Stereocontrolled photocyclization of 1,2-diketones applied to carbohydrate models: A new entry to C-ketosides

Article abstract of DOI:10.1055/s-2007-984523

Photolysis of 1-glycosyl-2,3-butanedione derivatives using visible light is a mild and selective procedure for the synthesis of chiral 1-hydroxy-1-methyl- 5-oxaspiro[3.5]nonan-2-one carbohydrate derivatives. The results strongly suggest that stereocontrol

Full text of DOI:10.1055/s-2007-984523

LETTER
1851
Stereocontrolled Photocyclization of 1,2-Diketones Applied to Carbohydrate
Models: A New Entry to C-Ketosides
S
tereocontrolledP
n
hotocyclizati
t
on of
1
o
,2-Diketonesnio J. Herrera,* María Rondón, Ernesto Suárez*
Instituto de Productos Naturales y Agrobiología del C.S.I.C, Carretera de La Esperanza 3, 38206 La Laguna, Tenerife, Spain
Fax +34(922)260135; E-mail: esuarez@ipna.csic.es; E-mail: ajherrera@ipna.csic.es
Received 16 March 2007
a very small rate constant related to alkyl and aryl ke-
Abstract: Photolysis of 1-glycosyl-2,3-butanedione derivatives
tones.3 However, in our cases, the reactions were accom-
plished within relatively short times. It is noteworthy that
a new factor has been introduced in these models. The hy-
using visible light is a mild and selective procedure for the synthesis
of chiral 1-hydroxy-1-methyl-5-oxaspiro[3.5]nonan-2-one carbo-
hydrate derivatives. The results strongly suggest that stereocontrol
of the cyclization is dependent on conformational and stereoelec- drogen atom to be transferred is geminate to oxygen and
tronic factors which can be modulated efficiently by using photo-
sensitizers in some cases. Further oxidative opening of the 1-
hydroxy-1-methyl-2-cyclobutanone moiety affords new C-ketoside
tive stabilizing interaction of the SOMO-C5 radical with
derivatives. This two-step process could be considered to be a
stereocontrolled 1,3-transfer of an acetyl group.
may be specially activated. Furthermore, the 1,4-diradical
intermediate II may be stabilized by a possible conjuga-
the lone pair at the ring oxygen and the s*-LUMO of the
C6–O bond.7 This C5-centered radical resembles the in-
Key words: photochemistry, spiro compounds, memory effect,
depth studied anomeric radical9 where the C5–H bond has
diastereoselectivity, glycosides
been replaced by a C5–alkyl, thus it will be named
pseudo-anomeric radical. Such stabilization may affect
the lifetime of intermediate II.
The Norrish–Yang photocyclization is an efficient meth-
od to generate regio- and stereocontrolled C–C bonds in
3
OH
2
mild conditions.1 This reaction has been employed in or-
O
O
H
X
O
X
O
hν, ISC
ganic synthesis, aliphatic and aromatic ketones, and a-
keto esters being the most widely used reactants.2 Al-
though the photocyclization of 1,2-diketones to generate
2-hydroxy-cyclobutanones has been well studied since
the early 1960s,3 this methodology has seldom been
applied3a,4 and, as far as we know, only one case involved
a chiral substrate.5 Diastereoselective C–C bond forma-
tion, absence of additional reagents, high yields, and pos-
sible use of sunlight are the most attractive features of this
methodology for the synthetic chemist and render the ex-
ploration of its scope and limitations highly interesting.
9
5
6
4
O
OR
OR
(RO)2
(RO)2
I
II (1–4)
OH
OH
OR
O
O
X
O
X
O
ISC
5
5
+
OR
(RO)2
(RO)2
IV inversion
III retention
X = OMe, Me, CH2OBn
Scheme 1 Photocyclization of 1,2-diketones10
Herein, we report on the highly efficient use of a Norrish–
Yang photocyclization to obtain new spirocyclic
monosaccharide derivatives of types III and IV via a
hydrogen-atom transfer (HAT) reaction promoted by a
1,2-diketone I, in its excited state, followed by C–C bond
formation in a diastereoselective manner (Scheme 1). The
conformational changes that the 1,4-diradical intermedi-
ate II suffers in its triplet state before the intersystem
crossing (ISC) occurs, governs the reaction course.
