Photochemistry of α-diketones in carbohydrates: Anomalous norrish typea II photoelimination and norrish-yang photocyclization promoted by the internal carbonyl group

Article abstract of DOI:10.1002/chem.201303843

A series of four α-diketones placed as 1α-pyruvoyl tethers on D-glucopyranose and D-glucopyranosiduronic acid skeletons was prepared in order to determine the influence of captodative and stereoelectronic effects on the regioselectivity of the hydrogen atom transfer (HAT) in Norrish typea II photochemical processes. We observed that the 1,5-HAT regioselectivity can be switched between the two potentially abstractable syn-1,3-diaxial hydrogens at H6 and H8. Highly unusual photoproducts from Norrish typea II photoelimination and Norrish-Yang photocyclization initiated by the excited internal carbonyl group were obtained, in some cases in excellent synthetic yield. The 1,5-HAT transition state in the Norrish typea II photoelimination was investigated by photochemical experiments in the crystalline state. Elimination versus cyclization: Photolysis of 1α-pyruvoyl diketones of D-glucopyranosyl and D-glucopyranosiduronic acid carbohydrate skeletons led to Norrish typea II photoelimination or Norrish-Yang photocyclization products via a completely regioselective 1,5-hydrogen atom transfer promoted by the excited internal carbonyl group, depending on the stability of the 1,4-biradical intermediate (see scheme, DPS=tert-butyldiphenylsilyl). Copyright

Full text of DOI:10.1002/chem.201303843

DOI: 10.1002/chem.201303843
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&
Carbohydrates
Photochemistry of a-Diketones in Carbohydrates: Anomalous
Norrish Type II Photoelimination and Norrish–Yang
Photocyclization Promoted by the Internal Carbonyl Group
Dimitri Alvarez-Dorta,[a] Elisa I. Leꢀn,*[a] Alan R. Kennedy,[b] Angeles Martꢁn,[a] Inꢂs Pꢂrez-
Martꢁn,[a] Concepciꢀn Riesco-Fagundo,[a] and Ernesto Suꢃrez*[a]
Abstract: A series of four a-diketones placed as 1a-pyruvoyl
tethers on d-glucopyranose and d-glucopyranosiduronic
acid skeletons was prepared in order to determine the influ-
ence of captodative and stereoelectronic effects on the re-
gioselectivity of the hydrogen atom transfer (HAT) in Norrish
type II photochemical processes. We observed that the 1,5-
HAT regioselectivity can be switched between the two po-
tentially abstractable syn-1,3-diaxial hydrogens at H6 and H8.
Highly unusual photoproducts from Norrish type II photoeli-
mination and Norrish–Yang photocyclization initiated by the
excited internal carbonyl group were obtained, in some
cases in excellent synthetic yield. The 1,5-HAT transition
state in the Norrish type II photoelimination was investigat-
ed by photochemical experiments in the crystalline state.
Introduction
In previous papers we described a sequential Norrish type II
photoelimination and intramolecular aldol cyclization of a-di-
ketones in carbohydrate systems as a method for the stereose-
lective synthesis of cyclopentitols.[1,2] Although the detailed hy-
drogen atom transfer (HAT) process of the photochemical reac-
tion was not completely understood at that time, the reaction
may proceed through a two-step mechanism initiated by the
excited internal carbonyl group, as exemplified for the photoly-
sis of nono-2,3-diulose 1 in Scheme 1. A b-cleavage of the ini-
tially formed 1,4-biradical I (R=H, H) affords the photoenol II
which cyclizes to cyclopentitol 2 by an intramolecular OH-b-
syn aldol process. The reaction proceeds with excellent regio-
selectivity abstracting only H8 and no products from the com-
petitive Norrish–Yang photocyclization (either by abstraction of
H6 or H8) were detected.
Scheme 1. Mechanism of sequential Norrish type II photoelimination/aldol
cyclization reaction.
These results are surprising because the Norrish type II pho-
toelimination is a very rare and minor process in a-diketones[3]
and the thermal non-catalyzed aldol cyclization in which a pho-
toenol acts as a preformed enolate has no literature prece-
dent.[4] Another important facet of the mechanism is the initial
HAT triggered by the excited carbonyl group. Little information
is available for the few examples of the Norrish type II photoe-
limination of a-diketones present in the literature, although
the biradical intermediate I (R=H, H) could be intuitively envi-
sioned to arise from a 1,5-HAT reaction promoted by the inter-
nal carbonyl group as proposed by Bishop.[3a] This contrasts
with the better documented Norrish–Yang photocyclization
where the abstraction occurs, in all the examples studied so
far, by the external carbonyl group via a six- or seven-mem-
bered transition state (TS) to form exclusively 2-hydroxycyclo-
butanones or 2-hydroxycyclopentanones as final products, re-
spectively. The alternative cyclization products through the in-
ternal carbonyl group, namely acylcyclobutanols, have never
been isolated.[1f,5]
[a] Dr. D. Alvarez-Dorta, Dr. E. I. Leꢀn, Dr. A. Martꢁn, Dr. I. Pꢂrez-Martꢁn,
Dr. C. Riesco-Fagundo, Prof. Dr. E. Suꢃrez
Instituto de Productos Naturales y Agrobiologꢁa del C.S.I.C.
Carretera de la Esperanza 3, 38203 La Laguna, Tenerife (Spain)
Fax: (+34)922-260-135
E-mail: eila@ipna.csic.es
esuarez@ipna.csic.es
[b] Dr. A. R. Kennedy
WestCHEM Department of Pure and Applied Chemistry
University of Strathclyde
295 Cathedral Street, Glasgow G1 1XL, Scotland (UK)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201303843.
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3
those of the related OH-b-syn-aldol 2, particularly JH4b,H5b
=
=
Results and Discussion
3
10.4 Hz which is significantly much larger than JH4a,H5b
To achieve a deeper insight into the mechanism of the Norrish
type II process in these a-diketones we decided to prepare
nono-2,3-diulose 3 (Scheme 2) from methyl d-glucopyranosi-
duronate as described in the Supporting Information. Our in-
tention was to increase the stability and consequently the life-
4.7 Hz.[2b] However, due to the flexibility of the ring, the cyclo-
pentane conformation was studied by pseudorotational analy-
7
sis. A twisted T6 (P=3.48) conformation was found to be pre-
ferred for this cyclopentane in which the hydrogens at C5, C6,
and C7 were in pseudoaxial orientation and with near eclipsed
hydrogens at C4 and C5 (calcd dihedral 21.38). This is in good
agreement with the large value observed for the ring coupling
constants: 3J4,5 =10.4 Hz (calcd 9.2 Hz), 3J5,6 =8.1 Hz (calcd
7.9 Hz), and J6,7 =9.2 Hz (calcd 10.1 Hz).[11] The observations of
3
HMBC correlation of H4 to C9 and NOESY interactions of 1-Me
and H6, and between the methyl groups of the acetate and
carboxylate also substantiate the OH-a-syn-aldol cyclization
and an S stereochemistry for the ketal.[12]
From the formation of 6 and although the low yield ob-
tained makes any generalization difficult we can draw the fol-
lowing two preliminary conclusions: a) The Norrish Type II pho-
toelimination behaved analogously for this captodative stabi-
lized 1,4-biradical, to give the analogous photoenol 4b which
was not stable enough to isolate; b) the pyruvate ester moiety
present in intermediate 4b acts as an aldol acceptor in the
OH-a-syn cyclization step. Inspection of the literature revealed
that while the intermolecular aldol addition of enolsilane to
pyruvate esters has been studied in depth, the intramolecular
version of this reaction has never been reported.[13]
Scheme 2. Photolysis of a-diketone 3. a) Daylight-lamp irradiation, CDCl3,
308C, 2.5 h, b) Ac2O, DMAP, Py, room temperature, 1.5 h, c) Adventitious O2.
The distances have been calculated over minimized structures. DMAP=4-di-
methylaminopyridine.
time of the 1,4-biradical I (Scheme 1, R=O) by a captodative
effect.[6] Owing to the reversibility of the initial HAT this may
have a strong influence on the regioselectivity of the final pho-
toproducts as has been observed in monoketones.[7] As far as
we know, there is no example of captodative stabilized radical
intermediates in the photochemistry of a-diketones to date.
