Sharpless Asymmetric Dihydroxylation on α,β-Unsaturated Diazoketones: A New Entry for the Synthesis of Disubstituted Furanones

Article abstract of DOI:10.1055/s-0036-1590977

The synthesis of enantiomerically pure 4,5-disubstituted 2-furanones is accomplished in three steps from aldehydes. The steps involve a highly enantioselective Sharpless asymmetric dihydroxylation of α,β-unsaturated diazoketones, followed by a photochemical Wolff rearrangement.

Full text of DOI:10.1055/s-0036-1590977

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
2017, 28, A–E
cluster
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A. G. Talero, A. C. Burtoloso
Cluster
Synlett
Sharpless Asymmetric Dihydroxylation on α,β-Unsaturated Diazo-
ketones: A New Entry for the Synthesis of Disubstituted Fura-
nones
O
Alexánder G. Talero
Ar
Antonio C. B. Burtoloso*
0
0
0
0
0-
0
0
3
2-
2
0
3
1-
5
5
6
O
P
O
Instituto de Química de São Carlos, Universidade de São Paulo,
CEP 13560-970, São Carlos, SP, Brazil
antonio@iqsc.usp.br
,
base
EtO
EtO
N2
OH
O
O
Wolff
rearrangement
HO
Sharpless asymmetric
dihydroxylation
Ar
Ar
O
OH N2
Ar
O
N2
enantiomerically pure
2-furanones
3 steps from aldehydes
up to >99% ee
α,β-unsaturated
diazoketone
multifunctional platforms
for the synthesis of different
O-heterocycles and polyols
Received: 31.05.2017
Accepted after revision: 10.07.2017
Published online: 15.08.2017
preliminary study on how we could accomplish not only
the racemic dihydroxylation of α,β-unsaturated diazoke-
tones, but also the enantioselective version. Moreover, ap-
plication in the short synthesis of enantiomeric pure disub-
stituted furanones in three steps from aldehydes is demon-
strated.
DOI: 10.1055/s-0036-1590977; Art ID: st-2017-b0414-c
Abstract The synthesis of enantiomerically pure 4,5-disubstituted 2-
furanones is accomplished in three steps from aldehydes. The steps in-
volve a highly enantioselective Sharpless asymmetric dihydroxylation of
α,β-unsaturated diazoketones, followed by a photochemical Wolff rear-
rangement.
O
unsaturated
diazoketone
R
dihydroxylation
Key words unsaturated diazoketones, Sharpless dihydroxylation, fura-
N2
nones, Wolff rearrangement, photochemistry, asymmetric synthesis
OH
O
O
HO
HO
α,β-Unsaturated α′-diazoketones1 have proven to be im-
portant building blocks in synthesis. Possessing in the same
molecule functions such as a diazo group, a carbonyl group
and a double bond, these compounds can furnish the short
and direct synthesis of several molecules, including hetero-
cycles. Although very promising, these diazoketones were,
for a long period of time, little studied or employed in syn-
thesis, mainly because of the difficulties associated with
their preparation. In the last few years our research group
developed two new olefination reagents that permitted the
selective synthesis of several E- and Z-α,β-unsaturated α′-
diazoketones in one step from aldehydes.2,3 By employing
these building blocks, we could synthesize several nitrogen
heterocycles such as pyrrolidines, indolizidines, quino-
lizidines, and piperidines by means of aza-Michael addi-
tion,4 Wolff rearrangement,5 and N–H insertion reactions6
as key steps.
As a continuation of our studies with this class of diazo-
compounds, we wondered whether a dihydroxylation of
the double bond could happen in the presence of the fragile
diazo function. This would furnish, for the first time, α,β-
dihydroxy α′-diazoketones that could be employed in the
direct synthesis of several oxygen heterocycles and polyols
as depicted in Figure 1. Herein, we would like to show our
R
O
R
R
O
OH N2
O
3-furanones
2-furanones
OR
O
OH OH
O
OH
R
polyols
3-oxetanones
OH
Figure 1 α,β-Dihydroxy α′-diazoketones as useful intermediates in
synthesis
We started our work by performing the classical Upjohn
dihydroxylation7 from unsaturated diazoketone 1, employ-
ing catalytic OsO4 and N-methylmorpholine N-oxide
(NMO), to prepare racemic diol 2 (Scheme 1). These condi-
tions resulted in complete decomposition of 1 to many
products, probably via the intermediacy of a reactive osmi-
um carbenoid.8 No diol was observed after careful analysis.
