Exploratory investigations probing a preparatively versatile, pyridinium salt photoelectrocyclization-solvolytic aziridine ring opening sequence

Article abstract of DOI:10.1021/jo960316i

A novel pyridinium salt photoelectrocyclization-nucleophilic bicyclic aziridine ring opening reaction sequence has been investigated in order to determine its preparative potential. N-Alkylpyridinium perchlorates were found to undergo photoinduced electrocyclization upon irradiation in nucleophilic solvents, such as H₂O and MeOH, to efficiently produce 6-alkyl-6-azabicyclo[3.1.0]hex-2-en-4-yl alcohols and ethers. The bicyclic aziridine photoproducts react with a number of different nucleophiles (e.g., H₂O, MeOH, AcOH, AcSH) under acid-catalyzed conditions to produce 5-(nucleophile-substituted)-4-(alkylamino)cyclopenten-3-yl alcohols and ethers. The aziridine ring opening processes are both regioselective and stereoselective, yielding trans,trans-trisubstituted cyclopentenes exclusively, apparently as a consequence of the operation of an SN₂ mechanism. The effects of C-alkyl substitution on the regiochemistry of the pyridinium cation photocyclization reaction were briefly probed, and a method was developed to produce trans,cis-trisubstituted cyclopentenes by use of this tandem preparative sequence.

Full text of DOI:10.1021/jo960316i

J . Org. Chem. 1996, 61, 4439-4449
4439
Exp lor a tor y In vestiga tion s P r obin g a P r ep a r a tively Ver sa tile,
P yr id in iu m Sa lt P h otoelectr ocycliza tion -Solvolytic Azir id in e
Rin g Op en in g Sequ en ce
Rong Ling, Mutsuo Yoshida,† and Patrick S. Mariano*
Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742
Received February 15, 1996X
A novel pyridinium salt photoelectrocyclization-nucleophilic bicyclic aziridine ring opening reaction
sequence has been investigated in order to determine its preparative potential. N-Alkylpyridinium
perchlorates were found to undergo photoinduced electrocyclization upon irradiation in nucleophilic
solvents, such as H2O and MeOH, to efficiently produce 6-alkyl-6-azabicyclo[3.1.0]hex-2-en-4-yl
alcohols and ethers. The bicyclic aziridine photoproducts react with a number of different
nucleophiles (e.g., H2O, MeOH, AcOH, AcSH) under acid-catalyzed conditions to produce 5-(nu-
cleophile-substituted)-4-(alkylamino)cyclopenten-3-yl alcohols and ethers. The aziridine ring
opening processes are both regioselective and stereoselective, yielding trans,trans-trisubstituted
cyclopentenes exclusively, apparently as a consequence of the operation of an SN2 mechanism.
The effects of C-alkyl substitution on the regiochemistry of the pyridinium cation photocyclization
reaction were briefly probed, and a method was developed to produce trans,cis-trisubstituted
cyclopentenes by use of this tandem preparative sequence.
In tr od u ction
bond isomerization processes. A flurry of research activ-
ity in the 1960-70 era uncovered a number of interesting
photoreactions of benzene and its alkyl-substituted and
condensed ring derivatives. An interesting example of
these valence bond isomerization processes is the pho-
tochemical conversion of benzene to benzvalene (2) by a
pathway involving formation and collapse of the inter-
mediate diradical 1. An intriguing observation by Mor-
rison and Ferree8 that trapping of this diradical by a
tethered olefin grouping leads to formation of a meta
intramolecular adduct (3 f 4) spawned a flurry of
activity which resulted in a wide variety of synthetic
applications of this excited state chemistry.9
Photochemistry continues to be a source of unusual
organic transformations, some of which have preparative
potential. Owing to numerous, thorough photophysical
and photochemical studies conducted in the past, it is
now easy to understand and often predict the electronic
and redox properties of photoexcited organic substances.
The special properties of electronic excited states are
responsible for the unique and interesting chemistry
found in photochemical transformations which, for the
most part, have no counterparts in electronic ground
states. Photochemical [2 + 2]-cycloadditions,1 dienone
type A rearrangements2 and single electron transfer
(SET) induced amine-enone â-additions3 are but a few
of the large number of examples of interesting chemical
processes which occur when organic substances are
irradiated with light in the UV-vis regions.4,5
Among the most fascinating organic photochemical
reaction are those that generate small-ring compounds.
As a consequence of the ring strain present in these
photoproducts, secondary reactions involving ring cleav-
age often occur with great facility. Tandem photochemi-
cal-ground state reaction sequences of this type can be
preparatively useful. A popular example of this is the
deMayo reaction in which [2 + 2]-photocycloaddition
between an olefin and enolizable â-diketone generates a
2-hydroxycyclobutyl ketone. Facile retro-aldol cleavage
then occurs to yield a 1,5-diketone.6
Two intriguing observations made early in this area
which have garnered far less attention in recent years
are found in the independent efforts of Berson and
Wilzbach and Kaplan. In 1966, Kaplan and Wilzbach10
described the photochemical 1,3-addition of alcohols to
Another group of interesting strained ring forming
photochemical reactions consists of the benzene valence
‡ On leave from Dojindo Laboratories, Kumamoto, J apan.
X Abstract published in Advance ACS Abstracts, J une 15, 1996.
(1) Weedon, A. C. In Synthetic Organic Photochemistry; Horspool,
W. M., Ed.; Plenum Press: New York, 1984; Chapter 2.
(2) Schaffner, K.; Demuth, M. In Rearrangements in Ground and
Excited States; deMayo, P., Ed.; Academic Press: New York, 1980; Vol.
3, Essay 18.
(3) Yoon, U. C.; Mariano, P. S.; Givens R. S.; Atwater, B. W. In
Advances in Electron Transfer Chemistry; Mariano, P. S., Ed.; J AI
Press: Greenwich, 1994; Vol. 4, Chapter 4.
(6) Weedon, A. C. In Organic Photochemistry and Photobiology;
Horspool, W. M., Song, P. S., Eds.; CRC Press: New York, 1994; pp
670-684.
(7) Gilbert, A. In Organic Photochemistry and Photobiology; Horspool,
W. M., Song, P. S., Eds.; CRC Press: New York, 1994; pp 229-236.
(8) Morrison, H.; Ferree, W. L. J . Chem. Soc., Chem. Commun. 1969,
268.
(9) DeKeukeleire, D. Aldrichchimica Acta 1994, 27, 59. Wender, P.
A.; Siggel, L.; Nuss, J . M. Organic Photochemistry; Padwa, A., Ed.;
Marcel-Dekker: New York, 1989; Vol. 10, Chapter 4.
(10) Kaplan, L.; Ritscher, J . S.; Wilzbach, K. E. J . Am. Chem. Soc.
1966, 88, 2881.
(4) See, for example: Organic Photochemistry and Photobiology;
Horspool, W. M., Song, P. S., Eds.; CRC Press: New York, 1994.
(5) See, for example: Photoinduced Electron Transfer; Fox, M. A.,
Chanon, M., Eds.; Elsevier: Amsterdam, 1988.
S0022-3263(96)00316-7 CCC: $12.00 © 1996 American Chemical Society

4440 J . Org. Chem., Vol. 61, No. 13, 1996
Ling et al.
benzenes. One example is found in the formation of the
bicyclic ether adducts 5 and 6 when a benzene in
trifluoroethanol solution is irradiated. A mechanism
involving formation and alcoholysis of benzvalene was
proposed by Kaplan and Wilzbach, later challenged by
Bryce-Smith and his co-workers,11 and finally proven by
Berson and Hasty12 through an elegant use of D-labeling
techniques. Clearly, this is yet another example of a
preparatively useful tandem photochemical-ground state
reaction sequence, involving formation and ring opening
of a strained ring intermediate.
and diradical coupling. In contrast, we observed that
irradiation of N-allylpyridinium perchlorate (13) under
identical conditions does not produce a related indolizi-
dine product. Rather 13 is efficiently (86%) transformed
upon irradiation in methanol (followed by basic workup)
to the stereochemically pure trans,trans-aminodimethox-
ycyclopentene 15. A careful investigation of this process
showed that 14 is produced initially and that 15 (and its
N-methyl analog) originates by stereo- and regiocon-
trolled methanolysis of this intermediate bicyclic aziri-
dine (and its N-methyl analog) under the acidic methanol
condition attending its formations.
Of greater relevance to the studies described below is
another early (1972) report by Wilzbach and Kaplan13
describing the photochemistry of N-methylpyridinium
chloride (7) and its simple ring methyl-substituted de-
rivatives. These workers observed that irradiation of 7
in 0.05 M aqueous KOH solution leads to production (no
yields given) of the bicyclic aziridinyl alcohol 9 as a single
exo-stereoisomer. The mechanism proposed for this
transformation (supported by ring alkyl labeling experi-
ments) involves initial photoproduction of the bicyclic
cation 8 followed by competitive capture of this cation
by water and rearrangement via the aza benzvalene
cation 10 (Scheme 1).
Sch em e 1
A comparison of these processes shows that pyridinium
cation excited states react by SET pathways when linked
to a good (low E1/2(+)) electron donor (e.g., trisubstituted
alkene) but that the Wilzbach-Kaplan-like, electro-
cyclization pathway dominates in the absence of a strong
SET-driving force (e.g., poor monosubstituted alkene
donor).
In the period since these initial observations were
made, no attention has been given to the pyridinium salt
photocyclization process. Recently, our interests re-
turned to this area when we recognized the potential
synthetic power of tandem sequences involving (1) pho-
toinduced cyclization of pyridinium cations, (2) stereo-
controlled nucleophile addition to produce bicyclic azir-
idines, and (3) stereocontrolled nucleophilic cleavage of
bicyclic aziridine to produce highly functionalized ami-
nocyclopentenes (Scheme 2). We believed that, when
This remarkable photochemical process has gone rela-
tively unnoticed since the time of its discovery in the
1970s. We became acquainted with this area of photo-
chemistry in the 1980s during the course of studies which
pointed out the divergent photochemical behaviors of
N-allylpyridinium perchlorates.14 For example, we ob-
served that irradiation of N-prenylpyridinium perchlorate
(11) in methanol solution leads to production of the
unstable bicyclic dihydropyridine 12. This process occurs
by a well-documented pathway involving SET from the
olefinic π-system to the excited pyridinium chromophore
followed by methanol addition to the olefin cation radical
Sch em e 2
conducted in a proper manner, these sequences could be
employed to prepare functionally rich cyclopentenes with
high degrees of regiochemical and stereochemical control
(Scheme 2). With this view in mind, we recently em-
barked on an exploratory study to probe the pyridinium
salt photocyclization process as well as the ring cleavage
chemistry of the bicyclic aziridine photoproducts. The
results of this effort which demonstrate the synthetic
versatility of this chemistry are described below.
(11) Bryce-Smith, D.; Gilbert, A.; Longuett-Higgins, H. C. J . Chem.
Soc., Chem. Commun. 1967, 240.
(12) Berson, J . A.; Hasty, N. M. J . Am. Chem. Soc. 1971, 93, 1549.
(13) Kaplan, L.; Pavlik, J . W.; Wilzbach, K. E. J . Am. Chem. Soc.
1972, 94, 3283.
(14) Yoon, U. C.; Quillen, S. L.; Mariano, P. S.; Swanson, R.;
Stavinoha, J . L.; Bay, E. J . Am. Chem. Soc. 1983, 105, 1204.
(15) Mariano, P. S. Acc. Chem. Res. 1983, 16, 130.