With the aim of rationalizing the role of the stereoelec-
tronic and conformational factors in the stereocontrol of
this process, we have synthesized a number of carbohy-
drate models shown in Table 1 and submitted to various
photolysis conditions.11
Model 1 was selected due to its conformationally restrict-
ed 4C1 pyranose ring.12 1,2-Diketone 1 was irradiated with
outdoor sunlight in its crystalline form for 20 hours until
the yellow color faded affording a mixture of compounds
from which the main product 5a was isolated in moderate
yield after silica gel chromatography as a sole stereoiso-
mer (entry 1). Side products of photooxidation and inter-
molecular reactions were formed, probably due to the
presence of oxygen, long reaction time, and restricted mo-
bility of the molecules in the crystalline net.13 However,
only one product 5a was obtained in quantitative yield
with CHCl3 or C6H6 as solvent (entries 2 and 3). Slightly
We point to three main factors that are responsible for the
behavior of transient intermediate II: lifetime of the 1,4-
diradical species,6 stereoelectronic interactions,6b,7 and
conformational restrictions.8
It has been reported that 1,2-diketones mainly undergo
ISC to their triplet state and abstract hydrogen atoms with
SYNLETT 2007, No. 12, pp 1851–1856
2
4
.0
7
.2
0
0
7
Advanced online publication: 25.06.2007
DOI: 10.1055/s-2007-984523; Art ID: G08007ST
© Georg Thieme Verlag Stuttgart · New York

1852
A. J. Herrera et al.
LETTER
shorter reaction time was required with benzene. It is im- 8). Under these singlet conditions, the cyclization of the
portant to note that the deoxygenation of solvents was not diradical II-2 (S1-spinisomer) intermediate is obviously
necessary since no products of photooxidation were de- so fast that rotations around the C4–C5 single bond do not
tected as long as the reaction time was not greatly extend- take place and the C2–C5 bond is formed completely with
ed. The reaction proceeded with total retention at C5. For retention, showing an excellent memory effect. The con-
this model, C5 presumably adopts a trigonal sp2 hybrid- figuration of the asymmetric center C2 in this last experi-
ization at the 1,4-diradical intermediate II-1 stage, and the ment is probably controlled by the existence of an
ring moiety should not undergo dramatic conformational intramolecular hydrogen bond, steric factors, and restrict-
changes, which are especially restricted by the anomeric ed rotation of C2–C3 in the short-lived singlet diradical
effect at C9. The existence of an intramolecular hydrogen II-2 intermediate.
bond probably enhanced the high stereocontrol at C2 and
4
The model 3 also adopts a C1 conformation12 with the
C5, since the introduction of a protic solvent led to a mix-
transferring hydrogen atom in axial position. Irradiation
of 3 either in chloroform or in benzene afforded the target
ture of diastereoisomers (entry 4).14
Irradiation of model 2 with sunlight or a medium-pressure compound 7 in good yields as a mixture of two diastereo-
mercury lamp15 gave the expected product 6 in excellent isomers with complete retention (entries 9 and 10). The
yields, as a mixture of three diastereoisomers (entries 5 addition of pyrene significantly increased the reaction
and 6). The reaction proceeded predominantly with reten- time but without altering the diastereoisomeric ratio at the
tion at C5 (6a and 6b), although the inversion product 6c C2 stereocenter (entry 11).
was also isolated, showing a remarkably good memory
Photocyclization of the substrate 4 with sunlight in chlo-
roform afforded the four possible stereoisomers of spiro
effect16of 12 and 21, respectively [(6a + 6b):6c = 12:1 and
21:1]. In this case, substrate 2 is in a 4C1 conformation,12
but the pyranosyl ring of the intermediate II-2 is confor-
mationally more flexible and distortions are more likely,
and even more so when placing the OMe group in the
compound 8 with good yield and a poor memory effect of
1
1.8 [(8a + 8b)/(8c + 8d) = 8:4.5] (entry 12). A H NMR
experiment indicated that starting compound 4 adopts a
4C1 conformation with the transferring hydrogen atom in
axial position, because of the anomeric effect at C9.
equatorial position.
