Photocycloaddition of N-acyl enamines to aldehydes and its application to the synthesis of diastereomerically pure 1,2-amino alcohols

Article abstract of DOI:10.1021/jo9819988

The regio- and stereoselective synthesis of the protected cis-3- aminooxetanes cis-5 and cis-7 is reported. The oxetanes were obtained by the photocycloaddition of aliphatic (6c-e) and aromatic (4, 6a) aldehydes to the corresponding enamides (1a-d,h) or enecarbamates (1e-g). The enamine derivatives used in the Paterno-Buchi reaction were either commercially available or prepared from the corresponding acetaldehyde imines 2 by acylation. The oxetane formation proceeded with good-to-excellent simple diastereoselectivity for aromatic aldehydes (56-82% yield) and moderate selectivity for aliphatic aldehydes (46-55% yield). The cis-3-aminooxetanes are precursors for syn- and anti-1,2-amino alcohols. The relative configuration established in the photochemical step was retained upon nucleophilic ring opening between the oxygen atom and carbon atom C-4. By this means, syn-1,2-amino alcohols such as 8 and 10 were available in good yields. In contrast, the N-Boc-protected cis-3-aminooxetanes cis-5e and cis- 5f were transformed into anti-1,2-amino alcohols. Upon treatment with trifluoroacetic acid, they underwent an intramolecular nucleophilic substitution at the carbon atom C-2 of the oxetane and the oxazolidinones 11 and 12 were formed. Because the substitution occurs with inversion of configuration, anti-1,2-amino alcohols, e.g., ephedrine (15), are accessible.

Full text of DOI:10.1021/jo9819988

J . Org. Chem. 1999, 64, 1265-1273
1265
P h otocycloa d d ition of N-Acyl En a m in es to Ald eh yd es a n d Its
Ap p lica tion to th e Syn th esis of Dia ster eom er ica lly P u r e 1,2-Am in o
Alcoh ols
Thorsten Bach* and J u¨rgen Schro¨der
Fachbereich Chemie der Philipps-Universita¨t Marburg, D-35032 Marburg, Germany
Received October 5, 1998
The regio- and stereoselective synthesis of the protected cis-3-aminooxetanes cis-5 and cis-7 is
reported. The oxetanes were obtained by the photocycloaddition of aliphatic (6c-e) and aromatic
(4, 6a ) aldehydes to the corresponding enamides (1a -d ,h ) or enecarbamates (1e-g). The enamine
derivatives used in the Paterno`-Bu¨chi reaction were either commercially available or prepared
from the corresponding acetaldehyde imines 2 by acylation. The oxetane formation proceeded with
good-to-excellent simple diastereoselectivity for aromatic aldehydes (56-82% yield) and moderate
selectivity for aliphatic aldehydes (46-55% yield). The cis-3-aminooxetanes are precursors for syn-
and anti-1,2-amino alcohols. The relative configuration established in the photochemical step was
retained upon nucleophilic ring opening between the oxygen atom and carbon atom C-4. By this
means, syn-1,2-amino alcohols such as 8 and 10 were available in good yields. In contrast, the
N-Boc-protected cis-3-aminooxetanes cis-5e and cis-5f were transformed into anti-1,2-amino alcohols.
Upon treatment with trifluoroacetic acid, they underwent an intramolecular nucleophilic substitu-
tion at the carbon atom C-2 of the oxetane and the oxazolidinones 11 and 12 were formed. Because
the substitution occurs with inversion of configuration, anti-1,2-amino alcohols, e.g., ephedrine (15),
are accessible.
In tr od u ction
good regio- and stereocontrol. Typical enamines derived
from secondary amines had proven unsuited for the
photochemical aminooxetane formation.5 1,3-Oxazoline
and its derivatives reacted well with aldehydes in a [2 +
2] photocycloaddition, but the regioselectivity was not
satisfactory.6 N-Substituted pyrroles gave almost exclu-
sively 1,3-difunctional 2-aminooxetanes.7 The consecutive
3-Heteroatom-substituted oxetanes are versatile syn-
thetic building blocks that can be transformed into 1,2-
difunctional or 1,2,3-trifunctional compounds by subse-
quent ring-opening reactions.1 The Paterno`-Bu¨chi reac-
tion2 of 3-heteroatom-substituted alkenes and aldehydes
represents a short and straightforward route to these
heterocycles.3 As a result of the photochemical “umpol-
ung” of the carbonyl compound, a 1,2-connectivity of the
former carbonyl carbon atom and the former R-carbon
atom of the alkene, which is more difficult to attain by
other methods, is established. In this respect, enamines
may serve as precursors for 3-aminooxetanes, which in
turn can be further used for the synthesis of 1,2-amino
alcohols4 (Scheme 1).
(4) For references to recent work on 1,2-amino alcohol synthesis by
diastereoselective formation of the central C-C bond, see (a) Henry
reaction: Kiess, F.-M.; Poggendorf, P.; Picasso, S.; J a¨ger, V. J . Chem.
Soc., Chem. Commun. 1998, 119. Ballini, R.; Bosica, G.; Forconi, P.
Tetrahedron 1996, 52, 1677. Fey, P. In Methoden der Organischen
Chemie (Houben-Weyl) 4te Aufl.; Helmchen, G., Hoffmann, R. W.,
Mulzer, J ., Schaumann, E., Eds. Thieme: Stuttgart, 1995; Vol. E 21c,
p 1776. Kiyooka, S.-i.; Tsutsui, T.; Maeda, H.; Kaneko, Y.; Isobe, K.
Tetrahedron Lett. 1995, 36, 6531. (b) Glycin enolates and their
equivalents: Kobayashi, S.; Furuta, T.; Hayashi, T.; Nishijama, M.;
Hanada, K. J . Am. Chem. Soc. 1998, 120, 908. Barrett, A. G. M.;
Seefeld, M. A.; White, A. J . P.; Williams, D. J . J . Org. Chem. 1996, 61,
2677. Hartwig, W. In Methoden der Organischen Chemie (Houben-
Weyl) 4te Aufl., Helmchen, G., Hoffmann, R. W., Mulzer, J ., Schau-
mann, E., Eds. Thieme: Stuttgart, 1995; Vol. E 21c, p 1769. Vassilev,
V. P.; Uchiyama, T.; Kajimoto, T.; Wong, C.-H. Tetrahedron Lett. 1995,
36, 4081. Patonay, T.; Hoffman, R. V. J . Org. Chem. 1995, 60, 2368.
Blank, S.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1993, 32, 1765.
(c) Other methods: Kobayashi, S.; Ishitani, H.; Ueno, M. J . Am. Chem.
Soc. 1998, 120, 431. Wilken, J .; Martens, J . Liebigs Ann. 1997, 563.
Gawley, R. E.; Zhang, P. J . Org. Chem. 1996, 61, 8103. Ebden, M. R.;
Simpkins, N. G.; Fox, D. N. A. Tetrahedron Lett. 1995, 36, 4081. Ito,
H.; Taguchi, T.; Hansawa, Y. Tetrahedron Lett. 1992, 31, 4469.
(5) Kawanisi, M.; Kamogawa, K.; Okada, T.; Nozaki, H. Tetrahedron
1968, 24, 6557.
(6) (a) Scholz, K.-H.; Heine, H.-G.; Hartmann, W. Tetrahedron Lett.
1978, 17, 1467. (b) Weuthen, M.; Scharf, H.-D.; Runsink, J . Chem. Ber.
1987, 120, 1023. (c) Weuthen, M.; Scharf, H.-D.; Runsink, J .; Vassen,
R. Chem. Ber. 1988, 121, 971.
(7) (a) J ulian, D. R.; Tringham, G. D. J . Chem. Soc., Chem. Commun.
1973, 13. (b) Nakano, T.; Rivas, C.; Perez, C.; Larrauri J . M. J .
Heterocycl. Chem. 1976, 13, 173. (c) Rivas, C.; Bolivar, R. A. J .
Heterocycl. Chem. 1976, 13, 1037. (d) J ones, G., II; Gilow, H. M.; Low,
J . J . Org. Chem. 1979, 44, 2949. (e) Nakano, T.; Rodr´ıguez, W.; de
Roche, S. Z.; Larrauri, J . M.; Rivas, C.; Perez, C. J . Heterocycl. Chem.
1980, 17, 1777.
Sch em e 1
Prior to our work, some studies were reported in regard
to the search for suitably protected cyclic or acyclic
enamines that undergo the Paterno`-Bu¨chi reaction with
(1) Reviews: (a) Bach, T. Liebigs Ann./ Recueil 1997, 1627. (b) Bach,
T. GIT Fachz. Lab. 1997, 41, 299.
(2) For recent reviews, see: (a) Mattay, J .; Conrads, R.; Hoffmann,
R. In Methoden der Organischen Chemie (Houben-Weyl) 4te Aufl.;
Helmchen, G., Hoffmann, R. W., Mulzer, J ., Schaumann, E., Eds.;
Thieme: Stuttgart, 1995; Vol. E 21c, p 3133. (b) Porco, J . A.; Schreiber,
S. L. In Comprehensive Organic Synthesis; Trost, B., Ed.; Pergamon
Press: Oxford, 1991; Vol. 5, p 151. (c) Carless, H. A. J . In Synthetic
Organic Photochemistry; Horspool, W. M., Ed.; Plenum Press: New
York, 1984; p 425. (d) J ones, G. In Organic Photochemistry; Padwa,
A., Ed.; Dekker: New York, 1981; Vol. 5; p 1.
(3) Review on synthetic applications: Bach, T. Synthesis 1998, 683.
10.1021/jo9819988 CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/03/1999

1266 J . Org. Chem., Vol. 64, No. 4, 1999
Bach and Schro¨der
Sch em e 2
reactions of these adducts with an additional equivalent
of aldehyde delivered 3-aminooxetanes, but the reaction
was not exploited any further.7c Good regio- and stereo-
selectivities were observed in the Paterno`-Bu¨chi reaction
of R-aminoacrylonitriles with benzil and its derivatives.8
The 3-amino-3-cyanooxetanes so obtained are less suited
for applications in stereoselective synthesis, however.