Unfortunately, irradiation with a daylight lamp[8] of a diketone
3 CDCl3 solution at 308C afforded a complex mixture of com-
pounds, that was purified after acetylation of the crude resi-
due. In the event, we were able to isolate only two pure prod-
ucts in modest yield (Scheme 2): the known d-glucono-1,5-lac-
tone derivative 5[9] (29%) and the OH-a-syn-aldol ring contrac-
tion 6 (28%), the former presumably generated via oxidative
degradation by adventitious oxygen of a transient photoenol
Furthermore, we would highlight the subtle aldol cyclization
stereochemistry. The OH-a-syn cyclization encountered is in
sharp contrast to the situation observed with analogous d-glu-
copyranosyl derivatives (for example, derivative 2 in Scheme 1)
where an OH-b-syn cyclization occurs exclusively.[2] The OH-a-
syn diastereoselectivity observed requires a transition state ge-
ometry TS6 with a 4Si,8Si topicity as outlined in Figure 1. The
3
intermediate 4a.[5b] The significantly low value of the JHax,Hax
between the axial ring hydrogens (J5,6 =J6,7 =J7,8 =ca. 4.5 Hz)
reveals that 3 exists in solution as a conformational equilibrium
7
4
4
1
between C4 and C7 pyranoid chairs (equivalent to C1 and C4
4
in the aldose series, respectively). A small JH5,H7 coupling de-
Figure 1. Models for the diastereomeric course of the aldol reaction. The
transition state (TS) of the major isomer is highlighted.
tected is also consistent with a large participation of an invert-
ed chair, where both hydrogens are equatorial in a W-type
planar arrangement. This equilibrium is undoubtedly responsi-
ble for the poor reaction efficiency observed, since the geo-
metrical parameters of the 1,5-HAT reaction are only satisfied
with the a-diketone tether and the H8 in a syn-1,3-diaxial rela-
tionship.[10]
b-syn cyclization is disfavored probably by steric interactions of
the trans-dicarbonyl system with the a-axial hydrogen at C6;
this type of interaction does not exist in the transition state of
d-glucosyl derivative 2 (TS2) where an 4Re,8Si ring closure is
favored.
The formation of cyclopentitol 6, although proceeding in
a disappointing yield, may throw some light on the reaction
mechanism and therefore the structure and stereochemistry
were carefully established. The OH-a-syn-aldol cyclization was
verified by comparison of its characteristic NMR data with
To circumvent this problem of conformational equilibrium in
a-diketone 3 we decided to restrict the hexopyranose ring in
7
a C4-chair conformation using a butane-2,3-bisacetal protector
(Ley protector) because of its trans-decalin-type system.[14]
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tion (BR7 and BR10). On the
other hand, models 14 and 16
(Scheme 4) with a 5,6-protection
may adopt a 5,8B conformation
(BR14 and BR16) so in these
cases a stabilization of the radi-
cal by the b-CO effect is possi-
ble. Thus, our principal concern
is now whether and to what
extent the conformational re-
striction of our bicyclic system
may affect the stability of the
biradical and hence the regiose-
lectivity of the Norrish type II
1,5-HAT.[17]
Scheme 3. Photolysis of 6,7-O-(2,3-dimethoxybutane-2,3-diyl)-nono-2,3-diuloses 7 and 10. a) Daylight-lamp irradia-
tion, crystalline state (308C, 7 h, then C6D6, 508C, 4.5 h), solution (CDCl3, 30–358C, 5 h); b) Daylight-lamp irradia-
tion, C6D6, 308C, 8 h; c) C6H6, 788C, 8 h; d) Ac2O, DMAP, CH2Cl2, room temperature, 1.5 h. DPS=tert-butyldiphenyl-
silyl.
The preparation of diketones
7, 10, 14, and 16 (see Schemes 3
and 4) was accomplished follow-
ing the general two-step proto-
col, synthesis of a-C-propynyl
glycosides[18] followed by oxida-
tion,[19,20] previously used by our
group (for details see the Sup-
porting Information).[2] Gratify-
ingly, diketone 7 is a yellow crys-
talline solid and its structure was
determined by X-ray crystallo-
graphic analysis.[21] From the
crystal structure it is evident that
the internal carbonyl group is
poised to abstract either H6 (C=
O···H, d=2.4 ꢅ) or H8 (2.6 ꢅ). The
values of d for the external car-
bonyl group are much larger H6
(5.1 ꢅ) and H8 (5.0 ꢅ) which pre-
cludes any participation of this
carbonyl group in the initial
HAT.[22] Visible light irradiation of
Scheme 4. Photolysis of 5,6-O-(2,3-dimethoxybutane-2,3-diyl)-nono-2,3-diuloses 14 and 16. a) Daylight-lamp irradi-
ation, C6H6, 308C, 6 h; b) Daylight-lamp irradiation, C6H6, 308C, 18 h then 708C, dark, 8 h; c) Ac2O, DMAP, CH2Cl2,
room temperature, 2 h.
Thus, diketones 7, 10, 14, and 16 were synthesized (see
Schemes 3 and 4). Moreover, we have to take into account
that pyranos-5-yl radicals of the aldose series adopt boat-like
4
conformations (B1,4) instead of retaining the C1 conformation
of the starting carbohydrate as determined by EPR spectrosco-
py (Figure 2).[15] These conformational preferences, that have
been much better studied in pyranos-1-yl radicals,[16] result
from a balance between several factors including the delocali-
zation of the radical by the lone pair of the ring oxygen, the
radical stabilization due to the interaction of the radical SOMO
with the s*-orbital of the adjacent b-CꢀO bond at C4 in a co-
planar arrangement (quasi-homo stabilization effect or b-CO
bond effect), and steric effects.
It has also been observed that a captodative substitution
pattern at C5 does not influence the conformation of the ring,
thus radicals d-GlcAp and d-Glcp have very similar B1,4 confor-
mations (Figure 2).[15] In our models a 6,7-protection pattern
like that which is present in 7 and 10 (Scheme 3) would dimin-
ish ring mobility and would prevent any biradical conforma-
tional movement that had the substituent at C7 in axial posi-
Figure 2. Conformation of d-glucopyranosyl radicals.
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crystals of diketone 7 afforded an oily residue, which was dis-
solved in [D6]benzene and the solution heated at 508C for
4.5 h in the dark in order to carry out the aldol reaction.[23] This
solid state photochemical experiment led exclusively to cyclo-
pentitol derivative 8 in 60% yield as a 5:1 mixture of hemiace-
tals, no detectable amount of products arising from HAT at H6
being observed (Scheme 3). The photochemistry of diketone 7
was also investigated in CDCl3 solution. The major photoprod-
uct was also 8 (48%) but in addition the acylcyclobutanol 9
was formed albeit in low yield (14%).
tone 10 where abstraction of the H8 is preferred (Scheme 3).
The spectroscopic characteristics of 15 are similar to those ob-
served for compound 9. A null value for the JH4,H5 coupling
3
constant (calcd 0.4 Hz, dihedral 92.58) that makes H4 and H5
appear as singlets and HMBC correlations of C3 with H5 and
H7 confirming the C3ꢀC6 biradical coupling are especially re-
markable. Analogously to compound 9, NOESY experiments
were also used to confirm the configuration at C3, which is in
agreement with an endo-acylcyclobutanol structure as shown.
The cyclization of 15 occurred stereoselectively, the exo-diaste-
reomer not being detected.
The formation of compound 8 can be rationalized by a Nor-
rish type II photoelimination/aldol reaction initiated by the in-
ternal carbonyl group, as described in Scheme 1, assuming
a stereoselective OH-a-syn intramolecular cyclization in the
aldol step. Moreover, acylcyclobutanol 9 was produced by ab-
straction of the H6 and subsequent cyclization by an anoma-
lous Norrish–Yang photocyclization process also initiated by
the internal carbonyl group.[1f,5]
The results obtained in the photolysis plus heating process
of a benzene solution of our next model 16 deserve comment
(Scheme 4). After acetylation of the photolysis mixture four
products were obtained by careful chromatographic separa-
tion. Two of them 17a,b are diastereomers formed by the se-
quential photoelimination/aldol reaction. The alcohol 18, that
remained unaffected under the acetylation conditions, and 19
are two new examples of the anomalous Norrish–Yang photo-
cyclization generated by initial HAT of H6 and H8, respectively.
In comparison with the photolysis of 10 the unstable photoen-
ol intermediate, that this time could not be isolated, cyclized
with higher selectivity through an OH-b-syn aldol process ex-
clusively to give hemiacetal acetates 17a,b.
The photoproducts were isolated by chromatography and
their complete structure and stereochemistry assigned on the
basis of 1D and 2D NMR experiments.[12] In particular, the
3JH4,H5 =9.4 Hz (calcd 8.6 Hz) and NOE interactions between H4
and H7 accounted for the a-syn cyclization in compound 8.
The 2-oxabicyclo[3.1.1]heptane framework of 9 was substanti-
3
1
ated by the coupling constants JH4,H5 ꢁ0.0 Hz (calcd 0.5 Hz),
The H NMR multiplicity for the four pyranose ring protons
3JH7,H8 =6.0 Hz (calcd 7.2 Hz), and HMBC correlations between
H7 and H5 with C3. Furthermore, NOE interactions of the hy-
droxylic hydrogen with the C5ꢀOMe and other protons of the
a-east side of the molecule indicated a structure of endo-acyl-
cyclobutanol with C3 (R)-stereochemistry.[12]
proved highly helpful for distinguishing between photoprod-
uct 18 with a 2-oxabicyclo[3.1.1]heptane skeleton (three dou-
blets and one ddd) versus 19 6-oxabicyclo[3.1.1]heptane skele-
ton (two doublets and two doublet of doublets). Besides, the
AB system observed for protons at C9 implies a 3,8-biradical
cyclization in compound 19. In both cases the photocyclization
afforded exclusively one diastereomer at C3, namely endo-acyl-
cyclobutanol for 18 and exo-acylcyclobutanol for 19 as deter-
mined from the NOESY spectra.
