Stereochemical memory in the temperature-dependent photodenitrogenation of bridgehead-substituted DBH-type azoalkanes: Inhibition of inverted-housane formation in the diazenyl diradical through the mass effect (inertia) and steric hindrance

Article abstract of DOI:10.1021/ja026321n

The photochemical denitrogenation of the cyclopentene-annelated DBH-type azoalkanes 1 has been examined in solution as a function of bridgehead substitution and temperature. For all derivatives, namely, the unsubstituted 1a(H/H), monomethyl 1b(Me/H) dimet

Full text of DOI:10.1021/ja026321n

Published on Web 09/19/2002
Stereochemical Memory in the Temperature-Dependent
Photodenitrogenation of Bridgehead-Substituted DBH-Type
Azoalkanes: Inhibition of Inverted-Housane Formation in the
Diazenyl Diradical through the Mass Effect (Inertia) and Steric
Hindrance
Waldemar Adam,*,† Hermenegildo Garc ´ı a,* Manfred Diedering, Vicente Mart ´ı ,
,‡
†
†
Massimo Olivucci,* and Emilio Palomares‡
,§
Contribution from the Institut f u¨ r Organische Chemie, UniVersit a¨ t W u¨ rzburg,
Am Hubland, D-97074 W u¨ rzburg, Germany, Instituto de Tecnolog ´ı a Qu ´ı mica CSIC-UPV,
Apartado 22012, E-46071, Valencia, Spain, and Dipartimento di Chimica, UniVersit a` di Siena,
Via Aldo Moro, I-53100 Siena, Italy
Received March 26, 2002
Abstract: The photochemical denitrogenation of the cyclopentene-annelated DBH-type azoalkanes 1 has
been examined in solution as a function of bridgehead substitution and temperature. For all derivatives,
namely, the unsubstituted 1a(H/H), monomethyl 1b(Me/H) dimethyl 1c(Me/Me), monophenyl 1d(Ph/H),
and diphenyl 1e(Ph/Ph), the temperature-dependent ratio of syn and anti housanes 2 provides experimental
support for a competition between the singlet (high temperature) and triplet (low temperature) reaction
channels in the direct photolysis. The syn/anti ratio of the housanes 2 depends on the extent and type of
bridgehead substitution; the amount of the anti diastereomer (retention) follows the order Ph > Me > H,
and double substitution is more effective than single. This stereochemical memory is interpreted in terms
of the mass effect (inertia) of the substituents and steric interaction (size) between the substituents at the
bridgehead and the methylene bridge during the deazetation step of the transient diazenyl diradical
1
1
conformations DZ (exo-ax) and DZ (exo-eq). These conformers are impulsively generated upon decay of
1
the (n,π*)-excited azoalkane, a trajectory assessed through computational work. The new mechanistic
feature disclosed by the unprecedented anti stereoselectivity (retention) is the intervention of a puckered
1
1
,3-cyclopentanediyl singlet diradical DR as product bifurcation step, whose conformational relaxation to
the planar species (loss of stereochemical memory) is encumbered by bridgehead substitution.
Introduction
[2.1.0]pentane (exo housane) is formed as the major product
Scheme 1). It was also shown that in the liquid-phase photolysis
inversion dominates.
(
The nitrogen extrusion of azoalkanes is a complex and
intriguing process that has attracted much attention for the last
almost forty years. Initially, Roth and Martin reported that
1
-7
1a
Several mechanisms have been postulated to explain this
unusual stereochemical preference (Scheme 1): The SH2
in the gas-phase thermolysis of exo-deuterated diazabicyclo-
1b
process involves the stepwise cleavage of the two C-N bonds,
[2.2.1]heptene (d2-DBH), the inverted exo-deuterated bicyclo-
1
with the singlet diazenyl diradical ( DZ) as the key intermedi-
6
*
Address correspondence to Institut f u¨ r Organische Chemie, Universit a¨ t
ate. Concerted backside displacement (analogous to the SN2
W u¨ rzburg, Am Hubland, D-97074 W u¨ rzburg, Germany. E-mail: adam@
chemie.uni-wuerzburg.de. Fax: +49-931-8884754. Internet: http//www-
organik.chemie.uni-wuerzburg.de.
1c
mechanism ) of the nitrogen molecule by the carbon-radical
site affords the inverted exo housane. In competition, denitro-
†
Universit a¨ t W u¨ rzburg.
Instituto de Tecnolog ´ı a Qu ´ı mica CSIC-UPV.
Universit a` di Siena.
(
5) (a) Yamamoto, N.; Olivucci, M.; Celani, P.; Bernardi, F.; Robb, M. A. J.
Am. Chem. Soc. 1998, 120, 2391-2407. (b) Nau, W. M.; Greiner, G.; Wall,
J.; Rau, H.; Olivucci, M.; Robb, M. A. Angew. Chem., Int. Ed. 1998, 37,
98-101.
‡
§
(
1) (a) Roth, W. R.; Martin, M. Liebigs Ann. Chem. 1967, 702, 1-5. (b) Roth,
W. R.; Martin, M. Tetrahedron Lett. 1967, 47, 4695-4698. (c) Porter, N.
A.; Cudd, M. A.; Miller, R. W.; McPhail, A. T. J. Am. Chem. Soc. 1980,
(6) (a) Adam, W.; Oppenl a¨ nder, T.; Zang, G. J. Org. Chem. 1985, 50, 3303-
3312. (b) Adams, J. S.; Weisman, R. B.; Engel, P. S. J. Am. Chem. Soc.
1990, 112, 9115-9121. (c) Simpson, C. J. S. M.; Wilson, G. J.; Adam, W.
J. Am. Chem. Soc. 1991, 113, 4728-4732. (d) Adam, W.; Denninger, U.;
Finzel, R.; Kita, F.; Platsch, H.; Walter, H.; Zang, G. J. Am. Chem. Soc.
1992, 114, 5027-5035. (e) Diau, E. W.-G.; Abou-Zied, O. K.; Scala, A.