Our approach to 3-aminooxetanes was based on the use
of acceptor-substituted enamines, which we hoped would
be electron-rich enough to account for the addition of the
photoexcited carbonyl compound and which should be
electron-deficient enough to avoid side reactions based
on a single electron transfer (SET). Indeed, it turned out
that N-acyl- and N-alkoxycarbonyl-protected enamines
(enamides and enecarbamates) are excellent substrates
for the Paterno`-Bu¨chi reaction. They react cleanly with
a variety of aldehydes to the corresponding oxetanes, and
their addition products can be further manipulated in
several ways. The following report gives a full account
on the preparation of these enamines, their photocycload-
dition to aldehydes,9 and the ring-opening reactions of
3-aminooxetanes to 1,2-amino alcohols.10
Sch em e 3
Ta ble 1. P h otocycloa d d ition of Alk en es 1 to
Ben za ld eh yd e (4) in Aceton itr ile Solu tion
entry
alkenea
timeb [h]
product
d.r.c
yieldd [%]
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
18
120
14
14
14
14
14
18
5a
5b
5c
5d
5e
5f
71/29
79/21
89/11
>90/10
90/10
87/13
>90/10
88/12
74
58e
81
71
56
77
74
82
Resu lts a n d Discu ssion
P r ep a r a tion of En a m id es a n d En eca r ba m a tes.
The structures of the alkene components used in this
study are shown. N-Vinylformamide (1a ) and N-vinyl-
1g
1h
5g
5h
a
In most cases an excess (2 equiv) of alkene was used (see the
b
c
Experimental Section). Irradiation time. Diastereomeric ratio
cis-5/trans-5 as determined from GLC and 1H NMR analysis of
d
the crude product mixture. Yield of isolated oxetane product.
In most cases, the cis-isomer cis-5 strongly prevails (d.r. ) g90/
10), although a complete separation could not always be achieved
(for the precise diastereomeric composition of the isolated product
see the Experimental Section). e The yield relative to the converted
amount of benzaldehyde is 79%.
2b with diphosgene (Cl3COCOCl) according to a pub-
lished procedure (Scheme 2).13
pyrrolidinone (1h ) are industrially used monomer build-
ing blocks and are consequently commercially available.
N-Vinylacetamide (1b) was obtained from vinyl isocyan-
ate via a published procedure.11 All other alkenes were
prepared by the N-acylation of acetaldehyde imines. For
the acetylation, we followed the procedure by Breederveld
in which acetic anhydride was used as the acylating
agent.12 In an analogous fashion, the tert-butyloxycar-
bonylation (tert-butyloxycarbonyl ) Boc) could be con-
ducted with Boc2O and NEt3 in benzene or toluene. By
this means, the enecarbamates 1e and 1f were obtained
from the imines 2a and 2b in 80% and 69% yield (Scheme
2). Attempts to use alkoxycarbonyl chlorides as N-
acylation agents did not give satisfactory results.
Oxeta n e F or m a tion . The Paterno`-Bu¨chi reaction of
N-acyl enamines 1 was first studied with benzaldehyde
(4) as the carbonyl substrate. A clean photocycloaddition
was observed, which yielded the corresponding 3-amino-
oxetanes 5 (Scheme 3, Table 1). The oxetanes were
formed with good-to-excellent simple diastereoselectivity
in favor of the cis-products. The relative configuraton was
assigned on the basis of NOE and NOESY studies on
oxetanes 5b, 5c, 5f, and 5h , the results of which are given
in the Experimental Section. The correlations accom-
plished by ring-opening reactions (vide infra) further
support the stereochemical assignments. Acetonitrile
proved to be a superior solvent for the photocycloaddition
as compared to aromatic (benzene, toluene) or aliphatic
(cyclohexane, n-hexane) hydrocarbons. The influence of
the solvent on the diastereoselectivity was minor, and
the diastereomeric ratio recorded for the irradiation of
benzaldehyde and enamide 1h in benzene, for example,
did not differ significantly from the results obtained in
acetonitrile solution. In most examples, except for oxe-
tanes 5c and 5d , the diastereomeric oxetane products
cis-5 and trans-5 could not be fully separated by chro-
matography. An enrichment of the major stereoisomer
The 2-trimethylsilylethyloxycarbonyl (Teoc)-protected
enamine 1g was available from carbamoyl chloride 3,
which in turn was synthesized by the reaction of aldimine
(8) (a) Do¨pp, D.; Memarian, H. R.; Fischer, M. A.; van Eijk, A. M.
J .; Varma, C. A. G. O. Chem. Ber. 1992, 125, 983. (b) Do¨pp, D.; Fischer,
M.-A. Recl. Trav. Chim. Pays-Bas 1995, 114, 498.
(9) Preliminary communication: Bach, T. Angew. Chem., Int. Ed.
Engl. 1996, 35, 884.
(10) Preliminary communication: Bach, T.; Schro¨der, J . Tetrahedron
Lett. 1997, 38, 3707.
(11) Schulz, R. C.; Hartmann, H. Monatsh. Chem. 1961, 92, 303.
(12) (a) Breederveld, H. Recl. Trav. Chim. Pays-Bas 1960, 79, 401.
(b) Meth-Cohn, O.; Westwood, K. T. J . Chem. Soc., Perkin Trans. 1
1984, 1173.
(13) Tamura, O.; Hashimoto, M.; Kobayashi, Y.; Katoh, T.; Nakatani,
K.; Kamada, M.; Hayakawa, I.; Akiba, T.; Terashima, S. Tetrahedron
1994, 50, 3889.

Photocycloaddition of N-Acyl Enamines to Aldehydes
J . Org. Chem., Vol. 64, No. 4, 1999 1267
Sch em e 4
conversion to the corresponding nπ* triplet states (T1)
via a fast ISC step (k ) >1010 s-1),2d and the O-C bond
formation has been shown to be the first step in the
Paterno`-Bu¨chi reaction of electron-rich alkenes leading
to a biradical intermediate (3D).2 Indications for a single-
electron transfer have not been found in our case. An
exciplex formation prior to the bond forming steps cannot
be excluded, however.
According to mechanistic arguments given above, the
C-C bond formation can be singled out as the stereose-
lectivity-determining step. For systems in which a singlet
1
biradical D (Scheme 4) either is extremely short-lived
or does not even represent a minimum on the energy
hypersurface, the ISC step of triplet biradical 3D is
responsible for the simple diastereoselectivity. On the
basis of earlier arguments put forward by Salem and
Rowland,20 Griesbeck and co-workers identified certain
ISC geometries that are suited to the facilitation of this
step by the maximization of the obligatory spin-orbit
coupling.21 According to their analysis, the orbitals which
bear the unpaired electrons are required to be orthogonal
to each other to allow a fast ISC to occur. Depending on
steric interactions in these conformations, the ISC rates
can differ significantly. This difference finally leads to
the preferential formation of a single oxetane diastereo-
isomer.
was possible, however (see Table 1 and Experimental
Section). Regioisomeric products were not detected in
significant quantities. Although the propensity of het-
eroatom-substituted alkenes to be attacked at the more
electron-rich â-position in Paterno`-Bu¨chi reactions is
well-known,14 the almost exclusive preference in favor of
this addition mode is remarkable. Indeed, R-unsubsti-
tuted enol derivatives such as enol acetates15 and enol
ethers16 react only with modest regioselectivity (65/35 to
75/25) in the Paterno`-Bu¨chi reaction. The regioselectiv-
ity increases if an R-alkyl substituent is present.1 Good
regioselectivities have been previously reported for the
photocycloaddition of vinyl sulfides to benzophenone.14,17
Preparatively, the [2 + 2] photocycloaddition of benz-
aldehyde and N-acyl enamines is easy to conduct, and
no precautions were taken to avoid exposure of the
reaction mixture to oxygen or water. In general, major
side reactions were not noticed except for the inevitable
pinacol formation, which is due to hydrogen abstraction
by the photoexcited benzaldehyde and its subsequent
addition to another benzaldehyde molecule.18 In the case
of the secondary enamides 1a and 1b, the formation of
polymeric byproducts was detected (entries 1 and 2). The
resulting precipitate retarded the velocity of the photo-
cyloaddition as it partially covered the glass wall of the
reaction vessel. Nonetheless, the yields of oxetanes 5a
and 5b are satisfactory. Apparently, the Paterno`-Bu¨chi
reaction can efficiently compete with a radical-type
polymerization of the alkene substrates.
The biradical conformation A encounters the least
steric strain because only the hydrogen atoms at the
radical centers get into close proximity to each other. Any
other conformation (B or C) requires that a larger
substituent resides in the congested situation, disfavoring
this arrangement and thus retarding the ISC step to the
trans-oxetane. The cis-product that is accessed from
conformation A is consequently obtained as the major
product. It should be noted, however, that these argu-
1
ments are valid only if the singlet biradical D (Scheme
4) cannot account for a separate selection step as a result
of the aforementioned reasons. On the basis of literature
precedent, indeed this appears to be the case for terminal
alkenes.15,16
For a mechanistic explanation of the high simple
diastereoselectivities recorded in the enamide photocy-
cloaddition, we rely on the picture of a stepwise formation
of the oxetane ring (Scheme 4).19 Initial O-C bond
formation by attack of the photoexcited aldehyde in its
triplet nπ* state at the alkene is succeeded by the C-C
bond-forming step, which occurs after intersystem cross-
ing (ISC). Indeed, it is known that the irradiation of
aromatic carbonyl compounds results in an efficient
As a variety of aromatic aldehydes were successfully
employed as carbonyl compounds in previous photocy-
cloaddition reactions of 3-heteroatom-substituted alk-
enes,1,22 only one additional example (aldehyde 6a ) was
tested in this study. Instead, we made an effort to look
into other potentially useful aldehydes as reaction part-
ners. Mostly, enecarbamate 1f served as the alkene
substrate. It was a pleasant surprise for us to note that
aliphatic aldehydes, which are known to be notoriously
sluggish carbonyl substrates for the Paterno`-Bu¨chi
(14) Khan, N.; Morris, T. H.; Smith, E. H.; Walsh, R. J . Chem. Soc.,
Perkin Trans. 1 1991, 865, and references therein.
