Preparation and intramolecular [2+2]-photocycloaddition of 1,5-dihydropyrrol-2-ones and 5,6-dihydro-1H-pyridin-2-ones with C-, N-, and O-linked alkenyl side chains at the 4-position

Article abstract of DOI:10.1021/jo7027129

(Chemical Equation Presented) The 1,5-dihydropyrrol-2-ones 2, 6, 9, and 11 were prepared from methyl tetramates (1a-c), N-Boc-protected tetramic acid (3), or N-Boc-protected tetramic acid bromide (7) in short reaction sequences and in very good overall yields. The homologous 5,6-dihydro-1H-pyridin-2-ones 16,18, 20, 21, 23, and 27 were prepared along analogous routes starting from piperidin-2,4-dione (19) or from its N-terf-butyl derivative 15. Optimized conditions for the [2+2]-photocycloaddition include the use of dichloromethane as the solvent and an irradiation with a mercury low-pressure lamp (λ = 254 nm). Upon applying these conditions at ambient temperature, the corresponding intramolecular photocycloaddition products 28-37 were obtained in good yields (52-79%) and with perfect diastereoselectivity. The constitution and configuration of the products was elucidated by NMR-spectroscopy. For the O-tethered substrates 2a and 20, a strong decrease of the photocycloaddition rate with temperature was observed. The effect was less pronounced for N- and C-tethered substrates 6, 9, 23, and 27. The use of a chiral complexing agent to achieve enantioselective reactions appears viable. Complexing agent (-)-38, however, is not suited because of its instability at λ = 254 nm.

Full text of DOI:10.1021/jo7027129

Preparation and Intramolecular [2+2]-Photocycloaddition of
1,5-Dihydropyrrol-2-ones and 5,6-Dihydro-1H-pyridin-2-ones with
C-, N-, and O-linked Alkenyl Side Chains at the 4-Position
Dominik Albrecht, Birte Basler, and Thorsten Bach*
Lehrstuhl fu¨r Organische Chemie I, Technische UniVersita¨t Mu¨nchen, D-85747 Garching, Germany
thorsten.bach@ch.tum.de
ReceiVed December 20, 2007
The 1,5-dihydropyrrol-2-ones 2, 6, 9, and 11 were prepared from methyl tetramates (1a-c), N-Boc-
protected tetramic acid (3), or N-Boc-protected tetramic acid bromide (7) in short reaction sequences
and in very good overall yields. The homologous 5,6-dihydro-1H-pyridin-2-ones 16, 18, 20, 21, 23, and
27 were prepared along analogous routes starting from piperidin-2,4-dione (19) or from its N-tert-butyl
derivative 15. Optimized conditions for the [2+2]-photocycloaddition include the use of dichloromethane
as the solvent and an irradiation with a mercury low-pressure lamp (λ ) 254 nm). Upon applying these
conditions at ambient temperature, the corresponding intramolecular photocycloaddition products 28-
37 were obtained in good yields (52-79%) and with perfect diastereoselectivity. The constitution and
configuration of the products was elucidated by NMR-spectroscopy. For the O-tethered substrates 2a
and 20, a strong decrease of the photocycloaddition rate with temperature was observed. The effect was
less pronounced for N- and C-tethered substrates 6, 9, 23, and 27. The use of a chiral complexing agent
to achieve enantioselective reactions appears viable. Complexing agent (-)-38, however, is not suited
because of its instability at λ ) 254 nm.
Introduction
Consecutive attack by another alkene moiety can occur either
intra- or intermolecularly, leading to a 1,4-biradical, which yields
the desired cyclobutane in a second C-C bond formation step.2
To ensure a reasonable lifetime of the excited-state, cyclic five-
or six-membered enones are preferred as substrates over
noncyclic enones, which can undergo rapid energy dissipation
by E/Z-isomerization. Due to their very general reactivity mode
The [2+2]-photocycloaddition reaction constitutes the easiest
and most convenient access to cyclobutanes.1 The key to a
successful reaction is the activation of one of the olefin reaction
partners by excitation with light. The R,â-unsaturated carbonyl
group represents a commonly used chromophor, which exhibits
a forbidden nπ*-transition at relatively long wavelength.
Intersystem crossing (ISC) is rapid and leads to a ππ*-triplet
state located mostly at the alkene part of the chromophor.
(2) For reviews of mechanistic studies on [2+2]-photocycloaddition
reactions, see: (a) Schuster, D. I. In CRC Handbook of Organic Photo-
chemistry and Photobiology, 2nd ed.; Horspool, W. M., Lenci, F., Eds.;
CRC Press: Boca Raton, FL, 2004; pp 72.1-72.24. (b) Weedon, A. C. In
CRC Handbook of Organic Photochemistry and Photobiology; Horspool,
W. M., Song, P.-S., Eds.; CRC Press: Boca Raton, FL, 1995; pp 634-
651. (c) Schuster, D. I. in CRC Handbook of Organic Photochemistry and
Photobiology; Horspool, W. M., Song P.-S., Eds.; CRC Press: Boca Raton,
FL, 1995; pp 652-669. (d) Mattay, J.; Conrads, R.; Hoffmann, R. In
Houben-Weyl Methods of Organic Chemistry, 4th ed.; Helmchen, G.,
Hoffmann, R. W., Mulzer, J., Schaumann, E., Eds.; Thieme: Stuttgart, 1995;
Vol. E 21c, pp 3085-3132. (e) Schuster, D. I.; Lem, G.; Kaprinidis, N. A.
Chem. ReV. 1993, 93, 3-22. (f) Gilbert, A.; Baggott, J. Essentials of
Molecular Photochemistry; Blackwell Science Ltd: Oxford, 1991; pp 267-
284.
(1) For general reviews on [2+2]-photocycloaddition reactions, see: (a)
Fleming, S. A. In Molecular and Supramolecular Photochemistry: Synthetic
Organic Photochemistry; Griesbeck, A. G., Mattay, J., Eds.; Dekker: New
York, 2005; Vol. 12, pp 141-160. (b) Margaretha, P. In Molecular and
Supramolecular Photochemistry: Synthetic Organic Photochemistry; Gries-
beck, A. G., Mattay, J., Eds.; Dekker: New York, 2005; Vol. 12, pp 211-
237. (c) Fleming, S. A.; Bradford, C. L.; Gao, J. J. In Molecular and
Supramolecular Photochemistry: Organic Photochemistry; Ramamurthy,
V., Schanze, K. S., Eds.; Dekker: New York, 1997; Vol. 1, pp 187-243.
(d) Pete, J.-P. AdV. Photochem. 1996, 21, 135-216. (e) Crimmins, M. T.;
Reinhold, T. L. Org. React. 1993, 44, 297-583. (f) Baldwin, S. W. Org.
Photochem. 1981, 5, 123-225.
10.1021/jo7027129 CCC: $40.75 © 2008 American Chemical Society
Published on Web 02/27/2008
J. Org. Chem. 2008, 73, 2345-2356
2345

Albrecht et al.
SCHEME 1. Intramolecular [2+2]-Photocycloaddition of
Tetronic Acid Derivatives A to Products B and of the Title
Compounds C to the Products D
SCHEME 2. Synthesis of 1,5-Dihydropyrrol-2-ones 2, 6, 9,
and 11 as [2+2]-Photocycloaddition Precursors
and their high reliability, enone [2+2]-photocycloaddition
reactions have been widely used in the synthesis of complex
molecules.3 If employed in the intramolecular mode, the reaction
leads to annelated cyclobutanes, whereby the tether connecting
the two reactive positions consists preferably of three or four
atoms yielding five- or six-membered ring annelation products.
When replacing cyclic enones with R,â-unsaturated lactones
or lactams as [2+2]-photocycloaddition substrates, one has to
consider the shorter absorption wavelengths of the latter
compound classes. Commonly, mercury low-pressure lamps are
used as irradiation sources, which emit a sharp light band at λ
) 254 nm. Provided that other functional groups in the starting
materials and products are photochemically stable under these
conditions, efficient [2+2]-photocycloaddition reactions of R,â-
unsatured lactones or lactams are possible, and they can lead
to valuable products.4,5 In this context, we have discovered
recently that O- and N-substituted 5H-furan-2-ones A, that is,
the esters and amides of tetronic acids, undergo a clean and
high yielding intramolecular [2+2]-photocycloaddition to the
corresponding tricyclic racemic products B (Scheme 1).6
Because the photocycloaddition proceeds with excellent simple
diastereoselectivity and because the lactone ring is readily
cleaved, compounds B represent attractive precursors for the
stereoselective synthesis of 2-aza-bicyclo[3.2.0]heptanes (n )
1, X ) NBoc) and 2-oxa-bicyclo[3.2.0]heptanes (n ) 1, X )
O). An application of this strategy to the synthesis of confor-
mationally constrained â-amino acid derivatives has been
described.7 In addition, it has been shown that the regio- and
diastereotopic discrimination of double bonds is possible in
tetronate [2+2]-photocycloaddition reactions.8
In this paper, we describe an extension of our studies to
tethered 1,5-dihydropyrrol-2-ones (C, m ) 1, tetramic acid
derivatives) and 5,6-dihydropyridin-2-ones (C, m ) 2). In
addition to variations previously performed with compounds
A, the ring size m and the additional nitrogen substituent R were
varied. The synthesis of the starting materials was elaborated,
and optimized reaction conditions for the photocycloaddition
were established. The relative configuration of products D was
elucidated. Preliminary studies were conducted to evaluate the
potential of free lactams (C, R ) H) for enantioselective
photochemical reactions in the presence of a chiral template.
Results and Discussion
(3) (a) Iriondo-Alberdi, J.; Greaney, M. F. Eur. J. Org. Chem. 2007,
4801-4815. (b) Namyslo, J. C.; Kaufmann, D. E. Chem. ReV. 2003, 103,
1485-1537. (c) Lee-Ruff, E.; Mladenova, G. Chem. ReV. 2003, 103, 1449-
1483. (d) Bach, T. Synthesis 1998, 683-703. (e) Winkler, J. D.; Bowen,
C. M.; Liotta, F. Chem. ReV. 1995, 95, 2003-2020. (f) Crimmins, M. T.
Chem. ReV. 1988, 88, 1453-1473. (g) Oppolzer, W. Acc. Chem. Res. 1982,
15, 135-141. (h) Bauslaugh, P. G. Synthesis 1970, 287-300.
(4) For intramolecular [2+2]-photocycloadditons of non-aromatic R,â-
unsatured lactones, see: (a) Coates, R. M.; Muskopf, J. W.; Senter, P. A.
J. Org. Chem. 1985, 50, 3541-3557. (b) Gimenez-Arnau, E.; Mabic, S.;
Lepoittevin, J.-P. Chem. Res. Toxicol. 1995, 8, 22-26. (c) Gomez, A. M.;
Mantecon, S.; Velazquez, S.; Valverde, S.; Herczegh, P.; Lopez, J. C. Synlett
1998, 1402-1404.
(5) For intramolecular [2+2]-photocycloadditons of non-aromatic R,â-
unsatured lactams, see: (a) Wrobel, M. N.; Margaretha, P. Chem. Commun.
1998, 541-542. (b) Wrobel, M. N.; Margaretha, P. HelV. Chim. Acta 2003,
86, 515-521.
(6) (a) Kemmler, M.; Bach, T. Angew. Chem., Int. Ed. 2003, 42, 4824-
4826. (b) Kemmler, M.; Herdtweck, E.; Bach, T. Eur. J. Org. Chem. 2004,
4582-4595.
(7) Basler, B.; Schuster, O.; Bach, T. J. Org. Chem. 2005, 70, 9798-
9808.
Preparation of 1,5-Dihydropyrrol-2-ones. The N-protected
methyl tetramates 1 (Scheme 2) were prepared from methyl
4-bromo-3-methoxy-2-butenoate9 and the corresponding amine.
Although compounds 1a10 and 1b11 have been previously
(8) Fleck, M.; Yang, C.; Wada, T.; Inoue, Y.; Bach, T. Chem. Commun.
2007, 822-824.
(9) (a) Weinreb, S. M.; Auerbach, J. J. Am. Chem. Soc. 1975, 97, 2503-
2506. (b) Welch, S. C.; Gruber, J. M. J. Org. Chem. 1982, 47, 385-389.
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40, 4129-4132. (d) Duthaler, R. O. HelV. Chim. Acta 1983, 66, 1475-
1492.
(10) (a) James, G. D.; Pattenden, G. Tetrahedron Lett. 1985, 26, 3617-
3620. (b) Duc, L.; McGarrity, J. F.; Meul, T.; Warm, A. Synthesis 1992,
391-394. (c) James, G. D.; Mills, S. D.; Pattenden, G. J. Chem. Soc., Perkin
Trans. 1, 1993, 2581-2584.
(11) (a) Jones, R. C. F.; Patience, J. M. J. Chem. Soc., Perkin Trans. 1,
1990, 2350-2351. (b) Jones, R. C. F.; Bates, A. D. Tetrahedron Lett. 1986,
27, 5285-5288.
2346 J. Org. Chem., Vol. 73, No. 6, 2008

