The photocyclodimers of 2,3-dihydro-2,2-dimethyl-4H-pyran-4-one

Article abstract of DOI:10.1002/hlca.200690183

On irradiation (350 nm) in benzene solution, dihydropyranone 3 affords predominantly (75%) the cis-anti-cis HH-dimer 4, hut in smaller amounts (12%) also dimer 5, wherein one of the six-membered rings is trans-fused to the (central) cyclobutane ring. The constitution and configuration of 5 was fully elucidated by NMR-analysis. On contact with SiO₂, 5 isomerizes quantitatively to the cis-anti-cis HT-dimer 7, the structure of which was established by X-ray crystal-structure determination.

Full text of DOI:10.1002/hlca.200690183

Helvetica Chimica Acta – Vol. 89 (2006)
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The Photocyclodimers of 2,3-Dihydro-2,2-dimethyl-4H-pyran-4-one
by Kerstin Schmidt, Jürgen Kopf, and Paul Margaretha*
Chemistry Department, University of Hamburg, Martin-Luther-King-Platz 6, D-20146 Hamburg
(phone: +4940428384316; fax: +4940428385592; e-mail: Paul.Margaretha@chemie.uni-hamburg.de)
Dedicated to Professor Heinz Heimgartner on the occasion of his 65th birthday
On irradiation (350 nm) in benzene solution, dihydropyranone 3 affords predominantly (75%) the
cis-anti-cis HH-dimer 4, but in smaller amounts (12%) also dimer 5, wherein one of the six-membered
rings is trans-fused to the (central) cyclobutane ring. The constitution and configuration of 5 was fully
elucidated by NMR-analysis. On contact with SiO2, 5 isomerizes quantitatively to the cis-anti-cis HT-
dimer 7, the structure of which was established by X-ray crystal-structure determination.
1. Introduction. – Sesquiterpenes display a large variety of substructures. Some of
them contain a cyclobutane ring, e.g., those bearing the (bicyclic) caryophillane, or
the (tricyclic) tritomarane, protoilludane, panasinsane, and bourbonane skeletons [1].
While the latter skeleton type contains a tricyclo[5.3.0.02,6]decane structural unit,
there are no examples of naturally occuring compounds exhibiting the homologous tri-
cyclo[6.4.0.02,7]dodecane substructure. Formally, these tricycles result from [2+2]
cyclodimerization of two cyclopentene or cyclohexene units, respectively. Whereas
the C10 parent hydrocarbon 1 occurs in only two diastereoisomeric forms, i.e., 1a and
1b, there are five possible diastereoisomers, i.e., 2a–2e, for the C12 parent hydrocarbon
2. Among them, the doubly trans-fused dimers 2c and 2d are of special interest with
respect to the strain incorporated in such molecules [2][3]. Interestingly, the trans-
anti-trans dimer 2c is a major product in the sensitized photocyclodimerization of cyclo-
hexene, whereas the trans-syn-trans dimer 2d remains unknown [4][5].
Insertion of a trigonal planar C-atom into the six-membered ring leads to a slight
increase in strain energy, e.g., 2.1 kcal/mol for cyclohexanone as compared to cyclohex-
ane [6]. It is, therefore, not surprising that, in the photocyclodimerization of cyclohex-2-
enones, cis-fused tricyclic dimers are formed predominantly. Nevertheless, a trans ring
ꢀ 2006Verlag Helvetica Chimica Acta AG, Zürich