The photoreaction of 2 in the presence of the triplet sensi-
tizer benzophenone led almost to the same ratio of diaste-
reoisomers of 6 (compare entries 6 and 7). The reaction
was complete in half time, though the yield slightly de-
creased. In contrast, in the presence of pyrene, not only as
a triplet quencher but also as a singlet sensitizer, product
6 was obtained with total diastereoselectivity and high
yield, although longer reaction time was required (entry
Changes in the radiation source and solvents did not alter
the outcome of the reaction considerably (entries 12–15).
This reaction can be performed in a very efficient and
environmentally friendly way as shown in entry 15.
Table 1 Photocyclization of 1,2-Diketones via HAT at a Pseudo-Anomeric Position10
Entry
Substrate
Conditionsa
Time (h)
Product ratiob
Yield (%)
a:b:c:d
HO
O
O
2
O
O
O
OMe
OBn
5
9
OMe
OBn
BnO
BnO
BnO
5
BnO
1
1
2
3
4
A
B
C
D
21
2
1:0:0:0
1:0:0:0
1:0:0:0
6:1:1:0
42
quant.
quant.
92
1.6
1.8
HO
O
O
2
O
O
O
5
OMe
OBn
9
OMe
OBn
BnO
BnO
BnO
BnO
6
2
Synlett 2007, No. 12, 1851–1856 © Thieme Stuttgart · New York

LETTER
Stereocontrolled Photocyclization of 1,2-Diketones
1853
Table 1 Photocyclization of 1,2-Diketones via HAT at a Pseudo-Anomeric Position10 (continued)
Entry
Substrate
Conditionsa
Time (h)
Product ratiob
Yield (%)
a:b:c:d
5
6
7
8
B
1
10:2:1:0
15:6:1:0
11:3:1:0
1:0:0:0
95
95
88
80
E
0.6
0.3
2.0
Ec
Ed
OH
2
O
O
O
O
O
5
TBSO
TBSO
7
OTBS
TBSO
OTBS
TBSO
3
9
10
11
B
4
3
0:0:1:3
0:0:1:4
0:0:1:4
78
83
87
C
Ed
13
OH
BnO
O
O
2
BnO
O
O
O
5
BnO
BnO
8
OBn
BnO
OBn
BnO
4
12
13
14
15
B
E
F
4.5
1
1:7:2.5:2
1:7:2:2
92
90
80
85
2
1:3:1:1.5
1:6:2:2.5
A
2.5
a Conditions: A: sunlight, neat; B: sunlight, CHCl3; C: sunlight, C6H6; D: sunlight, t-BuOH–CHCl3 (3:1); E: UV lamp, CHCl3; F: UV lamp,
neat.
b For better understanding, the main diastereomer is depicted; a = 2R,5R; b = 2S,5R; c = 2R,5S; d = 2S,5S; diastereoisomer pairs a, b and c, d
were formed with retention and inversion, respectively, in products 5, 6, and 8; c, d were formed with retention in 7. The ratios and stereo-
chemistries were determined by 1H NMR and NOE experiments, respectively.
c 0.5 M benzophenone, 38 mM substrate.
d 0.5 M pyrene, 38 mM substrate.
In addition to the cases commented in Table 1 (entries 8 suggest an excited triplet state but the high efficiency of
and 11), pyrene has also been added to substrate 4 with the pyrene in the stereocontrol of model 2 remains unclear at
aim of modulating the stereoselectivity. Indeed, pyrene present. Basically, model 4 differs from model 1 in the
strongly inhibits the process, extending reaction times nature of substituent X (OMe, CH2OBn), which could
over beyond 48 hours and leading to the formation of provide a different feature for the 1,4-diradical inter-
contaminating side products, but scant influence on the mediate II.
stereoselectivity was observed. On the other hand, per-
forming the photochemical reaction of substrates 2–4 in
the presence of naphthalene did not affect either the reac-
tion times or the diastereoisomeric ratios. The presence of
added benzophenone as triplet sensitizer significantly
reduced reaction times of models 1, 3, and 4 by approxi-
mately 30–50% but no changes were observed in the dias-
tereoisomeric ratios.17 These preliminary experiments
The 1-hydroxy-1-methyl-cyclobutan-2-one moiety could
be opened with oxidative conditions in a preparative man-
ner with excellent yield as depicted in Scheme 2.3d
A
diastereoisomeric mixture of compound 7 led to a single
product, 9, which after deprotection afforded a new C-
ketoside 10.
