Oxidation of primary amines to oxaziridines using molecular oxygen (O2) as the ultimate oxidant

Full text of DOI:10.1021/jo010965g

8282
J . Org. Chem. 2001, 66, 8282-8285
Oxid a tion of P r im a r y Am in es to
Oxa zir id in es Usin g Molecu la r Oxygen (O2)
a s th e Ultim a te Oxid a n t
Yun-Ming Lin and Marvin J . Miller*
Department of Chemistry and Biochemistry,
251 Nieuwland Science Hall, University of Notre Dame,
Notre Dame, Indiana 46556
marvin.j.miller.2@nd.edu
Received October 1, 2001
In tr od u ction
Hydroxylamines are important synthetic precursors for
hydroxamic acids that are found in many natural prod-
ucts, including microbial iron(III) chelators (sidero-
phores).1 Many unnatural hydroxamic acids also have
significant biological activity, perhaps most notably as
matrix metalloproteinase inhibitors.2 The most straight-
forward synthesis of hydroxamates is the N-acylation of
hydroxylamines. Due to the biological significance of
hydroxylamines, development of methods for syntheses
of N-alkyl hydroxylamines continues to attract attention.3
Scheme 1 summarizes some of the currently available
chemical synthetic methods for oxidation of primary
amines to hydroxylamines. Most recently, a direct mi-
crowave-induced oxidation of primary amines 1 with
oxone over silica gel or alumina was reported.4 Another
oxidation employed dimethyldioxirane (DMD) as the
oxidant to afford nitrone 2. Nitrone 2 can be hydrolyzed
under acidic conditions or treated with hydroxylamine
to afford the desired N-alkyl hydroxylamine 3.5 Forma-
tion of the nitrone intermediate avoids overoxidation.
Similarly, prior alkylation of amines with R-haloaceto-
nitrile followed by m-CPBA oxidation gives nitrone
derivatives 4, which can be converted into the desired
N-alkyl hydroxylamines.6 Alternatively, overoxidation
can also be avoided through the indirect oxidation of
primary amines 1.7 Primary amines can be first converted
into aryl-derived imines 5, which can be oxidized to afford
3-aryl oxaziridines 6.8 Acid-catalyzed isomerization of
oxaziridines 6 affords stable R-aryl nitrones 7.9 Acid-
catalyzed hydrolysis of either oxaziridines 6 or nitrones
7 gives hydroxylamines 3. On the other hand, when the
substituent in oxaziridine (9) is an alkyl group instead
of an aryl group, N-O bond cleavage of the three-
membered ring predominates to give the corresponding
amide 10.10
F igu r e 1. Structures of representative microbial iron chela-
tors (siderophores) that contain hydroxamic acids that are
essential for iron chelation.
Molecular oxygen (O2) has been used as the ultimate
oxidant in transition metal catalyzed Baeyer-Villiger
oxidations of ketones to lactones and epoxidations of
alkenes to epoxides.11 This transition metal catalyzed
oxidation features the in situ generation of peracid from
aldehydes.12 The advantage of this oxidation protocol is
the utilization of oxygen as an inexpensive and safe
source of oxidant, avoiding the use of large quantities of
peracid, especially in industrial settings.
Despite this advantage, the use of molecular oxygen
as the ultimate oxidant in oxidizing imines to oxaziri-
dines received little attention until 1995.13 J orgensen and
Martiny reported the first transition metal catalyzed
oxidation of imines 11 to oxaziridines 12 by employing
molecular oxygen as the oxidant in the presence of an
aliphatic aldehyde as the co-reductant (Scheme 2). Under
these catalytic oxidation conditions, imines that have a
secondary or tertiary alkyl group at R3 give oxaziridine
12 in high yield. However, when R3 is a primary alkyl
group, this catalytic oxidation affords the desired oxaziri-
dine 12 only in low yield, but gives substantial amounts
of byproducts such as alternate oxaziridine 13.
Lysine-based and ornithine-based hydroxamates are
important building blocks for mycobactins14 (14) and
exochelin MS15 (15, Figure 1, respectively). The N-alkyl
groups of these siderophores (microbial iron chelators)
and many other hydroxamate-derived siderophores are
often primary alkyl groups. In connection with our
interests in the syntheses of siderophores, siderophore
analogues, and siderophore-drug conjugates for biologi-
cal studies,16 we decided to expand the scope of the
reported catalytic oxidation method to oxidize imines to
(1) Neilands, J . B. J . Biol. Chem. 1995, 270, 26723.
