The Paterno-Buechi reaction of α-alkyl-substituted enecarbamates and benzaldehyde

Article abstract of DOI:10.1055/s-2001-15075

The α-substituted enecarbamates and enamides 5a-d, 5f and 6 were prepared in two steps from the corresponding ketone, N-benzylamine and an appropriate acylating agent (Boc₂O, Ac₂O). The [2+2] photocycloaddition reactions of benzaldeh

Full text of DOI:10.1055/s-2001-15075

PAPER
1117
The Paternò–Büchi Reaction of -Alkyl-Substituted Enecarbamates and
Benzaldehyde
Paternò–Büchi
h
eaction of
E
o
necarbamat
r
es withB
s
enzaldeh
t
yde en Bach,*a Jürgen Schröderb
a
Technische Universität München, Lehrstuhl für Organische Chemie I, Lichtenbergstr. 4, 85747 Garching, Germany
E-mail: E-Mail: thorsten.bach@ch.tum.de
b
Philipps-Universität Marburg, Fachbereich Chemie, 35032 Marburg, Germany
Received 18 December 2000
cently oxazoles have been successfully employed as alk-
ene components. They yield interesting bicyclic products
with high regio- and simple diastereoselectivity which can
be further converted into 3-hydroxy-2-aminoketones
Abstract: The -substituted enecarbamates and enamides 5a–d, 5f
and 6 were prepared in two steps from the corresponding ketone, N-
benzylamine and an appropriate acylating agent (Boc2O, Ac2O).
The [2+2] photocycloaddition reactions of benzaldehyde to the alk-
enes 5a–d which bear a primary or secondary alkyl substituent pro- upon hydrolysis.10 The use of -amino-substituted acry-
ceeded smoothly and gave the 3-aminooxetanes 8a–d in moderate
lonitriles in Paternò–Büchi reactions has been intensively
studied.11
to good yields (46–71%). The -phenyl-substituted enecarbamate
5f did not produce a photocycloaddition product presumably due to
Research in our group has centered on the [2+2] photocy-
cloaddition of -unsubstituted N-acyl enamines (enam-
ides) or N-alkoxycarbonyl enamines (enecarbamates) to
aldehydes.7,12 This reaction provides access to N-protect-
ed 3-aminooxetanes in good yields. As an example, the
photocycloaddition of enecarbamates 1 to various alde-
hydes is depicted in Scheme 1. The regioselectivity in fa-
vor of the 3-heteroatom-substituted oxetane is high. The
rapid energy transfer (triplet sensitization) from the photoexcited al-
dehyde. For less obvious reasons the tert-butyl-substituted enamide
6 did not react in the Paternò–Büchi reaction either. The 3-alkyl-3-
aminooxetanes 8 were obtained as a mixture of cis- and trans-dias-
tereoisomers. An increase in the steric bulk of the alkyl substituent
R shifted the diastereomeric ratio (cis-8/trans-8) in the direction of
the thermodynamically more stable cis-product (29:71 for R = CH3
up to 57:43 for R = cyclohexyl). The separated oxetane diastereoi-
somers cis-8a and trans-8a (R = CH3) underwent a smooth ring
opening/cyclization reaction upon treatment with trifluoroacetic ac- simple diastereoselectivity (cis-2/trans-2) is high for aro-
id. Oxetane trans-8a yielded the oxazolidinones 9 and trans-10
(92%), oxetane cis-8a gave exclusively the oxazolidinone cis-10
(54%).
matic aldehydes and lower for aliphatic aldehydes. Con-
secutive reactions of the 3-aminooxetanes 2 have been
investigated.7 In these reactions the readily removable N-
Keywords: cycloadditions, heterocycles, oxetanes, Paternò–Büchi
reactions, photochemistry
alkoxycarbonyl protective groups tert-butyloxycarbonyl
(Boc) and trimethylsilylethoxycarbonyl (Teoc) proved
more valuable and offered more flexibility than the N-acyl
protective groups.
Introduction
RCHO, hν
O
O
O
O
O
(MeCN)
3
3
+
The Paternò–Büchi reaction, i.e. the [2+2] photocycload-
dition of an alkene and a carbonyl compound, is the most
convenient and efficient way to synthesize substituted ox-
etanes.1,2 Recent work has been directed towards the use
of heteroatom-substituted alkenes as reaction partners
which gives access to 3-heteroatom-substituted oxetanes.3
Ring opening reactions lead to 1,2,3-trifunctional open
chain products.4 3-Aminooxetanes are particularly attrac-
tive target compounds.5 They exhibit interesting biologi-
cal properties6 and yield 1,2-amino alcohols and related
products upon ring opening.7 The choice of possible
enamine substrates which act as alkene components in the
Paternò–Büchi reaction is limited by the fact that electron-
rich alkenes undergo electron transfer reactions with pho-
toexcited carbonyl compounds. As a result the yields of 3-
aminooxetanes are low.8 Oxazolinones and oxazolines are
suitable substrates for the Paternò–Büchi reaction.9 Re-
R
N
R1
OR2
N
R1
OR2
R
N
R1
OR2
trans-2
cis-2
R = Aryl
56–77% d.r. = 90:10
1
R = Alkyl 46–55% d.r. = 65:35
Scheme 1
As an extension of our work we became interested in the
photocycloaddition of -substituted enecarbamates with
aldehydes. We chose to study the reaction of N-benzyl-N-
Boc-substituted enamines varying the substituent in -po-
sition. Major questions to be addressed were the chemose-
lectivity, regioselectivity and simple diastereoselectivity
of the reaction. The selection of the protective group was
based on the above-mentioned advantages associated with
N-Boc vs N-acyl protection. In addition, the second pro-
tective group (N-benzyl) can also be readily cleaved if de-
sired. Benzaldehyde was employed as the carbonyl
substrate. From previous work it is known that several
substituted aromatic aldehydes behave similarly to ben-
Synthesis 2001, No. 8, 18 06 2001. Article Identifier:
1437-210X,E;2001,0,08,1117,1124,fts,en;C10000SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1118
T. Bach, J. Schröder
PAPER
zaldehyde in the Paternò–Büchi reaction.2,13 From a syn-
thetic point of view the construction of 3-alkyl-3-amino-
substituted oxetanes by photocycloaddition chemistry
represents an interesting C–C-bond forming reaction. It
should make N,N-diprotected tert-alkylsubstituted amines
with an adjacent oxygen functionality available which are
difficult to prepare by other methods. In the following ac-
count we present the results of our study.
Table 1 N-Benzylimines 4 and Enamines 5 Prepared
R
Imine
4ab
4b
Yield (%)a Enamine
Yield (%)a
Me
Et
65
75
82
85
85
60
5a
5b
5c
5d
5e
5f
49
40
59
i-Pr
Chx
t-Bu
Ph
4c
4d
38
_c
4e
Results and Discussion
4f
26
Preparation of Enecarbamates: The preparation of the en-
ecarbamates 5 was conducted in a straightforward fashion
starting from the corresponding ketones 3 (Scheme 2).
Their conversion to the imines 4 was achieved by heating
a solution of the ketone 3 and N-benzyl amine in toluene
and by concurrent azeotropic removal of water in a Dean–
Stark apparatus.14 The acetone imine 4a was prepared un-
der basic conditions (basic alumina, activity I).15 The sub-
sequent N-acylation was performed with di-tert-butyl-
dicarbonate (Boc2O) and Et3N in benzene.16 The deproto-
nation of the intermediate N-tert-butoxycarbonyl-substi-
tuted iminium ion occurred regioselectively at the less
substituted, more accessible site. After stirring at room
temperature benzene was distilled off at atmospheric pres-
sure. According to our observations the comparably high
temperature required for the distillation served to com-
plete the reaction. With toluene as the solvent a double
bond isomerization occurred in some instances. Unfortu-
nately, we could not achieve a significant conversion of
imine 4e to the sterically congested compound 5e. Several
other transformations of 4 to 5 did only proceed in low or
moderate yields. Still, an optimization of the reaction con-
ditions was not attempted as the major aim of the study
was the investigation of the photocycloaddition. The
yields of the imines and enecarbamates prepared by the
discussed route are listed in Table 1.
a Yield of isolated product after distillation or chromatographic puri-
fication.
b The acetone imine was prepared from acetone (3a) and N-benzy-
lamine on basic alumina (activity I).
c No product was obtained.