Pyrrolone and Pyridone [2+2]-Photocycloaddition
reported, the yet unknown N-butyl product 1c was obtained in
70% yield. Transesterification to the photocycloaddition precur-
sors 2a-c was conducted at 100 °C in an excess of 3-buten-
1-ol as the solvent employing methanesulfonic acid (MsOH)
as the acidic catalyst. To provide alkenyl tetramate 1a with a
N-substituent that could be readily cleaved, we opted for a tert-
butyloxycarbonyl (Boc) protection. The use of acetonitrile as
solvent was decisive to obtain tetramate 2d in high yields (86%).
Attempts to obtain alkenyl amides of tetramic acids (C, m )
1, X ) N-R, Scheme 1) from methyl tetramates 1 by
aminodemethoxylation failed. Although various procedures for
the displacement of the methoxy group from methyl tetramates
by nitrogen nucleophiles have been reported,12 even the ap-
plication of harsh conditions allowed no conversion to the
desired products. Because tetronic acid bromide shows a strong
propensity for nucleophilic substitution reactions by primary
amines,13 an access to the corresponding bromide of tetramic
acid was desirable (Vide infra). Attempts to adopt conditions
reported for the conversion of 3-methoxy-2-cyclopentenone to
its vinylogous bromide led to complete decomposition of methyl
tetramates 1.14 Literature precedence for aminodehydroxylations
of tetronic acids15 and tetramic acids16 encouraged us to choose
the latter as precursors for the condensation with primary
amines. Many examples for the hydrolysis of tetramic esters
are reported.17 Nevertheless, saponification of methyl tetramates
1 appeared to be problematic, due to the fact that numerous
C-5 unsubstituted tetramic acids exhibit a strong tendency to
self-dimerization.16b,18 Therefore, the stable N-Boc-protected
tetramic acid 319 was selected as an easily accessible starting
material for further transformations. The vinylogous amide 4
could be obtained by condensation of but-3-enyl amine20 with
acid 3 by refluxing in benzene for 4 h in a Dean-Stark
apparatus. Acid-promoted aminodehydroxylation21 and the ap-
plication of microwave irradiation22 led to more rapid trans-
formations, but the product yields were lower. The necessity
of a protecting group for the tether nitrogen atom in 4 was
deduced from previous experience with photocycloaddition
products of N-unprotected tetronic acid amides, which proved
to be unstable and reacted further in a retro-Mannich reaction.7,23
The choice of protecting group was guided by previous
experience in our group.7,24 Alkoxycarbonyl protecting groups
such as N-tert-butyloxycarbonyl had turned out to be an
excellent choice to allow for the otherwise impossible [2+2]-
photocycloaddition reaction of enamines (λ ) 300-350 nm).25
The ethoxycarbonyl protecting group was chosen in this
particular instance because of its high stability and its orthogo-
nality to the Boc protecting group.26 Amide 4 was easily
protected using ethyl chloroformate in acetonitrile with an
admixture of DMAP and NEt3 furnishing protected amide 5 in
95% yield. Subsequent Boc-deprotection was performed with
trifluoroacetic acid (TFA) at ambient temperature in dichlo-
romethane in almost quantitative yield (99%).
Tetramic acid 3 could be transformed into the vinylogous
bromide 7 (Vide supra) by treatment with preformed Vilsmeier
reagent from oxalyl bromide and dimethylformamide (DMF)
in dichloromethane.27 The conventional procedure,28 according
to which DMF is added to a solution of (COBr)2 and the
substrate in dichloromethane, was not successful in our hands;
nor could DMF be used in catalytic amounts. Negishi cross-
coupling of 7 in DMA with pentenyl zinc bromide, prepared
(12) (a) Poschenrieder, H.; Ho¨fner, G.; Stachel, H.-D. Arch. Pharm.
(Weinheim, Ger.) 1999, 332, 309-316. (b) Stachel, H.-D.; Immerz-Winkler,
E.; Poschenrieder, H.; Windt, A.; Weigand, W.; Drescher, N.; Wu¨nsch, R.
HelV. Chim. Acta 2003, 86, 2471-2480.
(13) For similar reactions of tetronic acid bromide derivatives and amines,
see: (a) Farina, F.; Mart´ın, M. V.; Sa´nchez, F.; Maestro, M. C.; Mart´ın,
M. R. Synthesis 1983, 5, 397-398. (b) Jimenez, M. A.; Ortega, M. C.;
Tito, A.; Farina, F. Heterocycles 1984, 22, 1179-1187. (c) Mart´ın, M. R.;
Mateo, A. I. Tetrahedron: Asymmetry 1994, 5, 1385-1392. (d) Chen, Q.;
Geng, Z.; Huang, B. Tetrahedron: Asymmetry 1995, 6, 401-404.
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Welch, C. J.; Hillier, M. C.; Hughes, D. L.; Reider, P. J. J. Org. Chem.
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Schick, H.; Gru¨ndemann, E.; Ballschuh, D. J. Prakt. Chem. 1980, 322, 559-
568. (b) Grob Schmidt, D.; Seemuth, P. D.; Zimmer, H. J. Org. Chem.
1983, 48, 1914-1916. (c) Walter, K.-B.; Otto, H.-H. Arch. Pharm.
(Weinheim, Ger.) 1987, 320, 749-755. (d) Schlessinger, R. H.; Iwanowicz,
E. J. Tetrahedron Lett. 1988, 29, 1489-1492. (e) Momose, T.; Toyooka,
N.; Nishi, T.; Takeuchi, Y. Heterocycles 1988, 27, 1907-1923. (f)
Paulvannan, K.; Stille, J. R. J. Org. Chem. 1994, 59, 1613-1620. (g) Cook,
G. R.; Beholz, L. G.; Stille, J. R. J. Org. Chem. 1994, 59, 3575-3584. (h)
Pischetsrieder, M.; Larisch, B.; Mu¨ller, U.; Severin, T. J. Agric. Food Chem.
1995, 43, 3004-3006. (i) Hitotsuyanagi, Y.; Kobayashi, M.; Fukuyo, M.;
Takeya, K.; Itokawa, H. Tetrahedron Lett. 1997, 38, 8295-8296. (j) Amari,
M.; Fodili, M.; Nedjar-Kolli, B.; Hoffmann, P.; Perie, J. J. Heterocycl. Chem.
2002, 39, 811-816.
(16) (a) Soliman, F. S. G.; Kappe, T. Monatsh. Chem. 1982, 113, 475-
484. (b) Rida, S. M.; Soliman, F. S. G.; Badawy, E. A. M. Pharmazie 1986,
41, 563-565. (c) Kreher, R. P.; Dyker, G. Z. Naturforsch., B: Chem. Sci.
1987, 42, 473-477. (d) Sorokina, I. K.; Alekseeva, L. M.; Parshin, V. A.;
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J. Org. Chem, Vol. 73, No. 6, 2008 2347

Albrecht et al.
et al.,36 we decided to employ the yet unknown dione 15 as
starting material.37 The tert-butyl group appeared to be a suitable
protecting group due to its possible cleavage under acidic
conditions (Vide infra).38 Following Micovic’s strategy, we
started from commercially available potassium monomethyl
malonate (12). The in situ generated mixed anhydride formed
with pivaloyl chloride (PivCl) underwent smooth N-acylation
of â-amino acid methyl ester 13, which was prepared beforehand
from tert-butyl amine and methyl acrylate by conjugate addi-
tion.39 Amide 14 obtained in 75% yield was treated with sodium
hydride in refluxing cyclohexane. The cyclization product was
subjected to decarboxylation under reflux in aqueous acetic acid
yielding N-tert-butyl-piperidin-2,4-dione (15). Attempts to
perform an O-alkylation of this substrate under a variety of
conditions were less successful than in the tetramate case,
showing incomplete conversion and unsatisfactory chemose-
lectivity. A successful formation of the desired product 16 was
eventually achieved by heating 15 in neat but-3-en-1-ol in the
presence of H2SO4. For the preparation of amide 17, we chose
the conditions reported by Katzenellenbogen et al.40 for the
condensation of amines with dihydropyran-2,4-dione. Following
Katzenellenbogen’s procedure, the formation of vinylogous
amide 17 succeeded in 67% yield by stirring compound 15 with
excess but-3-enyl amine20 at ambient temperature in DMF.
Subsequent N-Boc-protection of the vinylogous amide 17
furnished the irradiation precursor 18 in quantitative yield.
Unfortunately, the desired N-deprotection of lactam 16 failed
under acidic conditions. The N-unprotected 5,6-dihydro-1H-
pyridin-2-ones, however, (Scheme 4) could be traced back to
piperidin-2,4-dione 19,41 which was available in turn by acidic
cleavage of the tert-butyl group from lactam 15. Because
attempts to isolate 19 were not fruitful, crude 19 was used for
further transformations. Acid-catalyzed esterification (Dean-
Stark trap) with but-3-en-1-ol transformed crude 19 into ester
20 in 90% yield over two steps. Subjecting pent-4-en-1-ol
instead of but-3-en-1-ol to identical reaction conditions gave
ester 21 in yields of 85% over two steps.
SCHEME 3. Synthesis of N-tert-Butyl-protected
5,6-Dihydropyridin-2-ones 16 and 18 as
[2+2]-Photocycloaddition Precursors
from 5-bromo-1-pentene via reductive zincation,29 proceeded
at ambient temperature within 14 h in 82% yield using Pd2-
(dba)3 (5 mol %) as catalyst and 20 mol % RuPhos (2-
dicyclohexylphosphino-2′′,6′′-diisopropoxy-1,1′′-biphenyl)30 as
ligand. Treatment with TFA in dichloromethane gave the desired
4-substituted 1,5-dihydropyrrol-2-one 9 in 99% yield.
For the synthesis of 1,5-dihydropyrrol-2-ones with O-linked
alkenyl side chains of varying lengths, acid 3 again turned out
to be a valuable starting material. Tetramic acid derivatives are
known to form methyl esters under Mitsunobu conditions31 or
by treatment with sulfuric acid dimethyl ester.32 Other O-
alkylations of tetramic acid derivatives by alkyl halides, except
for allylations and benzylations,33 have not been reported. For
various tetronic acid derivatives, cesium fluoride (CsF)34 or
NaH35 in DMF were shown to efficiently induce O-alkylation.
We found potassium tert-butoxide (KOtBu) most suitable to
generate ester 10 by O-alkylation of acid 3 with an appropriate
alkyl bromide. Almost quantitative (97%) cleavage of the Boc-
protecting group with TFA in dichloromethane furnished lactam
11.
To establish the other alkenyl linkers at the 4-position of 5,6-
dihydro-1H-pyridin-2-one, the corresponding 4-bromo precursor
22 stroke us as a suitable substrate. Vinylogous bromide 22
was accessible from â-ketolactam 15 within two steps with an
overall yield of 83%.27 Compound 22, the structural homologue
of bromide 7, underwent a clean Negishi cross-coupling reaction
with pentenyl zinc bromide to lactam 23 in 96% yield.
Preparation of 5,6-Dihydropyridin-2-ones. The 5,6-dihy-
dropyridin-2-ones (C, m ) 2, Scheme 1) were prepared to
compare their behavior in the [2+2]-photocycloaddition reac-
tions to the 1,5-dihydropyrrol-2-ones with identical side chains
at the 4-position. The N-protected 5,6-dihydropyridin-2-ones 16,
17, and 18 (Scheme 3) were obtained from N-tert-butyl-
piperidin-2,4-dione (15). Although syntheses of various N-
protected piperidin-2,4-diones had been reported by Micovic
Attempts to deprotect the tert-butyl protected lactams 17 and
18 under acidic conditions led to complete decomposition of
(36) Micovic, I. V.; Roglic, G. M.; Ivanovic, M. D.; Dosen-Micovic,
L.; Kiricojevic, V. D.; Popovic, J. B. J. Chem. Soc., Perkin Trans. 1 1996,
2041-2050.
(37) Oda, R.; Takashima, S.; Okano, M. Bull. Chem. Soc. Jpn. 1962,
35, 1843-1844.
(38) (a) Ko¨nig, K.-H.; Reitel, C.; Feuerherd, K.-H. Angew. Chem., Int.
Ed. 1980, 19, 201-202. (b) Giles, R. G. F.; Green, I. R.; Pestana, J. A. X.
J. Chem. Soc., Perkin Trans 1 1984, 2389-2396. (c) Reitz, D. B.; Massey,
S. M. J. Org. Chem. 1990, 55, 1375-1379. (d) Sattelkau, T.; Qandil, A.
M.; Nichols, D. E. Synthesis 2001, 262-266.
(39) (a) Deyrup, J. A.; Moyer, C. L. J. Org. Chem. 1969, 34, 175-179.
(b) Biggs, D. F.; Coutts, R. T.; Selley, M. L.; Towill, G. A. J. Pharm. Sci.
1972, 61, 1739-1745.
(40) Cesati, R. R.; Katzenellenbogen, J. A. Org. Lett. 2000, 2, 3635-
3638.
(29) Huo, S. Org. Lett. 2003, 5, 423-425.
(30) Milne, J. E.; Buchwald, S. L. J. Am. Chem. Soc. 2004, 126, 13028-
13032.
(31) (a) Patino, N.; Frerot, E.; Galeotti, N.; Poncet, J.; Coste, J.; Dufour,
M.-N.; Jouin, P. Tetrahedron 1992, 48, 4115-4122. (b) Suntornchashwej,
S.; Suwanborirux, K.; Isobe, M. Tetrahedron 2007, 63, 3217-3226.
(32) Pettit, G. R.; Thornton, T. J.; Mullaney, J. T.; Boyd, M. R.; Herald,
D. L.; Singh, S.-B.; Flahive, E. J. Tetrahedron 1994, 50, 12097-12108.
(33) Toyooka, N.; Nishio, M.; Shinoda, H.; Momose, T. Heterocycles
1999, 51, 1427-1432.
(34) Sato, T.; Yoshimatsu, K.; Otera, J. Synlett 1995, 843-846.
(35) (a) Gelin, S.; Pollet, P. Synth. Commun. 1980, 10, 805-812. (b)
Hlasta, D. J.; Ackerman, J. H.; Court, J. J.; Farrell, R. P.; Johnson, J. A.;
Kofron, J. L.; Robinson, D. T.; Talomie, T. G.; Dunlap, R. P.; Franke, C.
A. J. Med. Chem. 1995, 38, 4687-4692.
(41) (a) Lowe, G.; Yeung, H. W. J. Chem. Soc., Perkin Trans. 1 1973,
2907-2910. (b) Nakagawa, S.; Naito, T.; Kawaguchi, H. Heterocycles 1979,
13, 477-495. (c) Carroll, W. A.; Agrios, K. A.; Altenbach, R. J.; Buckner,
S. A.; Chen, Y.; Coghlan, M. J.; Daza, A. V.; Drizin, I. J. Med. Chem.
2004, 47, 3180-3192.
2348 J. Org. Chem., Vol. 73, No. 6, 2008

