Diastereoselective additions of titanium enolates from N-glycolyl thiazolidinethiones to acetals

Article abstract of DOI:10.1021/jo301569x

The stereochemical outcome of the Lewis acid-mediated glycolate addition of the titanium enolates from protected N-hydroxyacetyl-4-isopropyl-1,3- thiazolidine-2-thiones to dimethyl and dibenzyl acetals depends on the hydroxyl protecting group. Particularly, the pivaloyl protected glycolate derivative provides the reluctant anti adducts in high yields and diastereomeric ratios, which can be isolated and further converted in enantiomerically pure form to β-methoxy or β-benzyloxy α-pivaloyloxy carbonyl fragments in a straightforward manner.

Full text of DOI:10.1021/jo301569x

Note
pubs.acs.org/joc
Diastereoselective Additions of Titanium Enolates from N‑Glycolyl
Thiazolidinethiones to Acetals
Jessica Baiget,† Marta Caba,† Erik Galvez,† Pedro Romea,*,† Felix Urpí,*,† and Merce Font-Bardia‡,§
́
̀
̀
†Departament de Química Organ
‡Departament de Crystallografia, Mineralogia i Dipos
Barcelona, Catalonia, Spain
§Unitat de Difraccio
de RX, Centres Científics i Tecnolog
i Sabarís 1-3, 08028 Barcelona, Catalonia, Spain
̀
ica, Universitat de Barcelona, Carrer Martí i Franques
́
1-11, 08028 Barcelona, Catalonia, Spain
̀
its Minerals, Universitat de Barcelona, Carrer Martí i Franques
́
s/n, 08028
́
̀
ics de la Universitat de Barcelona (CCiTUB), Universitat de Barcelona,
Carrer Sole
́
S
* Supporting Information
ABSTRACT: The stereochemical outcome of the Lewis acid-
mediated glycolate addition of the titanium enolates from
protected N-hydroxyacetyl-4-isopropyl-1,3-thiazolidine-2-thio-
nes to dimethyl and dibenzyl acetals depends on the hydroxyl
protecting group. Particularly, the pivaloyl protected glycolate
derivative provides the reluctant anti adducts in high yields and
diastereomeric ratios, which can be isolated and further
converted in enantiomerically pure form to β-methoxy or β-
benzyloxy α-pivaloyloxy carbonyl fragments in a straightfor-
ward manner.
he ubiquitous presence of α,β-dihydroxy carbonyl motifs
Tin the structure of natural products has stimulated the
development of a plethora of synthetic methodologies. In this
arena, one of the most successful approaches to install the two
new oxygenated chiral centers relies on the aldol reaction of α-
hydroxy carbonyl compounds, namely, the glycolate aldol
reaction.1 Thereby, a significant number of asymmetric catalytic
procedures have been disclosed,2,3 although stereoselective
glycolate aldol reactions are still commonly carried out by using
chiral auxiliary-based methodologies.4−6 Of the various chiral
auxiliary-based approaches reported to date, boron or titanium-
(IV) enolates of oxazolidinone and oxazolidinethione glycolate
precursors are the most appropriate entries to the syn
adducts,7−9 whereas the more reluctant anti counterparts can
be obtained with variable diastereoselectivity from the
titanium(IV) enolates of oxazolidinethiones.10,11 Moreover,
Hulme has reported that boron enolates from a norephedrine-
derived chiral auxiliary can afford both stereochemistries
depending on the hydroxyl protecting group.12 In spite of
these accomplishments, there is a lack of methodologies
directed to the synthesis of related α-hydroxy β-methoxy
carbonyl moieties present in certain natural products like
peloruside A (Figure 1).13
Figure 1. Seco-acid from peloruside A containing α-hydroxy β-
methoxy carbonyl substructures.
to dimethyl acetals developed in our group14 might be
expanded to glycolic systems in order to gain access to the
above-mentioned structural motifs in a straightforward and
efficient manner.15 We were also aware that similar additions to
dibenzyl acetals16 might afford double protected dihydroxy
adducts capable to be immediately engaged in the synthesis of
more complex structures. Herein, we disclose our studies on
the Lewis acid-mediated addition of the titanium enolates from
protected N-hydroxyacetyl-4-isopropyl-1,3-thiazolidine-2-thio-
nes to dimethyl and dibenzyl acetals that provide the
Therefore, these systems are usually prepared in a two-step
process: (i) stereoselective glycolate aldol reaction and (ii)
alkylation of the resultant aldol adduct. Taking into account
that the second step is often troublesome and that the
integration of a multistep sequence in a single step trans-
formation increases the efficiency of a process, we envisaged
that the stereoselective Lewis acid-mediated addition of the
titanium enolates from chiral N-acyl 1,3-thiazolidine-2-thiones
Received: July 30, 2012
Published: September 5, 2012
© 2012 American Chemical Society
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The Journal of Organic Chemistry
Note
corresponding anti adducts in high yields and enantiomerically
pure form (Scheme 1).
the corresponding anti adducts in high diastereomeric ratios
(see entries 3−5 and 8−10 in Table 1).18
These findings prove that the appropriate choice of the
protecting group permits to access both to the syn and the anti
stereochemistries, although the latter are obtained in a more
stereocontrolled manner. In this context, we focused our
attention on the pivaloyl glycolate 3, since it was considered to
be the most suitable substrate to prepare the reluctant anti
adducts.
Scheme 1
Thus, experimental conditions were carefully optimized for
the addition of O-pivaloyl derivative 3 to dimethyl acetals a and
b. Importantly, these studies uncovered that the enolization
could be performed at 0 °C in 30 min and that the relatively
low reactivity of the resultant titanium enolates could be
overcome by using a substoichiometric amount of the acetal.19
Then, these optimized procedures were successfully applied to
a wide range of dimethyl acetals. Indeed, BF3-mediated addition
of 3 to dimethyl acetals of aromatic or α,β-unsaturated
aldehydes provided the corresponding anti adducts in excellent
diastereomeric ratios and good yields (entries 1−4 in Table 2),
whereas dimethyl acetals from lineal as well as branched
aliphatic aldehydes required a stronger Lewis acid as SnCl4 to
achieve similar results (see entries 5−8 in Table 2).
Furthermore, other dimethyl acetals containing different
functional groups also afforded the corresponding anti adducts
in high yields and excellent diastereomeric ratios (see entries
9−10 in Table 2) with the exception of methyl 3,3-
dimethoxypropanoate (k), which resulted completely unreac-
tive (entry 11 in Table 2). This lack of reactivity was likely due
to the electron-withdrawing character of the carboxylate group
that prevents the formation of the necessary oxocarbenium
intermediate.