Pyridinium Salt Photoelectrocyclization-Solvolytic Aziridine Ring Opening J . Org. Chem., Vol. 61, No. 13, 1996 4441
Resu lts a n d Discu ssion
An interesting aspect of the photochemistry of pyri-
dinium perchlorates 17 and 18 is that products arising
by internal capture of the bicyclic cation 25 with the
tethered amide and alcohol nucleophilic groups are not
formed. An attempt to enhance the probability of inter-
nal nucleophile attack has uncovered another intriguing
feature of this photoprocess. We reasoned that the use
of less nucleophilic solvents for these photoreactions
would provide a better opportunity for internal trapping
of the allyl cation moiety in intermediates 25. However,
the results suggest that this cannot be accomplished and
that the efficiency of the photoreactions are highly
sensitive to the solvent system used. Thus, while ir-
radiation of the (carbamoylmethyl)pyridinium perchlor-
ate 17 in ethanol (no base added before concentration of
the photolysate) leads to successful production of the
diethoxyaminocyclopentene 28, photoelectrocyclization
reactions of this substrate do not occur in isopropyl
alcohol or trifluoroethanol solvent systems. Moreover,
the efficiency of bicyclic aziridine 19 production via
irradiation of the N-propyl substrate 16 falls dramatically
as the proportion of methanol in methanol-acetonitrile
solvent systems is decreased (e.g., 15% of 19 in 1:3
MeOH-MeCN).
P yr id in iu m Sa lt P h otoelectr ocycliza tion Rea c-
tion s. One of the first aims of this exploratory investiga-
tion was to assess the scope and possible limitations of
the pyridinium salt photoelectrocyclization reaction dis-
covered in the early work of Wilzbach and Kaplan.13,14
For this purpose, the pyridinium perchlorates 16-18
were prepared by use of standard methods (see Experi-
mental Section) and subjected to photochemical study.
As anticipated,13,14 irradiation (λ > 220 nm, 20 °C, N2) of
the N-propyl substrate 16 (9 mM) in methanol, followed
by a workup procedure involving addition of solid NaH-
CO3 to the photolysate, concentration in vacuo, and
chromatographic separation on Fluorisil, led to isolation
of two major products identified as the bicyclic aziridine
19 (33%) and 4-aminocyclopentene 22 (22%). Structural
and stereochemical assignments to these substances were
made on the basis of characteristic spectroscopic data and
comparisons of the data to the N-methyl and N-allyl
analogs reported earlier.14 Photoreactions of the related
amide- and alcohol-containing substrates 17 and 18
followed by workup under the conditions described above
and silica gel chromatography provided the respective
bicyclic aziridines 20 (22%) and 21 (47%) and the ami-
nocyclopentenes 23 (58%) and 24 (22%).
A number of factors may be responsible for these
reactivity patterns. For example, a highly polar solvent
(H2O > MeOH > EtOH > iPrOH or MeCN) might be
required in order for the rate of electrocyclization of the
pyridinium salt excited state to be competitive with decay
to ground state. Alternatively, the effect of solvent
nucleophilicity may be an important factor since it is
expected (see below) that a dark electrocyclic ring opening
pathway could be available to return the photoproduced
cation intermediate 25 to the pyridinium salt ground
state. In this case, high concentration of good nucleo-
philes (e.g., solvent MeOH or H2O) may be needed to
bring the efficiency of bicyclic aziridine formation into
the detectable region.
Product formation in these processes is a consequence
of the mechanistic pathways described earlier.13,14 Ac-
cordingly, photolysis of the pyridinium salts induces
electrocyclization to generate the bicyclic cations 25
(Scheme 3) which are then trapped by the nucleophilic
Sch em e 3
In this light, the absence of products arising by internal
capture by amide and alcohol nucleophiles in the photo-
chemistry of 17 and 18 is still curious. One possible
reason for this might lie in ring strain and nucleophile
orientation effects in bicyclic allyl cations 29 arising from
the N-nucleophile-tethered substrates 17 and 18. Thus
cyclizations in 29 would require endo-conformers 29b and
would generate somewhat strained tricyclic products 30
(Scheme 4). In order to evaluate the importance of these
restrictions, the N-methylpyridinium salts 31 and 34,
both of which contain more favorably located nucleophilic
alcohol functions, were prepared and subjected to pho-
tochemical study. Irradiation of 31 in methanol contain-
ing KOH (3.8 mM), followed by concentration, chloroform
trituration (see below), and Fluorisil chromotographic
separation, led to isolation of two products characterized
as the bicyclic aziridines 32 (31%) and 33 (19%). The
latter substance is a single diastereomer to which we
have assigned the exo-methoxy stereochemistry on the
basis of mechanistic reasoning alone. Finally, analysis
solvent in an exo-stereocontrolled manner to produce the
bicyclic aziridinium salts 26. Under the acidic conditions
of their formation, the salts 26 partially undergo regio-
controlled (SN2 and not SN′2) methanol promoted ring
opening to produce the protonated aminocyclopentenes
27. Addition of base prior to concentration of the pho-
tolysate allows partial survival of the bicyclic aziridine
primary photoproducts. In accord with our earlier ob-
servation,14 when the photolysates are first concentrated
and then treated with base, the aminocyclopentenes are
the exclusive (55-80%) products isolated.
1
of the crude photolysate by H NMR spectroscopy and
TLC shows that 32 and 33 are the exclusive major

4442 J . Org. Chem., Vol. 61, No. 13, 1996
Ling et al.
Sch em e 4
Sch em e 5
another example of regioselective photoelectrocyclization
is seen in the transformation of the tetrahydroisoquino-
linium perchlorate 41 upon irradiation in KOH-MeOH
to the tricyclic aziridines 42 (26%) and 43 (14%).
products formed upon irradiation of 31 in a 3:2 ratio
which is unchanged by treatment with acidic methanol.
In a similar manner, irradiation of the 4-substituted
pyridinium salt 34 in KOH-MeOH (7.1 mM) followed
by the same workup and separation procedures yields
the bicyclic aziridine 35 (65%) exclusively as a 1:1
mixture of diastereomers. Clearly, internal capture of
the intermediate bicyclic allyl cations produced in pho-
toreactions of 31 and 34 does not compete with inter-
molecular addition of methanol. Thus, even in ideal cases
(in terms of orientation and ring strain) such as these,
photoelectrocyclization leads to formation of solvent-
pyridinium salt adducts.
As shown above, preparatively useful conversions of
pyridinium salts to bicyclic aziridine adducts can be
accomplished by conducting the photoreactions under
basic conditions. In these cases, acid-catalyzed opening
of the aziridine photoproduct by solvent is prevented.
Further examples, demonstrating the synthetic potential
of this procedure, are found in the photoreactions of the
pyridinium salts 16-18 in methanolic KOH solution (4-
15 mM) in which the respective bicyclic aziridines 19-
21 are efficiently produced in purified yields of 53%, 90%,
and 98%, respectively. Also, the bicyclic aziridinyl alco-
hols 44-46 are produced selectively when the pyridinium
salts 16-18 are irradiated in aqueous KOH (4-5 mM).
Bicyclic Azir id in e Rin g Op en in g Rea ction s. As
demonstrated in our early work in this area14 and again
in the above discussion of our current studies, photore-
actions of N-substituted pyridinium salts in neutral
methanol or water solutions followed by concentration
of the crude photolysate leads to direct generation of
aminocyclopentene products (e.g., conversions of 16-19
to 22-23). These observations suggest that the initially
formed bicyclic aziridines (e.g., 19-21) undergo ready,
stereocontrolled acid-catalyzed ring-opening reactions by
SN2 (rather than SN1 or SN′2) pathways. On the basis
of this proposal, we believed that sequential photoelec-
trocyclization-nucleophilic substitution sequences (Scheme
1) would serve as useful methods to prepare a variety of
functionally diverse and stereochemically defined ami-
The high degrees of regioselectivity observed in the
photoreactions of 31 and 34 are surprising. Kaplan and
Wilzbach,13 in their early photochemical studies with
simple polymethylated pyridinium salts, observed sig-
nificant degrees of ring scrambling. An example of this
is found in the photoreaction of 1,4-dimethylpyridinium
chloride (36) in aqueous base which is reported to yield
a 1:1:2 mixture of the regioisomeric bicyclic aziridines
38, 39, and 40. This was attributed to partial formation
and ring opening of azabenvalene 37 (Scheme 5). The
behavior of the hydroxypropyl derivative 34 is quite
different; the exclusive formation of bicyclic aziridine 35
suggests that a benzvalene intermediate related to 37
does not intervene in this photoprocess. Finally, yet

Pyridinium Salt Photoelectrocyclization-Solvolytic Aziridine Ring Opening J . Org. Chem., Vol. 61, No. 13, 1996 4443
Sch em e 6
dinium cation depending on the nature and concentration
of the trapping nucleophile.
In the aziridine ring opening reactions described above,
high degrees of stereocontrol are observed for formation
of the trans,trans-trisubstituted cyclopentenes as a con-
sequence of the SN2 nature of the processes. A procedure
to alter the stereochemical course of aziridine ring
opening and, thus, to allow potential access to cis,trans-
nocyclopentenes. To test the viability of this methodol-
ogy, the bicyclic aziridinyl ethers 19-21 were subjected
to acid-catalyzed ring-opening reactions with a number
stereoisomers of the aminocyclopentenes has been found.
of nucleophilic solvents. Ideal conditions for alcoholysis
The protocol is exemplified by the reaction sequence
and hydrolysis of these substances involve the use of
employed to convert aziridinyl ether 19 to the cis,trans-
millimolar concentrations of perchloric acid and ambient
temperatures. For example, 19 is transformed to the
aminocyclopentenyl alcohol 55. Accordingly, reaction of
cyclopentenes 22 (42%) and 47 (81%) by independent
reactions in methanol and water under these conditions.
Similarly, the amide analog 20 reacts in methanol or
ethanol to form the respective aminocyclopentenes 23
(93%) and 49 (79%). The acetates 48 (36%) and 50 (54%)
are likewise derived by reaction of the respective bicyclic
aziridines 19 and 20 in acetic acid at 25 °C and the
hydroxyethyl analog 21 yields 24 upon methanolysis.
Finally, reaction of 19 in thioacetic acid yields the
thioester amide 51 (74%) by a sequence involving aziri-
dine ring opening followed by thioacid-induced amidation.
19 with ethyl chloroformate in chloroform at 25 °C leads
to rapid generation of the chloro carbamate 54. When
stirred in a CHCl3 solution at reflux, 54 undergoes
The bicyclic aziridinyl alcohols 44-46 undergo the
azlactonization to yield cyclic carbamate 56 which upon
same types of ring-opening reactions as exemplified by
LAH reduction furnishes the cis,trans-cyclopentenol 55.
the formation of 47 (67%) and 52 (35%) from 44 and 53
Interestingly, when the amide derivative 20 is subjected
(99%) from 46.
to ethyl chloroformate ring opening the six-ring azlactone
product 57 (40%) is produced along with the chlorocar-
bamate 58. The exclusive formation of 57, rather than
a five-ring azlactone related to 56, in this process is
presumably the consequence of preferred displacement
of chloride in 58 by the amide rather than carbamate
nucleophilic carbonyl oxygen.