Synlett 2007, No. 12, 1851–1856 © Thieme Stuttgart · New York

1854
A. J. Herrera et al.
LETTER
been used.2 Further studies of the memory effect of this
reaction, applied to other carbohydrate derivatives as well
as noncyclic chiral compounds, are currently under way in
our laboratory.
OH
O
O
O
O
HIO4, MeOH
r.t., 0.5 h
CO2Me
OTBS
TBSO
TBSO
O
OTBS
95%
OTBS
OTBS
7
9
Acknowledgment
This work was supported by the Investigation programs No.
CTQ2004-06381/BQU and CTQ2004-02367/BQU of the
Ministerio de Educación y Ciencia, Spain, cofinanced with the
Fondo Europeo de Desarrollo Regional (FEDER). A.J.H. and M.R.
thank the Program I3P-CSIC and ULA-Venezuela, respectively, for
research contracts. We thank Dr. C. C. González and A. González
for fruitful discussions.
O
TsOH, MeOH
reflux, 30 h
CO2Me
HO
OH
85%
OH
10
Scheme 2 Synthesis of C-ketosides
References and Notes
This procedure introduces a new entry into C-ketosides,
which can only be accessed through chemical synthesis.18
The two-step conversion of 3 into 9 can be considered to
be a stereocontrolled 1,3-transfer of the acetyl group.
(1) For reviews on Norrish–Yang reaction, see: (a) Wagner, P.
J. Acc. Chem. Res. 1989, 22, 83. (b) Wagner, P. J.; Park, B.
In Organic Photochemistry; Padwa, A., Ed.; Marcel Dekker:
New York, 1991, 227. (c) Wagner, P. J.; Klán, P. In
Handbook of Organic Photochemistry and Photobiology,
2nd ed.; Horspool, W. M.; Lenci, F., Eds.; CRC Press: Boca
Raton, 2003, Chap. 52. (d) Hasegawa, T. In Handbook of
Organic Photochemistry and Photobiology, 2nd ed.;
Horspool, W. M.; Lenci, F., Eds.; CRC Press: Boca Raton,
2003, Chap. 55. (e) Wessig, P. In Handbook of Organic
Photochemistry and Photobiology, 2nd ed.; Horspool, W.
M.; Lenci, F., Eds.; CRC Press: Boca Raton, 2003, Chap.
57. (f) Wagner, P. J. In Handbook of Organic
This methodology can be also extended to furanosyl de-
rivatives. Ozonolysis of alkyne 11 followed by treatment
with Me2S11a afforded the 1,2-diketone 12 which was di-
rectly irradiated with sunlight to undergo the cyclization
(Scheme 3). Due to the instability of the photocyclization
products in silica gel, the oxidative opening was carried
out without purification. This protocol of three consecu-
tive steps protocol afforded the desired g-ketoester 13 in
moderate overall yield as an inseparable mixture of dia-
stereoisomers (4R:4S = 5:1). This result indicates that the
Norrish–Yang reaction proceeded predominantly with re-
tention albeit with a small memory effect of 5. Steric hin-
drance at the b-face of the bicyclic compound 12 may be
the reason to force the inversion on the pseudo-anomeric
radical.
Photochemistry and Photobiology, 2nd ed.; Horspool, W.
M.; Lenci, F., Eds.; CRC Press: Boca Raton, 2003, Chap.
58. (g) Wagner, P. J. In Synthetic Organic Photochemistry
(Molecular and Supramolecular Photochemistry), Vol. 12;
Griesbeck, A. G.; Mattay, J., Eds.; Marcel Dekker: New
York, 2005, 11.
(2) For recent reviews, see: (a) Wessig, P. In Radicals in
Organic Synthesis, Vol. 2; Renaud, P.; Sibi, M. P., Eds.;
Wiley-VCH: Weinheim, 2001, 523. (b) Wessig, P.;
Muehling, O. Eur. J. Org. Chem. 2007, 2219.
