5,5-Dimethyl-2-phenylamino-2-oxazoline as an effective chiral auxiliary for asymmetric alkylations

Article abstract of DOI:10.1016/j.tetlet.2007.09.001

The novel chiral auxiliaries, 5,5-diphenyl-2-phenylamino-2-oxazoline and 5,5-dimethyl-2-phenylamino-2-oxazoline, were prepared from l-valine methyl ester. The 5,5-dimethyl compound was shown to be a particularly effective chiral auxiliary for asymmetric alkylation affording high yields and diastereoselectivities.

Full text of DOI:10.1016/j.tetlet.2007.09.001

Tetrahedron Letters 48 (2007) 7834–7837
5,5-Dimethyl-2-phenylamino-2-oxazoline as an effective
chiral auxiliary for asymmetric alkylations
Thanh Nguyen Le,a Quynh Pham Bao Nguyen,a Jae Nyoung Kimb and
Taek Hyeon Kima,*
aDepartment of Applied Chemistry and Center for Functional Nano Fine Chemicals, College of Engineering,
Chonnam National University, Gwangju 500-757, Republic of Korea
bDepartment of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
Received 19 July 2007; revised 30 August 2007; accepted 3 September 2007
Available online 5 September 2007
Abstract—The novel chiral auxiliaries, 5,5-diphenyl-2-phenylamino-2-oxazoline and 5,5-dimethyl-2-phenylamino-2-oxazoline, were
prepared from L-valine methyl ester. The 5,5-dimethyl compound was shown to be a particularly effective chiral auxiliary for asym-
metric alkylation affording high yields and diastereoselectivities.
Ó 2007 Published by Elsevier Ltd.
1. Introduction
Recently, we documented the asymmetric alkylation of
N-acyl-2-phenylimino-2-oxazolidine with as a high yield
and diastereoselectivity as the chiral 2-oxazolidinones.7
We expected that the introduction of dialkyl or diaryl
groups at the 5-C position of our auxiliaries would have
a beneficial effect on the enolate chemistry and diastereo-
selectivity, impacting the conformation of the stereocon-
trolling group at 4-C. We herein report the synthesis of
the novel chiral auxiliaries, 5,5-diphenyl and 5,5-di-
methyl-2-phenylamino-2-oxazolines, and the asymmetric
alkylations of their N-acyl derivatives.
Chiral auxiliary-derived asymmetric alkylations have
been extensively studied and are now important and
general methods for asymmetric carbon–carbon bond
formation.1 The asymmetric alkylations of the enolates
of N-acyloxazolidinones 1, developed by Evans, are
widely used for the preparation of enantiopure a-sub-
stituted carboxylic acids and their derivatives.2
However, the removal of Evans’ auxiliaries with alkali
lead to undesired endocyclic cleavage rather than the
required exocyclic cleavage if the N-acyl fragment is
sterically demanding. To suppress the troublesome
endocyclic hydrolysis, hazardous lithium hydroperoxide
has been used in place of the hydroxide.3 Davies et al.
addressed the removal problem of Evans’ auxiliaries
by the introduction of auxiliaries 2 with dimethyl groups
at 5-C in chiral 2-oxazolidinones.4 Dimethyl substitu-
ents have dual functions, sterically blocking nucleophilic
attack to 2-oxazolidinone carbonyl and in addition serv-
ing to direct the conformation of the stereocontrolling
group at 4-C. Therefore, Davies’ auxiliaries do not suffer
from the undesired endocyclic cleavage and give good to
excellent diastereoselectivities in alkylation reactions.4a–c
Later, Gibson and Seebach modified and independently
reported the asymmetric alkylations of N-acyl-5,5-di-
aryl-2-oxazolidinones 3.5,6
2. Results and discussion
The 2-phenylamino-2-oxazolines 6a–b were readily pre-
pared in two steps from the appropriate 1,2-amino-
alcohols 4a–b, which were derived from commercially
available valine methyl ester hydrochloride.6b,8 The
reaction of the aminoalcohols with phenyl isothio-
cyanate afforded the N-(2-hydroxyethyl)thioureas 5a–b
in good yield, and the cyclization of the thioureas to
the 2-phenylamino-2-oxazolines by a one-pot reaction
using p-TsCl and NaOH yielded the chiral auxiliaries
6a–b (Scheme 1).9
We first studied the alkylation of their propanoic acid
derivatives. N-Acylations of the chiral auxiliaries 6a–b
were carried out by deprotonation with t-BuOK,
followed by treatment with propionyl chlorides to afford
the regiocontrolled N-endo products 7a–b (Scheme 2).7
*
Corresponding author. Tel.: +82 62 530 1891; fax: +82 62 530
1889; e-mail: thkim@chonnam.ac.kr
0040-4039/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2007.09.001

T. N. Le et al. / Tetrahedron Letters 48 (2007) 7834–7837
7835
O
1, R1 = PhCH2, Me2CH, or Me3C, R2 = H Evans' auxiliaries
2, R1 = PhCH2, Me2CH, Me, or Ph, R2 = Me Davies' auxiliaries
NH
R1
O
R2
3, R1 = Me2CH, R2 = Ph, 4-MeC6H4, or 2-naphthyl Gibson's & Seebach's auxiliaries
R2
S
NPh
TsCl, NaOH
THF
HO
R
R
NH2
Me
PhNCS
THF
PhHN
HO
NH
O
NH
R
R
R
R
Me
6a, 99%
6b, 99%
5a, 99%
5b, 85%
4a, R = Ph
4b, R = Me
Scheme 1. Synthesis of chiral auxiliaries.