Ac2O, py
O
DMAP (cat.)
(∆T, PhCH3)
O
O
+
tBu
N
tBu
N
tBu
NBn
Bn
Bn
4e
6
(8%)
7 (34%)
Scheme 3
Photocycloaddition Reactions: The Paternò–Büchi reac-
tions were conducted with benzaldehyde and an excess of
the enecarbamate 5 (2 equiv) in acetonitrile as the solvent
(Scheme 4). Rayonet lamps RPR 3000 Å ( = 300 nm)
were employed as the irradiation source. The regioselec-
tivity of the reaction was high. The formation of regioiso-
meric oxetane products could not be detected.
Remarkably, the total yields were good for the simple
alkyl-substituted enecarbamates 5a–c indicating a high
chemoselectivity. Although hydrogen abstraction at the
allylic position of the -alkyl substituted enecarbamates is
conceivable this side reaction appears to be considerably
slower than the addition of the photoexcited benzaldehyde
to the double bond. The cyclohexyl-substituted substrate
5d is expected to be most amenable to hydrogen abstrac-
tion which may account for the somewhat lower yield ob-
tained with this enecarbamate. The acetophenone-derived
enecarbamate 5f did not react (Table 2). This behaviour
can be explained by the low-lying triplet states of sty-
renes. Indeed, it is known that the Paternò–Büchi reaction
of aromatic aldehydes to aryl-substituted alkenes fails if
the the triplet energy of the alkene is lower than the triplet
energy of the aldehyde.2 Energy transfer (sensitization)
prevails and subsequent photochemical and photophysical
events occur from the styrene *-triplet. The oxetanes 8
were obtained by the [2+2] photocycloaddition as a mix-
ture of cis- and trans-products the ratio of which is sum-
marized in Table 2. For comparison the result obtained
with the -unsubstituted enamide 5g (R = H) has been in-
cluded in Table 2.
BnNH2
p-TsOH (cat.)
(∆T, PhCH3)
Boc2O, NEt3
(PhH)
O
R
N
OtBu
R
O
R
NBn
Bn
3
4
5
e: R = tBu; f: R= Ph
a: R = Me; b: R = Et; c: R = iPr; d: R =
;
Chx
Scheme 2
As an alternative to compound 5e whose synthesis was
not viable despite an intensive effort, we looked into the
N-acylation of imine 4e with acetic acid anhydride. In-
deed, it was possible to convert the imine 4e into the ena-
mide 6, albeit in very low yield. The major product 7 was
formed as the result of a Friedel–Crafts type acylation of
enamide 6 (Scheme 3).
Synthesis 2001, No. 8, 1117–1124 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Paternò–Büchi Reaction of Enecarbamates and Benzaldehyde
1119
NBnBoc
PhCHO, hν
(MeCN)
NBnBoc
Ph
4
4
Ph
O
O
O
O
2
2
+
5
R
NBnBoc
2
3
2
3
3
3
Ph
Ph
NBnBoc
R
H
CHMe2
H
CH3
6%
cis-8
trans-8
11%
8%
2%
Scheme 4
cis-8a
cis-8c
Table 2 [2+2]-Photocycloaddition of Enecarbamates 5 to Benzal-
dehyde
Figure 1 H NMR NOE data (360 MHz) obtained in DMSO-d6 at
373 K for the cis diastereoisomers cis-8a and cis-8c
R
Substrate Time (h)a Product Yield (%)b drc
are the cis-products cis-8. It is experimentally observed
that an increase in the size of the substituent R generally
shifts the diastereomeric ratio in favor of the more stable
diastereoisomer. Whereas enecarbamate 5g (R = H)
yields with high selectivity (dr = 87:13) the thermody-
namically less favored diastereoisomer cis-8g the selec-
tivity for the thermodynamically disfavored isomer trans-
8a in the case of the -substituted enecarbamate 5a
(R = Me) is less pronounced (dr = 29:71). It further de-
creases for enecarbamate 5b (R = Et), which produces a
selectivity of 34:66 in favor of trans-8b. For R = i-Pr the
preference is in favor of the thermodynamically more sta-
ble cis-isomer cis-8c (dr = 54:46). This result is in line
with the dr (57:43) recorded for the equally bulky cyclo-
hexyl-substituted enecarbamate 5d. It is unfortunate that
we were not able to study the tert-butyl-substituted ene-
carbamate 5e as it was expected to exhibit an even more
pronounced cis-selectivity. Its potential enamide substi-
tute 6 failed to yield an oxetane product upon irradiation
with benzaldehyde.
Me
Et
5a
5b
5cc
5d
5f
5
5
3
8a
8b
8c
8d
8f
70
69
71
46
29:71
34:66
54:46
i-Pr
Chx
Ph
H
4
57:43
_d
d
_d
_
5g
5
8g
77
87:13
a Time after which the reaction was complete according to GC.
b Combined yield of the isolated products cis- and trans-8 after chro-
matographic purification.
c The diastereomeric ratio (dr = cis-8/trans-8) was determined in the
crude product mixture by integration of appropriate 1H NMR signals.
d No product was obtained.
The 3-alkyl-substituted oxetane diastereoisomers cis-8
and trans-8 were separable by flash chromatography al-
though the separation was not always fully complete.
Their relative configuration was deduced from 1H NOE or
NOESY studies. In general, the cis-diastereoisomers
show a strong contact between H-2 and the protons at-
tached to the alkyl (Me, Et, i-Pr, Chx) substituent at C-3.
This phenomenon is illustrated in the Figure, which sum-
marizes the pertinent NOE data recorded for the diastere-
oisomers cis-8a and cis-8c. The trans-diastereoisomers
did not show significant NOEs between the substituents at
C-3 and the proton H-2. The chemical shift of the proton
H-2 is distinctly different in either pair of oxetane diaste-
reoisomers cis- and trans-8. It resonates at lower field in
the trans-isomer trans-8 ( = 5.66–5.83) and at higher
field in the cis-isomer cis-8 ( = 5.21–5.43). The differ-
A preference for thermodynamically more stable products
in the Paternò–Büchi reaction has also been observed for
-alkyl-substituted silyl enol ethers.18 It was associated
with a competition between cleavage and ring closure in
the intermediate 1,4-biradical. On the other hand, the pref-
erential formation of the thermodynamically less stable
oxetane product is precedented for a-unsubstituted and -
methyl-substituted cyclic enol ethers and related com-
pounds.19 The hypothesis of a kinetically controlled selec-
tion between diastereomeric 1,4-biradical conformations
in the intersystem crossing step has been put forward by
Griesbeck et al. to account for this behaviour.20 This hy-
pothesis can equally well be applied to -unsubstituted
enamides and enecarbamates, e.g. 5g.7 As the size of the
substituent increases the kinetic control in the ISC step is
possibly erased by the cleavage reaction and eventually
the steric factors dominate as it is the case in the above-
mentioned silyl enol ether photocycloaddition reactions.
ence
in each pair of diastereoisomers amounts to at
least 0.3 ppm. As a consequence of the aromatic ring cur-
rent, protons of alkyl groups, which are located cis to the
phenyl substituent at C-2 are shielded. The CH3 group of
diastereoisomer cis-8a (CH3 and Ph trans) for example
resonates at 1.75 ppm whereas the CH3 group of trans-8a
(CH3 and Ph cis) is responsible for an absorption at
= 1.14.