(15) Ruotsalainen, H.; Ka¨rki, T. Acta Chem. Scand. 1983, B37,
151.
(16) (a) Schroeter, S. H.; Orlando, C. M., J r. J . Org. Chem. 1969,
34, 1181. (b) Araki, Y.; Nagasawa, J .-i.; Ishido, Y. Carbohydr. Res. 1981,
91, 77.
(17) Morris, T. H.; Smith, E. H.; Walsh, R. J . Chem. Soc., Chem.
Commun. 1987, 964.
(18) Gilbert, A.; Baggott, J . Essentials of Molecular Photochemistry;
Blackwell: Oxford, 1991; p 302.
(19) (a) Freilich, S. C.; Peters, K. S. J . Am. Chem. Soc. 1981, 103,
6255. (b) Freilich, S. C.; Peters, K. S. J . Am. Chem. Soc. 1985, 107,
3819.
(20) Salem, L.; Rowland, C. Angew. Chem., Int. Ed. Engl. 1972, 11,
92.
(21) (a) Griesbeck, A. G.; Stadtmu¨ller, S. Chem. Ber. 1990, 123, 357.
(b) Griesbeck, A. G.; Stadtmu¨ller, S. J . Am. Chem. Soc. 1990, 112, 1281.
(c) Griesbeck, A. G.; Stadtmu¨ller, S. J . Am. Chem. Soc. 1991, 113, 6923.
(d) Griesbeck, A. G.; Mauder, H.; Peters, K.; Peters, E.-M.; von
Schnering, H. G. Chem. Ber. 1991, 124, 407. (e) Review: Griesbeck,
A. G.; Mauder, H.; Stadtmu¨ller, S. Acc. Chem. Res. 1994, 27, 70.
(22) Bach, T. Liebigs Ann. 1995, 855.

1268 J . Org. Chem., Vol. 64, No. 4, 1999
Bach and Schro¨der
Sch em e 5
Sch em e 6
Ta ble 2. P h otocycloa d d ition of En eca r ba m a te 1f to
Va r iou s Ald eh yd es 6 in Aceton itr ile Solu tion
timeb
yieldd
[%]
entrya
R
aldehyde [h] product d.r.c
1
2
3
4
5
2-PivOC6H4
n-BuOOC
n-Pr
6a
6b
6c
6d
6e
15
15
15
15
40
7a
7b
7c
7d
7e
>90/10 62
90/10 33
75/25 55
65/35 46e
69/31 54
failure could be interpreted and this problem might be
overcome. The test substrates 5c and 5f we frequently
employed to screen possible ring-opening reactions bear
a fully protected amino group at the C-3 carbon atom.
In combination with our work on 3-oxetanols, we had
previously noted that the silyl-protected 3-oxetanols are
not suited for nucleophilic ring opening at C-4.26 The
parent 3-oxetanols, however, do undergo these reactions
with ease.27 It was postulated that the free hydroxy group
in these oxetanes is able to coordinate the metal that
carries the potential nucleophile, thus rendering the
reaction intramolecular.25,28 If similar arguments were
applicable to 3-aminooxetanes, the secondary 3-oxetanyl-
amides 5a and 5b should be amenable to nucleophilic
substitution at C-4. Indeed, the formamide 5a readily
reacted with LiAlH4 to yield a ring-opened product that
was identified as pseudoephedrine (8) by comparison with
authentic material (Scheme 6). In a single step, the
reduction of the formyl group and the reductive ring
opening occurred. It was not possible by TLC to trace
back any intermediates, and it remains open what type
of reduction occurs more readily in this particular
example. In any case, the free NH group is apparently a
handle to achieve a successful ring opening of 3-amino-
oxetanes.
Despite the fact that 3-oxetanylamides such as 5a are
available directly from secondary amides, a drawback to
their use is the fact that any nucleophile will have at
least two positions to attack, i.e., either the electrophilic
C-4 carbon atom of the oxetane ring or the carbonyl group
of the amide. In the previous example, the double attack
was desirable, but in many other instances, this ambigu-
ity should be avoided. We therefore intended to remove
one of the acyl or alkoxycarbonyl protective groups from
the doubly protected 3-aminooxetanes 5c, 5f, or 5g, a
maneuver that should give access to the corresponding
N-benzyl-protected aminooxetane 9. Saponification of 5c
proved difficult under a variety of conditions, and the
acidic cleavage of the Boc group in oxetane 5f yielded an
unexpected result (vide infra). The removal of the Teoc
group emerged finally as the most reliable way to
generate oxetane 9 (Scheme 6). As expected, this oxetane
underwent ring-opening reactions and 1,2,3 functionality
can be established by this means. As an example, the
nucleophilic displacement by benzyl mercaptide,25e which
yielded compound 10, is depicted in Scheme 6. The
relative configuration established in the photochemical
key step is fully retained in these ring-opening reactions,
Me
TBDMSO(CH2)2
a
Except for entry 4, an excess of alkene was used (see the
Experimental Section). Irradiation time. c Diastereomeric ratio
b
cis-7/trans-7 as determined from GLC and/or 1H NMR analysis of
d
the crude product mixture. Yield of isolated oxetane product. The
diastereomeric composition of the isolated product is similar to
the crude d.r. (see the Experimental Section). e The alkene was
used as the limiting agent.
reaction because of competitive Norrish-type cleavage
reactions,2d underwent a fairly clean photocycloaddition
to the corresponding oxetane (Scheme 5). Some examples
are listed in Table 2.
Contrary to the 2-aryloxetanes 5 and 7a , the oxetanes
7c-e obtained from aldehydes 6c-e were formed with
only moderate diastereomeric excess. A likely reason for
this lack of stereoselectivity is the lower ISC rate of
photochemically excited aliphatic aldehydes (S1 f T1).2d
Subsequent photocycloaddition reactions are known to
occur at least partially in the singlet manifold.2 If this is
the case, factors other than the ones discussed above
govern the C-C bond-formation step and the simple
diastereoselectivity may decrease.21d Still, even with
aliphatic aldehydes there is an appreciable preference for
the cis-oxetane, as proven by NOESY studies on 7b and
7e, and altogether the Paterno`-Bu¨chi reaction of N-acyl
enamines is certainly the most direct approach for the
synthesis of cis-3-aminooxetanes. An application of this
method to the synthesis of the naturally occurring
antibiotic (()-oxetin via oxetane 7b has been recently
reported.23
Syn th esis of syn -1,2-Am in o Alcoh ols. Nucleophilic
displacement reactions were expected to occur at the
least-substituted C-4 position of the oxetanes 5 and 7.
The relative configuration established during the pho-
tocycloaddition at C-2 and C-3 would be retained by this
ring-opening mode, and syn-1,2-amino alcohols should be
formed. Most of the previously used reagents24,25 unfor-
tunately failed to facilitate the desired nucleophilic
substitution at C-4, and the question arose how this
(23) Bach, T.; Schro¨der, J . Liebigs Ann./ Recueil 1997, 2265-2267.
(24) Reviews: (a) Searles, S. In The Chemistry of Heterocyclic
Compounds; Weissberger, A., Ed.; Wiley-Interscience: New York, 1964;
Vol. 19-2,
p 983. (b) Searles, S. In Comprehensive Heterocyclic
Chemistry; Katritzky, A. R., Ed.; Pergamon Press: Oxford, 1984; Vol.
7, p 363.
(25) Recent examples: (a) Imai, T.; Nishida, S.; Tsuji, T. J . Chem.
Soc., Chem. Commun. 1994, 2353. (b) Chini, M.; Crotti, P.; Favero, L.;
Macchia, F. Tetrahedron Lett. 1994, 35, 761. (c) Crotti, P.; Favero, L.;
Macchia, F.; Pineschi, M. Tetrahedron Lett. 1994, 35, 7089. (d) Meguro,
M.; Asao, N.; Yamamoto, Y. J . Chem. Soc., Perkin Trans. 1 1994, 2597.
(e) Xianming, H.; Kellogg, R. M. Tetrahedron: Asymmetry 1995, 6,
1399. (f) Mizuno, M.; Kanai, M.; Iida, A.; Tomioka, K. Tetrahedron:
Asymmetry 1996, 7, 2483. (g) Ito, K.; Fukuda, T.; Katsuki, T. Synlett
1997, 387.
(26) Bach, T.; J o¨dicke, K. Chem. Ber. 1993, 126, 2457.
(27) (a) Bach, T.; Kather, K. J . Org. Chem. 1996, 61, 3900. (b) Bach,
T.; Eilers, F. Eur. J . Org. Chem. 1998, 2161.
(28) (a) Bach, T.; Lange, C. Tetrahedron Lett. 1996, 37, 4363. (b)
Bach, T.; Eilers, F.; Kather, K. Liebigs Ann./ Recueil 1997, 1529-1536.

Photocycloaddition of N-Acyl Enamines to Aldehydes
J . Org. Chem., Vol. 64, No. 4, 1999 1269
Sch em e 7
Sch em e 8
and the synthesis of syn-1,2-amino alcohols from cis-
aminooxetanes can indeed be achieved as suggested in
Scheme 1. In analogy to the 2-aryl-3-aminooxetanes, their
2-alkyl-substituted counterparts are equally amenable to
nucleophilic attack at the carbon atom C-4. Applications
of this route to syn-1,2-amino alcohols are currently being
studied.
Syn th esis of a n ti-1,2-Am in o Alcoh ols. By accident,
we found that anti-1,2-amino alcohols can be generated
from cis-aminooxetanes, which is a useful complement
to the above-mentioned ring-opening reactions. In at-
tempts to remove the Boc group from oxetane 5f by
trifluoroacetic acid (TFA) catalysis, we noticed the forma-
tion of an unexpected major product, which proved to be
the oxazolidinone 11. Because we had used a diastereo-
meric mixture of cis-5f and trans-5f (90/10) as the
starting material, the diastereoisomer of oxazolidinone
11 was also isolated in 5% yield. The relative configura-
tion of the products was established by NMR spectroscopy
(NOE experiments). We could demonstrate that the
reaction occurs stereospecifically,10,29 and the mechanism
depicted in Scheme 7 can be invoked to explain the
results.