tion with ethyl iodide afforded product 8c in higher yield
(75%), as compared with the 55% obtained for the
unsubstituted auxiliary,7 but required 4 equiv of base
to complete the reaction (entry 3).
NPh
NPh
N
O
t
-BuOK
R1
O
NH
O
R1CH2COCl
THF
R
R
R
R
6a, R= Ph
6b, R= Me
7a, R=Ph, R1=Me, 72%
7b, R=Me, R1=Me, 63%
7c, R=Me, R1=Ph, 50%
7d, R=Me, R1=Bn, 64%
On the other hand, the 5,5-dimethyl-2-phenylamino-2-
oxazoline (6b) was shown to have greater potential as
a chiral auxiliary for asymmetric alkylations. The
alkylation of 7b with benzyl bromide and allyl bromide
afforded the products 8d–e in quantitative yields with
excellent diastereomeric excess (de) (entries 4 and 5).11
The ethylation reaction also furnished product 8f with
a high yield of 88% (entry 6). In addition, the lithium
enolate of 7b reacted with the even less reactive n-PrI
to give product 8g in moderate yield (61%, entry 7).
These results show that the 5,5-dimethyl groups of 7b
play an important role in controlling the stereoselec-
tivity, in a similar manner to that observed with the
Scheme 2. N-Acylation reactions.
Asymmetric alkylations were performed using 7a–b.10
Lithium enolates were formed by treating 7a–b with
LiHMDS (2 equiv) at ꢀ78 °C for 30 min and the subse-
quent addition of the alkyl halide (3–5 equiv) led to the
formation of the corresponding a-alkylated products in
excellent diastereoselectivities (Scheme 3 and Table 1).
The alkylation reaction with benzyl bromide and allyl
bromide using the 5,5-diphenyl substituted compound
7a gave the required products in 72–75% yields (entries
1 and 2), which are slightly lower than those obtained
using the unsubstituted auxiliary (82–88%).7 The reac-
chiral
5,5-disubstituted-2-oxazolidinones.4
5,5-Di-
methyl-2-phenylamino-2-oxazoline 7b was shown to be
the most effective auxiliary for asymmetric alkylation
in our 2-phenylamino-2-oxazoline series.
We next investigated the alkylation reaction of other
N-acyl-5,5-dimethyl-2-phenyliminooxazolidines. Auxil-
iary 6b was acylated with phenylacetyl chloride and
hydrocinnamoyl chloride in the presence of t-BuOK to
give compounds 7c and 7d, respectively (Scheme 2).
The formation of the enolate was achieved with
LiHMDS, followed by treatment with methyl iodide to
give products 8h–i in high yields (74% and 90%, respec-
tively) and both with an excellent de of 99%.12 In the
Li
NPh
N
NPh
N
O
O
PhN
O
O
LiHMDS
THF
R2X
R1
R1
R1
O
O
N
R2
R
R
-78 ºC to rt
R
R
R
-78 ºC for 30 min
R
8a-i
7
Scheme 3. Alkylation of N-acyl 2-phenylimino-2-oxazolidines.