A.; Zewail, A. H. J. Am. Chem. Soc. 1998, 120, 3245-3246. (f) LeFeore,
G. N.; Crawford, R. J. J. Am. Chem. Soc. 1986, 108, 1019-1027. (g) Green,
J. G.; Dubay, G. R.; Porter, N. A. J. Am. Chem. Soc. 1977, 99, 1264-
1265. (h) Porter, N. A.; Landis, M. E.; Marnett, L. J. J. Am. Chem. Soc.
1971, 93, 795-796.
1
02, 414-416. (d) Allred, E. L.; Smith, R. L. J. Am. Chem. Soc. 1969, 91,
6
766-6775.
(
2) (a) Bauer, S. H. J. Am. Chem. Soc. 1969, 91, 3688-3689. (b) Bigot, B.;
Sevin, A.; Devaquet, A. J. Am. Chem. Soc. 1978, 100, 2639-2642. (c)
Dannenberg, J. J.; Rocklin, D. J. Org. Chem. 1982, 47, 4529-4534. (d)
Sherill, C. D.; Seidl, E. T.; Schaefer, H. F., III. J. Phys. Chem. 1992, 96,
3
712-3716.
3) Sorescu, D. C.; Thompson, D. L.; Raff, L. M. J. Chem. Phys. 1995, 102,
910-7924.
4) Liu, R.; Cui, Q.; Dunn, K. M.; Morokuma, K. J. Chem. Phys. 1996, 105,
333-2345.
(
(
7
(7) Adam, W.; Garc ´ı a, H.; Mart ´ı , V.; Moorthy, J. N. J. Am. Chem. Soc. 1999,
121, 9475-9476.
2
1
2192 J. AM. CHEM. SOC. 2002, 124, 12192-12199
9
10.1021/ja026321n CCC: $22.00 © 2002 American Chemical Society

Temperature-Dependent Photodenitrogenation
A R T I C L E S
5
a
Scheme 1
diazenyl functionality. This appears to be a general feature in
1
the R cleavage of (n,π*)-excited azoalkanes, as demonstrated
5
b
for pyrazoline and 2,3-diazabicyclo[2.2.2]octane. After the
transition state has been reached, the molecule evolves toward
a conical intersection (CI), located ca. 25 kcal/mol lower in
1
energy, where the σ,π and σ,σ states of the DZ diradical cross.
Decay to the ground state through the conical intersection leads
to the region of a singlet σ,σ-DZ structure in the exo-axial
configuration, which is located ca. 40 kcal/mol below the same
transition state. Since the reaction coordinate is substantially
dominated by a change in the C-N-N angle (i.e., the endo-
to-exo motion), a considerable fraction of the 50 kcal/mol of
kinetic energy is initially deposited in the C-N-N bending
mode of the σ,σ-DZ species. We argue that the apparent
coupling between C-N-N bending and the axial-to-equatorial
torsion will impulsively displace the exo-axial conformation
toward the exo-equatorial to generate ultimately the inverted
genation leads to the C2-symmetric2d singlet 1,3-cyclopen-
tanediyl diradical DR, which collapses to both the retained and
1
inverted housanes in equal amounts. Alternatively, in recent
work the dynamic model for the thermolysis of DBH has been
proposed, in which the intervention of the singlet diazenyl
8
housane. In contrast to the thermally activated process, a
1
diradical DZ was questioned on the basis of computational
reaction coordinate that describes the simultaneous breaking of
both CN bonds in the azoalkane has not been located in the
photochemical process.
8
results. It was concluded that the thermal denitrogenation of
1
DBH proceeds directly to a nonstatistical DR intermediate by
concerted cleavage of both CN bonds (Scheme 1), for which
prevalent inversion was rationalized in terms of the previously
proposed momentum conservation.1d
The mechanistic implications of these computations10 on the
photodenitrogenation of DBH are displayed in Scheme 3.
1
Passage through the conical intersection generates first the DZ
Qualitative considerations in terms of Dauben-Salem-Turro
(
exo-ax) diradical as bona fide intermediate, which generates
9
theory suggest that the photochemical azoalkane denitrogena-
1
the DZ (exo-eq) species. The latter leads to the inverted housane
tion6 proceeds stepwise. Indeed, our new computational results
a,d
by means of backside attack along the SH2 coordinate (a 2.2
1
indicate that the inverted housane may be formed from the DZ
1
0
kcal/mol barrier has been computed for this process). Alter-
intermediate by the SH2 process (Scheme 1). While a detailed
account of these computations will be given elsewhere, here
we report the computed reaction coordinate that describes the
singlet-excited-state evolution and the ground-state relaxation
1
natively, the DZ (exo-ax) intermediate loses N2 to afford
initially the puckered singlet 1,3-cyclopentanediyl diradical
1
DR(puckered), which is predestined to cyclize into the retained
housane (stereochemical memory effect). In competition, the
1
10
of the (n,π*)-excited DBH (Scheme 2). In this scheme are
1
1
DR(puckered) transient relaxes to the C2-symmetric DR(C2)
1
given the computed structures of the exo-axial [σ,σ- DZ
diradical, from which the retained and inverted housanes are
produced in equal amounts. Recent experimental work on the
viscosity dependence of the stereoselectivity in the photodeni-
trogenation of DBH derivatives confirmed the intermediacy of
1
(
exo-axial)] and exo-equatorial [σ,σ- DZ (exo-equatorial)]
conformations and their relative energies (kcal/mol) along the
1
reaction coordinate ( n,π*, σ,π-DZ-like and σ,π/σ,σ have been
taken from ref 5a). Our computations predict that the initially
1
11
the singlet diazenyl diradical DZ.
1
generated exo-axial σ,σ- DZ intermediate transforms to the
In a related study on the photodenitrogenation of the more
slightly higher-energy (0.7 kcal/mol) exo-equatorial conforma-
tion with an activation barrier of ca. 4.5 kcal/mol, the species
destined to afford inverted housane along the SH2 process.
