Contrasting responses of pyrido[2,1-a]isoindol-6-ones and their sultam counterparts to photochemical activation

Article abstract of DOI:10.1021/jo802476c

A ring-closing metathesis-based strategy has allowed access to an unreported pair of pyridoisoindolones and their previously unknown sultam counterparts. The synthetic routing takes advantage of the ready availability of N-allylphthalimide and N-allylsacc

Full text of DOI:10.1021/jo802476c

Contrasting Responses of Pyrido[2,1-a]isoindol-6-ones and Their
Sultam Counterparts to Photochemical Activation
Leo A. Paquette,* Robert D. Dura, and Isabelle Modolo
EVans Chemical Laboratories, The Ohio State UniVersity, Columbus, Ohio 43210-1185
paquette.1@osu.edu
ReceiVed NoVember 10, 2008
A ring-closing metathesis-based strategy has allowed access to an unreported pair of pyridoisoindolones
and their previously unknown sultam counterparts. The synthetic routing takes advantage of the ready
availability of N-allylphthalimide and N-allylsaccharin and proceeds via the proper incorporation of small
side chains into the heterocyclic ring. Positionally selective introduction of the conjugated diene
functionality was realized efficiently. Detailed study of the excited-state chemistry of 7 and 8 showed
both lactams to be subject to [4 + 2] dimerization under acetone-sensitized conditions. Different
regioselectivities are involved, with the response of 8 being far more efficient than that exhibited by 7.
No dimers could be isolated from the photolyzates of 9 and 10 under any conditions. While the latter
sultam undergoes extensive polymerization, 9 is transformed via direct irradiation at 350 nm into 46 and
47 via [1,3]-sigmatropy involving the S-N bond and heterocyclic ring cleavage, respectively.
Introduction
Lactams and sultams having a cyclic conjugated diene
chromophore as an integral structural component are known
to exhibit interesting reaction profiles when subjected to
photoactivation.1,2 Thus, 1 and 4 experience in common
stereocontrolled disrotatory ring closure to some degree.3
However, they differ notably in the competing isomerizations
that lead via retro-[2 + 2]-cycloaddition to 3 (eq 1) and [1,5]-
sigmatropic rearrangement to 6 (eq 2), respectively.
In the present investigation, attention has been directed to
the synthesis and photochemistry of a pair of representative
members of each of two previously unknown classes of
(1) Review: Paquette, L. A. Chemtracts-Organic Chemistry 2006, 19, 1.
(2) (a) Paquette, L. A.; Barton, W. R. S.; Gallucci, J. C. Org. Lett. 2004, 6,
1313. (b) Preston, A. J.; Gallucci, J. C.; Paquette, L. A. J. Org. Chem. 2006, 71,
6573.
(3) Paquette, L. A.; Dura, R. D.; Fosnaugh, N.; Stepanian, M. J. Org. Chem.
2006, 71, 8438.
heterocycle. The two representative pyrido[2,1-a]isoindol-
6-ones 7 and 84 and an equal number of 9-thia-8a-azafluorene
9,9-dioxides, viz. 9 and 10, have been specifically targeted,
1982 J. Org. Chem. 2009, 74, 1982–1987
10.1021/jo802476c CCC: $40.75 2009 American Chemical Society
Published on Web 02/04/2009

Contrasting Responses of Pyrido[2,1-a]isoindol-6-ones
thereby setting the stage for detailed probing of their
individual response to excitation with light.
nucleophilic attack of water would expectedly occur with high
levels of regio- and stereocontrol.
SCHEME 2
Results and Discussion
A striking consequence of this chemical event is the suitability
of 15 to subsequent dehydration. This transformation was best
accomplished by treatment with methanesulfonyl chloride in
pyridine, followed by direct heating of the corresponding
sulfonate ester with DBU at 95 °C for an extended time period.
The 1:3 mixture of 7 and 169 that results is believed to be
diagnostic of the operation of [1,5]-hydrogen shifting in order
to attain a more extended level of π-conjugation with the
benzene ring.
The bonding-specific arrangement in these dienes can be
better appreciated by initially pursuing the installation of an
angular OMOM substituent as in 23. The main strength of this
strategy resides in the benzylic nature of the C-O bond, the
heterolysis of which is thereby facilitated. Additionally, conver-
sion to the more thermodynamically favored 7 (see Table 1)
operates directly.