Pyrrolone and Pyridone [2+2]-Photocycloaddition
SCHEME 4. Synthesis of 5,6-Dihydro-1H-pyridin-2-ones 20,
21, 23, and 27 as [2+2]-Photocycloaddition Precursors
SCHEME 6. Intramolecular [2+2]-Photocycloaddition of
Tetramates 2
chemistry were not suitable for an irradiation of tetramates. At
λ ) 254 nm (irradiation source: Rayonet RPR-2537 Å),
reactions in acetonitrile, tert-butanol, or diethyl ether led to
significant decomposition, and the isolation of analytically pure
products was difficult or not feasible at all. The best result was
achieved in diethyl ether at a substrate concentration of 6 mM,
in the case of which 20% of product 28c (Scheme 5) was
isolated. Addition of acetone as a sensitizer (λ ) 300 nm) did
not result in a significant improvement. A major breakthrough
was achieved by employing dichloromethane as the solvent. At
a substrate concentration of 5 mM, analytically pure product
28c was isolated in 56% yield.
Similar reaction conditions were applied to the N-tert-butyl-
substituted 5,6-dihydro-1H-pyridin-2-ones 16 and 18, which
reacted equally well yielding the tricyclic products 29 and 30.
Again, ideal substrate concentrations were in the range of 5
mM, and the time in which the reaction was completed varied
from 1.25 h (30) to 3 h (29) to 7 h (28c). The extinction
maximum for the longest wavelength absorption of compound
16 was shifted by 11 nm to a longer wavelength when replacing
the solvent diethyl ether (λmax ) 218 nm) by dichloromethane
(λmax ) 229 nm). This observation may indicate that the
superiority of less polar dichloromethane as compared to the
more polar solvents is due to a solvatochromic effect. Indeed,
it was later shown that toluene and methylcyclohexane can also
be employed as solvents for some reactions, although substrate
solubility can become an issue (Vide infra).
SCHEME 5. Optimized Intramolecular
[2+2]-Photocycloaddition Reactions of Substrates 2c, 16, and
18 at c ) 5 mM in Dichloromethane
The different substituents at the nitrogen atom of tetramates
2 had a significant impact on the reaction course. The benzyl
group (tetramate 2b) proved to be unstable, and reaction yields
were diminished by competing side reactions (Scheme 6).
Similar observations were made in the reaction of N-Boc sub-
stituted substrate 2d. Besides complete deprotection, observed
at a substrate concentration of 5 mM, no other side reactions
were observed, however, and product 28a was obtained in 65%
yield. The instability of the Boc group took us by surprise
because neither in the above-mentioned reaction of substrate
18 nor in previous reactions with N-Boc protected tetronic acid
amides7 had there been an indication for a significant instability.
The reaction velocity of the transformation 2d f 28a was high,
presumably due to a rate acceleration by the electron withdraw-
ing protecting group. Conversion was complete after 1 h. At
higher substrate concentration (c ) 10 mM), some N-Boc
substituted product 28d was obtained (38%) together with
product 28a (27%). This finding supports the hypothesis that
deprotection occurs in the product 28d rather than in the
substrate 2d. Indeed, N-unsubstituted tetramate 2a reacted slowly
(full conversion after 4 h at c ) 7 mM) but cleanly, yielding
product 28a in a very good yield of 79% (Scheme 6).
the compounds. We circumvented this problem by employing
bromide 22 as the precursor for the nucleophilic substitution
by primary amines. Because substitution of bromide 22 with
primary amines would have led to a compound bearing a
N-unprotected lactam and a N-unprotected vinylogous amide,
lactam 22 was Boc-protected beforehand under standard condi-
tions with Boc2O, DMAP, and Hu¨nig’s base in acetonitrile (75%
yield). The subsequent substitution reaction to amide 25
proceeded in almost quantitative yield (99%). Installation of
an alkyloxy carbonyl protecting group as N-protecting group
was not trivial in the case of substrate 25 in contrast to its
structural analogue 17. A strong base such as LHMDS had to
be applied, and compound 26 was obtained in only 56% yield.
Application of amine bases or hydride bases did not show
satisfying conversion to the desired product. Finally, cleavage
of the Boc-protecting group from lactam 25 delivered [2+2]-
photocycloaddition precursor 27 in 99% yield.
Optimization of the Reaction Conditions and Proof of
Relative Configuration. Initial experiments to optimize the
irradiation conditions were conducted with N-butyl-substituted
tetramate 2c (Scheme 5). To our surprise, they revealed that
solvents previously employed in the tetronate photocycloaddition
The excellent result achieved with N-unprotected substrate
2a is testimony to the fact that electron-deficient nitrogen atoms,
J. Org. Chem, Vol. 73, No. 6, 2008 2349

Albrecht et al.
TABLE 1. Diastereoselective [2+2]-Photocycloaddition of Various
N-Unsubstituted 1,5-Dihydropyrrol-2-ones (m ) 1) and
5,6-Dihydro-1H-pyridin-2-ones (m ) 2)
entry substrate
m
Xa
n
t (h) product yield (%)b
1
2
3
4
5
6
7
8
2a
20
11
21
6
27
9
23
1
2
1
2
1
2
1
2
O
O
O
O
1
1
2
2
1
1
1
1
2.5
0.5
0.5
9
1
1
28a
31
32
33
34
35
36
37
79
60
70
55
72
58
61
52
NCOOEt
NCOOEt
CH2
1
1
CH2
a All reactions were conducted at a substrate concentration of 5 × 10-3
mol L-1 in dichloromethane as the solvent at ambient temperature using
Rayonet RPR-2537 Å lamps as irradiation source. b Yield of isolated
product.
FIGURE 1. 1H NMR spectroscopic determination of the regioselec-
tivity and simple diastereoselectivity in the [2+2]-photocycloaddition
of 1,5-dihydropyrrol-2-ones exemplified by product 28a and of 5,6-
dihydro-1H-pyridin-2-ones exemplified by product 31.
photocycloaddition of 5,6-dihydro-1H-pyridin-2-ones. Com-
pound 31 represents one member of this compound class, which
1
exhibits the diagnostic dd H NMR pattern for proton H-7 (3J
3
for example, in amides and lactams, frequently do not require
protecting groups in photochemical reactions. The statement is
supported by further reactions conducted both with 1,5-
dihydropyrrol-2-ones and with 5,6-dihydro-1H-pyridin-2-ones.
Nonetheless, it should be mentioned that the tert-butyl group
in product 29 could be removed by treatment with neat
trifluoroacetic acid under reflux yielding product 31 (Figure 1)
in 66% yield.
) 11.1 Hz, J ) 7.1 Hz) and NOE data, which compare well
with the data obtained for products 28a.
Variation of Substituent X and Tether Length n. In a
subsequent series of irradiation experiments, we investigated
the efficiency of the cycloaddition depending on the substitution
pattern at the 4-position of N-unsubstituted 1,5-dihydropyrrol-
2-ones and 5,6-dihydro-1H-pyridin-2-ones. The [2+2]-photo-
cycloaddition precursors were subjected to optimized irradiation
conditions (Vide supra) and the results are summarized in Table
1. In comparison to butenyloxy-substituted precursors 2a and
20 (entries 1, 2), pentenyloxy-substituted lactams 11 and 21
(entries 3, 4) performed the respective photocycloaddition
reactions with slightly lower yields of 70 and 55%. Interestingly,
the side chain elongation of 2a vs 20 resulted in shorter reaction
times, whereas extension of the side chain of 11 vs 21 led to a
decrease of the reaction rate. Amides 6 and 27 with N-linked
alkenyl side chains showed smooth formation of photoproducts
34 and 35 after 1 h irradiation time in yields of 72 and 58%
(entries 5, 6). Irradiation of lactams 9 and 23, bearing a non-
heteroatom-linked alkene tether attached to carbon atom C-4,
delivered the cycloaddition products 36 and 37 possessing the
all-carbon [3.2.0]bicycloheptane backbone in yields of 61 and
52% (entries 7, 8). In all cases, the simple diastereoselectivity
was high and only one diastereoisomer was detected. Applying
optimal reaction conditions delivered crude products of high
purity, and subsequent flash chromatography afforded analyti-
cally pure products. In general, it is apparent from the obtained
yields that 5,6-dihydro-1H-pyridin-2-ones (m ) 2) are slightly
inferior to their structural homologous 1,5-dihydropyrrol-2-ones
(m ) 1). In all cases, the use of anhydrous and degassed
dichloromethane was of decisive importance for the success of
the [2+2]-photocycloaddition reactions. In oxygen-containing
solvents, lower yields were observed due to decomposition
reactions, which were visible by coloration of the reaction
mixture and by formation of a precipitate, for example, when
irradiating amide 27.
All [2+2]-photocycloaddition reactions mentioned so far
proceeded with perfect regio- and simple diastereoselectivity.
The products shown were not contaminated with another regio-
nor with another diastereoisomer. Spectra of crude material did
not indicate formation of side products, either. The regioselective
formation of the straight vs the crossed photocycloaddition
product was unequivocally established by the NMR coupling
pattern in the individual products. The observations are il-
lustrated in Figure 1 for the 9-aza-2-oxa-tricyclo[5.3.0.01,5]-
decan-8-one skeleton generated by [2+2]-photocycloaddition
of butenyloxy-substituted tetramates 2. Product 28a serves as a
prototypical example. The proton in R-position to the carbonyl
group, which becomes proton H-7 in product 28a, resonates at
δ ) 2.81. A single doublet (d) was to be expected had the
photocycloaddition occurred in a crossed fashion. It exhibits,
however, a dd coupling pattern with two 3J coupling constants
of 10.0 and 4.0 Hz, indicating the formation of the straight
photocycloaddition product. The result is confirmed by looking
at proton H-6â, which derives from one of the former protons
at the terminal alkene carbon atom. If the connectivity is straight,
a ddd structure is expected originating from the 2J coupling to
3
H-6R and two J couplings to H-5 and H-7, which is indeed
observed. NOE contacts (Figure 1) prove the relative config-
uration, which is in line with the expectations based on the
diastereoselectivity in the photocycloaddition reactions of tetro-
nates (Scheme 1)6 and which was further corroborated by X-ray
crystallographic evidence.
The arguments provided above for the 9-aza-2-oxa-tricyclo-
[5.3.0.01,5]decan-8-one skeleton apply similarly to the 9-aza-2-
oxa-tricyclo[5.4.0.01,5]undecan-8-one skeleton generated by
The [2+2]-photocycloaddition reaction gives access to new
ring systems, which are difficult to prepare by other methods.
2350 J. Org. Chem., Vol. 73, No. 6, 2008