In the computed structures, the C-7 methylene group in DBH
7
complex cyclopentene-annelated DBH-type azoalkane 1a, also
1
a diazenyl diradical DZ was invoked to rationalize the unusual
temperature dependence on the product ratio of inverted (syn)
versus retained (anti) housanes 2a (Scheme 4). While at low
(the molecular fragment that undergoes the largest displacement)
1
temperature, isc from 1(n,π*) to the triplet-excited state
is shown in front views, side views have been chosen for the
cyclopentyl envelopes, in which the substituents have been
omitted to help visualize the conformational changes during the
3
1
(n,π*) is the major process (path B), at high temperature the
isc is circumvented, presumably because of efficient R-CN bond
1
cleavage to the diazenyl diradical DZ. The latter undergoes
1
inversion process. The (n,π*)-excited azoalkane breaks first
ring closure along the SH2 pathway to afford the inverted syn-2
housane. To understand the mechanistic intricacies of this
stereoselective inversion process, we have now examined the
bridgehead substituent effect on the syn/anti-housane ratio in
the photodenitrogenation of the unsymmetrical monomethyl- and
monophenyl-substituted azoalkanes 1b(Me/H) and 1d(Ph/H), as
well as the symmetrical dimethyl and diphenyl derivatives
one of the CN bonds5 to reach a transition state with singlet
a,5b
σ,π-DZ diradical character in the endo configuration of the
(
8) Reyes, M. B.; Carpenter, B. K. J. Am. Chem. Soc. 2000, 122, 10163-
0176.
9) Dauben, W. G.; Salem, L.; Turro, N. J. Acc. Chem. Res. 1975, 8, 41-54.
1
(
(
10) (a) Sinicropi, A.; Page, C.; Adam, W.; Olivucci, M. J. Am. Chem. Soc.
2
002, submitted. (b) All computations where carried out at the ab initio
CASSCF level of theory with the 6-31G* basis set and a 12 electron in 10
orbital active space; reevaluation of the energy barriers and relative
stabilities has then been carried out at the CAS-PT2 level of theory to
account for the effect of dynamic correlation, see also Supporting
(11) (a) Adam, W.; Marti, V.; Sahin, C.; Trofimov, A. V. J. Am. Chem. Soc.
2000, 122, 5002-5003. (b) Adam, W.; Marti, V.; Sahin, C.; Trofimov, A.
V. Chem. Phys. Lett. 2001, 340, 26-32. (c) Adam, W.; Gr u¨ ne, M.;
Diedering, M.; Trofimov, A. V. J. Am. Chem. Soc. 2001, 123, 7109-7112.
(d) Adam, W.; Diedering, M.; Trofimov, A. V. Chem. Phys. Lett. 2001,
350, 453-458. (e) Adam, W.; Diedering, M.; Trofimov, A. V. Phys. Chem.
Chem. Phys. 2002, 4, 1036-1039. (f) Adam, W.; Diedering, M.; Trofimov,
A. V. J. Am. Chem. Soc. 2002, 124, 5427-5430.
1
Information. The primary σ, σ- DZ conformation has been unambiguously
determined by computing the relaxation path through the evaluation of the
steepest descent path in mass-weighted coordinates (ref 10c) by starting
from the previously reported (ref 5a) σ, π/σ, σ conical intersection. (c)
Garavelli, M.; Celani, P.; Fato, M.; Bearpark, M. J.; Smith, B. R.; Olivucci,
M.; Robb, M. A. J. Phys. Chem. A 1997, 101, 2023-2032.
J. AM. CHEM. SOC.
9
VOL. 124, NO. 41, 2002 12193

A R T I C L E S
Adam et al.
Scheme 2
Scheme 3
Scheme 4
1c(Me/Me) and 1e(Ph/Ph). We demonstrate that the temperature
dependence of the syn/anti product ratio is a general feature in
the photolysis of these azoalkanes, irrespective of the extent
and type of bridgehead substitution. Equally mechanistically
significant, the present set of azoalkane derivatives requires an
additional product-branching point (dashed arrows in Scheme
1
4
) for the transient DZ structure, which modifies the product
distribution by enhancing the amount of anti housane 2 in the
order of the mass and the steric demand of the bridgehead
substituent: 1e(Ph/Ph) > 1d(Ph/H) > 1c(Me/ Me) > 1b(Me/
H) > 1a(H/H). We propose that the mass of the bridgehead
substituents and their steric interactions with the gem-dimethyl
group in the 1DZ diradical effectively encumber the ring-
inversion motion prompted by the excited-state relaxation
known; the latter was fully characterized (cf. Supporting
Information). The housanes anti- and syn-2a were obtained as
7,13
reported, the remaining anti- and syn-housanes 2 were fully
characterized by spectroscopic methods (cf. Supporting Infor-
mation). The configuration of the anti housanes was assigned
by means of an NOE effect between the syn-methyl group and
the C1-bridgehead hydrogen atom, and for the syn diastereomer,
between the anti-methyl group and the C6,7-methylene exo-
hydrogen atoms. Additional support for this assignment comes
(Scheme 2) and are, therefore, responsible for these unprec-
edented product data. Exclusive retention, as observed for the
diphenyl derivative 1e, has hitherto not been documented in
solution. In fact, only in the confined space of the crystal lattice
was mainly, but not exclusively, retention found in the photo-
denitrogenation of d2-DBH.1
a
(
12) (a) Beck, K.; H o¨ hn, A.; H u¨ nig, S.; Prokschy, F. Chem. Ber. 1984, 117,
Results
5
17-533. (b) Beck, K.; Burghard, H.; Fischer, G.; H u¨ nig, S.; Reinold, P.
Angew. Chem., Int. Ed. Engl. 1987, 26, 672-673.
13) Adam, W.; Harrer, H. M.; Nau, W. M.; Peters, K. J. Org. Chem. 1994, 59,
3786-3797.
