Competition between cyclization, cleavage, and reverse hydrogen transfer in 1,4-hydroxybiradicals: Crystal structure - Solid state reactivity correlations

Article abstract of DOI:10.1021/ol9912377

(formula presented) To provide experimental evidence on the relationship between stucture and reactivity in 1,4-hydroxybiradical intermediates, the Norrish type II photochemistry of a homologous series of spirobenzoyladamantane derivatives was investigated in the crystalline state and the outcome correlated with the structures of the compounds as determined by X-ray crystallography. The results provide an unusually detailed and compelling picture of the geometric factors responsible for the partitioning of these reactive intermediates among cleavage, cyclization, and reverse hydrogen transfer.

Full text of DOI:10.1021/ol9912377

ORGANIC
LETTERS
2000
Vol. 2, No. 1
77-80
Competition between Cyclization,
Cleavage, and Reverse Hydrogen
Transfer in 1,4-Hydroxybiradicals:
Crystal Structure−Solid State Reactivity
Correlations
Eugene Cheung, Matthew R. Netherton, John R. Scheffer,* and James Trotter
Department of Chemistry, UniVersity of British Columbia, 2036 Main Mall,
VancouVer, British Columbia, Canada V6T 1Z1
scheffer@chem.ubc.ca
Received November 9, 1999
ABSTRACT
To provide experimental evidence on the relationship between stucture and reactivity in 1,4-hydroxybiradical intermediates, the Norrish type
II photochemistry of a homologous series of spirobenzoyladamantane derivatives was investigated in the crystalline state and the outcome
correlated with the structures of the compounds as determined by X-ray crystallography. The results provide an unusually detailed and
compelling picture of the geometric factors responsible for the partitioning of these reactive intermediates among cleavage, cyclization, and
reverse hydrogen transfer.
The idealized and widely accepted model of 1,4-biradical
reactivity visualizes cleavage as occurring from either gauche
or anti conformers in which there is overlap of the breaking
σ bond with both half-occupied p-orbitals, whereas cycliza-
tion takes place exclusively from gauche conformers in
which there is poor orbital alignment for cleavage.1 What
this picture lacks is detail. For example, what degree of
orbital overlap is required for cleavage, and how close and
in what orientation should the radical centers be to one
another for cyclization to occur?
Our approach to answering these and related questions has
been to make use of the organic crystalline state. We have
shown that by low conversion irradiation of crystalline
ketones capable of undergoing the Norrish type II hydrogen
atom abstraction reaction, it is possible to generate and
observe the behavior of the corresponding 1,4-hydroxybi-
radicals as “guests” inside the parent ketone lattice.2 Because
it is likely that hydrogen transfer occurs in the solid state
with very little motion of the associated heavy atoms,3,4 the
(2) Ariel, S.; Ramamurthy, V.; Scheffer, J. R.; Trotter, J. J. Am. Chem.
Soc. 1983, 105, 6959.
(3) Gudmundsdottir, A. D.; Lewis, T. J.; Randall, L. H.; Scheffer, J. R.;
Rettig, S. J.; Trotter, J.; Wu, C.-H. J. Am. Chem. Soc. 1996, 118, 6167.
(4) Leibovitch, M.; Olovsson, G.; Scheffer, J. R.; Trotter, J. J. Am. Chem.
Soc. 1998, 120, 12755.
(5) (a) Because the biradicals are conformationally locked in the solid
state, this approach avoids the thorny problem of conformation-dependent
T1 to S1 intersystem crossing being the controlling factor determining
biradical reactivity as suggested by Scaiano.1b (b) For an experimental
structure-reactivity study of a carbene generated in the crystalline state,
see: Keating, A. E.; Shin, S. H.; Houk, K. N.; Garcia-Garibay, M. A. J.
Am. Chem. Soc. 1997, 119, 1474. For theoretical approaches to understand-
ing 1,4-biradical behavior, see: (c) Hoffmann, R.; Swaminathan, S.; Odell,
B. G.; Gleiter, R. J. Am. Chem. Soc. 1970, 92, 7091. (d) Borden, W. T.;
Davidson, E. R. J. Am. Chem. Soc. 1980, 102, 5409. (e) Doubleday, C., Jr.
J. Am. Chem. Soc. 1993, 115, 11968.
(6) Spiroketones 1-3 were synthesized via either standard Friedel-Crafts
(1, 2) or ring-closing metathesis reactions (3). All new starting materials
and photoproducts described in the present paper gave spectroscopic data
and elemental analyses completely in accord with their assigned structures.
Details will be provided in a subsequent full paper.
(1) (a) Wagner, P. J. In CRC Handbook of Organic Photochemistry and
Photobiology; Horspool, W. M., Song, P.-S., Eds.; CRC Press: Boca Raton,
FL, 1995; Chapter 38. (b) Scaiano, J. C.; Lissi, E. A.; Encina, M. V. ReV.
Chem. Intermed. 1978, 2, 139.
10.1021/ol9912377 CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/15/1999