A clear route to 23 began with the coupling of propargyl-
magnesium bromide to N-allylphthalimide (Scheme 3). This
organometallic reagent is distinctively reactive,10 such that 1,2-
carbonyl addition proceeds efficiently in ether at -10 °C without
ensuing C-N bond cleavage and ring opening. It will be
recognized that compound 20 is in a higher oxidation state than
required. However, the presence of a triple bond allows the
subsequent hydroxyl group protection to proceed with minimal
Preparation of 4H- and 10bH-Pyrido[2,1-a]isoindol-
6-ones. The initial strategy applied to the acquisition of 7 began
with the exposure of readily available N-allylphthalimide (11)5
in sequence to lithium triethylborohydride, acetic anhydride, and
allyltrimethylsilane/bismuth triflate6 (Scheme 1). The resultant
diene lactam 12 underwent ring-closing metathesis7 uneventfully
to generate tricyclic intermediate 13 in high yield. The dibro-
mination of 13 led to 14, whose projected role it was to serve
as progenitor to the diene upon two-fold dehydrobromination.
However, the targeted 7 was not observed, a single isomer of
allylic alcohol 15 being formed instead. Dibromide 14 proved
to be quite reactive toward Bu4N+F- in THF at 25 °C,3
conditions that led within 15 min to the crystalline carbinola-
mine,15 whose three-dimensional structure was established by
X-ray analysis.
This unexpected transformation may well materialize by
virtue of a significant level of activation provided by the
proximal amide nitrogen that directs well-defined proton
abstraction, as shown in Scheme 2. The generation of allylic
bromide 17 in this manner is likely conducive to the formation
of iminium ion 19,8 which resulted from electron donation away
from the nitrogen atom. Trapping of this intermediate by
SCHEME 1
J. Org. Chem. Vol. 74, No. 5, 2009 1983

Paquette et al.
TABLE 1. Relative Energies in kcal/mol
SCHEME 4
calculation method
7
16
16a
MMFF94s
B3LYP/631G*
B3LYP/6311+G**
0
0.82
0.61
11.04
0
0
18.06
9.10
7.59
SCHEME 3
dehydration leading from 24 to 25,11 the reactivity exhibited
during the five-stage acquisition of 29 proved closely parallel.
The relative configuration assigned to 29 is derived principally
from mechanistic analogy, closely comparable 1H and 13C NMR
spectra, and response to dehydration. As anticipated, compound
8 proved to be intrinsically stable to the dehydration conditions
employed.
Access to the 9-Thia-8a-azafluorene 9,9-Dioxides. From the
foregoing results, it could not be safely assumed that the
replacement of a carbonyl with a sulfonyl group would have
an entirely comparable effect on the closed carbinol/open ketone
equilibrium. To gain insight into this matter, effort was initially
directed to reduction of the known allyl saccharin 3012 with
Super-Hydride in CH2Cl2 at -60 °C (Scheme 5).
Direct ensuing acetylation delivered the overreduction prod-
ucts 31 and 32 in the approximate ratio of 1:2. Apparently, there
exists a relationship between the reducing power and chelation
capability of the hydride reagent, as the alternative use of
Dibal-H smoothly transformed 30 into the intact amino alcohol.
To achieve the isolation of 33, it was necessary first to quench
the reaction mixture and subsequently to perform direct acety-
lation of the crude product. Irrespective of the actual cause
underlying the isolation of 33, no further complications were
manifested during the subsequent allylation, ring-closing me-
tathesis, and bromination steps that led to 36.
The task of effecting the two-fold dehydrobromination of 36
proved complicated. Since an equivalent to acyliminium ion
intervention was less likely to facilitate this process,13 it seemed
advisable to abandon the use of relatively mild conditions in
favor of more powerful options. To this end, recourse was made
to the combination of TBAF in DMSO at 50 °C.14 The
operationally useful nature of this reagent combination was
demonstrated by its reproducible efficiency and the wholesale
migration of its conjugated diene unit into conjugation with the
benzene ring as in 9.
complication from spontaneous dehydration. The desired inter-
mediate 22 could be generated without event under Lindlar
conditions and subjected directly to ring-closing metathesis in
a manner paralleling that deployed earlier in the case of 12.
The final step, which utilizes trifluoroacetic acid in CH2Cl2 at
rt, proceeds to completion within a minute to deliver 7
quantitatively.