Application of experimental conditions optimized in former
studies to the Lewis acid-mediated reactions of titanium
enolates from valine-derived N-glycolyl thiazolidinethiones 1−
5 and model dimethyl acetals revealed that their stereochemical
outcome was highly dependent on the hydroxyl protecting
group and, in a minor extent, on the aromatic or aliphatic
character of the acetal. The additions of methyl ether and silyl
protected glycolates 1 and 2 to dimethyl acetal of benzaldehyde
and acetaldehyde (a and b respectively) illustrate this trend.
Indeed, methyl ether protected glycolate 1 afforded anti
adducts 6 but in variable diastereoselectivity: an excellent
diastereomeric ratio favoring anti adduct 6a for dimethyl acetal
of benzaldehyde and a barely equimolar anti/syn mixture of
adducts 6b and 7b for dimethyl acetal of acetaldehyde (see
entries 1 and 6 in Table 1). In contrast, additions of silyl
protected glycolate 2 to a and b furnished syn adducts 9a and
9b albeit in modest diastereomeric ratios (see entries 2 and 7 in
Table 1). Aiming to improve these results, we assessed the
influence of other silicon protecting groups and explored
different experimental conditions, but we were unable to obtain
pure syn adducts in a more efficient manner.17 Finally, it was
found that three ester protected glycolates 3−5 provided an
excellent anti selection with both dimethyl acetals and delivered
The anti configuration of adducts 10 was initially established
1
3
by H NMR analysis of the J2,3 coupling constants and was
later secured by X-ray diffraction analysis of 10d (see the
Supporting Information),20 which also confirmed the existence
Table 1. Preliminary Studies on the Influence of Protecting Group on the Lewis Acid-Mediated Addition of N-Glycolyl
Thiazolidinethiones to Dimethyl Acetals
a
b
entry
glycolate
PG
Me
LA
acetal
R
major adduct
dr (anti/syn)
yield (%)
1
2
3
4
5
6
7
8
9
10
1
2
3
4
5
1
2
3
4
5
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
SnCl4
a
a
a
a
a
b
b
b
b
b
Ph
6a
95:5
66
TBDPS
Piv
Ph
9a
30:70
93:7
(80)
57
Ph
10a
12a
14a
6b
Bz
Ph
89:11
95:5
69
Ac
Ph
30
Me
Me
Me
Me
Me
Me
60:40
23:77
92:8
(55)
(71)
70
TBDPS
Piv
SnCl4
9b
SnCl4
10b
12b
14b
Bz
SnCl4
87:13
95:5
75
Ac
SnCl4
50
a
b
1
Established by H NMR of the reaction mixture. Isolated yield of 2,3-anti diastereomer after chromatographic purification. Overall yield in
parentheses.
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Note
Table 2. Additions of O-Pivaloyl Derivative 3 to Dimethyl
Table 3. Additions to Dibenzyl Acetals
Acetals
a
b
cd
,
entry method
acetal
R
dr
yield (%)
1
A
A
A
A
B
B
B
B
B
B
B
a
c
d
e
b
f
Ph
91:9
95:5
93:7
97:3
94:6
95:5
95:5
97:3
>97:3
>97:3
85
80
67
70
77
82
75
75
97
93
a
bc
,
entry
glycolate
acetal
R
dr
yield (%)
2
3-MeOPh
4-ClPh
3
1
2
3
4
5
6
7
3
3
3
3
3
4
5
l
Ph
>97:3
89:11
92:8
88
4
(E)-PhCHCMe
m
n
o
p
p
p
Me
n-Pr
(96)
d
5
Me
70
6
n-Pr
CH2CH2OTIPS
CH2CH2NPhth
CH2CH2NPhth
CH2CH2NPhth
90:10
>97:3
>97:3
>97:3
72
87
82
7
g
h
i
i-Bu
8
i-Pr
9
CH2CH2OBn
CH2CH2NPhth
CH2CO2Me
54
b
a
10
11
j
1
Established by H NMR or HPLC of the reaction mixtures. Yield
based on the consumption of the acetal. Isolated yield. In parentheses,
overall yield. Isolated as the corresponding methyl ester (see
c
k
d
a
Method A: (i) TiCl4, DIPEA, 30 min, 0 °C; (ii) 1.1 equiv of
reference 14).
BF3·OEt2, −78 °C, 5 min; (iii) 0.55 equiv of RCH(OMe)2, −78 °C,
2.5 h. Method B: (i) TiCl4, DIPEA, 30 min, 0 °C; (ii) 0.55 equiv of
SnCl4, −78 °C, 5 min; (iii) 0.55 equiv of RCH(OMe)2, −78 °C, 30
Scheme 2
b
min, −20 °C, 5 h. Established by 1H NMR or HPLC analyses of the
c
reaction mixtures. Yield based on the consumption of the acetal.
d
Isolated yield after chromatographic purification.
of two intramolecular C−H···X (X = O, S) hydrogen bonds as
occurs in other adducts.21
The high levels of stereocontrol achieved in the reaction of
pivaloyl-protected N-glycolyl thiazolidinethione 3 and dimethyl
acetals led us to assess similar transformations with dibenzyl
acetals, aiming to obtain anti dihydroxy adducts with two
different protecting groups. In this scenario, the Lewis acid of
choice was SnCl4 since BF3·OEt2 was too weak even for the
most reactive dibenzyl acetals from conjugated aldehydes.16
Thus, application of the optimized conditions to glycolate 3
and dibenzyl acetals l−p provided the corresponding anti
adducts in high yields and excellent diastereomeric ratios (see
entries 1−5 in Table 3). Furthermore, the stereochemical
induction imparted by ester protected glycolate derivatives 4
and 5 was also tested with dibenzyl acetal p containing a
phtalimido group. Remarkably, a single diastereomer was
observed in all the reaction mixtures, and the corresponding
anti adducts 16−18 were easily isolated, although the yield for
acetyl-protected glycolate 5 was significantly low (compare
entries 5−7 in Table 3). All these results prove that the Lewis
acid-mediated addition of the titanium enolates from ester
protected glycolates 3−5 to dimethyl and dibenzyl acetals is a
powerful tool to prepare the corresponding anti adducts in a
highly efficient manner.
Irrespective of the results themselves, one of the most
appealing features of the thiazolidinethione-based method-
ologies is the easy removal of the chiral auxiliary.22 In
accordance to these expectations, treatment of enantiomerically
pure adduct 10i with the lithium enolate from ethyl isobutyrate
gave keto ester 19 in 80% yield (Scheme 2), which may be
considered as a model for the synthesis of C5−C11 fragment of
peloruside A shown in Figure 1.23 Moreover, chiral auxiliary
was removed under very mild conditions from benzyl adduct
16o to give enantiomerically pure Weinreb amide 20 in which
the alcohols at C2, C3, and C6 are protected with orthogonal
protecting groups (Scheme 2).