An interesting observation made in studying the aziri-
dine ring opening reactions of 44 and 46 appears to have
both a preparative (see below) and mechanistic signifi-
cance. Specifically, the methanolysis reactions of 44 and
46 occur cleanly when low concentrations (<1 mm) of the
perchloric acid catalyst are used. In contrast, when a
methanolic solution of 46 containing .10 mM HClO4 is
stirred at 25 °C, efficient production of the pyridinium
salt 18 occurs. This result suggests that at high acid
concentrations acid-catalzyed dehydration-aziridine ring
opening can occur via the intermediate allylic cation
(Scheme 6) and, consequently, that this same intermedi-
ate formed in the photoelectrocyclization process can
partition to bicyclic aziridine product or starting pyri-
P r ep a r a tive Asp ects of th e Am in ocyclop en ten e
Syn th etic P r ocess. As can be seen by viewing the
examples presented above, the photoelectrocyclization-
aziridine ring opening sequence serves as a concise
method to transform readily available pyridinium salts

4444 J . Org. Chem., Vol. 61, No. 13, 1996
Ling et al.
Sch em e 7
into highly functionalized aminocyclopentenes. Impor-
tantly, the process has great versatility in terms of the
ability to introduce differentiated functionality into the
five-membered ring and to control relative stereochem-
istry. One possible disadvantage of this chemistry
concerns the potentially narrow range of N-substituents
which can be present in the starting pyridinium salts
and, thus, can be incorporated into the amino group of
the cyclopentene products. In cases where a free (NH2)
or highly adorned amino function is required, it would
be necessary to have a nitrogen protecting group in place
in the starting pyridinium salt and then to remove this
group at the aminocyclopentene stage. The range of
nitrogen protecting groups that can be used for this
purpose is quite narrow. For example, while N-alkylpy-
ridinium salts undergo the photoelectrocyclization ef-
ficiently, their N-benzyl analogs are unreactive.16 This
is most probably due to quenching of the pyridinium
singlet excited state by intramolecular SET from the
electron rich arene ring.17 In addition, N-acyl- or N-
alkoxycarbonyl-protected pyridinium salts cannot be
employed for this purpose, since these substances will
not be stable in the nucleophilic solvent systems required
for the photochemical step.
As a consequence of these considerations, we have
briefly investigated the photochemical reactivity of
pyridinium perchlorate (59) to determine if, like its
N-alkyl analogs, this substance undergoes the photoelec-
trocyclization process. Interestingly, irradiation of 59 in
methanol containing 0.5 mM HClO4 (to insure full
protonation of the pyridine nucleus) followed by workup
and silica gel chromatography leads to isolation of the
aminocyclopentene 61 in a 48% yield. Thus, the N-H
pyridinium salt does indeed react to generate the bicyclic
aziridine 60 which, under the acidic methanol reaction
conditions, is transformed to 61. Clearly, this result
expands the applicability of this aminocyclopentene
synthetic methodology.
Sch em e 8
64 and 66 are formed in a highly acidic medium and,
therefore, apparently reconvert to the starting pyri-
dinium salts by the dehydrative ring opening chemistry
described earlier in the current publication.
The problem associated with the pyridinium-forming,
acid-catalyzed bicyclic aziridine alcohol (e.g., 44-46) ring
opening process is also encountered in photoreactions of
N-alkylpyridinium salts in water when base is not
present. UV spectroscopic monitoring of the photoreac-
tion of 16 at 25 °C in neutral water demonstrates that
16 is consumed efficiently. However, when the solution
is allowed to stand in the dark at 25 °C, a large fraction
of the pyridinium salt 16 re-forms. Thus, it appears that
the bicyclic alcohol 44 under the acidic conditions of its
formation is transformed competitively to 16 and the
cyclopentendiol 69 (Scheme 8). As a result, 69 is formed
in a low yield under these conditions even though UV
monitoring of the photolysate suggested complete conver-
sion of 16.
A partial solution to this problem is found in the use
of elevated temperature photochemical conditions. We
reasoned that at elevated temperatures the reconversion
of 44 to 16 as well as its transformation to 69 would occur
rapidly during the irradiation process. Consequently, it
should be possible to drive the reaction in the direction
of aminocyclopentendiol formation by applying simulta-
neous thermal and photochemical activation. (i.e., to
enhance the rates of dark conversion of 44 to 16 and 69
while simultaneously allowing for photochemical recon-
version of 16 to 44). In the event, extended irradiation
of 16 (1 g scale) in water at 45-70 °C, followed by
aqueous base workup, acylation of the crude product
A hint that simple N-H pyridinium salts would be
photoreactive is found in the early communication by
Wilzbach and Kaplan.13 These workers briefly stated
that irradiation of 3,5-lutidine (62) in acidic D2O results
in its disappearance and concomitant formation of d2-
2,4-lutidine 67. A pathway (Scheme 7) involving photo-
generation, rearrangement, and water capture of the
azabicyclic cation 63 appears reasonable to explain this
transformation. In this case, the alcohol photoproducts
(16) Irradiation of N-benzylpyridinium perchlorate in a MeOH-
KOH solution for an extended time period (as compared to the N-alkyl
analogs) does not lead to generation of the corresponding N-benzyl
bicyclic aziridine.
(17) For example, see: Borg, R. M.; Heuckeroth, R. D.; Lan, J . Y.;
Quillen, S. L.; Mariano, P. S. J . Am. Chem. Soc. 1987, 109, 2728. Lan,
J . Y.; Heuckeroth, R. O.; Mariano, P. S. J . Am. Chem. Soc. 1987, 109,
2738.

Pyridinium Salt Photoelectrocyclization-Solvolytic Aziridine Ring Opening J . Org. Chem., Vol. 61, No. 13, 1996 4445
the photolysis solution unless otherwise specified. The pho-
tolysis solutions were purged with N2 both before and during
irradiation. The progress of each preparative photochemical
reaction was monitored by UV absorption spectrometry (to
determine % conversions), TLC, and/or H NMR spectroscopy.
Large-scale preparative photoreactions were carried by use of
a Rayonet reactor using a bank of 254 nm lamps.
mixture, and chromatographic separation, led to isolation
of the diacetoxyamidocyclopentene 71. In a similar
fashion, pyridinium perchlorate (59) (1 g scale) is con-
verted to the triacetyl derivative 72 (25%) by extended
irradiation in aqueous HClO4 at 45-70 °C followed by
acetylation and purification.
1
1-P r op ylp yr id in iu m P er ch lor a te (16). A solution of
pyridine (20 g, 0.25 mol) and propyl iodide (43 g, 0.25mol) were
stirred at 90 °C for 3 h under N2 to yield a solid (55 g, 87%)
identified as 1-propylpyridinium iodide. A mixture of the
iodide salt (5 g, 0.02 mol), perchloric acid (2.9 g, 0.02 mol),
and silver carbonate (2.8 g, 0.01 mol) in 50 mL of methanol
was stirred at 25 °C for 1 h and filtered. Concentration in
vacuo of the filtrate gave a residue which was subjected to
column chromatography (alumina, acetone) to give 4.4 g
(98.8%) of the perchlorate salt 16: 1H NMR (D2O) 8.70 (d, J
) 6.1 Hz, 2H, H2, H6), 8.41 (m, 1H, H4 ), 7.93 (t, J ) 6.7 Hz,
2H, H3, H5), 4.43 (t, J ) 7.2 Hz, 2H, NCH2), 1.90 (m, 2H,
NCH2CH2), 0.81 (t, J ) 7,4 Hz, 3H, NCH2CH2CH3 ); 13C NMR
(D2O) 147.3, 146.0, 130.0 (heteroaromatic), 65.1 (NCH2), 25.9
(NCH2CH2), 11.5 (NCH2CH2CH3).
1-(Ca r ba m oylm eth yl)p yr id in iu m P er ch lor a te (17). A
mixture of 2-chloroacetamide (5.5 g, 58 mmol) and pyridine
(9.2 g, 116 mmol) was stirred at 80 °C for 30 min under N2 to
yield 9.1 g (91% yield) of a solid identified as 1-(carbamoyl-
methyl)pyridinium chloride. A solution of this chloride salt
(3.1 g, 18 mmol) in MeOH (30 mL) was then added into a warm
solution of silver carbonate (2.5 g, 9.0 mmol) and perchloric
acid (70%, 2.6 g, 18 mmol) in acetone (30 mL) and MeOH (30
mL). The reaction mixture was stirred at 25 °C for 30 min,
filtered, and concentrated in vacuo to give the crystalline
perchlorate 17, which was recrystallized from methanol to
yield 3.9 g (90% yield) of 17 (mp 167-169 °C): 1H NMR (D2O)
8.66 (d, J ) 6.2 Hz, 2H, H2, H6), 8.51 (t, J ) 7.7 Hz, 1H, H4),
7.99 (dd, J ) 7.7, 6.2 Hz, 2H, H3, H5), 5.38 (s, 2H, CH2); 13C
NMR (D2O) 171.1 (CdO), 149.7, 148.7, 131.0 (heteroaromatic),
64.4 (CH2); MS m/z (rel intensity) 138 (7), 137 (5), 79(100);
HRMS calcd m/z for C7H9NO2 137.0715, found 137.0709.
Su m m a r y
The results outlined above convincingly demonstrate
that pyridinium salts which lack appended electron donor
centers undergo efficient photoelectrocyclization to pro-
duce bicyclic aziridine ring containing, allylic cations.
Capture of these intermediates by nucleophilic solvents,
occurring in competition with dark conversion back to
their pyridinium cation precursors, produces bicyclic
aziridine products. The bicyclic aziridine photoproducts
are themselves reactive with nucleophiles, undergoing
acid-catalyzed ring opening to generate trans,trans-3,5-
disubstituted-4-aminocyclopentenes in a highly regio- and
stereocontrolled manner. The diversity of this methodol-
ogy for functionalized aminocyclopentene synthesis is
enhanced by the observation that the bicyclic aziridine
intermediates can be converted to trans,cis-3,5-disubsti-
tuted-4-aminocyclopentenes by use of a chloroformate
ring-opening-azlactonization sequence. Finally, the re-
markable degree of functional and stereochemical com-
plexity which can be assembled in a reasonably straight-
forward fashion by this photoelectrocyclization-aziridine
ring opening protocol is well-exemplified by short syn-
theses of the trans,trans-diacetoxy-4-acetamidocyclo-
pentenes described starting with pyridine. While more
needs to be explored to elucidate the full preparative
power of this chemistry, the results obtained thus far
suggest that pyridinium salt photochemistry holds in-
teresting synthetic potential.
1-(2-Hyd r oxyeth yl)p yr id in iu m P er ch lor a te (18).
A
mixture of 2-chloroethanol (5.0 g, 62 mmol) and pyridine (9.7
g, 123 mmol) was stirred at 120 °C for 5 h under N2 to yield
9.9 g (100% yield) of a solid identified as 1-(2-hydroxyethyl)-
pyridinium chloride. A solution of this chloride salt (1.4 g,
8.8 mmol) in MeOH (30 mL) was then added into a warm
solution of silver carbonate (1.2 g, 4.4 mmol) and perchloric
acid (70%, 1.2 g, 8.8 mmol) in acetone (30 mL) and MeOH (30
mL). The reaction mixture was stirred at 25 °C for 30 min,
filtered, and concentrated in vacuo to give 1.9 g (95% yield) of
perchlorate salt 18 as an oil: 1H NMR (D2O) 8.67 (d, J ) 5.7
Hz, 2H, H2, H6), 8.40 (t, J ) 7.8 Hz, 1H, H4), 7.91 (dd, J ) 7.8,
5.7 Hz, 2H, H3, H5), 4.54 (t, J ) 5.0 Hz, 2H, CH2OH), 3.89 (t,
J ) 5.0 Hz, 2H, CH2CH2OH); 13C NMR (D2O) 147.8, 146.5,
130.0 (heteroaromatic), 65.4 (CH2OH), 62.3 (CH2CH2OH); MS
m/z (rel intensity) 124 (2), 121 (2), 79 (100); HRMS calcd m/z
for C7H10NO 124.0762, found 124.0762.