Ring Opening to Oxazolidinones: The fact that the meth-
yl-substituted oxetanes 8a are separable allowed their iso-
lation in diastereomerically pure form. When the
diastereoisomers cis- and trans-8a were subjected to treat-
ment with trifluoroacetic acid they underwent an interest-
ing intramolecular substitution reaction which had
previously been observed with simple 3-N-Boc-aminoox-
etanes, such as 8g.7 The reaction leads to oxazolidinones
the relative configuration of which was proven by NMR
Based on steric arguments the relative thermodynamic
stability of the product oxetanes 8 can be roughly estimat-
ed. An increase in steric bulk for the substituents at C-3 in
the order H < NBnBoc Me Et < i Pr Chx is realistic
based on the tabulated A values.17 If R = H the thermody-
namically more stable isomer is the trans-product trans-
8g, if R H the thermodynamically more stable isomers
Synthesis 2001, No. 8, 1117–1124 ISSN 0039-7881 © Thieme Stuttgart · New York

1120
T. Bach, J. Schröder
PAPER
P = pentane, CH = cyclohexane, CH2Cl2, MeOH and EtOH) and
Ac2O were distilled prior to use. Anhyd CH2Cl2 was distilled from
CaH2, anhyd benzene and toluene from Na prior to use. Et3N was
distilled from CaH2. All other reagents and solvents were used as re-
ceived. Melting points (uncorrected): Reichert hot bench. IR: Bruk-
er IFS 88 FT-IR or Nicolet 510M FT-IR. MS: Varian CH7 (EI). 1H
and 13C NMR: Bruker ARX-200, Bruker AC-300, Bruker AM-400,
Bruker AMX-500, Varian uniti plus 600. 1H and 13C NMR spectra
were recorded in CDCl3 as solvent at ambient temperature unless
stated otherwise. Chemical shifts are reported relative to TMS as an
internal reference. Interchangeable assignments are marked with an
asteriks (*). NOESY contacts are reported as weak (‘), medium (‘‘)
or strong (‘‘‘). Elemental analysis: Elementar vario EL. Optical ro-
tations: Perkin-Elmer 241, determined at r.t. HPLC: Merck-Hitachi
L6200A equipped with an UV spectrometer detector (254 nm).
TLC: Merck aluminium sheets (0.2 mm silica gel 60 F254. Detection
by UV or by coloration with ceric ammonium molybdate (CAM).
Flash chromatography:21 Merck silica gel 60 (230–400 mesh
ASTM) (ca. 50 g for 1 g of material to be separated).
studies. In the case of compounds 8a the reaction ap-
peared interesting to study as the starting materials were
available in diastereomerically pure form. The major dias-
tereoisomer trans-8a yielded two products. One oxazolid-
inone 9 was the product of oxygen attack at the carbon
atom C-4 of the oxetane, the other oxazolidinone was the
pure trans-oxazolidinone trans-10 which is a result of at-
tack at C-2 (Scheme 5). Contrary to that, the ring opening
of oxetane cis-8a occurred regioselectively at C-2 and
gave the product cis-10 with inversion of configuration
(Scheme 5).
HO
CF3COOH
(CH2Cl2)
O
N
Ph
O
HO
+
trans-8a
N
O
Bn
92%
Bn
Ph
O
9
trans-10
tert-Butyl Benzyl(isopropenyl)carbamate (5a); Typical
Procedure
CF3COOH
(CH2Cl2)
Ph
OH
Freshly prepared imine 4a15 (1.47 g, 10 mmol) and Et3N (1.39 mL,
1.01 g, 10 mmol) were dissolved in benzene (4 mL). The mixture
was stirred and cooled to 5–8 °C, and a solution of di-tert-butyl di-
carbonate (Boc2O, 2.18 g, 10 mmol) in benzene (2 mL) was added.
After the addition, the mixture was stirred for 1.5 h at r.t. The sol-
vent was distilled under atmospheric pressure, and the unconverted
imine was removed by bulb-to-bulb distillation in vacuo. The resi-
due was purified by flash chromatography (CH–EA, 95:5); yield:
1.23 g (49%); Rf 0.31 (CH–EA, 90:10).
cis-8a
N
O
Bn
54%
O
cis-10
Scheme 5
Notably, there was no indication for an oxygen attack at
C-2 under retention of configuration. This observation
rules out a SN1-type displacement mechanism which
would involve a free carbeniumion. The conversion of the
oxetanes 8a to the products 10 proceeds stereospecifically
in an SN2-type process. Although this conclusion had been
drawn earlier for the reaction of the unsubstituted oxetane
8g it could not be proven unambiguosly at that point in
time as the two diastereoisomers cis-8g and trans-8g were
not separable.
IR (film): = 3070 (w, CarH), 2980 (s, CalH), 2940 (s, CalH), 1710
(vs, C=O), 1665 (m, C=C), 1380 (s), 1230 (s), 1170 cm–1 (s).
1H NMR (300 MHz): = 1.45 [s, 9 H, C(CH3)3], 1.87 (dd, 3 H,
J = 1.2, 0.4 Hz, CH3), 4.61 (s, 2 H, CH2Ph), 4.68 (q, 1 H, J = 1.2
Hz, =CHH), 4.73 (q, 1 H, J = 0.4 Hz, =CHH), 7.20–7.35 (m, 5
Harom).
13C NMR (75.5 MHz): = 21.6 (q, CH3), 28.3 [q, C(CH3)3], 52.9 (t,
CH2Ph), 80.2 [s, C(CH3)3], 109.1 (t, C=CH2), 126.9 (d, CarH), 127.4
(d, CarH), 128.3 (d, CarH), 138.9 (s, Car), 145.3 (s, C=CH2), 154.2
(s, CO).
MS (EI, 70 eV): m/z (%) = 190 (19) [M+ – C4H9], 146 (19) [M+ –
Conclusion and Outlook
+
+
COOC4H9], 130 (12), 91 (100) [C7H7 ], 77 (5) [C6H5 ], 65 (10)
+
+
+
[C5H5 ], 57 (71) [C4H9 ], 41 (44) [C3H5 ].
In summary, we have shown that -alkyl substituted ene-
carbamates can be readily prepared from the correspond-
ing imines and that these substrates undergo a clean [2+2]
photocycloaddition to benzaldehyde. Primary and sec-
Anal. Calcd for C15H21NO2 (247.3): C, 72.84; H, 8.56; N, 5.66.
Found: C, 72.97; H, 8.63; N, 5.73.
tert-Butyl Benzyl(1-ethylvinyl)carbamate (5b)
ondary alkyl substituents in the -position are best suited The enecarbamate 5b was prepared from imine 4b14 (1.61 g, 10
mmol) following the procedure provided for the transformation 4a
to 5a. Purification by flash chromatography (CH–EA, 95:5) yielded
the desired product (0.92 g, 40%); Rf 0.53 (CH–EA, 90:10).
to guarantee a high chemo- and regioselectivity. Although
the simple diastereoselectivity of the photochemical reac-
tion is low the method provides convenient and straight-
forward access to pure N,N-diprotected 3-alkyl-3-
aminooxetanes. Mechanistic explanations for the simple
diastereoselection have been put forward but they have
not been verified by the traditional methods of organic
photochemistry (determination of quantum yields,
IR (film): = 3110 (w, CarH), 3065 (w, CarH), 3030 (w, CarH), 2975
(s, CalH), 2935 (m, CalH), 2880 (w, CalH), 1700 (vs, C=O), 1650 (s,
C=C), 1450 (s), 1390 (s), 1170 cm–1 (s).
1H NMR (300 MHz): = 0.95 (t, 3 H, J = 7.4 Hz, CH2CH3), 1.46
[s, 9 H, C(CH3)3], 2.21 (q, 2 H, J = 7.4 Hz, CH2CH3), 4.58 (s, 2 H,
CH2Ph), 4.72 (s, 1 H, =CHH), 4.80 (t, 1 H, J = 1.4 Hz, =CHH),
7.23–7.33 (m, 5 Harom).
quenching experiments). Work along this line will be pur-
sued and reported in due course.
13C NMR (75.5 MHz): = 11.3 (q, CH2CH3), 26.9 (t, CH2CH3),
37.8 [q, C(CH3)3], 52.6 (t, CH2Ph), 79.5 [s, C(CH3)3], 107.8 (t,
All reactions involving water-sensitive compounds were carried out
in flame-dried glassware with magnetic stirring under argon. Com-
mon solvents (TBME = tert-BuOMe, Et2O, EA = EtOAc,
C=CH2), 127.3 (d, CarH), 127.4 (d, CarH), 127.7 (d, CarH), 138.7 (s,
Car), 150.4 (s, C=CH2), 153.9 (s, CO).
Synthesis 2001, No. 8, 1117–1124 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Paternò–Büchi Reaction of Enecarbamates and Benzaldehyde
1121
MS (EI, 70 eV): m/z (%) = 205 (15) [M+ – C4H8], 176 (6), 160 (22)
(d, CarH), 128.3 (d, CarH), 138.9 (s, Car), 145.3 (s, C=CH2), 154.2
(s, CO).
[M+ – COOC4H9], 146 (16), 91 (100) [C7H7 ], 77 (3) [C6H5 ], 57
+
+
+
+
(59) [C4H9 ], 41 (43) [C3H5 ].
