Synthesis of erythro-α-Amino β-hydroxy Carboxylic Acid Esters by Diastereoselective Photocycloaddition of 5-Methoxyoxazoles with Aldehydes

Article abstract of DOI:10.1021/jo034830h

A new photoaldol route to α-amino-β-hydroxy carboxylic acid esters is initiated by the photocycloaddition of aromatic or aliphatic aldehydes to 5-methoxyoxazoles. The 4-unsubstituted 5-methyloxazole 1 gave the cycloadducts 8a-f in high yields and excellent exo-diastereoselectivities. Hydrolysis of 8a-f gives the N-acetyl α-amino-β-hydroxy esters 9a-f, which could be subsequently converted into the corresponding Z-didehydro α-amino acids 10a-f. Quartenary α-amino-β-hydroxy esters 12, 14, 16, 18, and 20, which are stable against dehydration, were obtained from the 4-alkylated 5-methoxyoxazoles 2-6, in most cases highly erythro-selective due to the high degree of stereocontrol (exo) at the photocycloaddition (to give 11, 13, 15, 17, and 19) level. The relative configurations of the N-acetyl α-amino-β-hydroxy esters were determined by NMR spectroscopy and comparison with chiral pool-derived compounds as well as by X-ray structure determination of the ester 23, formed by hydrolysis of the cycloadduct 22, derived from photocycloaddition of propionaldehyde to the isoleucine-derived oxazole 21.

Full text of DOI:10.1021/jo034830h

Syn th esis of er yth r o-r-Am in o â-h yd r oxy Ca r boxylic Acid Ester s by
Dia ster eoselective P h otocycloa d d ition of 5-Meth oxyoxa zoles w ith
Ald eh yd es
Axel G. Griesbeck,* Samir Bondock, and J ohann Lex
Institut fu¨r Organische Chemie der Universita¨t zu Ko¨ln, Greinstr. 4, D-50939 Ko¨ln, Germany
griesbeck@uni-koeln.de
Received J une 15, 2003
A new photoaldol route to R-amino-â-hydroxy carboxylic acid esters is initiated by the photocy-
cloaddition of aromatic or aliphatic aldehydes to 5-methoxyoxazoles. The 4-unsubstituted 5-me-
thyloxazole 1 gave the cycloadducts 8a -f in high yields and excellent exo-diastereoselectivities.
Hydrolysis of 8a -f gives the N-acetyl R-amino-â-hydroxy esters 9a -f, which could be subsequently
converted into the corresponding Z-didehydro R-amino acids 10a -f. Quartenary R-amino-â-hydroxy
esters 12, 14, 16, 18, and 20, which are stable against dehydration, were obtained from the
4-alkylated 5-methoxyoxazoles 2-6, in most cases highly erythro-selective due to the high degree
of stereocontrol (exo) at the photocycloaddition (to give 11, 13, 15, 17, and 19) level. The relative
configurations of the N-acetyl R-amino-â-hydroxy esters were determined by NMR spectroscopy
and comparison with chiral pool-derived compounds as well as by X-ray structure determination
of the ester 23, formed by hydrolysis of the cycloadduct 22, derived from photocycloaddition of
propionaldehyde to the isoleucine-derived oxazole 21.
In tr od u ction
decades to provide flexible access to these target mol-
ecules. Besides the R-alkylation of amino acid enolates,
the aldol reaction is another suitable method to synthe-
size R,R-disubstituted amino acids. This reaction provides
the important class of R-alkylated R-amino â-hydroxy
acids which can also be found as substructures in
biologically active molecules such as myriocin or lacta-
cystin.8 While various syntheses of R-amino-â-hydroxy
acids by reaction of glycine with aldehydes are described
in the literature,9 only a few examples are known that
provide R-alkylated R-amino â-hydroxy acids by reaction
of other amino acid derivatives with aldehydes.10
Further, nonproteinogenic R-alkylated R-amino acids
are playing an important role in natural product chem-
istry and for biological investigation. Because of the
persubstituted central stereogenic carbon atom, they
possess high configurational stability. They exert a
remarkable influence on the configuration of the peptide
into which they could be incorporated and, thus, are often
used for the investigation of enzymatic mechanism and
also as enzyme inhibitors.11 These densely functionalized
amino acids are also useful buliding blocks for the
â-Hydroxy-R-amino acids constitute an important class
of amino acids that are found as building blocks in nature
(threonine, serine, â-hydroxyproline) as well as constitu-
ents of more complex natural products. For example,
â-hydroxytyrosine and â-hydroxyphenylalanine deriva-
tives are found in the clinically important antibiotic
glycopeptide vancomycin.1 â-Hydroxyleucine is found in
(+)-lactacystin2 and (E)-2-butenyl-4,N-dimethyl-L-threo-
nine is a prominent part of cyclosporine.3
R,R-Disubstituted (quaternary) amino acids represent
a highly interesting class of nonproteinogenic amino
acids,4 especially in view of their potential activity as
enzyme inhibitors.5 Incorporation of these components
into peptide structures results in conformational restric-
tions and increased rigidity, leading to enhanced resis-
tance toward protease enzymes6 and to the preference
of particular secondary structure motifs.7 Numerous
synthetic methods have been developed in the past
(1) Rao, A. V. R.; Gurjar, M. K.; Reddy, K. L.; Rao, A. S. Chem. Rev.
1995, 95, 2135-2167. Vancomycin: Williams, D. H. Acc. Chem. Res.
1984, 17, 364-369. Harris, C. M.; Kopecka, H.; Harris, T. M. J . Am.
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P. A.; Smith, A. B., III. J . Am. Chem. Soc. 1996, 118, 3584-3590.
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6761.
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Tetrahedron Lett. 1993, 34, 1653-1656.
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Omura, S.; Smith, A. B., III. J . Am. Chem. Soc. 1993, 115, 5302. (b)
Iwanowicz, E. J .; Blomgren, P.; Cheng, P. T. W.; Smith, K.; Lau, W.
F.; Pan, Y. Y.; Gu, H. H.; Malley, M. F.; Gougoutas, J . Z. Synlett 1998,
664-666. (c) Ooi, T.; Taniguchi, M.; Kameda, M.; Maruoka, K. Angew.
Chem., Int. Ed. 2002, 41, 4542-4544.
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264.
(5) Rando, R. R. Acc. Chem. Res. 1975, 8, 281-288.