The azoalkanes 1 were prepared according to the H u¨ nig
route,12 of which all but the monophenyl derivative 1d are
(
12194 J. AM. CHEM. SOC.
9
VOL. 124, NO. 41, 2002

Temperature-Dependent Photodenitrogenation
A R T I C L E S
from the quantitative thermal isomerization of the syn diaster-
eomers to the persistent anti housanes.7,14
The activation parameters for the syn-to-anti isomerization
diminished at the lower (entries 6/3, 12/9, 18/15, 23/20, and
28/25 at -75 °C) than at the higher (entries 5/1, 11/7, 17/13,
22/19, and 27/24 at g20 °C) temperatures. This remarkable
dependence of the housane syn/anti ratios on temperature and
bridgehead substitution for the various photochemical reaction
modes signifies competitive denitrogenation pathways for these
azoalkanes, which shall now be scrutinized in terms of the
mechanistic options given in Scheme 4.
of the housanes 2 were determined in toluene to be Ea ) 29 (
2
kcal/mol and log A ) 12.6 ( 0.9 s-1 for the housane 2a, Ea
-
1
)
(
(
26 ( 2 kcal/mol and log A ) 12.5 ( 0.9 s for 2b, Ea ) 23
-
1
2 kcal/mol and log A ) 12.4 ( 0.9 s for 2c, and Ea ) 22
-1
2 kcal/mol and log A ) 12.9 ( 0.9 s for 2d (cf. Supporting
Information). For the thermally labile diphenyl derivative 2e
half-life of ca. 100 min at -30 °C and ca. 190 s at 0 °C), only
approximate activation parameters could be estimated, namely,
Discussion
(
Dependence of the syn/anti-Housane Ratio on Tempera-
ture: Singlet Versus Triplet Pathways in the Denitrogena-
tion of the Azoalkanes 1. Our previous study on the denitro-
genation of azoalkane 1a showed that the intersystem-crossing
process (isc) dominates at low temperatures; in fact, at the low
temperature of -75 °C (entry 3), the R-CN-bond cleavage is
completely prevented in the (n,π*)-excited state. The results
in Table 1 demonstrate that this temperature dependence on the
singlet-triplet pathways is a general feature in the photochemi-
cal denitrogenation of the cyclopentene-annelated azoalkanes
-
1
Ea ca. 18 kcal/mol and log A ca. 12 s . Clearly, the thermal
persistence of the syn housanes decreases regularly with
bridgehead substitution; the order is 2a > 2b > 2c = 2d > 2e.
The activation parameters for the R-CN-bond cleavage of the
1(
n,π*)-excited azoalkanes 1a, c were determined from tem-
15
perature-dependent fluorescence quantum yields (φf), measured
1
7
in methylcyclopentane against anthracene as standard (cf.
-
1
Supporting Information). A plot of ln φf against the inverse
2
absolute temperature is linear (R ) 0.980). From these data
and the relation in eq 1 (kf is the fluorescence rate constant),
1
. Thus, the low-temperature direct and the benzophenone-
sensitized photolyses of the new derivatives 1b-e exhibit the
same behavior as the parent azoalkane 1a (entries 3/4, 9/10,
ln (1/φ ) ) - E /RT + ln (A/k )
(1)
f
a
f
1
5/16, 20/21, and 25/26). Clearly, the same denitrogenation
the activation energy of the R-CN bond cleavage was determined
pathway is followed in both photolysis modes, that is, the direct
at -75 °C and the sensitized at -40 °C! Under these conditions,
as we have shown previously for the parent azoalkane 1a, the
-
1
to be Ea ) 2.08 ( 0.04 kcal/mol and log A ) 13.2 ( 0.2 s
for 1a;16 for 1c they are Ea ) 1.18 ( 0.04 kcal/mol and log A
7
-1
)
11.0 ( 0.2 s . The activation parameters were not measured
low diastereoselectivity is due to the fact that the R-CN-bond
cleavage in the singlet route (low-temperature direct photolysis)
is slower compared to intersystem crossing of the singlet-excited
for the unsymmetrical azoalkane 1b. Unfortunately, the fluo-
rescence quantum yields of the phenyl-substituted derivatives
1
d and 1e are too low, nor are their syn housanes sufficiently
1
3
1
(n,π*) to its triplet-excited 1(n,π*) azoalkane. A lower-energy
thermally persistent, to determine the activation parameters of
process for isc versus R cleavage has been confirmed in recent
calculations on the parent DBH. In this case, a singlet-triplet
crossing region has been located <1 kcal/mol above the (n,π*)-
7
the CN-bond cleavage.
5,10
The results of the product studies for the azoalkanes 1 as a
function of temperature and reaction mode (direct, benzophe-
none-sensitized, and trans-piperylene-quenched photolyses) are
presented in Table 1. As reported previously for the 1a
1
excited azoalkane. In contrast, the R-cleavage transition state
has been located a few kcal/mol above the same excited-state
minimum. Thus, isc takes place spontaneously, and the triplet-
excited azoalkane denitrogenates to the planar triplet diradical
7
derivative, mixtures of the anti and syn housanes were also
obtained for the other azoalkanes 1b-e. Unquestionably, the
syn/anti ratio depends on the temperature and the reaction mode.
At high temperatures, the direct photolysis of the azoalkane 1a
3
DR (Scheme 4). After intersystem crossing to the singlet
1
diradical DR, the latter cyclizes to the syn/anti-2 housanes;
the energy profile of this process is shown in Figure 1. In view
of the shallow energy well (<3 kcal/mol
singlet diradical DR, fast ring closure affords nearly equal
amounts of the syn and anti housanes even at -75 °C; thus,
the transition state does not sense the substantial (ca. 6 kcal/
mol) energy bias in favor of the anti product. The fact that the
syn-2e housane is preferred in the triplet process of the azoalkane
7
affords preferably the syn isomer (entry 1), while for 1b-e
2d,17
) of the planar
the anti dominates (entries 7, 13, 19, and 24). Clearly, the
amount of anti housane follows the order 2e > 2d > 2c > 2b
1
>
2a. In contrast, at low temperature (-75 °C), the direct
photolysis leads to similar syn/anti ratios for the azoalkanes
a-d (entries 3, 9, 15, and 20), with a slight preference of the
1
anti housane. For the diphenyl derivative 1e, even more syn
isomer has been obtained (entry 25). These syn/anti ratios are
within the experimental error about the same as those for the
benzophenone-sensitized photolysis (entries 4, 10, 16, 21, and
1
e (entries 25 and 26) suggests that in the transition state for
the ring-closure process, the steric repulsions of the annelated
cyclopentene ring with the bridgehead phenyl substituents are
slightly more effective than with the gem-dimethyl-substituted
bridge.