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Helvetica Chimica Acta – Vol. 89 (2006)
fusion has been assigned to a minor dimer of the (parent) cyclohex-2-enone, as it
showed twelve distinct peaks in its 13C-NMR spectrum, although its structure was
not assigned [7]. Similarly, it has been reported that a minor dimer of 4,4- dimethylcy-
clohex-2-enone isomerized to a – now – cis-fused tricyclic dimer, and, therefore, it was
tentatively concluded, that it may be a trans-fused dimer [8]. Here, we now report on
the first full spectroscopic characterization (1H- and 13C-NMR) of such a trans-fused tri-
cyclo[6.4.0.02,7]dodecanedione.
2. Results. – Long time ago, we had reported [9] that irradiation of 2,3-dihydro-2,2-
dimethyl-4H-pyran-4-one (3) in either MeCN or hexane affords the cis-anti-cis dimer 4
selectively (>95%). We have now repeated the same experiment in benzene at differ-
ent enone concentrations and found that, on irradiation (350 nm) of a 1M solution of 3
in this solvent, the relative amount of 4 formed was reduced to 75%, while three other
tricyclic dimers 5–7 were formed in appreciable amounts of 12, 9, and 4%, respectively
(Scheme).
Scheme
The structure elucidation of dimers 5–7 was facilitated by the fact that dimer 4 was
only slightly soluble in Et2O. Trituration of the original dimer mixture with this solvent
G
allowed the separation of ca. 2/3 of 4 by filtration, affording a new mixture with the (rel-
ative) composition 40 :27:22 :11 of the same four dimers. Attempted separation of this
mixture by column chromatography on SiO2 afforded fractions which contained mix-
tures of 4, 6, and 7 without any clue of dimer 5. Indeed, stirring of this mixture over
SiO2, both in the absence or presence of traces of Et3N, altered the composition of
G
the mixture to 40 :0 :22 :38 without any loss of material, indicating that 5 was quantita-
tively converted to 7 under these conditions. From this mixture, both dimers 6 and 7
were successfully isolated by column chromatography on SiO2 with CH2Cl2/MeOH
99 :1 as eluent, whereby 7 exhibited a just slightly higher Rf value than 4, while the
Rf value of 6 was distinctly lower. The structure assignment for dimers 4, 6, and 7
was confirmed by X-ray crystal-structure determinations, whereas the assignment of
a trans-ring fusion in 5 (Figure) resulted from both the observation of its isomerization
to 7 and its NMR data.

Helvetica Chimica Acta – Vol. 89 (2006)
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Figure. Selected NMR data of 5. 1H-NMR Coupling constants J in
Hz: H1,H2 =4.3, H2,H7 =4.5, H7,H8 =8.2, H1,H8 =10.9, H5,H5 =14.8,
H11,H11 =13.5. 13C-NMR Chemical shifts in CDCl3 in ppm: C(1) 56.1,
C(2) 71.1, C(4) 78.1, C(5) 52.2, C(6) 205.5, C(7) 53.1, C(8) 76.2, C(10)
82.1, C(11) 54.2, C(12) 199.2.
3. Discussion. – Usually, the variation of the (isotropic) solvent in enone photocy-
clodimerization reactions only moderately affects the regio- and stereochemical out-