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Becker, E. L.; Polinelli, S.; Boesten, W. H. J .; Schoemaker, H. E.;
Meijer, E. M.; Kamphuis, J .; Freer, R. Peptide Res. 1991, 4, 66-71.
(7) Paul, P. K. C.; Sukumar, M.; Bardi, R.; Piazzesi, A. M.; Valle,
G.; Toniolo, C.; Balaram, P. J . Am. Chem. Soc. 1986, 108, 6363-6370.
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2407-2418.
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10.1021/jo034830h CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/27/2003
J . Org. Chem. 2003, 68, 9899-9906
9899

Griesbeck et al.
asymmetic synthesis of â-lactams.12 As a consequence of
the pivotal role that can be induced by these amino acids
in biological systems and their utility as synthetic build-
ing blocks, a number of useful strategies have been
devised for their preparation.13 Most synthetic routes to
these amino acids are based on the alkylation of enolates
from bislactim ethers, oxazolidinones, imidazolidinones,
or other chiral building blocks. In most of these ap-
proaches, the stereochemistry of alkylation steps can be
perfectly controlled, whereas the formation of more than
one new stereogenic center, e.g., via aldol addition to
chiral enolates, proceeds only with moderate to accept-
able diastereoselectivities. Multistep stoichiometric prepa-
ration and careful purification of each reaction interme-
diate is therefore often requried for these syntheses.14
Recently, catalytic enantioselective methods were added,
such as the Sharpless asymmetric epoxidiation,15 Sharp-
less asymmetric dihydroxylation,16 electrophilic amina-
tion,17 and hydroxylation,18 stereoselective hydrolysis of
aziridine carboxylate esters,19 aldol condensation20 in-
volving oxazolidinone intermediates,21 and the stereose-
lective reduction of R-amino ketones.22
A possible photochemical approach to R-alkylated
R-amino â-hydroxy acids is the photoaldol route. The
thermal counterpart, the aldol reaction, is the archetype
carbonyl reaction combining a CH-acidic carbonyl com-
pound with an electrophilic carbonyl substrate. By this
process, â-hydroxy carbonyl compounds are available that
can be subsequently transformed into valuable product
structures. An efficient photochemical route has been
developed by Schreiber and co-workers for the synthesis
of â-hydroxy carbonyl compounds by light-induced cy-
cloaddition of aldehydes to furan and substituted furans.23
Enol ethers are, however, not applicable as enolate
equivalents in Paterno`-Bu¨chi reactions24 because the
SCHEME 1. P h otocycloa d d ition of Ald eh yd es to
F ive-Mem ber ed Heter ocycles
regioselectivity of the excited-state carbonyl addition
results in 3-alkoxyoxetanes that do not correspond to
masked aldols. Furans as the alkene addends are more
advantageous because the regioselectivity becomes re-
versed and protected aldols are formed with unusual high
regio- and diastereoselectivity. The Paterno`-Bu¨chi reac-
tion of furan and furan derivatives, respectively, with
electronically excited aliphatic as well as aromatic alde-
hydes proceeds highly regioselective to give the 2,7-
dioxabicyclo[3.2.0]hept-3-enes with the substituent at C-6
preferentially in exo-position. The exo/endo selectivity is
remarkably high (e.g., 212:1 for the benzaldehyde/furan
case) for a triplet photocycloaddition.25 Aliphatic alde-
hydes react with slightly lower exo-selectivity, and a weak
spin-selectivity effect26 was also determined for aliphatic
aldehydes: singlets favor the formation of the exo-
diastereoisomer less pronounced than the corresponding
triplets.27 These photocycloadditions to furans have been
extensively used for synthetic applications especially
because of the extraordinary high degree of diastereo-
control (Scheme 1).28
Several other five-membered aromatic heterocycles
were used as alkene components in the Paterno`-Bu¨chi
photocycloaddition.29 Recently, we have reported on the
oxazole-based route to R-amino â-hydroxy ketones. The
commercially available 2,4,5-trimethyloxazole was used
as our first model substrate, and excellent regio- and (exo-
)diastereoselectivities were observed for the photocy-
cloaddition with aldehydes.30 Further extension of this
concept is described in the present paper.31
(12) (a) Miller, M. J . Acc. Chem. Res. 1986, 19, 49-56. (b) Lotz, B.
T.; Miller, J . J . J . Org. Chem. 1993, 58, 618-625.
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Rose, N. G. W.; Wilkinson, S.; Luo, Y.; Lajoie, G. A. J . Org. Chem.
1998, 63, 3631-3646. (b) Williams, R. M. Synthesis of Optically Active
R-Amino Acids; Pergamon: Oxoford, U. K., 1989.
Resu lts a n d Discu ssion
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4352. (d) Divas, F. A.; Zhou, P.; Reddy, R. E. J . Org. Chem. 1994, 59,
3243-3245.
An attractive family of target molecules which might
be available by the photoaldol route are derivatives of
(24) Griesbeck, A. G.; Bondock, S. In CRC Handbook of Photochem-
istry and Photobiology; Horspool, W. M., Lenci, F., Eds.; CRC Press:
Boca Raton, 2003; Chapter 60, pp 1-21.
(25) Griesbeck, A. G.; Buhr, S.; Fiege, M.; Schmickler, H.; Lex, J . J .
Org. Chem. 1998, 63, 3847-3854.
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(27) Griesbeck, A. G.; Bondock, S. Unpublished results.
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6723-6724. (b) Schreiber, S. L.; Hoveyda, A. H.; Wu, H. J . J . Am.
Chem. Soc. 1983, 105, 660-661. (c) Schreiber, S. L.; Satake, K.
Tetrahedron Lett. 1986, 27, 2575-2578. (d) Schreiber, S. L.; Desmaele,
D.; Porco, J . A., J r. Tetrahedron Lett. 1988, 29, 6689-6692.
(29) Thiophenes: Rivas, C.; Pacheco, D.; Vargas, F.; Ascanio, J . J .
Heterocycl. Chem. 1981, 18, 1065-1067. Pyrroles: J ones, G., II; Gilow,
H. M.; Low, J . J . Org. Chem. 1979, 44, 2949-2951. Rivas, C.; Bolivar,
R. A. J . Heterocycl. Chem. 1976, 13, 1037-1040. Imidazoles: Matsuura,
T.; Banba, A.; Ogura, K. Tetrahedron 1971, 27, 1211-1219. Indoles:
J ulian, D. R.; Tringham, G. D. J . Chem. Soc., Chem. Commun. 1973,
13-14. Thiazoles, isothiazoles, and isoxazoles: Nakano, T.; Rodriquez,
W.; de Roche, S. Z.; Larrauri, J . M.; Rivas, C.; Pe´rez, J . Heterocycl.