26). Moreover, the trans-piperylene-quenched photolyses show
that the conversion of the azoalkanes is more significantly
Despite the similar structure of the azoalkanes 1, the variation
of the syn/anti ratio differs with temperature for the direct
photolysis: While the syn/anti ratio inverts for azoalkane 1a
(
14) (a) Chesik, J. P. J. Am. Chem. Soc. 1962, 84, 3250-3253. (b) Baldwin, J.
E.; Ollerenshaw, J. J. Org. Chem. 1981, 46, 2116-2119. (c) Coms, F. D.;
Dougherty, D. A. J. Am. Chem. Soc. 1989, 111, 6894-6896. (d) Adam,
W.; Platsch, H.; Wirz, J. J. Am. Chem. Soc. 1989, 111, 6896-6898.
15) (a) Mirbach, M. F.; Mirbach, M. J.; Liu, K.; Turro, N. J. J. Photochem.
(entries 1-3) as the temperature is lowered [more syn at high
(
(
7
(+40 °C) and more anti at low (-75 °C) temperature], the
1
978, 8, 299-306. (b) Kirby, E. P.; Steiner, R. F. J. Phys. Chem. 1970,
7
4, 4480-4490.
anti housane prevails for the 1b-d cases at all temperatures
16) To estimate the log A values of the azoalkanes 1a and 1c in eq 1, a singlet
1
lifetime ( τ ) of 2 ns was used, cf. Adam, W.; Fragale, G.; Klapstein, D.;
Nau, W. M.; Wirz, J. J. Am. Chem. Soc. 1995, 117, 12578-12592.
(17) Buchwalter, S. L.; Closs, G. L. J. Am. Chem. Soc. 1975, 97, 3857-3858.
J. AM. CHEM. SOC.
9
VOL. 124, NO. 41, 2002 12195

A R T I C L E S
Adam et al.
Table 1. Product Studies of the Photochemical Denitrogenation of Azoalkanes 1a-e
a
In d8-toluene; for the direct and trans-piperylene-quenched (1 M) photolyses, the 351-nm (2 W) line of the argon-ion laser was used, for the benzophenone-
b
1
sensitized (1 M) one, the 333-nm (2.4 W) line. Determined by H NMR analysis; normalized to 100% conversion; mass balance g95%; error (5% of the
stated values. Within the experimental error, the same syn/anti ratios were obtained at 20 °C. d In parentheses is given the syn/anti ratio corrected for the
thermal isomerization during the direct photolysis; the corrected value is essentially the same within the experimental error of the NMR analysis. The H
NMR spectra of the photolyzates were recorded at -50 °C. cis-Stilbene was used for the quenched photolysis. At this temperature, the labile syn-2e
housane is thermally isomerized completely to its anti isomer during the direct photolysis (see text).
c
e
1
f
g
(Table 1), but the syn isomer dominates at low temperatures for
4)dominates,atlowtemperature,thetripletone(pathB),thatis,isc
the diphenyl system 1e (entries 25 and 26). What is structurally
different between the azoalkanes 1a versus 1b-e that may
explain this temperature behavior on the syn/anti-housane ratio?
Since isc (an entropy-controlled process) is independent of
becomes more competitive with R cleavage. By means of the
1
5
temperature-dependent fluorescence method (eq 1) employed
in this study, the activation energy for the R cleavage of the
singlet-excited azoalkane 1a(n,π*) was 2.08 ( 0.04 kcal/mol
18
temperature for azoalkanes (Eisc ≈ 0 kcal/mol), the temperature
19
and 1.18 ( 0.04 kcal/mol for 1c(n,π*). Expectedly, the
effect must reside in the R-CN-bond cleavage (an enthalpy-
moderately stabilizing methyl group facilitates the breakage of
the CN bond in the azoalkane 1c. By analogy, we infer for the
unsymmetrical azoalkane 1b (not measured) also first cleavage
of the CN bond proximate to the methyl-carrying bridgehead
position. Similar photochemical behavior should pertain to the
1
controlled process) of the singlet-excited azoalkane 1(n,π*).
Thus, at high temperature, the singlet process (path A in Scheme
(
18) Adam, W.; Nau, W. M.; Sendelbach, J. J. Am. Chem. Soc. 1994, 116, 7049-
7
054.
12196 J. AM. CHEM. SOC.
9
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Temperature-Dependent Photodenitrogenation
A R T I C L E S
tion of the incipient radical center on account of the bridgehead
substituent such that the isc process is less effective.18 The lower
activation energy for the dimethyl derivative 1c (Ea = 1.2 kcal/
mol) compared to the unsubstituted 1a (Ea = 2.1 kcal/mol) is
1
in accord with enhanced R cleavage in the azoalkane (n,π*)-
excited state.
Dependence of the syn/anti-Housane Ratio on Bridgehead
Substitution: Enhancement of the anti Diastereomer through
the Mass Effect (Inertia) and Steric Hindrance in the
Inversion Process. In the previous section, it was shown that
the extent and type of substitution at the bridgehead position
of the azoalkanes 1a-e produces only minor changes in the
syn/anti ratio (entries 4, 10, 16, 21, and 26) of the triplet process
(path B in Scheme 4). In fact, nearly the same amounts of syn
and anti housanes are formed. The same is not the case for the
singlet process (path A), especially at the moderately high
temperatures (g20 °C), at which the triplet pathway is negligible
compared to R cleavage. The syn/anti product data under these
conditions disclose a significant dependence on the extent and
type of bridgehead substitution (Table 1). The amount of anti
product follows the order 1e(Ph/Ph) > 1d(Ph/H) > 1c(Me/Me)
> 1b(Me/H) > 1a(H/H), which spans a range in the quantity
of anti isomer from 100% for 1e(Ph/Ph) to only 38% for 1a(H/
H). Thus, disubstitution is more effective than monosubstitution
and the phenyl more than the methyl group in promoting the
formation of anti housane. Most significant, the amount of anti
product in the direct photolysis at g20 °C is substantially higher
than for the triplet process, except 1a.