Figure 1. ORTEP diagrams for ketones 1 (a), 2 (b), and 3 (c).
structures of the biradicals can be inferred from a knowledge
of the crystal structures of the parent ketones, and this allows
experimental structure-reactivity relationships to be estab-
lished for these elusive species.5
the plane bisecting the adamantane ring, whereas as the
geometric restraints are reduced in ketones 2, 3, and 4, this
angle increases to 59°, 80°, and 86°, respectively (Figure
1). As we shall see, this is the key structural difference
influencing biradical behavior in these systems.
Photolysis of ketone 1 in both the solid state and solution
leads exclusively to products derived from Norrish type II
cleavage. Irradiation (Pyrex, 4 h, ambient temperature) of 1
in 2:1 tert-butyl alcohol/benzene with anhydrous BaO leads
to formation of enol 5 (Scheme 1). This enol has been
The compounds chosen for study in the present instance
were the spiroketones 1-3.6 Included for comparison
purposes is the nonspiro analogue 4 investigated previously.4
By varying the number of methylene units in the carbonyl-
containing ring from 1 to 3, the geometry of the 1,4-biradicals
produced by γ-hydrogen atom abstraction could be altered,
and these structural changes (as determined by X-ray
crystallography of the parent ketones) were correlated with
the solid state chemical behavior of these species as deduced
from product studies. The results of this investigation provide
an unusually detailed and compelling picture of the geometric
factors responsible for the cyclization, cleavage, and reverse
hydrogen transfer of 1,4-hydroxybiradicals.
Scheme 1
1
observed by H NMR8 and is readily converted to its two
epimeric ketone tautomers, 6, on workup or on prolonged
standing at room temperature. If the photolysis is carried
out in a solvent that contains trace amounts of trifluoroacetic
acid or ammonia, tautomerization of 5 occurs in situ, and
only products derived from photolysis of 6 are observed.9
Irradiation of crystals of ketone 1 to low conversions led to
formation of 6 as the sole product. At higher conversions,
secondary photolysis of 6 predominates, as in solution.
In contrast to the reactivity of the five-membered ring
spiroketone 1, no photoproducts could be detected when the
six-membered ring analogue 2 was irradiated (Pyrex filter,
2:1 tert-butyl alcohol/benzene). This lack of observed
reactivity may be explained by efficient back abstraction of
the hydroxyl hydrogen atom in the intermediate 1,4-biradi-
The X-ray crystal structures of ketones 1-3 were suc-
cessfully determined7 and, along with the crystal structure
of compound 4 determined previously,4 showed that the
carbonyl group of ketone 1 is only 9° out of planarity with
(7) Ketone 1: P21/c; a ) 6.7952(6) Å, b ) 6.7557(8) Å, c ) 28.909(3)
Å; â ) 92.94(1)°; Z ) 4; R ) 5.3%. Ketone 2: C2/c; a ) 17.788(2) Å, b
) 12.827(2) Å, c ) 12.960(1) Å; â ) 104.178°; Z ) 8, R ) 4.9%. Ketone
3: P1h; a ) 10.898(4) Å, b ) 11.213(2) Å, c ) 7.218(6) Å; R ) 99.52(3)°,
â ) 109.01(4)°, γ ) 62.27(2)°; Z ) 2; R ) 4.8%.
(8) Photolysis (Pyrex, 0°, 4 h) of ketone 1 in CD3CN gives rise to new
signals at δ 6.32 (s, enol OH), 5.87 (m, vinyl H), and 5.50 (m, vinyl H).
These signals disappear on addition of catalytic amounts of trifluoroacetic
acid and are replaced by the four vinylic signals of the epimers of
photoproduct 6.
(9) Compounds 6 undergo efficient Norrish type II cleavage to afford
1-indanone (isolated) and bicyclo[3.3.1]nona-2,6-diene and bicyclo[3.3.1]-
nona-2,7-diene (both observed by GC-MS).
78
Org. Lett., Vol. 2, No. 1, 2000