The use of potassium osmate, instead of osmium tetroxide,
was also fruitless. We next decided to carry out a Sharpless
type racemic dihydroxylation9–11 employing DABCO as the
ligand for the osmium catalyst. This could enhance the ste-
ric hindrance around the metal and, perhaps, hinder the
formation of the undesired osmium carbenoid. In fact, by
using the classical conditions for the Sharpless asymmetric
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

B
A. G. Talero, A. C. Burtoloso
Cluster
Synlett
We started the optimization study by increasing the
amount of potassium osmate and chiral ligand (DHQ)2PHAL
found in commercially AD-mix-α, as well as employing the
milder base NaHCO3 in place of K2CO3 (Table 1, entry 1).
These conditions furnished 20% yield of diol 2, based on the
recovery of diazoketone 1 (56% conversion). Raising the
amount of ligand provided a better conversion, but gave al-
most the same yield (entry 2). Increasing the amount of po-
tassium osmate to 5.0 mol% (keeping the amount of ligand
or increasing it also to 5.0 mol%) caused faster decomposi-
tion of diazoketone 1, leading to many by-products (entries
3 and 4). From the conditions in entries 1–4, prolonged re-
action times (48 to 120 h), as well as higher concentrations
of NaHCO3, MSA and K3Fe(CN)6 did not furnish better yields
(data not shown). Returning to commercially AD-mix-α re-
agent proportions, but enhancing the amount of MSA (en-
try 5) and of the base/K3Fe(CN)6 (entry 6) also did not lead
to any appreciable change in the yield. Interestingly, reduc-
ing the reaction time to 10 hours improved the yield to 48%,
keeping the same reaction conversion (entry 7). This sug-
gested that diol 2 was being decomposed with time. In fact,
the detection of benzaldehyde in reactions with prolonged
times was evidence of the decomposition of 2 by a retro-al-
dol reaction. When the temperature was increased to 40 °C
AD-mix-α,
AD-mix proportion
using DABCO
as ligand, MSA,
25 °C, 24 h
MSA,
OH
O
OH
O
25 °C, 24 h
(or 0 °C, 5 d)
O
Ph
(+)-2
Ph
(+/-)-2
Ph
t-BuOH/H2O
t-BuOH/H2O
1
OH N2
OH N2
~10%
N2
(1:1)
(1:1)
~10%, ≥99% ee
MSA: methanesulfonamide
Scheme 1 First and unoptimized results in the dihydroxylation reac-
tion from α,β- unsaturated diazoketone 1
dihydroxylation (SAD),9 but replacing the chiral ligand by
achiral DABCO, a 5% yield of diol 2 could be obtained after
24 hours, along with a substantial amount of unreacted di-
azoketone 1. Increasing the temperature from 0 to 25 °C
raised this yield to approximately 10%. Once again, unreact-
ed 1 was recovered, but much less decomposition product
was observed. To evaluate the enantioselectivity of the re-
action, we also performed this reaction with commercially
available AD-mix-α. Although the same low yield was ob-
served, high enantiomeric excess (≥ 99%) could be obtained
in this first attempt. This result encouraged us to perform
an optimization study for the SAD, aiming to get better
yields and reaction conversions.