Chem. 1980, 17, 1777-1780.
(20) Blaser, D.; Seebach, D. Liebigs Ann. Chem. 1991, 1067-1078.
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1771-1772. (b) Williams, L.; Zhang, Z.; Shao, F.; Carroll, P. J .; J oullie,
M. M. Tetrahedron 1996, 52, 11673-11694. (c) Kanemasa, S.; Mori,
T.; Wada, E.; Tatsukawa, A. Tetrahedron Lett. 1993, 34, 677-680.
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1095-1098. (b) Roemmele, R. C.; Rapoport, H. J . Org. Chem. 1989,
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590.
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J . Chem. 2003, 81, 555-559.
(23) Schreiber, S. L. Science 1985, 227, 857-863.
9900 J . Org. Chem., Vol. 68, No. 26, 2003

Synthesis of erythro-R-Amino â-hydroxy Carboxylic Acid Esters
SCHEME 2. P h otocycloa d d ition of a Ser ies of Ar om a tic a n d Alip h a tic Ald eh yd es 7a -f to Oxa zole 1;
Hyd r olytic Rin g Op en in g of th e Oxeta n es 8a -f Resu lts in th e 1,2-Acyla m in o Alcoh ols 9a -f
relative configuration of the bicyclic oxetanes, assuming
retention of configuration at C7, the erythro configuration
for the R-amino â-hydroxy esters 9 was predicted. In fact,
the relative configurations of the methyl esters of phe-
nylserine (9a )35 and â-hydroxyleucine (9e)36 were eluci-
dated in the literature, and by comparison with our data,
the erythro (S*,S*) configuration for the major diastereo-
F IGURE 1. Structures of bicyclic oxetanes from photocy-
isomers of 9a -f was established: for the threo â-hy-
cloaddition of aldehydes to furan and 5-methoxyoxazoles and
droxyleucine derivative 9e a chemical shift (13C NMR)
the independently synthesized reference compound 9g.
was reported for the â-carbon: 77.2 ppm for R*S* (threo);
69.8 ppm was determined for the major diastereoisomer
(erythro) 9e obtained via the photoaldol route. Indepen-
R-amino â-hydroxy carboxylic acids, either with a tertiary
(from a corresponding glycine equivalent) or a quaternary
dent synthesis of the threo-diastereomer of N-acetyl
stereogenic R-carbon center. To investigate this concept,
1
methyl threoniate (9g) was also performed, and H NMR
we applied in a first series the 4-unsubstituted 5-meth-
comparison revealed different relative configurations
oxyoxazole 132 as diene component in the photocycload-
[values for HR ) for erythro-9d , 4.88 ppm; erythro-9e, 4.75
dition with aldehydes 7a -f. Photolyses could be per-
ppm; erythro-9f, 4.87 ppm, compared with the threonine
formed either in Rayonet photochemical reactors with
derivative threo-9g, 4.35 ppm].
coated mercury low-pressure lamps emitting at λ ) 300
Thus, the photoaldol route serves as an efficient and
( 10 nm or in a XeCl-excimer falling-film reactor with a
highly diastereoselective route to erythro R-amino â-hy-
3 kW XeCl (λ ) 308 nm) emitter.33 High conversions could
droxy esters. Furtheron, applying more harsh conditions,
be achieved (>90%) and in all cases only one regioiso-
these products could be converted into the Z-didehydro
meric bicyclic oxetane 8a -f was detected in the crude
R-amino acids 10a ,d -f (Scheme 3, not examined for 9b
photolysis mixture. Even more important, in all cases
and 9c). For compounds 10d -f, the E-isomers were also
only one diastereoisomer was formed (Scheme 2).
detected in the NMR spectra as minor diastereoisomers.
The benzaldehyde adduct 8a showed a strong ring-
The configuration of compound 10f (derived from leucine)
current-induced upfield shift in the 1H NMR for H-1
was determined by low-temperature ROESY and NOE
(Figure 1, R ) H, note the switch in numbering of the
spectroscopy (-63 °C, because of overlapping amide NH
bicyclohept[3.2.0]enes) in line with the results obtained
signals and rapid H/D exchange at room temperature).
for the furan/benzaldehyde adduct.25 This effect corre-
For the minor diastereoisomer, a strong enhancement of
sponds also to the NMR data obtained for the trimethyl-
the vinylic hydrogen (δdCH ) 6.95 ppm) was observed
oxazole photocycloadducts30 as well as to effects detected
during saturation of the amide hydrogen (δNH ) 7.75
for in â-lactams which resulted from Yang-cyclization of
ppm), whereas no such effect was observed for the major
amino acid derived chiral butyrophenone derivatives34
diastereoisomer during saturation of the amide hydrogen
and confirmed the exo-configuration of the product 8a .
(δNH ) 7.58 ppm, δdCH ) 6.75 ppm). The acid-catalyzed
The exo/endo selectivity was excellent also when the
elimination does not follow a E2 path but results in the
aliphatic aldehydes 7c-f were applied and the exo-
thermodynamically more stable Z-isomers as described
diastereoisomers were formed in near-quantitative yields.
already for the para-hydroxy derivative of 9a (â-p-
Purification was, however, problematic because the pri-
hydroxyphenylserine).37 The phenyl-substituted deriva-
mary photoproducts 8a -f were hydrolytically unstable
tive 10a could be cyclized by a Bischler-Napieralski
and underwent 2-fold ring opening to give the â-hydroxy
reaction to give the literature-known isoquinoline 25.38
R-amino acid esters 9a -f even upon chromatography on
In a next series of experiments, we investigated
silica. Except for the propionaldehyde adducts 8d /9d , the
5-methoxyoxazoles 2-6 as substrates with an additional
diastereoisomeric ratio of the ring-opened products 9
matched the dr of the oxetane precursors 8. From the
(35) Legters, J .; Thijs, L.; Zwanenburg, B. Recl. Trav. Chim. Pays-
Bas 1992, 111, 16-21.
(32) Singh, R. S.; Singh, R. M. Ind. J . Chem. Sect. B 2000, 39, 688-
693.
(33) Griesbeck, A. G.; Maptue, N.; Bondock, S.; Oelgemo¨ller, M.