MS (EI, 70 eV): m/z (%) = 252 (33) [M+ – C4H9], 208 (100) [M+ –
+
+
Anal. Calcd for C16H23NO2 (261.4): C, 73.53; H, 8.87; N, 5.36.
Found: C, 73.43; H, 8.89; N, 5.30.
CO2C4H9], 162 (16), 117 (5), 91 (97) [C7H7 ], 77 (15) [C6H5 ], 65
+
+
+
(15) [C5H5 ], 57 (73) [C4H9 ], 41 (44) [C3H5 ].
Anal. Calcd for C20H23NO2 (309.4): C, 77.64; H, 7.49; N, 4.53.
Found: C, 77.65; H, 7.46; N, 4.56.
tert-Butyl Benzyl(1-isopropylvinyl)carbamate (5c)
The enecarbamate 5c was prepared from imine 4c14,22 (1.75 g, 10
mmol) following the procedure provided for the transformation 4a
to 5a. Purification by flash chromatography (CH–EA, 95:5) yielded
the desired product (1.62 g, 59%); Rf 0.31 (CH–EA, 90:10).
N-Benzyl-N-[(1-tert-butyl)vinyl]acetamide (6)
A solution of imine 4e14,22 (3.00 g, 15.8 mmol), Ac2O (2.96 mL,
3.22 g, 15.8 mmol), pyridine (1.28 mL, 1.25 g, 15.8 mmol) and a
catalytic amount of DMAP in toluene (60 mL) was refluxed for 1 h.
Upon cooling to r.t. the mixture was poured into aq 0.1 M HCl (30
mL). The aqueous layer was extracted with Et2O (3 30 mL). The
combined organic layers were washed with brine (50 mL) and dried
(MgSO4). After filtration the solvent was removed in vacuo and the
residue was purified by flash chromatography (P–TBME, 60:40). In
addition to the desired product (300 mg, 8%) its acyl derivative 7
was isolated (1.51 g, 34%).
IR (film): = 3060 (w, CarH), 3025 (w, CarH), 2960 (s, CalH), 2920
(m, CalH), 2870 (w, CalH), 1690 (s, C=O), 1640 (m, C=C), 1450
(m), 1385 (s), 1170 cm–1 (s).
1H NMR (300 MHz, acetone-d6): = 1.02 [d, 6 H, J = 6.9 Hz,
CH(CH3)2], 1.45 [s, 9 H, C(CH3)3], 2.53–2.57 [m, 1 H, CH(CH3)2],
4.57 (s, 2 H, CH2Ph), 4.70 (br s, 1 H, =CHH), 4.80 (d, 1 H, J = 1.2
Hz, =CHH), 7.18–7.35 (m, 5 Harom).
13C NMR (75.5 MHz, acetone-d6): = 22.3 [q, CH(CH3)2], 28.9 [q,
C(CH3)3], 33.6 [d, CH(CH3)2], 50.2 (t, CH2Ph), 80.4 [s, C(CH3)3],
108.3 (t, C=CH2), 128.1 (d, CarH), 129.0 (d, CarH), 129.4 (d, CarH),
140.9 (s, Car), 155.6 (s, C=CH2), 157.0 (s, CO).
6
Rf 0.85 (P–TBME, 60:40).
IR (film): = 3105 (w, CarH), 3065 (w, CarH), 3030 (w, CarH), 2970
(s, CalH), 2975 (w, CalH), 2875 (w, CalH), 1710 (s, C=O), 1650 (s,
C=C), 1455 (s), 1390 (s), 1170 (s), 730 (s), 700 cm–1 (s).
1H NMR (300 MHz): = 1.46 [s, 9 H, C(CH3)3], 2.09 (s, 3 H, CH3),
3.87 (d, 1 H, J = 14.4 Hz, CHHPh), 4.58 (s, 1 H, =CHH), 5.18 (s, 1
H, =CHH), 5.50 (d, 1 H, J = 14.4 Hz, CHHPh), 7.15–7.33 (m, 5
Harom).
13C NMR (75.5 MHz): = 22.4 (q, CH3), 30.8 [q, C(CH3)3], 37.1
[s, C(CH3)3], 50.6 (t, CH2Ph), 116.0 (t, C=CH2), 127.1 (d, CarH),
128.1 (d, CarH), 128.8 (d, CarH), 137.5 (s, Car), 155.9 (s, C=CH2),
170.6 (s, CO).
MS (EI, 70 eV): m/z (%) = 218 (38) [M+ – C4H9], 174 (28) [M+ –
+
+
COOC4H9], 160 (28), 146 (16), 91 (100) [C7H7 ], 65 (13) [C5H5 ],
+
+
57 (81) [C4H9 ], 41 (51) [C3H5 ].
Anal. Calcd for C17H25NO2 (275.4): C, 74.14; H, 9.15; N, 5.09.
Found: C, 73.86; H, 9.37; N, 5.17.
tert-Butyl Benzyl(1-cyclohexylvinyl)carbamate (5d)
The enecarbamate 5d was prepared from imine 4d14,23 (2.15 g, 10
mmol) following the procedure provided for the transformation 4a
to 5a. Purification by flash chromatography (CH–EA, 95:5) yielded
the desired product (1.28 g, 38%); Rf 0.53 (CH–EA, 90:10).
MS (EI, 70 eV): m/z (%) = 232 (19) [M+], 188 (34) [M+ – C4H9],
IR (film): = 3090 (w, CarH), 3065 (w, CarH), 3005 (w, CarH), 2975
(s, CalH), 2930 (s, CalH), 2850 (m, CalH), 1700 (vs, C=O), 1640 (m,
C=C), 1385 (s), 1320 (s), 1170 cm–1 (s).
+
+
140 (24), 106 (33), 91 (100) [C7H7 ], 57 (21) [C4H9 ], 43 (53).
HRMS: m/z calcd for C15H21NO 231.1623; found 231.1622.
1H NMR (300 MHz): = 1.01–1.19 (m, 6 H, 3 CH2), 1.44 [s, 9 H,
C(CH3)3], 1.65–1.85 (m, 4 H, 2 CH2), 2.11–2.19 [m, 1 H,
CH(CH2)2], 4.55 (s, 2 H, CH2Ph), 4.66 (s, 1 H, =CHH), 4.78 (s, 1 H,
=CHH), 7.21–7.31 (m, 5 Harom).
13C NMR (75.5 MHz): = 26.3 (t, CH2), 26.6 (t, CH2), 28.3 [q,
C(CH3)3], 32.1 (t, CH2), 42.5 [d, CH(CH2)2], 55.8 (t, CH2Ph), 79.9
[s, C(CH3)3], 108.3 (t, C=CH2), 126.9 (d, CarH), 127.7 (d, CarH),
128.2 (d, CarH), 139.2 (s, Car), 154.4 (s, C=CH2), 154.8 (s, CO).
N-Benzyl-N-[(E)-3-oxobut-1-enyl]acetamide (7)
Rf 0.21 (P–TBME, 60:40).
IR (film): = 3185 (w, CarH), 3065 (w, CarH), 3030 (w, CarH), 2970
(s, CalH), 2870 (w, CalH), 1700 (s, C=O), 1650 (s, C=C), 1615 (s),
1385 (s), 1355 (s), 1150 (s), 720 (s), 700 cm–1 (s).
1H NMR (300 MHz): = 1.25 [s, 9 H, C(CH3)3], 1.63 (s, 3 H, CH3),
2.07 (s, 3 H, CH3), 4.13 (d, 1 H, J = 14.6 Hz, CHHPh), 5.18 (d, 1
H, J = 14.6 Hz, CHHPh), 6.27 (s, 1 H, =CH), 7.21–7.31 (m, 5
MS (EI, 70 eV): m/z (%) = 315 (<1) [M+], 258 (39) [M+ – C4H9],
Harom).
+
214 (14) [M+ – COOC4H9], 168 (17), 57 (100) [C4H9 ].
13C NMR (75.5 MHz): = 22.7 (q, CH3), 30.2 (q, CH3), 30.9 [q,
C(CH3)3], 38.0 [s, C(CH3)3], 50.9 (t, CH2Ph), 126.4 (d, CarH), 127.4
(d, CarH), 128.6 (d, CarH), 130.0 (d, =CH), 136.6 (s, Car), 158.3 (s,
C=CH), 170.5 (s, CO), 196.2 (s, CO).