Photolysis of diketone 10 in [D6]benzene solution afforded
exclusively photoenol 11 in high yield (96%) which was suffi-
ciently stable at room temperature to permit complete analyti-
cal and spectroscopic characterization (Scheme 3). The aldol
cyclization performed by heating the [D6]benzene solution at
reflux temperature for 8 h afforded a complex mixture which
was resolved by chromatography after acetylation. Compounds
from OH-b-syn 12a,b and OH-a-syn 13 intramolecular aldol
Conclusion
We have demonstrated that at least in these restricted sys-
tems, without abstractable hydrogens by the external carbonyl
group via a five-membered TS, the photolysis of a-diketones
may be initiated by 1,5-HAT from the internal carbonyl group
as depicted in Scheme 5. The 1,4-biradicals originated (3,8-BR
and 3,6-BR) can participate in Norrish type II photoelimination
1
cyclizations were obtained and distinguished by H NMR spec-
troscopy. In these conformationally restricted cyclopentane sys-
3
tems the JH4,H5 is significantly smaller in b-isomers 12 than in
the a-isomer 13; 5.4 Hz (calcd 5.0 Hz) and 5.3 Hz (calcd 5.1 Hz)
for 12a,b, respectively, versus 9.2 Hz (calcd 8.4 Hz) for 13.
We next investigated the pho-
tochemical reactivity of analo-
gous nono-2,3-diuloses 14 and
16 with the Ley protective
group
at
5,6
positions
(Scheme 4). The irradiation of
a benzene solution of diketone
14 proceeded regioselectively by
exclusive H6 abstraction to give
acylcyclobutanol 15 via Norrish–
Yang photocyclization in high
yield (93%). Interestingly, the
present regioselectivity is oppo-
Scheme 5. Mechanism of the Norrish type II photoelimination and Norrish–Yang photocyclization promoted by
site to that observed for dike- the internal carbonyl group in a-diketones.
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Compound 6: colorless oil; [a]D = +41 cm3 gꢀ1dmꢀ1 (c=0.41 in
CHCl3); H NMR (500 MHz, CDCl3; note: hydrogen atoms at C4 and
and in Norrish–Yang photocyclization reactions, in some cases
in excellent synthetic yields. These latter reactions lead to the
formation of acylcyclobutanols, a type of compounds that has
never been observed in the photochemistry of a-diketones.[25]
Indeed, the internal carbonyl group behaves, from the photo-
chemical point of view, in a similar manner as would an isolat-
ed carbonyl group.
1
C5 have very similar chemical shifts and as a consequence the cou-
pled hydrogen at C6 appears as a complex signal by virtual cou-
pling. The data of hydrogens at C4–C6 shown below have been
calculated by iterative simulation using program DAISY as imple-
mented in Bruker Topspin v. 2.1): d=1.55 (s, 3H), 2.01 (s, 3H), 3.46
(s, 3H), 3.51 (s, 3H), 3.53 (s, 3H), 3.62 (complex signal, dd, J=9.2,
7.9 Hz, 1H), 3.69 (d, J=9.2 Hz, 1H), 3.76 (s, 3H), 3.86 (complex
signal, dd, J=10.1, 7.9 Hz, 1H), 3.88 ppm (complex signal, d, J=
This internal carbonyl group behavior has been confirmed
by studies on crystalline state photochemistry of a-diketone 7.
Particularly remarkable is the regioselectivity observed in the
solid state, since the geometric parameters for the hydrogen
transfer of H6 and H8 are very similar (see Table S1 in the Sup-
porting Information). This could be related to the strain in-
1
10.1 Hz, 1H); H NMR (500 MHz, C6D6): d=1.48 (s, 3H), 1.58 (s, 3H),
3.26 (s, 3H), 3.33 (s, 3H), 3.39 (s, 6H), 3.64 (dd, J=10.4, 7.9 Hz, 1H),
3.82 (dd, J=9.2, 8.2 Hz, 1H), 3.87 (d, J=9.1 Hz, 1H), 4.03 ppm (d,
J=10.4 Hz, 1H); 13C NMR (100.6 MHz, CDCl3): d=20.1 (CH3), 21.2
(CH3), 52.4 (CH), 52.7 (CH3), 58.9 (CH3), 59.3 (CH3), 59.7 (CH3), 81.9
(CH), 86.4 (CH), 87.2 (CH), 87.5 (C), 101.4 (C), 170.9 (C), 172.2 (C),
202.9 ppm (C); 13C NMR (125.7 MHz, C6D6): d=19.7 (CH3), 21.5
(CH3), 52.0 (CH3), 53.2 (CH), 58.82 (CH3), 58.84 (CH3), 59.0 (CH3), 82.3
(CH), 87.0 (CH), 87.8 (CH), 88.0 (C), 101.9 (C), 170.9 (C), 172.6 (C),
203.0 ppm (C); IR (film): n˜ =2930, 1768, 1732 cmꢀ1; MS (ESI+): m/z
(%): 369 (100) [M+Na]+; HRMS (ESI+): m/z calcd (%) for
C15H22NaO9: 369.1162 [M+Na]+; found: 369.1161; elemental analy-
sis calcd (%) for C15H22O9 (346.33): C 52.02, H 6.40; found: C 52.07,
H 6.74.
volved in forming the cyclization product in the crystal.[24]
A
similar enhanced regioselectivity in the crystalline state has
been observed in the Yang photocyclization of monoketo-
nes.[7d,e]
As commented previously, the observed regioselectivity
changes cannot be attributable only to the increased stability
of the biradical due to the captodative effect, but also to ste-
reoelectronic effects present in these carbohydrate systems.
The more stable 3,8-biradical BR14 (captodative plus b-CO sta-
bilizing effects) rearranges to a 3,6-biradical through the rever-
sibility of the initial 1,5-HAT which finally led exclusively to
acylcyclobutanol 15 by Norrish–Yang photocyclization in high
yield. On the contrary, the more reactive 3,8-biradical BR10
(neither captodative nor b-CO effects) led directly to Norrish
type II photoelimination and to the formation of photoenol 11
also in excellent yield. The biradicals of intermediate stability
BR7 (captodative effect) and BR16 (b-CO effect) impair regiose-
lection as a consequence of competitive H6 and H8 HAT reac-
tions.
Photocyclization of methyl 2,6-anhydro-3,4-O-[(2S,3S)-2,3-di-
methoxybutane-2,3-diyl]-9-deoxy-5-O-methyl-d-glycero-l-
gulo-nono-7,8-diulosonate (7)
Method A (irradiation in CDCl3 solution): A deoxygenated solu-
tion of diketone 7 (12.7 mg, 0.03 mmol) in purified CDCl3 (0.6 mL)
was placed in a resonance tube and irradiated with a daylight-
lamp (Philips master PL electronic, 23 W/865) at 30–358C for 5 h.
Progress of the reaction was monitored by 1H NMR spectroscopy
and upon completion was concentrated under reduced pressure.
The residue was purified by silica gel column chromatography
(hexanes/EtOAc=1:1) to give 9 (1.8 mg, 0.01 mmol, 14%) and
methyl
(2R,3aR,4S,5R,6S,6aR)-5,6-O-[(2S,3S)-2,3-dimethoxybutane-
Experimental Section
2,3-dioxy]-2-hydroxy-4-methoxy-2-methyl-3-oxohexahydro-6aH-cy-
clopenta[b]furan-6a-carboxylate (8) (6.2 mg, 0.02 mmol, b/a, 5:1,
48%).
Compound 9: colorless oil, [a]D = +135 cm3 gꢀ1dmꢀ1 (c=0.19 in
Photolysis of methyl 2,6-anhydro-9-deoxy-3,4,5-tri-O-
methyl-d-glycero-l-gulo-nono-7,8-diulosonate (3)
1
A deoxygenated solution of diketone 3 (38 mg, 0.125 mmol) in pu-
rified CDCl3 (0.7 mL), was placed in a resonance tube and irradiated
with a daylight-lamp (Philips master PL electronic, 23 W/865) at
CHCl3); H NMR (500 MHz, CDCl3): d=1.25 (s, 3H), 1.27 (s, 3H), 2.33
(s, 3H), 3.27 (s, 3H), 3.40 (s, 3H), 3.52 (s, 3H), 3.64 (s, 1H), 3.79 (s,
3H), 4.12 (s, 1H), 4.49 (d, J=6 Hz, 1H), 5.13 ppm (d, J=5.7 Hz, 1H);
13C NMR (100.6 MHz, CDCl3): d=17.9 (CH3), 18.2 (CH3), 27.5 (CH3),
47.9 (CH3), 50.5 (CH3), 52.4 (CH3), 58.4 (CH3), 73.2 (CH), 74.7 (CH),
76.2 (C), 78.3 (CH), 85.9 (C), 87.2 (CH), 99.9 (C), 100.7 (C), 171.8 (C),
203.9 ppm (C); IR (CHCl3, 0.2 mm): n˜ =3471, 2953, 1752, 1718,
1143 cmꢀ1; MS (ESI+): m/z (%): 413 (100) [M+Na]+; HRMS (ESI+):
m/z calcd (%) for C17H26NaO10: 413.1424 [M+Na]+; found:
413.1426; elemental analysis calcd (%) for C17H26O10 (390.38):
C 52.30, H 6.71; found: C 52.24, H 6.93.