(2) Michaelides, M. R.; Curtin, M. L. Curr. Pharm. Des. 1999, 5,
787.
(3) Romine, J . L. Org. Prep. Proc. Intl. 1996, 28, 251.
(4) Fields, J . D.; Kropp, P. J . J . Org. Chem. 2000, 65, 5937.
(5) (a) Breuer, E. In Nitrones, Nitronates and Nitroxides; Patai, S.,
Rappoport, Z., Eds.; J ohn Wiley & Sons: New York, 1989; Chapters 2
and 3. (b) Hu, J .; Miller, M. J . J . Org. Chem. 1994, 59, 4858.
(6) Tokuyama, H.; Kuboyama, T.; Amano, A.; Yamashita, T.; Fuku-
yama, T. Synthesis 2000, 1299.
(7) Naegeli, H.-U.; Keller-Schierlein, W. Helv. Chim. Acta 1978, 61,
2088.
(8) Kloc, K.; Kubicz, E.; Mlochowski, J .; Syper, L. Synthesis 1987,
1084.
(11) Mukaiyama, T.; Takai, T.; Yamada, T.; Rhode, O. Chem. Lett.
1991, 1.
(12) (a) Murahashi, S.-I.; Oda, Y.; Naota, T. Tetrahedron Lett. 1992,
33, 7557. (b) For a mechanistic study in the absence of transition
metals, see: J arboe, S.; Beak, P. Org. Lett. 2000, 2, 357.
(13) Martiny, L.; J orgensen, K. A. J . Chem. Soc., Perkin Trans. 1
1995, 699.
(14) Hu, J .; Miller, M. J . J . Am. Chem. Soc. 1997, 119, 3462.
(15) Sharman, G. J .; Williams, D. H.; Ewing, D. F.; Ratledge, C.
Biochem. J . 1995, 305, 187.
(9) Lin, Y.-M.; Miller, M. J . J . Org. Chem. 1999, 64, 7451.
(10) Davis, F. A.; Sheppard, A. C. Tetrahedron 1989, 45, 5703.
10.1021/jo010965g CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/31/2001

Notes
J . Org. Chem., Vol. 66, No. 24, 2001 8283
Sch em e 1
Sch em e 2
Sch em e 3
Sch em e 4
Sch em e 5
oxaziridines containing primary alkyl groups on nitrogen.
Herein, we report detailed studies of a cobalt-catalyzed
process with molecular oxygen that allows oxidation of
imines from primary alkylamines, including imine 16
derived from L-lysine methyl ester (Scheme 3). Isomer-
ization of the resulting 3-phenyloxaziridine 17 gives
R-phenyl nitrone 18, a stable protected form of key
hydroxylamine siderophore components.17
Resu lts a n d Discu ssion
When the above catalytic oxidation protocol was at-
tempted on imine 16 derived from N2-Cbz-L-lysine methyl
ester (Scheme 5), however, no oxidation reaction oc-
curred. Addition of a small quantity of water initiated
the reaction immediately as indicated by rapid color
changes in the reaction mixture. The desired oxaziridine
17 was isolated only in 8% yield, and the undesired
oxaziridine 24 was isolated in 17% yield.
The formation of oxaziridines 22 and 24 in the above
oxidation reactions was intriguing. We speculated that
a rapid imine exchange reaction catalyzed by moisture
present in the reaction mixture could occur to give a
mixture of imine 26 and 28 under the reaction conditions
(Scheme 6). Imine 28 formed during the reaction was also
oxidized to give the undesired oxaziridine 29. Under
extremely dry reaction conditions, to suppress this imine
exchange process, however, no catalytic oxidation of
The Co(II)-mediated catalytic oxidation reaction was
first examined using 6-aminocaproic acid methyl ester
19 as a model substrate. Treatment of methyl ester 19
with benzaldehyde in the presence of molecular sieves
afforded the desired imine (20) in quantitative yield
(Scheme 4). Under 1 atm of oxygen, imine 20 was
oxidized to give about a 6:1 ratio of oxaziridines 21 and
22 in the presence of 5 mol % of cobalt chloride and 2
equiv of pivaldehyde. Indeed, this oxidation proved to be
irreproducible in the amount of the undesired oxaziridine
22 produced.