In summary, highly stereoselective Lewis acid-mediated
additions of titanium enolates from N-hydroxylacetyl-4-
isopropyl-1,3-thiazolidine-2-thiones to a wide range of dimethyl
and dibenzyl acetals have been developed. The choice of the
protecting group has proved crucial for achieving highly
stereocontrolled transformations. Thereby, ester-protected
glycolates and especially pivaloyl-protected glycolate provide a
highly stereoselective and straightforward access to the
corresponding anti adducts, which can be easily isolated and
further converted in enantiomerically pure β-methoxy or β-
benzyloxy α-pivaloyloxy carbonyl fragments capable of being
immediately used in the synthesis of natural products.
EXPERIMENTAL SECTION
■
General Methods. All reactions were conducted in oven-dried
glassware with distilled and anhydrous solvents under an atmosphere
of N2. Thin-layer chromatography was carried out on silica gel 60 F254
plates. Specific rotations were determined at 20 °C. IR spectra were
1
obtained as thin films on NaCl plates or KBr discs. H NMR spectra
were recorded in CDCl3 and reported as δ ppm downfield from
internal TMS (δ 0). 13C NMR spectra were also recorded in CDCl3
and referenced to solvent residual peak for CDCl3 (δ 77). High
resolution mass spectra (HRMS) were obtained by using ESI−TOF
techniques.
Preparation of Glycolate 3. A mixture of glycolic acid (1.52 g, 20
mmol) and pivaloyl chloride (4.4 mL, 36 mmol) was stirred at room
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Note
temperature for 48 h. Then, the volatiles were removed, obtaining 2.73
g of O-pivaloylglycolic acid, which were used in the next step without
further purification.
+247.4 (c 0.9, CHCl3); IR (KBr) ν 3005, 2968, 2868, 1735, 1698,
1486, 1145, 1095 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.28−7.22 (m,
1H), 7.14 (d, J = 7.6 Hz, 1H), 7.14 (dd, J = 2.6, 1.5 Hz, 1H), 7.02 (dt,
J = 7.6, 1.5 Hz, 1H), 6.86 (ddd, J = 8.3, 2.6, 1.0 Hz, 1H), 5.30 (ddd, J =
8.3, 5.9, 1.1 Hz, 1H), 4.61 (d, J = 7.6 Hz, 1H), 3.82 (s, 3H), 3.60 (dd, J
= 11.4, 8.4 Hz, 1H), 3.20 (s, 3H), 3.02 (dd, J = 11.4, 1.1 Hz, 1H),
2.39−2.27 (m, 1H), 1.12 (d, J = 6.8 Hz, 3H), 1.10 (s, 9H), 1.02 (d, J =
6.9 Hz, 3H); 13C NMR (100.6 MHz, CDCl3) δ 202.6, 177.5, 170.3,
159.6, 139.2, 129.0, 120.7, 114.5, 113.0, 83.9, 72.9, 71.7, 56.9, 55.2,
38.3, 30.5, 30.3, 26.8, 19.0, 17.5; HRMS m/z calcd for [M + H]+
C22H32NO5S2 454.1716, found 454.1714; calcd for [M + Na]+
C22H31NNaO5S2 476.1536, found 476.1539.
(S)-N-[(2R,3S)-3-(4-Chlorophenyl)-3-methoxy-2-pivaloyloxy-
propanoyl]-4-isopropyl-1,3-thiazolidine-2-thione (10d). Yellow
solid (167 mg, 67%): mp 100−103 °C; Rf (hexanes/EtOAc 90:10)
0.30; [α]D +124.4 (c 1.3, CHCl3); IR (KBr) ν 2961, 2872, 1730, 1704,
1477, 1372, 1148 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.42−7.32 (m,
4H), 7.09 (d, J = 7.6 Hz, 1H), 5.27 (ddd, J = 8.2, 6.1, 1.1 Hz, 1H), 4.64
(d, J = 7.6 Hz, 1H), 3.61 (dd, J = 11.4, 8.2 Hz, 1H), 3.20 (s, 3H), 3.02
(dd, J = 11.4, 1.1 Hz, 1H), 2.36−2.26 (m, 1H), 1.11 (d, J = 6.4 Hz,
3H), 1.10 (s, 9H), 1.02 (d, J = 6.9 Hz, 3H); 13C NMR (100.6 MHz,
CDCl3) δ 202.8, 177.5, 169.9, 136.0, 134.4, 129.6, 128.4, 81.3, 72.8,
71.7, 57.0, 38.4, 30.5 (×2), 26.8, 18.9, 17.5; HRMS m/z calcd for [M +
H]+ C21H29ClNO4S2 458.1221, found 458.1225; calcd for [M + Na]+
C21H28ClNNaO4S2 480.1040, found 480.1052.
(S)-4-Isopropyl-N-[(2R,3R,4E)-3-methoxy-4-methyl-5-phenyl-
2-pivaloyloxy-4-pentenoyl]-1,3-thiazolidine-2-thione (10e).
Yellow oil (177 mg, 70%): Rf (hexanes/EtOAc 90:10) 0.35; [α]D
+222.0 (c 2.1, CHCl3); IR (film) ν 2966, 2874, 1732, 1700, 1364,
1176, 1149 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.37−7.19 (m, 5H),
7.18 (d, J = 7.5 Hz, 1H), 6.55 (br s, 1H), 5.31 (ddd, J = 8.5, 5.7, 1.1
Hz, 1H), 4.26 (d, J = 7.5 Hz, 1H), 3.57 (dd, J = 11.5, 8.5 Hz, 1H), 3.25
(s, 3H), 2.99 (dd, J = 11.5, 1.1 Hz, 1H), 2.32−2.22 (m, 1H), 1.66 (d, J
= 1.3 Hz, 3H), 1.10 (s, 9H), 1.05 (d, J = 6.8 Hz, 3H), 0.96 (d, J = 6.9
Hz, 3H); 13C NMR (CDCl3, 100.6 MHz) δ 202.5, 177.6, 170.3, 136.8,
134.5, 131.4, 128.9, 128.1, 126.8, 87.5, 71.6, 70.8, 56.3, 38.4, 30.5, 29.9,
26.9, 18.8, 17.1, 13.2; HRMS m/z calcd for [M + Na]+
C24H33NNaO4S2 486.1744, found 486.1742.
A mixture of this acid, (S)-4-isopropyl-1,3-thiazolidine-2-thione
(1.612 g, 10 mmol), EDC (2.6 mL, 15 mmol), and DMAP (60 mg, 0.5
mmol) in CH2Cl2 (15 mL) was stirred at 0 °C for 15 min and was
allowed to reach room temperature for 3 h under a N2 atmosphere. It
was partitioned with Et2O and 0.5 M HCl; the organic layer was
washed with 0.5 M NaOH, H2O, and brine, dried, and concentrated.