1
308C for 2.5 h. Progress of the reaction was monitored by H NMR
spectroscopy and upon completion was concentrated under re-
duced pressure. The residue was dissolved in dry pyridine (0.4 mL),
cooled to 08C and acetylated by adding Ac2O (0.3 mL) and DMAP
(8 mg, 0.132 mmol) followed by stirring at room temperature for
1.5 h. The reaction mixture was concentrated under reduced pres-
sure and the residue purified by silica gel column chromatography
(CH2Cl2/EtOAc=97:3), to give the known lactone 5[9] (9 mg,
0.036 mmol, 29%), and an inseparable mixture of products (26 mg)
which was subsequently purified by silica gel column chromatogra-
phy (hexanes/EtOAc=6:4) to give compound 6 (12 mg,
0.035 mmol, 28%) and an unidentified product (8 mg).
Compound 5: colorless oil, 1H NMR (400 MHz, CDCl3): d=3.43 (s,
3H), 3.44 (s, 3H), 3.53 (ddd, J=5.3, 2.1, 1.7 Hz, 1H), 3.61 (s, 3H),
3.81 (s, 3H), 3.87 (dd, J=2.9, 2.4 Hz, 1H), 3.96 (d, J=5.3 Hz, 1H),
5.03 ppm (dd, J=2.9, 1.6 Hz, 1H); 13C NMR (100.6 MHz, CDCl3): d=
52.8 (CH3), 56.8 (CH3), 57.8 (CH3), 59.5 (CH3), 75.1 (CH), 77.1 (CH),
79.0 (CH), 82.9 (CH), 168.1 (C), 168.6 ppm (C).
Compound 8: colorless oil, [a]D = +157 cm3 gꢀ1dmꢀ1 (c=1.75 in
CHCl3); H NMR (500 MHz, CDCl3) major b-isomer: d=1.33 (s, 3H),
1
1.37 (s, 3H), 1.53 (s, 3H), 3.27 (s, 6H), 3.33 (d, J=9.4 Hz, 1H), 3.49
(s, 3H), 3.84 (s, 3H), 4.01 (dd, J=9.4, 9.4 Hz, 1H), 4.09 (dd, J=10.6,
9.4 Hz, 1H), 4.25 (d, J=10.6 Hz, 1H), 4.46 ppm (s, 1H); 13C NMR
(125.7 MHz, CDCl3) major b-isomer: d=17.85 (CH3), 17.88 (CH3),
21.3 (CH3), 47.9 (CH3), 48.0 (CH3), 52.3 (CH), 53.6 (CH3), 59.1 (CH3),
70.2 (CH), 73.2 (CH), 78.3 (CH), 84.2 (C), 100.5 (C), 101.3 (C), 101.4
(C), 172.6 (C), 205.8 ppm (C); IR (CHCl3, 0.2 mm): n˜ =3448, 2952,
1746, 1143 cmꢀ1; MS (ESI+): m/z (%): 413 (100) [M+Na]+, 85);
Chem. Eur. J. 2014, 20, 2663 – 2671
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HRMS (ESI+): m/z calcd (%) for C17H26NaO10: 413.1424 [M+Na]+;
found: 413.1431; elemental analysis calcd (%) for C17H26O10
(390.38): C 52.30, H 6.71; found: C 52.60, H 6.84.
Aldol condensation of (3Z,5S,6S,7S)-9-(tert-butyldiphenylsily-
l)oxy-6,7-O-{[(2S,3S)-2,3-dimethoxybutane-2,3-diyl]oxy}-3-hy-
droxy-5-methoxy-3-nonene-2,8-dione (11)
Method B (irradiation in C6H6 solution): A deoxygenated solution
of diketone 7 (74.4 mg, 0.19 mmol) in purified C6H6 (2.3 mL) was
placed in a Schlenk tube and irradiated with a daylight-lamp (Phi-
lips master PL electronic, 23 W/865) at 308C for 10 h. Then the so-
lution was heated at 408C for 4 h in the dark and concentrated
under reduced pressure. The residue was purified by silica gel
column chromatography (hexanes/EtOAc=1:1) to give 9 (6.7 mg,
0.019 mmol, 10%) and 8 (29.9 mg, 0.076 mmol, 40%).
The crude photoenol 11 (81 mg, 0.135 mmol, assuming 100% con-
version for the previous reaction) in dry C6H6 (1.6 mL) was heated
in the dark at 788C for 8 h. The solution was concentrated under
reduced pressure and the residue (80.8 mg) dissolved in dry CH2Cl2
(1.5 mL), cooled to 08C and acetylated by adding Ac2O (38 mL,
0.405 mmol) and DMAP (49.5 mg, 0.405 mmol) followed by stirring
at room temperature for 1.5 h. The reaction mixture was concen-
trated under reduced pressure and the residue purified by repeat-
ed Chromatotron chromatography (benzene/EtOAc=95:5) to give
12a (12.6 mg, 0.02 mmol, 15%), 12b (13 mg, 0.02 mmol, 15%),
and 13 (8.8 mg, 0.014 mmol, 10%).
Method C (irradiation in solid state): The procedure consisted in
crushing yellow crystals of diketone 7 (10.9 mg, 0.028 mmol) be-
tween two Pyrex microscope slides, taping the plates together,
sealing the resulting “sandwich” under nitrogen in a polyethylene
bag, and irradiating the ensemble on both sides with a daylight-
lamp (Philips master PL electronic, 23 W/865) for 7 h at 308C. The
crude residue was dissolved in C6D6 (0.5 mL) and the solution
heated at 508C for 4.5 h in the dark. After silica gel column chro-
matography (benzene/EtOAc 9:1!7:3) 8 was obtained (6.3 mg,
0.016 mmol, 60%).
Compound 12a: crystalline solid, m.p. 126.9–127.98C (n-hexane/
EtOAc); [a]D = +102 cm3 gꢀ1dmꢀ1 (c=1.15 in CHCl3); 1H NMR
(500 MHz, CDCl3): d=1.07 (s, 9H), 1.32 (s, 3H), 1.43 (s, 3H), 1.48 (s,
3H), 1.88 (s, 3H), 3.05 (s, 3H), 3.24 (s, 3H), 3.57 (s, 3H), 3.58 (d, J=
9.5 Hz, 1H), 3.68 (d, J=5.4 Hz, 1H), 3.73 (dd, J=8.2, 5.7 Hz, 1H),
3.82 (d, J=11.4 Hz, 1H), 4.10 (d, J=9.5 Hz, 1H), 4.54 (dd, J=11.4,
8.2 Hz, 1H), 7.39 (m, 6H), 7.81 ppm (m, 4H); 13C NMR (100.6 MHz,
CDCl3): d=17.9 (CH3), 18.0 (CH3), 19.2 (C), 20.3 (CH3), 23.9 (CH3),
26.7 (3ꢆCH3), 47.6 (CH3), 47.7 (CH3), 52.8 (CH), 58.0 (CH3), 62.1
(CH2), 73.7 (CH), 76.2 (CH), 79.8 (CH), 85.7 (C), 100.4 (C), 100.9 (C),
101.1 (C), 127.5 (2ꢆCH), 127.6 (2ꢆCH), 129.4 (CH), 129.6 (CH),
132.5 (C), 133.3 (C), 135.9 (2ꢆCH), 136.1 (2ꢆCH), 169.4 (C),
Method D (irradiation with pyrene): A solution of crude diketone
7 (10.5 mg, 0.027 mmol) and pyrene (70.7 mg, 0.35 mmol) in dry
C6D6 (0.71 mL) was placed in a resonance tube and irradiated with
a daylight-lamp at 308C for 14 h. No reaction was detected by
1H NMR under these conditions.
208.4 ppm (C); IR (CHCl3, 0.2 mm): n˜ =2933, 1758, 1139, 1106 cmꢀ1
;
MS (ESI+): m/z (%): 665 (100) [M+Na]+; HRMS (ESI+): m/z calcd (%)
for C34H46NaO10Si: 665.2758 [M+Na]+; found: 665.2744; elemental
analysis calcd (%) for C34H46O10Si (642.81): C 63.53, H 7.21; found:
C 63.41, H 7.16.
Photolysis of 1-O-(tert-butyldiphenylsilyl)-2,6-anhydro-3,4-O-
[(2S,3S)-2,3-dimethoxybutane-2,3-diyl]-9-deoxy-5-O-methyl-
d-glycero-l-gulo-nono-7,8-diulose (10)
Compound 12b: colorless oil, [a]D = +121 cm3 gꢀ1dmꢀ1 (c=0.71 in
CHCl3); H NMR (400 MHz, CDCl3): d=1.04 (s, 9H), 1.18 (s, 3H), 1.26
A deoxygenated solution of diketone 10 (31.6 mg, 0.053 mmol) in
dry C6D6 (0.8 mL) was placed in a NMR tube and irradiated with
a daylight-lamp (Philips master PL electronic, 23 W/865) at 308C for
1
(s, 3H), 1.53 (s, 3H), 2.06 (s, 3H), 3.08 (s, 3H), 3.12 (s, 3H), 3.19 (d,
J=5.3 Hz, 1H), 3.55 (s, 3H), 3.83 (dd, J=11.3, 8.8 Hz, 1H), 3.86 (d,
J=11.7 Hz, 1H), 3.91 (d, J=11.7 Hz, 1H), 4.18 (dd, J=8.9, 5.4 Hz,
1H), 4.34 (d, J=11.3 Hz, 1H), 7.42 (m, 6H), 7.71 ppm (m, 4H);
13C NMR (100.6 MHz, CDCl3): d=17.8 (CH3), 17.9 (CH3), 19.2 (C), 20.5
(CH3), 22.7 (CH3), 26.9 (3ꢆCH3), 47.3 (CH3), 47.7 (CH3), 52.0 (CH3),
58.1 (CH), 64.9 (CH2), 73.7 (CH), 75.1 (CH), 80.1 (CH), 85.6 (C), 100.3
(C), 100.4 (C), 102.8 (C), 127.9 (4ꢆCH), 129.84 (CH), 129.86 (CH),
132.5 (C), 132.9 (C), 135.6 (2ꢆCH), 135.8 (2ꢆCH), 169.1 (C),
1
8 h. Progress of the reaction was monitored by H NMR spectrosco-
py and upon completion was concentrated under reduced pres-
sure (30.5 mg, 0.051 mmol), leading to exclusive formation of pho-
toenol 11, which was not stable enough to withstand chromato-
graphic purification (silica gel or alumina). Notwithstanding, the
crude residue was pure enough to allow the complete analytical
and spectroscopic characterization.