Photochem. Photobiol. Sci. 2003, 2, 450-451.
(34) Griesbeck, A. G.; Heckroth, H. Synlett 2002, 131-133.
(36) Cardillo, G.; Gentilucci, L.; Gianotti, M.; Tolomelli, A. Tetra-
hedron: Asymmetry 2001, 12, 563-569.
(37) Bolhofer, W. A. J . Am. Chem. Soc. 1953, 75, 4469-4473.
(38) Hickey, D. M. B.; Mackenzie, A. R.; Moody, C. J .; Ress, C. W.
J . Chem. Soc., Perkin Trans. 1 1987, 921-926.
J . Org. Chem, Vol. 68, No. 26, 2003 9901

Griesbeck et al.
SCHEME 3. Deh yd r a tion of 1,2-a cyla m in o a lcoh ols 9 Lea d s to Z-d id eh yd r o Am in o Acid s 10;
Bisch ler -Na p ier a lsk i Cycliza tion of 10a Gives th e Isoqu in olin e 25
SCHEME 4. P h otocycloa d d ition of Ald eh yd es 7a -f to 4-Su bstitu ted 5-Meth oxy Oxa zoles 2-6 a n d
Su bsequ en t Hyd r olytic Rin g-Op en in g of th e Bicyclic Oxeta n es
SCHEME 5. P h otocycloa d d ition of Ald eh yd es 7 to 4-Isop r op yl 5-Meth oxy Oxa zole 5 a n d Su bsequ en t
Hyd r olytic Rin g-Op en in g of th e Bicyclic Oxeta n es 17
substituent at C-4. These substrates were available from
the amino acids alanine, R-amino butyric acid, valine,
norvaline, leucine, and isoleucine by a three-step proce-
dure.39 The photocycloadditions of 2-6 and the aldehydes
7a -f were performed using equimolar amounts of the
substrates in benzene, irradiations were performed in
Rayonet photoreactors with lamps emitting at λ ) 300
( 10 nm (Scheme 4). The primary photoadducts were
formed with high to excellent diastereoselectivities except
for the benzaldehyde additions to oxazole substrates with
bulky substituents R2 (vide infra). 2-Naphthaldehyde (7b)
was applied only in the photocycloaddition to 2,4-di-
methyl-5-methoxyoxazole (2), 3-phenylpropionaldehyde
(7c) in the photocycloaddition to 2 and to 2-methyl-4-
isopropyl-5-methoxy-oxazole (5).
The relative configurations of the predeeding oxetanes
were confirmed by NMR spectroscopy, and the relative
configurations of the R-acylamino â-hydroxy carboxylic
acid esters by spectral comparison with representative
literature-known anti-products.11,40 The photocycloaddi-
tions of propionaldehyde (7d ) and isobutyraldehyde (7e)
were exo-selectivitve with all oxazoles substrates inves-
tigated. The only remarkable drop in cycloaddition dia-
stereoselectivity was observed with the isopropyl-substi-
tuted oxazole 5 (Scheme 5). In case of the vicinal bis-
isopropyl-substituted oxetane 17e, however, the exo-
diastereoisomer was again the only detectable product
in high yield. The serve strain generated in this product
due to the cis-alignment of two bulky groups in a four-
membered ring clearly indicates the kinetic control of
oxetane formation. The marginal decline in exo-diaste-
reoselectivity for 17a ,c, and 17f might be due to triplet
biradical geometries (vide infra), compensating the steric
strain, and is, however, improved again in the (S*,S*)
Upon chromatography on silica, the photocycloaddition
products were hydrolyzed to give the (S*,S*) R-acylamino
â-hydroxy carboxylic acid esters 12, 14, 16, 18, and 20.
(39) (a) Karrer, P.; Granacher, C. Helv. Chim. Acta 1924, 7, 740-
758. (b) Doktorova, N. D.; Ionova, L. V.; Karpeisky, M. Y. A.;
Padyukova, N. S.; Turchin, K. F.; Florentiev, V. L. Tetrahedron 1969,
25, 3527-3553. (c) Tolstikov, G. A.; Shul’ts, E. E. J . Org. Chem. USSR
1984, 20, 2230-2235.
(40) (a) Duthaler, R. O. Tetrahedron 1994, 50, 1539-1650. (b)
Seebach, D.; Sting, A. R.; Hoffmann, M. Angew. Chem., Int. Ed. Engl.
1996, 35, 2708-2749.
9902 J . Org. Chem., Vol. 68, No. 26, 2003

Synthesis of erythro-R-Amino â-hydroxy Carboxylic Acid Esters
SCHEME 6. P h otocycloa d d ition of P r op ion a ld eh yd e to th e Isoleu cin e-Der ived Oxa zole 21 a n d Hyd r olytic
Rin g-Op en in g of 22 To Give th e 1,2-Acyla m in o Alcoh ol 23
SCHEME 7. Tr a n s-Acyla tion Obser ved for th e
1,2-Acyla m in o Alcoh ol 16d To Give th e
1,2-Acyloxya m in e 24d
reactions to furan and other heterocyclic dienes. It has
been described as a consequence of spin-orbit-coupling
geometries for triplet-1,4-biradicals in combination with
secondary orbital interactions.25 Aliphatic aldehydes,
which can also react from their first excited singlet state,
also show high exo-selectivity. When high concentrations
of the trapping reagent (furan or oxazole, respectively)
are used in the presence of aliphatic aldehydes, a drop
in exo/endo-diastereoselectivity is observed.27 Thus, the
F IGURE 2. Crystal structure of 23; internal hydrogen bonds
singlet excited carbonyl compounds add to oxazoles with
are indicated by broken lines.
slightly lower exo/endo-selectivity, albeit by a different
mechanism.26
R-acylamino â-hydroxy carboxylic acid esters 18a ,c, and
18f, obviously due to an enrichment effect during workup.
The ultimate proof for the relative configuration of the
quaternary R-acylamino â-hydroxy carboxylic acid esters
came from the X-ray structure analysis of compound 23,
which resulted from the hydrolytic ring-opening of the
oxetane 22 (Scheme 6). In the crystal, conformational
locking is achieved by strong internal hydrogen-bonding.