Table 1 Optimization Studies on the SAD of Unsaturated Diazoketone 1a
O
OH
O
[K2OsO2(OH)4], (DHQ)2PHAL,
base, MSA, K3Fe(CN)6
Ph
Ph
(+)-2 OH N2
t-BuOH/H2O (1:2), 25 °C
1
N2
Entry MSA (equiv) and base (equiv) K3Fe(CN)6 (equiv) [K2OsO2(OH)4] (mol%) (DHQ)2PHAL (mol%) Time (h)
Conv. (%)
Yield (%)b
e.r.c
>99:1
1
2
3
4
5
6
7
8d
9
1 and 1 NaHCO3
1 and 1 NaHCO3
1 and 1 NaHCO3
1 and 1 NaHCO3
3 and 3 K2CO3
3 and 6 K2CO3
3 and 6 K2CO3
3 and 6 K2CO3
1 and 3 K2CO3
3 and 6 K2CO3
3 and 6 K2CO3
3 and 6 K2CO3
6 and 12 K2CO3
6 and 12 K2CO3
6 and 12 K2CO3
3
3
1
2.5
5
24
24
24
24
24
24
10
10
10
10
10
10
20
20
20
56
72
–
20
1
17
–
3
5
1
trace
trace
18
–
3
5
5
–
–
3
0.4
0.4
0.4
0.4
0.4
2.5
0.4
0.4
0.8
0.8
5
1
60
72
68
50
30
84
72
74
94
84
100
–
6
1
13
–
6
1
48
>99:1
95:5
>99:1
–
6
1
75
3
1
20
10
6
5
49
11
6
5
49
99:1
99:1
99:1
99:1
–
12
6
10
55
13e
14e
15e
12
12
12
20
2
57
52
10
20
a All reactions were carried out with diazoketone 1 (25.0 mg, 0.145 mmol) in a concentration of 0.1 M.
b Isolated yields based on the recovery of starting material.
c Measured by HPLC using chiral columns (see the Supporting Information for details). The synthesis of the racemic samples employed the same reaction condi-
tions, but replacing the chiral ligand (DHQ)2PHAL by achiral DABCO.
d Performed at 40 °C.
e SAD reagents added in two portions: half at 0 h and the other half after 10 h.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

C
A. G. Talero, A. C. Burtoloso
Cluster
Synlett
(entry 8), the yield was boosted to 75%, but at a cost to en-
antioselectivity (95:5) and to diazoketone conversion (50%).
It is worth mentioning that when we repeated SAD using
AD-mix-α proportions, but with the reduced reaction time
(10 h), low yield and conversion was obtained (entry 9),
showing that higher concentration of MSA,12 base and Fe
co-oxidant is important. At this point, the conditions shown
in entry 7 appeared to be the best option. From these best
conditions, increasing the quantity of both osmium salt and
ligand raised the conversion of 1 to 16%, but provided basi-
cally the same yield (entry 10). Dropping the amount of po-
tassium osmate and keeping the ligand to 5 mol% did not
change the yield, but reduced the conversion in 12% (entry
11). Keeping the conditions in entry 11, but increasing the
ligand concentration gave a higher yield with the same con-
version of 1 (entry 12). Finally, repeating this best condi-
tions (entry 12) and after 10 h adding the same proportions
of reagents again, 94% conversion of 1, together with 57%
chemical yield, was obtained (entry 13). The next two stud-
ies were done by repeating entries 7 and 10 in the same
way described in entry 13 (adding the SAD reagents in two
portions). As can be seen in Table 1, after this optimization
study, best conditions are described in entries 13 and 14.
Entry 13 provided the best yield and conversion, but at the
cost of more chiral ligand.13
more like those observed for 1. Electron-withdrawing
groups such as 4-Cl-Ph and 4-NO2-Ph provided moderate
yields. All these results indicate that electronic effects may
not rule too much the reaction yield. Other studies are on-
going to better understand this SAD behavior in unsaturat-
ed diazoketones. The Z isomer of diazoketone 1 also provid-
ed good yield for the SAD, indicating that the double bond
geometry has little influence in the chemical yield. This
opened the reactional scope for the synthesis of trans diols.