In order to reposition the conjugated chromophore in these
networks, attention was directed to proper installation of an
angular methyl group. This tactic was expected to deter the
operation of undesired sigmatropic migration during the final
dehydration step. As shown in Scheme 4, the addition of
methylmagnesium bromide to 11 at low temperature initiated a
series of steps comparable to that detailed previously in the
conversion of 12 to 15. With the exception of modest levels of
(4) Dura, R. D.; Modolo, I.; Paquette, L. A. Heterocycles 2007, 74, 145.
(5) (a) Johnson, T. B.; Breese, J. D. Am. Chem. J. 1911, 45, 343. (b) Pearson,
D. E.; Sigal, M. V., Jr.; Krug, R. H. J. Org. Chem. 1960, 15, 1048. (c) Elderfield,
R. C.; Mertel, H. E.; Mitch, R. T.; Wempen, I. M.; Weble, E. J. Am. Chem. Soc.
1955, 77, 4816.
(6) Pin, F.; Comesse, S.; Garrigues, B.; Marchalin, S.; Da¨ıch, A. J. Org.
Chem. 2007, 72, 1181.
(7) (a) Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28,
446. (b) Speckamp, W. N.; Moolenaar, M. J. Tetrahedron 2000, 56, 3817.
(8) (a) Speckamp, W. N.; Hiemstra, H. Tetrahedron 1988, 41, 4367. (b)
Speckamp, W. N.; Moolenaar, M. J. Tetrahedron 2000, 56, 3817.
(9) (a) Wada, M.; Nakai, H.; Sato, Y.; Kanaoka, Y. Chem. Pharm. Bull.
1982, 30, 3414. (b) Abe, Y.; Ohsawa, A.; Igota, H. Heterocycles 1982, 19, 49.
(10) (a) Dmitrieva, L. L.; Nikitina, L. P.; Albanov, A. I.; Nedolya, N. A.
Russ. J. Org. Chem. 2005, 41, 1583. (b) Yanagisawa, A. Sci. Synth. 2004, 7,
541–547. (c) Marshall, J. A. Chem. ReV. 2000, 100, 3163–3185. (d) Brandsma,
L. PreparatiVe Acetylenic Chemistry, 2nd ed.; Elsevier: Amsterdam, The
Netherlands, 1988; pp 35-36.
The melding of these observations alongside those associated
with the generation of lactam 8 prompted exploration of the
(11) (a) Couty, S.; Liegault, B.; Meyer, C.; Cossy, J. Tetrahedron 2006, 62,
3882. (b) Couty, S.; Liegault, B.; Meyer, C.; Cossy, J. Org. Lett. 2004, 6, 2511.
(12) (a) Merritt, L. L.; Levey, S.; Cutter, H. B. J. Am. Chem. Soc. 1939, 61,
15. (b) Rice, H. L.; Pettit, G. R. J. Am. Chem. Soc. 1954, 76, 302.
(13) Weinreb, S. W. Top. Curr. Chem. 1977, 190, 131.
(14) Dura, R. D.; Paquette, L. A. Synthesis 2006, 2837.
1984 J. Org. Chem. Vol. 74, No. 5, 2009

Contrasting Responses of Pyrido[2,1-a]isoindol-6-ones
SCHEME 5
SCHEME 6
SCHEME 7
Photochemical Studies. The launching point for this phase
of the investigation was the unsaturated lactam 7. The chro-
mophore presenting this minimally substituted pyrodoisoin-
dolone was expected to lend itself to several photochemical
responses. Indeed, 7 exhibits a substantive sensitivity to light,
giving rise within short time frames to a very broad array of
products (TLC analysis) under a wide range of conditions. These
included, but are not limited to, direct irradiation at several
wavelengths and triplet sensitization in a number of solvent
systems.
Ultimately, we settled on the use of a reaction medium
consisting of a 1:1 ratio of acetonitrile and acetone with a 300
nm light source through quartz at 20 °C in a Rayonet reactor.
By means of preparative thin layer chromatography on silica
gel, it proved possible to isolate in pure form a component of
the gross mixture in 2% yield (Scheme 7).