The resulting residue was purified through flash chromatography
(from 50:50 to 70:30 CH2Cl2/hexanes) to afford 2.62 g (8.6 mmol,
86%) of (S)-4-isopropyl-N-(pivaloyloxyacetyl)-1,3-thiazolidine-2-thi-
one, 3, as a yellow oil: Rf (CH2Cl2/hexanes 70:30) 0.50; [α]D +232.8
1
(c 1.00, CHCl3); IR (film) ν 2965, 2874, 1740, 1714, 1141 cm−1; H
NMR (300 MHz, CDCl3) δ 5.44 (s, 2H), 5.11 (ddd, J = 8.2, 5.9, 1.2
Hz, 1H), 3.63 (dd, J = 11.6, 8.2 Hz, 1H), 3.09 (dd, J = 11.6, 1.2 Hz,
1H), 2.43−2.32 (m, 1H), 1.27 (s, 9H), 1.06 (d, J = 6.9 Hz, 3H), 0.98
(d, J = 7.0 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 202.5, 177.9,
168.1, 71.4, 65.0, 38.7, 31.4, 30.7, 27.1, 19.0, 17.5; HRMS m/z calcd
for [M + H]+ C13H22NO3S2 304.1036, found 304.1037; m/z calcd for
[M + Na]+ C13H21NNaO3S2 326.0855, found 326.0859.
Experimental Procedure for Method A. Neat TiCl4 (0.12 mL,
1.1 mmol) is added dropwise to a solution of 3 (303 mg, 1.0 mmol) in
CH2Cl2 (8 mL), at 0 °C. The orange suspension is stirred for 5 min at
0 °C, and a solution of i-Pr2NEt (0.19 mL, 1.1 mmol) in CH2Cl2 (1.5
mL) is added. The dark brown enolate solution is stirred for 30 min at
0 °C and cooled at −78 °C. Then, recently distilled BF3·OEt2 (140 μL,
1.1 mmol) and dimethyl acetal (0.55 mmol) are added, and the
resulting mixture is stirred for 2.5 h at −78 °C.
The reaction is quenched by the addition of saturated NH4Cl and
extracted with CH2Cl2. The combined organic extracts are dried and
1
concentrated. The residue is analyzed by HPLC or H NMR and
purified through flash column chromatography with deactivated silica
gel (2.5% Et3N) using CH2Cl2 or 90:10 hexanes/EtOAc mixtures as
solvents to afford the anti adduct as a pure diastereomer.
Experimental Procedure for Method B. Neat TiCl4 (0.12 mL,
1.1 mmol) is added dropwise to a solution of 3 (303 mg, 1.0 mmol) in
CH2Cl2 (8 mL), at 0 °C. The orange suspension is stirred for 5 min at
0 °C, and a solution of i-Pr2NEt (0.19 mL, 1.1 mmol) in CH2Cl2 (1.5
mL) is added. The dark brown solution is stirred for 30 min at 0 °C
and cooled at −78 °C. Then, a 1 M SnCl4 solution (0.55 mL, 0.55
mmol) and dimethyl acetal (0.55 mmol) are added, and the resulting
mixture is stirred for 30 min at −78 °C and 5 h at −20 °C. Quenching
and purification of the reaction mixture is the same as in Method A.
(S)-4-Isopropyl-N-[(2R,3R)-3-methoxy-3-phenyl-2-pivaloy-
loxypropanoyl]-1,3-thiazolidine-2-thione (10a). Yellow solid
(197 mg, 85%): mp 142−143 °C; Rf (hexanes/CH2Cl2 50:50) 0.40;
[α]D +210.7 (c 1.15, CHCl3); IR (KBr) ν 2962, 1728, 1707, 1368,
1178, 1149 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.48−7.27 (m, 5H),
7.14 (d, J = 7.6 Hz, 1H), 5.29 (ddd, J = 8.2, 6.0, 1.2 Hz, 1H), 4.64 (d, J
= 7.6 Hz, 1H), 3.60 (dd, J = 11.4, 8.2 Hz, 1H), 3.20 (s, 3H), 3.01 (dd,
J = 11.4, 1.2 Hz, 1H), 2.38−2.27 (m, 1H), 1.20 (d, J = 6.9 Hz, 3H),
1.08 (s, 9H), 1.02 (d, J = 6.9 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
δ 202.6, 177.5, 170.3, 137.5, 128.5, 128.2, 128.1, 83.9, 73.0, 71.7, 56.9,
38.3, 30.6, 30.3, 26.8, 18.9, 17.5; HRMS m/z calcd for [M + H]+
C21H30NO4S2 424.1611, found 424.1625.
(S)-4-Isopropyl-N-[(2R,3R)-3-methoxy-2-pivaloyloxyhexano-
yl]-1,3-thiazolidine-2-thione (10f). Yellow solid (174 mg, 82%):
mp 51−53 °C; Rf (hexanes/EtOAc 90:10) 0.55; [α]D +236.3 (c 1.2,
CHCl3); IR (KBr) ν 2966, 2873, 1731, 1700, 1362, 1182, 1114 cm−1;
1H NMR (400 MHz, CDCl3) δ 6.93 (d, J = 4.3 Hz, 1H), 5.26 (ddd, J
= 8.4, 6.0, 1.3 Hz, 1H), 3.91−3.87 (m, 1H), 3.62 (dd, J = 11.5, 8.4 Hz,
1H), 3.42 (s, 3H), 3.02 (dd, J = 11.5, 1.3 Hz, 1H), 2.31−2.23 (m, 1H),
1.75−1.66 (m, 1H), 1.60−1.46 (m, 2H), 1.40−1.32 (m, 1H), 1.24 (s,
9H), 1.05 (d, J = 6.8 Hz, 3H), 0.96 (d, J = 6.9 Hz, 3H), 0.91 (t, J = 7.1
Hz, 3H); 13C NMR (100.6 MHz, CDCl3) δ 202.5, 178.1, 169.7, 79.2,
72.7, 71.6, 58.2, 38.6, 32.1, 30.5 (×2), 27.0, 18.9, 18.8, 17.3, 14.1;
HRMS m/z calcd for [M + Na]+ C18H31NNaO4S2 412.1587, found
412.1589.