1-Meth yl-3-(h yd r oxyp r op yl)p yr id in iu m P er ch lor a te
(31). A mixture of 3-pyridyl-1-propanol (5.0 g, 36 mmol) and
iodomethane (10 g, 72 mmol) was stirred at 0 °C for 30 min
under N2 to yield 9.4 g (94% yield) of a solid identified as
1-methyl-3-(hydroxypropyl)pyridinium iodide. A solution of
this iodide salt (5.0 g, 18 mmol) in MeOH (30 mL) was then
added into a solution of silver carbonate (2.5 g, 9.0 mmol) and
perchloric acid (70%, 2.6 g, 18 mmol) in acetone (30 mL) and
MeOH (30 mL). The reaction mixture was stirred at 25 °C
for 30 min, filtered, and concentrated in vacuo to give 4.1 g
(92% yield) of the perchlorate salt 31: 1H NMR (D2O) 8.56 (s,
1H, H2), 8.48 (d, J ) 5.8 Hz, 1H, H6), 8.28 (d, J ) 7.9 Hz, 1H,
H4), 7.83 (dd, J ) 7.9, 5.8 Hz, 1H, H5), 4.23 (s, 3H, CH3), 3.53
(t, J ) 6.3 Hz, 2H, CH2O), 2.80 (t, J ) 7.5 Hz, 2H, CH2CH2-
CH2OH), 1.82 (m, 2H, CH2CH2CH2OH); 13C NMR (D2O) 147.5,
146.8, 145.5, 144.9, 129.8 (heteroaromatic), 62.9 (CH2OH), 50.3
(CH3), 34.2, 30.8 (CH2CH2CH2OH); MS m/z (rel intensity) 152
(13), 151 (45), 134 (11), 120 (100), 93 (53); HRMS calcd for
m/z C9H14NO 152.10075, found 152.1077.
Exp er im en ta l Section
Gen er a l. 1H NMR and 13C NMR spectra were recorded
using CDCl3 solutions unless specified otherwise, and chemical
shifts are reported in ppm relative to CHCl3 (δ 7.24 ppm for
1H and δ 77.0 ppm for 13C) which was used as a chemical shift
internal standard for samples in CDCl3, 13C NMR resonance
assignments were aided by the use of the DEPT technique to
determine numbers of attached hydrogens. IR spectral vibra-
tional frequencies are expressed in wave numbers (cm-1).
Column chromatography was performed with Merck-EM type
60 (230-400 mesh) silica gel, Alcoa type F-20 alumina
(neutral, 80-200 mesh), or Fluorisil (100-200 mesh) absor-
bants. Preparative TLC was performed on 20 × 20 cm plates
coated with Merck-EM type 60 GF-254 silica gel. Mass spectra
were recorded by using electron impact ionization unless
specified as chemical ionization by CI. All reactions were run
under a dry N2 atmosphere unless otherwise noted. Organic
extracts obtained following workup of reaction mixtures were
dried over anhydrous Na2SO4 or MgSO4. All compounds
prepared in this study were oils and were judged by NMR to
be >90% pure unless otherwise noted.
Preparative photochemical reactions were conducted with
an apparatus consisting of a 450 W Hanovia medium pressure
mercury lamp surrounded by a Vycor glass filter immersed in
1-Met h yl-4-(3-h yd r oxybu t yl)p yr id in iu m P er ch lor a t e

4446 J . Org. Chem., Vol. 61, No. 13, 1996
Ling et al.
(34). To a solution of 4-picoline (2.5 g, 27 mmol) in anhydrous
THF (20 mL) at -78 °C was added dropwise n-butyllithium
(20 mL, 32 mmol). This resulting mixture was stirred for 2 h
followed by warming gradully to 0 °C and adding dropwise
propylene oxide (2.3 mL, 32 mmol). The reaction mixture was
stirred at 25 °C for 4 h, then the reaction was quenched with
ice-water, and the solution was extracted with CHCl3. The
organic extracts were dried and concentrated in vacuo to give
4.1 g (100%) of 4-(3-hydroxybutyl)pyridine: 1H NMR (CDCl3)
8.45 (d, J ) 6.5 Hz, 2H, H2, H6), 7.11 (d, J ) 6.5 Hz, 2H, H3,
H5), 3.81 (m, 1H, CH(OH)CH3), 2.85-2.60 (m, 2H, CH2CH2-
CH(OH)CH3), 1.72 (m, 2H, CH2CH(OH)CH3), 1.20 (d, J ) 6.3
Hz, 3H, CH3); 13C NMR (CDCl3) 151.3, 149.6, 123.9 (heteroaro-
matic), 67.0 (CH(OH)CH3), 39.5 (CH2CH2CH(OH)CH3), 31.4
(CH2CH(OH)CH3), 23.7 (CH3).
A solution of 4-(3-hydroxybutyl)pyridine (2.4 g, 16 mmol)
and iodomethane (2.9 g, 20 mmol) in CHCl3 (15 mL) was
stirred at 60 °C for 1 h under N2 to yield 4.5 g (97% yield) of
a solid identified as 1-methyl-4-(3-hydroxybutyl)pyridinium.
A solution of the iodide salt (4.5 g, 15 mmol) in MeOH (30
mL) was then added to a solution of silver carbonate (2.1 g,
7.6 mmol) and perchloric acid (70%, 2.2 g, 15 mmol) in acetone
(30 mL) and MeOH (30 mL). The reaction mixture was stirred
at 25 °C for 30 min, filtered, and concentrated in vacuo to give
3.5 g (88% yield) of perchlorate salt 34: 1H NMR (D2O) 8.46
(d, J ) 6.5 Hz, 2H, H2, H6), 7.74 (d, J ) 6.5 Hz, 2H, H3, H5),
4.18 (s, 3H, NCH3), 3.80-3.68 (m, 1H, CH(OH)CH3), 2.93-
2.78 (m, 2H, CH2CH2CH(OH)CH3), 1.82-1.68 (m, 2H, CH2-
CH(OH)CH3), 1.08 (d, J ) 6.3 Hz, 3H, CH(OH)CH3); 13C NMR
(D2O) 165.5, 146.7, 130.2 (heteroaromatic), 69.4 (CH(OH)CH3),
49.8 (NCH3), 40.1 (CH2CH2CH(OH)CH3), 33.9 (CH2CH(OH)-
CH3), 24.4 (CH(OH)CH3); MS m/z (rel intensity) 166 (3), 165
(9), 120 (100); HRMS calcd m/z for C10H16NO 166.1232, found
166.1247.
2-Meth yl-5,6,7,8-tetr a h yd r oisoqu in olin iu m P er ch lor -
a te (41). A mixture of 5,6,7,8-tetrahydroisoquinoline (2.0 g,
14 mmol) and iodomethane (4.6 g, 32 mmol) was stirred at 0
°C for 15 min under N2 to yield 3.6 g (92% yield) of a solid
identified as 2-methyl-5,6,7,8-tetrahydroisoquinolinium iodide.
A solution of this iodide salt (2.0 g, 7.2 mmol) in MeOH (30
mL) was then added to a solution of silver carbonate (1.0 g,
3.6 mmol) and perchloric acid (70%, 1.0 g, 7.2 mmol) in acetone
(30 mL) and MeOH (30 mL). The reaction mixture was stirred
at 25 °C for 30 min, filtered, and concentrated in vacuo to give
the crystalline salt, which was recrystallized from methanol
to yield 1.6 g (89% yield) of perchlorate salt 41 (mp 60-62
°C): 1H NMR (D2O) 8.29 (s, 1H, H1), 8.18 (d, J ) 6.3 Hz, 1H,
H3), 7.53 (d, J ) 6.3 Hz, 1H, H4), 4.11 (s, 3H, CH3), 2.90-2.70
(m, 4H, H5, H8), 1.73 (p, J ) 3.3 Hz, 4H, H6, H7); 13C NMR
(D2O) 160.7, 146.3, 142.7, 141.0, 130.0 (heteroaromatic), 49.3
(CH3), 31.3, 28.2, 23.0, 23.0 (C5, C6, C7, C8); MS m/z (rel
intensity) 148 (8), 146 (100), 132 (13); HRMS calcd m/z for
C10H14N 148.1126, found 148.1120.
P yr id in iu m P er ch lor a te (59). Perchloric acid (70%, 3.7
g, 25 mmol) was added dropwise to a stirred solution of
pyridine (2.0 g, 25 mmol) in CHCl3 (5 mL). The formed
crystalline pyridinium perchlorate was recrystallized from
methanol to yield 4.2 g (93% yield) of perchlorate salt 59 (mp
287-289 °C); 1H NMR (D2O) 8.73 (d, J ) 6.2 Hz, 2H, H2, H6),
8.55 (t, J ) 7.7 Hz, 1H, H4), 7.99 (dd, J ) 7.7, 6.2 Hz, 2H, H3,
H5); 13C NMR (D2O) 149.6, 143.4, 129.8 (heteroaromatic); MS
m/z (rel intensity) 80 (9), 79 (100); HRMS calcd m/z for C5H6N
80.0500, found 80.0492.
H5), 2.20 (m, 2H, NCH2), 1.60 (m, 2H, NCH2CH2), 0.95 (t, J )
7,4 Hz, 3H, NCH2CH2CH3); 13C NMR 136.5, 134.7 (CHdCH),
84.5 (C4), 60.2 (NCH2), 55.6 (OCH3), 47.9 (C5), 46.8 (C1), 25.9
(NCH2CH2), 11.5 (NCH2CH2CH3); MS m/z (rel intensity) 154-
(1), 122(57), 80(100); HRMS calcd m/z for C9H15NO 153.1154,
found 153.1164.
22: 1H NMR 6.20 (s, 2H, vinyl), 4.05 (d, 2H, H3,H5), 3.40 (s,
6H, OCH3), 3.31 (t, 1H, H1,H4), 2.72 (t, 2H, NCH2), 1.56 (m,
2H, NCH2CH2), 0.95 (t, J ) 7,4 Hz, 3H, NCH2CH2CH3); 13C
NMR 131.9 (CHdCH), 86.7 (C3,C5), 69.7 (C4), 56.4 (OCH3), 50.1
(NCH2), 21.7 (NCH2CH2), 11.4 (NCH2CH2CH3); MS m/z (rel
intensity) 185(6), 154(100), 122(27), 99(19), 80(24); HRMS
calcd m/z for C10H19NO2 1185.1416, found 1185.1410.
Ir r a d ia tion of 16 in MeOH-KOH. An N2-purged solution
of 16 (300 mg, 1.35 mmol) and KOH (76 mg, 1.35 mmol) in
100 mL of absolute methanol was irradiated for 2.25 h. The
photolysate was concentrated in vacuo, and the residue was
subjected to the “normal workup procedure B” (triturated with
CHCl3, triturate filtered and concentrated in vacuo) to yield a
residue which was subjected to column chromatography (Flo-
risil, CHCl3) to give 80 mg (53%) of 19.
Ir r a d ia tion of 1-(Ca r ba m oylm eth yl)p yr id in iu m P er -
ch lor a te (17) in MeOH. An N2-purged solution of 17 (96 mg,
0.40 mmol) in anhydrous MeOH (100 mL) was irradiated in a
preparative apparatus for 90 min. The photolysate was
subjected to the normal workup procedure A to give a residue
which was subjected to column chromatography (silica gel,
chloroform:acetone 90/10) to yield 12 mg (22% yield at 82%
conversion) of 4-methoxy-6-(carbamoylamidomethyl)-6-aza-
bicyclo[3.1.0]hex-2-ene (20) and 38 mg (58% yield at 82%
conversion) of the 4-(carbamoylmethyl)amino-3,5-dimethoxy-
cyclopentene (23).