No other product was isolable in quantities allowing full
characterization. Compound 42 was identified as a dimer on
the strength of spectroscopic data, most particularly its 1H NMR
spectrum in conjunction with several 2D techniques which
included COSY, HMQC, and NOE experiments in CDCl3 or
C6D6 as solvents. The atom connectivity in 42, a colorless waxy
substance, is shown in Figure 1. The distinctive chemical shift
differences exhibited by the two sets of benzene ring protons
hold interest. A possible root cause of this phenomenon may
be the high level of strain inherent to this structure, one
consequence of which is to alter the overlap of one amide group
consequences of adding methylmagnesium bromide to 30 at low
temperature (Scheme 6). Of the variety of conditions that were
explored, none produced ketone 37 at a level exceeding 40%.
Evidently, its consumption in second-stage reaction with
CH3MgBr operates at a level competitive with the initial addition
to 30. Eventually, we settled upon the chromatographic separa-
tion of 37 from 38. When purified, 37 was subjected to the action
of boron trifluoride etherate and allyltrimethylsilane in aceto-
nitrile. Direct conversion to 39 took place. The utilization of 2
equiv of Lewis acid proved most efficacious, in line with ready
ionization of the carbinolamine following the initial cyclization
that reconstitutes the heterocyclic ring. The considerable
advantage offered by this transformation provided the under-
girding necessary to reach sultam 10 without incident.
J. Org. Chem. Vol. 74, No. 5, 2009 1985

Paquette et al.
FIGURE 1. Atom connectivity in 42.
SCHEME 8
SCHEME 9
the photolyzates derived from sultams 9 and 10. As conditions
for evaluating their photochemical behavior were being re-
searched, note was taken of the fact that triplet sensitization
invariably resulted in extensive degradation and/or polymeri-
zation. In contrast, the irradiation of 9 in hexane solution with
a 350 nm lamp source provided predominantly a two-component
mixture that proved amenable to chromatographic separation.
The less polar product, isolated in 35% yield, was identified as
the previously described16 benzo[4,5]thieno[3,2-b]pyridine 5,5-
dioxide (46) (Scheme 9). The origin of 46 likely stems from
sequential operation of a [1,3]-sigmatropic shift after S-N bond
cleavage, followed by aromatization to generate the thienopy-
ridine core.
with the attached aromatic ring. The resulting disruption of full
conjugation lessens the electron-withdrawing effect. This state
of affairs also manifests itself in the 13C NMR spectrum where
one amide carbonyl appears at 167.4 ppm and the second at
165.6 ppm. These data also attest to the absence of symmetry
in this photoproduct.
In contrast, the excited-state chemistry of 8 in which the 1,2-
diene system is no longer conjugated to the benzene ring proved
to be essentially unidirectional in delivering 43 very efficiently
(acetone, 300 nm, 96% yield).15 However, the efficiency of this
process suffered when lactam 8 was subjected to direct
irradiation in hexanes. Prolonged exposure under these condi-
tions led to the wholesale decomposition of 43.
The 1H NMR spectrum of the more polar 47 featured an array
of olefinic proton signals suggestive of the presence of an
olefinic chain housing a central trans double bond. Corroborative
proof of the formation of 47, presumably initiated via homolysis
of the weaker C-N bond in 9, was also derived from X-ray
crystallographic analysis. The near-identical extent to which the
pathways giving rise to 46 and 47 operate reflects the closely
competitive nature of these processes.
In contrast, the ability of methyl homologue 10 to deliver
well-defined photoproducts under a host of experimental
variables could not be harnessed. The results showed 10 to be
notably prone to photopolymerization. For all experiments, the
responsiveness of 10 to activation by light proved not to be
controllable.
This product (8) was shown to exhibit spectral properties
consistent with its assignment as an unsymmetrical dimer.
Principal supportive evidence was gained by high-resolution
mass spectral analysis ([M + Na]+ calcd 417.1579, obsd
1
417.1582) and H NMR data recorded at 500 MHz. The latter
Overview
confirmed the existence of a single enamide functionality and
an isolated olefinic site, neither of which were styrenyl in nature
(COSY measurements). Additional supportive evidence for the
structural assignment as 43 was gained by way of a chemical
interconversion. Specifically, reaction of the glassy photoproduct
with dimethyl dioxirane in aqueous acetone at 0 °C led to the
smooth formation of 44 (37%) and 45 (33%), both of which
are highly crystalline solids amenable to X-ray crystallographic
analysis15 (Scheme 8).