The protonation of the carbonyl oxygen of the Boc
group, which is a prerequisite for its succesive cleavage,
cannot compete against the electrophilic attack of the
proton that occurs at the more accessible and more basic30
oxetane oxygen atom. Activated by this means, the
oxetane undergoes displacement at C-2 by the intramo-
lecular oxygen nucleophile, and the tert-butyl cation acts
as an electrophilic leaving group. The formation of a free
carbenium ion can be ruled out on the basis of the
stereospecifity of the reaction. On the contrary, in some
related cases in which the ring opening of 3-oxetanol
derivatives was studied, the intermediacy of carbenium
ions appears to be likely.31 The regioselective attack at
C-2 is attributed to the conformational preference of 3-N-
Boc-amino-2-phenyloxetanes, with the carbonyl oxygen
of the Boc group oriented toward the electrophilic center.
For 2-alkyloxetanes such as 7c, the regioselectivity was
less pronounced and a mixture of regioisomeric ring-
opening products was obtained.
As a short example for the application of the ring
opening to anti-1,2-amino alcohols, we have prepared
ephedrine (15) and N-methylephedrine (16). The amino-
oxetane 5e was used as the starting material and upon
treatment with TFA underwent smooth ring expansion
to oxazolidinone 12. After conversion of the primary
hydroxy group in 12 to a leaving group and subsequent
reductive dehydrotosylation32 of compound 13, the hy-
drolysis of oxazolidinone 14 gave the target compound
(Scheme 8).
The conversion of tosylate 13 to N-methylephedrine
(16) was even more facile with LiAlH4 as the reducing
agent (97% yield).
Con clu sion
The photochemical “umpolung” of a carbonyl compound
can be successfully employed for the construction of 1,2-
difunctionality in the photocycloaddition of aldehydes and
acceptor-substituted enamines. The reactions proceeded
with excellent regioselectivity and yielded exclusively the
corresponding 3-aminooxetanes. In addition, the simple
diastereoselectivity in preference of the cis-product is
high if aromatic aldehydes are used. An explanation for
the preferential formation of the apparently less stable
cis-products is based on a kinetic scheme in which the
ISC rates of a putative triplet 1,4-biradical are respon-
sible for the stereoselection. The rates differ for various
conformations of the biradical, and the geometry favored
on steric arguments accounts for the fastest ISC. In the
singlet manifold, this selection does not apply and
aliphatic aldehydes that react partially via their singlet
excited states consequently show a lower simple diaste-
reoselectivity in the photocycloaddition.
Preparatively, the cis-3-aminooxetanes obtained by the
Paterno`-Bu¨chi reaction not only are interesting by
themselves but also serve as building blocks for the
stereoselective construction of 1,2-amino alcohols. The
obvious pathway to achieve an oxetane ring opening is a
nucleophilic substitution at the less-substituted C-4
carbon atom of the ring, which yields syn-1,2-amino
alcohols. Indeed, this route is feasible if one ensures the
presence of an acidic NH group in the aminooxetanes. If
secondary enamides are used as alkene substrates in the
photocycloaddition, the NH group is already introduced
in the oxetane during this step. Tertiary enecarbamates
lead to carbamoyl-protected secondary aminooxetanes,
the carbamate protective group of which can be readily
removed. For the latter purpose, the trimethylsilyleth-
oxycarbonyl (Teoc) group proved to be best suited.
anti-1,2-Amino alcohols are accessible from N-Boc-
protected cis-2-aryl-3-aminooxetanes via oxazolidinone
intermediates. Upon acid treatment, these oxetanes
undergo a cyclization with concomitant oxetane ring
cleavage, which occurs by an intramolcular nucleophilic
substitution at carbon atom C-2 of the oxetane. The
oxygen atom of the Boc group attacks the oxetane nucleus
in a SN2-type reaction while the tert-butyl cation is
simultaneously cleaved. As the substitution proceeds
with inversion at the former C-2 carbon atom, the
(29) J . Schro¨der, projected Ph.D. Thesis, Universita¨t Marburg.
(30) pKa [HO(CH2C(CH3)2CH2)+] ) -2.6, cf. ref 22b; pKa [HOC-
(NMe2)OR+] ) -3.1, cf. Homer, R. B.; J ohnson, C. D. In The Chemistry
of Functional Groups; Patai, S., Ed.; The Chemistry of Amides; Zabicky,
J ., Ed.; Interscience: London, 1970; p 211.
(31) Bach, T.; Kather, K.; Kra¨mer, O. J . Org. Chem. 1998, 63, 1910.
(32) Hutchins, R. O.; Kandasamy, D.; Dux, F., III; Maryanoff, C.
A.; Rotstein, D.; Goldsmith, B.; Burgoyne, W.; Cistone, F.; Dalessandro,
J .; Puglis, J . J . Org. Chem. 1978, 43, 2259.

1270 J . Org. Chem., Vol. 64, No. 4, 1999
Bach and Schro¨der
Gen er a l Ir r a d ia tion P r oced u r e. In a quartz tube, the
aldehyde (1.5 mmol) and the N-acyl enamine (3.0 mmol) were
dissolved in 10 mL of acetonitrile. This mixture was irradiated
for the time period indicated in Tables 1 or 2 (λ ) 300 nm;
light source: Rayonet RPR 3000). The course of the reaction
was monitored by TLC and GLC. Upon complete conversion
of the aldehyde, the solvent was evaporated in vacuo. The
resulting N-alkyloxazolidinones have anti-configuration
and they can be saponified to anti-1,2-amino alcohols.
Exp er im en ta l Section
Gen er a l. All reactions involving water-sensitive chemicals
were carried out in flame-dried glassware with magnetic
stirring under Ar. Irradiation experiments were performed in
acetonitrile (Merck p.a.) or benzene (Merck p.a.) under Ar.
Chlorotrimethylsilane, N,N-di-i-propylamine, triethylamine,
DMSO, and pyridine were distilled from calcium hydride.
Common solvents (tert-butyl methyl ether, pentane, cyclohex-
ane, and ethyl acetate), acetic anhydride, and BF3-etherate
were distilled prior to use. THF and Et2O were distilled from
K/Na immediately prior to use. All other reagents and solvents
were used as received. 1H and 13C NMR spectra were recorded
in CDCl3 as solvent at 303 K unless stated otherwise. Chemical
shifts are reported relative to tetramethylsilane as an internal
reference. Apparent multiplets which occur as a result of the
accidental equality of coupling constants to those of magneti-
cally nonequivalent protons are marked as virtual (virt.). The
multiplicities of the 13C NMR signals were determined by
attached proton test (APT) experiments. NOESY contacts are
reported as weak (′), medium (′′), or strong (′′′) TLC was
performed on Aluminum sheets (0.2 mm silica gel 60 F254), and
a pentane (PE)/tert-butyl methyl ether (MTBE) mixture or a
cyclohexane (CH)/ethyl acetate (EA) mixture was used as
eluent. Detection was by UV or by coloration with ceric
ammonium molybdate (CAM). Flash chromatography33 was
performed on silica gel 60 (230-400 mesh) (ca 50 g for 1 g of
material to be separated), with the eluent given in brackets.
(1,1-Dim eth yleth yl)-N-m eth yl-N-vin ylca r ba m a te (1e).
To a solution of 10 mmol of N-methylethylidenamine34 (0.57
g) and 10 mmol of triethylamine (1.01 g, 1.39 mL) in dry
toluene (5 mL) was added 10 mmol of di-tert-butyl dicarbonate
(2.18 g). After the addition, the mixture was stirred for 1 h at
room temperature. The solvent was distilled under atmo-
spheric pressure, and nonconverted starting compounds were
evaporated by bulb-to-bulb distillation (80 °C/1 mbar). The
residue was purified by flash chromatography (PE/MTBE )
90/10). Compound 1e was obtained as a colorless oil. Yield:
1.3 g (80%). Rf ) 0.44 (PE/MTBE ) 90/10). IR (film): 1710
1
simple diastereoselectivity (d.r.) was determined by H NMR
and GLC analysis of the crude product mixture, and the results
are listed in Tables 1 and 2. The excess enamide was separated
from the desired oxetane by distillation, or it was separated
in the course of the subsequent flash chromatography. The
diastereomeric ratio of the isolated product as determined by
GLC is given in the Experimental Section. The oxetanes were
obtained as colorless oils. Relative configurations were deter-
mined by 1H NMR spectroscopy (NOE or NOESY experi-
ments). Some selected data are provided.
(2RS,3RS)-N-(2-P h en yloxeta n -3-yl)for m a m id e (cis-5a ).
According to the general irradiation procedure, 1.5 mmol of
benzaldehyde (159 mg, 152 µL) and 2.5 mmol of N-acyl
enamine 1a (178 mg) were irradiated for 15 h. The mixture
was filtered, and 1 equiv of N-acyl enamine 1a (1.0 mmol, 71
mg) was added. After further irradiation for 3 h, the mixture
was worked up as described in the general procedure. Flash
chromatography (CH/EA ) 30/70) yielded oxetane 5a as a
mixture of diastereoisomers (196 mg, 74%, d.r. ) 90/10). The
diastereoisomers were not fully separable. Analytical data are
provided for the major diastereoisomer cis-5a . Rf ) 0.15 (CH/
EA ) 30/70). IR (film): 1670 cm-1 (vs, CONH), 995 (s, COC).
1H NMR: δ 4.36 (virt. t, J = 6.6 Hz, 1 H), 4.92 (virt. t, J = 7.3
Hz, 1 H), 5.21-5.31 (m, 1 H), 5.87 (d, J ) 7.6 Hz, 1 H), 5.95-
6.15 (s, b, 1 H), 7.21-7.66 (m, 5 H), 7.66 (s, 1 H). 13C NMR: δ
45.7 (d), 76.1 (t), 85.8 (d), 125.4 (d), 128.4 (d), 128.7 (d), 136.8
(s), 160.3 (d). Anal. Calcd for C10H11NO2 (177.2): C, 67.78; H,
7.90; N, 6.26. Found C, 67.84; H, 7.99; N, 6.17.