20: 1H NMR 6.29 (d, J ) 6.0 Hz, 1H, vinyl), 5.92 (m, 1H,
vinyl), 4.17 (s, 1H, H4), 3.40 (s, 3H, OCH3), 3.07 and 2.95 (ABq,
J ) 16.6 Hz, 2H, CH2), 2.65 (brs, 2H, H1, H5); 13C NMR 172.5
(CdO), 135.6, 135.3 (CHdCH), 83.4 (C4), 60.2 (CH2), 55.8
(OCH3), 48.2, 47.7 (C1, C5); IR (neat) 2928, 1668, 1374, 1086;
MS m/z (rel intensity) 168 (2), 137 (100), 93 (18), 80 (59);
HRMS calcd m/z for C8H12N2O2 168.0899, found 168.0906.
23: 1H NMR 6.01 (s, 2H, vinyl), 4.01 (d, J ) 5.1 Hz, 2H, H3,
H5), 3.45 (s, 2H, CH2), 3.37 (s, 6H, 2OCH3), 3.15 (t, J ) 5.1
Hz, 1H, H4); 13C NMR 174.5 (CdO), 132.0 (CHdCH), 88.1 (C3,
C5), 70.5 (C4), 56.4 (OCH3), 50.4 (CH2); IR (neat) 2928, 1667,
1371, 1083; MS m/z (rel intensity) 200 (1), 185 (3), 169 (40),
137 (100), 127 (25), 110 (54), 80 (29); HRMS calcd m/z for
C9H16N2O3 200.1161, found 200.1162.
Ir r a d ia tion of 17 in MeOH-KOH. An N2-purged solution
of 17 (100 mg, 0.42 mmol) and potassium hydroxide (40 mg,
0.71 mmol) in anhydrous MeOH (100 mL) was irradiated in a
preparative apparatus for 140 min. The photolysate was
concentrated in vacuo to give a residue which was subjected
to column chromatography (silica gel, chloroform:acetone 80/
20) to yield 57 mg (90% yield at 98% conversion as indicated
by UV) of 4-methoxy-6-(carbamoylmethyl)-6-azabicyclo[3.1.0]-
hex-2-ene (20).
Ir r a d ia tion of 1-(2-Hyd r oxyeth yl)p yr id in iu m P er ch lo-
r a te (18) in MeOH. An N2-purged solution of 18 (110 mg,
0.49 mmol) in anhydrous MeOH (90 mL) was irradiated in a
preparative apparatus for 180 min. The photolysate was
concentrated in vacuo and subjected to the normal workup
procedure A to give a residue which was subjected to column
chromatography (silica gel, first with chloroform:ether 50/50,
chloroform:acetone 50/50) to yield 33 mg (47% yield at 93%
conversion) of 4-methoxy-6-(hydroxyethyl)-6-azabicyclo[3.1.0]-
hex-2-ene (21) and 19 mg (22% yield at 93% conversion) of
4-[N-(2-hydroxyethyl)amino]-3,5-dimethoxycyclopentene (24).
21: 1H NMR 6.28 (d, J ) 5.6 Hz, 1H, vinyl), 5.89 (m, 1H,
vinyl), 4.16 (s, 1H, H4), 3.69 (t, J ) 5.4 Hz, 2H, CH2OH), 3.38
(s, 3H, OCH3), 2.57 (brs, 2H, H1, H5), 2.46 (m, 2H, CH2CH2-
OH); 13C NMR 136.1, 135.0 (CHdCH), 83.3 (C4), 61.6 (CH2-
OH), 59.8 (CH2CH2OH), 55.7 (OCH3), 47.7, 46.8 (C1, C5); IR
(neat) 3418, 2931, 1667, 1645, 1455, 1372, 1115, 1084; MS m/z
(rel intensity) 156 (4), 155 (5), 124 (100), 110 (7), 80 (88); HRMS
calcd m/z for C8H13NO2 155.0946, found 155.0933.
Ir r a d ia tion of 1-P r op ylp yr id in iu m P er ch lor a te (16).
An N2-purged solution of 16 (200 mg, 0.90 mmol) in 100 mL
of absolute methanol was irradiated for 1.75 h. The photoly-
sate was subjected to the “normal workup procedure A”
(neutralized with NaHCO3 concentrated in vacuo, residue
triturated with CHCl3, triturate filtered, and filtrate concen-
trated in vacuo) to yield a residue which was subjected to
column chromatography (Florisil, CHCl3) to give 40 mg (33%)
of 4-methoxy-6-propyl-6-azabicyclo[3.1.0]hex-2-ene (19) and 36
mg (22%) of 3,5-dimethoxy-4-(N-propylamino)cyclopentene
(22).
19: 1H NMR 6.31 (d, J ) 5.8 Hz, 1H, vinyl), 5.88 (m, 1H,
vinyl), 4.15 (s, 1H, H4), 3.40 (s, 3H, OCH3), 2.45 (brs, 2H, H1,
24: 1H NMR 6.09 (s, 2H, vinyl), 4.48 (d, J ) 4.7 Hz, 2H, H3,
H5), 3.85 (t, J ) 5.3 Hz, 2H, CH2OH), 3.40 (s, 3H, OCH3), 3.29

Pyridinium Salt Photoelectrocyclization-Solvolytic Aziridine Ring Opening J . Org. Chem., Vol. 61, No. 13, 1996 4447
(t, J ) 4.7 Hz, 1H, H4), 3.15 (t, J ) 5.3 Hz, 2H, CH2CH2OH);
13C NMR 131.2 (CHdCH), 83.6 (C3, C5), 69.4 (C4), 57.4 (CH2-
OH), 56.5 (OCH3), 50.0 (CH2CH2OH); IR (neat) 3427, 1654,
1455, 1372, 1089; MS m/z (rel intensity) 187 (2), 156 (100),
124 (46), 80 (30); HRMS calcd m/z for C9H17NO3 187.1209,
found 187.1212.
Ir r a d ia tion of 18 in MeOH-KOH. An N2-purged solution
of 18 (110 mg, 0.49 mmol) and potassium hydroxide (40 mg,
0.71 mmol) in anhydrous MeOH (100 mL) was irradiated in a
preparative apparatus for 210 min. The photolysate was
concentrated in vacuo, giving a residue which was subjected
to column chromatography (silica gel, chloroform:acetone 80/
20) to yield 71 mg (98% yield at 96% conversion) of 4-methoxy-
6-(hydroxyethyl)-6-azabicyclo[3.1.0]hex-2-ene (21).
Ir r a d ia tion of 17 in EtOH. An N2-purged solution of 17
(100 mg, 0.42 mmol) in anhydrous EtOH (100 mL) was
irradiated in a preparative apparatus for 80 min. The pho-
tolysate was subjected to the normal workup procedure A to
give a residue which was subjected to column chromatography
(silica gel, chloroform:acetone 80/20) to yield 61 mg (71% yield
at 90% conversion) of 4-((carbamoylmethyl)amino)-3,5-di-
ethoxycyclopentene (28): 1H NMR 5.96 (s, 2H, vinyl), 4.09 (d,
J ) 5.3 Hz, 2H, H3, H5), 3.60 (m, 4H, 2OCH2CH3), 3.48 (s, 2H,
CH2CONH2), 3.18 (t, J ) 5.3 Hz, 1H, H4), 1.19 (t, J ) 7.0 Hz,
6H, 2OCH2CH3); 13C NMR 174.4 (CdO), 132.3 (CHdCH), 86.4
(C3, C5), 71.3 (C4), 64.4 (OCH2CH3), 50.4 (CH2CONH2), 15.6
(OCH2CH3); IR (neat) 2974, 2873, 1673, 1372, 1086; MS m/z
(rel intensity) 229(1), 228(1),183 (32), 170 (9), 165(12), 155 (12),
137 (100), 124 (23); HRMS calcd m/z for C11H20N2O3 228.1474,
found 228.1482.
Ir r a d ia tion of 1-Meth yl-3-(h yd r oxyp r op yl)p yr id in iu m
P er ch lor a te (31) in MeOH-KOH. An N2-purged solution
of 31 (98 mg, 0.38 mmol) and potassium hydroxide (32 mg,
0.57 mmol) in anhydrous MeOH (90 mL) was irradiated in a
preparative apparatus for 90 min. The photolysate was
concentrated in vacuo to give a residue which was subjected
to column chromatography (Florisil, hexanes:acetone 50/50)
to yield 18 mg (31% yield at 84% conversion) of bicyclic
aziridine 32 and 11 mg (19% yield at 84% conversion) of
bicyclic aziridine 33.
intensity) 198 (M + 1, 20), 197 (5), 196 (11), 166 (100), 150
(14), 134 (20), 120 (74); HRMS(CI) calcd m/z for C11H20NO2
198.1494, found 198.1493.
Ir r a d ia tion of 2-Meth yl-5,6,7,8-tetr a h yd r oisoqu in olin -
iu m P er ch lor a te (41) in MeOH-KOH. An N2-purged
solution of 41 (109 mg, 0.44 mmol) and potassium hydroxide
(40 mg, 0.71 mmol) in anhydrous MeOH (90 mL) was irradi-
ated in a preparative apparatus for 120 min. The photolysate
was concentrated in vacuo to give a residue which was
subjected to column chromatography (silica gel, hexanes:
acetone 60/40) to yield 15 mg (26% yield at 74% conversion)
of 42 and 12 mg (21% yield at 74% conversion) of a mixture of
42 and 43 (NMR 1:2 ratio). This mixture was subjected to
preparative TLC (silica gel, hexanes:acetone 50/50) to give 3
mg of pure 43. Spectroscopic data for 43 were obtained on
pure material (1H NMR, IR, and MS) or on a mixture of 42
and 43 (13C NMR).
42: 1H NMR 3.97 (s, 1H, H4), 3.39 (s, 3H, OCH3), 2.30 (s,
3H, NCH3), 2.27 (s, 1H, H5), 2.26 (s, 1H, H1), 2.19-2.10 (m,
4H, CH2CH2CH2CH2), 1.60 (m, 4H, CH2CH2CH2CH2); 13C NMR
141.3, 139.2 (CdC), 85.6 (C4), 55.6 (OCH3), 50.1 (NCH3), 47.3,
44.9 (C1, C5), 24.7, 23.3, 22.7, 22.1 (CH2CH2CH2CH2); IR (neat)
3015, 2930, 2836, 1660, 1449, 1320, 1082; MS m/z (rel
intensity) 180 (M + 1, 4), 179 (2), 164 (3), 148 (100), 120 (18);
HRMS(CI) calcd m/z for C11H18NO 180.1388, found 180.1390.
43: 1H NMR 5.83 (s, 1H, vinyl), 3.18 (s, 3H, OCH3), 2.28 (s,
3H, NCH3), 2.13 (s, 1H, H5), 2.12 (s, 1H, H1), 2.00 (m, 4H, CH2-
CH2CH2CH2), 1.69 (m, 4H, CH2CH2CH2CH2); 13C NMR 147.9
(C)CH), 125.6 (C)CH), 83.8 (C4), 50.9 (OCH3), 50.0 (NCH3),
46.8, 44.9 (C1, C5), 34.2, 26.6, 26.0, 21.1 (CH2CH2CH2CH2); IR
(neat) 2931, 2861, 1705, 1453, 1096; MS m/z (rel intensity) 180
(M + 1, 31), 179 (11), 164 (23), 148 (100), 120 (17); HRMS(CI)
calcd m/z for C11H18NO180.1388, found 180.1384.