Anal. Calcd for C20H29NO2 (315.5): C, 76.15; H, 9.29; N, 4.44.
Found: C, 75.87; H, 9.08; N, 4.43.
tert-Butyl Benzyl(1-phenylvinyl)carbamate (5f)
The enecarbamate 5f was prepared from imine 4f14,22 (2.09 g, 10
mmol) following the procedure provided for the transformation 4a
to 5a. Purification by flash chromatography (CH–EA, 95:5) yielded
the desired product (0.82 g, 26%); Rf 0.31 (CH–EA, 90:10).
MS (EI, 70 eV): m/z (%) = 230 (51) [M+ – COCH3], 216 (2) [M+ –
+
+
+
C4H9], 174 (5), 91 (100) [C7H7 ], 65 (7) [C5H5 ], 57 (7) [C4H9 ], 43
(23).
Anal. Calcd for C17H23NO2 (273.4): C, 74.69; H, 8.48; N, 5.12.
Found: C, 74.61; H, 8.49; N, 5.17.
IR (film): = 3040 (w, CarH), 3015 (w, CarH), 2975 (m, CalH), 2920
(w, CalH), 1690 (s, CO), 1630 (m, C = C), 1385 (s), 1335 (s), 1150
(s), 700 cm–1 (s).
1H NMR (300 MHz): = 1.24 [s, 9 H, C(CH3)3], 4.73 (s, 2 H,
CH2Ph), 4.96 (s, 1 H, =CHH), 5.26 (s, 1 H, =CHH), 7.27–7.33 (m,
10 Harom).
tert-Butyl Benzyl(3-methyl-2-phenyloxetan-3-yl)carbamate
(8a); Typical Procedure
In a quartz tube benzaldehyde (152 L, 159 mg, 1.5 mmol) and the
enecarbamate 5a (741 mg, 3.0 mmol) were dissolved in MeCN (10
mL). This mixture was irradiated for period indicated in Table 2
13C NMR (75.5 MHz): = 21.6 (q, CH3), 28.3 [q, C(CH3)3], 52.9 (t,
CH2Ph), 80.2 [s, C(CH3)3], 109.1 (t, C=CH2), 126.9 (d, CarH), 127.4
(
= 300 nm; light source: Rayonet RPR 3000). The course of the
reaction was monitored by TLC and GC. Upon complete conver-
Synthesis 2001, No. 8, 1117–1124 ISSN 0039-7881 © Thieme Stuttgart · New York

1122
T. Bach, J. Schröder
PAPER
sion the solvent was evaporated in vacuo. The simple diastereose-
lectivity (dr = 29:71) was determined by 1H NMR and GC analysis
of the crude product mixture. The excess enecarbamate was recov-
ered in the course of the subsequent flash chromatography (CH–
EA, 90:10). The oxetanes cis-8a and trans-8a were fully separable.
Total yield: 370 mg (70%).
J = 7.5 Hz, CHHCH3), 2.37 (dq, 1 H, J = 14.3, 7.5 Hz, CHHCH3),
3.87 (d, 1 H, J = 16.2 Hz, CHHPh), 4.29–4.32 (m, 2 H, OCHH,
CHHPh), 5.03 (d, 1 H, J = 6.6 Hz, OCHH), 5.26 (s, 1 H, PhCHO),
6.95–7.41 (m, 10 Harom).
1H NOE (360 MHz, DMSO-d6, 373 K): H (2.23): H(2.37) [21.7%],
H(5.26) [4.2%]; H (2.37): H(2.23) [10.4%], H(5.26) [2.4%]; H (5.26):
IR (film): = 3085 (w, CarH), 3040 (w, CarH), 2985 (s, CalH), 2895
(s, CalH), 1690 (vs, C=O), 1170 (s), 1070 (s), 985 cm–1 (m, COC).
H(2.23) [2.3%], H(2.37) [1.9%].
13C NMR (75.5 MHz, DMSO-d6): = 25.8 (q, CH2CH3), 27.2 [q,
C(CH3)3], 27.7 (t, CH2CH3), 48.8 (t, CH2Ph), 64.7 (s, CCH2), 74.3
(t, OCH2), 78.7 [s, C(CH3)3], 90.2 (d, PhCHO), 125.8 (d, CarH),
125.9 (d, CarH), 126.4 (d, CarH), 126.5 (d, CarH), 126.8 (d, CarH),
127.0 (d, CarH), 138.3 (s, Car), 138.7 (s, Car), 154.0 (s, CO).
Anal. Calcd for C22H27NO3 (353.5): C, 74.75; H, 7.70; N, 3.96.
Found: C, 74.68; H, 7.85; N, 4.19.
Minor Diastereoisomer cis-8a
Yield: 115 mg (22%); Rf 0.55 (CH–EA, 60:40).
MS (EI, 70 eV): m/z (%) = 280 (8) [M+ – H2CO – C4H9], 204 (22),
1H NMR (360 MHz, DMSO-d6, 373 K): = 1.18 [s, 9 H, C(CH3)3],
1.75 (s, 3 H, CH3), 4.13–4.19 (m, 3 H, CH2Ph, CHH), 5.13 (d, 1 H,
J = 6.6 Hz, CHH), 5.21 (s, 1 H, PhCHO), 7.19–7.43 (m, 10 Harom).
161 (15), 151 (36), 106 (18), 91 (97) [C7H7 ], 77 (5) [C6H5 ], 57
+
+
+
(100) [C4H9 ].
Major Diastereoisomer trans-8b
Rf 0.32 (CH–EA, 90:10).
1H NOE (360 MHz, DMSO-d6, 373 K): H (1.75): H(5.21) [11.2%]; H
(5.21): H(1.74) [1.8& hairsp;%].
1H NMR (600 MHz, DMSO-d6, 373 K): = 0.59 (t, 3 H, J = 7.5
Hz, CH2CH3), 1.35 [s, 9 H, C(CH3)3], 1.64 (dq, 1 H, J = 15.0 Hz,
J = 7.5 Hz, CHHCH3), 1.85 (dq, 1 H, J = 15.0, 7.5 Hz, CHHCH3),
4.32 (d, 1 H, J = 6.8 Hz, OCHH), 4.32 (d, 1 H, J = 16.5 Hz, CHH-
Ph), 4.51 (d, 1 H, J = 16.5 Hz, CHHPh), 4.84 (d, 1 H, J = 6.8 Hz,
OCHH), 5.69 (s, 1 H, PhCHO), 7.32–7.45 (m, 10 Harom).
1H NOE (360 MHz, DMSO-d6, 373 K): no significant NOEs be-
tween ring substituents.
13C NMR (75.5 MHz, DMSO-d6): = 25.1 (q, CH2CH3), 25.8 (t,
CH2CH3), 27.4 [q, C(CH3)3], 48.5 (t, CH2Ph), 66.0 (s, CCH2), 75.9
(t, OCH2), 79.1 [s, C(CH3)3], 86.6 (d, PhCHO), 125.5 (d, CarH),
126.0 (d, CarH), 126.4 (d, CarH), 127.3 (d, CarH), 127.4 (d, CarH),
127.8 (d, CarH), 137.3 (s, Car), 139.1 (s, Car), 154.0 (s, CO).
13C NMR (75.5 MHz): = 27.7 (q, CH3), 27.7 [q, C(CH3)3], 48.3 (t,
CH2Ph), 61.3 (s, CCH2), 78.0 (t, OCH2), 79.7 [s, C(CH3)3], 93.0 (d,
PhCHO), 126.4 (d, CarH), 126.9 (d, CarH), 127.3 (d, CarH), 128.3 (d,
CarH), 128.5 (d, CarH), 128.6 (d, CarH), 138.3 (s, Car), 138.3 (s, Car),
155.0 (s, CO).
MS (EI, 70 eV): m/z (%) = 266 (4) [M+ – H2CO – C4H9], 222 (4)
[M+ – H2CO – COOC4H9], 190 (24), 146 (27), 130 (21), 91 (99)
+
+
+
+
[C7H7 ], 77 (11) [C6H5 ], 65 (11) [C5H5 ], 57 (54) [C4H9 ], 41 (100)
+
[C3H5 ].
Major Diastereoisomer trans-8a
Yield: 255 mg (48%); Rf 0.58 (CH–EA, 60:40).