Compound 11: colorless oil, [a]D = +93 cm3 gꢀ1dmꢀ1 (c=1.78 in
1
208.4 ppm (C); IR (CHCl , 0.2 mm): n=2933, 1768, 1747, 1141,
˜
3
CHCl3); H NMR (500 MHz, C6D6): d=1.10 (s, 3H), 1.23 (s, 3H), 1.25
1111 cmꢀ1; MS (ESI+): m/z (%): 665 (100) [M+Na]+; HRMS (ESI+):
m/z calcd (%) for C34H46NaO10Si: 665.2758 [M+Na]+; found:
665.2759; elemental analysis calcd (%) for C34H46O10Si (642.81):
C 63.53, H 7.21; found: C 63.24, H 7.61.
(s, 9H), 1.81 (s, 3H), 2.79 (s, 3H), 2.88 (s, 3H), 3.23 (s, 3H), 4.05 (dd,
J=9.8, 2.8 Hz, 1H), 4.80 (d, J=18.6 Hz, 1H), 4.83 (d, J=9.8 Hz, 1H),
4.86 (dd, J=8.2, 2.8 Hz, 1H), 4.89 (d, J=18.6 Hz, 1H), 5.72 (d, J=
8.2 Hz, 1H), 6.79 (brs, 1H), 7.20 (m, 6H), 7.81 ppm (m, 4H);
13C NMR (125.7 MHz, C6D6): d=17.4 (CH3), 17.6 (CH3), 19.7 (C), 22.7
(CH3), 27.0 (3ꢆCH3), 47.3 (CH3), 47.8 (CH3), 57.0 (CH3), 68.1 (CH2),
70.2 (CH), 72.5 (CH), 74.5 (CH), 99.0 (C), 99.2 (C), 111.8 (CH), 128.3
(4ꢆCH), 130.0 (2ꢆCH), 133.5 (C), 133. 7 (C), 136.0 (2ꢆCH), 136.1
(2ꢆCH), 149.4 (C), 194.4 (C), 203.9 ppm (C); IR (CHCl3, 0.2 mm): n˜ =
3438, 2929, 1738, 1682, 1662, 1143, 1113 cmꢀ1; UV/Vis (CH2Cl2) lmax
(e)=272 (sh, 3524), 265 (4478), 261 (4598), 255 nm (sh,
4130 molꢀ1 m3 cmꢀ1); MS (ESI+): m/z (%): 623 (100) [M+Na]+;
HRMS (ESI+): m/z calcd (%) for C32H44NaO9Si: 623.2652 [M+Na]+;
found: 623.2667; elemental analysis calcd (%) for C32H44O9Si
(600.77): C 63.98, H 7.38; found: C 63.92, H 7.44.
Compound 13: colorless oil, [a]D = +98 cm3 gꢀ1dmꢀ1 (c=0.97 in
1
CHCl3); H NMR (400 MHz, C6D6): d=1.18 (s, 9H), 1.26 (s, 3H), 1.36
(s, 3H), 1.38 (s, 3H), 1.72 (s, 3H), 3.16 (s, 3H), 3.18 (s, 3H), 3.43 (s,
3H), 3.71 (d, J=9.1 Hz, 1H), 3.99 (dd, J=9.1, 9.1 Hz, 1H), 4.21 (d,
J=9.5 Hz, 1H), 4.24 (d, J=9.8 Hz, 1H), 4.29 (dd, J=11.0, 10.1 Hz,
1H), 4.49 (d, J=11.4 Hz, 1H), 7.20 (m, 6H), 7.73 (m, 2H), 7.81 ppm
(m, 2H); 1H NMR (400 MHz, CDCl3): d=1.10 (s, 9H), 1.31 (s, 3H),
1.33 (s, 3H), 1.56 (s, 3H), 1.82 (s, 3H), 3.10 (s, 3H), 3.23 (s, 3H), 3.56
(s, 3H), 3.58 (1H, complex signal by virtual coupling), 3.78 (d, J=
9.8 Hz, 1H), 3.82 (d, J=9.6 Hz, 1H), 3.86 (m, 2H), 4.11 (1H, complex
signal by virtual coupling), 7.37 (m, 6H), 7.64 ppm (m, 4H);
13C NMR (100.6 MHz, C6D6): d=18.1 (CH3), 18.2 (CH3), 19.5 (C), 20.0
(CH3), 22.5 (CH3), 27.2 (3ꢆCH3), 47.6 (CH3), 48.0 (CH3), 50.0 (CH3),
58.7 (CH), 63.3 (CH2), 68.9 (CH), 73.3 (CH), 80.1 (CH), 86.9 (C), 101.0
(C), 101.5 (C), 102.6 (C), 128.05 (2ꢆCH), 128.13 (2ꢆCH), 130.1 (CH),
Chem. Eur. J. 2014, 20, 2663 – 2671
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130.2 (CH), 133.5 (C), 133.6 (C), 136.1 (2ꢆCH), 136.3 (2ꢆCH), 169.6
(C), 203.8 ppm (C); IR (CHCl3, 0.2 mm): n˜ =2933, 1764, 1749, 1141,
1107 cmꢀ1; MS (ESI+): m/z (%): 665 (100) [M+Na]+; HRMS (ESI+):
m/z calcd (%) for C34H46NaO10Si: 665.2758 [M+Na]+; found:
665.2763; elemental analysis calcd (%) for C34H46O10Si (642.81):
C 63.53, H 7.21; found: C 63.44, H 7.23.
1H NMR (500 MHz, C6D6): d=1.21 (s, 3H), 1.23 (s, 9H), 1.38 (s, 3H),
1.40 (s, 3H), 1.42 (s, 3H), 3.12 (s, 3H), 3.24 (s, 3H), 3.42 (s, 3H), 3.86
(d, J=10.7 Hz, 1H), 3.95 (d, J=9.1 Hz, 1H), 4.06 (d, J=10.1 Hz, 1H),
4.17 (dd, J=10.1, 10.1 Hz, 1H), 4.25 (d, J=9.1 Hz, 1H), 4.74 (dd, J=
10.4, 10.4 Hz, 1H), 7.28 (m, 6H), 7.95 ppm (m, 4H); 13C NMR
(125.7 MHz, CDCl3): d=17.9 (CH3), 18.0 (CH3), 19.4 (C), 20.3 (CH3),
23.8 (CH3), 26.8 (3ꢆCH3), 47.4 (CH), 47.8 (CH3), 48.0 (CH3), 58.8
(CH3), 62.3 (CH2), 69.1 (CH), 74.1 (CH), 86.9 (CH), 89.6 (C), 100.7 (C),
101.3 (C), 101.5 (C), 127.6 (2ꢆCH), 127.6 (2ꢆCH), 129.5 (CH), 129.6
(CH), 132.8 (C), 133.1 (C), 135.8 (2ꢆCH), 135.9 (2ꢆCH), 169.4 (C),
207.4 ppm (C); 13C NMR (125.7 MHz, C6D6): d=18.2 (2ꢆCH3), 19.6
(CH3), 19.7 (C), 24.2 (CH3), 27.1 (3ꢆCH3), 47.7 (CH3), 47.9 (CH3), 48.0
(CH), 58.7 (CH3), 62.9 (CH2), 69.9 (CH), 74.8 (CH), 87.8 (CH), 90.0 (C),
101.1 (C), 101.6 (C), 102.0 (C), 128.0 (2ꢆCH), 128.1 (2ꢆCH), 129.85
(CH), 129.91 (CH), 133.2 (C), 133.7 (C), 136.3 (2ꢆCH), 136.4 (2ꢆCH),
169.7 (C), 207.4 ppm (C); IR (CHCl3, 0.2 mm): n˜ =2925, 2858, 1762,
1751, 1141, 1111, 1093 cmꢀ1; MS (ESI+): m/z (%): 665 (100) [M+
Na]+; HRMS (ESI+): m/z calcd (%) for C34H46NaO10Si: 665.2758 [M+
Na]+; found: 665.2753; elemental analysis calcd (%) for C34H46O10Si
(642.81): C 63.53, H 7.21; found: C 63.29, H 7.36.