(S)-4-Isopropyl-N-[(2R,3R)-3-methoxy-5-methyl-2-pivaloy-
loxyhexanoyl]-1,3-thiazolidine-2-thione (10g). Yellow solid (165
mg, 75%): mp 56−58 °C; Rf (CH2Cl2) 0.65; [α]D +244.9 (c 0.8,
CHCl3); IR (KBr) ν 2959, 2871, 1731, 1702, 1363, 1179, 1153 cm−1;
1H NMR (400 MHz, CDCl3) δ 6.94 (d, J = 3.7 Hz, 1H), 5.27 (ddd, J
= 8.4, 5.9, 1.2 Hz, 1H), 4.03 (ddd, J = 9.9, 3.7, 2.7 Hz, 1H), 3.63 (dd, J
= 11.5, 8.4 Hz, 1H), 3.44 (s, 3H), 3.02 (dd, J = 11.5, 1.3 Hz, 1H),
2.30−2.21 (m, 1H), 1.85−1.70 (m, 3H), 1.25 (s, 9H), 1.05 (d, J = 6.8
Hz, 3H), 0.97 (d, J = 6.9 Hz, 3H), 0.94 (d, J = 6.6 Hz, 3H), 0.87 (d, J
= 6.5 Hz, 3H); 13C NMR (100.6 MHz, CDCl3) δ 202.5, 178.2, 169.3,
77.3, 72.8, 71.6, 58.1, 38.9, 38.7, 30.6, 30.4, 27.0, 24.4, 23.7, 21.7, 19.0,
17.3; HRMS m/z calcd for [M + H]+ C19H34NO4S2 404.1924, found
404.1928; calcd for [M + Na]+ C19H33NNaO4S2 426.1743, found
426.1747.
(S)-4-Isopropyl-N-[(2R,3R)-3-methoxy-2-pivaloyloxybutano-
yl]-1,3-thiazolidine-2-thione (10b). Yellow oil (152 mg, 77%): Rf
(CH2Cl2) 0.35; [α]D +216.1 (c 0.65, CHCl3); IR (film) ν 2967, 2932,
1730, 1702, 1363, 1154 cm−1; 1H NMR (300 MHz, CDCl3) δ 6.82 (d,
J = 3.7 Hz, 1H), 5.23 (ddd, J = 8.2, 6.4, 1.1 Hz, 1H), 4.06 (qd, J = 6.4,
3.7 Hz, 1H), 3.65 (dd, J = 11.5, 8.2 Hz, 1H), 3.38 (s, 3H), 3.03 (dd, J
= 11.5, 1.1 Hz, 1H), 2.29−2.22 (m, 1H), 1.27 (d, J = 6.4 Hz, 3H), 1.25
(s, 9H), 1.06 (d, J = 6.7 Hz, 3H), 0.96 (d, J = 7.0 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3) δ 202.4, 178.1, 169.4, 75.3, 73.5, 71.5, 56.9, 38.7,
30.9, 30.5, 26.9, 18.9, 17.6, 14.2; HRMS m/z calcd for [M + H]+
C16H28NO4S2 362.1454, found 362.1468.
(S)-4-Isopropyl-N-[(2R,3R)-3-methoxy-4-methyl-2-pivaloy-
loxypentanoyl]-1,3-thiazolidine-2-thione (10h). Yellow solid
(160 mg, 75%): mp 88−90 °C; Rf (CH2Cl2) 0.40; [α]D +168.6 (c
1.4, CHCl3); IR (KBr) ν 2964, 2873, 1722, 1697, 1364, 1180, 1155
(S)-4-Isopropyl-N-[(2R,3R)-3-methoxy-3-(3-methoxyphenyl)-
2-pivaloyloxypropanoyl]-1,3-thiazolidine-2-thione (10c). Yel-
low solid (198 mg, 80%): mp 85−88 °C; Rf (CH2Cl2) 0.55; [α]D
1
cm−1; H NMR (400 MHz, CDCl3) δ 6.94 (d, J = 7.0 Hz, 1H), 5.23
8812
dx.doi.org/10.1021/jo301569x | J. Org. Chem. 2012, 77, 8809−8814

The Journal of Organic Chemistry
Note
(ddd, J = 8.3, 5.8, 1.1 Hz, 1H), 3.61 (dd, J = 11.4, 8.3 Hz, 1H), 3.57
(dd, J = 7.0, 4.4 Hz, 1H), 3.38 (s, 3H), 3.02 (dd, J = 11.4, 1.2 Hz, 1H),
2.37−2.28 (m, 1H), 2.08−1.99 (m, 1H), 1.21 (s, 9H), 1.07 (d, J = 6.8
Hz, 3H), 1.04 (d, J = 6.8 Hz, 3H), 1.01 (d, J = 7.0 Hz, 3H), 1.00 (d, J
= 6.9 Hz, 3H); 13C NMR (100.6 MHz, CDCl3) δ 202.8, 177.9, 170.6,
85.4, 71.7, 71.6, 60.2, 38.4, 30.7, 30.5, 30.2, 26.9, 19.9, 19.0, 17.6, 17.2;
HRMS m/z calcd for [M + H]+ C18H32NO4S2 390.1767, found
390.1768; calcd for [M + Na]+ C18H31NNaO4S2 412.1587, found
412.1586.
Hz, 1H), 5.22 (ddd, J = 8.2, 6.2, 1.2 Hz, 1H), 4.80 (d, J = 11.4 Hz,
1H), 4.64−4.59 (m, 1H), 4.61 (d, J = 11.4 Hz, 1H), 3.90−3.77 (m,
2H), 3.63 (dd, J = 11.4, 8.2 Hz, 1H), 3.02 (dd, J = 11.4, 1.2 Hz, 1H),
2.28−2.19 (m, 1H), 2.00−1.92 (m, 1H), 1.88−1.79 (m, 1H), 1.24 (s,
9H), 1.07−1.03 (m, 21H), 1.00 (d, J = 6.7 Hz, 3H), 0.93 (d, J = 6.9
Hz, 3H); 13C NMR (100.6 MHz, CDCl3) δ 202.4, 178.3, 168.9, 138.6,
128.2, 127.5, 127.5, 73.7, 72.9, 71.9, 71.6, 59.2, 38.6, 33.0, 30.9, 30.6,
26.9, 19.1, 18.0, 17.5, 11.9; HRMS m/z calcd for [M + H]+
C32H54NO5S2Si 624.3207, found 624.3212; m/z calcd for [M +
Na]+ C32H53NNaO5S2Si 646.3027, found 646.3034.
(S)-N-[(2R,3R)-5-Amino-3-benzyloxy-N,N-ftaloyl-2-pivaloy-
loxypentanoyl]-4-isopropyl-1,3-thiazolidine-2-thione (16p).