(3) (a) Urry, W. H.; Trecker, D. J. J. Am. Chem. Soc. 1962, 84,
118. (b) Urry, W. H.; Trecker, D. J.; Winey, D. A.
Tetrahedron Lett. 1962, 3, 609. (c) Turro, N. J.; Lee, T.-J. J.
Am. Chem. Soc. 1969, 91, 5651. (d) Urry, W. H.; Duggan, J.
C.; Pai, M.-S. H. J. Am. Chem. Soc. 1970, 92, 5785.
(4) (a) Hamer, N. K. Tetrahedron Lett. 1982, 23, 473.
(b) Hamer, N. K. J. Chem. Soc., Perkin Trans. 1 1983, 61.
(c) Hamer, N. K. Tetrahedron Lett. 1986, 27, 2167.
(5) Obayashi, M.; Mizuta, E.; Noguchi, S. Chem. Pharm. Bull.
1979, 27, 1679.
(6) For discussions of the lifetime of diradicals in solution, see:
(a) Johnston, L. J.; Scaiano, J. C. Chem. Rev. 1989, 89, 521;
and references cited therein. (b) Cai, X.; Cygon, P.;
Goldfuss, B.; Griesbeck, A. G.; Heckroth, H.; Fujitsuka, M.;
Majima, T. Chem. Eur. J. 2006, 12, 4662.
(7) (a) Dupuis, J.; Giese, B.; Rüegge, D.; Fischer, H.; Korth, H.-
G.; Sustman, R. Angew. Chem., Int. Ed. Engl. 1984, 23, 896.
(b) Giese, B. Angew. Chem., Int. Ed. Engl. 1989, 28, 969.
(c) Brunckova, J.; Crich, D. Tetrahedron 1995, 51, 11945;
and references therein.
(8) (a) Griesbeck, A. G.; Mauder, H.; Stadtmüller, S. Acc.
Chem. Res. 1994, 27, 70. (b) Ihmels, H.; Scheffer, J. R.
Tetrahedron 1999, 55, 885. (c) Giese, B.; Wettstein, P.;
Stähelin, C.; Barbosa, F.; Neuburger, M.; Zehnder, M.;
Wessig, P. Angew. Chem. Int. Ed. 1999, 38, 2586; and
references therein.
CO2Me
O
O
O
O
O
OBn
OBn
OBn
O
4
a
b
O
O
O
O
O
O
11
12
13
Scheme 3 Reagents and conditions: (a) O3, CH2Cl2–MeOH (9:1),
–78 °C, and then Me2S, r.t., 0.5 h; (b) irradiation with sunlight, 40
min, and then HIO4, MeOH, r.t., 1.5 h, 54% (over 3 steps).
C-Ketoside derivatives 10 and 13 are sugar-fused g-ke-
toesters susceptible to be further modified to engineer
versatile scaffolds and building blocks.
In summary, we have developed an efficient new strategy
to synthesise C-ketosides using a diastereocontrolled
Norrish–Yang photocyclization.19 These preliminary re-
sults, regarding the memory effect observed, appear
promising to expand the scope of this Norrish–Yang reac-
tion with 1,2-diketones in asymmetric synthesis in the
same way as arylketones or a-keto esters have already
Synlett 2007, No. 12, 1851–1856 © Thieme Stuttgart · New York

LETTER
Stereocontrolled Photocyclization of 1,2-Diketones
1855
(9) For recent reviews, see: (a) Giese, B.; Zeitz, H.-G. In
Preparative Carbohydrate Chemistry; Hanessian, S., Ed.;
Marcel Dekker: New York, 1997, 507. (b) Pearce, A. J.;
Mallet, J.-M.; Sinaÿ, P. In Radicals in Organic Synthesis,
Vol. 2; Renaud, P.; Sibi, M. P., Eds.; Wiley-VCH:
Weinheim, 2001, 523.
(10) The numbering system used throughout the text is based on
1-methyl-2,3-alkanedione and corresponds to that depicted
in structures of Table 1 and Schemes 1–3.
(CH), 90.5 (C), 101.2 (CH), 128.2–129.3 (15 × CH), 136.5
(C), 138.5 (C), 138.7 (C), 208.2 (C). MS (EI): m/z (rel.
int.) = 518 (<1) [M+], 427 (<1), 412 (<1), 395 (<1), 91 (100).