cal.10 Evidence for this interpretation comes from the fact
that irradiation of ketone 2 in 2:1 t-BuOD/benzene or 7%
D2O in acetonitrile leads to deuterium incorporation at the
γ-positions;11 2H NMR analysis of the deuterated photo-
product was consistent with exchange of only the axial
γ-hydrogens on the adamantane ring.12 Analogous exchange
processes are surprisingly rare in Norrish/Yang type II
photochemistry.13
Scheme 2
As in solution, irradiation of crystalline samples of ketone
2 crushed between two Pyrex plates led to no detectable
reaction. However, photolysis of ground crystals of 2
suspended in water containing a trace of added surfactant
(sodium dodecyl sulfonate) led to the formation of rearranged
alcohol 8 (Scheme 2) whose structure was confirmed by
X-ray crystallography.14 This product can arise via formation
of the expected strained cyclobutanol 7 followed by a
cyclobutyl to cyclopropylcarbinyl cation rearrangement. The
nature of the difference in solid state reactivities (anhydrous
versus water suspension) is not clear at this time but likely
involves interactions between water and the ketone molecules
on the solid surface.15
Irradiation of ketone 3 in both the solid state and solution
led exclusively to the Yang cyclization (cyclobutanol)
product 9 (Scheme 2), whose structure was confirmed by
X-ray crystallography.16 An analogous cyclobutanol (10), is
formed in the solution and solid state photochemistry of the
nonspiro ketone 4.4
The geometry of the 1,4-biradical intermediates in these
photoreactions may be characterized by three torsion angles
as defined with reference to structure 11 in Scheme 2.
Assuming that the hybridization of the radical centers is sp2,
we define æ1 as the dihedral angle between the C2-C3 σ
bond and the p-orbital lobe on C1 with which it most nearly
overlaps; æ4 is defined as the analogous angle involving the
C2-C3 σ bond and the most favorably oriented p-orbital lobe
on C4. The third angle is given the symbol ψ and refers to
the C1-C2-C3-C4 torsion angle. In the present instance,
this angle is fixed at 63 ( 1° (gauche) owing to the rigid
adamantane carbon skeleton. Finally, we define D as the
distance in angstroms between C1 and C4. The values of æ1,
æ4, ψ, and D, taken from the X-ray crystal structures of
ketones 1-4, are given in Table 1. The angles æ1 and æ4
are also presented as cos æ1 and cos æ4, because these
functions are proportional to the overlap between a 2pz
atomic orbital and an adjacent σ type orbital17 and provide
a more intuitive picture of the geometric relationships
involved.
(10) Wagner, P. J.; Kochevar, I. E.; Kemppainen, A. E. J. Am. Chem.
Soc. 1972, 94, 7489.
(11) For example, irradiation of ketone 2 in 2:1 t-BuOD/benzene for 29
h led to a 50% recovery of starting material after chromatography, which
consisted of 2-d0 (48%), 2-d1 (42%), and 2-d2 (10%) as determined by mass
spectrometry (31% overall deuteration assuming two exchangeable γ-hy-
drogen atoms).
(12) One peak at δ 2.20 (2:1 CH3OH-C6H6) was observed in the proton-
decoupled 2H spectrum. This corresponds to a 2H doublet in the 1H NMR
spectrum which is produced by hydrogens on a carbon γ to the carbonyl
carbon.
As mentioned above, biradical cleavage is expected to be
best when there is complete overlap between the orbitals of
(13) Attempts to observe such exchange in γ,γ-d2-nonaphenone were
unsuccessful. See: Wagner, P. J.; Kelso, P. A.; Kemppainen, A. E.;
McGrath, J. M.; Schott, H. N.; Zepp, R. G. J. Am. Chem. Soc. 1971, 94,
7506. For an example in which photoinduced H/D exchange occurs at the
δ-position of a ketone as the result of reversible hydrogen atom abstraction,
see: Hu, S.; Neckers, D. C. J. Chem. Soc., Perkin Trans. 2 1999, 1771.
(14) Photoproduct 8: P1h; a ) 19.871(3) Å, b ) 24.676(4) Å, c )
13.000(1) Å; R ) 99.87(1)°, â ) 101.20(1)°, γ ) 109.14(1)°; Z ) 16; R
) 5.04%.
Table 1. Geometric Data for Biradicals 1-4
BR æ1 (deg) cos æ1 æ4 (deg) cos æ4 ψ (deg) D (Å) reactna
1b
-21
40
-87
70
0.93
0.77
0.05
0.34
0.41
29
-30
31
30
30
0.87
0.87
0.86
0.87
0.87
-64
62
-63
-62
-63
3.03
3.08
3.07
3.02
3.02
CL
2
3
4
c
CY
CY
(15) The suspended crystals become fluffy as the reaction proceeds. This
may result from the photoproduct sloughing off, thus exposing a new crystal
surface to the water.
66
a CL ) cleavage; CY ) cyclization. b See footnote 18. c Unreactive in
solid state and solution; products derived from cyclization isolated only
when solid state reaction is carried out in a water suspension.
(16) Photoproduct 9: P21/c; a ) 8.763(3) Å, b ) 14.060(5) Å, c )
11.890(2) Å; â ) 90.51(2)°; Z ) 4; R ) 4.5%.
(17) Burdett, J. K. Molecular Shapes; Wiley-Interscience: New York,
1980; p 6.
Org. Lett., Vol. 2, No. 1, 2000
79