(16) For recent reviews, see: (a) Roosenberg, J . M.; Lin, Y.-M.; Lu,
Y.; Miller, M. J . Curr. Med. Chem. 2000, 7, 159. (b) Vergne, A. F.; Walz,
A. J .; Miller, M. J . Nat. Prod. Rep. 2000, 17, 99.
(17) Lin, Y.-M.; Miller, M. J . Presented at the 36th National Organic
Symposium, University of WisconsinsMadison, J une 13-17, 1999;
Poster 157.

8284 J . Org. Chem., Vol. 66, No. 24, 2001
Notes
Sch em e 6
Sch em e 8
eliminated the imine exchange problem. Indeed, when
the green catalyst was dried by stirring with molecular
sieves at 0 °C for 2.5 h before the substrate was added,
catalytic oxidation of imine 20 employing the O2/isobu-
tyraldehyde system afforded the desired cis-oxaziridine
31 and trans-oxaziridine 32 in a combined 80% yield.
Under these optimized reaction conditions, none of the
undesired oxaziridine was observed. A mixture of oxaziri-
dines 31 and 32 was isomerized to nitrone 33 in 63% yield
when treated with TFA.
Sch em e 7
This improved catalytic oxidation procedure was suc-
cessfully extended to the lysine-derived imine 16 (Scheme
8). In the presence of molecular sieves, subjecting imine
16 to the preformed catalyst 30 afforded the desired cis-
oxaziridine 34 and trans-oxaziridine 35 in 60% combined
yield. Again, undesired oxaziridine resulting from the
imine exchange process was not observed. Isomerization
of oxaziridines 34 and 35 with TFA gave the desired
nitrone 18 in 64% yield. We have previously shown that
nitrones such as 18 are readily converted to the corre-
sponding hydroxylamines and hydroxamic acid compo-
nents needed for syntheses and studies of important
siderophores and analogues used for iron transport-
mediated drug delivery.9,14,16
In summary, we have developed an improved proce-
dure for the catalytic oxidation of imines to oxaziridines
using cobalt as the catalyst and molecular oxygen as the
ultimate oxidant. We have found that water plays an
important role in the initial formation of the catalyst
needed for this catalytic oxidation utilizing molecular
oxygen. This modified protocol provides an alternative
method for synthesizing cis- and trans-oxaziridines even
from primary amines containing primary alkyl groups
in high yield.
imine 26 was observed. Water apparently played a
pivotal role in this catalytic oxidation of imines. Also, it
was observed that successful catalytic oxidation reactions
always gave rise to an olive green color. Finally, attempts
to use benzaldehyde as the co-reductant were unsuccess-
ful.
We then carried out a series of control experiments to
determine the role water played in this cobalt-catalyzed
reaction. Isobutyraldehyde was chosen as the co-reduc-
tant because it was cheaper than pivaldehyde. A vigor-
ously stirred mixture of anhydrous cobalt(II) chloride,
potassium bicarbonate, and isobutyraldehyde in meth-
ylene chloride gave no apparent color changes after 5 h
at 0 °C or at room temperature. Addition of 0.1% (v/v of
methylene chloride used) of water resulted in a color
change in less than 15 min and gave the desired green
color within 0.5 h. In the absence of potassium bicarbon-
ate, the color change took a much longer time.
The addition of water apparently increased the solubil-
ity of CoCl2 in methylene chloride. Isobutyraldehyde then
coordinated to the solublized cobalt(II). The presence of
KHCO3 facilitated this ligand exchange reaction and
presumably formed a cobalt aldehyde complex CoLn (30,
Scheme 7), as indicated by color changes. This complex
indeed catalyzed the O2-mediated oxidation of imines to
oxaziridines in the presence of isobutyraldehyde, al-
though the undesired oxaziridine resulting from the
imine exchange reaction was also observed. Addition of
molecular sieves as a drying agent to the catalyst mixture
Exp er im en ta l Section
Gen er a l. All reactions were carried out under N2 unless
otherwise stated. Instruments and general methods used have
been described previously.9,14
6-Am in oca p r oic Acid Meth yl Ester (19). To 100 mL of
methanol at 0 °C was added thionyl chloride (16.0 mL, 219
mmol). The solution was stirred at 0 °C for 20 min. To this
solution at 0 °C was added 6-aminocaproic acid (13.0 g, 100
mmol). The solution was stirred at room temperature for 3.5 h.