Pyrrolone and Pyridone [2+2]-Photocycloaddition
TABLE 2. Variation of Solvent and Temperature Θ in the
[2+2]-Photocycloaddition 20 f 31 and Observed Progress in
Conversion
FIGURE 2. Structure of the chiral complexing agent (-)-38.
In addition, the heteroatoms in products 28a, 31-37 invite ring
opening reactions that can lead to bicyclic products incorporating
a strained cyclobutane. Lactam ring opening, for example, gives
access to bicyclo[3.2.0]heptane or bicyclo[4.2.0]octanes with a
heteroatom (O for 28a, 31, 32, 33 or N for 34, 35) in the
2-position. Cleavage of the carbon-oxygen or carbon-nitrogen
bond of the linker produces a 3-azabicyclo[3.2.0]heptane
skeleton. In addition, one can consider ring opening reactions
occurring at the cyclobutane3b,c,42 ring, which makes various
spiro compounds accessible in a highly diastereoselective
fashion.
Solvent and Temperature Variation, Enantioselectivity.
A possible approach to conduct enantioselective photochemical
reactions in solution is based on the stoichiometric use of the
chiral complexing agent (-)-38 (Figure 2), which transfers its
chiral information to a corresponding substrate bound by
noncovalent interactions.43 The sterically demanding tetrahy-
dronaphthalene backbone of 38 shields one of the enantiotopic
faces of a bound substrate. So far, this principle has been
successfully employed in Norrish-Yang cyclizations,44 photo-
chemically induced Diels-Alder reactions,45 [6π]-cyclizations,46
[4+4]-photocycloaddition reactions,47 radical cyclizations,48 and
in intra- and intermolecular [2+2]-photocycloaddition reac-
tions.49 Enantioselectivities up to 95% ee were observed in
specific cases.
entry
solventa
Θ (°C)
t (h)
conversion (%)b
1
2
3
4
5
6
7
8
CH2Cl2
toluene
MCHc
CH2Cl2
MCH
toluene
toluene
toluene
-60
-60
-60
+30
+30
+30
0
3.0
3.0
3.0
0.5
2.0
3.0
1.0
1.0
5
6
0.5
100
100
100
7
-20
6
a All reactions were conducted at a substrate concentration of 7 × 10-3
mol L-1 using Rayonet RPR-2537 Å as the irradiation source. b Conversions
determined by GC-analysis. c MCH ) methylcyclohexane.
TABLE 3. Enantioselective [2+2]-Photocycloaddition 20 f (+)-31
in the Presence of Chiral Template (-)-38
entry
t (h)
conversion (%)b
ee [%]c
1
2
3
4
5
3.0
6.0
8.5
18.5
29.0
6
14
22
35
45
75
69
67
65
59
a All reactions were conducted at a substrate concentration of 7 × 10-3
mol L-1 using Rayonet RPR-2537 Å as the irradiation source in toluene at
-60 °C. b Conversions determined by GC-analysis. c The ee values were
calculated from the enantiomeric ratios, which were determined by GC
analysis.
Based on this precedence, N-unsubstituted lactams C (Scheme
1) appeared to us as possible substrates for enantioselective
[2+2]-photocycloaddition experiments. Facial stereocontrol
increases with an increasing amount of complexing agent (-)-
38, lower temperatures, and less polar solvents because these
parameters favor the formation of the template-substrate com-
plex. Different solvents and temperatures were consequently
tested in preliminary work for enantioselective [2+2]-photo-
cycloaddition reactions.
Due to its easy accessibility, 5,6-dihydro-1H-pyridin-2-one
20 was selected for optimizing reaction conditions. At ambient
temperature (Table 2, entries 4-6), completion of the [2+2]-
photocycloaddition reactions required only 30 min (in dichlo-
romethane) or a few hours in the case of less-polar solvents
like methylcyclohexane and toluene. Cooling down the reaction
mixture dramatically decreased the reaction rate. At -60 °C,
the standard temperature applied in many [2+2]-photocycload-
dition reactions,49 the reaction proceeded sluggishly with poor
conversions (0.5-6%) after 3 h (entries 1-3).
A possible reason why the reaction progress in methylcy-
clohexane is literally nearly frozen might be the high viscosity
of the solvent at -60 °C. Unfortunately, in toluene, the most
appropriate solvent for applications of complexing agent (-)-
38 in highly enantioselective [2+2]-photocycloaddition reac-
tions,49 an impressively drop of the reaction rate was already
observed by lowering the reaction temperature from 30 to 0 °C
(entries 7 and 8).
Although [2+2]-photocycloaddition precursor 20 revealed
only slow formation of product 31 by [2+2]-photocycloaddition
at -60 °C, we applied chiral template (-)-38 in 2.5 equiv to
investigate a potential induction of chirality. To our delight,
the addition of (-)-38 did not lead to a further decrease of the
reaction rate and afforded (+)-31 with 75% ee after 3 h of
irradiation and 6% conversion (Table 3). Upon continued
irradiation of the reaction mixture, the ee of product (+)-31
(42) (a) Fu, N.-Y.; Chan, S.-H.; Wong, H. N. C. In The Chemistry of
Functional Groups: The Chemistry of Cyclobutanes: The Application of
Cyclobutane DeriVatiVes in Organic Synthesis; Rappoport, Z., Liebman, J.
F., Eds.; Wiley: Chichester, 2005; pp 357-440. (b) Tanko, J. M. In The
Chemistry of Functional Groups: The Chemistry of Cyclobutanes: Rear-
rangements of Cyclobutanes; Rappoport, Z., Liebman, J. F., Eds.; Wiley:
Chichester, 2005; pp 497-519. (c) Horspool, W. M. in The Chemistry of
Functional Groups: The Chemistry of Cyclobutanes: Photochemistry of
Cyclobutanes: Synthesis and ReactiVity; Rappoport, Z., Liebman, J. F.,
Eds.; Wiley: Chichester, 2005; pp 715-805.
(43) (a) Wessig, P. Angew. Chem., Int. Ed. 2006, 45, 2168-2171. (b)
Bach, T. In Asymmetric Synthesis - The Essentials; Christmann, M., Bra¨se,
S., Eds.; Wiley-VCH: Weinheim, 2006; pp 166-170.
(44) Bach, T.; Aechtner, T.; Neumu¨ller, B. Chem.-Eur. J. 2002, 8,
2464-2475.
(45) (a) Grosch, B.; Orlebar, C. N.; Herdtweck, E.; Massa, W.; Bach, T.
Angew. Chem., Int. Ed. 2003, 42, 3693-3696. (b) Grosch, B.; Orlebar, C.
N.; Herdtweck, E.; Kaneda, M.; Wada, T.; Inoue, Y.; Bach, T. Chem.-
Eur. J. 2004, 10, 2179-2189.
(46) Bach, T.; Grosch, B.; Strassner, T.; Herdtweck, E. J. Org. Chem.
2003, 68, 1107-1116.
(47) Bach, T.; Bergmann, H.; Harms, K. Org. Lett. 2001, 3, 601-603.
(48) (a) Aechtner, T.; Dressel, M.; Bach, T. Angew. Chem., Int. Ed. 2004,
43, 5849-5851. (b) Dressel, M.; Bach, T. Org. Lett. 2006, 8, 3145-3147.
(49) (a) Bach, T.; Bergmann, H.; Harms, K. Angew. Chem. 2000, 112,
2391-2393; Angew. Chem., Int. Ed. 2000, 39, 2302-2304. (b) Bach, T.;
Bergmann, H. J. Am. Chem. Soc. 2000, 122, 11525-11526. (c) Bach, T.;
Bergmann, H.; Grosch, B.; Harms, K. J. Am. Chem. Soc. 2002, 124, 7982-
7990. (d) Brandes, S.; Selig, P.; Bach, T. Synlett 2004, 2588-2590. (e)
Selig, P.; Bach, T. J. Org. Chem. 2006, 71, 5662-5673.
J. Org. Chem, Vol. 73, No. 6, 2008 2351

Albrecht et al.
SCHEME 7. Intermolecular [2+2]-Photocycloaddition of
Tetronate 1a and Cyclopentene
IR (film) νmax 3103 (w, CHolef), 2956 (s, CH), 2926 (s, CH), 2870
(s, CH), 1680 (s, CdO), 1626 (s, CdC), 1454 (s), 1409 (s), 1354
(s), 1230 (s), 1173 (m), 1139 (m), 1067 (m), 999 (s), 915 (s), 802
(s), 744 (w), 629 (m) cm-1; MS (EI, m/z, %) 169 (38) [M+], 154
(2) [(M - CH3)+], 140 (3) [(M - C2H5)+], 126 (100) [(M -
C3H7)+], 113 (12) [(M - C4H8)+], 99 (3), 94 (18), 83 (9), 69 (9),
53 (9), 43 (14) [C3H7+]; HRMS (EI) calcd for C9H15NO2 169.1103,
found: 169.1103.
4-But-3-enyloxy-1,5-dihydro-pyrrol-2-one (2a). A total of 339
mg (3.00 mmol) of 4-methoxy-pyrrolin-2-one (1a)10 was dissolved
in 2.10 mL (1.73 g, 24.0 mmol) of 3-buten-1-ol at rt; 29.0 mg (0.33
mmol) of methanesulfonic acid was added, and the mixture was
stirred at 100 °C in an open flask for 1 h. The reaction was cooled
to rt and concentrated under reduced pressure. The resulting oil
was dissolved in EtOAc (40 mL), and the organic layer was washed
with H2O (40 mL), saturated aqueous NaHCO3, and brine (40 mL).
The organic layer was dried over MgSO4, filtered, concentrated,
and subjected to column chromatography (EtOAc/MeOH ) 19/1)
to afford 256 mg (1.67 mmol, 56%) of 4-but-3-enyloxy-1,5-dihydro-
pyrrol-2-one (2a) as colorless crystals. Rf ) 0.22 (EtOAc/MeOH
) 95/5); mp 123 °C; 1H NMR (360 MHz, CDCl3) δ 6.11 (br. s, 1
H), 5.81 (ddt, 3J ) 17.1, 3J ) 10.3, 3J ) 6.7 Hz, 1 H), 5.10-5.18
decreased, which is likely due to the fact that chiral template
(-)-38 decomposes significantly at an irradiation wavelength
of λ ) 254 nm. The recovery yield was low (<50%).
With the decomposition of template (-)-38 being a significant
drawback, further enantioselective experiments with the sub-
strates 2a, 6, 9, 11, 21, 23, and 27 were not extensively pursued.
In general, substrates with an oxygen atom in the tether showed
a strong rate decrease at lower reaction temperature. The
substrates 9 and 23 with an all-carbon tether exhibited the best
performance regarding their reaction rate but the achieved
enantioselectivities were not satisfactory. As a typical example,
substrate 23 furnished lactam (+)-37 in 80% yield and 34% ee
upon irradiation for 6 h in the presence of template (-)-38.
3
(m, 2 H), 5.06 (s, 1 H), 4.00 (t, J ) 6.7 Hz, 2 H), 3.93 (s, 2 H),
3
4
2.51 (virt. qt, J ≈ 6.7, J ≈ 1.3 Hz, 2 H); 13C NMR (90 MHz,
CDCl3) δ 175.7 (C), 175.2 (C), 133.4 (CH), 118.0 (CH2), 94.5 (CH),
70.8 (CH2), 47.0 (CH2), 33.0 (CH2); Anal. Calcd for C8H11NO2
(153.18): C, 62.73; H, 7.24; N, 9.14. Found: C, 62.45; H, 7.28;
N, 9.07; IR (film) νmax 3208 (s, NH), 3102 (m, CHolef), 2922
(s, CH), 2853 (s, CH), 1682 (s, CdO), 1614 (s, CdC), 1464
(s), 1428 (m), 1405 (m), 1376 (s), 1225 (s), 1090 (m), 1058 (m),
1010 (w), 984 (m), 935 (m), 911 (m), 866 (m), 822 (m), 729 (m)
cm-1; MS (EI, m/z, %) 153 (38) [M+], 125 (2), 122 (4), 110 (3),
99 (21) [(M - C4H6)+], 82 (5), 69 (15), 55 (100) [C4H7+], 43 (8),
39 (26); HRMS (EI) calcd for C8H11NO2 153.0790, found:
153.0789.
Conclusion
In summary, we could show that the title compounds undergo
a clean and diastereoselective intramolecular [2+2]-photocy-
cloaddition. An extension to intermolecular [2+2]-photocy-
cloaddition seems feasible. Upon irradiation of tetramate 1a in
the presence of cyclopentene (20 equiv) for 9 h at ambient
temperature, product 39 (exo/endo ) 4.6/1) was isolated in 64%
(Scheme 7).
All starting materials for the intramolecular reactions were
readily accessible from N-protected or unprotected â-ketolac-
tams, that is, from compounds 3, 15, and 19. Attempts to
conduct the intramolecular [2+2]-photocycloaddition enantio-
selectively were met with moderate success mostly because of
the insufficient stability of the chiral template (-)-38 under the
reactions conditions.
1-Benzyl-4-but-3-enyloxy-1,5-dihydro-pyrrol-2-one (2b). A
total of 610 mg (3.00 mmol) of 1-benzyl-4-methoxy-1,5-dihydro-
pyrrol-2-one (1b)11 was dissolved in 5.17 mL (4.33 g, 60.0 mmol)
of 3-buten-1-ol at rt; 32.0 mg (0.33 mmol) of methanesulfonic acid
was added, and the mixture was stirred at 100 °C in an open flask
for 1 h. The reaction was cooled to rt and concentrated under
reduced pressure. The resulting oil was dissolved in EtOAc (40
mL), and the organic layer was washed with H2O (40 mL), saturated
aqueous NaHCO3, and brine (40 mL). The organic layer was dried
over MgSO4, filtered, concentrated, and subjected to column
chromatography (P/EtOAc ) 1/2) to afford 616 mg (2.53 mmol,
84%) 1-benzyl-4-but-3-enyloxy-1,5-dihydro-pyrrol-2-one (2b) as
Experimental Section
Preparation of Starting Materials. 4-Methoxy-pyrrolin-2-one
(1a),10 1-benzyl-4-hydroxy-1,5-dihydro-pyrrol-2-one (1b),11 â-ami-
no acid methyl ester 13,39 the chiral complexing agent (-)-38,50
and but-3-enyl amine20 were synthesized according to reported
procedures. 5-Bromo-1-pentene and 3-buten-1-ol are commercially
available.
1
colorless crystals. Rf ) 0.35 (P/EtOAc ) 1/4); mp 39-41 °C; H
3
NMR (360 MHz, CDCl3) δ 7.21-7.35 (m, 5 H), 5.78 (ddt, J )
3
3
17.1, J ) 10.3, J ) 6.7 Hz, 1 H), 5.06-5.84 (m, 3 H), 4.57 (s,
3
3
2 H), 3.96 (t, J ) 6.7 Hz, 2 H), 3.72 (s, 2 H), 2.48 (virt. q, J ≈
6.7 Hz, 2 H); 13C NMR (90 MHz, CDCl3) δ 172.3 (C), 172.2 (C),
137.4 (C), 133.3 (CH), 128.7 (CH), 128.0 (CH), 127.5 (CH), 117.7
(CH2), 94.4 (CH), 70.2 (CH2), 50.1 (CH2), 45.4 (CH2), 32.8 (CH2);
IR (film) νmax 3100 (w, CHar), 3064 (w, CHolef), 3030 (w, CHar),
2916 (s, CH), 2852 (s, CH), 1666 (s, CdO), 1614 (s, CdC), 1494
(w), 1463 (s), 1407 (m), 1372 (s), 1216 (s), 1068 (w), 1028 (w),
989 (w), 923 (m), 823 (m), 739 (w), 695 (s) cm-1; MS (EI, m/z,
%) 243 (100) [M+], 215 (5), 189 (25) [(M - C4H6)+], 188 (80)
[(M - C4H7)+], 153 (4), 146 (7), 139 (7), 120 (10), 110 (20), 106
(20), 91 (90) [C7H7+], 85 (31), 69 (14), 55 (55) [C4H7+], 43 (12);
HRMS (EI) calcd for C15H17NO2 243.1259, found: 243.1258.
4-But-3-enyloxy-1-butyl-1,5-dihydro-pyrrol-2-one (2c). A total
of 728 mg (4.30 mmol) of 1-butyl-4-methoxy-1,5-dihydro-pyrrol-
2-one (1c) was dissolved in 5.00 mL (4.19 g, 58.1 mmol) of
3-buten-1-ol at rt; 41.0 mg (0.43 mmol) of methanesulfonic acid
was added, and the mixture was stirred at 100 °C in an open flask
for 1 h. The reaction was cooled to rt and concentrated under
reduced pressure. The resulting oil was dissolved in EtOAc (40
1-Butyl-4-methoxy-1,5-dihydro-pyrrol-2-one (1c). At 0 °C,
2.13 g (10.2 mmol) of 4-bromo-3-methoxy-2-butenoate9 was added
via syringe pump over 1 h to 4.94 mL (3.66 g, 50.0 mmol) of
n-butyl amine. The mixture was stirred for another 30 min at 0 °C
and then at rt for an additional 18 h. The mixture was poured into
a separatory funnel, and 50 mL of EtOAc was added. This solution
was washed with saturated aqueous solution NH4Cl (2 × 50 mL)
and brine (50 mL). The organic layer was dried over MgSO4,
filtered, concentrated, and subjected to column chromatography
(EtOAc 100%) to afford 1.21 g (7.15 mmol, 70%) 1-butyl-4-
methoxy-1,5-dihydro-pyrrol-2-one (1c) as a pale-yellow oil. Rf )
0.16 (EtOAc 100%); 1H NMR (360 MHz, CDCl3) δ 5.04 (s, 1 H),
3.81 (s, 2 H), 3.77 (s, 3 H), 3.36 (t, 3J ) 7.3 Hz, 2 H), 1.47-1.55
3
(m, 2 H), 1.27-1.37 (m, 2 H), 0.92 (t, J ) 7.3 Hz, 3 H); 13C
NMR (90 MHz, CDCl3) δ 172.9 (C), 171.9 (C), 94.6 (CH), 58.0
(CH3), 50.3 (C), 41.1 (CH2), 30.6 (CH2), 20.0 (CH2), 13.7 (CH3);
(50) Bach, T.; Bergmann, H.; Grosch, B.; Harms, K.; Herdtweck, E.
Synthesis 2001, 1395-1405.
2352 J. Org. Chem., Vol. 73, No. 6, 2008