come of such reactions, whereas zeolites have been shown to exert a more significant
influence [7]. It is, thus, noteworthy that the substitution of, e.g., hexane by benzene
induces a quite important change in the photocyclodimerization product ratio of oxa-
enone 3, as the dielectric constants of these two solvents are quite similar. A plausible
explanation for the differing product distribution in these bimolecular reactions could
be related to the difference in viscosities, h=0.313 cp for hexane and 0.649 cp for ben-
zene. The advantage of using oxaenone 3 as a ꢁmodelꢂ cyclohex-2-enone is straightfor-
1
ward, regarding the simplicity of the first order H-NMR spectra of the photodimers.
Identification of the H-atoms adjacent to both the O-atom and the C=O group in
the six-membered rings is unambiguous, and subsequent C,H-correlation spectra
then allow a full assignment of the their constitution and (relative) configuration.
Nonetheless, the structures of 4, 6, and 7 have been additionally confirmed by X-ray
1
crystal-structure determination. The H-NMR data of the two six-membered rings in
dimer 5 reflect the expected differences between a trans- and a cis-fused bicy-
clo[4.2.0]octan-2-one [10]. Indeed, the vicinal coupling constant for the H-atoms at
the fusion site is larger, and the magnitude of the geminal coupling constant of the
CH2 H-atoms vicinal to the C=O group is smaller in the trans-fused moiety. Similarly,
the 13C-NMR data support this assignment, as all tetrahedral C-atoms in the trans-fused
moiety resonate at lower field than the corresponding C-atoms in the cis-fused moiety,
whereas the opposite is observed for the C=O C-atoms [10]. In conclusion, we have, for
the first time, identified and fully characterized spectroscopically a trans-cis-fused tri-
cyclic cyclohexenone photodimer. Isolation of such compounds by conventional col-
umn chromatography is totally hampered by the ease of isomerization to a (less
strained) cis-cis-fused diastereoisomer. We are, therefore, now studying the photodime-
rization of the analogous thia-enone, 2,3-dihydro-2,2-dimethyl-4H-thiopyran-4-one,
hoping that the corresponding – more flexible – trans-fused six-membered thia-cyclic
moiety will be more resistant towards isomerization under these conditions.
Experimental Part
1. General. Photolyses were run in a Rayonet RPR-100 photoreactor equipped with 16350-nm lamps
and solvents of spectrophotometric grade. Column chromatography (CC): silica gel 60 (Merck; 230–400
mesh). 1H- and 13C-NMR spectra (including two-dimensional plots): in CDCl3 at 500.13 and 125.8 MHz,
resp., d in ppm, J in Hz. GC/EI-MS: at 70 eV; 30-m SE-30 cap. column. X-Ray analyses were run on an
Bruker APEX CCD three-circle diffractometer at 153 K with MoKa radiation (l=0.71073 Š).
2. Starting Materials. 2,3-Dihydro-2,2-dimethyl-4H-pyran-4-one (3) was synthesized according to
[11].