Figure 1. Energy diagram for the syn/anti-housane formation in the thermal
syn-to-anti isomerization of the housanes 2 through the singlet diradical
1
DR (solid curve) and in the triplet-sensitized and direct (-75 °C)
photochemical denitrogenation of the azoalkanes 1 after isc of the triplet
3
1
diradical DR (dashed curve) to DR; energy values (kcal/mol) refer to the
unsubstituted derivatives 1a and 2a.
phenyl derivatives 1d, e (not measurable because of practical
problems, cf. Results section); in fact, R cleavage should be
more effectively promoted by phenyl stabilization. Conse-
quently, R cleavage should be more facile for all the bridgehead-
substituted azoalkanes 1b-e than for the unsubstituted 1a. It
follows that the temperature-dependent syn/anti ratios (Table
An impressive case is the diphenyl derivative 1e, for which
the syn/anti selectivity changes from 0:100 at 20 °C (entry 24)
to 67:33 at -75 °C (entry 25) in the direct photolysis, that is,
from complete retention (stereochemical memory) to moderate
inversion. In view of the thermal lability of the syn-2e housane,
the pertinent question was whether the syn-2e was not detected
because of thermal isomerization under the direct photolysis
conditions at 20 °C or whether it was not formed at all. As
control experiment, the quenched photolysis was conducted at
1
) for the substituted azoalkanes 1b-e should be more similar
to one another and different from the unsubstituted 1a. This is
most evident in the direct photolysis, since the anti housane
dominates for 1b-d (entries 7, 13, 19, and 24), whereas it is
the syn housane in the case of 1a (entry 1). Be this as it may,
this substituent effect does not explain why in the direct
photolysis the amount of anti housane depends on the extent
and type of bridgehead substitution of the azoalkane (Table 1),
namely, 1e(Ph/Ph) > 1d(Ph/H) > 1c(Me/Me) > 1b(Me/H)
-75 °C (entry 28) to assess whether the syn isomer is formed
or not in the direct photolysis of 1e at the elevated temperature
of 20 °C (entry 24). Also under these conditions, the syn/anti
ratio is 0:100 and again no syn-2e housane was observed.
However, had the syn-2e housane been formed, it should have
survived for low-temperature NMR-spectral detection, as in the
direct (-75 °C) and sensitized (-40°C) photolyses (entries 25
and 26) of 1e. Thus, in the quenched photolysis at -75 °C, the
triplet pathway is efficiently inhibited (no syn housane) and only
the singlet process operates, to give exclusively anti housane.
We contend that the lack of observing the syn housane in the
direct photolysis at 20 °C (entry 24) is not due to facile thermal
isomerization to its anti isomer at this temperature, but that the
syn housane is not formed under these conditions.
>
1a(H/H), but this shall be addressed in the next section.
The trans-piperylene-quenched process also supports the
involvement of the triplet pathway at -75 °C (Table 1). For
azoalkane 1a, the denitrogenation is completely inhibited (entries
6
versus 3), which indicates that at this temperature only the
triplet pathway is active. For the bridgehead-substituted azoal-
kanes 1b (entries 9 and 12), 1c (entries 15 and 18), 1d (entries
2
0 and 23), and 1e (entries 25 and 28), the quenching effect is
not as efficient, as manifested by only partial inhibition of the
denitrogenation even at -75 °C. As already stated in the
preceding paragraph, some denitrogenation takes place in the
singlet channel because of enhanced CN cleavage by stabiliza-
The following mechanistically pertinent questions arise: Why
do the substituted derivatives 1c-e afford a higher amount of
the anti diastereomer than the unsubstituted 1a? Why is for these
azoalkanes significantly more anti housane formed in the direct
photolysis than in the triplet-sensitized one? As already pointed
(
a
19) The previous E value of 3.6 kcal/mol obtained for the azoalkane 1a from
the kinetic analysis of the temperature-dependent syn/anti product distribu-
tion is significantly higher than the present value of 2.08 kcal/mol,
determined by the temperature-dependent fluorescence method. This
8
difference may be rationalized in terms of solvent effects since d -toluene
was used in the product-distribution study, while methylcyclopentane was
employed in the fluorescence measurements. It is known that solvents affect
10
out in the Introduction, new computational studies on the
a
the E values determined by fluorescence (ref 15b). Furthermore, fluores-
cence quenching through solvent-assisted radiationless deactivation by C-H
bonds is expected to be more effective for the aliphatic solvent methyl-
cyclopentane, cf. Nau, W. M.; Adam, W.; Scaiano, J. C. Chem. Phys. Lett.
parent DBH indicate that the axial and equatorial conformations
1
of the exo-configured singlet diazenyl diradical σ,σ- DZ inter-
1
1
996, 253, 92-96.
vene in the denitrogenation of the (n,π*)-excited azoalkane
J. AM. CHEM. SOC.
9
VOL. 124, NO. 41, 2002 12197

A R T I C L E S
Scheme 2). This constitutes the pivotal product-branching point
Adam et al.
(
Scheme 5
to rationalize the preferred formation of inverted housane in
the direct photolysis of DBH (Scheme 3). We infer that this
theoretically based mechanistic scenario also applies to the
bridgehead-substituted, cyclopentenyl-annelated DBH-type de-
rivatives 1a-e and accounts for the observed syn/anti-housane
ratios (Table 1) in their direct photolysis (path A in Scheme 4);
however, no computations are available as yet on these
structurally more complex azoalkanes.