Pyrrolone and Pyridone [2+2]-Photocycloaddition
mL), and the organic layer was washed with H2O (40 mL), saturated
aqueous NaHCO3, and brine (40 mL). The organic layer was dried
over MgSO4, filtered, concentrated, and subjected to column
chromatography (P/EtOAc ) 1/3) to afford 686 mg (3.28 mmol,
76%) of 4-but-3-enyloxy-1-butyl-1,5-dihydro-pyrrol-2-one (2c) as
a pale-yellow oil. Rf ) 0.36 (P/EtOAc ) 1/4); 1H NMR (360 MHz,
CDCl3) δ 5.80 (ddt, 3J ) 17.1, 3J ) 10.3, 3J ) 6.7 Hz, 1 H), 5.03-
5.17 (m, 3 H), 3.95 (t, 3J ) 6.6 Hz, 2 H), 3.81 (s, 2 H), 3.36 (t, 3J
) 7.0 Hz, 2 H), 2.43-2.55 (m, 2 H), 1.44-1.56 (m, 2 H), 1.24-
2-Oxo-4-pent-4-enyloxy-2,5-dihydro-pyrrole-1-carboxylic Acid
tert-Butyl Ester (10). To a solution of 500 mg (2.51 mmol) of
4-hydroxy-2-oxo-2,5-dihydro-pyrrole-1-carboxylic acid tert-butyl
ester (3) in 40 mL of dry DMF were added 310 mg (2.76 mmol)
of potassium tert-butoxide and 326 µL (2.76 mmol) of 5-bromo-
1-pentene at 0 °C. After the reaction mixture was stirred at rt for
14 h, the solvent was removed under reduced pressure. After
purification by flash chromatography (cyclohexane/EtOAc ) 1/1),
489 mg (1.83 mmol, 73%) of 2-oxo-4-pent-4-enyloxy-2,5-dihydro-
pyrrole-1-carboxylic acid tert-butyl ester (10) was obtained as
colorless crystals. Rf ) 0.40 (P/EtOAc ) 1/1); mp 64 °C; 1H NMR
3
1.38 (m, 2 H), 0.91 (t, J ) 7.3 Hz, 3 H); 13C NMR (90 MHz,
CDCl3) δ 172.1 (C), 171.9 (C), 133.3 (CH), 117.7 (CH2), 94.7 (CH),
70.2 (CH2), 50.5 (CH2), 41.1 (CH2), 32.8 (CH2), 30.6 (CH2), 19.9
(CH2), 13.7 (CH3); IR (film) νmax 3077 (w, CHolef), 2955 (s, CH),
2929 (s, CH), 2870 (m, CH), 1681 (vs, CdO), 1624 (vs, CdC),
1458 (s), 1401 (m), 1345 (s), 1217 (s), 1137 (w), 1067 (w), 987
(m), 916 (m), 802 (m) cm-1; MS (EI, m/z, %) 209 (29) [M+], 194
(9) [(M - CH3)+], 180 (6) [(M- C2H5)+], 166 (100) [(M -
C3H7)+], 155 (17) [(M - C4H6)+], 138 (4), 126 (9), 112 (59) [(166
- C4H6)+], 99 (9), 84 (33), 69 (7), 55 (23) [C4H7+], 42 (9); HRMS
(EI) calcd for C12H19NO2 209.1416, found: 209.1416.
3
(360 MHz, CDCl3) δ 5.79 (ddt, J ) 16.9, 10.2, 6.7 Hz, 1 H),
5.08-5.01 (m, 3 H), 4.17 (s, 2 H), 3.98 (t, 3J ) 6.4 Hz, 2 H), 2.18
(virt. q, 3J = 7.0 Hz, 2 H), 1.90-1.82 (m, 2 H), 1.53 (s, 9 H); 13
C
NMR (63 MHz, CDCl3) δ 173.8 (C), 169.4 (C), 149.5 (C), 136.9
(CH), 116.0 (CH2), 95.2 (CH), 82.6 (C), 71.1 (CH2), 49.5 (CH2),
29.8 (CH2), 28.2 (CH3), 27.6 (CH2); Anal. Calcd for C14H21NO4
(267.32): C, 62.90; H, 7.92; N, 5.24. Found: C, 62.91; H, 8.09;
N, 5.25; IR (film) νmax 3019 (w, CHolef), 2985 (w, CH), 1738 (s,
CdO), 1681 (s, CdO), 1631 (s, CdC), 1467 (w), 1454 (w), 1371
(m), 1332 (s), 1309 (s), 1244 (m), 1144 (m), 1088 (m), 978 (m),
921 (w), 852 (w), 820 (w), 772 (w), 701 (w), 675 (w) cm-1; MS
(EI, m/z, %) 252 (2) [(M - CH3)+], 212 (8) [(M - C4H7)+], 194
(30) [(M - OC4H9)+], 167 (54) [(M - C4H8 - CO2)+], 149 (26),
69 (61), 57 (100) [C4H9+], 41 (82); HRMS (EI) calcd for C14H21-
NO4 - C4H7 212.0923, found: 212.0921.
4-But-3-enylamino-2-oxo-2,5-dihydro-pyrrole-1-carboxylic Acid
tert-Butyl Ester (4). A solution of 5.00 g (25.1 mmol) of 2-oxo-
4-pent-4-enyloxy-2,5-dihydro-pyrrole-1-carboxylic acid tert-butyl
ester (3) and 3.57 g (50.2 mmol) of but-3-enyl amine20 in 20 mL
dry benzene was refluxed using Dean-Stark water separator for 4
h. Solvent and unreacted but-3-enyl amine were removed under
reduced pressure. After purification by flash chromatography
(cyclohexane/EtOAc ) 1/9), 3.42 g (13.6 mmol, 54%) of 4-but-
3-enylamino-2-oxo-2,5-dihydro-pyrrole-1-carboxylic acid tert-butyl
ester (4) was obtained as colorless crystals. Rf ) 0.62 (EtOAc/
N-tert-Butyl-N-(2-methoxycarbonyl-ethyl)-malonamic Acid
Methyl Ester (14). To a solution of 9.38 g (60.1 mmol) of
monomethyl malonate potassium salt in 120 mL of anhydrous Et2O
was added 6.83 mL (6.69 g, 55.5 mmol) of pivaloyl chloride at 0
°C. After the mixture was stirred at this temperature for 4 h,
successively 7.73 mL (5.64 g, 55.7 mmol) of NEt3, 0.81 g (6.63
mmol) of DMAP, and 8.02 g (50.4 mmol) of â-amino acid methyl
ester39 (13) were added. The mixture was stirred at rt for 18 h and
washed with saturated aqueous NaHCO3 (3 × 100 mL) and brine
(100 mL). The organic layer was dried over Na2SO4, filtered, and
concentrated. Flash column chromatography (P/EtOAc ) 7/3)
afforded 9.84 g (37.9 mmol, 75%) of N-tert-butyl-N-(2-methoxy-
carbonyl-ethyl)-malonamic acid methyl ester (14) as colorless oil.
1
MeOH ) 9/1); H NMR (360 MHz, CDCl3) δ 5.80-5.69 (m, 2
H), 5.11-5.06 (m, 2 H), 4.67 (s, 1 H), 4.20 (s, 2 H), 3.15 (virt. q,
3
3J ≈ 6.4 Hz, 2 H), 2.33 (virt. q, J ≈ 6.9 Hz, 2 H), 1.49 (s, 9 H);
13C NMR (90 MHz, CDCl3) δ 171.2 (C), 162.0 (C), 149.8 (C),
134.8 (CH), 117.7 (CH2), 88.0 (CH), 81.7 (C), 49.3 (CH2), 43.7
(CH2), 32.9 (CH2), 28.3 (CH3); Anal. Calcd for C13H20N2O3
(252.15) C, 61.88; H, 7.99; N, 11.10. Found: C, 62.23; H, 7.73;
N, 10.80; IR (film) νmax 3247 (m, NH), 2978 (w, CHolef), 2931 (w,
CH), 1774 (s, CdO), 1598 (s, CdC), 1532 (w), 1438 (w), 1377
(m), 1365 (m), 1252 (w), 1164 (m), 1083 (m), 998 (w), 906 (w),
775 (w), 733 (w) cm-1; MS (EI, m/z, %) 252 (11) [M+], 179 (20)
[(M - OC4H9)+], 152 (58) [(M - C4H8 - CO2)+], 111 (100), 57
(53) [C4H9+], 41 (23); HRMS (EI) calcd for C13H20N2O3 252.1474,
found: 252.1470.
1
Rf ) 0.31 (P/EtOAc ) 7/3); H NMR (360 MHz, CDCl3) δ 3.72
(s, 3 H), 3.68 (s, 3 H), 3.57-3.61 (m, 2 H), 3.46 (s, 2 H,), 2.56-
2.60 (m, 2 H), 1.43 (s, 9 H); 13C NMR (90.6 MHz, CDCl3) δ 171.1
(C), 168.4 (C), 166.7 (C), 57.9 (C), 52.3 (CH3), 51.9 (CH3), 43.5
(CH2), 41.5 (CH2), 36.1 (CH2), 28.8 (CH3); IR (film) νmax 2957
(m, CH), 1738 (s, CdO), 1652 (s, CdO), 1436 (s), 1399 (s), 1367
(s), 1324 (s), 1262 (s), 1200 (s), 1061 (m), 1023 (m), 899 (w), 840
(w) cm-1; MS (EI, m/z, %) 259 (6) [M+], 244 (10) [(M - CH3)+],
228 (3) [(M - OCH3)+], 204 (21), 186 (5) [(M - C3H5O2)+], 172
(31) [(M - C4H7O2)+], 158 (7) [(M- C4H5O3)+], 144 (100) [C7H14-
NO2+], 130 (26), 112 (13) [(M - CH4O)+], 102 (33) [C4H8NO2+],
70 (23), 57 (44) [C4H9+], 40 (21); HRMS (EI) calcd C12H21NO5
259.1420, found: 259.1416.
4-(But-3-enyl-ethoxycarbonyl-amino)-2-oxo-2,5-dihydro-pyr-
role-1-carboxylic Acid tert-Butyl Ester (5). One gram (3.96 mmol)
of 4-but-3-enylamino-2-oxo-2,5-dihydro-pyrrole-1-carboxylic acid
tert-butyl ester (4) was dissolved in 10 mL of dry acetonitrile. At
0 °C, 575 mg (4.75 mmol) of 4-dimethylaminopyridine, 830 µL
(5.94 mmol) of anhydrous NEt3, and 930 µL (11.88 mmol) of ethyl
chloroformate were added, and the solution was stirred at 0 °C for
30 min and then at rt for 16 h. The solvent was evaporated at
reduced pressure, and the resulting crude product was purified by
flash column chromatography (P/EtOAc ) 9/1) to give 1.22 g (3.76
mmol, 95%) of 4-(but-3-enyl-ethoxycarbonyl-amino)-2-oxo-2,5-
dihydro-pyrrole-1-carboxylic acid tert-butyl ester (5) as a colorless
N-tert-Butyl-piperidine-2,4-dione (15). A suspension of 3.10
g of NaH (60%; 77.5 mmol) in 120 mL of dry cyclohexane was
heated to reflux and a solution of 9.84 g of N-tert-butyl-N-(2-
methoxycarbonyl-ethyl)-malonamic acid methyl ester (14) (37.9
mmol) in 10 mL of anhydrous toluene was added dropwise over 1
h. Stirring and heating was continued for 2 h during which time
hydrogen was evolved and a pale-yellow precipitate was formed.
The mixture was cooled to rt and filtered. The precipitate was
washed with cyclohexane, dried under vacuum, and transferred to
a flask with 150 mL of 10% aq AcOH. The mixture was stirred at
reflux for 3 h until CO2 evolution ceased. After cooling to rt, the
mixture was neutralized with saturated aqueous NaHCO3 and
extracted with CH2Cl2 (3 × 50 mL). The combined extracts were
dried over MgSO4, filtered, and concentrated. Purification by flash
chromatography (P/EtOAc ) 1/1) yielded 5.13 g (30.3 mmol, 80%)
of N-tert-butyl-piperidine-2,4-dione (15) as colorless crystals. Rf
1
oil. Rf ) 0.30 (P/EtOAc ) 9/1); H NMR (360 MHz, CDCl3) δ
5.74-5.62 (m, 1 H), 5.29 (s, 1 H), 5.04-4.99 (m, 2 H), 4.71 (s, 2
3
3
H), 4.22 (q, J ) 7.1 Hz, 2 H), 3.65 (t, J ) 7.5 Hz, 2 H), 2.33-
2.27 (m, 2 H), 1.48 (s, 9 H), 1.29 (t, 3J ) 7.1 Hz, 3 H); 13C NMR
(90 MHz, CDCl3) δ 168.6 (C), 156.6 (C), 152.8 (C), 149.2 (C),
133.6 (CH), 117.8 (CH2), 102.6 (CH), 82.5 (C), 63.4 (CH2), 51.7
(CH2), 47.1 (CH2), 31.2 (CH2), 28.1 (CH3), 14.2 (CH3); IR (film)
νmax 2977 (w, CHolef), 2928 (w, CH), 1776 (m, CdO), 1722 (vs,
CdO), 1601 (s, CdC), 1437 (w), 1394 (m), 1332 (s), 1293 (m),
1228 (m), 1158 (m), 1099 (m), 1075 (m), 1038 (w) cm-1; MS (EI,
m/z, %) 324 (4) [M+], 251 (31) [(M - OC4H9)+], 224 (100) [(M
- C4H8 - CO2)+], 206 (58), 111 (65), 57 (95) [C4H9+]; HRMS
(EI) calcd for C16H24N2O5 324.1685, found: 324.1683.
1
) 0.24 (P/EtOAc ) 1/1); mp 92-96 °C; H NMR (360 MHz,
J. Org. Chem, Vol. 73, No. 6, 2008 2353