Several possible mechanisms can be envisioned to rationalize
the photochemical reactivity of 7-10. It appears almost certain
that triplet state photoproducts are first formed when acetone
serves as the reaction medium either neat or as mixed 1:1 with
acetonitrile. During the ensuing dimerization, cycloadducts are
formed by exo π2 + π4 bonding, although in diverse fashion.
When 7 is involved, the benzene rings are oriented anti. For 8,
the orbital overlap is reversed, but also favoring an anti approach
The proclivity of 7 and 8 to undergo photodimerization
provided considerable inducement for the close inspection of
(16) (a) Klemm, L. H.; Merrill, R. E. J. Heterocycl. Chem. 1971, 8, 931. (b)
Klemm, L. H.; Merrill, R. E. J. Heterocycl. Chem. 1972, 9, 293. (c) Klemm,
L. H.; Rottschaefer, S.; Merrill, R. E. J. Heterocycl. Chem. 1975, 12, 1265. (d)
Klemm, L. H.; Lee, F. H. W.; Lawrence, R. F. J. Heterocycl. Chem. 1979, 16,
73. (e) Muchiri, D. R.; Midgley, J. M. J. Kenyan Chem. Soc. 1999, 1, 5.
(15) Paquette, L. A.; Dura, R. D.; Gallucci, J. C. Heterocycles 2008, 76,
129.
1986 J. Org. Chem. Vol. 74, No. 5, 2009

Contrasting Responses of Pyrido[2,1-a]isoindol-6-ones
Oxidation of 43 with Dimethyl Dioxirane. A cold (0 °C)
solution of 43 (35 mg, 0.093 mmol) in 1:1 acetone/water (1 mL)
was admixed with NaHCO3 (78 mg, 0.93 mmol). Oxone (288 mg,
0.469 mmol) was introduced portionwise over 20 min, and stirring
was maintained for an equal length of time. The reaction mixture
was filtered through a pad of Celite, concentrated, and purified over
silica gel (elution with 4:1 hexane/ethyl acetate) to provide 44 as
a colorless, crystalline solid (15 mg, 37%), mp 214-216 °C: IR
of the two reactants. No [4 + 4] product(s) is (are) observed,
and no endo approach of the dienophile component proved
operational.
Worthy of serious consideration is the efficiency with which
43 is formed and the exceptional susceptibility of its enamide
double bond to oxidative cleavage. These transformations are
most probably due to the enhanced level of π-electron density
resident in this site of unsaturation. The results of the studies
conducted so far in this area have led to the unmasking of several
novel photochemical reactions involving the chromophores
resident in 7-10. These excited-state processes, evidently quite
varied, demonstrate the wealth of information that can be made
available from the examination of structurally related systems.
1
(thin film, cm-1) 1740, 1698, 1300; H NMR (400 MHz, CDCl3)
δ 9.09 (s, 1H), 8.24 (d, J ) 5.5 Hz, 1H), 7.89 (dd, J ) 17.0, 7.5
Hz, 1H), 7.73-7.66 (m, 2H), 7.59-7.54 (m, 4H), 7.44 (d, J ) 7.5
Hz, 1H), 6.80 (t, J ) 7.0 Hz, 1H), 6.44 (td, J ) 6.5, 1.0 Hz, 1H),
4.83-4.80 (m, 1H), 3.64 (d, J ) 6.0 Hz, 1H), 3.17-3.13 (m, 1H),
3.01 (d, J ) 9.5 Hz, 1H), 1.60 (s, 3H), 1.48 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ 199.9, 173.9, 167.4, 160.3, 151.9, 149.2,
135.5, 134.5, 133.1, 133.0, 129.9, 129.7, 129.3, 129.0, 125.9, 125.3,
123.1, 120.8, 70.2, 66.6, 57.6, 51.2, 43.5, 40.3, 29.7, 27.8, 26.6;
HRMS [M + Na]+ calcd 449.1477, obsd 449.1461.