Table 1. Diastereoselective alkylation of N-acyl 2-phenylimino-2-oxazolidines 7a–d
Entry
Substrate
R
R1
R2X
Producta
Yieldb (%)
dec (%)
1
2
3
4
5
6
7
8
9
7a
7a
7a
7b
7b
7b
7b
7c
7d
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
C6H5CH2Br
CH2@CHCH2Br
CH3CH2I
C6H5CH2Br
CH2@CHCH2Br
CH3CH2I
CH3CH2CH2I
CH3I
CH3I
8a
8b
8c
8d
8e
8f
75
72
75
99
99
88
61
74
90
>99
96
>99
>99
>99
>99
>99
>99
>99
8g
8h
8i
Bn
a The configuration as verified by correlation with authentic sample after removal of the chiral auxiliary.
b Isolated yield after purification.
c Determined by HPLC (Spherisorb ODS column).

7836
T. N. Le et al. / Tetrahedron Letters 48 (2007) 7834–7837
Ager, D. J.; Prakash, I.; Schaad, D. R. Aldrichim. Acta
NPh
NPh
N
O
O
1997, 30, 3.
R1
R1
2M NaOH
O
O
NH
HO
3. (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.
4. (a) Davies, S. G.; Sanganee, H. J. Tetrahedron: Asymmetry
1995, 6, 671; (b) Bull, S. D.; Davies, S. G.; Jones, S.;
Sanganee, H. J. J. Chem. Soc., Perkin Trans. 1 1999, 387;
(c) Bull, S. D.; Davies, S. G.; Key, M.-S.; Nicholson, R.
L.; Savory, E. D. Chem. Commun. 2000, 18, 1721; (d) Bull,
S. D.; Davies, S. G.; Garner, A. C.; Kruchinin, D.; Key,
M.-S.; Roberts, P. M.; Savory, E. D.; Smith, A. D.;
Thomson, J. E. Org. Biomol. Chem. 2006, 4, 2945.
5. Hintermann, T.; Seebach, D. Helv. Chim. Acta 1998, 81,
2093.
R2
Dioxane
reflux for 1 h
R
R
R2
R
R
8a, R= Ph, R1= Me, R2 =Bn
8b, R= Ph, R1= Me, R2 =Allyl
8d, R= Me, R1= Me, R2 =Bn
8i, R= Me, R1 = Bn, R2 = Me
9a, 74%
9b, 88%
9a, 82%
9c, 85%
6a, 88%
6a, 99%
6b, 98%
6b, 97%
Scheme 4. Hydrolysis and recovery of chiral auxiliaries.
case of 7d, 4 equiv of base was employed to force the
reaction to completion. These high diastereoselectivities
might be due to the conformational control of the
stereodirecting isopropyl group depending on the
dimethyl group at 5-C as proposed by Davies’ group.4c
6. (a) Gibson, C. L.; Gillon, K.; Cook, S. Tetrahedron Lett.
1998, 39, 6733; (b) Alexander, K.; Cook, S.; Gibson, C. L.;
Kennedy, A. R. J. Chem. Soc., Perkin Trans. 1 2001, 13,
1538.
7. Lee, G. J.; Kim, T. H.; Kim, J. N.; Lee, U. Tetrahedron:
Asymmetry 2002, 13, 9.
The alkylated products 8 were hydrolyzed by 2 M
sodium hydroxide in dioxane to furnish the correspond-
ing alkylated carboxylic acids 9a–c (74–88%) and the
recovered chiral auxiliaries 6a–b (88–99%) (Scheme 4).
As expected, no products resulting from endocyclic
cleavage were observed in the cleavage reaction. Herein,
compound 8d (R = Me, R1 = Me, R2 = Ph) with the
dimethyl group also gave a better yield of both the
recovered chiral auxiliary and chiral acid than the corre-
sponding diphenyl substituted compound 8a (R = Ph,
R1 = Me, R2 = Ph) (Scheme 3). The absolute configura-
tions and enatiomeric purity of acids 9a–c were deter-
mined by comparing the measured optical rotations
with the known values.13
8. (a) Denmark, S. E.; Stavenger, R. A.; Faucher, A.-M.;
Edwards, J. P. J. Org. Chem. 1997, 62, 3375; (b) Na, H.-S.;
Kim, T. H. J. Korean Chem. Soc. 2003, 47, 671; (c) Ortiz,
A.; Quintero, L.; Hernandez, H.; Maldonado, S.; Men-
doza, G.; Bernes, S. Tetrahedron Lett. 2003, 44, 1129.