Photocyclization of methyl 2,6-anhydro-4,5-O-[(2S,3S)-2,3-di-
methoxybutane-2,3-diyl]-9-deoxy-3-O-methyl-d-glycero-l-
gulo-nono-7,8-diulosonate (14)
A deoxygenated solution of diketone 14 (160 mg, 0.41 mmol) in
dry C6H6 (5 mL) was placed in a Schlenk tube and irradiated with
a daylight-lamp (Philips master PL electronic, 23 W/865) at 308C for
1
6 h. Progress of the reaction was monitored by H NMR spectrosco-
py, and upon completion, was concentrated under reduced pres-
sure. The residue was purified by silica gel column chromatogra-
phy (hexanes/EtOAc=1:1) to give 15 (149 mg, 0.38 mmol, 93%):
colorless oil, [a]D =ꢀ42 cm3 gꢀ1dmꢀ1 (c=1.21 in CHCl3); 1H NMR
(500 MHz, CDCl3): d=1.38 (s, 3H), 1.44 (s, 3H), 2.27 (s, 3H), 3.29 (s,
3H), 3.50 (s, 3H), 3.51 (s, 3H), 3.73 (s, 1H), 3.78 (s, 3H), 4.00 (d, J=
4.4 Hz, 1H), 4.33 (s, 1H), 4.36 ppm (d, J=4.7 Hz, 1H); 1H NMR
(500 MHz, C6D6): d=1.10 (s, 3H), 1.18 (s, 3H), 2.41 (s, 3H), 2.88 (s,
3H), 3.03 (s, 3H), 3.22 (s, 6H), 4.06 (s, 1H), 4.23 (d, J=4.4 Hz, 1H),
4.67 (s, 1H), 4.78 (dd, J=4.7, 0.9 Hz, 1H), 6.47 ppm (s, 1H);
13C NMR (125.7 MHz, CDCl3): d=17.6 (CH3), 18.2 (CH3), 27.2 (CH3),
48.9 (CH3), 49.7 (CH3), 52.6 (CH3), 59.9 (CH3), 72.7 (CH), 76.9 (2ꢆCH),
78.4 (C), 82.1 (C), 86.4 (CH), 97.9 (C), 99.1 (C), 171.7 (C), 205.5 ppm
(C); 13C NMR (125.7 MHz, C6D6): d=17.6 (CH3), 18.3 (CH3), 27.4
(CH3), 48.5 (CH3), 49.3 (CH3), 51.9 (CH3), 59.5 (CH3), 73.5 (CH), 77.63
(CH), 77.64 (CH), 78.9 (C), 83.0 (C), 87.2 (CH), 98.0 (C), 99.3 (C), 172.1
(C), 204.0 ppm (C); IR (CHCl3, 0.2 mm): n˜ =3323, 2955, 2840, 1753,
1721, 1138, 1109, 1035 cmꢀ1; MS (ESI+): m/z (%): 413 (100) [M+
Na]+; HRMS (ESI+): m/z calcd (%) for C17H26NaO10: 413.1424 [M+
Na]+; found: 413.1431; elemental analysis calcd (%) for C17H26O10
(390.38): C 52.30, H 6.71; found: C 52.01, H 7.08.
Compound 17b: colorless oil, [a]D =ꢀ55 cm3 gꢀ1dmꢀ1 (c=1.3 in
1
CHCl3); H NMR (400 MHz, C6D6): d=1.22 (s, 9H), 1.48 (s, 3H), 1.51
(s, 3H), 1.56 (s, 3H), 1.71 (s, 3H), 3.19 (s, 3H), 3.39 (s, 3H), 3.45 (s,
3H), 3.72 (d, J=8.8 Hz, 1H), 4.20 (d, J=11.3 Hz, 1H), 4.31 (d, J=
11.3 Hz, 1H), 4.35 (dd, J=10.3, 10.3 Hz, 1H), 4.56 (d, J=10.5 Hz,
1H), 5.31 (dd, J=9.8, 9.1 Hz, 1H), 7.30 (m, 6H), 7.88 ppm (m, 4H);
13C NMR (125.7 MHz, C6D6): d=18.2 (CH3), 18.3 (CH3), 19.5 (C), 20.1
(CH3), 22.9 (CH3), 27.1 (3ꢆCH3), 47.3 (CH), 47.6 (CH3), 47.7 (CH3),
58.8 (CH3), 66.6 (CH2), 70.0 (CH), 76.4 (CH), 85.6 (CH), 89.5 (C), 101.3
(C), 101.9 (C), 103.2 (C), 128.2 (2ꢆCH), 128.3 (2ꢆCH), 130.1 (CH),
130.2 (CH), 132.9 (C), 133.3 (C), 135.9 (2ꢆCH), 136.1 (2ꢆCH), 169.0
(C), 208.2 ppm (C); IR (CHCl3, 0.2 mm): n˜ =2929, 1770, 1751, 1141,
1109 cmꢀ1; MS (ESI+): m/z (%): 665 (100) [M+Na]+; HRMS (ESI+):
m/z calcd (%) for C34H46NaO10Si: 665.2758 [M+Na]+; found:
665.2752; elemental analysis calcd (%) for C34H46O10Si (642.81):
C 63.53, H 7.21; found: C 63.35, H 7.31.
Compound 18: colorless oil, [a]D =ꢀ21 cm3 gꢀ1dmꢀ1 (c=1.08 in
1
CHCl3); H NMR (500 MHz, CDCl3): d=1.08 (s, 9H), 1.38 (s, 3H), 1.48
Photocyclization of 1-O-(tert-butyldiphenylsilyl)-2,6-anhydro-
4,5-O-[(2S,3S)-2,3-dimethoxybutane-2,3-diyl]-9-deoxy-3-O-
methyl-d-glycero-l-gulo-nono-7,8-diulose (16)
(s, 3H), 2.30 (s, 3H), 3.16 (s, 3H), 3.48 (s, 3H), 3.51 (s, 3H), 3.60 (dd,
J=11.4, 2.8 Hz, 1H), 3.70 (s, 1H), 3.70 (ddd, J=5.7, 2.8, 2.8 Hz, 1H),
3.76 (dd, J=11.4, 3.8 Hz, 1H), 4.00 (d, J=6.3 Hz, 1H), 4.26 (s, 1H),
6.51 (s, 1H), 7.39 (m, 6H), 7.69 ppm (m, 4H); 13C NMR (125.7 MHz,
CDCl3): d=17.8 (CH3), 18.4 (CH3), 19.4 (C), 26.91 (CH3), 26.96 (3ꢆ
CH3), 49.0 (CH3), 49.6 (CH3), 60.4 (CH3), 64.1 (CH2), 73.9 (CH), 76.3
(CH), 78.6 (CH), 78.5 (C), 82.4 (C), 83.8 (CH), 97.7 (C), 99.0 (C), 127.71
(2ꢆCH), 127.75 (2ꢆCH), 129.73 (CH), 129.75 (CH), 133.0 (C), 133.3
A deoxygenated solution of diketone 16 (376 mg, 0.63 mmol) in
dry C6H6 (8 mL) was placed in a Schlenk tube and irradiated with
a daylight-lamp (Philips master PL electronic, 23 W/865) at 308C for
1
18 h. Progress of the reaction was monitored by H NMR spectros-
copy, and upon completion, the solution was heated in the dark to
788C for 8 h and concentrated under reduced pressure. Attempts
to separate the isomeric alcohols by silica gel column chromatog-
raphy or HPLC were unsuccessful. The residue in dry CH2Cl2 (7 mL)
was then acetylated by adding at 08C, Ac2O (0.18 mL, 1.9 mmol)
and DMAP (230 mg, 1.9 mmol). The solution was stirred at room
temperature for 2 h and concentrated under reduced pressure. The
crude mixture of acetates (846 mg) was purified by careful silica
gel column chromatography (hexanes/EtOAc 9:1!8:2) to give
17a (90.5 mg, 0.141 mmol, 22%), 17b (45.3 mg, 0.071 mmol,
12%), 19 (24 mg, 0.037 mmol, 6%), and 18 (67.1 mg, 0.105 mmol,
18%).
1
(C), 135.6 (2ꢆCH), 135.7 (2ꢆCH), 205.3 ppm (C); H NMR (500 MHz,
C6D6): d=1.15 (s, 9H), 1.18 (s, 3H), 1.22 (s, 3H), 2.45 (s, 3H), 2.94 (s,
3H), 3.07 (s, 3H), 3.36 (s, 3H), 3.57 (dd, J=11.4, 2.8 Hz, 1H), 3.81
(dd, J=11.4, 3.2 Hz, 1H), 3.91 (s, 1H), 4.11 (ddd, J=6.6, 2.8, 2.8 Hz,
1H), 4.18 (d, J=6.3 Hz, 1H), 4.68 (s, 1H), 7.20 (m, 6H), 7.79 ppm
(m, 4H); 13C NMR (100.6 MHz, C6D6): d=17.8 (CH3), 18.4 (CH3), 19.6
(C), 27.1 (CH3), 27.2 (3ꢆCH3), 48.9 (CH3), 49.2 (CH3), 60.2 (CH3), 64.6
(CH2), 74.9 (CH), 77.1 (CH), 78.8 (CH), 78.9 (C), 83.4 (C), 84.5 (CH),
97.8 (C), 99.2 (C), 128.0 (2ꢆCH), 128.1 (2ꢆCH), 129.98 (CH), 130.01
(CH), 133.7 (C), 133.9 (C), 136.0 (2ꢆCH), 136.1 (2ꢆCH), 203.4 ppm
(C); IR (CHCl3, 0.2 mm): n˜ =3309, 2933, 1715, 1225, 1112 cmꢀ1; MS
(ESI+): m/z (%): 623 (100) [M+Na]+; HRMS (ESI+): m/z calcd (%) for
C32H44NaO9Si: 623.2652 [M+Na]+; found: 623.2657; elemental anal-
ysis calcd (%) for C32H44O9Si (600.77): C 63.97, H 7.38; found:
C 63.89, H 7.64.