Finally, employing (DHQD)2PHAL (found in AD-mix-β), in-
stead of (DHQ)2PHAL, gave the other enantiomer of 2 in
good yield (47%, 56% based on recovery of starting material)
and in more than 99% enantiomeric excess. The same reac-
tion was also performed in a larger scale (250 mg of 1, 1.45
mmol; see the Supporting Information), furnishing the
same yield. The observed absolute configuration of enantio-
meric pure diol 2 is in accordance with Sharpless model and
was determined by converting compound 2 into a known
furanone, as will be further discussed.
As already noted, chiral dihydroxy diazoketones have
not been described before, but can be powerful intermedi-
ates for the synthesis of several class of compounds, em-
ploying diazo chemistry.6 One of the many possible applica-
tions is the synthesis of disubstituted furanones. Well-
known O–H insertion reactions6 and Wolff rearrangement5
could provide 3- and 2-furanones, respectively, directly. Fu-
ranones15 are an important class of compounds with several
interesting biological activities.16 Moreover, with appropri-
ate substitution, these compounds can be useful in the syn-
thesis of important tetrahydrofurans, such as the natural
compounds jaspine A17 and B.18 To demonstrate one of
these applications, some of the synthesized dihydroxy di-
azoketones by SAD were converted into 4,5-disubstituted 2-
Having established the best conditions14 to perform SAD
from 1, we turned our attention to other unsaturated di-
azoketones. Although a high enantiomeric ratio could be
obtained for all diazoketones, yields were moderate to good
and were substrate dependent (Figure 2). Electron-rich di-
azoketones, containing a 4-OMe-Ph or an aliphatic group in
the β-position furnished the worst yields. On the other
hand, diazoketones with 4-Me-Ph and 4-Ph-Ph gave yields
OH
O
OH
O
OH
O
H
H
H
OH N2
OH N2
OH N2
(+)-2
(-)-2
3
53% (57% based on RSM) Using (DHQD)2PHAL; 47% (56%) Using a diazoketone
O
with a Z geometry; 43% (57%)
e.r. = 80:20
[α]25D –86.0 (c = 0.5, MeOH)
e.r. = 99:1
e.r. ≥ 99:1
O
P
O
0.5 M NaOH
25 °C
O
[α]25D +141.6 (c = 0.5, MeOH)
[α]25D –154.4 (c = 0.5, MeOH)
+
H
EtO
EtO
0.5 M in EtOH/H2O
R
R
N2
N2
OH
O
OH
O
OH
O
SAD
H
H
H
O
P
O
t-BuOK, THF
0 to 25 °C
O
R
O
OH N2
OH N2
OH N2
4
5
6
Me
+
Ph
Cl
PhO
PhO
H
38% (51%)
17% (25%)
19% (29%)
R
N2
e.r. ≥ 99:1
e.r. = 99:1
[α]25D +135.6 (c = 0.5, MeOH)
e.r. = 98:1
N2
[α]25D +130.6 (c = 0.5, MeOH)
[α]25D +119.8 (c = 0.5, MeOH)
OH
O
OH
O
OH
O
H
H
H
OH N2
OH N2
OH N2
7
8
9
O2N
MeO
14% (25%)
<10%
<10%
e.r. ≥ 99:1
[α]25D +168.4 (c = 0.5, MeOH)
Figure 2 Substrate scope for the SAD on unsaturated diazoketones
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

D
A. G. Talero, A. C. Burtoloso
Cluster
Synlett
furanones19 in very good yields (70–90%) and high enantio-
meric ratios after the exposure to a 300 W xenon lamp for
12 hours (Figure 3). With respect to the stereochemical out-
come of the SAD, comparison of the optical rotation values
of the cyclized products (+)-10 and (–)-10 with the report-
ed values20 unambiguously confirmed the absolute configu-
ration of diol 2. This result is in complete accordance with
Sharpless model for asymmetric diydroxylation. For the
other dihydroxylation products, we assume the same ste-
reochemistry.
dehydes) is among the shortest ways to prepare enantio-
pure 2-furanones. Additional studies, such as the use of
other chiral ligands, will be undertaken to improve the
yields of some substrates and to better understand this SAD
on unsaturated diazoketones. Finally, other demonstra-
tions, such as the synthesis of 3-furanones and the applica-
tion in the synthesis of natural jaspines A and B, will be car-
ried out.