9. Kim, T. H.; Lee, N.; Lee, G.-J.; Kim, J. N. Tetrahedron
2001, 57, 7137.
10. General procedure for asymmetric alkylation of N-acyl 5,5-
disubstituted 2-phenylimino-2-oxazolidines. To
a
dry
round-bottomed flask under nitrogen was added com-
pound 7 (0.1 g) in anhydrous THF (4 mL). The solution
was cooled to ꢀ78 °C. A solution of lithium bis(tri-
methylsilylamide) (LiHMDS) in THF (1.0 M, 2–4 equiv)
was added dropwise, and the solution was allowed to stir
for 30 min. The mixture was treated with halide (3–
8 equiv). After stirring for 30 min at ꢀ78 °C and 1 h at
0 °C, the reaction mixture was quenched with saturated
ammonium chloride (4 mL) and water (20 mL) and
extracted with ether. The combined extracts were dried
over magnesium sulfate, filtered, and concentrated. HPLC
analysis of the crude product revealed the isomer ratios.
Purification by flash chromatography (hexane/EtOAc 8:2)
afforded the major diastereomer 8.
In summary, we have developed a new chiral auxiliary,
5,5-dimethyl-2-phenylamino-2-oxazolidine, which has
great potential for asymmetric alkylations. The alkyl-
ated products were obtained in high yields with excellent
diastereoselectivities. The chiral auxiliary was easily
recovered by hydrolysis with sodium hydroxide afford-
ing the chiral a-alkylated carboxylic acids.
20
Compound 8a: Yield 75%; oil; ½aꢁD +21.8 (c 0.73, CHCl3);
Rf = 0.5 (ethyl acetate/hexane 1:4); 1H NMR (CDCl3) d
7.39–7.14 (20H, m), 5.50 (1H, d, J = 3.3 Hz), 4.41–4.44
(m, 1H), 3.30 (1H, dd, J = 10.4 Hz, 6.3 Hz), 2.58 (1H, dd,
J = 10.4 Hz, 6.3 Hz), 1.96–1.91 (1H, m), 0.81 (3H, d,
J = 6.9 Hz), 0.76 (3H, d, J = 6.8 Hz), 0.73 (3H, d,
J = 6.9 Hz); 13C NMR (CDCl3) d 176.4, 145.7, 145.4,
142.6, 139.8, 138.6, 129.2, 128.7, 128.6, 128.2, 128.1, 128.1,
127.6, 125.9, 125.7, 125.4, 123.5, 122.8, 89.9, 64.2, 39.5,
38.3, 29.6, 21.5, 16.4, 15.8.
Acknowledgment
This work was supported by the Basic Research Pro-
gram of the Korean Science and Engineering Founda-
tion (Grant No. R05-2004-000-11207-0) (now
controlled under the authority of the Korea Research
Foundation). The spectroscopic data were obtained
from the Korea Basic Science Institute, Gwangju
branch.
20
Compound 8b: Yield 72%; oil; ½aꢁD +10.8 (c 0.3, CHCl3);
Rf = 0.5 (ethyl acetate/hexane 1:4); 1H NMR (CDCl3) d
7.41–7.13 (15H, m), 5.85–5.79 (m, 1H), 5.50 (1H, d,
J = 3.3 Hz), 5.13–4.99 (m, 2H), 4.20–4.08 (m, 1H), 2.65–
2.60 (m, 1H), 2.18–2.04 (m, 1H), 1.99–1.95 (1H, m), 0.90
(3H, d, J = 6.9 Hz), 0.84 (3H, d, J = 6.8 Hz), 0.74 (3H, d,
J = 6.9 Hz); 13C NMR (CDCl3) d 176.4, 145.7, 145.4,
142.7, 138.7, 136.2, 129.2, 128.7, 128.7, 128.3, 128.2, 127.6,
125.8, 125.5, 123.5, 122.8, 116.4, 90.0, 64.3, 37.7, 36.3,
29.7, 21.6, 16.6, 16.0.
References and notes
1. (a) Seyden-Penne, J. Chiral Auxiliaries and Ligands in
Asymmetric Synthesis; Wiley: New York, 1995; (b) Gawley,
R. E.; Aube, J. Principles of Asymmetric Synthesis. In
Tetrahedron Organic Chemistry Series; Baldwin, J. E.,
Magnus, P. D., Eds.; Elsevier Press: Oxford, 1996; Vol. 14.