Albrecht et al.
CDCl3) δ 3.65 (t, 3J ) 6.0 Hz, 2 H), 3.34 (s, 2 H), 2.50 (t, 3J ) 6.0
Hz, 2 H), 1.47 (s, 9 H); 13C NMR (90.6 MHz, CDCl3) δ 204.7 (C),
166.8 (C), 57.9 (C), 52.2 (CH2), 39.7 (CH2), 39.5 (CH2), 28.7 (CH3);
Anal. Calcd for C9H15NO2 (169.2209): C, 63.88; H, 8.93; N, 8.28.
Found: C, 63.76; H, 9.17; N, 8.23; IR (film) νmax 2922 (s, CH),
2853 (s, CH), 1650 (w, CdO), 1614 (m, CdO), 1556 (s), 1463
(s), 1430 (s), 1357 (s), 1319 (s), 1280 (m), 1227 (s), 1190 (s), 994
(w), 835 (m), 689 (w) cm-1; MS (EI, m/z, %) 169 (77) [M+], 154
(77) [(M - CH3)+], 141 (3), 126 (19) [C6H8NO2+], 114 (66), 112
(26) [(M - C4H9)+], 84 (11) [(112 - CO)+], 70 (100), 57 (47)
[C4H9+], 41 (34); HRMS (EI) calcd C9H15NO2 169.1103, found:
169.1104.
of 4-but-3-enyloxy-5,6-dihydro-1H-pyridin-2-one (20) was obtained
as colorless crystals. Rf ) 0.30 (EtOAc/MeOH ) 95/5); mp 66
°C; 1H NMR (360 MHz, CDCl3) δ 5.81 (ddt, 3J ) 17.1, 3J ) 10.3,
3J ) 6.8 Hz, 1 H), 5.68 (br. s, 1 H), 5.08-5.16 (m, 2 H), 5.04 (s,
3
3
3
1 H), 3.88 (t, J ) 6.6 Hz, 2 H), 3.40 (virt. td, J ≈ 7.2, J ≈ 2.5
Hz, 2 H), 2.42-2.51 (m, 4 H); 13C NMR (90 MHz, CDCl3) δ 169.7
(C), 169.4 (C), 133.7 (CH), 117.4 (CH2), 94.1 (CH), 67.4 (CH2),
38.7 (CH2), 32.8 (CH2), 27.9 (CH2); IR (film) νmax 3193 (m, NH),
3074 (m, CHolef), 2954 (m, CH), 2922 (s, CH), 2856 (s, CH), 1694
(s, CdO), 1610 (s, CdC), 1463 (s), 1427 (m), 1366 (s), 1344 (s),
1223 (s), 1187 (s), 1129 (w), 1056 (m), 996 (m), 907 (m), 810 (s),
718 (w), 690 (w) cm-1; MS (EI, m/z, %) 167 (25) [M+], 152 (3)
[(M - CH3)+], 139 (6), 111 (10) [(152 - C3H5)+], 96 (31), 85
(13), 69 (13), 55 (100) [C4H7+], 43 (26); HRMS (EI) calcd for
C9H13NO2 167.0946, found: 167.0946.
4-But-3-enyloxy-1-tert-butyl-5,6-dihydro-1H-pyridin-2-one (16).
To a solution of 507 mg (3.00 mmol) of N-tert-butyl-piperidine-
2,4-dione (15) in 1.29 mL (1.08 g, 15.0 mmol) of 3-buten-1-ol was
added two drops of concentrated H2SO4. The reaction mixture was
stirred at 90 °C for 5 h and cooled to rt After 3-buten-1-ol was
removed under reduced pressure, the resulting crude product was
subjected to column chromatography to afford 312 mg (1.40 mmol,
47%) of 4-but-3-enyloxy-1-tert-butyl-5,6-dihydro-1H-pyridin-2-one
(16) as colorless crystals. Rf ) 0.28 (P/EtOAc ) 3/1); mp 51 °C;
1H NMR (360 MHz, CDCl3) δ 5.80 (ddt, 3J ) 17.1, 3J ) 10.3, 3J
4-But-3-enylamino-6-oxo-3,6-dihydro-2H-pyridine-1-carboxy-
lic acid tert-butyl ester (25). A total of 786 mg (2.85 mmol) of
4-bromo-6-oxo-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl
ester (24) was dissolved in 2 mL of dry tetrahydrofuran, and 404
mg (5.69 mmol) of but-3-enyl amine20 and 975 µL (5.69 mmol) of
anhydrous diisopropyl ethylamine were added. The reaction mixture
was stirred at rt for 60 h and filtered. The filtrate was evaporated
to dryness, and the crude product was purified by column
chromatography (EtOAc ) 100%) to give 753 mg (2.83 mmol,
99%) of 4-but-3-enylamino-6-oxo-3,6-dihydro-2H-pyridine-1-car-
boxylic acid tert-butyl ester (25) as pale-yellow crystals. Rf ) 0.34
3
) 6.7 Hz, 1 H), 5.06-5.15 (m, 2 H), 4.98 (s, 1 H), 3.83 (t, J )
6.7 Hz, 2 H), 3.39 (t, 3J ) 6.9 Hz, 2 H), 2.45 (virt. qt, 3J ≈ 6.7, 4J
≈ 1.2 Hz, 2 H), 2.34 (t, 3J ) 6.9 Hz, 2 H), 1.43 (s, 9 H); 13C NMR
(90 MHz, CDCl3) δ 168.7 (C), 167.2 (C), 133.9 (CH), 117.2 (CH2),
97.3 (CH), 67.3 (CH2), 56.2 (C), 41.0 (CH2), 32.9 (CH2), 28.9
(CH2), 28.8 (CH3); IR (film) νmax 3078 (w, CHolef), 2957 (s, CH),
2914 (s, CH), 1654 (s, CdO), 1627 (s, CdC), 1466 (m), 1412 (s),
1370 (s), 1322 (s), 1293 (w), 1188 (s), 1030 (m), 996 (m), 947
(w), 918 (w), 830 (m), 804 (w) cm-1; MS (EI, m/z, %) 223 (41)
[M+], 208 (75) [(M - CH3)+], 180 (18), 167 (16) [(208 - C3H5)+],
154 (15) [(208 - C4H6)+], 139 (24), 124 (11), 112 (21), 97 (11),
84 (20), 70 (58), 55 (100) [C4H7+], 40 (19); HRMS (EI) calcd for
C13H21NO2 223.1572, found: 223.1571.
1
(EtOAc 100%); mp 104-106 °C; H NMR (360 MHz, CDCl3) δ
5.79-5.68 (m, 1 H), 5.14-5.09 (m, 2 H), 4.77 (s, 1 H), 4.42 (br.
s, 1 H), 3.82 (t, 3J ) 6.4 Hz, 2 H), 3.15 (virt. q, 3J ≈ 6.2 Hz, 2 H),
2.39-2.31 (m, 4 H), 1.51 (s, 9 H); 13C NMR (90 MHz, CDCl3) δ
167.0 (C), 159.4 (C), 152.5 (C), 134.8 (CH), 117.1 (CH2), 87.6
(CH), 81.5 (C), 42.8 (CH2), 42.0 (CH2), 32.3 (CH2), 28.6 (CH2),
28.1 (CH3); Anal. Calcd for C14H22N2O3 (266.16): C, 63.13; H,
8.33; N, 10.52. Found: C, 63.05; H, 8.46; N, 10.33; IR (film) νmax
3279 (vs, NH), 3085 (w, CHolef), 2933 (w, CH), 1700 (s), 1634 (s,
CdO), 1595 (s), 1551 (vs, CdC), 1474 (m), 1365 (m), 1319 (m),
1307 (m), 1225 (m), 1208 (m), 1142 (s), 1056 (w), 921 (w), 854
(w) cm-1; MS (EI, m/z, %) 266 (24) [M+], 193 (21) [(M -
OC4H9)+], 166 (100) [(M - C4H8 - CO2)+], 125 (100), 57 (74)
[C4H9+]; HRMS (EI) calcd for C14H22N2O3 266.1631, found:
266.1635.
4-But-3-enylamino-1-tert-butyl-5,6-dihydro-1H-pyridin-2-
one (17). To a solution of 169 mg (1.00 mmol) of N-tert-butyl-
piperidine-2,4-dione (15) in 3 mL of dry DMF 213 mg (3.00 mmol)
was added but-3-enyl amine20 at rt. After the reaction mixture was
stirred at rt for 18 h, the reaction was quenched with 75 mL H2O.
The aqueous layer was extracted with EtOAc (2 × 50 mL). The
combined organic layers were dried over MgSO4, filtered, concen-
trated, and subjected to column chromatography (P/EtOAc ) 1/1)
to afford 149 mg (0.67 mmol, 67%) of 4-but-3-enylamino-1-tert-
butyl-5,6-dihydro-1H-pyridin-2-one (17) as a pale-yellow oil. Rf
) 0.23 (P/EtOAc ) 1/1); 1H NMR (360 MHz, CDCl3) δ 5.75 (ddt,
3J ) 17.1, 3J ) 10.2, 3J ) 6.6 Hz, 1 H), 5.08-5.13 (m, 2 H), 4.68
(s, 1 H), 3.71 (br. s, 1 H), 3.36 (t, 3J ) 6.6 Hz, 2 H), 3.07 (virt. q,
General Procedure for the [2+2]-Photocycloaddition Reac-
tions. In a quartz vessel, a solution of the respective tetramic acid
derivate or its six-membered ring homologue in anhydrous,
degassed (argon purge under ultrasound for 20 min) dichlo-
romethane was irradiated at rt and 254 nm until GC and TLC
analysis indicated complete conversion (light source: Rayonet RPR-
2537 Å). The solvent was then evaporated under reduced pressure,
and the remaining residue was purified by column chromatography
to give the desired compound.
3
3
3J ≈ 6.6 Hz, 2 H), 2.33 (virt. q, J ≈ 6.6 Hz, 2 H), 2.25 (t, J )
6.6 Hz, 2 H), 1.43 (s, 9 H); 13C NMR (90 MHz, CDCl3) δ 170.2
(C), 154.1 (C), 135.1 (CH), 117.3 (CH2), 91.3 (CH), 55.8 (C), 41.7
(CH2), 41.1 (CH2), 32.7 (CH2), 30.0 (CH2), 28.9 (CH3); IR (film)
νmax 3218 (s, NH), 3031 (s, CdC), 2922 (s, CH), 2860 (s, CH),
1629 (s, CdO), 1588 (s), 1454 (s), 1360 (s), 1321 (s), 1242 (s),
1204 (s), 1150 (m), 1099 (w), 994 (m), 919 (m), 806 (m), 790 (m),
690 (m) cm-1; MS (EI, m/z, %) 222 (49) [M+], 207 (54) [(M -
CH3)+], 194 (18), 166 (50) [(M - C4H8)+], 151 (28), 137 (18),
125 (100) [(166 - C3H5)+], 108 (26), 95 (33), 70 (79) [C4H8N+],
57 (38) [C4H9+]; HRMS (EI) calcd for C13H22N2O 222.1732,
found: 222.1731.
Hexahydro-1-oxa-6-aza-cyclobuta[1,2:1,4]dicyclopenten-5-
one (28a). The compound was prepared from 77.0 mg (0.50 mmol)
of 4-but-3-enyloxy-1,5-dihydro-pyrrol-2-one (2a) in 72 mL of
anhydrous dichloromethane by irradiation for 4 h. Column chro-
matography (EtOAc/MeOH ) 19/1) yielded 61.0 mg (0.40 mmol,
79%) of the desired product as colorless crystals. Rf ) 0.20 (EtOAc/
1
MeOH ) 95/5); mp 138 °C; H NMR (360 MHz, CDCl3) δ 6.76
2
3
3
(br. s, 1 H), 4.23 (virt. t, J ≈ J ≈ 8.7 Hz, 1 H), 3.98 (ddd, J )
2
3
2
11.5, J ) 8.7, J ) 5.3 Hz, 1 H), 3.53 (d, J ) 10.3 Hz, 1 H),
2
3
3.45 (d, J ) 10.3 Hz, 1 H), 2.90-2.96 (m, 1 H), 2.81 (dd, J )
4-But-3-enyloxy-5,6-dihydro-1H-pyridin-2-one (20). A solution
of 1.67 g (10.0 mmol) of N-tert-butyl-piperidine-2,4-dione (15) in
20 mL triflouroacetic acid was refluxed for 1 h. After removal of
the solvent, the crude product was dissolved in 20 mL of dry
benzene; 2.60 mL (30.0 mmol) of 3-buten-1-ol and 2 drops of concd
H2SO4 were added before the reaction mixture was refluxed using
a Dean-Stark water separator for 2 h. Solvent and 3-buten-1-ol
were removed under reduced pressure. After purification by flash
chromatography (EtOAc/MeOH ) 95/5), 1.50 g (9.0 mmol, 90%)
3
2
3
3
10.0, J ) 4.0 Hz, 1 H), 2.22 (ddd, J ) 12.9, J ) 8.6, J ) 4.0
2
3
Hz, 1 H), 1.88-2.00 (m, 2 H), 1.73 (dd, J ) 12.6, J ) 5.3 Hz,
1 H); 13C NMR (90 MHz, CDCl3) δ 179.0 (C), 86.8 (C), 68.5 (CH2),
49.5 (CH2), 42.8 (CH), 42.5 (CH), 31.8 (CH2), 25.9 (CH2); IR (film)
νmax 3188 (br. m, NH), 2922 (s, CH), 2853 (s, CH), 1679 (s, Cd
O), 1481 (m), 1456 (m), 1375 (m), 1316 (m), 1238 (m), 1190 (m),
1070 (m), 990 (m), 954 (w), 898 (w), 803 (m), 713 (w), 670 (m),
636 (m) cm-1; MS (EI, m/z, %) 153 (49) [M+], 122 (25), 99 (45),
2354 J. Org. Chem., Vol. 73, No. 6, 2008