1
As to the fate of the DZ transient, the two mechanistic
pathways in Scheme 1 shall be considered: On one hand, the
7
,11
10
experimentally
and theoretically established conventional
SH2 process may take place to afford exclusively the inverted
housane syn-2, in which the N2 departure is concomitant with
the ring inversion by backside attack of the unpaired electron
in the carbon-centered 2p orbital; on the other hand, in
1
inversion (SH2) trajectory, the gem-dimethyl group must move
past the bridgehead substituents to afford the syn housane. This
process is expectedly more difficult the heavier and the larger
the substituent at the bridgehead, that is, Ph > Me > H and
double more than single substitution. Thus, the SH2 mode of
inversion is encumbered by bridgehead substituents through the
mass effect and steric interactions, as manifested by the fact
that proportionally more anti-2 housane results in the observed
order 1e(Ph/Ph) > 1d(Ph/H) > 1c(Me/Me > 1b(Me/H) > 1a(H/
H). For the diphenyl derivative 1e, these synergetic effects are
so dominant that the anti housane is the exclusive product.
In Scheme 5, we provide the mechanistic rationale for these
unusual results (Table 1) in terms of the transient diazenyl
competition, a nitrogen-free DR species may be involved to
generate both the syn and anti products. For a thermally
1
equilibrated, planar DR intermediate, the energy diagram in
Figure 1 provides a detailed account of the housane formation.
In view of the shallow (<3 kcal/mol) potential energy well for
1
the planar singlet diradical DR, essentially equal amounts of
the syn- and the anti-housane 2 are expected. Such a planar
1
20
DR species is generated through isc of the long-lived,
3
thermally equilibrated, planar triplet diradical DR and it follows
that the syn/anti ratio for the planar DR should be that given
1
3
for the nitrogen-free DR of the triplet process (path B in
Scheme 4).2
1,22
1
It is remarkable that the ring closure of the DR
species is essentially independent of the extent and type of
bridgehead substitution (entries 4, 10, 16, 21, and 26). This lack
of stereoselectivity clearly manifests that the mass effect of the
bridgehead substituents and their steric interactions are negligible
when a thermally fully equilibrated, planar 1DR diradical
1
5,10
diradical DZ, in analogy to the computed reaction coordinate
for the parent DBH (Scheme 2), and its stereochemical
implications (Scheme 3). We propose that initially the exo-axial
1
diazenyl diradical DZ(exo-ax), formed by decay through the
conical intersection, carries sufficient energy to transform
intervenes.
dynamically (path a-1) to the exo-equatorial conformation
The experimental facts for the singlet process (path A in
Scheme 4) display a definite effect on bridgehead substitution
in that the amount of anti housane follows the order 1e > 1d >
1
DZ(exo-eq), that is, prior to thermal equilibration; subsequently,
the latter loses N2 by backside attack to afford inverted housane
syn-2(inV) along the SH2 trajectory. Alternatively, denitroge-
1
c > 1b > 1a (entries 1, 7, 13, 19, and 24). More importantly,
1
nation of DZ(exo-ax) to generate initially the puckered cyclo-
in the azoalkanes 1c-e, the amount of anti diastereomer for
the singlet process exceeds significantly that of the triplet one
1
pentanediyl diradical DR(puckered) competes (path a-2) with
1
the conformational change to DZ(exo-eq) along path a-1. The
(entries 13 vs 16, 19 vs 21, and 24 vs 26). None of the
1
DR(puckered) transient subsequently either cyclizes directly
mechanisms in Scheme 1 explain these unprecedented results.
1
(path b-1) to the retained (stereochemical memory) housane anti-
2(ret) or conformationally relaxes (path b-2) to the planar
Evidently, there must exist an additional pathway for the DZ
1
transient to generate the anti housane (dashed arrow from DZ
1
nitrogen-free diradical DR(planar). The latter, that is, the
to anti-2 in Scheme 4). This pathway is promoted by bridgehead
substituents, the phenyl is more effective than the methyl group,
and double more than single substitution!
intermediate proposed to be formed from the planar triplet
3
diradical DR (cf. Scheme 4) on intersystem crossing, is destined
1
to afford essentially equal amounts of anti-2(ret) and syn-2(inV)
housanes (Figure 1), as manifested by the product data for the
triplet process (entries 3, 10, 16, 21, and 26) in Table 1.
An alternative mechanism would be to suppose that the singlet
Inspection of molecular models reveals that during the DZ
1
(
exo-ax)-to- DZ (exo-eq) inversion process along the ring-
(
20) Adam, W.; Grabowski, S.; Wilson, R. M. Acc. Chem. Res. 1990, 23, 165-
72.
1
(
21) Buchwalter, S. L.; Closs, G. L. J. Am. Chem. Soc. 1979, 101, 4688-4694.
In this seminal work, the energy diagram for intersystem crossing of the
triplet cyclopentanediyl diradical to its singlet species was proposed as an
essential feature for the generation of the bicyclo[2.1.0]pentane product.
At very low temperatures (<20 K) under matrix isolation, the triplet
diradical may cyclize directly to the bicyclopentane by tunneling instead
of intersystem crossing. This pathway does not apply to the substituted
triplet diradicals 3DR derived from the azoalkanes 1 at the elevated
temperatures (>20 °C) of the triplet-sensitized photolysis, as unequivocally
stated by Buchwalter and Closs in the citation,“The unambiguous observa-
tion of tunneling in organic reactions is rare. While in the reaction described
here tunneling is the sole pathway at temperatures below 20 K, its
diazenyl diradical DZ(exo-ax) cyclizes to a vibrationally excited
1
azoalkane. The latter thermally expels N2 concertedly to generate
1
a nonstatistical nitrogen-free DR diradical, which on account
of dynamic effects favors inversion to the syn housane, the
8
pathway reported for the thermolysis of DBH. If this were so,
1
we would expect more cyclization of the DZ(exo-ax) to its
azoalkane in a more viscous solvent and, thus, more syn housane
(inversion) should be formed. Our recent results for the dimethyl
derivative 1c disclose, however, that with increasing viscosity
11
contribution at room temperature of course is negligible (∼1 part in 10 ).”