(2RS,3RS)-N-(2-P h en yloxeta n -3-yl)a ceta m id e (cis-5b).
The general irradiation procedure was slightly modified. Six
mmol of N-acyl enamine 1b11 (510 mg) was added in small
portions to a solution of 1.5 mmol of benzaldehyde (159 mg,
152 µL) in acetonitrile (10 mL) within 10 h. After irradiation
for 140 h, the mixture was worked up as described in the gen-
eral procedure. Flash chromatography (CH/EA ) 40/60 f 20/
80) yielded oxetane 5b as a mixture of diastereoisomers (165
mg, 58%, d.r. ) 80/20). Benzaldehyde (40 mg, 25%) was recov-
ered. The diastereoisomers were not fully separable. Analytical
data are provided for the major diastereoisomer cis-5b. Rf )
0.10 (CH/EA ) 40/60). IR (film): 3250 cm-1 (s, b, NH), 1640
(vs, CONH), 1540 (vs, CONH), 970 (s, COC). 1H NMR: δ 1.70
(s, 3 H), 4.54 (virt. t, J = 6.6 Hz, 1 H), 5.05 (virt. t, J = 7.2 Hz,
1 H), 5.30-5.38 (m, 1 H), 5.50 (s, b, 1 H), 5.99 (d, J ) 7.5 Hz,
1 H), 7.30-7.49 (m, 5 H). NOE experiment (600 MHz) H
(5.99): HN [0.4%]; HN (5.34): H [0.4%], Hb [0.3%]; Hb (5.05):
HN [0.3%], Ha [1.2%]; Ha (4.54): Hb [1.4%]. 13C NMR: δ 22.7
(q), 47.2 (d), 76.3 (t), 86.2 (d), 125.4 (d), 128.1 (d), 128.6 (d),
137.2 (s), 169.5 (s). C11H13NO2 HRMS: Calcd 191.0946; found
191.0943.
1
cm-1 (vs, CdO), 1625 (vs, CdC). H NMR (DMSO-d6, 373 K):
δ 1.46 (s, 9 H), 2.94 (s, 3 H), 4.19 (d, J ) 9.4 Hz, 1 H), 4.30 (d,
J ) 15.8 Hz, 1 H), 7.05 (dd, J ) 15.8 Hz, J ) 9.4 Hz, 1 H). 13
C
NMR: δ 27.4 (q), 28.0 (q), 81.0 (s), 90.6 (t), 134.3 (d), 146.8
(s). HRMS: Calcd 157.1102; found 157.1095. Anal. Calcd for
C8H15NO2 (157.1): C, 61.12; H, 9.62; N, 8.91. Found: C, 61.22;
H, 9.65; N, 8.85.
N -P h en ylm et h yl-(2-t r im et h ylsilyl)-N -vin ylca r b a m -
a te (1g). To a solution of 36 mmol of 2-(trimethylsilyl)ethanol
(4.3 g) in Et2O (50 mL) was slowly added 30 mmol of n-BuLi
(19.2 mL, 1.56 M in hexanes) at -5 °C. After 1 h of stirring,
25 mmol of N-benzyl-N-vinylcarbamoylchlorid (3)13 (4.9 g) was
added dropwise to the mixture at this temperature. Stirring
was continued for 1 h. The reaction was quenched with a
saturated aqueous solution of NH4Cl (20 mL), and the mixture
was extracted with Et2O (3 × 30 mL). The organic extracts
were combined, washed with brine (30 mL), dried over MgSO4,
filtered, and concentrated in vacuo. The residue was purified
by flash chromatography (PE/MTBE ) 95/5). Compound 1g
was obtained as a colorless oil. Yield: 6.6 g (95%). Rf ) 0.90
(PE/MTBE ) 90/10). IR (film): 1710 cm-1 (vs, CdO), 1630 (vs,
N-P h en ylm eth yl-N-(2-ph en yloxetan -3-yl)acetam ide (5c).
According to the general irradiation procedure, 1.5 mmol of
benzaldehyde (159 mg, 152 µL) and 3 mmol of N-acyl enamine
1c12b (526 mg) were irradiated for 14 h. Flash chromatography
(CH/EA ) 75/25 f 70/30) yielded oxetane 5c as a mixture of
separable diastereoisomers (340 mg, 81%, d.r. ) 89/11).
(2RS,3RS)-isomer (cis-5c): Rf ) 0.41 (CH/EA ) 40/60). IR
(film): 1640 cm-1 (vs, CdO), 980 (s, COC).1H NMR: δ 1.82 (s,
3 H), 4.06 (d, J ) 18.3 Hz, 1 H), 4.32 (d, J ) 18.3 Hz, 1 H),
4.52 (virt. t, J = 7.2 Hz, 1 H), 4.86 (virt. t, J = 8.0 Hz, 1 H),
5.96 (virt. q, J = 7.4 Hz, 1 H), 6.07 (d, J ) 7.4 Hz, 1 H), 6.87-
6.97 (m, 2 H), 7.14-7.46 (m, 8 H). 13C NMR: δ 21.8 (q), 49.0
(t), 52.6 (d), 71.8 (t), 87.3 (d), 124.9 (d), 125.0 (d), 127.3 (d),
127.4 (d), 128.2 (d), 128.9 (d), 137.6 (s), 138.3 (s), 171.8 (s).
NOESY experiment (see General): H (6.07)-H (5.96)′′′; H
1
CdC). H NMR (DMSO-d6, 373 K): δ 0.02 (s, 9 H), 1.03 (t, J
) 8.2 Hz, 2 H), 4.24-4.32 (m, 3 H), 4.38 (d, J ) 15.9 Hz, 1 H),
4.76 (s, 2 H), 7.09 (dd, J ) 15.9 Hz, J ) 9.3 Hz, 1 H), 7.21-
7.25 (m, 3 H), 7.30-7.34 (m, 2 H). 13C NMR (DMSO-d6, 373
K): δ -0.7 (q), 18.2 (t), 47.4 (t), 65.1 (t), 94.0 (t), 127.3 (d),
127.7 (d), 129.2 (d), 133.6 (s), 138.2 (d), 154.8 (s). Anal. Calcd
for C15H23NO2Si (277.4): C, 64.95; H, 8.36; N, 5.05. Found:
C, 64.80; H, 8.13; N, 5.20.
(5.96)-H (4.86)′′′; H (4.86)-H (4.52)′′′. Anal. Calcd for C18H19
-
NO2 (281.4): C, 76.84; H, 6.81; N, 4.98. Found: C, 76.79; H,
6.85; N, 4.83. (2RS,3SR)-isomer (trans-5c): Rf ) 0.34 (CH/
EA ) 40/60).1H NMR (DMSO-d6, 373 K): δ 1.97 (s, 3 H), 4.59
(33) Still, W. C.; Kahn, M.; Mitra, A. J . J . Org. Chem. 1978, 43,
2923.
(34) Karabatsos, G. J .; Lande, S. S. Tetrahedron 1968, 24, 3907.

Photocycloaddition of N-Acyl Enamines to Aldehydes
J . Org. Chem., Vol. 64, No. 4, 1999 1271
(m, 2 H), 4.85 (s, 2 H), 5.06 (virt. q, J = 7.4 Hz, 1 H), 5.65 (d,
J ) 6.8 Hz, 1 H), 7.18-7.39 (m, 10 H).13C NMR (75.5 MHz):
δ ) 24.2 (q), 51.2 (t), 59.7 (d), 74.1 (t), 88.8 (d), 127.7 (d), 128.2
(d), 129.8 (d), 130.6 (d), 130.9 (d), 131.2 (d), 139.1 (s), 142.3
(s), 173.9 (s).
N-(2-P h en yloxeta n -3-yl)-p yr r olid in -2-on e (5h ). Accord-
ing to the general irradiation procedure, 1.5 mmol of benzal-
dehyde (159 mg, 152 µL) and 4.5 mmol of enamine 1h (500
mg, 480 µL) were irradiated for 14 h. Flash chromatography
(CH/EA ) 40/60 f 20/80) yielded oxetane 5h as a mixture of
diastereoisomers (270 mg, 82%, d.r. ) 88/12). The diastereo-
isomers were not fully separable. Analytical data are provided
for both diastereoisomers. (2RS,3RS)-isomer (cis-5h ): Rf )
(2RS,3RS)-N-(2-P h en yloxet a n -3-yl)-N-p r op yla cet a m -
id e (cis-5d ). According to the general irradiation procedure,
1.5 mmol of benzaldehyde (159 mg, 152 µL) and 3.75 mmol of
N-acyl enamine 1d 12a (477 mg) were irradiated for 14 h. Flash
chromatography (CH/EA ) 80/20 f 40/60) yielded oxetane cis-
5d in diastereomerically pure form (250 mg, 71%, d.r. ) >90/
10). Rf ) 0.24 (CH/EA ) 40/60). IR (film): 1640 cm-1 (vs, CdO),
1
0.19 (EA). IR (film): 1680 cm-1 (vs, CdO), 980 (s, COC); H
NMR: δ 1.36 (m, 1 H), 1.71 (m, 1 H), 2.12 (ddd, J ) 16.9 Hz,
J ) 9.4 Hz, J ) 5.6 Hz, 1 H), 2.23 (ddd, J ) 16.9 Hz, J ) 9.3
Hz, J ) 7.8 Hz, 1 H), 2.75 (virt. dt, J = 8.8 Hz, J ) 4.7 Hz, 1
H), 3.22 (virt. q, J = 8.0 Hz, 1 H), 4.84 (virt. t, J = 6.8 Hz, 1
H), 5.06 (virt. t, J = 7.8 Hz, 1 H), 5.54 (virt. q, J = 7.4 Hz, 1
H), 6.03 (d, J ) 7.8 Hz, 1 H), 7.20-7.40 (m, 5 H). NOE
experiment (360 MHz) Har (7.25): H [2.7%], Ha [0.5%], H5
[0.7%]; H (6.03): HN [4.4%]; HN (5.54): H [5.9%], Hb [2.2%];
Hb (5.06): HN [4.4%], Ha [11.8%]; Ha (4.84): Hb [18.0%], H5
[2.8%]; H5 (3.22): Ha [2.5%]. 13C NMR: δ 18.7 (t), 30.8 (t), 44.9
(t), 49.7 (d), 71.1 (t), 86.8 (d), 124.2 (d), 127.2 (d), 128.0 (d),
138.2 (s), 175.2 (s). C13H16NO2 HRMS: Calcd. 218.1181; found
218.1179. (2RS,3SR)-isomer (trans-5h ): Rf ) 0.19 (EA).1H
NMR: δ 2.07-2.17 (m, 2 H), 2.42 (virt. t, J = 8.1 Hz, 2 H),
3.73 (virt. t, J = 8.8 Hz, 2 H), 4.75 (m, 1 H), 4.82-4.86 (m, 1
H), 5.13 (virt. q, J = 7.6 Hz, 1 H), 6.03 (d, J ) 6.6 Hz, 1 H),
7.15-7.35 (m, 5 H). NOE experiment (360 MHz) HN (5.13):
Ha [2.0%]; Hb (4.85): Ha [12.3%]; H5 (3.73): H [5.9%]. 13C
NMR: δ 18.0 (t), 31.0 (t), 44.0 (t), 53.7 (d), 70.2 (t), 85.8 (d),
125.3 (d), 128.2 (d), 128.4 (d), 140.0 (s), 174.8 (s).