The volatiles were removed, and the residue was recrystallized
from hexanes/ethyl acetate/methanol to give 17.9 g (quantitative)
of methyl ester 19 as a white solid. Mp 120.0-121.0 °C. 1H NMR
(300 MHz, CDCl3) δ 8.19 (br, 3H), 3.67 (s, 3H), 3.05 (br, 2H),
2.35 (t, J ) 7.2 Hz, 2H), 1.84 (m, 2H), 1.65 (m, 2H), 1.46 (m,
2H). 13C NMR (75 MHz, CDCl3) δ 173.5, 51.2, 34.4, 33.3, 26.7,
25.6, 23.8. IR (KBr) 3444, 1731, 1617, 1577 cm-1
.
Im in e 20. To a solution of KOH (1.12 g, 20.0 mmol) in
methanol (50 mL) at room temperature were added methyl ester
19 (3.60 g, 20.0 mmol), benzaldehyde (2.12 mL, 20.9 mmol), and
3 Å molecular sieves. The mixture was stirred at room temper-

Notes
J . Org. Chem., Vol. 66, No. 24, 2001 8285
ature for 24 h. The molecular sieves were filtered off and washed
with methanol. The filtrate was concentrated to give 5.03 g
(quantitative) of imine 20 as a light yellow oil. 1H NMR (300
MHz, CDCl3) δ 8.22 (s, 1H), 7.71 (m, 2H), 7.36 (m, 3H), 3.61 (s,
3H), 3.57 (t, J ) 6.6 Hz, 2H), 2.29 (t, J ) 7.5 Hz, 2H), 1.69 (m,
4H), 1.38 (m, 2H). 13C NMR (75 MHz, CDCl3) δ 173.5, 160.3,
135.9, 130.0, 128.1, 127.6, 60.9, 50.9, 33.5, 30.1, 26.4, 24.3. IR
1360 cm-1. HRFABMS calcd for C14H20NO3 (M + H+) 250.1443,
found 250.1452.
Oxa zir id in es 34 a n d 35. To a suspension of CoCl2 (5.0 mg,
0.038 mmol) in methylene chloride (4 mL) at 0 °C were added
KHCO3 (9.0 mg, 0.090 mmol), isobutyraldehyde (0.085 mL, 0.937
mmol), and H2O (4 µL). The mixture was stirred at 0 °C for 1 h.
Then 3 Å molecular sieves were added and the mixture was
stirred at 0 °C for another 2.5 h. The resulting green mixture
was used as catalyst 30 in the following oxidation reaction. To
the above catalyst at 0 °C was added a solution of imine 16 (0.300
g, 0.785 mmol) in methylene chloride (4 mL), followed by
isobutyraldehyde (0.170 mL, 1.88 mmol). The mixture was
degassed under vacuum and then stirred under an atmosphere
of oxygen for 1.5 h. The solid was filtered through Celite and
washed with methylene chloride. The filtrate was washed with
half-saturated sodium bicarbonate, water, and brine, dried (Na2-
SO4), filtered, concentrated, and separated by flash column
chromatography on Et3N-deactivated SiO2 (4:1 to 2:1 hexanes/
ethyl acetate) to give 0.187 g (60%) of oxaziridines 34 and 35 as
(neat) 1737, 1644, 1576, 1447, 1443, 1364 cm-1
.
Im in e 16. To a solution of methyl ester hydrochloride 23 (1.25
g, 3.79 mmol) in methanol (20 mL) at room temperature were
added KOH (0.223 g, 3.98 mmol) and benzaldehyde (0.40 mL,
3.94 mmol), followed by 3 Å molecular sieves. The reaction
mixture was stirred at room temperature for 15 h. The solid was
filtered off and washed with methanol. The filtrate was concen-
trated to give a residue, which was dissolved in methylene
chloride (40 mL), and the insoluble material was filtered off. The
methylene chloride filtrate was concentrated to give 1.39 g (92%)
of imine 16 as a light yellow oil. 1H NMR (300 MHz, CDCl3) δ
8.24 (s, 1H), 7.71 (m, 2H), 7.39 (m, 3H), 7.38 (m, 5H), 5.41 (d, J
) 8.4 Hz, 1H), 5.08 (s, 2H), 4.38 (m, 1H), 3.69 (s, 3H), 3.58 (t, J
) 6.6 Hz, 2H), 1.84-1.71 (m, 4H), 1.42 (m, 2H). 13C NMR (75
MHz, CDCl3) δ 173.0, 161.1, 155.8, 136.1, 130.5, 129.7, 129.0,
128.6, 128.5, 128.1, 128.0, 66.9, 61.1, 53.8, 52.3, 32.3, 30.3, 22.9.