Yellow solid (283 mg, 87%): mp 46−47 °C; Rf (CH2Cl2) 0.40;
[α]D +142.4 (c 0.95, CHCl3); IR (KBr) ν 3030, 2966, 2933, 1772,
1713, 1467, 1363 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.81−7.79 (m,
2H), 7.69−7.67 (m, 2H), 7.36−7.21 (m, 5H), 7.03 (d, J = 3.1 Hz,
1H), 5.20 (ddd, J = 8.2, 6.1, 1.2 Hz, 1H), 4.78 (d, J = 11.3 Hz, 1H),
4.65 (d, J = 11.3 Hz, 1H), 4.33 (dt, J = 9.8, 2.9 Hz, 1H), 3.91−3.78 (m,
2H), 3.65 (dd, J = 11.5, 8.3 Hz, 1H), 3.00 (dd, J = 11.5, 1.3 Hz, 1H),
2.22−2.12 (m, 1H), 2.00−1.91 (m, 1H), 1.24 (s, 9H), 0.98 (d, J = 6.7
Hz, 3H), 0.85 (d, J = 6.9 Hz, 3H); 13C NMR (100.6 MHz, CDCl3) δ
202.4, 178.2, 168.8, 168.2, 138.3, 133.8, 132.1, 128.2, 127.7, 127.5,
123.1, 75.1, 72.1, 71.5, 71.5, 38.7, 35.0, 30.9, 30.6, 28.5, 27.0, 18.9,
17.4; HRMS m/z calcd for [M + H]+ C31H37N2O6S2 597.2088, found
597.2092; m/z calcd for [M + Na]+ C31H36N2NaO6S2 619.1907, found
619.1911.
Synthesis of Keto Ester 19. Ethyl isobutyrate (475 μL, 3.5 mmol)
was added to a freshly prepared 0.5 M solution of LDA in THF (7 mL,
3.5 mmol) at −78 °C. Stirring continued for 1 h, and a solution of 10i
(566 mg, 1.2 mmol) in THF (0.75 + 0.25 mL) was carefully added.
The reaction mixture was stirred for 30 min at −78 °C and 3.5 h at
−50 °C, quenched with saturated NH4Cl, and partitioned with
CH2Cl2 and water. The organic layer was dried and concentrated, and
the resultant residue was purified by flash chromatography (hexanes/
EtOAc 85:15), affording 410 mg (0.94 mmol, 80% yield) of ethyl
(4R,5R)-7-benzyloxy-5-methoxy-2,2-dimethyl-3-oxo-4-pivaloyloxyhep-
tanoate (19) as a colorless oil: Rf (hexanes/EtOAc 85:15) 0.55; [α]D
+49.0 (c 1.5, CHCl3); IR (film) ν 3030, 2979, 2872, 1742, 1711, 1456,
1274, 1137 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.36−7.26 (m, 5H),
5.96 (d, J = 3.2 Hz, 1H), 4.53 (d, J = 11.9 Hz, 1H), 4.45 (d, J = 11.9
Hz, 1H), 4.20−4.01 (m, 2H), 3.89 (dt, J = 9.4, 3.2 Hz, 1H), 3.57−3.53
(m, 2H), 3.28 (s, 3H), 1.79−1.63 (m, 2H), 1.43 (s, 3H), 1.32 (s, 3H),
1.25−1.15 (m, 12H); 13C NMR (100.6 MHz, CDCl3) δ 205.4, 177.3,
172.5, 138.5, 128.3, 127.7, 127.5, 78.3, 75.4, 72.8, 66.5, 61.4, 57.5, 53.8,
40.0, 30.5, 27.1, 22.4, 21.6, 13.8; HRMS m/z calcd for [M + H]+
C24H37O7 437.2542, found 437.2534.
Synthesis of Weinreb Amide 20. A solution of 16o (67 mg, 107
μmol), MeONHMe·HCl (16 mg, 0.16 mmol), DMAP (15 mg, 107
μmol), and Et3N (15 μL, 107 μmol) in CH2Cl2 (1 mL) was stirred for
16 h at rt. The reaction mixture was diluted in Et2O and washed with
0.5 M HCl, 0.5 M NaOH, H2O, and brine, dried and concentrated.
The resultant colorless oil was filtered over silica gel (eluted with
CH2Cl2/EtOAc 95:5), yielding 47 mg (90 μmol, 84%) of (2R,3R)-3-
benzyloxy-N-methoxy-N-methyl-2-pivaloyloxy-5-triisopropylsilyloxy-
pentanamide (20) as a colorless oil: Rf (CH2Cl2/EtOAc 95:5) 0.40;
[α]D +6.3 (c 1.2, CHCl3); IR (film) ν 3031, 2942, 2866, 1733, 1684,
1463, 1159, 1100 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.33−7.25 (m,
5H), 5.55 (s, 1H), 4.64 (d, J = 11.5 Hz, 1H), 4.57 (d, J = 11.5 Hz, 1H),
4.17−4.13 (m, 1H), 3.86−3.76 (m, 2H), 3.74 (s, 3H), 3.17 (s, 3H),
1.88−1.84 (m, 2H), 1.27 (s, 9H), 1.09−1.01 (m, 21H); 13C NMR
(100.6 MHz, CDCl3) δ 178.5, 168.3, 138.3, 128.3, 127.8, 127.7, 74.5,
72.4, 71.6, 61.1, 59.1, 38.8, 33.9, 27.1, 18.0, 11.9; HRMS m/z calcd for
[M + H]+ C28H50NO6Si 524.3402, found 524.3412.
(S)-N-[(2R,3R)-4-Benzyloxy-3-methoxy-2-pivaloyloxypenta-
noyl]-4-isopropyl-1,3-thiazolidine-2-thione (10i). Yellow oil
(256 mg, 97%): Rf (CH2Cl2) 0.55; [α]D +187.8 (c 1.2, CHCl3); IR
1
(film) ν 3029, 2967, 2872, 1731, 1363, 1153 cm−1; H NMR (400
MHz, CDCl3) δ 7.35−7.25 (m, 5H), 6.98 (d, J = 3.5 Hz, 1H), 5.25
(ddd, J = 8.4, 5.9, 1.3 Hz, 1H), 4.51 (d, J = 12.0 Hz, 1H), 4.50 (d, J =
12.0 Hz, 1H), 4.16−4.12 (m, 1H), 3.61 (dd, J = 11.4, 8.4 Hz, 1H),
3.61−3.58 (m, 2H), 3.41 (s, 3H), 3.01 (dd, J = 11.4, 1.2 Hz, 1H),
2.29−2.20 (m, 1H), 1.98−1.88 (m, 2H), 1.22 (s, 9H), 1.00 (d, J = 6.7
Hz, 3H), 0.94 (d, J = 6.9 Hz, 3H); 13C NMR (100.6 MHz, CDCl3) δ
202.5, 178.1, 169.3, 138.5, 128.3, 127.6, 127.5, 76.1, 72.8, 72.7, 71.6,
66.2, 58.3, 38.6, 30.6, 30.5, 30.2, 26.9, 19.0, 17.2; HRMS m/z calcd for
[M + H]+ C24H36NO5S2 482.2029, found 482.2023; calcd for [M +
Na]+ C24H35NNaO5S2 504.1849, found 504.1840.
(S)-N-[(2R,3R)-5-Amino-3-methoxy-N,N-phtaloyl-2-pivaloy-
loxypentanoyl]-4-isopropyl-1,3-thiazolidine-2-thione (10j).
