then warmed
to room temperature and extracted with dichloro-
methane. Combined extracts were dried over magnesium
sulfate, filtered, and concentrated. Purification by flash

2992
C. C. Chun et al. / Tetrahedron: Asymmetry 16 (2005) 2989–2992
chromatography (hexane/EtOAc 7:3) afforded the alkyl-
ation product 4.
51.2, 46.8, 39.5, 38.4; HRMS calcd for C32H30N2O3:
490.2256. Found 490.2250.
20
20
Compound 4a: Yield 87%; oil; ½aŠ ¼ þ35:1 (c 1.49,
Compound 4e: Yield 85%; oil; ½aŠ ¼ þ28:6 (c 0.71,
D
D
CHCl3); 1H NMR (CDCl3, 300 MHz) d 7.56–7.11 (m,
15H), 5.47 (dd, 1H, J = 9.3, 3.3 Hz), 4.52 (d, 1H,
J = 11.7 Hz), 4.42–4.36 (m, 1H), 4.34 (d, 1H, J =
11.7 Hz), 3.86 (t, 1H, J = 9.6 Hz), 3.54 (dd, 1H, J = 9.6,
2.7 Hz), 3.27 (dd, 1H, J = 13.6, 3.3 Hz), 2.96 (dd, 1H,
J = 13.6, 9.3 Hz), 2.41–2.27 (m, 1H), 0.94 (d, 3H,
J = 6.9 Hz), 0.76 (d, 3H, J = 6.9 Hz); 13C NMR (CDCl3,
75 MHz) 173.0, 152.6, 138.4, 137.8, 137.8, 129.8, 129.1,
128.1, 128.0, 127.9, 127.4, 126.4, 124.7, 119.4, 79.1, 72.6,
54.4, 43.7, 39.9, 28.9, 17.9, 14.7; HRMS calcd for
CHCl3); 1H NMR (CDCl3, 300 MHz) d 7.39–7.24 (m,
15H), 6.05–5.97 (m, 1H), 5.31 (dd, 1H, J = 7.1, 4.5 Hz),
5.24–5.12 (m, 2H), 4.65 (d, 1H, J = 11.6 Hz), 4.64–4.61
(m, 1H), 4.51 (d, 1H, J = 11.6 Hz), 3.80 (t, 1H,
J = 9.3 Hz), 3.55 (dd, 1H, J = 9.6, 2.3 Hz), 3.28 (dd, 1H,
J = 13.3, 3.2 Hz), 2.75–2.61 (m, 3H); 13C NMR (CDCl3,
75 MHz) 172.6, 151.9, 138.4, 137.9, 135.8, 133.6, 129.4,
129.0, 128.8, 128.2, 128.1, 127.2, 124.7, 119.3, 117.8, 77.3,
72.4, 51.8, 46.7 38.5, 37.5; HRMS calcd for C28H28N2O3:
440.2100. Found 440.2104.
20
D
C28H30N2O3: 442.2256. Found 442.2255.
Compound 4f: Yield 72%; white solid; ½aŠ ¼ þ48:2 (c
20
D
Compound 4b: Yield 87%; oil; ½aŠ ¼ þ47:0 (c 5.57,
0.50, CHCl3); 1H NMR (CDCl3,300 MHz) d 7.38–7.14
(m, 15H), 5.29 (q, 1H, J = 6.6 Hz), 4.68–4.66 (m, 1H), 4.65
(d, 1H, J = 11.4 Hz), 4.47 (d, 1H, J = 11.4 Hz), 3.87 (t,
1H, J = 9.4 Hz), 3.58 (dd, 1H, J = 9.6, 2.3 Hz), 3.25 (dd,
1H, J = 13.4, 3.2 Hz), 2.82 (dd, 1H, J = 13.4, 9.0 Hz), 1.58
(d, 3H, J = 6.6 Hz); 13C NMR (CDCl3, 75 MHz) 173.9,
151.9, 138.4, 137.9, 135.7, 129.5, 129.0, 128.8, 128.3,
128.1, 127.7, 127.2, 124.8, 119.4, 74.3, 72.1, 51.2, 46.9,
38.5, 19.0; HRMS calcd for C26H26N2O3: 414.1943.
Found 414.1950.