Ir r a d ia tion of 16 in H2O-KOH. An N2-purged solution
of 16 (200 mg, 0.90 mmol) and KOH (51 mg, 0.90 mmol) in
100 mL of water was irradiated for 1.5 h. The photolysate
was subjected to the normal workup procedure B to yield 71
mg (57%) of 6-propyl-6-azabicyclo[3.1.0]hex-3-en-2-ol (44): 1H
NMR 6.25 (d, 1H, vinyl), 5.83 (m, 1H, vinyl), 4.43 (s, 1H, H2),
2.45, 2.41 (brs, 2H, H1, H5), 2.24 (t, 2H, NCH2), 1.56 (m, 2H,
NCH2CH2), 0.90 (t, J ) 7,4 Hz, 3H, NCH2CH2CH3); 13C NMR
137.2, 135.5 (CHdCH), 74.8 (C2), 60.0 (NCH2CH2), 0.90 (NCH2-
CH2CH3); 55.5, 46.8 (C1, C5), 22.6 (NCH2CH2), 11.7 (NCH2-
CH2CH3); MS m/z (rel intensity) 139(7), 122(68), 96(17),
80(100); HRMS calcd m/z for C8H13NO 139.0997, found
139.0989.
Ir r a d ia tion of 17 in H2O-KOH. An N2-purged solution
of 17 (100 mg, 0.42 mmol) and potassium hydroxide (40 mg,
0.71 mmol) in H2O (100 mL) was irradiated in a preparative
apparatus for 180 min. The photolysate was concentrated
under reduced pressure to give a residue, which was subjected
to column chromatography (silica gel, chloroform:acetone 90/
10) to yield 24 mg (41% yield at 90% conversion) of the
6-(carbamoylmethyl)-6-azabicyclo[3.1.0]hex-3-en-2-ol (45): 1H
NMR 6.27 (d, J ) 5.6 Hz, 1H, vinyl), 5.92 (d, J ) 5.6 Hz, 1H,
vinyl), 4.49 (s, 1H, H2), 3.01 (s, 3H, OCH3), 3.07 and 2.94 (ABq,
J ) 16.7 Hz, 2H, CH2), 2.64 (brs, 2H, H1, H5); 13C NMR 172.5
(CdO), 137.8, 135.0 (CHdCH), 75.2 (C2), 60.1 (CH2), 50.7, 47.6
(C1, C5); IR (neat) 3382, 1683, 1418, 1318, 1126, 1037; MS m/z
(rel intensity) 154 (2), 137 (100), 120 (5), 93 (15); HRMS calcd
m/z for C7H10N2O2 154.0742, found 154.0742.
Ir r a d ia tion of 18 in H2O-KOH. An N2-purged solution
of 18 (100 mg, 0.45 mmol) and potassium hydroxide (40 mg,
0.71 mmol) in H2O (100 mL) was irradiated in a preparative
apparatus for 135 min. After the normal workup procedure
B and column chromatography (silica gel, chloroform:acetone
50/50), 57 mg (100% yield at 90% conversion) of 6-(2-hydroxy-
ethyl)-6-azabicyclo[3.1.0]hex-3-en-2-ol (46) was obtained: 1H
NMR 6.35 (d, J ) 5.8 Hz, 1H, vinyl), 5.82 (m, 1H, vinyl), 4.50
(s, 1H, H2), 3.71 (t, J ) 5.2 Hz, 2H, CH2OH), 2.55 (brs, 2H,
H1, H5), 2.41 (t, J ) 5.2 Hz, 2H, CH2CH2OH); 13C NMR 137.4,
135.3 (CHdCH), 74.7 (C2), 61.5 (CH2OH), 59.7 (CH2CH2OH),
50.5, 46.6 (C1, C5); IR (neat) 3389, 2930, 1660, 1642, 1349,
1114, 1038; MS m/z (rel intensity) 142 (4), 141 (2), 140 (6),
124 (100), 96 (14), 80 (84); HRMS calcd m/z for C7H11NO2
141.0790, found 141.0794.
32: 1H NMR 5.49 (s, 1H, vinyl), 4.10 (s, 1H, H4), 3.64 (m,
2H, CH2OH), 3.38 (s, 3H, OCH3), 2.43 (s, 1H, H1 or H5), 2.32
(s, 3H, NCH3), 2.31 (s, 1H, H5 or H1), 2.30 (m, 2H, CH2CH2-
OH), 1.78 (m, 2H, CH2CH2CH2OH); 13C NMR 151.2 (CHdC),
127.3 (CHdC), 83.3 (C4), 62.2 (CH2OH), 55.6 (OCH3), 49.6
(NCH3), 49.7, 44.6 (C1, C5), 31.0, 27.7 (CH2CH2CH2OH); IR
(neat) 3369, 2938, 2868, 1630, 1452, 1093; MS m/z (rel
intensity) 184 (M + 1, 4), 182 (6), 152 (100), 107 (27); HRMS
(CI) calcd m/z for C10H18NO2 184.1338, found 184.1336.
33: 1H NMR 6.24 (m, 1H, vinyl), 5.53 (m, 1H, vinyl), 3.55
(m, 2H, CH2OH), 3.18 (s, 3H, OCH3), 2.41 (s, 1H, H1 or H5),
2.30 (s, 3H, NCH3), 2.23 (s, 1H, H5 or H1), 1.80 (m, 4H, CH2CH2-
CH2OH); 13C NMR 137.3, 135.1 (CHdCH), 87.6 (C4), 63.2 (CH2-
OH), 50.6, 50.1 (OCH3, NCH3), 48.3, 45.0 (C1, C5), 32.2, 28.8
(CH2CH2CH2OH); IR (neat) 3393, 3056, 2939, 2869, 1648,
1454, 1065; MS m/z (rel intensity) 184 (M + 1, 7), 183 (6), 182
(9), 152 (100), 124 (52); HRMS (CI) calcd m/z for C10H18NO2
184.1338, found 184.1338.
Ir r a d ia t ion 1-Met h yl-4-(3-h yd r oxyb u t yl)p yr id in iu m
P er ch lor a te (34) in MeOH-KOH. An N2-purged solution
of 34 (188 mg, 0.71 mmol) and potassium hydroxide (44 mg,
0.78 mmol) in anhydrous MeOH (100 mL) was irradiated in a
preparative apparatus for 6 h. The photolysate was concen-
trated in vacuo to give a residue which was subjected to column
chromatography (Florisil, hexanes:acetone 50/50) to yield 43
mg (65% yield at 47% conversion) of the bicyclic aziride 35 as
a 1:1 mixture of diastereomers: 1H NMR 5.91, 5.89 (s, 1H,
vinyl), 4.09, 4.00 (s, 1H, H4), 3.75 (m, 1H, CH(OH)CH3), 3.41,
3.40 (s, 3H, OCH3), 2.36 (brs, 1H, H5), 2.33 (brs, 1H, H1), 2.30,
2.29 (s, 3H, NCH3), 2.16 (m, 2H, CH2CH(OH)CH3), 1.55 (m,
2H, CH2CH2CH(OH)CH3), 1.12 (m, 3H, CH(OH)CH3); 13C NMR
149.5, 149.4 (CdCH), 128.9, 128.6 (CdCH), 85.2, 84.5 (C4),
67.8, 67.1 (CH(OH)CH3), 55.8, 55.7 (OCH3), 48.2, 48.1 (C5), 47.8
47.7 (C1), 44.7, 44.6 (NCH3), 37.2, 37.1 (CH2CH(OH)CH3), 25.2,
24.3 (CH2CH2CH(OH)CH3), 23.4, 23.3 (CH(OH)CH3); IR (neat)
3382, 2965, 2928, 1601, 1454, 1370, 1101; MS m/z (rel

4448 J . Org. Chem., Vol. 61, No. 13, 1996
Ling et al.
Meth an olysis of 3-Meth oxy-6-pr opyl-6-azabicyclo[3.1.0]-
h ex-2-en e (19). A solution of 19 (20 mg, 0.13 mmol) and
perchloric acid (0.13 mmol) in 2 mL of absolute methanol was
stirred at 25 °C for 4.5 h. The normal workup procedure A
and column chromatography (silica gel, ether-acetone) gave
10 mg (42%) of 22.
Hyd r olysis of 19. A solution of 19 (20 mg, 0.13 mmol) and
perchloric acid (0.13 mmol) in 1 mL of 1:9 H2O-THF was
stirred at 25 °C for 5.5 h. The reaction mixture was subjected
to the normal workup procedure A to yield 18 mg (81%) of
crude product 4-(N-propylamino)-5-methoxycyclopenten-3-ol
(47): 1H NMR 6.00 (d, 1H, vinyl), 5.92 (d, 1H, vinyl), 4.46 (d,
1H, H3), 4.05 (d, 1H, H5), 3.39 (s, 3H, OCH3), 3.08 (t,1H, H4),
2.79 (t, 2H, NCH2), 1.58 (m, 2H, NCH2CH2), 0.93 (t, J ) 7.4
Hz, 3H, NCH2CH2CH3); 13C NMR 135.4, 131.2 (CHdCH), 88.2
(C3), 79.5 (C5), 73.7 (OCH3), 56.3 (C4), 50.1 (NCH2), 22.7
(NCH2CH2), 11.6 (NCH2CH2CH3); MS m/z (rel intensity) 171-
(6), 154(37), 140(56), 122(40), 82(100); HRMS calcd m/z for
C9H15NO 171.1259, found 171.1248.
Rea ction of 19 w ith Acetic Acid . A solution of 19 (20
mg, 0.13 mmol) in 1 mL of acetic acid was stirred at 25 °C for
72 h. The normal workup procedure A and column chroma-
tography (silica gel, ether-CHCl3) gave 10 mg (36%) of
3-acetoxy-4-(N-propylamino)-5-methoxycyclopentene (48): 1H
NMR 6.10 (d, 1H, vinyl), 5.85 (d, 1H, vinyl), 5.31 (s, 1H, H3),
4.16 (s, 1H, H5), 3.40 (s, 3H, OCH3), 3.18 (t, 1H, H4), 2.69 (m,
2H,NCH2), 2.09 (s, 3H, OCOCH3), 1.55 (m, 2H, NCH2CH2), 0.95
(t, J ) 7,4 Hz, 3H, NCH2CH2CH3); 13C NMR 171.7 (CdO),
134.0, 131.4 (CHdCH), 88.5 (C3), 82.6 (C5), 70.6 (OCH3), 56.5
(C4), 49.8 (NCH2), 30.3 (OCOCH3), 22.8 (NCH2CH2), 11.6
(NCH2CH2CH3); MS m/z (rel intensity) 214(12), 154(100), 122-
(44), 80(24); HRMS calcd m/z for C11H20NO3 214.1443, found
214.1452.
Met h a n olysis of 4-Met h oxy-6-(ca r b a m oylm et h yl)-6-
a za bicyclo[3.1.0]h ex-2-en e (20). A solution of 20 (8 mg,
0.048 mmol) and perchloric acid (0.2 mL, 0.02 mmol) in MeOH
(10 mL) was stirred at 25 °C for 5 h. The normal workup
procedure A and column chromatography (silica gel, chloro-
form:ether 50/50) gave 9 mg (93%) of 4-((carbamoylmethyl)-
amino)-3,5-dimethoxycyclopentene (23).