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Helvetica Chimica Acta – Vol. 89 (2006)
3. Prep. Photolysis. An Ar-degassed soln. of 3 (504 mg, 4 mmol) in benzene (5 ml) was irradiated for
72 h up to 90% conversion. After evaporation of the solvent, 1H-NMR analysis of the residue (504 mg,
mixture A) indicated the formation of four products 4–7 in a 75 :12 :9 :4 ratio. The residue was stirred at
r.t. in Et2O (5 ml) for 10 min and then filtered to afford 252 mg (50%) pure 1a,2b,7b,8a-4,4,11,11-tetra-
G
methyl-3,12-dioxatricyclo[6.4.0.02,7]dodecane-6,9-dione (4). M.p. 134–1368. 1H-NMR: 4.36, 3.26
(AA’XX’, JAX =5.2, JAAꢀ =8.4, JAXꢀ =À1.1, JXX’ =À0.5, 4 H); 2.57, 2.34 (AB, J=15.9, 4 H); 1.37, 1.23
(2s, 4 Me). 13C-NMR: 206.5 (s); 77.1 (s); 74.2 (d); 51.2 (t); 47.2 (d); 31.1, 25.0 (q, Me). MS: 252 (0.05,
M+), 127 (30), 111 (40), 82 (55), 71 (60), 41 (100).
1H-NMR Analysis of the filtrate (mixture B) after evaporation of the solvent (148 mg) indicated a
40 :27:22 :11 composition ratio of products 4–7. This residue was redissolved in CH2Cl2 (5 ml), and
1
SiO2 (800 mg) was added, and the mixture was stirred at r.t. for 4 h. H-NMR Analysis of the residue
(mixture C) after filtration and evaporation of the solvent indicated a 40 :0 :22 :38 composition, i.e., 5
was quantitatively converted to 7. The following spectroscopic data for 1a,2a,7a,8b-4,4,10,10-tetra-
methyl-3,9-dioxatricyclo[6.4.0.02,7]dodecane-6,12-dione (5) were directly from product mixture B. 1H-
NMR: 4.80 (dd, J=4.3, 4.5); 4.62 (dd, J=8.2, 10.9); 2.94 (dd, J=4.5, 8.2); 2.87 (dd, J=4.3, 10.9); 2.62
(d, J=14.8); 2.38 (d, J=13.5, 2.29 (d, J=14.8); 2.29 (d, J=13.5); 1.42, 1.412, 1.38, 1.17 (4s, 4 Me). 13C-
NMR: 205.5 (s); 199.2 (s); 82.1 (s); 78,1 (s); 76.2 (d); 71.1 (d); 56.1 (d); 54.2 (t); 53.1 (d); 52.2 (t);
31.5, 30.5, 25.2, 24.3 (4q, 4 Me). MS: 252 (25, M+), 155 (90), 99 (75), 43 (100).
Mixture C (148 mg) was subjected to CC (2.5”60-cm column; CH2Cl2/MeOH 99 :1). The first frac-
tion (12 mg, 2.4%) contained pure 1a,2b,7b,8a-4,4,10,10-tetramethyl-3,9-dioxatricyclo[6.4.0.02,7]-
dodecane-6,12-dione (7). M.p. 144–1468. 1H-NMR: 4.86, 3.01 (AA’XX’, JAX =6.3, JAA’ =0.0, JAX’ =4.1,
J
XX’ =0.0, 4 H); 2.45, 2.38 (AB, J=16.4, 4 H); 1.34, 1.28 (2s, 4 Me). 13C-NMR: 207.5 (s); 77.1 (s); 71.7
(d); 52.2 (t); 52.1 (d); 30.5, 26.1 (2q, 4 Me). MS: 252 (0.05, M+), 127 (80), 71 (100).
The second fraction (101 mg, 20%) consisted of a 2 :3 mixture of 7 and 4. The third fraction (15 mg,
3%) contained pure 1a,2a,7a,8a-4,4,10,10-tetramethyl-3,9-dioxatricyclo[6.4.0.02,7]dodecane-6,12-dione
1
(6). M.p. 154–1568. H-NMR: 4.76, 3.09 (AA’XX’, JAX =5.6, JAA’ =0.0, JAX’ꢁ =5.7, JXX’ =0.0, 4 H); 2.57,
2.35 (AB, J=16.1, 4 H); 1.33, 1.13 (2s, 4 Me). 13C-NMR: 206.2 (s); 76.2 (s); 71.2 (d); 54.1 (t); 47.2 (d);
30.5, 25.1 (2q, 4 Me). MS: 252 (0.05, M+), 127 (35), 126(40), 111 (45), 71 (100).
X-Ray Crystal-Structure Determination of 41). Pale colorless needles (0.38”0.07”0.05 mm) from
Et
c=6.440(3) Š, b=117.699(7)8; V=1322.5(9) Š3, Dx =1.267 g cmÀ3
X-Ray Crystal-Structure Determination of 61). Pale colorless blocks (0.45”0.25”0.20 mm) from
2O, C14H20O4, Mr 252.30: monoclinic, space group P21/c, Z=4, a=10.363(3), b=8.067(2),
c=16.340(4) Š, b=98.415(5)8; V=1351.3(6) Š3, Dx =1.240 g cmÀ3
X-Ray Crystal-Structure Determination of 71). Pale colorless blocks (0.19”0.17”0.05 mm) from
2O, C14H20O4, Mr 252.30: monoclinic, space group C2/c, Z=4, a=11.687(5), b=19.846(8),
.
Et
ACHTREUNG
.
Et2O, C14H20O4, Mr 252.30: monoclinic, space group P21/c, Z=4, a=11.078(2), b=10.904(2),
G
c=12.427(2) Š, b=118.826(11)8; V=1315.1(4) Š3, Dx =1.274 g cmÀ3
.
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1
)
CCDC-613920, CCDC-613921, and CCDC-613922 contain the supplementary crystallographic data
for 4, 6, and 7, respectively. This data can be obtained free of charge via www.ccdc.cam.ac.uk/data_
request/cif.

Helvetica Chimica Acta – Vol. 89 (2006)
1931
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Received July 5, 2006