CHCl3); 1H NMR (CDCl3, 300 MHz) d 7.55–7.26 (m,
10H), 6.05–5.91 (m, 1H), 5.36 (dd, 1H, J = 7.2, 4.4 Hz)
5.22–5.09 (m, 2H), 4.62 (d, 1H, J = 11.6 Hz), 4.47 (d, 1H,
J = 11.6 Hz), 4.43–4.37 (m, 1H), 3.86 (t, 1H, J = 9.5 Hz),
3.55 (dd, 1H, J = 9.6, 2.6 Hz), 2.75–2.69 (m, 1H), 2.65–
2.57 (m, 1H), 2.39–2.33 (m, 1H), 0.94 (d, 3H, J = 7.0 Hz),
0.83 (d, 3H, J = 6.9 Hz); 13C NMR (CDCl3, 75 MHz) d
172.8, 152.5, 138.4, 137.9, 133.6, 129.1, 128.2, 128.1, 127.6,
124.7, 119.3, 117.7, 77.5, 72.4, 54.3, 43.5, 37.9, 28.9,
17.9, 14.7; HRMS calcd for C24H28N2O3: 392.2100.
13. Prasad et al. reported that chiral N-acylated 2-imidazol-
idinones have been demonstrated to undergo highly
diastereoselective benzylations and methylations via their
sodium enolates and the chiral auxiliaries can be readily
recycled with refluxing 2 M NaOH/dioxane (1:1) (30 min)
without racemization; see: Konigsberger, K.; Prasad, K.;
Repic, O.; Blacklock, T. J. Tetrahedron: Asymmetry 1997,
8, 2347–2354.
Found 392.2104.
20
D
Compound 4c: Yield 75%; white solid; ½aŠ ¼ þ39:0 (c
1
0.73, CHCl3); H NMR (CDCl3, 300 MHz) d 7.56–7.18
(m, 10H), 5.33 (q, 1H, J = 6.6 Hz), 4.62 (d, 1H,
J = 11.3 Hz), 4.48 (d, 1H, J = 11.3 Hz), 4.48–4.43 (m,
1H), 3.91 (t, 1H, J = 9.5 Hz), 3.58 (dd, 1H, J = 9.6,
2.8 Hz), 2.44–2.38 (m, 1H), 1.57 (d, 3H, J = 6.6 Hz), 0.96
(d, 1H, J = 7.0 Hz), 0.85 (d, 3H, J = 6.9); 13C NMR
(CDCl3, 75 MHz) d 174.1, 152.5, 138.4, 137.9, 129.1,
128.3, 128.1, 127.6, 124.6, 119.2, 74.4, 72.1, 54.3, 43.7,
28.9, 19.4, 17.9, 14.7; HRMS calcd for C22H26N2O3:
14. The crude auxiliary was recovered by extracting the
reaction mixture with CH2Cl2 and purified by column
chromatography in 87% yield. The required carboxylic
acid was isolated almost quantitatively by extracting with
EtOAc after acidifying the aqueous layer to pH 2. Specific
366.1943. Found 366.1938.
20
D
19
D
25
D
Compound 4d: Yield 82%; oil; ½aŠ ¼ þ32:0 (c 2.80,
rotation: 4a: ½aŠ ¼ þ76:1 (c 0.73, EtOH), lit.15a ½aŠ
¼
19
D
CHCl3); 1H NMR (CDCl3, 300 MHz) d 7.46–7.12 (m,
20H), 5.44 (dd, 2H, J = 9.2, 3.5 Hz), 4.66–4.60 (m, 1H),
4.55 (d, 1H, J = 11.9 Hz), 4.38 (d, 1H, J = 11.9 Hz), 3.82
(t, 1H, J = 9.3 Hz), 3.53 (dd, 1H, J = 9.5, 2.3 Hz), 3.29
(dd, 1H, J = 13.4, 3.5 Hz), 3.18 (dd, 1H, J = 13.4, 3.2 Hz),
3.02 (dd, 1H, J = 13.4, 9.2 Hz), 2.71 (dd, 1H, J = 13.4,
9.1 Hz); 13C NMR (CDCl3, 75 MHz) 172.8, 151.9, 138.3,
137.8, 137.7, 135.7, 129.9, 129.4, 129.0, 128.7, 128.1, 128.0,
127.8, 127.4, 127.1, 126.4, 124.7, 119.5, 78.9, 72.6, 60.3,
þ79:1 (c 2.37, EtOH); 4b: ½aŠ ¼ þ53:0 (c 0.81, EtOH),
18
19
lit.15b ½aŠ ¼ þ54:0 (c 2.3, benzene); 4c: ½aŠ ¼ þ97:0 (c
D
D
0.71, EtOH).
15. For (2R)-2-benzyloxy-3-phenylpropionic acid, see: (a)
Siraja, V.; Deshmukh, A. R. A. S.; Puranik, V. G.;
Bhawal, B. M. Tetrahedron: Asymmetry 1996, 7, 2733–
2738; For (2R)-2-benzyloxypropionic acid, see: (b) Nak-
ata, M.; Arai, M.; Tomooka, K.; Ohsawa, N.; Kinoshita,
M. Bull. Chem. Soc. Jpn. 1989, 62, 2618–2635.