Pyrrolone and Pyridone [2+2]-Photocycloaddition
98 (43) [(M - C3H3O)+], 79 (17), 69 (31), 55 (100) [C3H3O+], 51
- C3H3O)+], 69 (18), 57 (43) [C4H9+], 55 (89) [C3H3O+]; HRMS
(EI) calcd for C13H19NO4 - CH3 238.1079, found: 238.1082.
(22); HRMS (EI) calcd for C8H11NO2 153.0790, found: 153.0792.
6-tert-Butyl-hexahydro-1-oxa-6-aza-cyclopenta1,4cyclobuta1,2
-
6-Benzyl-hexahydro-1-oxa-6-aza-cyclobuta[1,2:1,4]dicyclo-
penten-5-one (28b). The compound was prepared from 41.0 mg
(0.17 mmol) of 1-benzyl-4-but-3-enyloxy-1,5-dihydro-pyrrol-2-one
(2b) in 48 mL of anhydrous dichloromethane by irradiation for 4
h. Column chromatography (EtOAc 100%) yielded 14.0 mg (0.06
mmol, 34%) of the desired product as a pale-yellow oil. Rf ) 0.33
benzen-5-one (29). The compound was prepared from 56.4 mg
(0.25 mmol) of 4-but-3-enyloxy-1-tert-butyl-5,6-dihydro-1H-pyri-
din-2-one (16) in 36 mL of anhydrous dichloromethane by
irradiation for 2.5 h. Column chromatography (P/EtOAc ) 2/1)
afforded 42.0 mg (0.19 mmol, 74%) of the desired product as
colorless crystals. Rf ) 0.23 (P/EtOAc ) 2/1); mp 59 °C; 1H NMR
(500 MHz, CDCl3) δ 4.13-4.17 (m, 1 H), 1.44 (s, 9 H), 3.96 (ddd,
3J ) 11.2, 2J ) 9.3, 3J ) 5.5 Hz, 1 H), 3.61 (ddd, 2J ) 13.3, 3J )
1
(EtOAc 100%); H NMR (360 MHz, CDCl3) δ 7.24-7.36 (m, 5
H), 4.58 (d, 2J ) 14.8 Hz, 1 H), 4.46 (d, 2J ) 14.8 Hz, 1 H), 4.20
3
(virt. t, 2J ≈ J ≈ 8.7 Hz, 1 H), 3.96 (ddd, 3J ) 11.4, 2J ) 8.7, 3J
3
2
3
3
) 5.4 Hz, 1 H), 3.43 (d, 2J ) 10.4 Hz, 1 H), 3.27 (d, 2J ) 10.4 Hz,
1 H), 2.94 (dd, 3J ) 10.0, 3J ) 4.1 Hz, 1 H), 2.76-2.83 (m, 1 H),
5.9, J ) 4.0 Hz, 1 H), 3.38 (ddd, J ) 13.3, J ) 9.7, J ) 3.3
2
3
3
Hz, 1 H), 1.70 (dd, J ) 12.6, J ) 5.5 Hz, 1 H), 2.94 (ddd, J )
11.0, 3J ) 7.1, 4J ) 1.0 Hz, 1 H), 2.60 (virt. td, 3J ) 8.7, 3J ) 4.4
Hz, 1 H), 1.81-2.02 (m, 5 H); 13C NMR (90 MHz, CDCl3) δ 173.3
(C), 84.7 (C), 67.2 (CH2), 57.6 (C), 45.4 (CH), 41.2 (CH2), 39.1
(CH), 32.3 (CH2), 32.0 (CH2), 28.6 (CH3), 24.9 (CH2); NOE-
contacts H-3R/H-4R, H-3R/H-6R, H-3R/H-7, H-3â/H-4â, H-5/H-
4â, H-5/H-6â, H-5/H-10â, H-7/H-6R; IR (film) νmax 2922 (s, CH),
2853 (s, CH), 1655 (s, CdO), 1458 (s), 1376 (s), 1323 (s), 1204
(m), 1104 (w), 1061 (w), 1022 (w), 938 (w), 722 (m) cm-1; MS
(EI, m/z, %) 223 (38) [M+], 208 (29) [(M - CH3)+], 180 (18), 166
(15) [(M - C4H9)+], 139 (18), 124 (9), 110 (25), 84 (38), 70 (62),
57 (57) [C4H9+], 55 (100) [C3H3O+]; HRMS (EI) calcd for C13H21-
NO2 223.1572, found: 223.1571.
2
3
3
2.23 (ddd, J ) 13.0, J ) 8.6, J ) 4.1 Hz, 1 H), 1.84-1.98 (m,
2 H), 1.72 (dd, 2J ) 12.6, 3J ) 5.4 Hz, 1 H); 13C NMR (90 MHz,
CDCl3): δ ) 175.3 (C), 136.1 (C), 128.8 (CH), 128.0 (CH), 127.6
(CH), 83.8 (C), 68.4 (CH2), 53.7 (CH2), 46.4 (CH2), 44.0 (CH),
42.5 (CH), 31.9 (CH2), 26.2 (CH2); IR (film) νmax 2942 (m, CH),
2861 (m, CH), 1682 (s, CdO), 1483 (m), 1446 (m), 1420 (m),
1355 (w), 1316 (m), 1243 (w), 1183 (w), 1116 (w), 1081 (m), 990
(w), 953 (w), 909 (w), 700 (m) cm-1; MS (EI, m/z, %) 243 (100)
[M+], 215 (8), 188 (53) [(M - C3H3O)+], 152 (9), 139 (8), 106
(25), 91 (81) [C7H7+], 84 (16), 69 (11), 55 (63) [C3H3O+], 40 (35);
HRMS (EI) calcd for C15H17NO2 243.1259, found: 243.1258.
6-Butyl-hexahydro-1-oxa-6-aza-cyclobuta[1,2:1,4]dicyclopenten-
5-one (28c). The compound was prepared from 70.0 mg (0.33
mmol) of 4-but-3-enyloxy-1-butyl-1,5-dihydro-pyrrol-2-one (2c) in
72 mL of anhydrous dichloromethane by irradiation for 7 h. Column
chromatography (EtOAc 100%) yielded 39.0 mg (0.19 mmol, 56%)
of the desired product as a pale-yellow oil. Rf ) 0.29 (EtOAc
6-tert-Butyl-5-oxo-octahydro-1,6-diaza-cyclopenta1,4cyclobuta1,2-
benzene-1-carboxylic Acid tert-Butyl Ester (30). The compound
was prepared from 38.0 mg (0.12 mmol) of but-3-enyl-(1-tert-butyl-
6-oxo-1,2,3,6-tetrahydro-pyridin-4-yl)-carbamic acid tert-butyl ester
(18) in 24 mL of anhydrous dichloromethane by irradiation for 1.75
h. Column chromatography (P/EtOAc ) 1/1) afforded 23.0 mg
(0.07 mmol, 61%) of the desired product as colorless crystals. Rf
3
100%); 1H NMR (360 MHz, CDCl3) δ 4.22 (virt. t, 2J ≈ J ≈ 8.8
3
2
3
Hz, 1 H), 3.96 (ddd, J ) 11.5, J ) 8.8, J ) 5.3 Hz, 1 H), 3.54
1
) 0.27 (P/EtOAc ) 1/1); mp 64-67 °C; H NMR (500 MHz,
(d, 2J ) 10.2 Hz, 1 H), 3.26-3.39 (m, 3 H), 2.80-2.88 (m, 2 H),
DMSO-d6, 353 K) δ 3.62-3.69 (m, 2 H), 3.29-3.39 (m, 2 H),
2
3
3
2.15 (ddd, J ) 12.9, J ) 8.5, J ) 4.3 Hz, 1 H), 1.85-2.00 (m,
3
3
2.69-2.78 (m, 1 H), 2.66 (dd, J ) 10.2, J ) 6.1 Hz, 1 H), 2.29
2
3
3
2 H), 1.72 (dd, J ) 12.6, J ) 5.3 Hz, 1 H), 1.52 (virt. quint., J
2
3
3
(virt. td, J ≈ J ≈ 12.4, J ) 4.3 Hz, 1 H), 1.99-2.05 (m, 2 H),
1.89-1.95 (m, 1 H), 1.66-1.72 (m, 1 H), 1.49-1.56 (m, 1 H),
1.40 (s, 9 H), 1.39 (s, 9 H); 13C NMR (90 MHz, DMSO-d6, 353
K) δ 171.8 (C), 152.7 (C), 78.3 (C), 63.8 (C), 55.9 (C), 47.3 (CH2),
43.9 (CH), 39.8 (CH2), 39.1 (CH), 29.8 (CH2), 29.0 (CH2), 27.8
(CH3), 27.6 (CH3), 25.9 (CH2); IR (film) νmax 2971 (s, CH), 2872
(m, CH), 1694 (s, CdO), 1644 (s, CdO), 1480 (m), 1454 (s), 1392
3
3
≈ 7.4 Hz, 2 H), 1.33 (virt. sext., J ≈ 7.4 Hz, 2 H), 0.93 (t, J )
7.4 Hz, 3 H); 13C NMR (90 MHz, CDCl3) δ 175.1 (C), 83.8 (C),
68.4 (CH2), 54.2 (CH2), 44.1 (CH), 42.5 (CH), 42.1 (CH2), 32.0
(CH2), 29.1 (CH2), 26.2 (CH2), 20.0 (CH2), 13.7 (CH3); IR (film)
νmax 2957 (s, CH), 2863 (s, CH), 1682 (s, CdO), 1485 (m), 1428
(m), 1312 (s), 1242 (w), 1179 (w), 1080 (m), 991 (m), 954 (w),
911 (w) cm-1; MS (EI, m/z, %) 209 (64) [M+], 194 (16) [(M -
CH3)+], 180 (9) [(M- C2H5)+], 166 (100) [(M - C3H7)+], 154
(39) [(M - C3H3O)+], 138 (11), 126 (9), 112 (39), 98 (17), 84
(25), 69 (10), 55 (69) [C3H3O+], 40 (21); HRMS (EI) calcd for
C12H19NO2 209.1416, found: 209.1415.
(s), 1326 (s), 1250 (m), 1172 (s), 1094 (m), 938 (w), 773 (w) cm-1
;
MS (EI, m/z, %) 322 (15) [M+], 307 (2) [(M - CH3)+], 266 (10)
[(M - C4H8)+], 249 (4), 237 (6), 222 (9) [(266 - CO2)+], 210
(11), 193 (5), 166 (19), 137 (11), 122 (13), 108 (11), 95 (36), 84
(28), 57 (100) [C4H9+]; HRMS (EI) calcd for C18H30N2O3 322.2257,
found: 322.2251.
5-Oxo-hexahydro-1-oxa-6-aza-cyclobuta[1,2:1,4]dicyclopen-
tene-6-carboxylic Acid tert-Butyl Ester (28d). The compound was
prepared from 168 mg (0.66 mmol) of 4-but-3-enyloxy-2-oxo-2,5-
dihydro-pyrrole-1-carboxylic acid tert-butyl ester (2d) in 67 mL
of anhydrous dichloromethane by irradiation for 1.5 h. Column
chromatography (P/EtOAc ) 1/1 f EtOAc/MeOH ) 19/1 as
eluent) afforded 45.0 mg (0.18 mmol, 27%) of the desired product
28d as colorless crystals and 38.0 mg (0.25 mmol, 38%) of
Hexahydro-1-oxa-6-aza-cyclopenta1,4cyclobuta1,2benzen-5-
one (31). The compound was prepared from 28.0 mg (0.17 mmol)
of 4-but-3-enyloxy-5,6-dihydro-1H-pyridin-2-one (20) in 26 mL of
anhydrous dichloromethane by irradiation for 3.5 h. Column
chromatography (CH2Cl2/MeOH ) 95/5) afforded 22.0 mg (0.13
mmol, 79%) of the desired product as colorless crystals. Rf ) 0.16
1
(CH2Cl2/MeOH ) 95/5); mp 91 °C; H NMR (360 MHz, CDCl3)
1
3
δ 6.72 (br. s, 1 H), 4.18 (virt. t, 2J ≈ J ≈ 9.0 Hz, 1 H), 4.00 (ddd,
compound 28a. Rf ) 0.20 (EtOAc/MeOH ) 95/5); mp 86 °C; H
2
3
3J ) 10.8, 2J ) 9.0, 3J ) 5.4 Hz, 1 H,), 3.38-3.45 (m, 2 H), 2.88
(dd, 3J ) 11.1, 3J ) 7.1 Hz, 1 H), 2.71 (virt. td, 3J ≈ 8.7, 3J ) 4.7
Hz, 1 H), 2.08 (ddd, 2J ) 13.2, 3J ) 8.7, 3J ) 7.1 Hz, 1 H), 1.90-
NMR (500 MHz, CDCl3) δ 4.24 (virt. t, J ≈ J ≈ 8.8 Hz, 1 H),
3
2
3
2
3.96 (ddd, J ) 11.2, J ) 8.8, J ) 5.3 Hz, 1 H), 3.84 (d, J )
11.7 Hz, 1 H), 1.54 (s, 9 H), 3.80 (d, 2J ) 11.7 Hz, 1 H), 2.97 (dd,
3J ) 10.2, 3J ) 4.1 Hz, 1 H), 2.89-2.93 (m, 1 H), 2.25 (ddd, 2J )
2
3
1.99 (m, 3 H), 1.80 (virt. dt, J ) 13.5, J ≈ 4.0 Hz, 1 H), 1.73
3
3
2
3
(dd, J ) 12.6, J ) 5.4 Hz, 1 H); 13C NMR (90 MHz, CDCl3) δ
174.8 (C), 85.0 (C), 67.2 (CH2), 43.1 (CH), 39.6 (CH), 39.2 (CH2),
32.0 (CH2), 30.4 (CH2), 25.1 (CH2); NOE-contacts H-3R/H-4R,
H-3R/H-7, H-3â/H-4â, H-5/H-6â, H-5/H-10â, H-5/H-11â, H-6â/
H-10â, H-10/NH; IR (film) νmax 3192 (m, NH), 2949 (s, CH), 2872
(s, CH), 1682 (s, CdO), 1464 (s), 1448 (s), 1410 (m), 1352 (s),
1237 (w), 1188 (w), 1103 (m), 1042 (m), 997 (m), 929 (w), 819
(m), 757 (w), 681 (m) cm-1; MS (EI, m/z, %) 167 (32) [M+], 152
(2) [(M - CH3)+], 138 (5), 122 (4), 111 (17), 96 (66), 84 (15), 72
13.1, J ) 8.6, J ) 4.1 Hz, 1 H), 1.93-2.01 (m, 2 H), 1.75 (dd,
2J ) 12.7, 3J ) 5.3 Hz, 1 H). 13C NMR (90 MHz, CDCl3) δ 175.0
(C), 150.0 (C), 83.2 (C), 81.9 (C), 68.4 (CH2), 53.4 (CH2), 45.1
(CH), 42.3 (CH), 31.9 (CH2), 28.0 (CH3), 25.7 (CH2); IR (film)
νmax 2977 (m, CH), 1782 (s, CdO), 1744 (s, CdO), 1716 (s, Cd
O), 1477 (w), 1368 (s), 1296 (s), 1258 (m), 1158 (s), 1110 (m),
1045 (w), 989 (w), 907 (w), 853 (w), 780 (w), 731 (w) cm-1; MS
(EI, m/z, %) 238 (<1) [(M - CH3)+], 197 (5) [(M- C4H8)+], 180
(15), 153 (100) [(197 - CO2)+], 135 (82), 122 (23), 98 (71) [(153
J. Org. Chem, Vol. 73, No. 6, 2008 2355