(2RS,3RS)-(1,1-Dim et h ylet h yl)-N-[2-[2-(1,1-d im et h yl-
eth ylca r bon yloxy)p h en yl]oxeta n -3-yl]-N-p h en ylm eth yl-
ca r ba m a te (cis-7a ). According to the general irradiation
procedure, 1.5 mmol of aldehyde 6a (1.5 mmol) and 3 mmol of
N-acyl enamine 1f23 (699 mg) were irradiated for 15 h. Flash
chromatography (CH/EA ) 90/10) yielded oxetane cis-7a in
diastereomerically pure form (409 mg, 62%, d.r. ) >90/10). Rf
) 0.25 (CH/EA ) 90/10). IR (film): 1695 cm-1 (vs, CdO), 985
(m, COC). 1H NMR (DMSO-d6, 373 K): δ 1.14 (s, 9 H), 1.18 (s,
9 H), 4.13 (d, J ) 17.0 Hz, 1 H), 4.26 (d, J ) 17.0 Hz, 1 H),
4.72 (virt. t, J = 7.7 Hz, 1 H), 4.88 (virt. t, J = 7.7 Hz, 1 H),
5.52 (virt. q, J = 7.7 Hz, 1 H), 5.96 (d, J ) 7.7 Hz, 1 H), 6.94-
7.72 (m, 9 H). 13C NMR: δ 27.0 (q), 28.2 (q), 39.3 (s), 47.7 (t),
53.5 (d), 73.3 (t), 80.2 (s), 85.1 (d), 122.2 (d), 125.4 (d), 126.5
(d), 127.0 (d), 128.3 (d), 128.6 (d), 130.3 (s), 139.9 (s), 147.9
(s), 155.1 (s). Anal. Calcd for C26H33NO5 (439.6): C, 71.05; H,
7.57; N, 3.19. Found C, 70.82; H, 8.08; N, 3.21.
(2RS,3RS)-(1,1-Dim et h ylet h yl)-N-p h en ylm et h yl-N-(2-
p r op yloxeta n -3-yl)ca r ba m a te (cis-7c). According to the
general irradiation procedure, 1.5 mmol of aldehyde 6c (108
mg) and 22.5 mmol of N-acyl enamine 1f23 (5.25 g) were
irradiated for 15 h. Flash chromatography (PE/MTBE ) 95/
5) yielded oxetane 7c as a mixture of diastereoisomers (250
mg, 55%, d.r. ) 75/25). The diastereoisomers were not fully
separable. The collection of selected chromatography fractions
yielded diastereoisomer cis-7c in diastereomerically pure form
(168 mg, 37%). Rf ) 0.37 (PE/MTBE ) 90/10). IR (film): 1695
cm-1 (vs, CdO), 975 (m, COC). 1H NMR (DMSO-d6, 373 K): δ
0.89 (t, J ) 7.4 Hz, 3 H), 1.26 (m, 1 H), 1.35 (m, 1 H), 1.39 (s,
9 H), 1.47 (m, 1 H), 1.70 (m, 1 H), 4.36-4.54 (m, 3 H), 4.68
(m, 1 H), 4.74 (d, J ) 16.5 Hz, 1 H), 4.91 (virt. q, J = 6.9 Hz,
1 H), 7.16-7.34 (m, 5 H). 13C NMR (DMSO-d6, 373 K): δ 14.4
(q), 18.3 (t), 28.8 (q), 33.1 (t), 49.2 (t), 53.8 (d), 71.0 (t), 80.5
(s), 87.3 (d), 127.2 (d), 127.6 (d), 129.2 (d), 140.2 (s), 156.0 (s).
Anal. Calcd for C18H27NO3 (305.4): C, 70.79; H, 8.91; N, 4.59.
Found C, 70.59; H, 8.68; N, 4.61.
(2RS,3RS)-(1,1-Dim et h ylet h yl)-N-(2-m et h yloxet a n -3-
yl)-N-p h en ylm eth ylca r ba m a te (cis-7d ). The general ir-
radiation procedure was modified. Aldehyde 6d (22.5 mmol,
990 mg) and 1.5 mmol of N-acyl enamine 1f23 (350 mg) were
irradiated for 15 h. Flash chromatography (PE/MTBE ) 40/
60) yielded oxetane 7d as a mixture of diastereoisomers (190
mg, 46%, d.r. ) 86/14). Analytical data are provided for the
major diastereoisomer cis-7d . Rf ) 0.66 (PE/MTBE ) 25/75).
IR (film): 1695 cm-1 (vs, CdO), 975 (s, COC); 1H NMR (DMSO-
d6, 373 K): δ 1.23 (d, J ) 6.0 Hz, 3 H), 1.40 (s, 9 H), 4.40 (virt.
1
980 (s, COC). H NMR: δ 0.75 (t, J ) 7.4 Hz, 3 H), 1.12-1.40
(m, 2 H), 1.86 (s, 3 H), 2.74 (ddd, J ) 15.6 Hz, J ) 10.3 Hz, J
) 5.7 Hz, 1 H), 2.95 (ddd, J ) 15.6 Hz, J ) 10.3 Hz, J ) 5.5
Hz, 1 H), 4.80 (virt. t, J = 7.3 Hz, 1 H), 5.00 (dd, J ) 7.3 Hz,
J ) 8.2 Hz, 1 H), 5.68 (virt. q, J = 7.8 Hz, 1 H), 5.97 (d, J )
7.7 Hz, 1 H), 7.20-7.42 (m, 5 H).13C NMR: δ 10.7 (q), 21.3
(q), 23.7 (t), 47.2 (t), 52.5 (d), 71.7 (t), 87.6 (d), 125.2 (d), 127.2
(d), 127.9 (d), 138.0 (s), 170.7 (s). Anal. Calcd for C14H19NO2
(233.3): C, 72.07; H, 8.21; N, 6.00. Found: C, 71.74; H, 8.25;
N, 6.06.
(2RS,3RS)-(1,1-Dim eth yleth yl)-N-m eth yl-N-(2-p h en yl-
oxet a n -3-yl)ca r ba m a t e (cis-5e). According to the general
irradiation procedure, 1.5 mmol of benzaldehyde (159 mg, 152
µL) and 2.5 mmol of N-acyl enamine 1e (393 mg) were
irradiated for 14 h. Flash chromatography (CH/EA ) 90/10)
yielded oxetane 5e as a mixture of diastereoisomers (221 mg,
56%, d.r. ) 90/10). The diastereoisomers were not fully
separable. Analytical data are provided for the major diaste-
reoisomer cis-5e. Rf ) 0.47 (CH/EA ) 75/25). IR (film): 1720
1
cm-1 (vs, CdO), 990 (s, COC). H NMR (DMSO-d6, 373K): δ
1.35 (s, 9 H), 2.46 (s, 3 H), 4.85 (virt. t, J = 7.2 Hz, 1 H), 4.92
(virt. t, J = 7.2 Hz, 1 H), 5.27 (virt. q, J = 7.2 Hz, 1 H), 5.85
(d, J ) 7.2 Hz, 1 H), 7.25-7.43 (m, 5 H). 13C NMR (DMSO-d6,
373 K): δ ) 27.5 (q), 30.2 (q), 53.6 (d), 70.6 (t), 78.6 (s), 86.4
(d), 124.7 (d), 126.6 (d), 127.3 (d), 138.2 (s), 154.0 (s). Anal.
Calcd for C15H21NO3 (263.2): C, 68.42; H, 8.04; N, 5.32.
Found: C, 68.10; H, 8.21; N, 5.21.
(2RS,3RS)-(1,1-Dim et h ylet h yl)-N-p h en ylm et h yl-N-(2-
p h en yloxeta n -3-yl)ca r ba m a te (cis-5f). According to the
general irradiation procedure 1.5 mmol of benzaldehyde (159
mg, 152 µL) and 3.75 mmol of enamine 1f23 (875 mg) were
irradiated for 14 h. Flash chromatography (CH/EA ) 98/2 f
96/4) yielded oxetane 5f as a mixture of diastereoisomers
(395 mg, 77%, d.r. ) 87/13). The diastereoisomers were not
fully separable. Analytical data are provided for the major
diastereoisomer cis-5f. Rf ) 0.66 (CH/EA ) 60/40). IR (film):
1
1680 cm-1 (vs, CdO), 980 (s, COC). H NMR (DMSO-d6, 373
K): δ 1.30 (s, 9 H), 4.11 (d, J ) 16.8 Hz, 1 H), 4.25 (d, J )
16.8 Hz, 1 H), 4.68-4.76 (m, 2 H), 5.34 (virt. q, J = 7.4 Hz, 1
H), 5.84 (d, J ) 7.2 Hz, 1 H), 7.00-7.05 (m, 2 H), 7.15-7.41
(m, 8 H). NOE experiment (360 MHz, DMSO-d6, 373 K) H
(5.84): HN [15.2%]; HN (5.34): H [16.9%]. 13C NMR (DMSO-
d6, 373 K): δ 28.6 (q), 48.4 (t), 54.9 (d), 72.1 (t), 80.3 (s), 88.0
(d), 126.6 (d), 126.7 (d), 127.3 (d), 128.1 (d), 128.6 (d), 128.9
(d), 139.2 (s), 139.9 (s), 155.3 (s). Anal. Calcd for C21H25NO3
(339.4): C, 74.31; H, 7.42; N, 4.13. Found: C, 74.34; H, 7.32;
N, 4.25.