HRMS: m/z calcd for C31H34O7: 518.2305; found: 518.2322.
Anal. Calcd for C31H34O7: C, 71.80; H, 6.61. Found: C,
71.90; H, 6.59.
Compound 6a (2R,5R): colorless oil; [a]D +1.4 (c 1.0). 1H
NMR (400 MHz, CDCl3): d = 1.51 (3 H, s), 2.42 (1 H, d,
J = 17.5 Hz), 3.03 (1 H, d, J = 17.5 Hz), 3.43 (1 H, dd,
J = 8.1, 9.1 Hz), 3.61 (3 H, s), 3.86 (1 H, d, J = 9.5 Hz), 4.00
(1 H, br s), 4.15 (1 H, t, J = 9.4 Hz), 4.62 (1 H, d, J = 7.7 Hz),
4.68 (1 H, d, J = 10.9 Hz), 4.72 (1 H, d, J = 11.4 Hz), 4.75 (1
H, d, J = 11.7 Hz), 4.82 (1 H, d, J = 11.1 Hz), 4.93 (1 H, d,
J = 11.1 Hz), 4.96 (1 H, d, J = 10.9 Hz), 7.15 (2 H, dd,
J = 1.9, 7.1 Hz), 7.28–7.36 (13 H, m). 13C NMR (100 MHz,
CDCl3): d = 17.7 (CH3), 50.1 (CH2), 57.7 (CH3), 75.1 (CH2),
75.6 (C), 76.1 (CH2), 76.5 (CH2), 81.6 (CH), 82.2 (CH), 82.8
(CH), 90.5 (C), 102.8 (CH), 128.1–129.2 (15 × CH), 136.5
(C), 138.6 (C), 138.7 (C), 206.6 (C). MS (EI): m/z (rel.
int.) = 518 (<1) [M+], 476 (1.1), 427 (<1), 395 (1), 91 (100).
HRMS: m/z calcd for C31H34O7: 518.2305; found: 518.2319.
Compound 7d (2S,5S) [data taken from a (4:1) mixture of
7d–c]: colorless oil. 1H NMR (400 MHz, CDCl3): d = 0.08
(3 H, s), 0.09 (3 H, s), 0.10 (3 H, s), 0.11 (6 H, s), 0.12 (3 H,
s), 0.88 (18 H, s), 0.92 (9 H, s), 1.29 (3 H, d, J = 6.4 Hz), 1.34
(3 H, s), 2.75 (1 H, d, J = 17.5 Hz), 3.00 (1 H, d, J = 17.5
Hz), 3.42 (1 H, dq, J = 5.4, 6.4 Hz), 3.57 (1 H, dd, J = 2.0,
5.4 Hz), 3.76 (1 H, t, J = 2.0 Hz), 4.38 (1 H, d, J = 2.3 Hz),
4.71 (1 H, s, OH). 13C NMR (100 MHz, CDCl3): d = –5.2
(CH3), –4.6 (CH3), –4.3 (CH3), –4.2 (CH3), –3.9 (CH3), –3.8
(CH3), 17.8 (C), 17.9 (C), 18.0 (C), 18.9 (CH3), 20.6 (CH3),
25.6 (3 × CH3), 25.8 (6 × CH3), 51.4 (CH2), 73.5 (CH), 75.7
(C), 76.1 (CH), 76.3 (CH), 77.4 (CH), 90.5 (C), 210.1 (C).
MS (EI): m/z (rel. int.) = 574 (5) [M+], 529 (17), 517 (22), 73
(100). HRMS: m/z calcd for C28H58O6Si3: 574.3541; found:
574.3534.