The oxazole 21 was obtained from enantiomerically pure
isoleucine by the standard procedure described above and
Surprisingly, also the trisubstituted oxazoles 2-6 and
21 gave the exo-diastereoisomers with high excesses upon
photocycloaddition. This behavior was unprecedented,
because in the triplet photocycloaddition to cycloal-
kenes,41 ring alkylation always led to a decrease in
selectivity and in some case to selectivity inversion due
to interference with the spin-orbit-coupling geometries.42
This is obviously not the case for the oxazole photocy-
cloadditions described herein, which indicates that the
secondary orbital interaction model originally applied for
was originally applied in order to study possible face-
the benzaldehyde-furan reaction is operating.25 Figure 3
selectivity effects. The photocycloaddition of all aldehydes
shows the triplet 1,4-biradical conformers A-C with
investigated herein proceeded with high exo-selectivity
but with no particular facial selectivity. The hydrolytic
ring-opening of the propionaldehyde adduct 22 resulted
in the 1,2-acylamino alcohol 23 which was purified by
chromatography (Figure 2). By fractional crystallization,
one out of the two diastereoisomers resulting from
different facial attack (both anti) was isolated and could
be characterized by X-ray analysis. Enantiomerically
reactive spin-orbit coupling (“90°-conformers”) geom-
etries, as also expected from theoretical calculations.43
If most of the spin inversion process is directed through
the channel C due to high spin-orbit-coupling interaction
and secondary orbital interactions, high exo-selectivity
is expected. The endo-contribution from A only becomes
relevant for bulky groups R1 and R2 (as for 17a ), because
steric encumbrance is alreay substantial at the stage of
pure products were obtained as also could be deduced
the triplet biradical structure C. Also the singlet excited
from the chiral space group P212121.
aldehydes do show high exo-selectivity and thus both
In contrast to the 1,2-amido alcohols 9, the quaternary
mechanisms act cooperatively.
compounds isolated from photocycloaddition/hydrolysis
of 4-substituted 5-methoxyoxazoles could not undergo
dehydration. Prolonged treatment with aqueous HCl did,
Exp er im en ta l P a r t
however, result in quantitative transacylation and the
formation of â-acyloxy R-amino acid esters, as shown in
Scheme 7 for the transacylation of 16d into 24d .
Syn th esis of th e Oxa zole Su bstr a tes. 2-Meth yl-5-m eth -
oxyoxa zole (1). A mixture of 13.1 g of N-acetylglycine methyl
Mech a n istic Scen a r io. The high exo-selectivity ob-
served for the photocycloaddition of electronically excited
aromatic as well as aliphatic aldehydes to the C4-
unsubstituted oxazole 1 is analogous to Paterno`-Bu¨chi
(41) Griesbeck, A. G.; Stadtmu¨ller, S. J . Am. Chem. Soc. 1991, 113,
6923-6928.
(42) Griesbeck, A. G.; Stadtmu¨ller, S.; Mauder, H. Acc. Chem. Res.
1994, 27, 70-75.
(43) Kutateladze, A. J . Am. Chem. Soc. 2001, 123, 9279-9282.
J . Org. Chem, Vol. 68, No. 26, 2003 9903

Griesbeck et al.
F IGURE 3. 1,4-Triplet biradical intermediates in the photocycloaddition of triplet RCHO to 4-substituted oxazoles.
ester (0.1 mol) and 40.0 g of phosphorus pentoxide (0.15 mol)
in 100 mL of chloroform was heated to reflux with mechanical
stirring for 24 h. After being cooled to room temperature, the
residual phosphorus pentoxide was carefully crushed, and the
resulting thick suspension was slowly added, in small portions,
to ice-cold saturated sodium bicarbonate maintaining a pH of
6-7. The organic layer was separated, and the aqueous layer
was extracted with 4 × 75 mL of methylene chloride. The
combined extracts were then washed with brine, dried over
anhydrous magnesium sulfate, concentrated and distilled to
afford 10.0 g (80%) of 132 as a colorless oil: bp 64-66 °C, 10
Torr; 1H NMR δ 2.27 (s, 3H), 3.79 (s, 3H), 5.87 (s, 1H); 13C
NMR δ 13.9, 58.4, 97.8, 152.0, 160.5.
Syn th esis of Am in o Acid Meth yl Ester Hyd r och lo-
r id es: Gen er a l P r oced u r e. A 250 mL, two-necked, round-
bottomed flask, containing a magnetic stirring bar, was
equipped with a dropping funnel and reflux condenser, pro-
tected from moisture by a calcium chloride-filled drying tube
and a rubber septum. The dropping funnel was charged with
4.2 mL of thionyl chloride (60 mmol). The flask was charged
with 50 mL of absolute methanol and cooled with an ice-salt
bath to -10 °C. Thionyl chloride was added dropwise over a
period of 5 min. The solution was stirred for another 5 min,
and then the solid L-amino acid (30 mmol) was added in one
portion and the solution was slowly heated to reflux. Heating
to reflux was continued for 3 h, and then the solution was
allowed to cool to room temperature and the solvent was
removed under reduced pressure to give the amino acid methyl
ester hydrochloride as a colorless crystalline solid that was
directly used without further purification.
Syn th esis of N-Acetyla m in o Acid Meth yl Ester s: Gen -
er a l P r oced u r e. To a stirred suspension of the amino acid
methyl ester hydrochloride (100 mmol) in 150 mL of chloroform
was added 28 mL of triethylamine (200 mmol) at 0 °C, and
the mixture was stirred for 15 min at room temperature. Acetyl
chloride (7.2 mL, 100 mmol) was added dropwise, and stirring
was continued for 45 min. The solvent was removed under
reduced pressure, 750 mL of ethyl acetate was added, and the
mixture was filtered through a pad of silica gel. Evaporation
of the solvent under reduced pressure afforded the amide in
high purity.
Syn t h esis of 4-Su b st it u t ed 2-Met h yl-5-m et h oxyox-
a zoles 2-6: Gen er a l P r oced u r e. N-Acetyl-L-amino acid
methyl ester (0.1 mol) was dissolved in 20 mL of chloroform
in a 250 mL flask, 20.8 g (0.1 mol) of phosphorus pentachloride
was added, and the flask was fitted with a calcium chloride
tube. The solution was gently warmed by means of a water
bath (ca. 60 °C) with stirring until the HCl gas evolution
ceased and the solution became intensively yellow. Then, the
flask was cooled by an ice-salt bath, and 50 mL of absolute
ether was added. To the cooled mixture was added 20%
aqueous KOH dropwise until neutralization with vigorous
stirring. The mixture was stirred at room temperature for 30
min. The organic layer was subsequently separated, and the
aqueous layer was extracted with 2 × 200 mL of ether. The
combined organic extracts were washed with water and brine
and dried over anhydrous MgSO4. After removal of the solvents
under vacum, the remaining oil was distilled by a Bu¨chi
Kugelrohr apparatus to give the product 2-6. Yields and
spectroscopic data for 244 and 3-639 are given as Supporting
Information.