Experimental Section
Photodimerization of 7. Diene 7 (100 mg, 0.55 mmol) was
dissolved in a 1:1 mixture of acetone/acetonitrile (400 mL), placed
in a quartz flask, and deoxygenated with argon for 30 min. The
solution was then irradiated at 300 nm for 45 min and concentrated
to leave an orange gum, which was quickly purified on silica gel
(elution with 10:1 to 1:1 dichloromethane/ethyl acetate). The latter
fractions were combined and repurified by preparative TLC (silica
gel, elution with dichloromethane/ethyl acetate, 2:1) to give 42 as
a colorless waxy solid (4 mg, 2%): IR (thin film, cm-1) 1694, 1682;
1H NMR (400 MHz, CDCl3) δ 7.81-7.34 (m, 3H), 7.63 (t, J )
6.0 Hz, 1H), 7.57 (t, J ) 6.0 Hz, 1H), 7.37 (t, J ) 6.0 Hz, 1H),
7.13 (t, J ) 6.0 Hz, 1H), 7.07 (t, J ) 6.0 Hz, 1H), 5.67-5.64 (m,
1H), 4.57 (dd, J ) 14.0, 4.4 Hz, 1H), 4.07 (dd, J ) 6.0, 1.6 Hz,
1H), 3.37 (d, J ) 14.0 Hz, 1H), 3.25-3.20 (m, 1H), 3.17 (d, J )
8.8 Hz, 1H), 3.13 (br s, 1H); 13C NMR (100 MHz, CD3COCD3) δ
167.2, 164.8, 148.7, 142.9, 138.1, 134.5, 133.2, 132.6, 131.8, 130.8,
129.1, 128.9, 128.2, 125.9, 124.3, 122.9 (2C), 121.5, 68.9 (2C),
39.7, 38.7, 38.3, 37.3; HRMS ES [M + Na]+ calcd 389.1266, obsd
389.1263.
The NMR data are also reported in benzene (solvent used for
the COSY and NOESY experiments): 1H NMR (400 MHz, C6D6)
δ 7.83 (d, J ) 7.6 Hz, 1H), 7.78 (d, J ) 7.6 Hz, 1H), 7.21-7.19
(m, 1H), 7.12-7.10 (m, 1H), 7.06 (t, J ) 7.6 Hz, 1H), 6.85 (t, J )
7.6 Hz, 1H), 6.67 (t, J ) 7.6 Hz, 1H), 6.10 (t, J ) 7.6 Hz, 1H),
5.96 (dd, J ) 7.6, 1.2 Hz, 1H), 5.65 (d, J ) 7.6 Hz, 1H), 5.48 (dd,
J ) 10.0, 8.4 Hz, 1H), 4.89-4.85 (m, 1H), 4.65 (dd, J ) 17.6, 8.4
Hz, 1H), 3.77 (dd, J ) 11.2, 2.4 Hz, 1H), 3.35 (d, J ) 17.2 Hz,
1H), 2.85 (d, J ) 17.2 Hz, 1H), 2.32 (br s, 1H), 2.08 (br s, 1H);
13C NMR (100 MHz, C6D6) δ 167.4, 165.6, 148.8, 142.9, 136.7,
135.0, 133.8, 133.5, 131.1, 130.8, 129.3, 129.0 (2C), 124.8, 124.0,
123.9, 123.8, 121.2, 69.0, 68.9, 39.5, 39.1, 39.0, 37.3.
Photodimerization of 8. A solution of 8 (50 mg, 0.25 mmol) in
255 mL of acetone was deoxygenated with argon for 30 min in a
quartz reaction vessel and irradiated in a Rayonet reactor with a
bank of 300 nm lamps for a period of 3 h. The solvent was
evaporated, and the residue was purified directly on silica gel (ethyl
acetate) to yield 48 mg (96%) of 43 as an off-white, sticky gum:
IR (thin film, cm-1) 1693, 1682, 1407, 1360; 1H NMR (500 MHz,
CDCl3) δ 7.89 (d, J ) 7.5 Hz, 1H), 7.85 (d, J ) 7.5 Hz, 1H),
7.67-7.64 (m, 2H), 7.54-7.49 (m, 2H), 7.26 (d, J ) 7.5 Hz, 1H),
7.09 (d, J ) 7.5 Hz, 1H), 6.78 (d, J ) 7.5 hz, 1H), 6.35-6.32 (m,
1H), 5.91 (t, J ) 7.5 Hz, 1H), 5.25 (dd, J ) 8.0, 3.5 Hz, 1H),
4.90-4.87 (m, 1H), 3.20-3.17 (m, 1H), 2.52 (d, J ) 6.5 Hz, 1H),
1.80 (d, J ) 8.5 Hz, 1H), 1.18 (s, 3H), 1.17 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ 174.2, 163.4, 152.5, 149.3, 133.2, 132.8,
132.2, 131.1, 131.0, 130.2, 128.7, 128.8, 124.8, 124.6, 122.6, 121.3,
120.7, 113.5, 68.8, 62.3, 52.5, 41.6, 40.6, 38.5, 27.8, 27.1; HRMS
[M + Na]+ calcd 417.1579, obsd 417.1582.