Compound 8b (2S,5R) [data taken from a (3:1) mixture of
8b–c]: colorless oil. 1H NMR (400 MHz, CDCl3): d = 1.37
(3 H, s), 2.62 (1 H, d, J = 17.5 Hz), 3.31 (1 H, d, J = 17.5
Hz), 3.50 (1 H, m), 3.55 (1 H, m), 3.60 (1 H, t, J = 8.8 Hz),
3.70 (1 H, d, J = 8.6 Hz), 3.61–3.79 (2 H, m), 4.44 (1 H, d,
J = 11.7 Hz), 4.46 (1 H, d, J = 11.8 Hz), 4.53 (1 H, d,
J = 10.8 Hz), 4.58 (1 H, d, J = 10.8 Hz), 4.71 (1 H, d,
J = 10.8 Hz), 3.74 (1 H, d, J = 10.8 Hz), 4.85 (1 H, d,
J = 10.8 Hz), 5.04 (1 H, d, J = 11.4 Hz), 7.09–7.28 (20 H,
m). 13C NMR (100 MHz, CDCl3): d = 16.6 (CH3), 44.7
(CH2), 68.3 (CH2), 73.3 (CH2), 73.7 (CH2), 74.1 (CH2), 75.1
(CH2), 75.5 (CH), 76.2 (CH), 76.9 (C), 77.7 (CH), 86.4
(CH), 89.5 (C), 127.0–128.5 (20 × CH), 137.5 (C), 137.7
(C), 137.8 (C), 138.0 (C), 208.4 (C). MS (EI): m/z (rel.
int.) = 608 (<1) [M+] , 580 (1), 566 (<1), 517 (<1), 457 (1),
91 (100). HRMS: m/z calcd for C38H40O7: 608.2777; found:
608.2770.
(11) The 1,2-diketones 1–4 shown in Table 1 were prepared from
their corresponding alkynes via ozonolysis: (a) Favino, T.
F.; Fronza, G.; Fuganti, C.; Fuganti, D.; Graselli, P.; Mele,
A. J. Org. Chem. 1996, 61, 8975. (b) Or by oxidation with
RuO2/NaIO4: Zibuck, R.; Seebach, D. Helv. Chim. Acta
1988, 71, 237.
(12) Conformation of substrates 1–4 were determined by 1H
NMR spectroscopic analysis.
(13) Ihmels, H.; Scheffer, J. R. Tetrahedron 1999, 55, 885.
(14) Walther, K.; Kranz, U.; Henning, H.-G. J. Prakt. Chem.
1987, 329, 859.
(15) A 450 W ACE-Hanovia medium-pressure mercury lamp in
an immersion well with 4.8 mm Pyrex walls.
(16) (a) The term of ‘memory of chirality’ is used here with the
meaning that was proposed by Fuji: Fuji, K.; Kawabata, T.
Chem. Eur. J. 1998, 4, 373. (b) For a discussion on the
memory effect in photochemical reactions, see: Giese, B.;
Wettstein, P.; Stähelin, C.; Barbosa, F.; Neuburger, M.;
Zehnder, M.; Wessig, P. Angew. Chem. Int. Ed. 1999, 38,
2586; and references therein.
(17) Conditions: 1,2-diketone (40 mM), pyrene, naphthalene or
benzophenone (0.5 M), CHCl3, UV lamp (10 cm).
(18) To see a list of procedures to generate C-ketosides: Roberts,
S. W.; Rainier, J. D. Org. Lett. 2005, 7, 1141.
(19) General Procedure for the Photocyclization of 1,2-
Diketones
The corresponding 1,2-diketone placed in a Pyrex vessel
with or without the indicated solvent (approx. 0.05 M) was
irradiated with sunlight or a UV lamp, placed at 10 cm
distance from the flask, until the reaction turned colorless. If
it proceeded, the mixture was concentrated in vacuo.
Column or Chromatotron® chromatography of the residue
(hexanes–EtOAc mixtures) afforded the cyclic compounds.
General Procedure for the Photocyclization of 1,2-
Diketones with Photosensitizers
The corresponding 1,2-diketone (0.038 mmol) and
photosensitizer (benzophenone or pyrene; 0.5 mmol) was
dissolved in CDCl3 (1 mL) and placed in a NMR tube. The
reaction mixture was irradiated with an UV lamp, placed at
10 cm distance from the flask, until complete conversion and
the solvent was removed under vacuum. The reaction was
monitored by 1H NMR. Chromatotron® chromatography of
the residue with hexanes to remove the photosensitizer
followed by elution with hexanes–EtOAc mixtures afforded
the cyclic compounds.
Data of some representative compounds are included; only
the major compound from the mixtures is shown.