1H NMR (360 MHz, DMSO-d6, 373 K): = 1.14 (s, 3 H, CH3), 1.38
[s, 9 H, C(CH3)3], 4.28 (d, 1 H, J = 16.7 Hz, CHHPh), 4.28 (d, 1 H,
J = 6.5 Hz, CHH), 4.50 (d, 1 H, J = 16.7 Hz, CHHPh), 4.81 (d, 1
H, J = 6.5 Hz, CHH), 5.66 (s, 1 H, PhCHO), 7.20–7.45 (m, 10
MS (EI, 70 eV): m/z (%) = 367 (1) [M+], 310 (2) [M+– C4H9], 280
(13) [M+ – H2CO – C4H9], 248 (10), 204 (33), 105 (14), 91 (100)
+
+
+
[C7H7 ], 77 (10) [C6H5 ], 57 (40) [C4H9 ].
Harom).
1H NOE (360 MHz, DMSO-d6, 373 K): no significant NOEs be-
tween ring substituents.
tert-Butyl Benzyl(3-isopropyl-2-phenyloxetan-3-yl)carbamate
(8c)
The oxetanes 8c were prepared from enecarbamate 5c (825 mg, 3.0
mmol) and benzaldehyde (152 L, 159 mg, 1.5 mmol) following the
procedure provided for the transformation 5a to 8a (dr = 54:46).
Purification by flash chromatography (CH–EA, 90:10) yielded the
desired products (338 mg, 71%), which were not fully separable.
13C NMR (75.5 MHz): = 18.5 (q, CH3), 28.3 [q, C(CH3)3], 47.8 (t,
CH2Ph), 63.3 (s, CCH2), 79.5 (t, OCH2), 81.6 [s, C(CH3)3], 86.9 (d,
PhCHO), 126.1 (d, CarH), 126.8 (d, CarH), 127.0 (d, CarH), 128.1 (d,
CarH), 128.3 (d, CarH), 128.6 (d, CarH), 137.6 (s, Car), 139.0 (s, Car),
155.0 (s, CO).
IR (film): = 3090 (m, CarH), 3070 (m, CarH), 2980 (s, CalH), 2925
(m, CalH), 2855 (m, CalH), 1705 (vs, C=O), 1460 (s), 1395 (s), 1170
(m), 990 cm–1 (m, COC).
MS (EI, 70 eV): m/z (%) = 266 (3) [M+ – H2CO – C4H9], 222 (2)
[M+ – H2CO – COOC4H9], 190 (27), 146 (27), 130 (18), 91 (100)
+
+
+
+
[C7H7 ], 77 (10) [C6H5 ], 65 (11) [C5H5 ], 57 (54) [C4H9 ], 41 (89)
+
Anal. Calcd for C24H31NO3 (381.5): C, 75.56; H, 8.19; N, 3.67;
found C, 75.35; H, 8.33; N, 3.74.
[C3H5 ].
tert-Butyl Benzyl(3-ethyl-2-phenyloxetan-3-yl)carbamate (8b)
The oxetanes 8b were prepared from enecarbamate 5b (783 mg, 3.0
mmol) and benzaldehyde (152 L, 159 mg, 1.5 mmol) following the
procedure provided for the transformation 5a to 8a (dr = 34:66).
Purification by flash chromatography (CH–EA, 95:5) yielded the
desired products (380 mg, 69%), which were not fully separable.
Major Diastereoisomer cis-8c
Rf 0.58 (CH–EA, 60:40).
1H NMR (360 MHz, DMSO-d6, 373 K): = 0.93 (d, 3 H, J = 7.0
Hz, CHCH3), 1.18 [s, 9 H, C(CH3)3], 1.34 (d, 3 H, J = 7.0 Hz,
CHCH3), 2.43 [septet, 1 H, J = 7.0 Hz, CH(CH3)2], 3.70 (d, 1 H,
J = 16.0 Hz, CHHPh), 4.29 (d, 1 H, J = 16.0 Hz, CHHPh), 4.45 (d,
1 H, J = 7.0 Hz, OCHH), 4.97 (d, 1 H, J = 7.0 Hz, OCHH), 5.41 (s,
1 H, PhCHO), 7.15–7.55 (m, 10 Harom).
IR (film): = 3060 (w, CarH), 3015 (w, CarH), 2965 (s, CalH), 2935
(s, CalH), 2880 (m, CalH), 1690 (vs, C=O), 1450 (s), 1170 (s), 990
cm–1 (m, COC).
1H NOE (360 MHz, DMSO-d6, 373 K): H (0.93): H(5.41) [2.7%]; H
(1.34): H(5.41) [13.1%]; H (2.43): H(5.41) [8.1%]; H (5.41): H(0.93)
[1.0%], H(1.34) [2.6%], H(2.43) [5.7%].
Anal. Calcd for C23H29NO3 (367.5): C, 75.14; H, 7.95; N, 3.81;
found C, 75.23; H, 8.10; N, 3.87.
Minor Diastereoisomer cis-8b
Rf 0.28 (CH–EA, 90:10).
1H NMR (600 MHz, DMSO-d6, 373 K): = 0.99 (t, 3 H, J = 7.5
Hz, CH2CH3), 1.20 [s, 9 H, C(CH3)3], 2.23 (dq, 1 H, J = 14.3 Hz,
13C NMR (75.5 MHz): = 16.8 [d, CH(CH3)2], 17.1 (q, CHCH3),
17.3 (q, CHCH3), 27.6 [q, C(CH3)3], 50.7 (t, CH2Ph), 68.5 (s,
CCH2), 71.6 (t, OCH2), 88.4 (d, PhCHO), 89.1 [s, C(CH3)3], 126.0
Synthesis 2001, No. 8, 1117–1124 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Paternò–Büchi Reaction of Enecarbamates and Benzaldehyde
1123
(d, CarH), 126.1 (d, CarH), 127.1 (d, CarH), 127.4 (d, CarH), 127.6 (d,
CarH), 128.1 (d, CarH), 138.4 (s, Car), 1139.1 (s, Car), 154.3 (s, CO).
1H NOESY (400 MHz, DMSO-d6, 373 K): no significant NOESY
contacts between ring substituents.
MS (EI, 70 eV): m/z (%) = 294 (1) [M+ – H2CO – C4H9], 281 (1)
13C NMR (75.5 MHz, DMSO-d6): = 26.9 (t, CH2), 27.5 (t, CH2),
27.7 (t, CH2), 28.5 (t, CH2), 28.6 (t, CH2), 28.7 [q, C(CH)3], 44.3 (s,
CH), 51.4 (t, PhCH2), 70.4 (d, CN), 75.1 (t, OCH2), 80.3 (s, CMe3),
87.8 (d, PhCH), 126.5 (d, CarH), 127.2 (d, CarH), 128.0 (d, CarH),
128.7 (d, CarH), 128.9 (d, CarH), 129.1 (d, CarH), 139.6 (s, Car),
140.9 (s, Car), 155.1 (s, CO).
[M+ – C4H8 – CO2], 218 (35) [M+ – PhCHO – C4H9], 208 (5), 174
+
(16) [M+ – PhCHO – COOC4H9],, 160 (13), 91 (100) [C7H7 ], 77
+
+
+
+
(10) [C6H5 ], 65 (11) [C5H5 ], 57 (62) [C4H9 ], 41 (55) [C3H5 ].
Minor Diastereoisomer trans-8c
Rf 0.53 (CH–EA, 60:40).
MS (EI, 70 eV): m/z (%) = 420 [M+ – H], 364 (1) [M+– C4H9], 334
(14) [M+ – H2CO – C4H9], 321 (2) [M+ –CO2C4H9], 283 (8), 258
(63) [M+ – PhCHO – C4H9], 214 (33) [M+ – PhCHO – CO2C4H9],
1H NMR (360 MHz, DMSO-d6, 373 K): = 0.44 (d, 3 H, J = 6.8
Hz, CHCH3), 0.91 (d, 3 H, J = 6.8 Hz, CHCH3), 1.30 [s, 9 H,
C(CH3)3], 2.39 [septet, 1 H, J = 6.8 Hz, CH(CH3)2], 4.35–4.52 (m,
3 H, PhCH2, OCHH), 4.86 (d, 1 H, J = 7.2 Hz, OCHH), 5.83 (s, 1
H, PhCHO), 7.15–7.55 (m, 10 Harom).