the central σ bond and the two p-orbitals (i.e., æ1 ) æ4 ) 0°
and cos æ1 ) cos æ4 ) 1).1 Inspection of Table 1 reveals
that none of the four biradicals generated in the present study
has this ideal geometry, but that the biradical derived from
ketone 1 is close, with cos æ1 lying between 77% and 93%
of the ideal value and cos æ4 at 87% of maximum.18 This is
significant, as ketone 1 is the only one of the four ketones
to undergo type II cleavage. The biradicals derived from
ketones 3 and 4, in which overlap is very good on one side
and poor on the other, prefer cyclization to cleavage. The
behavior of the biradical derived from ketone 2 is unique.
In solution, and presumably in the anhydrous solid state as
well, it undergoes reverse hydrogen atom transfer to regener-
ate starting material. Only when the solid state photolysis is
carried out in a water suspension is a cyclization-derived
product observed. We discuss this result further in the next
paragraph, but note at this point that the failure of biradical
2 to cleave is consistent with its poor geometry for this
process, which is the worst of the four compounds studied.
Overall, therefore, we conclude that while perfect orbital
overlap is not required for cleavage, it should at least be
very good and should involve both p-orbitals. The data
clearly indicate that excellent overlap on one side and poor
overlap on the other does not lead to cleavage.
values well under 3.40 Å. We must also take into consid-
eration the directionality of the p-orbitals on C1 and C4, i.e.,
how well these orbitals overlap. Maximum overlap occurs
when the p-orbital on C1 is pointing directly at the top lobe
of the orbital on C4, i.e., when the C1 orbital is parallel to
the C2-C4 vector. The crystal structure data reveal that
ketone 1 deviates from this ideal geometry by 52-69° 18 and
that the corresponding deviation from ideality in ketones 2,
3, and 4 is 59°, 39°, and 32°, respectively. Thus, biradical
1, which has the most favorable geometry for cleavage, has
the least favorable geometry for cyclization, and it is hardly
surprising that cleavage dominates completely in this case.
Biradical 2 has a geometry that is imperfect for both cleavage
and cyclization, and this is probably a major factor in the
preference of this species for reverse hydrogen transfer in
solution and the anhydrous solid state. The high strain energy
of the cyclobutanol in this case (7) is undoubtedly a
contributing factor as well.
In summary, the photochemical reactivity displayed by the
benzoyladamantane system is exquisitely sensitive to the
geometry of the intermediate 1,4-hydroxybiradicals, with
cleavage predominating when the radical-containing orbitals
overlap poorly with one another and well with the central
carbon-carbon bond (ketone 1). In contrast, Yang photo-
cyclization takes over for biradicals that are reasonably well
aligned for closure and poorly aligned for cleavage (ketones
3 and 4), and in perhaps the most interesting case of all,
reverse hydrogen transfer dominates for the biradical in
which both cleavage and cyclization are geometrically
disadvantaged (ketone 2).
Having dealt with the structural features that favor 1,4-
hydroxybiradical cleavage, it is equally important to focus
on the geometric factors that favor cyclization. Intuitively,
it makes sense that Yang photocyclization will be favored
when the radical-containing carbon atoms C1 and C4 are close
to one another, probably e 3.40 Å, which is the sum of the
van der Waals radii for two carbon atoms. Table 1 reveals
that the 1,4-biradicals generated in this study all have D
Acknowledgment is made to the donors of the Petroleum
Research Fund, administered by the American Chemical
Society, for partial support of this research. Financial support
by the Natural Sciences and Engineering Research Council
of Canada is also gratefully acknowledged.
(18) This analysis is based on identifying which of the two possible
γ-hydrogen atoms is abstracted. This is clear in the case of ketones 2-4,
where one hydrogen is much closer to the ketone oxygen than the other,
but for compound 1, the two hydrogens are nearly equidistant (2.33 Å as
opposed to 2.36 Å). Because it is not clear which hydrogen is abstracted,
both sets of data are presented.
OL9912377
80
Org. Lett., Vol. 2, No. 1, 2000