Funding Information
HO
We would thank FAPESP (Research Supporting Foundation of the State of
Sao Paulo) for financial support (2013/25504-1; 2013/18009-4)
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Acknowledgment
O
O
jaspine A
jaspine B
2- and 3-furanones
HO
We thank CNPq for a research fellowship to A.C.B.B. and a fellowship
to A.G.T. We also thank IQSC-USP for facilities and FAPESP
(2013/50228-8; 2009/54040-8) for HRMS multiuser equipment.
OH
O
MeCN (0.04M),
H
hν, 12 h
O
O
OH N2
R
R
Supporting Information
HO
HO
HO
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1590977.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
O
O
O
O
O
O
Ph
Me
12
68%
11
80%
(+)-10 90%
[α]25D +36.0
(c = 0.3, MeOH)
e.r. = 97:3
[α]25D +34.4
(c = 1.0, MeOH)
[α]25D +32.9
(c = 0.7, MeOH)
e.r. = 99:1
References and Notes
(Lit. +35.6, c = 1.0, MeOH)
(1) Burtoloso, A. C. B.; Dias, R. M. P.; Bernardim, B. Acc. Chem. Res.
2015, 48, 921.
(2) Pinho, V. D.; Burtoloso, A. C. B. J. Org. Chem. 2011, 76, 289.
(3) Rosset, I. G.; Burtoloso, A. C. B. J. Org. Chem. 2013, 78, 9464.
(4) Rulev, A. Y. Russ. Chem. Rev. 2011, 80, 197.
(5) (a) Wolff, L. Justus Liebigs Ann. Chem. 1902, 325, 129. (b) Kirmse,
W. Eur. J. Org. Chem. 2002, 2193. (c) Gill, G. B. In Comprehensive
Organic Synthesis; Fleming, B. M. T., Ed.; Pergamon: Oxford,
1991, 887.
(6) (a) Gillingham, D.; Fei, N. Chem. Soc. Rev. 2013, 42, 4918.
(b) Ford, A.; Miel, H.; Ring, A.; Slattery, C. N.; Maguire, A. R.;
Mckervey, M. A. Chem. Rev. 2015, 115, 9981. (c) Ye, T.;
Mckervey, M. A. Chem. Rev. 1994, 94, 1091. (d) Doyle, M. P.;
Mackervey, M. A.; Ye, T. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds: from Cyclopropanes to Ylides;
Wiley: New York, 1998.
e.r. = 99:1
HO
HO
O
O
O
O
72%
Cl
O2N
85%
13
14
[α]25D +40.0 (c = 0.3, MeOH)
[α]25D +41.6 (c = 0.5, MeOH)
e.r. = 99:1
e.r. = 99:1
HO
OH
O
MeCN (0.04M),
hν, 12 h
H
O
O
OH N2
(–)-10 86%
[α]25D –36.3 (c = 1.0, MeOH)
(Lit. –37.7, c = 0.9, MeOH)
e.r. = 99:1
(7) Vanrheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976, 23,
1973.
(8) (a) Smith, D. A.; Reynolds, D. N.; Woo, L. K. J. Am. Chem. Soc.
1993, 115, 2511. (b) Demonceau, A.; Lemoine, C. A.; Noels, A. F.
Tetrahedron Lett. 1996, 37, 1025.
Figure 3 Application of the SAD products in the synthesis of enantio-
pure 2-furanones
In summary, we have demonstrated our preliminary re-
sults in the asymmetric functionalization of α,β-unsaturat-
ed diazoketones by means of a Sharpless asymmetric dihy-
droxylation. Moderate to good yields and excellent enantio-
selectivities were obtained in the synthesis of a new
platform, containing a diazo function: enantiopure α,β-di-
hydroxy α′-diazoketones. Moreover, application of these in-
termediates in the direct synthesis of chiral 2-furanones
shows one of the many versatilities of these platforms. To
our knowledge, this sequence (three steps starting from al-
(9) (a) Sharpless, K. B.; Amberg, W.; Benani, Y. L.; Crispino, G. A.;
Hartung, J.; Jeong, K-S.; Kwong, H.-L.; Morikawa, K.; Wang, Z.-
M.; Xu, D.; Zhang, X.-L. J. Org. Chem. 1992, 57, 2768. (b) Kolb, H.;
VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94,
2483.