(2RS,3RS)-N-P h en ylm eth yl-(2-tr im eth ylsilyl)-N-(2-ph en -
yloxeta n -3-yl)ca r ba m a te (cis-5g). According to the general
irradiation procedure, 1.5 mmol of benzaldehyde (159 mg, 152
µL) and 3 mmol of N-acyl enamine 1g (832 mg) were irradiated
for 14 h. Flash chromatography (PE/MTBE ) 90/10) yielded
oxetane cis-5g in diastereomerically pure form (427 mg, 74%,
d.r. ) >90/10). Rf ) 0.20 (PE/MTBE ) 90/10). IR (film): 1695
cm-1 (vs, CdO), 985 (m, COC). 1H NMR (DMSO-d6, 373 K): δ
-0.01 (s, 9 H), 0.87 (t, J ) 8.1 Hz, 2 H), 3.93-4.20 (m, 3 H),
4.32 (d, J ) 16.8 Hz, 1 H) 4.72 (m, 2 H), 5.37 (virt. q, J = 7.3
Hz, 1 H), 5.86 (d, J ) 7.2 Hz, 1 H), 6.99-7.43 (m, 10 H). 13C
NMR (DMSO-d6, 373 K): δ -2.9 (q), 16.8 (t), 47.1 (t), 53.7 (d),
62.4 (t), 70.8 (t), 86.6 (d), 125.2 (d), 125.5 (d), 126.2 (d), 127.0
(d), 127.5 (d), 127.8 (d), 137.9 (s), 138.3 (s), 155.1 (s). Anal.
Calcd for C22H29NO3Si (383.5): C, 68.89; H, 7.62; N, 3.65.
Found: C, 68.62; H, 7.58; N, 3.82.

1272 J . Org. Chem., Vol. 64, No. 4, 1999
Bach and Schro¨der
t, J = 7.3 Hz, 1 H), 4.48 (d, J ) 16.5 Hz, 1 H), 4.57 (virt. t, J
= 6.8 Hz, 1 H), 4.72 (d, J ) 16.5 Hz, 1 H), 4.75-4.88 (m, 2 H),
7.17-7.24 (m, 3 H), 7.30-7.45 (m, 2 H). 13C NMR (DMSO-d6,
373 K): δ 17.2 (q), 28.9 (q), 48.9 (t), 53.9 (d), 71.0 (t), 80.5 (s),
83.6 (d), 127.4 (d), 127.7 (d), 129.2 (d), 140.0 (s), 156.0 (s). Anal.
Calcd for C16H23NO3 (277.4): C, 69.29; H, 8.36; N, 5.05. Found
C, 69.62; H, 8.60; N, 5.44.
mL). The organic extracts were combined, washed with brine
(5 mL) and dried over MgSO4. The mixture was filtered and
concentrated in vacuo. The residue was purified by flash
chromatography on silica gel (PE/MTBE ) 40/60). Compound
10 was obtained as a white solid. Yield: 152 mg (84%). Mp:
170 °C. Rf ) 0.26 (PE/MTBE ) 40/60). IR (KBr): 3410 cm-1
(b, NH), 3320 (s, OH). 1H NMR (MeOH-d4): δ 2.54 (dd, J )
14.7 Hz, J ) 4.7 Hz, 1 H), 2.65 (dd, J ) 14.7 Hz, J ) 7.8 Hz,
1 H), 3.41 (ddd, J ) 8.2 Hz, J ) 7.8 Hz, J ) 4.7 Hz, 1 H), 3.62
(d, J ) 13.7 Hz, 1 H), 3.92 (d, J ) 13.7 Hz, 1 H), 4.20 (s, 2 H),
4.86 (d, J ) 8.2 Hz, 1 H), 6.90-6.94 (m, 2 H), 7.07-7.10 (m, 3
H), 7.26-7.36 (m, 10 H). 13C NMR (MeOH-d4): δ 30.2 (t), 36.9
(t), 51.2 (t), 63.4 (d), 73.6 (d), 128.3 (d), 128.6 (d), 130.0 (d),
130.3 (d), 130.4 (d), 130.7 (d), 131.1 (d), 131.5 (d), 132.6 (s),
139.1 (s), 141.9 (s). C23H26NOS HRMS; CI, M + H+: Calcd
364.1735; found 364.1729.
(2RS,3RS)-(1,1-Dim eth yleth yl)-N-[2-[(1,1-d im eth yleth -
yl)d im eth ylsilyloxy]eth yloxeta n -3-yl]-N-p h en ylm eth yl-
ca r ba m a te (cis-7e). According to the general irradiation
procedure, 1.5 mmol of aldehyde 6e35 (282 mg) and 3 mmol of
N-acyl enamine 1f23 (699 mg) were irradiated for 15 h. Flash
chromatography (PE/MTBE ) 90/10) yielded oxetane 7e as a
mixture of diastereoisomers (337 mg, 54%, d.r. ) 85/15). The
diastereoisomers were not fully separable. The collection of
selected chromatography fractions yielded diastereoisomer cis-
7e in diastereomerically pure form (284 mg, 45%). Rf ) 0.20
(PE/MTBE ) 90/10). IR (film): 1700 cm-1 (vs, CdO), 970 (w,
(4SR,5RS)-4-Hyd r oxym eth yl-5-p h en yl-3-p h en ylm eth -
yloxa zolid in -2-on e (11). To a stirred solution of 2 mmol of
trifluoroacetic acid (226 mg, 160 µL) in CH2Cl2 (7 mL) was
added 1 mmol of oxetane 5f (339 mg, d.r. ) 87/13) in CH2Cl2
(2 mL) at -78 °C. The mixture was slowly warmed to room
temperature. The solution was concentrated in vacuo, and the
trifluoroacetic acid was removed by azeotropic distillation with
toluene (2 × 5 mL). The residue was purified by flash
chromatography on silica gel (CH/EA ) 80/20). Compound 11
was the major product, obtained as a white solid. Yield: (211
mg, 75%). In addition 15 mg (5%) of the (4RS,5RS)-isomer of
compound 11 was isolated. Mp: 131-132 °C. Rf ) 0.41 (CH/
EA ) 40/60). IR (KBr): 1690 cm-1 (vs, CdO). 1H NMR (DMSO-
d6): δ 3.02 (virt. dt, J ) 11.4 Hz, J = 4.2 Hz, 1 H), 3.20 (virt.
dt, J ) 11.4 Hz, J = 4.2 Hz, 1 H), 3.92 (dt, J ) 8.4 Hz, J ) 4.2
Hz, 1 H), 4.29 (d, J ) 15.6 Hz, 1 H), 4.68-4.72 (m, 2 H), 5.69
(d, J ) 8.4 Hz, 1 H), 7.28-7.41 (m, 10 H). 13C NMR: δ 46.5
(t), 59.1 (d), 59.2 (t), 76.2 (d), 125.5 (d), 125.5 (d), 127.6 (d),
127.7 (d), 128.4 (d), 128.5 (d), 134.2 (s), 135.9 (s), 157.8 (s).
NOE experiment (600 MHz, DMSO-d6) H (5.69): HN [3.6%];
HN (3.92): H [3.5%]. Anal. Calcd for C17H17NO3 (283.3): C,
72.07; H, 6.05; N, 4.94. Found C, 72.25; H, 6.34; N, 5.00.
(4SR,5RS)-4-Hyd r oxym eth yl-3-m eth yl-5-p h en yloxa zo-
lid in -2-on e (12). To a stirred solution of 2 mmol of trifluoro-
acetic acid (226 mg, 160 µL) in CH2Cl2 (7 mL) was added 1
mmol of oxetane 5e (263 mg, d.r. ) 90/10) in CH2Cl2 (2 mL)
at -78 °C. The mixture was slowly warmed to room temper-
ature. The solution was concentrated in vacuo, and the
trifluoroacetic acid was removed by azeotropic distillation with
toluene (2 × 5 mL). The residue was purified by flash
chromatography on silica gel (CH/EA ) 70/30). Compound 12
was obtained as a white solid. Yield: 119 mg (58%). Mp: 66
°C. Rf ) 0.55 (CH/EA ) 40/60). IR (KBr): 1730 cm-1 (vs, Cd
1
COC). H NMR (DMSO-d6, 373 K): δ 0.05 (s, 6 H), 0.90 (s, 9
H), 1.42 (s, 9 H), 1.73 (ddd, J ) 18.5 Hz, J ) 7.5 Hz, J ) 3.7
Hz, 1 H), 1.92 (ddd, J ) 18.5 Hz, J ) 10.5 Hz, J ) 5.3 Hz, 1
H), 3.64 (m, 2 H), 4.43 (virt. t, J = 7.2 Hz, 1 H), 4.48 (d, J )
16.4 Hz, 1 H), 4.57 (virt. t, J = 7.2 Hz, 1 H), 4.73 (d, J ) 16.4
Hz, 1 H), 4.81 (m, 1 H), 4.92 (virt. q, J = 7.1 Hz, 1 H), 7.17-
7.35 (m, 5 H). 13C NMR (DMSO-d6, 373 K): δ -4.5 (q), 18,7
(t), 26.6 (q), 28.8 (q), 34.5 (s), 49.1 (t), 53.5 (d), 59.2 (t), 71.1
(t), 80.6 (s), 84.3 (d), 127.3 (d), 127.7 (d), 129.2 (d), 140.0 (s),
156.0 (s). NOESY experiment: H (4.92)-H (4.81)′′; H (4.92)-H
(4.43)′′; H (4.57)-H (4.43)′′′. C19H30NSiO3 (HRMS): Calcd
348.1995; found 348.2000.