P h otolyses of 2-Meth yl-5-m eth oxyoxa zole (1) w ith
Ald eh yd es 7a -f: Gen er a l P r oced u r e. 2-Methyl-5-meth-
oxyoxazole (1) (0.56 g, 5 mmol) and the corresponding aldehyde
(5 mmol) were dissolved in 50 mL of benzene, and the solution
was transferred to a vacuum-jacket quartz tube and degassed
with a steady stream of N2 gas. The reaction mixture was
irradiated at 10 °C in a Rayonet photoreactor (RPR 300 nm)
for 24 h. The solvent was evaporated (40 °C, 20 Torr), and the
residue was submitted to 1H NMR analysis for determination
of the diastereomeric ratios. Purification was carried out by
bulb-to-bulb distillation. The thermally and hydrolytically
unstable primary products could in most cases not be fully
characterized by combustion analysis and were hydrolyzed
subsequently to the stable R-amino-â-hydroxy esters.
exo-5-Meth oxy-3-m eth yl-7-p h en yl-4,6-d ioxa -2-a za bicy-
clo[3.2.0]h ep t-2-en e (exo-8a ). From benzaldehyde (0.53 g, 5
mmol) according to the general procedure. Distillation of the
solvent under vaccum afforded 0.82 g of the oxetane 8a as a
pale yellow oil: 75%; IR (Film) ν˜(cm-1) ) 2987, 1635, 1600,
1558, 1440, 1341, 1012, 967; 1H NMR (300 MHz, CDCl3) δ 2.11
(s, 3H), 3.79 (s, 3H), 4.58 (d, J ) 7.7 Hz, 1H), 5.68 (d, J ) 7.7
Hz, 1H), 7.26-7.31 (m, 5H); 13C NMR δ 15.9, 52.8, 76.2, 83.0,
122.9, 125.4, 126.2, 128.1, 134.3, 167.7; HRMS (C12H13NO3,
M ) 219.09 g/mol) calcd 219.0892, found 219.0886.
Yields and spectroscopic data for exo-8b-f are given as
Supporting Information.
H yd r olysis of t h e Bicyclic Oxet a n es 8a -f: Gen er a l
P r oced u r e. To a solution of the oxetane 8a -f (2 mmol) in 20
mL of methylene chloride was added 0.5 mL of concentrated
HCl. The mixture was stirred in an open flask at room
temperature for 2 h and the reaction controlled by TLC. After
complete conversion, the reaction mixture was poured into 20
mL of water and extracted with 2 × 20 mL of methylene
(44) Suga, H.; Shi, X.; Ibata, T.; Kakehi, A. Heterocycles 2001, 55,
1711-1726.
9904 J . Org. Chem., Vol. 68, No. 26, 2003

Synthesis of erythro-R-Amino â-hydroxy Carboxylic Acid Esters
chloride. The organic layer was washed with 5% NaHCO3 and
brine and dried over MgSO4. The solvent was removed in
vacuo, and the residue was purified by preparative chroma-
tography using a mixture of ethyl acetate and n-hexane as
eluent.
P h otolyses of 4-Su bstitu ted 2-Meth yl-5-m eth oxyox-
a zoles 2-6 w ith Ald eh yd es 7a -f: Gen er a l P r oced u r e. A
solution of the 5-methoxyoxazole 2-6 (5 mmol) and the
aldehyde 7a -f (5 mmol) in 50 mL of benzene was transferred
to a vacuum-jacket quartz vessel and degassed with a steady
stream of N2 gas. The reaction mixture was irradiated at 10
°C in a Rayonet photoreactor (RPR 300 nm) for 24 h. The
solvent was evaporated (40 °C, 20 Torr), and the residue was
analyzed by 1H NMR analysis. Purification was carried out
by bulb-to-bulb distillation. The thermally and hydrolytically
unstable primary products could in most cases not be char-
acterized by combustion analysis and were hydrolyzed subse-
quently to the corresponding R-amino-â-hydroxy esters.
exo-5-Meth oxy-1,3-dim eth yl-7-ph en yl-4,6-dioxa-2-azabi-
cyclo[3.2.0]h ep t-2-en e (exo-11a ). From benzaldehyde (0.53
g, 5 mmol) and 2,4-dimethyl-5-methoxyoxazole (2) (0.64 g, 5
mmol). Distillation of the solvent under vaccum afforded 0.96
g of the oxetane 11a as a pale yellow oil: 82%; 1H NMR δ 0.79
(s, 3H), 1.99 (s, 3H), 3.52 (s, 3H), 5.19 (s, 1H), 7.21-7.25 (m,
5H); 13C NMR δ 13.4, 14.8, 51.2, 75.8, 89.3, 124.5, 125.7, 128.6,
129.3, 136.9, 164.9; HRMS (C13H15NO3, M ) 233.1 g/mol) calcd
233.0762, found 233.0758.
Meth yl (2S*,3S*) 2-Acetyla m in o-3-h yd r oxy-3-p h en yl-
p r op ion a te (er yth r o-9a ). According to the general procedure,
oxetane 8a (0.44 g, 2 mmol) was hydrolyzed in 3 h. Preparative
chromatography yielded 0.33 g of 9a as a colorless oil: 70%;
1H NMR δ 2.07 (s, 3H), 3.97 (s, 3H), 4.45 (d, J ) 9.7 Hz, 1H),
5.85 (d, J ) 9.7 Hz, 1H), 6.37 (bs, 1H), 7.28-7.35 (m, 5H); 13
C
NMR δ 23.7, 52.4, 75.4, 81.6, 126.2, 128.9, 129.6, 134.3, 169.3,
170.3. Anal. (C12H15 NO4, M ) 237.10 g/mol) Calcd: C, 60.75;
H, 6.37; N, 5.90. Found: C, 60.86; H, 6.52; N, 6.00.
Yields and spectroscopic data for erythro-9b-f are given as
Supporting Information.