Albrecht et al.
(15), 55 (100) [C3H3O+]; HRMS (EI) calcd for C9H13NO2 167.0946,
found: 167.0947.
(w), 1340 (w), 1318 (w), 1260 (w), 1215 (w), 1144 (w), 1124 (w),
1068 (w), 1025 (w), 932 (w), 820 (w) cm-1; MS (EI, m/z, %) 165
(100) [M+], 150 (14), 136 (29), 122 (31), 109 (78), 82 (58), 55
(42); HRMS (EI) calcd for C10H15NO 165.1154, found: 165.1153.
3a-Methoxy-octahydro-cyclopenta3,4cyclobuta[1,2-c]pyrrol-1-
one (39). The compound was prepared from 100 mg (0.75 mmol)
of 1,5-dihydro-4-methoxy-2H-pyrrol-2-one (1a) and 1.37 mL (15.0
mmol) of cyclopentene in 150 mL of anhydrous dichloromethane
by irradiation for 9 h. Column chromatography (EtOAc/MeOH )
19/1) afforded 87.0 mg (0.48 mmol, 64%) of the major diastere-
oisomer 39 (exo/endo selectivity ) 4.6/1) as colorless crystals. Rf
5-Oxo-octahydro-1,6-diaza-cyclobuta[1,2:1,4]dicyclopentene-
1-carboxylic Acid Ethyl Ester (34). The compound was prepared
from 20.0 mg (0.09 mmol) of but-3-enyl-(5-oxo-2,5-dihydro-1H-
pyrrol-3-yl)-carbamic acid ethyl ester (6) in 18 mL of anhydrous
dichloromethane by irradiation for 1 h. Column chromatography
(EtOAc/MeOH ) 19/1) yielded 14.5 mg (0.06 mmol, 72%) of the
desired product as colorless crystals. Rf ) 0.45 (EtOAc/MeOH )
9/1); mp 118-120 °C; 1H NMR (500 MHz, CDCl3) δ 7.04 (br. s,
1 H), 4.12 (q, 3J ) 6.9 Hz, 2 H), 3.96 (br. s, 1 H), 3.70 (br. s, 1 H),
3.15 (br. s, 1 H), 2.98-2.94 (m, 1 H), 2.79 (br. s, 1 H), 2.31-2.26
1
) 0.36 (EtOAc/MeOH ) 95/5); mp 92-94 °C; H NMR (250
3
MHz, CDCl3) δ 5.98 (br. s, 1 H), 3.65 (d, 3J ) 10.8 Hz, 1 H), 3.42
(m, 2 H), 2.07-2.00 (m, 2H), 1.78-1.72 (m, 1 H), 1.22 (t, J )
6.9 Hz, 3 H); 13C NMR (90 MHz, CDCl3) δ 179.2 (C), 155.2 (C),
67.6 (C), 61.4 (CH2), 48.9 (CH2), 47.2 (CH), 44.0 (CH2), 40.4 (CH),
28.3 (CH2), 26.0 (CH2), 14.7 (CH3); IR (film) νmax 3195 (m, NH),
2965 (m, CH), 1690 (vs, CdO), 1664 (s, CdO), 1461 (w), 1396
(w), 1376 (w), 1360 (w), 1339 (w), 1309 (w), 1221 (w), 1169 (w),
1122 (w), 1097 (w), 1052 (w), 1009 (w), 894 (w), 832 (w), 805
3
3
(d, J ) 10.7 Hz, 1 H), 3.17 (s, 3 H), 2.75 (virt. t, J ≈ 7.3 Hz, 1
3
H), 2.62-2.54 (m, 1 H), 2.37 (d, J ) 4.0 Hz, 1 H), 2.07-1.99
(m, 1 H), 1.87-1.75 (m, 2 H), 1.70-1.57 (m, 2 H), 1.50-1.40
(m, 1 H); 13C NMR (90 MHz, CDCl3) δ 179.0 (C), 77.3 (C), 52.4
(CH2), 50.6 (CH3), 48.3 (CH), 46.9 (CH), 38.7 (CH), 33.5 (CH2),
27.0 (CH2), 24.4 (CH2); Anal. Calcd for C10H15NO2 (181.23): C,
66.27; H, 8.34; N, 7.73. Found: C, 66.10; H, 8.23; N, 7.55; IR
(film) νmax 3202 (m, NH), 2939 (m, CH), 1671 (vs, CdO), 1495
(w), 1438 (w), 1369 (w), 1331 (w), 1304 (w), 1291 (w), 1261 (w),
1240 (w), 1207 (w), 1131 (w), 1079 (w), 1058 (w), 1038 (w), 1002
(w), 762 (w), 691 (w), 674 (w), 652 (w) cm-1; MS (EI, m/z, %)
181 (1) [M+], 166 (1) [(M - CH3)+], 114 (100), 82 (28).
(w), 775 (w), 748 (w), 727 (w), 708 (w), 692 (w), 673 (w) cm-1
;
MS (EI, m/z, %) 224 (100) [M+], 196 (5) [(M - C2H4)+], 169
(70), 123 (18), 97 (36); HRMS (EI) calcd for C11H16N2O3 224.1161,
found: 224.1153.
Octahydro-6-aza-cyclopenta1,4cyclobuta1,2benzen-5-one (37).
The compound was prepared from 16.0 mg (0.10 mmol) of 4-pent-
4-enyl-5,6-dihydro-1H-pyridin-2-one (23) in 20 mL of anhydrous
dichloromethane by irradiation for 1 h. Column chromatography
(EtOAc/MeOH ) 19/1) yielded 8.5 mg (0.05 mmol, 52%) of the
desired product as colorless crystals. Rf ) 0.30 (EtOAc/MeOH )
Acknowledgment. This project was supported by the Fonds
der Chemischen Industrie (FCI) and the Deutsche Forschungs-
gemeinschaft. D.A. is grateful to the FCI for a Kekule´
scholarship and for support by the Studienstiftung des deutschen
Volkes.
1
9/1); mp 97-99 °C; H NMR (500 MHz, CDCl3) δ 6.04 (br. s, 1
3
3
H), 3.56 (dt, J ) 12.8, J ) 1.8 Hz, 2 H), 3.40-3.35 (m, 1 H),
3
3
2.54 (dd, J ) 10.7, J ) 6.8 Hz, 1 H), 2.42 (br. s, 1 H), 2.15-
2.09 (m, 1 H), 1.96-1.83 (m, 3 H), 1.74-1.68 (virt. dt, 3J ≈ 13.4,
Supporting Information Available: Complete experimental and
analytical data of compounds 2d, 6-9, 11, 18, 21-27, 32, 33, 35,
and 36. This material is available free of charge via the Internet at
http://pubs.acs.org.
3J ≈ 4.6 Hz, 1 H), 1.64-1.57 (m, 4 H), 1.35 (dt, J ) 12.6, J )
6.7 Hz, 1 H); 13C NMR (90 MHz, CDCl3) δ 176.4 (C), 47.8 (C),
40.9 (CH), 40.6 (CH2), 39.7 (CH2), 38.6 (CH), 33.0 (CH2), 31.7
(CH2), 27.8 (CH2), 24.9 (CH2); IR (film) νmax 3177 (w, NH), 2923
(s, CH), 2854 (m, CH), 1659 (vs, CdO), 1489 (w), 1443 (w), 1409
3
3
JO7027129
2356 J. Org. Chem., Vol. 73, No. 6, 2008