(10) Minato, M.; Yamamoto, K.; Tsuji, J. J. Org. Chem. 1990, 55, 766.
(11) Eames, J.; Mitchell, H. J.; Nelson, A.; O’brien, P.; Warren, S.;
Wyatt, P. J. Chem. Soc., Perkin Trans. 1 1999, 1095.
(12) Junttila, M. H.; Hormi, O. O. E. J. Org. Chem. 2009, 74, 3038.
(13) Jacobsen, E. N.; Markó, I.; Mungall, W. S.; Schröder, G.;
Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 1968.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

E
A. G. Talero, A. C. Burtoloso
Cluster
Synlett
(14) General Procedure for Asymmetric Dihydroxylation of α,β-
Unsaturated Diazoketones: To a 3 mL glass vial containing a
magnetic stirrer and fitted with a cap, was added 418 mg of an
oxidizing mixture containing K3Fe(CN)6 (6 equiv, 286.8 mg, 0.87
mmol), K2CO3 (6 equiv, 120.4 mg, 0.87 mmol), (DHQ)2PHAL
(11.3 mg, 0.0145 mmol), and K2OsO2(OH)4 (0.214 mg, 0.0581
mmol). Then, a t-BuOH/H2O mixture (1:2, 1.5 mL) was added
and the mixture was vigorously stirred. CH3SO2NH2 (3 equiv,
41.4 mg, 0.435 mmol) and α,β-unsaturated diazoketone (1
equiv, 0.145 mmol) were added and the mixture was allowed to
react for 10 hours. After this time, another portion of the oxidiz-
ing mixture (418 mg) and CH3SO2NH2 (41.4 mg) were added and
the mixture was stirred for an additional 10 h (progress of the
reaction monitored by TLC). After this time, H2O (30 mL) was
added to the reaction mixture and the aqueous phase was
extracted with a mixture of CH2Cl2 and 2-propanol (3:1, 2 × 10
mL), followed by another extraction with pure CH2Cl2 (3 × 10
mL) (conventional work-up with Na2SO3 and base led to degra-
dation of the products). The organic phase was dried over
Na2SO4, filtered and concentrated. The products were purified
by flash chromatography (silica gel, 1:1 hexane/EtOAc) to afford
the pure solid diols (Note: all racemic diols were synthesized by
using DABCO as the ligand in similar yields; For larger scales,
the conditions described in Table 1, entry 14, was preferred).
(3R,4S)-1-Diazo-3,4-dihydroxy-4-phenylbutan-2-one [(+)-2]:
Yield: 16 mg (53% yield; 57% based on recovery of starting
material; diazoketone recovered: 1.5 mg); crystalline yellow
solid; mp 97–99 °C; Rf = 0.15 (silica gel, 1:1 EtOAc/hexane); IR:
3332, 3268, 3118, 2918, 2115, 1599, 1363, 1300, 1140, 1047,
(15) Carter, N. B.; Nadany, A. E.; Sweeney, J. B. J. Chem. Soc., Perkin
Trans. 1 2002, 2324.
(16) (a) Shah, N. C.; Pringle, S. D.; Donan, P. T.; Struthers, A. D.
J. Hypertens. 2007, 25, 2345. (b) Raju, R.; Gromyko, O.;
Fedorenko, V.; Herrmann, J.; Luzhetskyy, A.; Müller, R. Tetrahe-
dron Lett. 2013, 54, 900. (c) Yabu, Y.; Yoshida, A.; Suzuki, T.;
Nihei, C.; Kawai, K.; Minagawa, N.; Hosokawa, T.; Nagai, K.;
Ohta, N. Parasitol. Int. 2003, 52, 155.