In d ep en d en t Syn th esis of Meth yl (2S*,3R*) 2-Acetyl-
a m in o-3-h yd r oxybu ta n oa te (th r eo-9g). A 100 mL, three-
necked, round-bottomed flask, containing a magnetic stirring
bar, was equipped with a dropping funnel and reflux con-
denser. The dropping funnel was charged with 7.8 mL of acetyl
chloride. The flask was subsequently charged with 50 mL of
methanol and cooled with an ice bath to 0 °C. Acetyl chloride
was added dropwise over a period of 10 min. The solution was
stirred for a further 5 min, L-threonine (4.5 g, 38 mmol) was
added in one portion, and the solution was slowly heated to
reflux. Reflux was continued for 3 h, and then the solution
was allowed to cool to room temperature and the solvent
removed under reduced pressure to give 4.8 g (94%) of methyl
threoniate hydrochloride. A 250 mL two-necked flask was
equipped with a magnetic stirring bar, a reflux condenser, and
a pressure-equalizing dropping funnel that was charged with
acetyl chloride (2.1 mL, 30 mmol). Methyl threoniate hydro-
chloride (4.6 g, 30 mmol) was placed in the flask and suspended
in 100 mL of chloroform and triethylamine (7.6 mL, 60 mmol).
The resulting white suspension was cooled with an ice bath,
and the solution of acetyl chloride was added dropwise over a
period of 30 min. After 15 min of additional stirring, the ice
bath was removed and the suspension stirred for a further 2
h. The solvent was removed under vacuo, ethyl acetate (150
mL) was added, and the mixture was filtered through a pad
of silica gel. Evaporation of the solvent under reduced pressure
afforded 4.9 g (89%) of N-acetyl methyl threoniate as colorless
Yields and spectroscopic data for further bicyclic oxetanes
are given as Supporting Information.
Syn th esis of er yth r o-(2S*,3S*)-R-Acetam ido-R-alkylated-
â-h yd r oxy Ester s: Gen er a l P r oced u r e. To a solution of the
oxetane (2 mmol) in 20 mL of methylene chloride, 0.5 mL of
concentrated HCl was added. The mixture is stirred in an open
flask at room temperature for 2 h and the reaction was
controlled by TLC. The reaction mixture was quenched with
water and extracted with methylene chloride (3 × 20 mL). The
organic layer was washed with 5% NaHCO3 and brine and
dried over anhydrous MgSO4. The solvent was removed in
vacuo, and the residue was purified by preparative chroma-
tography.
er yth r o-Meth yl (2S*,3S*)-2-(N-Acetylam in o)-3-h ydr oxy-
2-m eth yl-3-p h en ylp r op a n oa te (er yth r o-12a ). Following the
general procedure, oxetane 11a (0.47 g, 2 mmol) was hydrolzed
in 3 h. Preparative chromatography yielded 0.33 g of 12a as a
colorless oil: 65%; IR (film) ν˜(cm-1) ) 3350, 3320, 2988, 1720,
1680, 1580, 1440, 1340, 1062, 987; 1H NMR δ 1.23 (s, 3H),
2.12 (s, 3H), 3.79 (s, 3H), 4.06 (s, 1H), 7.32 (m, 5H); 13C NMR
δ 13.5, 21.4, 23.4, 47.7, 49.1, 52.9, 127.6, 128.4, 133.5, 169.9,
179.4; MS (EI, 70 eV) m/z 249 (M+ - H2, 4), 236 (M+ - Me, 8),
202 (8), 192 (M+ - CO2Me, 15), 191 (78), 160 (10), 132 (12),
1
crystals: mp 106-108 °C (lit.45 mp 105-106 °C); H NMR δ
0.92 (d, J ) 6.4 Hz, 3H), 1.97 (s, 3H), 3.59 (s, 3H), 4.16 (ddq,
J ) 2.6, 6.0, 6.4 Hz, 1H), 4.35 (dd, J ) 8.8, 2.6 Hz, 1H). 13C
NMR δ 13.4, 20.2, 52.1, 57.6, 67.3, 171.3, 171.4.
131 (100), 105 (50), 91 (20), 77 (30), 51 (10); HRMS (C13H17
-
NO4, M ) 251.12 g/mol) calcd 251.1254, found 251.1249.
Syn th esis of (Z)-R,â-Did eh yd r oa m in o Acid Der iva tives
10a -f: Gen er a l P r oced u r e. The photoaldol product (1
mmol) was added to 10 mL of methylene chloride, presaturated
with concentrated HCl, for 5 min and the solution stirred at
room temperature until Tlc indicated completion of the reac-
tion. The reaction mixture was then washed with saturated
NaHCO3 and saturated NaCl, dried over anhydrous Na2SO4,
and then evaporated. The residue was purified by preparative
thick-layer chromatography.
Yields and spectroscopic data for further erythro-(2S*,3S*)-
R-acetamido-R-alkylated-â-hydroxy esters are given as Sup-
porting Information.
4-sec-Bu tyl-2-m eth yl-5-m eth oxyoxa zole (21). Reaction
of methyl N-acetylamino isoleucinate (18.7 g, 0.1 mol) and PCl5
(20.8 g, 0.1 mol) according to the general procedure afforded
12.7 g (75%) of 21 as a colorless liquid: bp 89-93 °C, 10 Torr;
1H NMR δ 0.77 (t, J ) 7.4 Hz, 3H), 1.12 (d, J ) 7.1 Hz, 3H),
1.50 (m, 2H), 2.26 (s, 3H), 2.42 (m, 1H), 3.79 (s, 3H); 13C NMR
δ 11.9, 14.1, 19.3, 28.6, 31.5, 61.3, 119.9, 152.1, 154.1.