Compound 17a: colorless oil, [a]D =ꢀ72 cm3 gꢀ1dmꢀ1 (c=1.75 in
1
CHCl3); H NMR (500 MHz, CDCl3): d=1.09 (s, 9H), 1.34 (s, 3H), 1.37
(s, 3H), 1.53 (s, 3H), 1.83 (s, 3H), 3.11 (s, 3H), 3.28 (s, 3H), 3.50 (s,
3H), 3.57 (d, J=9.2 Hz, 1H), 3.65 (d, J=10.1 Hz, 1H), 3.74 (d, J=
10.7 Hz, 1H), 3.82 (dd, J=10.1, 10.1 Hz, 1H), 3.95 (d, J=9.5 Hz, 1H),
4.40 (dd, J=10.4, 10.4 Hz, 1H), 7.39 (m, 6H), 7.77 ppm (m, 4H);
Compound 19: colorless oil, [a]D =ꢀ114 cm3 gꢀ1dmꢀ1 (c=0.82 in
1
CHCl3); H NMR (400 MHz, CDCl3): d=1.03 (s, 9H), 1.25 (s, 3H), 1.38
Chem. Eur. J. 2014, 20, 2663 – 2671
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[4] a) Modern Aldol Reactions, Vols. 1, 2 (Ed.: R. Mahrwald), Wiley-VCH, Wein-
heim, 2004; b) E. M. Carreira, A. Fettes, C. Martꢁ, Org. React. 2006, 67, 1–
216.
[5] a) W. H. Urry, D. J. Trecker, J. Am. Chem. Soc. 1962, 84, 118–120; b) P. J.
Wagner, R. G. Zepp, K.-C. Liu, M. Thomas, T.-J. Lee, N. J. Turro, J. Am.
Chem. Soc. 1976, 98, 8125–8134.
(s, 3H), 2.15 (s, 3H), 2.22 (s, 3H), 3.28 (s, 3H), 3.35 (s, 3H), 3.51 (d,
J=11.7 Hz, 1H), 3.68 (s, 3H), 3.99 (d, J=11.7 Hz, 1H), 4.09 (d, J=
8.6 Hz, 1H), 4.34 (dd, J=9.0, 2.2 Hz, 1H), 4.95 (d, J=2.2 Hz, 1H),
5.08 (dd, J=8.8, 8.9 Hz, 1H), 7.39 (m, 6H), 7.65 ppm (m, 4H);
1H NMR (500 MHz, C6D6): d=1.13 (s, 9H), 1.23 (s, 3H), 1.38 (s, 3H),
1.82 (s, 3H), 2.08 (s, 3H), 2.95 (s, 3H), 3.21 (s, 3H), 3.63 (s, 3H), 3.92
(d, J=11.7 Hz, 1H), 4.28 (d, J=8.5 Hz, 1H), 4.32 (d, J=11.7 Hz, 1H),
4.58 (dd, J=8.8, 2.2 Hz, 1H), 5.15 (d, J=1.9 Hz, 1H), 5.29 (dd, J=
8.6, 8.6 Hz, 1H), 7.18 (m, 6H), 7.80 ppm (m, 4H); 13C NMR
(125.7 MHz, C6D6): d=18.0 (CH3), 18.2 (CH3), 19.5 (CH3), 19.5 (C),
26.5 (CH3), 26.9 (3ꢆCH3), 47.4 (CH3), 47.5 (CH3), 60.5 (CH3), 62.9
(CH2), 70.7 (CH), 73.6 (CH), 80.0 (CH), 81.1 (C), 81.6 (CH), 93.3 (C),
101.8 (C), 102.1 (C), 128.2 (2ꢆCH), 128.3 (2ꢆCH), 130.1 (CH), 130.2
(CH), 132.7 (C), 133.6 (C), 135.8 (2ꢆCH), 136.2 (2ꢆCH), 169.1 (C),
200.1 ppm (C); IR (CHCl3, 0.2 mm): n˜ =2929, 1749, 1721, 1137,
1113 cmꢀ1; MS (ESI+): m/z (%): 665 (100) [M+Na]+; HRMS (ESI+):
m/z calcd (%) for C34H46NaO10Si: 665.2758 [M+Na]+; found:
665.2771; elemental analysis calcd (%) for C34H46O10Si (642.81):
C 63.53, H 7.21; found: C 63.50, H 7.38.
[6] For examples of the captodative effect in the photochemistry of mono-
ketones, see: a) T. Y. Kim, B. S. Park, Bull. Korean Chem. Soc. 1997, 18,
141–142; b) R. L. Blankespoor, R. L. De Jong, R. Dykstra, D. A. Hamstra,
D. B. Rozema, D. P. VanMeurs, P. Vink, J. Am. Chem. Soc. 1991, 113,
3507–3513. For general reviews on the captodative effect, see: c) H. G.
Viehe, Z. Janousek, B. Merenyi, L. Stella, Acc. Chem. Res. 1985, 18, 148–
154; d) L. Stella, J. N. Harvey in Radicals in Organic Synthesis, Vol. 1 (Eds.:
P. Renaud, M. Sibi), Wiley-VCH, Weinheim, 2001, pp. 298–314.
[7] a) P. J. Wagner, J. Am. Chem. Soc. 1967, 89, 5898–5901; b) R. R. Sauers,
S.-Y. Huang, Tetrahedron Lett. 1990, 31, 5709–5712; c) U. Lindemann, G.
Reck, D. Wulff-Molder, P. Wessig, Tetrahedron 1998, 54, 2529–2544; d) K.
Vishnumurthy, E. Cheung, J. R. Scheffer, C. Scott, Org. Lett. 2002, 4,
1071–1074; e) D. Braga, S. Chen, H. Filson, L. Maini, M. R. Netherton,
B. O. Patrick, J. R. Scheffer, C. Scott, W. Xia, J. Am. Chem. Soc. 2004, 126,
3511–3520.
[8] Philips master PL electronic lamp 23 W/865.
[9] a) G. A. Adams, C. T. Bishop, J. Am. Chem. Soc. 1956, 78, 2842–2844;
b) S. Mukherjee, H. C. Srivastava, J. Am. Chem. Soc. 1955, 77, 422–423.
[10] For parameters of the TS in solid state photochemistry of monoketones,
see: a) H. Ihmels, J. R. Scheffer, Tetrahedron 1999, 55, 885–907; b) A. Na-
tarajan, T. T. Mague, V. Ramamurthy, J. Am. Chem. Soc. 2005, 127, 3568–
3576; c) W. Xia, J. R. Scheffer, M. Botoshansky, M. Kaftory, Org. Lett.
2005, 7, 1315–1318.
Acknowledgements
This work was supported by the Investigation Programs of the
Ministerio de Economꢁa y Competitividad (CTQ2010-18244)
and of the Gobierno de Canarias (SolSub20081000192). D.A.-D.
thanks the Ministerio de Economꢁa y Competitividad for a fel-
lowship. C.R.-F. thanks the Programa I3P-CSIC for a postdoctoral
contract.
[11] Coupling constants and dihedrals were calculated with Maestro 9.0
using MacroModel, Schrçdinger, LLC, New York, NY, 2009. Program
PSEUROT as implemented in Matlab GUI (P. M. S. Hendrickx, J. C. Martins,
Chem. Cent. J. 2008, 2, 20) was used for the pseudorotational analysis.
3
3
The JH4,H5,
3JH5,H6, and JH6,H7 experimental constants were obtained by
iterative simulation of the spectra using DAISY as implemented in TOP-
SPIN v. 2.1 for Bruker.
[12] For the most significant NOESY and HMBC correlations for photoprod-
ucts see Figure S3 in the Supporting Information.
Keywords: carbohydrates
photochemistry · radicals
·
cyclization
·
diketones
·
[13] For intramolecular enolsilane additions to a-keto esters, see: a) D. A.
Evans, M. C. Kozlowski, C. S. Burgey, D. W. C. MacMillan, J. Am. Chem.
Soc. 1997, 119, 7893–7894; b) D. A. Evans, C. S. Burgey, M. C. Kozlowski,
S. W. Tregay, J. Am. Chem. Soc. 1999, 121, 686–699; c) K. Juhl, N. Gather-
good, K. A. Jorgensen, Chem. Commun. 2000, 2211–2212; d) R. Roers,
G. L. Verdine, Tetrahedron Lett. 2001, 42, 3563–3565; e) S. Orlandi, A.
Mandoli, D. Pini, P. Salvadori, Angew. Chem. 2001, 113, 2587–2589;
Angew. Chem. Int. Ed. 2001, 40, 2519–2521; f) P. I. Dalko, L. Moisan, J.