Compound 5a (2R,5R): colorless oil; [a]D +23.8 (c 0.3). 1H
NMR (400 MHz, CDCl3): d = 1.38 (3 H, s), 2.36 (1 H, d,
J = 17.3 Hz), 2.91 (1 H, d, J = 17.3 Hz), 3.50 (1 H, dd,
J = 3.7, 9.8 Hz), 3.53 (3 H, s), 3.76 (1 H, d, J = 9.8 Hz), 3.99
(1 H, br s), 4.34 (1 H, t, J = 9.8 Hz), 4.57 (1 H, d, J = 3.9 Hz),
4.66 (1 H, d, J = 11.9 Hz), 4.67 (1 H, d, J = 10.9 Hz), 4.75 (1
H, d, J = 10.9 Hz), 4.82 (1 H, d, J = 10.6 Hz), 4.83 (1 H, d,
J = 12.0 Hz), 4.98 (1 H, d, J = 11.1 Hz), 7.15 (2 H, dd,
J = 2.0, 7.6 Hz), 7.28–7.38 (13 H, m). 13C NMR (100 MHz,
CDCl3): d = 19.6 (CH3), 50.6 (CH2), 59.7 (CH3), 74.0 (CH2),
76.0 (CH2), 76.7 (CH2), 77.8 (C), 78.2 (CH), 80.8 (CH), 83.3
Compound 10: colorless oil; [a]D –81.2 (c 0.16). 1H NMR
(400 MHz, CD3OD + D2O): d = 1.32 (3 H, d, J = 6.1 Hz),
2.28 (3 H, s), 3.01 (1 H, d, J = 15.4 Hz), 3.07 (1 H, d,
J = 15.4 Hz), 3.43 (1 H, dd, J = 8.0, 10.3 Hz), 3.58 (1 H, dq,
J = 10.4, 6.0 Hz), 3.66 (3 H, s), 3.67 (1 H, dd, J = 3.2, 5.0
Hz), 3.86 (1 H, d, J = 3.28 Hz). 13C NMR (100 MHz,
CD3OD): d = 19.1 (CH3), 28.5 (CH3), 38.2 (CH2), 52.6
(CH3), 72.9 (CH), 73.2 (CH), 74.2 (CH), 75.3 (CH), 86.6
(C), 171.7 (C), 213.9 (C). MS (EI): m/z (rel int.) = 263 (<1)
[M+ + H], 245 (<1), 231 (8), 201 (8). HRMS: m/z calcd for
C11H19O7: 263.1131; found: 263.1143. Anal. Calcd for
C11H18O7: C, 50.38; H, 6.92. Found: C, 50.28; H, 7.11.
Compound 13 (4R) [data taken from a (5:1) mixture]: white
solid. 1H NMR (400 MHz, CDCl3): d = 1.25 (3 H, s), 1.45
Synlett 2007, No. 12, 1851–1856 © Thieme Stuttgart · New York

1856
A. J. Herrera et al.
LETTER
(C), 108.2 (CH), 112.9 (C), 127.6–128.5 (5 × CH), 136.9
(C), 170.0 (C), 208.9 (C). MS (EI): m/z (rel. int.) = 349 (1)
[M+ – CH3], 321 (8), 91 (100). HRMS: m/z calcd for
C18H21O7: 349.1287; found: 349.1278. Anal. Calcd for
C19H24O7: C, 62.63; H, 6.64. Found: C, 62.88; H, 6.63.
(3 H, s), 2.38 (3 H, s), 2.87 (1 H, d, J = 15.9 Hz), 3.36 (1 H,
d, J = 16.1 Hz), 3.63 (3 H, s), 4.42 (1 H, d, J = 11.7 Hz), 4.65
(1 H, d, J = 5.8 Hz), 4.67 (1 H, d, J = 11.4 Hz), 4.75 (1 H, d,
J = 5.8 Hz), 5.33 (1 H, s), 7.27–7.37 (5 H, m). 13C NMR (100
MHz, CDCl3): d = 23.9 (CH3), 25.7 (CH3), 27.9 (CH3), 41.9
(CH2), 51.7 (CH3), 69.8 (CH2), 85.2 (CH), 85.6 (CH), 92.4
Synlett 2007, No. 12, 1851–1856 © Thieme Stuttgart · New York

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