exo-1-sec-Bu tyl-7-eth yl-5-m eth oxy-3-m eth yl-4,6-d ioxa -
2-a za bicyclo[3.2.0]h ep t-2-en e (exo-22). A solution of pro-
pionaldehyde (0.29 g, 5 mmol) and 4-sec-butyl-2-methyl-5-
methoxyoxazole (21) (0.84 g, 5 mmol) in benzene (50 mL) was
irradiated for 24 h. Distillation of the solvent under vaccum
afforded 1.0 g of the oxetane 22 as a pale yellow oil. The
product was thermally unstable and was subsequently hydro-
lyzed to give the corresponding R-amino-â-hydroxy ester 23:
88%; 1H NMR δ 0.76 (d, J ) 6.6 Hz, 3H), 0.83 (m, 3H), 0.92 (t,
J ) 7.4 Hz, 3H), 1.43 (m, 1H), 1.83 (m, 2H), 2.10 (s, 3H), 3.47
(s, 3H), 4.16 (dd, J ) 3.7, 7.5 Hz, 1H); 13C NMR δ 9.0, 11.5,
12.9, 13.9, 23.5, 24.9, 32.0, 51.8, 80.4, 91.0, 124.6, 164.9; MS
Meth yl 2-Acetyla m in o-3-p h en yla cr yla te (Z-10a ). Ac-
cording to the general procedure, methyl 2-acetylamino-3-
hydroxy-3-phenylpropionate 9a (0.24 g, 1 mmol) was dehy-
drated in 20 h. Preparative chromatography yielded 0.17 g of
the product as a colorless oil which was solidified from a
mixture of chloroform and petroleum ether as a colorless
powder: 80%; mp 122-124 °C (ref 125 °C).46
Yields and spectroscopic data for Z-10d ,47 Z-10e,48 and
Z-10f49 are given as Supporting Information.
(45) Pfister, K.; Robinson, C. A.; Shabica, A. C.; Tishler, M. J . Am.
Chem. Soc. 1949, 71, 1101-1103.
(46) Cook, A. H.; Harris, G.; Heilbron, I.; Shaw, G. J . Chem. Soc.
1948, 1056-1060.
(47) Burk, M. J .; Feaster, J . E.; Nugent, W. A.; Harlow, R. L. J .
Am. Chem. Soc. 1993, 115, 10125-10138.
(49) Kuwano, R.; Sawamura, M.; Ito, Y. Bull. Chem. Soc. J pn. 2000,
73, 2571-2578.
(48) Poisel, H.; Schmidt, U. Chem. Ber. 1975, 108, 2547-2553.
J . Org. Chem, Vol. 68, No. 26, 2003 9905

Griesbeck et al.
(EI, 70 eV) m/z 216 (M+ - Et, 10), 196 (5), 186 (18), 170 (20),
169 (35), 168 (52), 155 (32), 144 (75), 126 (100), 112 (43), 99
(20), 95 (15), 84 (55), 70 (18), 57 (60).
(t, J ) 6.0 Hz, 2H), 1.10 (t, J ) 7.6 Hz, 3H), 1.42 (m, 2H), 1.75
(m, 2H), 1.98 (s, 3H), 3.69 (s, 3H), 5.30 (dd, J ) 10.9, 2.6 Hz,
1H), 6.38 (bs, 2H); 13C NMR δ 9.2, 11.3, 13.3, 17.6, 23.7, 36.0,
52.8, 67.8, 77.6, 172.9, 173.6; HRMS (C11H21 NO4, M ) 231.15
g/mol) calcd 231.1473, found 231.1471.
Cyclization of th e Z-Am idoacr ylate 10a. Meth yl 1-Meth -
yl-isoqu in olin e-3-ca r boxyla te (25). To an ice-cooled solution
of 210 mg (1 mmol) of methyl (Z)-2-acetylamino-3-phenylacry-
late (10a ) in 20 mL of methylene chloride was added 200 mg
(1.5 mmol) of phosphorus oxychloride, and the solution was
heated to 60 °C for 2 h. After being cooled to room temperature
and quenched with 25 mL of saturated sodium bicarbonate,
the mixture was extracted with methylene chloride (3 × 10
mL) and dried over MgSO4. After evaporation of the solvent,
the residue was purified by column chromatography to give
290 mg (78%) of the isoquinoline 25 as a colorless powder with
mp 105-107 °C (lit.38 mp 104-105 °C).
er yth r o-Meth yl (2S*,3S*) 2-Acetyla m in o-2-(1-h yd r oxy-
p r op yl)-3-m et h ylp en t a n oa t e (er yth r o-23). Following the
general procedure, oxetane 22 (0.45 g, 2 mmol) was hydrolyzed
in 3h. Preparative chromatography yielded 0.37 g of 23 as a
colorless oil. Single crystals suitable for X-ray crystal structure
analysis were obtained by recrystallization from chloroform:
1
75%; mp 43-45 °C; H NMR δ 0.76 (d, J ) 6.9, Hz, 3H), 0.85
(t, J ) 7.2, Hz, 3H), 0.96 (t, J ) 7.1 Hz, 3H), 1.21 (m, 1H),
2.08 (s, 3H), 2.42 (m,1H), 3.77 (s, 3H), 4.62 (dd, J ) 11.7, 1.7
Hz, 1H), 6.90 (bs, 1H); 13C NMR δ 10.8, 12.3, 13.3, 13.9, 23.7,
27.3, 37.4, 52.9, 73.7, 74.2, 170.8, 172.8. Anal. (C12H23NO4, M
) 245.32 g/mol) Calcd: C, 58.75; H, 9.45; N, 5.71. Found: C,
59.03; H, 9.38; N, 5.62.
Tr a n sa cyla tion : Gen er a l P r oced u r e. To a solution of the
R-acetamido-â-hydroxy ester (approximately 300 mg, 15 mmol)
in 15 mL of chloroform was added 0.2 mL of 1 N aq HCl at
room temperature and the mixture stirred overnight. After the
reaction was quenched with water (15 mL), the mixture was
extracted with methylene chloride (3 × 15 mL), the organic
extract was washed with 5% sodium bicarbonate solution and
dried over MgSO4, and the solvent was removed under
vacuum. The residue was purified by preparative thin-layer
chromatography.
Meth yl (2S*,3S*)-3-Acetoxy-2-a m in o-2-p r op ylp en ta n -
oa te (er yth r o-24d ). From 16d following the gernal procedure.
Preparative chromatography yielded 0.24 g of the product as
a colorless oil: 79%; 1H NMR δ 0.78 (t, J ) 7.4, Hz, 3H), 0.84
Ack n ow led gm en t. We thank the Deutsche Fors-
chungsgemeinschaft and the Fonds der Chemischen
Industrie for financial support. S.B. thanks the Egyp-
tian government for a Ph.D. grant (2000-2003).
Su p p or tin g In for m a tion Ava ila ble: Yields and spectro-
scopic data for substrates, bicyclic oxetanes, and R-acetamido-
â-hydroxy esters, 13C NMR spectra of bicyclic oxetanes, and
X-ray crystallographic data for compound 23. This material
is available free of charge via the Internet at http://pubs.acs.org.
J O034830H
9906 J . Org. Chem., Vol. 68, No. 26, 2003