22) Sponsler, M. B.; Jain, R.; Coms, F. D.; Dougherty, D. A. J. Am. Chem.
Soc. 1989, 111, 2240-2252.
(
1
1e
the extent of inversion decreases.
On the basis of these
12198 J. AM. CHEM. SOC.
9
VOL. 124, NO. 41, 2002

Temperature-Dependent Photodenitrogenation
experimental results, we argue that dynamic effects are not
A R T I C L E S
8
1
CN-bond cleavage to afford the DZ transient, for which the
2p orbital is centered on the methyl-substituted or on the
unsubstituted bridgehead carbon atom. The former is subject
to a mass effect exerted by the methyl group, the latter is not.
Although there will be an energy bias in favor of the CN-bond
homolysis next to the substituted bridgehead site in the excited
state because of methyl stabilization of the incipient carbon-
radical center, if both CN bonds were to cleave equally likely,
the syn/anti ratio for the monosubstituted azoalkane 1b(Me/H)
would be expected to be between those of the symmetrical ones
1a(H/H) and 1c(Me/Me), namely, 41:59, as computed from the
entries 1 and 13 (Table 1). This is remarkably close (essentially
the same within the experimental error) to the experimental value
of 35:65 (entry 7) and corroborates the validity of the inertia
effect of the bridgehead substituent. For the monophenyl
derivative 1d(Ph,H), phenyl stabilization of the radical center
is so effective that the excited-state homolysis of the adjacent
CN bond dominates to such an extent that the inversion process
is almost completely suppressed through the mass effect, but
also by steric hindrance, and the anti-housane product is favored
by far (entry 19). The synergetic interplay between the mass
effect (inertia) and steric interactions (size) allows to rationalize
the dominance of the anti-housane diastereomer in the direct
photolysis of the azoalkanes 1b-e (Table 1).
1
1
detectable in the photodenitrogenation of azoalkanes. Ad-
ditionally, recent computations5 indicate that the n,π*-singlet-
excited DBH generates initially the 1DZ(exo-ax) diradical
,10
(Scheme 3), which prefers to denitrogenate rather than reclose
to DBH through its endo-configured conformer. This is con-
sistent with the reported quantum yield of ca. 100% for nitrogen
loss.23 In analogy, for the present set of azoalkanes 1 (Scheme
1
5
), the intermediary DZ(exo-ax) diradical does not have enough
time to reclose to a “hot” azoalkane and afford on thermolysis
inverted housane through dynamic effects.8
It remains to rationalize the observed syn/anti ratios in Table
1
for the direct photolysis of the azoalkanes 1a-e in terms of
the influence of the bridgehead substituents on the two bifurca-
tion steps in Scheme 5, namely, paths a-1/a-2 and paths b-1/
b-2. As already mentioned, two factors influence the confor-
mational changes: These are the mass effect (inertia) and steric
hindrance (size), both follow the order Ph > Me > H. Thus,
the larger mass imparts a drag (inertia) on the bridgehead
substituent during the inversion, whereas the larger size imposes
a higher steric barrier in moving the bridgehead substituent past
the gem-dimethyl bridge; both expectedly slow the conforma-
tional changes.
We shall first scrutinize the two extreme cases, which are
the unsubstituted derivative 1a (entry 1) and the diphenyl case
Conclusion
1
e (entry 24). For 1a(H/H), both the mass drag and the steric
In this study, we have established that the temperature-
dependent competition between the singlet and triplet pathways
in the denitrogenation of the n,π*-excited cyclopentene-anne-
lated azoalkanes 1 is a general feature. We have also demon-
strated an unprecedented influence of the apparently innocuous
bridgehead substituent on this process, in that anti-2 housane
is formed more effectively by phenyl versus methyl substituents
and by double versus single substitution. The mass effect
hindrance are minimal on the conformational change along path
a-1 and most of the singlet-state denitrogenation proceeds by
the SH2 mechanism to afford mainly inverted housane syn-
2
2
place, but beyond this point it is difficult to assess even
qualitatively what happens stereochemically, because no infor-
mation is available on the relative importance of the path b-1
versus path b-2 in the subsequent bifurcation step. If we assume
that all of the DR(puckered) relaxes to DR(planar) along path
b-2 (no memory effect), ca. one-third of the direct photolysis
goes through the SH2 process and ca. two-thirds through the
a(inV). Since substantial amounts of retained housane anti-
a(ret) are produced, denitrogenation along path a-2 must take
(inertia) of the bridgehead substituent and its steric hindrance
with the gem-dimethyl-substituted methylene bridge encumber
1
1
the formation of the syn housane through the inversion process
1
(
SH2 pathway). Instead, the transient DZ diradical affords
proportionally more of the anti stereoisomer (retention) through
1
thermally equilibrated DR(planar) diradical. In contrast, the
1
the puckered nitrogen-free DR species (memory effect).
stereochemical analysis of the 1e(Ph/Ph) case is straightforward,
since only the retained housane anti-2e(ret) is obtained, that is,
complete stereochemical memory. In this case, both the mass
and steric factors operate so efficiently that only the a-2 and
b-1 paths are pursued by the respective diradicals DZ(exo-ax)
and DR(puckered); the conformational changes in the a-1 and
Acknowledgment. We thank the Deutsche Forschung Ge-
meinschaft, the Volkswagen-Stiftung, and the Fonds der Che-
mischen Industrie for the generous financial support. M. O. is
grateful to the Universit a` di Siena (Progetto di Ateneo A. A.
00/02) and CINECA, V. M. is indebted to the European
Commission for a postdoctoral fellowship (1998-2000).
1
1
b-2 paths are too slow to compete with the a-2 and b-1 paths.
An informative case is the monomethyl derivative 1b. Its
unsymmetrical (n,π*)-excited state has two options to undergo
Supporting Information Available: Experimental and com-
putational details (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
1
(
23) Solomon, B. S.; Thomas, T. F.; Steel, C. J. Am. Chem. Soc. 1968, 90,
2
249-2258.
JA026321N
J. AM. CHEM. SOC.
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