Eth a n olysis of 20. A solution of 20 (25 mg, 0.15 mmol)
and perchlorate acid (1.0 mL, 0.10 mmol) in EtOH (20 mL)
was stirred at 25 °C for 72 h. The normal workup procedure
A and column chromatography (silica gel, chloroform:acetone
80/20) gave 25 mg (79%) of 4-((carbamoylmethyl)amino)-3-
methoxy-5-ethoxycyclopentene (49): 1H NMR 6.01 (s, 2H,
vinyl), 4.20 (d, J ) 5.2 Hz, 1H, H3 or H5), 4.13 (d, J ) 5.2 Hz,
1H, H3 or H5), 3.56 (s, 2H, CH2CONH2), 3.56 (q, J ) 7.0 Hz,
2H, OCH2CH3), 3.37 (s, 3H, OCH3), 3.23 (t, J ) 5.2 Hz, 1H,
H4), 1.10 (t, J ) 7.0 Hz, 3H, OCH2CH3); 13C NMR 173.5 (CdO),
132.6, 131.5 (CHdCH), 87.3, 86.0 (C3, C5), 70.6 (C4), 64.5
(OCH2CH3), 56.3 (OCH3), 50.0 (CH2CONH2), 15.6 (OCH2CH3);
IR (neat) 2977, 2884, 1653, 1374, 1087; MS m/z (rel intensity)
215 (2), 214 (1), 183 (21), 169 (10), 156 (9), 141 (12), 137 (100),
124 (19), 110 (25), 80 (23); HRMS calcd m/z for C10H18N2O3
214.1317, found 214.1322.
Rea ction of 20 w ith Acetic Acid . A solution of 20 (23 mg,
0.14 mmol) and acetic acid (0.3 mL, 5.2 mmol) in MeCN (20
mL) was stirred at reflux for 48 h. The normal workup
procedure A and column chromatography (silica gel, chloro-
form:acetone 80/20) afforded 11 mg (34%) of 4-((carbamoylm-
ethyl)amino)-3-acetoxy-5-methoxycyclopentene (50): 1H NMR
6.12 (d, J ) 6.1 Hz, 1H, vinyl), 5.86 (d, J ) 6.1 Hz, 1H, vinyl),
5.35 (d, J ) 4.2 Hz, 1H, H3), 4.17 (d, J ) 4.2 Hz, 1H, H5), 3.50
(s, 2H, CH2), 3.39 (s, 3H, OCH3), 3.26 (t, J ) 4.2 Hz, 1H, H4),
2.08 (s, 3H, OCOCH3); 13C NMR 174.6, 171.5 (CdO), 133.7,
131.3 (CHdCH), 87.7 (C3), 81.5 (C5), 70.7 (C4), 56.6 (OCH3),
49.9 (CH2), 21.0 (OCOCH3); IR (neat) 2933, 1733, 1652, 1368,
1256, 1078, 1025, 968; MS m/z (rel intensity) 229 (M + 1, 4),
184 (6), 137 (100), 110 (27), 94 (20), 80 (30); HRMS(CI) calcd
m/z for C10H17N2O4 229.1188, found 229.1182.
subjected to the normal workup procedure A to yield 12 mg
(99%) of 24.
Rea ction of 19 w ith Th ioa cetic Acid . A solution of 19
(20 mg, 0.13 mmol) in 0.5 mL of thioacetic acid was stirred at
25 °C for 4.5 h. The normal workup procedure A and column
chromatography (silica gel, hexane-CHCl3) yielded 26 mg
(74%) of 3-(thioacetoxy)-4-(N-propylamino)-5-methoxycyclo-
pentene (51): 1H NMR 5.96 (m, 1H, vinyl), 5.78 (m, 1H, vinyl),
4.92 (d, 1H, H3), 4.75 (d, 1H, H5), 3.61 (t, 1H, H4), 3.35 (s, 3H,
OCH3), 3.20 (m, 2H,NCH2), 2.28 (s, 3H, SCOCH3), 2.11 (s, 3H,
NCOCH3), 1.62 (m, 2H, NCH2CH2), 0.90 (t, J ) 7,4 Hz, 3H,
NCH2CH2CH3); 13C NMR 194.9 (SCOCH3), 170.9 (NCOCH3),
133.3, 131.4 (CH)CH), 87.5 (C3), 72.9 (C5), 56.8 (OCH3), 53.2
(NCH2), 48.7 (C4), 30.3 (SCOCH3), 22.9 (NCH2CH2), 22.5
(NCOCH3), 11.0 (NCH2CH2CH3); MS m/z (rel intensity) 272
(1), 196 (100), 154 (57), 128 (14), 84 (17); HRMS calcd m/z for
C13H22NO3S 272.1321, found 272.1322.
Meth a n olysis of 6-P r op yl-6-a za bicyclo[3.1.0]h ex-2-en -
3-ol (44). A solution of 44 (85 mg, 0.61 mmol) and perchloric
acid (0.61 mmol) in 2 mL of absolute methanol was stirred at
25 °C for 18 h. The normal workup procedure A and column
chromatography (silica gel, ether-acetone) gave 70 mg (67%)
of 47.
Rea ction of 44 w ith Th ioa cetic Acid . A solution of 44
(25 mg, 0.18 mmol) in 0.5 mL of thioacetic acid was stirred at
25 °C for 16 h. The normal workup procedure A and column
chromatography (silica gel, ether-CHCl3) gave 16 mg (34%)
of 3-(thioacetoxy)-4-(N-propyl-N-acetylamino)cyclopenten-5-ol
(52): 1H NMR 5.88 (m, 1H, vinyl), 5.70 (m, 1H, vinyl), 4.99
(d, 1H, H3), 4.79 (m, 1H, H5), 3.86 (t, 1H, H4), 3.23 (m, 2H,
NCH2), 2.31 (s, 3H, SCOCH3), 2.13 (s, 3H, NCOCH3), 1.60 (m,
2H, NCH2CH2), 0.90 (t, 3H, NCH2CH2CH3); 13C NMR 195.3
(SCOCH3), 171.8 (NCOCH3), 134.5, 132.3 (CHdCH), 79.7 (C3),
74.4 (C5), 52.1 (NCH2), 48.5 (C4), 30.5 (SCOCH3), 23.2
(NCH2CH2), 22.4 (NCOCH3), 11.1 (NCH2CH2CH3); MS m/z (rel
intensity) 257 (1), 182 (100), 140 (81); HRMS calcd m/z for
C12H19NO3S 257.1085, found 257.1108.
Meth a n olysis of 6-(2-Hyd r oxyeth yl)-6-a za bicyclo[3.1.0]-
h ex-3-en -2-ol (46). A solution of 46 (25 mg, 0.18 mmol) and
perchloric acid (0.3 mL, 0.03 mmol) in anhydrous MeOH (10
mL) was stirred at 60 °C for 48 h. The normal workup
procedure A gave 31 mg (99%) of 4-[N-(2-hydroxyethyl)amino]-
3-hydroxy-5-methoxycyclopentene (53): 1H NMR 5.96 (d, J )
5.9 Hz, 1H, vinyl), 5.88 (d, J ) 5.9 Hz, 1H, vinyl), 4.39 (d, J )
4.7 Hz, 1H, H3), 4.01 (d, J ) 4.7 Hz, 1H, H5), 3.71 (t, J ) 5.3
Hz, 2H, CH2OH), 3.38 (s, 3H, OCH3), 3.07 (t, J ) 4.7 Hz, 1H,
H4), 2.94 (t, J ) 5.3 Hz, 2H, CH2CH2OH); 13C NMR 135.5, 130.9
(CHdCH), 88.9 (C5), 79.6 (C3), 73.7 (C4), 61.2 (CH2OH), 56.3
(OCH3), 49.7 (CH2CH2OH); IR (neat) 3361, 2980, 1651, 1548,
1361, 1057; MS m/z (rel intensity) 174 (4), 173 (3), 156 (61),
142 (100), 124 (69), 110 (62), 97 (18), 81 (58); HRMS calcd m/z
for C8H15NO3 173.1052, found 173.1057.
Rea ction of 19 w ith Eth yl Ch lor ofor m a te. A solution
of 19 (70 mg, 0.46 mmol) and ethyl chloroformate (0.2 mL, 2.09
mmol) in 3mL of CHCl3 was stirred at 25 °C for 1 h and
concentrated in vacuo to yield 110 mg (92%) of 3-chloro-4-(N-
propylamino)-5-methoxycyclopentene (54) which was not sub-
jected to further purification: 1H NMR 6.01 (d, 1H, vinyl), 5.87
(m, 1H,vinyl), 5.16 (bs, 1H, H3), 4.68 (m, 1H, H5), 4.11(q, 2H,
NCO2CH2CH3 and t, 1H, H4), 3.36 (s, H, OCH3), 3.24 (t, 2H,
NCH2), 1.61 (m, 2H, NCH2CH2), 1.23 (t, 3H, NCO2CH2CH3),
0.83 (t, 3H, NCH2CH2CH3); 13C NMR 155.6 (CdO), 134.0, 132.5
(CHdCH), 95.5 (C3), 86.5 (C5), 65.3 (C4), 61.2 (NCO2CH2CH3),
56.9 (OCH3), 52.2 (NCH2) 22.8 (NCH2CH2), 14.5 (NCOCH2CH3),
10.9 (NCH2CH2CH3); MS m/z (rel intensity) 264 (2), 262 (4),
226 (100), 198 (11), 181 (11), 164 (15), 154 (8); HRMS calcd
m/z for C12H20NO335Cl 261.11361, found 261.11434, HRMS
calcd m/z for C12H20NO337Cl 263.1102, found 263.1106.
P r ep a r a tion of Azla cton e 56 by Cycliza tion of 54. A
solution of carbamate 54 (110 mg, 0.42 mmol) in 3 mL of CHCl3
was stirred at 65 °C for 17 h and then concentrated in vacuo
to yield a residue which was subjected to column chromatog-
raphy (silica gel, hexane-ether) to give 40 mg (48%) of
azlactone 56: 1H NMR 6.18 (m, 1H, vinyl), 6.10 (m, 1H, vinyl),
5.44 (m, 1H, H3), 4.32 (m, 1H, H5), 4.02 (d, 1H, H4), 3.38 (s,
3H, OCH3), 3.47, 3.06 (m, 2H, NCH2,), 1.67 (m, 2H, NCH2CH2),
Meth a n olysis of 4-Meth oxy-6-(h yd r oxyeth yl)-6-a za bi-
cyclo[3.1.0]h ex-2-en e (21). A solution of 21 (10 mg, 0.064
mmol) and perchloric acid (0.5 mL, 0.05 mmol) in anhydrous
MeOH (10 mL) was stirred at 25 °C for 6 h. The residue was

Pyridinium Salt Photoelectrocyclization-Solvolytic Aziridine Ring Opening J . Org. Chem., Vol. 61, No. 13, 1996 4449
0.93 (t, 3H, NCH2CH2CH3); 13C NMR 156.7 (CdO), 135.1,133.6
(CHdCH), 87.5 (C3), 80.8 (C5), 62.7 (C4), 56.9 (OCH3), 44.6
(NCH2), 20.5 (NCH2CH2),11.1 (NCH2CH2CH3); MS m/z (rel
intensity) 197(1), 153(13), 122(100), 110(31); HRMS calcd m/z
for C10H15NO3 197.1052, found 197.1705.
reaction mixture was subjected to the normal workup proce-
dure A to yield 700 mg of 69. The purity of 69 was determined
to be ca. 60% by 1H NMR. A solution of this material (490
mg, 3.12 mmol), diisopropylethylamine (3.7 mL, 21 mmol),
acetic anhydride (2 mL, 21 mmol), and 4-(dimethylamino)-
pyridine (60 mg) in 2 mL of CH3CN was stirred at 25 °C for
17 h. The reaction mixture was poured into ice-water,
neutralized with NaHCO3, trituated with CHCl3, filtered, and
concentrated to yield the crude product, which was subjected
to column chromatography (silica gel, CHCl3-ether) to give
230 mg (26% from pyridinium salt 16) of the diacetoxy amide
71: 1H NMR 5.90 (s, 2H, vinyl), 5.86 (d, 2H, H3, H5), 3.48 (t,
1H, H4), 3.14 (t, 2H, NCH2CH2CH3), 2.00 (s, 3H, NCOCH3),
1.97 (s, 6H, 2OCOCH3), 1.49 (m, 2H, NCH2CH2CH3), 0.82 (t,
3H, NCH2CH2CH3); 13C NMR 170.8 (OCOCH3), 170.2
(NCOCH3), 132.8 (CHdCH), 78.9 (C3, C5), 71.3 (C4), 53.0
(NCH2), 22.6 (NCH2CH2), 22.1 (OCOCH3), 20.8 (NCOCH3),
10.7 (NCH2CH2CH3); MS m/z (rel intensity) 283 (11), 224 (38),
181 (75), 140 (100), 122 (23); HRMS calcd m/z for C14H21NO5
283.1419, found 283.1406.