IR (neat) 3321, 1746, 1716, 1642 cm-1. HRFABMS calcd for
C22H27N2O4 (M + H+) 383.1971, found 383.2000.
Ca ta lyst 30. To a suspension of CoCl2 (19.0 mg, 0.146 mmol)
in methylene chloride (20.0 mL) at 0 °C were added KHCO3 (35.0
mg, 0.35 mmol), isobutyraldehyde (0.33 mL, 3.64 mmol), and
H2O (20.0 µL). The mixture was stirred at 0 °C for 1 h. Then 3
Å molecular sieves were added and the mixture was stirred at
0 °C for another 2.5 h. The resulting green mixture was used as
catalyst 30 in the following oxidation reaction.
1
colorless oils. For oxaziridine 34: H NMR (300 MHz, CDCl3) δ
7.41 (m, 5H), 7.34 (m, 5H), 5.29 (d, J ) 8.4 Hz, 1H), 5.25 (s,
1H), 5.09 (s, 2H), 4.32 (m, 1H), 3.72 (s, 3H), 2.42 (t, J ) 6.9 Hz,
2H), 1.78-1.33 (m, 6H); 13C NMR (75 MHz, CDCl3) δ 172.8,
161.1, 155.8, 136.2, 131.6, 129.4, 128.5, 128.2, 128.1, 128.0, 127.8,
127.5, 79.4, 66.9, 53.7, 52.7, 52.6, 52.6, 32.3, 27.5, 27.4, 22.9;
HRFABMS calcd for C22H27N2O5 (M + H+) 399.1920, found
399.1922. For oxaziridine 35: 1H NMR (300 MHz, CDCl3) δ 7.42-
7.30 (m, 10H), 5.35 (d, J ) 8.1 Hz, 1H), 5.10 (m, 2H), 4.47 (s,
1H), 4.39 (m, 1H), 3.72 (s, 3H), 3.02 (m, 1H), 2.67 (m, 1H), 1.90-
1.72 (m, 4H), 1.56-1.44 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
172.8, 155.8, 136.2, 134.6, 130.0, 128.5, 128.4, 128.1, 128.0, 127.8,
127.5, 80.4, 66.9, 61.7, 61.6, 53.7, 52.3, 32.4, 27.5, 23.0, 22.9; IR
(neat) 3341, 1746, 1724 cm-1; HRFABMS calcd for C22H27N2O5
(M + H+) 399.1920, found 399.1931.
Oxa zir id in es 31 a n d 32. To the above catalyst mixture at 0
°C was added a solution of imine 20 (0.70 g, 3.0 mmol) in
methylene chloride (10 mL), followed by isobutyraldehyde (0.66
mL, 7.3 mmol). The mixture was degassed under vacuum and
then stirred under an atmosphere of oxygen at 0 °C for 1.5 h.