Yellow solid (132 mg, 93%): mp 47−50 °C; Rf (CH2Cl2) 0.25;
[α]D +150.5 (c 1.0, CHCl3); IR (KBr) ν 2965, 2932, 1772, 1713, 1467,
1364 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.85−7.82 (m, 2H), 7.72−
7.70 (m, 2H), 6.98 (d, J = 3.5 Hz, 1H), 5.21 (ddd, J = 8.2, 6.2, 1.2 Hz,
1H), 4.04 (ddd, J = 9.3, 3.5, 2.7 Hz, 1H), 3.90−3.78 (m, 2H), 3.61
(dd, J = 11.5, 8.2 Hz, 1H), 3.48 (s, 3H), 3.00 (dd, J = 11.5, 1.0 Hz,
1H), 2.24−2.15 (m, 1H), 2.13−2.04 (m, 1H), 1.99−1.91 (m, 1H),
1.24 (s, 9H), 0.98 (d, J = 6.7 Hz, 3H), 0.88 (d, J = 6.9 Hz, 3H); 13C
NMR (100.6 MHz, CDCl3) δ 202.4, 178.2, 169.0, 168.2, 133.9, 132.2,
123.1, 76.8, 71.8, 71.5, 57.8, 38.7, 34.9, 30.8, 30.6, 28.4, 26.9, 18.9,
17.4; HRMS m/z calcd for [M + H]+ C25H33N2O6S2 521.1775, found
521.1776; calcd for [M + Na]+ C25H32N2NaO6S2 543.1594, found
543.1596.
(S)-N-[(2R,3R)-3-Benzyloxy-3-phenyl-2-pivaloyloxypropano-
yl]-4-isopropyl-1,3-thiazolidine-2-thione (16l). Yellow oil (240
mg, 88%): Rf (hexanes/CH2Cl2 50:50) 0.15; [α]D +159.2 (c 1.0,
CHCl3); IR (film) ν 3030, 2967, 2873, 1732, 1698, 1178, 1150 cm−1;
1H NMR (400 MHz, CDCl3) δ 7.53−7.50 (m, 2H), 7.39−7.20 (m,
8H), 7.06 (d, J = 7.4 Hz, 1H), 5.20−5.16 (m, 1H), 4.93 (d, J = 7.4 Hz,
1H), 4.48 (d, J = 11.7 Hz, 1H), 4.28 (d, J = 11.7 Hz, 1H), 3.56 (dd, J =
11.4, 8.2 Hz, 1H), 2.97 (dd, J = 11.4, 0.6 Hz, 1H), 2.26−2.14 (m, 1H),
1.08 (s, 9H), 0.91 (d, J = 6.7 Hz, 3H), 0.88 (d, J = 6.8 Hz, 3H); 13C
NMR (100.6 MHz, CDCl3) δ 202.7, 177.6, 169.9, 137.7, 137.5, 128.6,
128.4, 128.2, 128.1, 127.5, 127.4, 81.6, 73.1, 71.7, 70.7, 38.4, 30.7, 30.5,
26.8, 19.0, 17.4; HRMS m/z calcd for [M + H]+ C27H34NO4S2
500.1924, found 500.1924; m/z calcd for [M + Na]+ C27H33NNaO4S2
522.1743, found 522.1745.
(S)-N-[(2R,3R)-3-Benzyloxy-2-pivaloyloxybutanoyl]-4-iso-
propyl-1,3-thiazolidine-2-thione (16m). Yellow oil (230 mg, 96%,
dr 89:11): Rf (CH2Cl2) 0.55; [α]D +236.1 (c 1.15, CHCl3); IR (film) ν
3029, 2968, 2873, 1730, 1702, 1364, 1154 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.34−7.31 (m, 5H), 6.82 (d, J = 3.4 Hz, 1H), 5.20 (ddd, J =
8.1, 6.3, 1.2 Hz, 1H), 4.66−4.59 (m, 2H), 4.32 (qd, J = 6.4, 3.4 Hz,
1H), 3.62 (dd, J = 11.5, 8.2 Hz, 1H), 3.01 (dd, J = 11.5, 1.2 Hz, 1H),
2.28−2.20 (m, 1H), 1.31 (d, J = 6.5 Hz, 3H), 1.25 (s, 9H), 0.99 (d, J =
6.8 Hz, 3H), 0.92 (d, J = 6.9 Hz, 3H); 13C NMR (100.6 MHz, CDCl3)
δ 202.5, 178.2, 169.2, 138.4, 128.3, 127.6, 127.5, 73.6, 73.3, 71.6, 70.8,
38.7, 31.0, 30.6, 27.0, 19.0, 17.5, 14.8; HRMS m/z calcd for [M + H]+
C22H32NO4S2 438.1767, found 438.1772; calcd for [M + Na]+
C22H31NNaO4S2 460.1587, found 460.1593.
ASSOCIATED CONTENT
(S)-N-[(2R,3R)-3-Benzyloxy-2-pivaloyloxy-5-triisopropylsily-
loxypentanoyl]-4-isopropyl-1,3-thiazolidine-2-thione (16o).
Yellow oil (245 mg, 72%): Rf (CH2Cl2) 0.45; [α]D +163.8 (c 2.3,
CHCl3); IR (film) ν 3031, 2962, 2866, 1731, 1700, 1463, 1153 cm−1;
1H NMR (400 MHz, CDCl3) δ 7.36−7.22 (m, 5H), 6.96 (d, J = 3.1
■
S
* Supporting Information
1
Copies of H and 13C NMR spectra for adducts 10 and 16,
derivatives 19 and 20, and data for X-ray crystal structure of
8813
dx.doi.org/10.1021/jo301569x | J. Org. Chem. 2012, 77, 8809−8814

The Journal of Organic Chemistry
Note
(13) For an insightful example on a Mukaiyama aldol addition of an
achiral silyl enol ether from an α-OBn ketone to a chiral aldehyde
followed by methylation of the resultant aldol for the preparation of
C1−C12 fragment of peloruside A, see: Engers, D. W.; Bassindale, M.
J.; Pagenkopf, B. L. Org. Lett. 2004, 6, 663−666.
adduct 10d. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: felix.urpi@ub.edu; pedro.romea@ub.edu.
(14) (a) Cosp, A.; Romea, P.; Talavera, P.; Urpí, F.; Vilarrasa, J.;
Font-Bardia, M.; Solans, X. Org. Lett. 2001, 3, 615−617. (b) Cosp, A.;
Romea, P.; Urpí, F.; Vilarrasa, J. Tetrahedron Lett. 2001, 42, 4629−
Notes
4631. (c) Baiget, J.; Cosp, A.; Gal
Urpí, F. Tetrahedron 2008, 64, 5637−5644. (d) Checa, B.; Gal
Parello, R.; Sau, M.; Romea, P.; Urpí, F.; Font-Bardia, M.; Solans, X.