Cossy, Angew. Chem. 2002, 114, 647–650; Angew. Chem. Int. Ed. 2002,
41, 625–628; g) H. L. van Lingen, J. K. W. van de Mortel, K. F. W. Hekking,
F. L. van Delft, T. Sonke, F. P. J. T. Rutjes, Eur. J. Org. Chem. 2003, 317–
324; h) P. Dambruoso, A. Massi, A. Dondoni, Org. Lett. 2005, 7, 4657–
4660; For an example of intramolecular carbonyl ene reaction where
a pyruvate moiety acts as enophile, see: i) S. Kaden, M. Hiersemann,
Synlett 2002, 1999–2002.
[14] a) A. Hense, S. V. Ley, H. M. I. Osborn, D. R. Owen, J.-F. Poisson, S. L.
Warriner, K. E. Wesson, J. Chem. Soc. Perkin Trans. 1 1997, 2023–2031;
b) H. Liu, R. Nasi, K. Jayakanthan, L. Sim, H. Heipel, D. R. Rose, B. M.
Pinto, J. Org. Chem. 2007, 72, 6562–6572; For a review on Ley protec-
tors, see: c) S. V. Ley, D. K. Baeschlin, D. J. Dixon, A. C. Foster, S. J. Ince,
H. W. M. Priepke, D. J. Reynolds, Chem. Rev. 2001, 101, 53–80.
[15] H.-G. Korth, J. P. Praly, L. Somsꢃk, R. Sustmann, Chem. Ber. 1990, 123,
1155–1160.
[16] a) J. Dupuis, B. Giese, D. Ruegge, H. Fischer, H.-G. Korth, R. Sustmann,
Angew. Chem. 1984, 96, 887–888; Angew. Chem. Int. Ed. Engl. 1984, 23,
896–898; b) H.-G. Korth, R. Sustmann, J. Dupuis, B. Giese, J. Chem. Soc.
Perkin Trans. 2 1986, 1453–1459; c) H.-G. Korth, R. Sustmann, K. S. Grç-
ninger, T. Witzel, B. Giese, J. Chem. Soc. Perkin Trans. 2 1986, 1461–
1464; d) H.-G. Korth, R. Sustmann, K. S. Grçninger, M. Leisung, B. Giese,
J. Org. Chem. 1988, 53, 4364–4369; e) H.-G. Korth, R. Sustmann, B.
Giese, B. Rꢇckert, K. S. Grçninger, Chem. Ber. 1990, 123, 1891–1898; For
a review, see: f) J.-P. Praly, Adv. Carbohydr. Chem. Biochem. 2000, 56, 65–
151.
[1] For reviews on Norrish/Yang reaction, see: a) P. J. Wagner in Synthetic
Organic Photochemistry (Molecular and Supramolecular Photochemistry),
Vol. 12 (Eds.: A. G. Griesbeck, J. Mattay), Marcel Dekker, New York, 2005,
pp. 11–39; b) P. Wessig, O. Mꢇhling in Synthetic Organic Photochemistry
(Molecular and Supramolecular Photochemistry), Vol. 12 (Eds.: A. G. Gries-
beck, J. Mattay), Marcel Dekker, New York, 2005, pp. 41–87; c) P. J.
Wagner, P. Klꢃn in Handbook of Organic Photochemistry and Photobiolo-
gy, Vol. 1 (Eds.: W. M. Horspool, F. Lenci), CRC, Boca Raton, 2003, chap-
ter 52, pp. 1–31; d) T. Hasegawa in Handbook of Organic Photochemistry
and Photobiology, Vol. 1 (Eds.: W. M. Horspool, F. Lenci), CRC, Boca
Raton, 2003, chapter 55, pp. 1–23; e) P. Wessig in Handbook of Organic
Photochemistry and Photobiology, Vol. 1 (Eds.: W. M. Horspool, F. Lenci),
CRC, Boca Raton, 2003, chapter 57, pp. 1–20; f) P. J. Wagner in Hand-
book of Organic Photochemistry and Photobiology, Vol. 1 (Eds.: W. M.
Horspool, F. Lenci), CRC Press, Boca Raton, 2003, chapter 58, pp. 1–70;
g) P. J. Wagner, B.-S. Park in Organic Photochemistry, Vol. 11 (Ed.: A.
Padwa), Marcel Dekker, New York, 1991, pp. 227–365; h) P. J. Wagner,
Acc. Chem. Res. 1989, 22, 83–91.
[2] a) D. ꢈlvarez-Dorta, E. I. Leꢀn, A. R. Kennedy, C. Riesco-Fagundo, E.
Suꢃrez, Angew. Chem. 2008, 120, 9049–9051; Angew. Chem. Int. Ed.
2008, 47, 8917–8919; b) D. Alvarez-Dorta, E. I. Leꢀn, A. R. Kennedy, A.
Martꢁn, I. Pꢂrez-Martꢁn, C. Riesco-Fagundo, E. Suꢃrez, Chem. Eur. J. 2013,
19, 10312–10333.
[3] a) R. Bishop, J. Chem. Soc. Chem. Commun. 1972, 1288–1289; b) S.
Mohr, Tetrahedron Lett. 1980, 21, 593–594. The issue of which of the
two carbonyl groups initially abstracts the hydrogen atom in the forma-
tion of a-hydroxycyclopentanones by photolysis of a-diketones has
been a point of some controversy, see: c) Y. Ogata, K. Takagi, J. Org.
Chem. 1974, 39, 1385–1386; d) T. Burkoth, E. Ullman, Tetrahedron Lett.
1970, 11, 145–148; e) R. Bishop, N. K. Hamer, J. Chem. Soc. C 1970,
1193–1197.
Chem. Eur. J. 2014, 20, 2663 – 2671
www.chemeurj.org
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4
[17] For one example of conformation of d-glucopyranos-1-yl radicals in C1-
Scheffer, J. Trotter, C.-H. Wu, Tetrahedron Lett. 1997, 38, 6549–6552;
b) see also Ref. [3b]; For reviews on solid state photochemistry of mon-
oketones, see: c) J. R. Scheffer, C. Scott in Handbook of Organic Photo-
chemistry and Photobiology, Vol. 1, 2nd ed., chapter 54, (Eds.: W. M.
Horspool, F. Lenci), CRC, Boca Raton, 2003, pp. 1–25; d) V. Ramamurthy,
K. Venkatesan, Chem. Rev. 1987, 87, 433–481; e) see also Ref. [10a].
[24] For reactions conducted in the crystalline state a direct correlation be-
tween hydrogen abstractability and product structure has been sug-
gested, see: a) E. Cheung, T. Kang, J. R. Raymond, J. R. Scheffer, J. Trot-
ter, Tetrahedron Lett. 1999, 40, 8729–8732; b) M. Leibovitch, G. Olovs-
son, J. R. Scheffer, J. Trotter, J. Am. Chem. Soc. 1998, 120, 12755–12769;
c) A. D. Gudmundsdottir, T. J. Lewis, L. H. Randall, J. R. Scheffer, S. J.
Rettig, J. Trotter, C.-H. Wu, J. Am. Chem. Soc. 1996, 118, 6167–6184;
d) P. J. Wagner, R. Pabon, B.-S. Park, A. R. Zand, D. L. Ward, J. Am. Chem.
Soc. 1994, 116, 589–596.
restricted chair, see Refs. [16b, e]. For radical reactivity of restricted and
unrestricted d-glucose derivatives at the anomeric center, see: H. Abe,
M. Terauchi, A. Matsuda, S. Shuto, J. Org. Chem. 2003, 68, 7439–7447;
H. Abe, S. Shuto, A. Matsuda, J. Am. Chem. Soc. 2001, 123, 11870–
11882.
[18] a) T. Nishikawa, M. Ishikawa, M. Isobe, Synlett 1999, 123–125; b) M.
Isobe, R. Nishizawa, S. Hosokawa, T. Nishikawa, Chem. Commun. 1998,
2665–2676; c) L. F. Tietze, U. Griesbach, I. Schuberth, U. Bothe, A. Marra,
A. Dondoni, Chem. Eur. J. 2003, 9, 1296–1302.
[19] For a review on a-diketones, see: a) Y. Landais, J. M. Vincent, Sci. Synth.
2004, 26, 649–730; b) P. S. Bailey, Chem. Rev. 1958, 58, 925–1010;
c) T. F. Favino, G. Fronza, C. Fuganti, D. Fuganti, P. Graselli, A. Mele, J.
Org. Chem. 1996, 61, 8975–8979; d) L. Re, B. Maurer, G. Ohloff, Helv.
Chim. Acta 1973, 56, 1882–1894.
[20] a) M. Schrçder, Chem. Rev. 1980, 80, 187–213; b) R. Zibuck, D. Seebach,
Helv. Chim. Acta 1988, 71, 237–240.
[25] One example of the formation of an alkoxycarbonyl-cyclobutanol by
photolysis of an a-ketoester has been reported, see: S. Hu, D. C. Neck-
ers, J. Chem. Soc. Perkin Trans. 2 1999, 1771–1778.
[21] CCDC-893121 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[22] The other Scheffer geometrical parameters (D, w, D, and q) of crystal-
line 7 are described in the Supporting Information.
Received: October 1, 2013
[23] Little information on solid state photochemistry of a-diketones is avail-
able; for irradiation of two cyclic a-diketones, see: a) G. Olovsson, J. R.
Published online on January 17, 2014
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