2. (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)
Compound 8c: Yield 75%; white solid; mp 116–118 °C;
20
½aꢁD +6.3 (c 3.4, CHCl3); Rf = 0.5 (ethyl acetate/hexane
1:4); 1H NMR (CDCl3) d 7.41–7.10 (15H, m), 5.50 (1H, d,
J = 3.3 Hz), 4.00–3.93 (m, 1H), 2.00–1.91 (m, 1H), 1.88–
1.82 (m, 1H), 1.45–1.36 (1H, m), 0.95 (3H, d, J = 6.9 Hz),

T. N. Le et al. / Tetrahedron Letters 48 (2007) 7834–7837
7837
0.91 (3H, d, J = 6.9 Hz), 0.85 (3H, d, J = 6.8 Hz), 0.72
(3H, d, J = 6.9 Hz); 13C NMR (CDCl3) d 177.1, 145.7,
145.5, 142.8, 138.7, 128.7, 128.6, 128.2, 128.1, 127.6, 125.8,
125.4, 123.5, 122.8, 89.9, 64.3, 38.2, 29.6, 26.7, 21.7, 16.6,
16.0, 11.8.
178.0, 146.4, 145.9, 128.5, 123.2, 123.0, 83.2, 65.9, 36.7,
36.2, 29.6, 28.3, 21.7, 21.3, 20.4, 17.0, 16.7, 14.1.
Compound 8h: Yield 75%; oil; ½aꢁ2D0 +108.8 (c 0.67, CHCl3);
Rf = 0.5 (ethyl acetate/hexane 1:4); 1H NMR (CDCl3) d
7.32–6.88 (10H, m), 5.65 (1H, q, J = 6.7 Hz), 4.30 (1H, d,
J = 3.2 Hz), 2.14–2.07 (1H, m), 1.56 (3H, d, J = 6.7 Hz),
1.34 (3H, s), 1.10 (3H, d, J = 6.7 Hz), 1.02 (3H, d,
J = 6.8 Hz), 0.86 (3H, s); 13C NMR (CDCl3) d 174.8,
146.9, 145.8, 141.3, 129.1, 128.5, 128.4, 128.3, 126.8, 123.2,
122.7, 83.6, 67.0, 42.9, 29.7, 27.8, 21.7, 21.3, 19.5, 17.0.
20
Compound 8d: Yield 99%; oil; ½aꢁD +126.0 (c 0.4, CHCl3);
Rf = 0.5 (ethyl acetate/hexane 1:4); 1H NMR (CDCl3) d
7.34–7.07 (10H, m), 4.70 (1H, m), 4.30 (1H, d, J = 3.2 Hz),
3.39 (1H, dd, J = 13.1 Hz, 6.1 Hz), 2.60 (1H, dd,
J = 13.1 Hz, 8.8 Hz), 2.10–2.05 (1H, m), 1.45 (3H, s),
1.33 (3H, s), 1.12 (3H, d, J = 6.7 Hz), 0.92 (3H, d,
J = 6.8 Hz), 0.90 (3H, d, J = 6.7 Hz); 13C NMR (CDCl3) d
177.1, 146.5, 145.9, 129.3, 128.6, 128.1, 126.0, 123.2, 123.0,
83.3, 65.9, 40.0, 38.7, 29.7, 28.3, 21.5, 21.3, 16.8, 16.1.
20
Compound 8i: Yield 90%; oil; ½aꢁD +70.1 (c 0.34, CHCl3);
Rf = 0.5 (ethyl acetate/hexane 1:4); 1H NMR (CDCl3) d
7.32–7.00 (10H, m), 4.86–4.79 (1H, m), 4.11 (1H, d,
J = 3.2 Hz), 3.07 (1H, dd, J = 13.3 Hz, 9.0 Hz), 2.60 (1H,
dd, J = 13.3 Hz, 6.0 Hz), 2.10–2.04 (1H, m), 1.35 (3H, s),
1.32 (3H, d, J = 6.7 Hz), 1.03 (3H, d, J = 6.7 Hz), 1.00
(3H, d, J = 6.7 Hz), 0.83 (3H, s); 13C NMR (CDCl3) d
177.0, 146.6, 146.0, 140.1, 129.0, 128.5, 128.2, 126.0, 123.2,
122.8, 83.3, 65.8, 39.8, 38.7, 29.6, 27.4, 21.6, 21.2, 18.3,
17.0.