+
+
168 (40), 160 (55), 105 (42), 91 (91) [C7H7 ], 77 (14) [C6H5 ], 57
(100) [C4H9 ].
+
(4R)-3-Benzyl-4-[(R)-(hydroxy(phenyl)methyl]-4-methyl-1,3-
oxazolidin-2-one (9)
1H NOE (360 MHz, DMSO-d6, 373 K): no significant NOEs be-
tween ring substituents.
To a stirred solution of trifluoroacetic acid (80 L, 113 mg, 1 mmol)
in CH2Cl2 (4 mL) oxetane trans-8a (176 mg, 0.5 mmol) in CH2Cl2
(0.5 mL) was added at –78 °C. The mixture was slowly warmed to
r.t. The solution was concentrated in vacuo, and the trifluoroacetic
acid was removed by azeotropic distillation with toluene (2 5 mL).
The residue was dissolved in CH2Cl2 and washed with sat. aq
Na2CO3 solution (15 mL). The aqueous layer was extracted with
CH2Cl2 (3 30 mL). The combined organic layers were dried
(MgSO4) and filtered. After evaporation of the solvent in vacuo the
residue so obtained was purified by flash chromatography (CH–
EA, 80:20). Compound 9 was the major product and it was obtained
as a white solid (99 mg, 67%). In addition, the diastereomerically
pure oxazolidinone trans-10 was isolated (37 mg, 25%).
MS (EI, 70 eV): m/z (%) = 294 (1) [M+ – H2CO – C4H9], 218 (9)
[M+ – PhCHO – C4H9], 174 (11) [M+ – PhCHO – COOC4H9],, 160
+
+
+
(10), 91 (100) [C7H7 ], 77 (10) [C6H5 ], 65 (11) [C5H5 ], 57 (49)
+
+
[C4H9 ], 41 (42) [C3H5 ].
tert-Butyl Benzyl(3-cyclohexyl-2-phenyloxetan-3-yl)carbamate
(8d)
The oxetanes 8d were prepared from enecarbamate 5d (945 mg, 3.0
mmol) and benzaldehyde (152 L, 159 mg, 1.5 mmol) following the
procedure provided for the transformation 5a to 8a (dr = 57:43).
Purification by flash chromatography (CH–EA, 95:5) yielded the
desired products (290 mg, 46%), which were not fully separable.
IR (film): = 3090 (w, CarH), 3065 (w, CarH), 3030 (w, CarH), 2975
(m, CalH), 2930 (s, CalH), 2855 (m, CalH), 1695 (vs, C=O), 1455
(m), 1390 (s), 1170 (m), 990 cm–1 (m, COC).
9
Rf 0.41 (CH–EA, 40:60), mp 139–140 °C.
IR (KBr): = 3380 (s, br, OH), 3040 (w, CarH), 2960 (s, CalH), 2930
(s, CalH), 1750 cm–1 (vs, C=O).
Anal. Calcd for C27H35NO3 (421.3): C, 76.92; H, 8.37; N, 3.32.
Found: C, 76.84; H, 8.24; N, 3.18.
1H NMR (300 MHz, DMSO-d6): = 1.02 (s, 3 H, CH3), 3.39 (d, 1
H, J = 8.6 Hz, CHH), 4.36 (d, 1 H, J = 16.0 Hz, CHHPh), 4.48 (d,
1 H, J = 8.6 Hz, CHH), 4.56 (d, 1 H, J = 16.0 Hz, CHHPh), 5.83
(d, 1 H, J = 3.9 Hz, PhCHOH), 7.22–7.55 (m, 10 Harom).
13C NMR (75.5 MHz): = 21.6 (q, CH3), 44.7 (t, CH2Ph), 65.1 (s,
CNCH3), 69.0 (t, CCH2), 75.2 (d, PhCHOH), 127.1 (d, CarH), 127.9
(d, CarH), 128.0 (d, CarH), 128.5 (d, CarH), 128.6 (d, CarH), 129.0 (d,
CarH), 138.1 (s, Car), 138.2 (s, Car), 158.9 (s, CO).
Major diastereoisomer cis-8d
Rf 0.49 (CH–EA, 90:10).
1H NMR (400 MHz, DMSO-d6, 373 K): = 1.12–1.92 [m, 18 H, 9
Chx-H, C(CH3)3], 2.26–2.30 (m, 1 H, 1 Chx-H), 2.43–2.45 (m, 1 H,
1 Chx-H), 3.62 (d, 1 H, J = 16.3 Hz, CHHPh), 4.29 (d, 1 H,
J = 16.3 Hz, CHHPh), 4.46 (d, 1 H, J = 6.9 Hz, OCHH), 4.97 (d, 1
H, J = 6.9 Hz, OCHH), 5.43 (s, 1 H, PhCHO), 6.91–7.41 (m, 10
Harom).
MS (EI, 70 eV): m/z (%) = 298 (8) [M+ – H], 266 (30), 222 (26),
1H NOESY (400 MHz, DMSO-d6, 373 K): H (2.26–2.30)-H
(5.43)‘‘‘, H (2.43–2.45)-H (5.43)‘‘‘.
+
190 (43) [M+ – C7H7O], 130 (23), 105 (28), 91 (100) [C7H7 ], 77
+
+
(28) [C6H5 ], 65 (37) [C5H5 ].
13C NMR (75.5 MHz, DMSO-d6): = 25.5 (t, CH2), 25.8 (t, CH2),
25.9 (t, CH2), 26.5 (t, CH2), 26.8 (t, CH2), 27.3 [q, C(CH)3], 42.7 (s,
CH), 49.9 (t, PhCH2), 67.6 (d, CN), 71.7 (t, OCH2), 78.7 (s, CMe3),
87.7 (d, PhCH), 125.7 (d, CarH), 126.7 (d, CarH), 127.0 (d, CarH),
127.1 (d, CarH), 127.3 (d, CarH), 127.9 (d, CarH), 138.6 (s, Car),
138.7 (s, Car), 153.7 (s, CO).
Anal. Calcd for C18H19NO3 (297.4): C, 72.71; H, 6.44; N, 4.71.
Found: C, 72.79; H, 6.47; N, 4.72.
trans-10
Rf 0.22 (CH–EA, 40:60); mp 89–90 °C.
IR (KBr): = 3560 (m, OH), 3410 (s, OH), 3065 (w, CarH), 3040
(w, CarH), 2990 (w, CalH), 2925 (w, CalH), 1740 (vs, C=O), 1410
cm–1 (s).
1H NMR (300 MHz, DMSO-d6): = 0.46 (s, 3 H, CH3), 3.39 (dd, 1
H, J = 11.7 Hz, J = 5.5 Hz, CHHOH), 3.58 (dd, 1 H, J = 11.7 Hz,
J = 5.5 Hz, CHHOH), 4.23 (d, 1 H, J = 16.0 Hz, CHHPh), 4.47 (d,
1 H, J = 16.0 Hz, CHHPh), 5.34 (t, 1 H, J = 5.5 Hz, CH2OH), 5.47
(s, 1 H, PhCHO), 7.22–7.42 (m, 10 Harom).
1H NOE (300 MHz, DMSO-d6): H (3.39): H(5.47) [2.5%]; H (3.58):
H(5.47) [1.2%]; H (5.47): H(3.39) [1.0%], H(3.58) [0.3%].
13C NMR (75.5 MHz): = 17.2 (q, CH3), 44.7 (t, CH2Ph), 64.8 (t,
CH2OH), 66.3 (s, CCH3), 79.8 (d, PhCHO), 126.2 (d, CarH), 127.7
MS (EI, 70 eV): m/z (%) = 334 (10) [M+ – H2CO – C4H9], 282 (15),
258 (55) [M+ – PhCHO – C4H9], 214 (8), 168 (16), 160 (24), 91
+
+
+
(100) [C7H7 ], 77 (2) [C6H5 ], 57 (83) [C4H9 ].
Minor Diastereoisomer trans-8d
Rf 0.46 (CH–EA, 90:10).