(17) Ledroit, V.; Debitus, C.; Lavaud, C.; Massiot, G. Tetrahedron Lett.
2003, 44, 225.
(18) (a) Kuroda, I.; Musman, M.; Ohtani, I. I.; Ichiba, T.; Tanaka, J.;
Gravalos, D. C.; Higa, T. J. Nat. Prod. 2002, 65, 1505.
(b) Martinková, M.; Gonda, J. Carbohydr. Res. 2016, 423, 1.
(19) General Procedure for the Synthesis of 4,5-Disubstituted 2-
Furanones: In a quartz cell of 1 cm light path, containing a
magnetic stirrer and fitted with a rubber septum, was added
the diol (0.1 mmol) and anhydrous acetonitrile (2.5 mL, 0.04 M)
under argon atmosphere. The reaction mixture was irradiated
with an Osram 150 xenon arc lamp for 10 h under magnetic
stirring at room temperature. The solvent was then removed
under reduced pressure in a rotatory evaporator and the crude
product was purified by flash chromatography with a short pad
of silica (CHCl3 as the eluent). Lactones were obtained as solids.
(4S,5S)-4-Hydroxy-5-phenyldihydrofuran-2(3H)-one [(+)-10]:
Yield: 16 mg (90% yield); pale-yellow solid; mp 78–80 °C; Rf =
0.2 (silica gel, CHCl3, twice eluted); IR: 3432, 2929, 1773, 1454,
1310, 1154, 1075, 1020, 742, 699 cm–1 1H NMR (500 MHz,
;
CDCl3): δ = 7.47–7.43 (m, 2 H), 7.42–7.37 (m, 3 H), 5.52 (d,
J = 3.5 Hz, 1 H), 4.63 (m, 1 H), 2.90 (dd, J = 17.5, 5.1 Hz, 1 H),
2.74 (d, J = 17.5 Hz, 1 H), 1.48 (s, 1 H); 13C NMR (101 MHz,
CDCl3): δ = 175.3, 132.3, 129.1, 129.0, 126.3, 85.0, 70.2, 38.5;
[α]D25 +34.4 (c = 0.98, MeOH); HPLC conditions: Lux® amilose-2
8:2 (n-hexane/IPA); flow rate: 1.1 mL/min; λ = 206 nm;
tR = 18.58 (major), 22.06 (minor) min; e.r. = 98:02.
708 cm–1 1H NMR (500 MHz, CD3CN): δ = 7.40–7.32 (m, 4 H),
;
7.27 (tt, J = 7.2, 1.3, 1.3 Hz, 1 H), 5.88 (s, 1 H), 4.95 (dd, J = 5.5,
2.9 Hz, 1 H), 4.16 (d, J = 3.3 Hz, 1 H), 3.74 (d, J = 6.8 Hz, 1 H),
3.64 (d, J = 5.9 Hz, 1 H); 13C NMR (126 MHz, CD3CN): δ = 196.6,
142.4, 128.9, 128.3, 127.4, 80.2, 74.8, 54.5; [α]D25 +141.6 (c = 0.5,
MeOH); HRMS (ESI-TOF): m/z [M++Na] calcd for C10H10N2NaO3:
229.05836; found: 229.05801; HPLC conditions: Chiralpak AD-
H, 1:1 (n-hexane/IPA); flow rate: 1.0 mL/min; λ = 254 nm;
tR = 4.60 (minor), 8.74 (major) min; e.r. = 99:1.
(20) (a) Wang, Z.-M.; Zhang, X.-L.; Sharpless, K. B.; Sinha, S. C.;
Sinha-Bagchi, A.; Keinan, E. Tetrahedron Lett. 1992, 33, 6407.
(b) Reddy, G. V.; Sreevani, V.; Iyengar, D. S. Tetrahedron Lett.
2001, 42, 531. (c) Eissler, S.; Nahrwold, M.; Neumann, B.;
Stammler, H.-G.; Sewald, N. Org. Lett. 2007, 9, 817.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E