Org. Lett. 2009, 11, 2193−2196.
́
vez, E.; Gom
́
ez-Pinal, L.; Romea, P.;
The authors declare no competing financial interest.
́
vez, E.;
́
ACKNOWLEDGMENTS
■
(15) For recent applications of these methodologies to the synthesis
of natural products, see: (a) Harrison, T. J.; Ho, S.; Leighton, J. L. J.
Am. Chem. Soc. 2011, 133, 7308−7311. (b) Crimmins, M. T.; Hughes,
C. O. Org. Lett. 2012, 14, 2168−2171. (c) Pulukuri, K. K.;
Chakraborty, T. K. Org. Lett. 2012, 14, 2858−2861.
Financial support from the Spanish Ministerio de Ciencia e
Innovacio
́
n (MICINN), Fondos FEDER (Grant No.
CTQ2009-09692), and the Generalitat de Catalunya
(2009SGR825) as well as a doctorate studentship (Universitat
de Barcelona) to E.G. is acknowledged.
(16) (a) Cosp, A.; Larrosa, I.; Vilasís., I.; Romea, P.; Urpí, F.;
Vilarrasa, J. Synlett 2003, 1109−1112. (b) Gal
́ ́
vez, E.; Parello, R.;
Romea, P.; Urpí, F. Synlett 2008, 2951−2954.
REFERENCES
■
(17) Related TIPS-protected glycolate afforded the corresponding
syn adducts in a poorly stereocontrolled manner, whereas TBS-
protected counterpart unexpectedly provided the opposite anti
stereochemistry. The reasons of these results are still unclear.
(18) Only two of the four possible isomers have been observed
across all the reactions. These results are in accordance to our previous
studies on the Lewis acid-mediated additions of titanium enolates to
acetals, which established the absolute stereocontrol provided by the
chiral auxiliary on the R configuration of the α-stereocenter in these
processes. See reference 14 for further details.
(1) For insightful overviews on the reactivity of dihydroxyacetone
and related compounds, see: (a) Enders, D.; Voith, M.; Lenzen, A.
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́ ́
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(19) Importantly, 0.25−0.35 mmol of acyl thiazolidinethione 3 are
commonly recovered after chromatographic purification of the
reaction mixtures, whereas minor amounts of the chiral auxiliary are
observed in these mixtures.
(3) For recent contributions, see: (a) Markert, M.; Mulzer, M.;
Schetter, B.; Mahrwald, R. J. Am. Chem. Soc. 2007, 129, 7258−7259.
(b) Denmark, S. E.; Chung, W.-j. J. Org. Chem. 2008, 73, 4582−4595.
(c) Trost, B. M.; Seganish, W. M.; Chung, C. K.; Amans, D. Chem.
Eur. J. 2012, 18, 2948−2960 and references therein.
(20) Crystallographic data for 10d have been deposited at the
Cambridge Crystallographic Data Centre as supplementary publication
number CCDC-885194. Copy of the data can be obtained free of
charge on application to CCDC (e-mail: deposit@ccdc.cam.ac.uk).
(21) Cosp, A.; Larrosa, I.; Anglada, J. M.; Bofill, J. M.; Romea, P.;
Urpí, F. Org. Lett. 2003, 5, 2809−2812.
(4) Ley, S. V.; Sheppard, T. D.; Myers, R. M.; Chorghade, M. S. Bull.
Chem. Soc. Jpn. 2007, 80, 1451−1472.
(5) Alternatively, substrate-controlled glycolate aldol reactions based
on chiral ketones can be highly successful, see: (a) Paterson, I.; Tillyer,
R. D. J. Org. Chem. 1993, 58, 4182−4184. (b) Paterson, I.; Wallace, D.
́
(22) Galvez, E.; Romea, P.; Urpí, F. Org. Synth. 2009, 86, 81−91 and
references therein.
(23) Removal of the chiral auxiliary by using an enolate is
uncommon. For precedents, see: (a) Smith, T. E.; Djang, M.;
Velander, A. J.; Downey, C. W.; Carroll, K. A.; van Alphen, S. Org. Lett.
2004, 6, 2317−2320. (b) Crimmins, M. T.; McDougall, P. J.; Ellis, J.
M. Org. Lett. 2006, 8, 4079−4082.
́
J.; Velazquez, S. M. Tetrahedron Lett. 1994, 35, 9083−9086. (c) Díaz-
Oltra, S.; Carda, M.; Murga, J.; Falomir, E.; Marco, J. A. Chem.Eur. J.
2008, 14, 9240−9254 and references therein.
(6) For other successful approaches based on chiral esters, see:
(a) Andrus, M. B.; Mendenhall, K. G.; Meredith, E. L.; Sekhar, B. B. V.
S. Tetrahedron Lett. 2002, 43, 1789−1792. (b) Ley, S. V.; Dixon, D. J.;
Guy, R. T.; Palomero, M. A.; Polara, A.; Rodríguez, F.; Sheppard, T. D.
Org. Biomol. Chem. 2004, 2, 3618−3627.
(7) For boron enolates, see: (a) Evans, D. A.; Bartroli, J.; Shih, T. L. J.
Am. Chem. Soc. 1981, 103, 2127−2129. (b) Evans, D. A.; Bender, S. L.;
Morris, J. J. Am. Chem. Soc. 1988, 110, 2506−2526. (c) Davies, S. G.;
Hunter, I. A.; Nicholson, R. L.; Roberts, P. M.; Savory, E. D.; Smith, A.
D. Tetrahedron 2004, 60, 7553−7577.
(8) For titanium enolates, see: (a) Crimmins, M. T.; Tabet, T. A. J.
Am. Chem. Soc. 2000, 122, 5473−5476. (b) Crimmins, M. T.; She, J.
Synlett 2004, 1371−1374. (c) Crimmins, M. T.; Ellis, J. M. J. Org.
Chem. 2008, 73, 1649−1660. (d) Crimmins, M. T.; Ellis, J. M.;
Emmitte, K. A.; Haile, P. A.; McDougall, P. J.; Parrish, J. D.;
Zuccarello, J. L. Chem.Eur. J. 2009, 15, 9223−9234.
(9) For a related approach based on oxazilidineselenones, see: Li, Z.;
Wu, R.; Michalczyk, R.; Dunlap, R. B.; Odom, J. D.; Silks, L. A., III. J.
Am. Chem. Soc. 2000, 122, 386−387.
(10) Crimmins, M. T.; McDougall, P. J. Org. Lett. 2003, 5, 591−594.
(11) For a highly diastereoselective anti glycolate aldol reaction
provided by the titanium enolates from tert-butyl glycolic ester, see:
Gawas, D.; Kazmaier, U. J. Org. Chem. 2009, 74, 1788−1790.
(12) Fanjul, S.; Hulme, A. N. J. Org. Chem. 2008, 73, 9788−9791.
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