1H NMR (400 MHz, DMSO-d6, 373 K): = 0.62–1.87 [m, 16 H, 7
Chx-H, C(CH3)3], 1.49–1.53 (m, 1 H, 1 Chx-H), 1.70–1.73 (m, 1 H,
1 Chx-H), 1.82–1.86 (m, 1 H, 1 Chx-H), 2.00–2.06 (m, 1 H, 1 Chx-
H), 4.30 (d, 1 H, J = 16.3 Hz, CHHPh), 4.43–4.46 (m, 2 H, CHHPh,
OCHH), 4.82 (d, 1 H, J = 7.1 Hz, OCHH), 5.79 (s, 1 H, PhCHO),
7.25–7.47(m, 10 Harom).
Synthesis 2001, No. 8, 1117–1124 ISSN 0039-7881 © Thieme Stuttgart · New York

1124
T. Bach, J. Schröder
PAPER
(3) Reviews: (a) Bach, T. Liebigs Ann./Recueil 1997, 1627.
(d, CarH), 128.2 (d, CarH), 128.5 (d, CarH), 128.6 (d, CarH), 129.1 (d,
CarH), 135.4 (s, Car), 138.2 (s, Car), 158.4 (s, CO).
(b) Bach, T. Synthesis 1998, 683.
(4) (a) Bach, T.; Jödicke, K.; Kather, K.; Fröhlich, R. J. Am.
Chem. Soc. 1997, 119, 2437. (b) Bach, T.; Eilers, F. Eur. J.
Org. Chem. 1998, 2161.
MS (EI, 70 eV): m/z (%) = 266 (22) [M+ – CH2OH],, 222 (14), 105
(3), 91 (100) [C7H7 ], 77 (8) [C6H5 ], 65 (37) [C5H5 ].
+
+
+
Anal. Calcd for C18H19NO3 (297.4): C, 72.71; H, 6.44; N, 4.71.
Found: C, 72.78; H, 6.71; N, 4.78.
(5) Review: Bach, T. Synlett 2000, 1699.
(6) (a) Omura, S.; Murata, M.; Imamura, N.; Iwai, Y.; Tanaka,
H.; Furusaki, A.; Matsumoto, T. J. Antibiot. 1984, 37, 1324.
(b) Kawahata, Y.; Takatsuto, S.; Ikekawa, N.; Murata, M.;
Omura, S. Chem. Pharm. Bull. 1986, 34, 3102.
(7) (a) Bach, T.; Schröder, J. Tetrahedron Lett. 1997, 38, 3707.
(b) Bach, T.; Schröder, J. J. Org. Chem. 1999, 64, 1265.
(8) Kawanisi, M.; Kamogawa, K.; Okada, T.; Nozaki, H.
Tetrahedron 1968, 24, 6557.
(9) (a) Scholz, K.-H.; Heine, H.-G.; Hartmann, W. Tetrahedron
Lett. 1978, 17, 1467. (b) Sekretár, S.; Kopecky, J.; Martvon,
A. Collect. Czech. Chem. Commun. 1982, 47, 1848.
(c) Weuthen, M.; Scharf, H.-D.; Runsink, J. Chem. Ber.
1987, 120, 1023. (d) Weuthen, M.; Scharf, H.-D.; Runsink,
J.; Vaßen, R. Chem. Ber. 1988, 121, 971.
(10) Griesbeck, A. G.; Fiege, M.; Lex, J. Chem. Commun. 2000,
589.
(11) (a) Döpp, D.; Memarian, H. R.; Fischer, M. A.; vanEijk, A.
M. J.; Varma, C. A. G. O. Chem. Ber. 1992, 125, 983.
(b) Döpp, D.; Fischer, M.-A. Recl. Trav. Chim. Pays-Bas
1995, 114, 498.
(12) (a) Bach, T. Angew. Chem., Int. Ed. Engl. 1996, 35, 884.
(b) Bach, T.; Schröder, J. Liebigs Ann./Recueil 1997, 2265.
(c) Bach, T.; Schröder, J.; Brandl, T.; Hecht, J.; Harms, K.
Tetrahedron 1998, 54, 4507. (d) Bach, T.; Schröder, J.;
Harms, K. Tetrahedron Lett. 1999, 40, 9003. (e) Bach, T.;
Brummerhop, H. Angew. Chem., Int. Ed. Engl. 1998, 37,
3400. (f) Achenbach, T. V.; Brummerhop, H.; Bach, T.;
Slater, E. P.; Müller, R. Antimicrob. Agents Chemother.
2000, 44, 2794. (g) Bach, T.; Brummerhop, H.; Harms, K.
Chem.–Eur. J. 2000, 6, 3838.
(4S,5S)-3-Benzyl-4-(hydroxymethyl)-4-methyl-5-phenyl-1,3-
oxazolidin-2-one (cis-10)
The oxazolidinone cis-10 was prepared from oxetane cis-8a (176
mg, 0.5 mmol) following the procedure provided for the transfor-
mation trans-8a to 9. Purification by flash chromatography (CH–
EA, 80:20) yielded the expected product in diastereomerically pure
form (80 mg, 54%); Rf 0.39 (CH–EA, 40:60).
IR (KBr): = 3465 (s, OH), 3420 (s, OH), 3040 (w, CarH), 2940 (w,
CalH), 2885 (w, CalH), 1755 cm–1 (vs, C=O).
1H NMR (300 MHz, DMSO-d6): = 1.14 (s, 3 H, CH3), 2.81 (dd, 1
H, J = 11.7 Hz, J = 4.3 Hz, CHHOH), 3.16 (dd, 1 H, J = 11.7 Hz,
J = 4.3 Hz, CHHOH), 4.18 (d, 1 H, J = 16.1 Hz, CHHPh), 4.55 (d,
1 H, J = 16.1 Hz, CHHPh), 4.80 (t, 1 H, J = 4.3 Hz, CH2OH), 5.30
(s, 1 H, PhCHO), 7.20–7.43 (m, 10 Harom).
1H NOE (300 MHz, DMSO-d6): H (1.14): H(5.30) [1.7%], H (5.30):
H(1.14) [1.7%].
13C NMR (75.5 MHz): = 20.2 (q, CH3), 44.3 (t, CH2Ph), 61.8 (t,
CH2OH), 65.7 (s, CCH3), 84.4 (d, PhCHO), 126.9 (d, CarH), 127.0
(d, CarH), 127.0 (d, CarH), 127.4 (d, CarH), 128.1 (d, CarH), 128.4 (d,
CarH), 135.5 (s, Car), 139.1 (s, Car), 158.8 (s, CO).
MS (EI, 70 eV): m/z (%) = 266 (61) [M+ – CH2OH], 222 (12), 91
+
+
+
(100) [C7H7 ], 77 (3) [C6H5 ], 65 (6) [C5H5 ].
Anal. Calcd for C18H19NO3 (297.4): C, 72.71; H, 6.44; N, 4.71.
Found: C, 72.75; H, 6.58; N, 4.72.
Acknowledgements
(13) Bach, T. Liebigs Ann. Chem. 1995, 855.
(14) Cornforth, J.; Patrick, V. A.; White, A. H. Aust. J. Chem.
1984, 37, 1453.
(15) Texier-Boullet, F. Synthesis 1985, 679.
(16) Meth-Cohn, O.; Westwood, K. T. J. Chem. Soc., Perkin
Trans 1 1984, 1173.
(17) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic
Compunds; Wiley: New York, 1994, 696.
(18) Bach, T.; Jödicke, K. Chem. Ber. 1993, 126, 2457.
(19) (a) Griesbeck, A. G.; Stadtmüller, S. J. Am. Chem. Soc.
1990, 112, 1281. (b) Griesbeck, A. G.; Stadtmüller, S. J.
Am. Chem. Soc. 1991, 113, 6923.
(20) Griesbeck, A. G.; Mauder, H.; Stadtmüller, S. Acc. Chem.
Res. 1994, 27, 70.
(21) Still, W. C.; Kahn, M.; Mitra, A. J. J. Org. Chem. 1978, 43,
2923.
(22) Armesto, D.; Soledad, S.; Horspool, W. M.; Martin, J.-A. F.;
Martinez-Alcazar, P.; Perez-Ossorio, R. J. Chem. Soc.,
Perkin Trans. 1 1989, 751.
(23) Willoughby, C. A.; Buchwald, S. L. J. Am. Chem. Soc. 1994,
116, 8952.
This work was supported by the Deutsche Forschungsgemeinschaft
(Ba 1372/3–2) and by the Fonds der Chemischen Industrie.
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Synthesis 2001, No. 8, 1117–1124 ISSN 0039-7881 © Thieme Stuttgart · New York