Continued elution led to the isolation of 45 as a colorless
crystalline solid (15 mg, 33%), mp 259-260 °C: IR (thin film,
1
cm-1) 1738, 1697, 1300; H NMR (500 MHz, CDCl3) δ 9.12 (s,
1H), 8.87 (s, 1H), 7.94 (dd, J ) 11.5, 7.5 Hz, 2H), 7.76 (t, J ) 7.5
Hz, 2H), 7.59 (t, J ) 7.5 Hz, 1H), 7.41 (d, J ) 7.5 Hz, 1H), 5.22
(t, J ) 4.5 Hz, 1H), 3.91 (t, J ) 5.0 Hz, 1H), 3.57 (t, J ) 4.5 Hz,
1H), 3.29 (d, J ) 5.0 Hz, 1H), 2.80 (d, J ) 11.0 Hz, 1H), 2.59
(dd, J ) 10.5, 4.5 Hz, 1H), 1.73 (s, 3H), 1.52 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ 196.4, 174.2, 167.9, 160.3, 151.3, 150.6,
134.9, 133.4, 129.6, 129.5, 127.9, 126.0, 125.4, 123.2, 120.6, 68.2,
66.5, 56.3, 53.8, 50.4, 49.5, 41.2, 36.9, 29.7, 28.2, 27.4; HRMS
[M + Na]+ calcd 465.1426, obsd 465.1420.
Benzo[4,5]thieno[3,2-b]pyridine 5,5-Dioxide (46). Diene 9 (50
mg, 0.23 mmol) was dissolved in 1 mL of dichloromethane and
added to 228 mL of hexane. This solution was then deoxygenated
for 1 h with argon and irradiated at 350 nm in a quartz reaction
vessel. After 2 h, the reaction mixture was concentrated and purified
directly over silica gel (elution with 10:1 dichloromethane/ethyl
acetate) to yield 46 as an off-white solid (18 mg, 36%), mp
222-223 °C (lit16b,c mp 221-222 °C): 1H NMR (500 MHz, CDCl3)
δ 8.82 (d, J ) 4.5 Hz, 1H), 8.19 (d, J ) 7.5 Hz, 1H), 8.12 (d, J )
7.5 Hz, 1H), 7.88 (d, J ) 7.5 Hz, 1H), 7.75 (t, J ) 7.5 Hz, 1H),
7.66 (t, J ) 7.5 Hz, 1H), 7.45 (dd, J ) 7.5, 5.0 Hz, 1H); 13C NMR
(125 MHz, CDCl3) δ 154.5, 150.6, 139.1, 134.3, 132.8, 132.3,
132.2, 129.9, 124.0, 122.6, 121.8.
3-Buta-1,3-dienylbenzo[d]isothiazole 1,1-Dioxide (47): Isolated
as a colorless crystalline solid (14 mg, 30%); mp 220 °C dec; IR
1
(thin film, cm-1) 1519, 1323, 1169; H NMR (500 MHz, CDCl3)
δ 7.96-7.64 (m, 1H), 7.89 (dd, J ) 15.0, 11.5 Hz, 1H), 7.79-7.72
(m, 3H), 6.79 (d, J ) 15.0 Hz, 1H); 13C NMR (125 MHz, CDCl3)
δ 166.9, 147.7, 140.6, 135.2, 133.6, 133.5, 129.5, 123.7, 122.8,
118.1; HRMS [M + Na]+ calcd 242.0252, obsd 242.0258.
Acknowledgment. The authors would like to thank Judith
Gallucci for the crystallographic determination of structures 15,
44, 45, and 47, and Xiaozhao Wang for performing the
calculations reported in Table 1.
Supporting Information Available: Experimental details for
1
the preparation of 7-10, H and 13C NMR spectra for all new
compounds reported herein, and X-ray crystallographic data for
15, 44, 45, and 47. This material is available free of charge via
the Internet at http://pubs.acs.org.
JO802476C
J. Org. Chem. Vol. 74, No. 5, 2009 1987