Ir r a d ia tion of 59 in H2O-HClO4. Sm a ll Sca le. An N2-
purged solution of 59 (211 mg, 1.17 mmol) and perchloric acid
(70%, 0.5 mL) in H2O (120 mL) was irradiated in a preparative
apparatus for 24 h. The photolysate was concentrated in vacuo
and the residue subjected to the normal workup procedure A
to yield 4-amino-3,5-dihydroxycyclopentene (70) (96% con-
version): 1H NMR (d6-acetone) 5.76 (s, 2H, vinyl), 4.43 (d, J
) 5.4 Hz, 2H, H3, H5), 2.82 (t, J ) 5.4 Hz, 1H, H4); 13C NMR
(d6-acetone) 136.0, (CHdCH), 81.5 (C3, C5), 76.0 (C4).
P r ep a r a tion of 5-Meth oxy-4-(N-m eth yl-N-p r op yla m i-
n o)cyclop en ten -3-ol (55) by Red u ction of 56. A solution
of 56 (32 mg, 0.16 mmol) and LiAlH4 (20 mg, 0.56 mmol) in 3
mL of anhydrous ether was stirred at 25 °C for 3 h under N2,
diluted with H2O, and then extracted with ether. The ethereal
extracts were concentrated in vacuo to yield 17 mg (62%) of
cyclopentenol 55: 1H NMR 6.10 (d, 2H, vinyl), 4.45 (m, 1H,
H5), 4.38 (m, 1H, H3), 3.34 (s, 3H, OCH3), 2.69 (t, 1H, H4), 2.45
(m, 2H, NCH2), 2.32 (s, 3H, NCH3), 1.52 (m, 2H, NCH2CH2),
0.86 (t, 3H, NCH2CH2CH3); 13C NMR 135.0, 133.7 (CHdCH),
85.7 (C5), 71.9 (C3), 71.7 (OCH3), 57.6 (NCH2), 56.3 (C4), 39.7
(NCH3), 20.3 (NCH2CH2), 11.6 (NCH2CH2CH3); MS m/z (rel
intensity) 171 (2), 154 (100), 142 (12), 128 (18), 122 (11); HRMS
calcd m/z for C9H17NO2 171.1259, found 171.1261.
Rea ction of 20 w ith Eth yl Ch lor ofor m a te. A solution
of 20 (20 mg, 0.12 mmol) and ethyl chloroformate (0.4 mL, 4.2
mmol) in CHCl3 (10 mL) was stirred at reflux for 12 h. The
reaction mixture was concentrated in vacuo, and the residue
was subjected to column chromatography (silica gel, acetone:
hexanes 80/20) to afford 12 mg (41%) of 5-(ethoxycarbonyl)-
7-methoxy-6-aza-2-oxabicyclo[4.3.0]non-8-en-3-one (57) and 6
mg (18%) of 4-(N-(carbamoylmethyl)-N-(ethoxycarbonyl)amino)-
3-chloro-5-methoxycyclopentene (58).
57: 1H NMR 6.26 (d, J ) 6.0 Hz, 1H, vinyl), 6.09 (d, J )
6.0 Hz, 1H, vinyl), 5.66 (d, J ) 6.8 Hz, 1H, H1), 4.37 (s, 1H,
H7), 4.20 (q, J ) 6.9 Hz, 2H, OCH2CH3), 3.45 (s, 3H, OCH3),
3.36 (m, 1H, H6), 1.28 (t, J ) 6.9 Hz, 3H, OCH2CH3); 13C NMR
166.7, 155.0 (CdO), 136.8, 133.9 (CHdCH), 88.0 (C1), 81.8 (C7),
62.6 (OCH2CH3), 57.7 (OCH3), 54.4 (C6), 42.9 (CH2), 14.5
(OCH2CH3); MS m/z (rel intensity) 242 (7), 241 (10), 196 (43),
182 (32), 168 (100), 152 (35), 138 (35), 124 (40), 94 (41), 84
(58); HRMS calcd m/z for C11H15NO5 241.0950, found 241.0955.
58: 1H NMR 5.90 (d, J ) 5.8 Hz, 1H, vinyl), 5.79 (d, J )
5.8 Hz, 1H, vinyl), 4.69 (s, 1H, H3), 4.19 (q, J ) 7.0 Hz, 2H,
OCH2CH3), 4.04 (s, 1H, H5), 3.80 (s, 2H, NCH2), 3.52 (s, 3H,
OCH3), 3.38 (t, J ) 4.0 Hz, 1H, H4), 1.26 (t, J )7.0 Hz, 3H,
OCH2CH3); 13C NMR 171.5, 157.0 (CdO), 134.4, 132.5
(CHdCH), 94.0 (C5), 67.2 (C3), 64.6 (OCH2CH3), 62.4 (OCH3),
58.3 (C4), 53.9 (NCH2), 14.5 (OCH2CH3); MS m/z (rel intensity)
277 (1), 241 (100), 137 (28); HRMS calcd m/z for C11H17ClN2O4
276.0877, found 276.0894.
Without purification, a solution of 70 in anhydrous pyridine
(10 mL) was stirred at 0 °C, and acetyl chloride (440 mg, 5.61
mmol) was then added dropwise. The solution was stirred at
0 °C under N2 for an additional 1 h. The reaction mixture
was poured into ice-water, neutralized with NaHCO3, and
extracted with CHCl3. The extracts were concentrated in
vacuo to give a residue (98 mg), which was subjected to column
chromatography (silica gel, chloroform and acetone-hexanes
60/40) to yield 72 mg (30%) of 4-acetamido-3,5-diacetoxy-
cyclopentene (72) as a crystalline material (mp 167-171 °C):
1H NMR 5.93 (s, 2H, vinyl), 5.56 (d, J ) 5.2 Hz, 2H, H3, H5),
4.22 (dt, J ) 5.2 Hz, J ) 7.6 Hz, 1H, H4), 2.05 (s, 6H, 2CO2-
CH3), 1.95 (s, 3H, NHCOCH3); 13C NMR 170.8, 170.7 (CdO),
132.9 (CHdCH), 80.1 (C3, C5), 62.6 (C4), 23.2, 20.9 (CO2CH3,
NHCOCH3); IR (neat) 3301, 3072, 2950, 1738, 1656, 1547,
1228, 1020; MS m/z (rel intensity) 242 (M + 1, 5), 241 (1), 198
(5), 182 (13), 139 (100), 97 (81); HRMS(CI) calcd m/z for C11H16
-
NO5 242.1028, found 242.1040.
Ir r a d ia tion of P yr id in iu m P er ch lor a te (59) in MeOH-
HClO4. An N2-purged solution of 59 (202 mg, 1.12 mmol) and
perchloric acid (70%, 0.5 mL) in anhydrous MeOH (100 mL)
was irradiated in a preparative apparatus for 9 h. The
photolysate was concentrated in vacuo and the residue sub-
jected to the normal workup procedure A to yield 48 mg (48%
yield at 62% conversion) of 4-amino-3,5-dimethoxycyclopentene
(61): 1H NMR 6.04 (s, 2H, vinyl), 5.72 (brs, 2H, NH2), 4.33 (d,
J ) 4.8 Hz, 2H, H3, H5), 3.47 (t, J ) 4.8 Hz, 1H, H4), 3.42 (s,
6H, 2OCH3); 13C NMR 132.0, (CHdCH), 86.1 (C3, C5), 62.4 (C4),
56.4 (OCH3); IR (neat) 3072, 2939, 2832, 1556, 1095; MS m/z
(rel intensity) 143 (2), 142 (3), 128 (17), 112 (75), 80 (100);
HRMS calcd m/z for C7H13NO2 143.0946, found 143.0943.
Ir r a d ia tion of N-P r op ylp yr id in iu m P er ch lor a te (16)
in H2O. Sm a ll Sca le. An N2-purged solution of 16 (200 mg,
0.90 mmol) in 100 mL of water was irradiated for 2 h and then
heated in the dark at 70 °C for 5 h. The reaction mixture was
subjected to the normal workup procedure A to yield 142 mg
(99%) of the aminocyclopentendiol 69. The purity of 69 was
La r ge Sca le. An N2-purged solution of 59 (1.60 g, 8.91
mmol) and perchloric acid (70%, 5.0 mL) in H2O (1000 mL)
was irradiated for 48 h. The photolysate was concentrated in
vacuo and the residue subjected to the normal workup pro-
cedure A to yield 70 (74% conversion as indicated by UV).
Without further purification, a solution of 70 in anhydrous
pyridine (60 mL) was stirred at 0 °C, and acetyl chloride (6.62
g, 84.4 mmol) was then added dropwise. The solution was stir-
red at 0 °C under N2 for 24 h. The reaction mixture was pour-
ed into ice-water, neutralized with NaHCO3, and extracted
with CHCl3. The extracts were concentrated in vacuo to give
a residue which was subjected to column chromatography
(silica gel, chloroform and acetone:hexanes 60/40) to yield 346
mg (22%) of 4-acetamido-3,5-acetoxycyclopentene (72).
Ack n ow led gm en t. Support for this research by the
National Science Foundation (CHE-94-20889) and NIH
(GM-27251) is gratefully acknowledged. Also we ex-
press our sincere appreciation for the very kind and
generous monetary gift provided by Dr. Keiyu Ueno
from Dojindo Laboratories in J apan.
1
determined to be ca. 40% by H NMR. This material was not
subjected to further purification. 69: 1H NMR (d6-acetone)
5.70 (s, 2H, vinyl), 4.37 (d, 2H, H3,H5), 2.93 (t, 1H, H4), 2.70
(t, 2H, NCH2CH2CH3), 1.48 (m, 2H, NCH2CH2CH3), 0.83 (t,
3H, NCH2CH2CH3); 13C NMR (d6-acetone) 134.7 (CHdCH),
79.6 (C3,C5), 68.9 (C4), 50.1 (NCH2CH2CH3), 23.2 (NCH2CH2-
CH3), 11.8 (NCH2CH2CH3); MS m/z (rel intensity) 157 (12),
140 (100), 122 (56), 110 (43), 96 (30); HRMS calcd m/z for
C8H15NO2 157.1102, found 157.1090.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra are provided for all new compounds characterized in
this work (77 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
La r ge Sca le. An N2-purged solution of 16 (1.0 g, 4.5 mmol)
in 500 mL of water was irradiated at 45-70 °C for 25 h. The
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