20
Compound 8e: Yield 99%; oil; ½aꢁD +119.0 (c 0.65,
CHCl3); Rf = 0.5 (ethyl acetate/hexane 1:4); 1H NMR
(CDCl3) d 7.31–7.25 (2H, m), 7.08–7.02 (3H, m), 5.96–5.82
(m, 1H), 5.16–5.02 (m, 2H), 4.41–4.35 (m, 1H), 4.29 (1H,
d, J = 3.1 Hz), 2.73–2.64 (m, 1H), 2.27–2.15 (m, 1H),
2.16–2.07 (1H, m), 1.46 (3H, s), 1.33 (3H, s), 1.17 (3H, d,
J = 6.8 Hz), 1.03 (3H, d, J = 6.7 Hz), 0.99 (3H, d,
J = 6.9 Hz); 13C NMR (CDCl3) d 177.0, 146.4, 145.8,
136.1, 128.5, 123.2, 123.0, 116.4, 83.3, 65.9, 38.2, 36.6,
29.7, 28.3, 21.6, 21.2, 17.0, 16.2.
11. Davies’ group reported that the benzylation of N-acyl
derivatives in their chiral auxiliary furnished the desired
product in 93% yield with 95% de.4b
12. The diastereoselectivities of same reactions with the
Davies’ oxazolidinones were 94% de in 8h4d and 95% de
in 8i.4a
20
Compound 8f: Yield 88%; oil; ½aꢁD +107.0 (c 0.44,
CHCl3); Rf = 0.5 (ethyl acetate/hexane 1:4); 1H NMR
(CDCl3) d 7.31–7.26 (2H, m), 7.08–7.02 (3H, m), 4.29 (1H,
d, J = 3.1 Hz), 4.19 (m, 1H), 2.14–2.11 (m, 1H), 1.96–1.89
(1H, m), 1.54–1.41 (1H, m), 1.46 (3H, s), 1.32 (3H, s), 1.17
(3H, d, J = 6.8 Hz), 1.04 (3H, d, J = 6.7 Hz), 1.02 (3H, d,
J = 6.9 Hz), 1.00 (3H, t);13C NMR (CDCl3) d 177.7,
146.4, 145.9, 128.5, 123.2, 123.0, 83.2, 65.9, 38.4, 29.6,
28.3, 27.2, 21.6, 21.3, 17.0, 16.2, 11.7.
13. The crude auxiliary was recovered by extracting the
reaction mixture with ethyl acetate. The required carbox-
ylic acid was isolated almost quantitatively by extract-
ing with CH2Cl2 after acidifying the aqueous layer to pH
24
2. Specific rotation: 9a: ½aꢁD ꢀ24.0 (c 0.17, CHCl3),
20
24
lit.14 ½aꢁD ꢀ23.1 (c 1, CHCl3); 9b: ½aꢁD ꢀ8.0 (c 0.14,
20
24
CHCl3); lit.15 ½aꢁD ꢀ8.2 (c 1, CHCl3); 9c: ½aꢁD +24.2
20
20
Compound 8g: Yield 75%; brown oil; ½aꢁD +108.2 (c 0.35,
(c 0.19, CHCl3); lit.16 ½aꢁD +25.5 (c 1, CHCl3).
CHCl3); Rf = 0.5 (ethyl acetate/hexane 1:4); 1H NMR
(CDCl3) d 7.31–7.25 (2H, m), 7.07–7.02 (3H, m), 4.32–4.28
(m, 1H), 4.29 (1H, d, J = 3.1 Hz), 2.14–2.09 (m, 1H), 1.45–
1.41 (3H, m), 1.54–1.41 (1H, m), 1.45 (3H, s), 1.39 (3H, s),
1.16 (3H, d, J = 6.8 Hz), 1.04 (3H, d, J = 6.7 Hz), 1.00
(3H, d, J = 6.9 Hz), 0.99 (3H, t); 13C NMR (CDCl3) d
14. Tyrrell, E.; Tsang, M. W. H.; Skinner, G. A.; Fawcett, J.
Tetrahedron 1996, 52, 9841.
15. Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem.
Soc. 1982, 107, 1737.
16. Oppolzer, W.; Lienard, P. Helv. Chim. Acta 1992, 75,
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