The solid was filtered through Celite and washed with methylene
chloride. The filtrate was washed with half-saturated sodium
bicarbonate, water, and brine, dried (Na2SO4), filtered, concen-
trated, and separated by flash column chromatography on Et3N
deactivated SiO2 (8:1 to 4:1 hexanes/ethyl acetate) to give 0.60
g (80%) of oxaziridines 31 and 32. For oxaziridine 31: 1H NMR
(300 MHz, CDCl3) δ 7.41 (m, 5H), 5.26 (s, 1H), 3.64 (s, 3H), 2.45
(m, 2H), 2.25 (m, 2H), 1.66-1.52 (m, 4H), 1.35 (m, 2H); 13C NMR
(75 MHz, CDCl3) δ 174.0, 131.7, 129.4, 128.2, 127.8, 79.5, 52.8,
Nitr on e 18. To a mixture of oxaziridines 34 and 35 (0.316 g,
0.794 mmol) at room temperature was added TFA (2 mL),
followed by methylene chloride (2 mL). The yellow solution was
stirred at room temperature for 1 h, and the volatiles were
removed. To the residue were added 2:1 hexanes/ethyl acetate
(10 mL), benzaldehyde (0.2 mL), and 3 Å molecular sieves. The
mixture was stirred at room temperature for 18 h. The molecular
sieves were filtered off, and the filtrate was concentrated and
separated by flash column chromatography on SiO2 (2:1 hexanes/
ethyl acetate to ethyl acetate) to give 0.202 g (64%) of nitrone
18 as a light yellow oil. 1H NMR (300 MHz, CDCl3) δ 8.24-8.20
(m, 3H), 7.40 (m, 3H), 7.34 (m, 5H), 5.47 (d, J ) 8.1 Hz, 1H),
5.07 (s, 2H), 4.37 (m, 1H), 3.90 (t, J ) 6.9 Hz, 2H), 3.69 (s, 3H),
2.04-1.76 (m, 4H), 1.44 (m, 2H). 13C NMR (75 MHz, CDCl3) δ
172.7, 155.9, 136.2, 134.4, 130.4, 128.5, 128.2, 128.1, 67.0, 66.7,
53.6, 52.4, 32.1, 27.1, 22.2. IR (neat) 3314, 3235, 1744, 1715,
1529, 1450 cm-1. HRFABMS calcd for C22H27N2O5 (M + H+)
399.1920, found 399.1915.
51.4, 33.8, 27.5, 26.7, 24.6; IR (neat) 1738, 1452, 1432 cm-1
;
HRFABMS calcd for C14H20NO3 (M + H+) 250.1443, found
250.1448. For oxaziridine 32: 1H NMR (300 MHz, CDCl3) δ 7.40
(m, 5H), 4.49 (s, 1H), 3.66 (s, 3H), 3.22 (dt, J ) 12.6, 7.2 Hz,
1H), 2.34 (dt, J ) 12.3, 7.2 Hz, 1H), 2.34 (t, J ) 7.5 Hz, 2H),
1.80-1.63 (m, 4H), 1.53-1.45 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ 174.0, 134.7, 130.0, 128.4, 127.5, 80.4, 61.9, 51.4, 33.8,
27.6, 26.8, 24.7; IR (neat) 1732, 1457, 1437 cm-1
.
Ack n ow led gm en t. We gratefully acknowledge fi-
nancial support by the National Institutes of Health
(GM 25845 and AI 30988). Y.-M. Lin thanks the
University of Notre Dame for a Reilly Fellowship. We
appreciate assistance in the Lizzadro NMR facility at
Notre Dame by Don Schifferl and Dr. J aroslav Zajicek,
mass spectral assistance by Dr. William Boggess and
Nonka Sevov, and Maureen Metcalf’s assistance with
the manuscript.
Nitr on e 33. To a mixture of oxaziridines 31 and 32 (0.195 g,
0.783 mmol) at room temperature was added TFA (1 mL),
followed by methylene chloride (1 mL). The resulting yellow
solution was stirred at room temperature for 1 h, and the
volatiles were removed to give an oily residue. To this residue
were added 2:1 hexanes/ethyl acetate (10 mL), benzaldehyde
(0.20 mL), and 3 Å molecular sieves. The mixture was stirred
at room temperature for 18 h. The solid was filtered off, and
the filtrate was concentrated and separated through flash
column chromatography on SiO2 (2:1 hexanes/ethyl acetate to
ethyl acetate) to give 0.123 g (63%) of nitrone 33 as a light yellow
oil. 1H NMR (500 MHz, CDCl3) δ 8.24 (m, 2H), 7.42 (m, 3H),
7.39 (s, 1H), 3.94 (t, J ) 7.0 Hz, 2H), 3.65 (s, 3H), 2.33 (t, J )
7.5 Hz, 2H), 2.03 (m, 2H), 1.70 (m, 2H), 1.43 (m, 2H). 13C NMR
(125 MHz, CDCl3) δ 173.8, 134.3, 130.4, 130.3, 128.5, 128.4, 66.9,
51.5, 33.7, 27.3, 25.9, 24.3. IR (neat) 1732, 1674, 1582, 1444,
Su p p or tin g In for m a tion Ava ila ble: NMR spectra of
compounds 18, 19, 20, 22, 31, 32, 33, 34, and 35. This material
is available free of charge via the Internet at http://pubs.acs.org.
J O010965G