(()-P seu d oep h ed r in e (8). To a mixture of 3 mmol of
LiAlH4 (114 mg) in THF (1 mL) was added a solution of 1 mmol
of oxetane 5a (177 mg, d.r.) 90/10) in THF (5 mL) at 0 °C.
The mixture was warmed to room temperature, and stirring
was continued for 15 h. To this solution were added succes-
sively water (0.11 mL), aqueous NaOH (15%, 0.11 mL), and
water (0.33 mL). After 1 hr of stirring, the mixture was filtered,
and the residue was washed with EA (30 mL). The organic
extracts were dried over MgSO4, filtered, and concentrated
in vacuo. Compound 8 was obtained as a white solid. Yield:
142 mg (86%). According to GLC, the product was g95% pure.
The NMR data were in agreement with the literature
values.36
(2RS,3RS )-2-P h en yl-3-( N -p h en ylm et h yla m in o )oxe-
ta n e (9). TBAF (6.8 mmol, 2.13 g) was added to a solution of
3.4 mmol of oxetane 5g (1.30 g, d.r. ) >95/5) in acetonitrile
(60 mL). After 2 h of stirring at 50 °C, the mixture was
concentrated in vacuo. The residue was purified by flash
chromatography (PE/MTBE ) 60/40). Compound 9 was ob-
tained as a colorless oil. Yield: 500 mg (62%). Rf ) 0.31 (40/
60). IR (film): 3340 cm-1 (b, NH), 1750 (vs, CdO), 980 (s, COC).
1H NMR: δ 3.38 (s, 2 H), 4.23 (ddd, J ) 7.5 Hz, J ) 7.0 Hz, J
) 6.5 Hz, 1 H), 4.40 (dd, J ) 6.7 Hz, J ) 6.5 Hz, 1 H), 4.92
(dd, J ) 7.5 Hz, J ) 6.7 Hz, 1 H), 5.95 (d, J ) 7.0 Hz, 1 H),
6.93 (m, 2 H), 7.19 (m, 3 H), 7.43 (m, 5 H). 13C NMR: δ 51.6
(t), 56.4 (d), 78.5 (t), 89.0 (d), 126.9 (d), 127.5 (d), 128.5 (d),
128.8 (d), 129.0 (d), 129.0 (d), 138.5 (s), 139.9 (s). Anal. Calcd
for C16H17NO (239.3): C, 80.30; H, 7.16; N, 5.85. Found C,
80.31; H, 7.07; N, 6.12.
1
O). H NMR (300 MHz): δ ) 3.00 (s, 3 H), 3.41 (dd, J ) 11.9
Hz, J ) 4.3 Hz, 1 H), 3.49 (dd, J ) 11.9 Hz, J ) 4.3 Hz, 1 H),
3.95 (virt. dt, J ) 8.6 Hz, J ) 4.3 Hz, 1 H), 5.66 (d, J ) 8.6 Hz,
1 H), 7.31-7.45 (m, 5 H). 13C NMR: δ 30.1 (q), 59.8 (t), 62.3
(d), 77.5 (d), 125.7 (d), 125.9 (d), 128.9 (d), 134.7 (s), 176.1 (s).
Anal. Calcd for C11H13NO3 (207.2): C, 63.76; H, 6.32; N, 6.76.
Found C, 63.89; H, 6.42; N, 6.92.
(4SR,5RS)-3-Met h yl-4-(4-m et h ylp h en ylsu lfon yloxy-
m eth yl)-5-p h en yloxa zolid in -2-on e (13). To a stirred solu-
tion of 0.55 mmol of alcohol 12 (144 mg) in pyridine (2 mL)
was added 2.7 mmol of p-toluenesulfonyl chloride (525 mg) at
5 °C. After 15 h of stirring, the reaction mixture was quenched
with 2 M aqueous HCl (10 mL) and extracted with Et2O (3 ×
30 mL). The organic extracts were dried over MgSO4, filtered,
and concentrated in vacuo. The residue was purified by flash
chromatography on silica gel (CH/EA ) 80/20 f 70/30).
Compound 13 was obtained as a white solid. Yield: 194 mg
(98%). Rf ) 0.24 (CH/EA ) 40/60). IR (KBr): 1735 cm-1 (vs,
CdO). 1H NMR: δ 2.46 (s, 3 H), 2.90 (s, 3 H), 3.66 (dd, J )
12.2 Hz, J ) 4.0 Hz, 1 H), 3.76 (dd, J ) 12.2 Hz, J ) 3.8 Hz,
1 H), 3.95 (m, 1 H), 5.61 (d, J ) 8.4 Hz, 1 H), 7.20-7.38 (m, 7
H), 7.52-7.59 (m, 2 H). 13C NMR: δ 30.5 (q) 30.9 (q), 60.0 (t),
67.0 (d), 77.3 (d), 126.0 (d), 127.8 (d), 128.8 (d), 129.1 (d), 129.9
(d), 132.2 (s), 137.6 (s), 145.7 (s), 175.1 (s). Anal. Calcd for
(1RS,2SR)-1-P h en yl-2-(N-p h en ylm eth yla m in o)-2-p h en -
ylm eth ylsu lfa n yl-1-p r op a n ol (10).25e,27b To a solution of 2
mmol of benzylmercaptan (248 mg, 230 µL) in THF (5 mL)
was slowly added 2 mmol of n-BuLi (1.3 mL, 1.56 M in
hexanes) at 0 °C. After 1 h of stirring, 0.5 mmol of oxetane 9
(120 mg) in THF (1 mL) was added at -78 °C. After 20 min,
2 mmol of BF3-etherate (1.3 mL) was added to the reaction
mixture. Stirring was continued for 1 h, and the reaction was
subsequently quenched with a saturated aqueous solution of
NH4Cl (5 mL). The mixture was extracted with Et2O (3 × 10
(35) J enmalm, A.; Berts, W.; Li, Y.-L.; Luthman, K.; Cso¨regh, I.;
Hacksell, U. J . Org. Chem. 1994, 59, 1139.
(36) (a) Lyle, G. G.; Keefer, L. K. J . Org. Chem. 1966, 31, 3921. (b)
Pouchert, C. J .; Behnke, J . The Aldrich Library of 13C and 1H FT-
NMR Spectra; Aldrich Chemical: Milwaukee, 1993; p 578.
C
18H19NO5S (361.4): C, 59.82; H, 5.30; N, 3.88; found C, 60.00;
H, 5.53; N, 3.99.

Photocycloaddition of N-Acyl Enamines to Aldehydes
J . Org. Chem., Vol. 64, No. 4, 1999 1273
(4SR,5RS)-3,4-Dim eth yl-5-ph en yloxazolidin -2-on e (14).32
Sodium borohydride (0.38 mmol, 14.3 mg) was added to a
solution of 0.19 mmol of tosylate 13 (70 mg) in DMSO (1 mL).
The mixture was heated to 150 °C and kept at this tempera-
ture for 2 h. After cooling to room temperature, the solution
was diluted with water (5 mL) and extracted with CH2Cl2 (3
× 30 mL). The organic extracts were combined, washed with
brine (10 mL), dried over MgSO4, filtered, and concentrated
in vacuo. Compound 14 was obtained as a white solid. Yield:
mmol of oxazolidinone 14 (155 mg) in THF (5 mL) at 0 °C.
The mixture was refluxed for 2 h. To this solution were added
successively water (0.11 mL), aqueous NaOH (15%, 0.11 mL),
and water (0.33 mL). After 1 h of stirring, the mixture was
filtered and the residue was washed with EA (30 mL). The
solution was dried over MgSO4, filtered, and concentrated in
vacuo. Yield: 75 mg (97%). According to GLC, the product was
g95% pure. The NMR data were in agreement with the
literature values.39
1
26 mg (72%). Rf ) 0.10 (CH/EA ) 40/60). H NMR: δ ) 0.76
(d, J ) 6.2 Hz, 3 H), 2.86 (s, 3 H), 4.02 (m, 1 H), 5.56 (d, J )
7.9 Hz, 1 H), 7.28-7.38 (m, 5 H). All other analytical data are
in agreement with the literature values.37
Ack n ow led gm en t. This research project was sup-
ported by the Deutsche Forschungsgemeinschaft (Ba
1372/3-1) and the Fonds der Chemischen Industrie. We
thank Dr. Heinrich Luftmann (Universita¨t Mu¨nster) for
recording the CI-HRMS data and Dr. J acques Dupuis
(BASF AG, ZDH) for a generous donation of N-vinyl-
formamide.
(()-Ep h ed r in e (15). An aqueous solution of KOH (20%
KOH in water/ethanol 1/1, 1 mL) was added to 0.95 mmol of
oxazolidinone 14 (18 mg). After 2 h of refluxing, the mixture
was cooled to room temperature and neutralized with a
saturated aqueous NH4Cl solution (10 mL). The product was
extracted with CH2Cl2 (3 × 20 mL). The organic extracts were
dried over MgSO4, filtered, and concentrated in vacuo. Com-
pound 15 was obtained as a white solid. Yield: 12 mg (77%).
According to GLC, the product was g95% pure. The NMR data
were in agreement with the literature values.38
Su p p or tin g In for m a tion Ava ila ble: Further analytical
data (NMR assignments, IR, MS) for compounds 1e, 1g, 5, 7,
9-13 and NMR spectra (1H, 13C) of compounds 5b, 5h , 7e,
and 10. This material is available free of charge via the
Internet at http://pubs.acs.org.
(()-N-Meth ylep h ed r in e (16). To a mixture of 1.3 mmol
of LiAlH4 (49 mg) in THF (1 mL) was added a solution of 0.43
J O9819988
(37) Moreno-Man˜as, M.; Padros, I. J . Heterocyclic Chem. 1993, 30,
1235.
(38) Fujita, M.; Hiyama, T. J . Org. Chem. 1988, 53, 5415.
(39) Fujita, M.; Hiyama, T. J . Org. Chem. 1988, 53, 5405.