Palladium(II)-Catalyzed Intramolecular Aminocarbonylation of endo-Carbamates under Wacker-Type Conditions

Article abstract of DOI:10.1021/jo961988b

Pd(II)-catalyzed intramolecular aminocarbonylation of olefins bearing many types of nitrogen nucleophiles has been examined under two typical conditions: acidic conditions [conditions A, typically PdCl₂ (0.1 equiv) and CuCl₂ (3.0 equiv) under 1 atm of CO at room temperature in methanol] and buffered conditions [conditions B, typically PdCl₂ (0.1 equiv) and CuCl₂ (2.3 equiv) under 1 atm of CO at 30°C in trimethyl orthoacetate]. Among nitrogen nucleophiles, endocarbamates 7 display distinctive reactivity: endo-carbamates 7a-k smoothly undergo intramolecular aminocarbonylation under conditions B to furnish 4-[(methoxycarbonyl)methyl]-2-oxazolidinones 8a-k in good yields, while they would not undergo the expected reaction under conditions A. Other nitrogen nucleophiles (exo-ureas 1, endo-ureas 3, exo-carbamates 5, and exo-tosylamides 9), on the other hand, satisfactorily undergo aminocarbonylation only under conditions A to give rise to 2,4,6, and 10, respectively, in good yields. Under conditions B, they are unreactive and provide either the expected products in poor yields or intractable mixtures of products. On the basis of this contrasting reactivity between endo-carbamates and other nitrogen nucleophiles, the chemoselective aminocarbonylation of 71-o has been achieved; aminocarbonylation takes place at the endo-carbamate moieties to furnish 81-o exclusively under conditions B, and aminocarbonylation occurs at the exo-carbamate, exo-urea, and exo-tosylamide moieties to yield 13a-d exclusively under conditions A.

Full text of DOI:10.1021/jo961988b

J . Org. Chem. 1997, 62, 2113-2122
2113
P a lla d iu m (II)-Ca ta lyzed In tr a m olecu la r Am in oca r bon yla tion of
en d o-Ca r ba m a tes u n d er Wa ck er -Typ e Con d ition s
Hiroto Harayama, Atsuhiro Abe, Tomonori Sakado, Masanari Kimura, Keigo Fugami,†
Shuji Tanaka, and Yoshinao Tamaru*
Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1-14 Bunnkyo,
Nagasaki 852, J apan
Received October 23, 1996X
Pd(II)-catalyzed intramolecular aminocarbonylation of olefins bearing many types of nitrogen
nucleophiles has been examined under two typical conditions: acidic conditions [conditions A,
typically PdCl2 (0.1 equiv) and CuCl2 (3.0 equiv) under 1 atm of CO at room temperature in
methanol] and buffered conditions [conditions B, typically PdCl2 (0.1 equiv) and CuCl2 (2.3 equiv)
under 1 atm of CO at 30 °C in trimethyl orthoacetate]. Among nitrogen nucleophiles, endo-
carbamates 7 display distinctive reactivity: endo-carbamates 7a -k smoothly undergo intramo-
lecular aminocarbonylation under conditions B to furnish 4-[(methoxycarbonyl)methyl]-2-
oxazolidinones 8a -k in good yields, while they would not undergo the expected reaction under
conditions A. Other nitrogen nucleophiles (exo-ureas 1, endo-ureas 3, exo-carbamates 5, and exo-
tosylamides 9), on the other hand, satisfactorily undergo aminocarbonylation only under conditions
A to give rise to 2, 4, 6, and 10, respectively, in good yields. Under conditions B, they are unreactive
and provide either the expected products in poor yields or intractable mixtures of products. On
the basis of this contrasting reactivity between endo-carbamates and other nitrogen nucleophiles,
the chemoselective aminocarbonylation of 7l-o has been achieved; aminocarbonylation takes place
at the endo-carbamate moieties to furnish 8l-o exclusively under conditions B, and aminocarbo-
nylation occurs at the exo-carbamate, exo-urea, and exo-tosylamide moieties to yield 13a -d
exclusively under conditions A.
In tr od u ction
Despite its importance as an efficient and straightfor-
ward method for preparation of physiologically valuable
â-amino acid derivatives, the transition-metal-catalyzed
aminocarbonylation of olefins has not been intensively
studied.1
We have demonstrated that nitrogen nucleophiles,
depending on the structure type, display completely
different reaction behavior in the Wacker-type intramo-
lecular aminocarbonylation (eqs 1-4). For example,
ureas 1 and 32,3 and carbamate 53 smoothly undergo
intramolecular aminocarbonylation under the Wacker-
type conditions utilizing palladium(II) chloride as a
catalyst and copper(II) chloride as an oxidant under 1
atm of carbon monoxide in methanol at an ambient
temperature or below (eqs 1-3, conditions A, Table 1).
Carbamates 7 (R ) Me, Ph, Ts), on the other hand, do
not undergo aminocarbonylation under similar condi-
tions:2 They either are unreactive or provide intractable
mixtures of products.
In order to conveniently differentiate the structure type
of these substrates, carbamates 5 and 7 are referred to
as exo- and endo-carbamates, respectively. exo-Carbam-
ates are those that, on cyclization, provide nitrogen
heterocycles possessing a carbamate functionality as a
ring substituent. endo-Carbamates are those giving rise
to nitrogen heterocycles containing a carbamate moiety
as a ring constituent. In a similar way, ureas 1 and 3
may be termed as exo- and endo-ureas, respectively.
As is apparent from the reaction temperatures and
times shown in eqs 1 and 2, endo-ureas are, in general,
more reactive than exo-ureas. In view of the relative
reactivity between endo- and exo-ureas, the exceedingly
low reactivity of endo-carbamates (eq 4), as compared
with exo-carbamates (eq 3), has long been a question to
be addressed.4
* To whom correspondence should be addressed.
† Department of Chemistry, Faculty of Engineering, Gunma Uni-
versity, Tenjin-cho 1-5-1, Kiryu 376, J apan.
X Abstract published in Advance ACS Abstracts, March 15, 1997.
(1) Hegedus, L. S. Comprehensive Organic Synthesis; Trost, B. M.;
Fleming, I.; Semmelhack, M. F., Eds.; Pergamon Press: Oxford, U.K.,
1991; Vol. 4, pp 559-563.
(2) Tamaru, Y.; Hojo, M.; Higashimura, H.; Yoshida, Z. J . Am. Chem.
Soc. 1988, 110, 3994-4002. See also, Ba¨ckvall, J .-E.; Andersson, P.
G. J . Am. Chem. Soc. 1990, 112, 3683-3685.
(3) Tamaru, Y.; Hojo, M.; Yoshida, Z. J . Org. Chem. 1988, 53, 5731-
5741.
We report here that the aminocarbonylation of endo-
carbamates 7 is greatly facilitated by a slight modifica-
S0022-3263(96)01988-3 CCC: $14.00 © 1997 American Chemical Society

2114 J . Org. Chem., Vol. 62, No. 7, 1997
Harayama et al.
Ta ble 1. Typ ica l Rea ction Con d ition s for th e
In tr a m olecu la r Am in oca r bon yla tion of en d o-Ca r ba m a tes
7 a n d 11a
of the reaction mixture by flash column chromatography
over silica gel.
With 3 equiv of sodium acetate (run 3, Table 2), the
reaction ceased essentially at ca. 50% conversion owing
to precipitation of palladium black. From the reaction
mixture, 8e was isolated in 43% yield (based on 48%
conversion). We took the precipitation of palladium black
as the result of abuse of CuCl2 for some PdCl2-mediated
side reactions under such basic conditions, e.g., oxidation
of methanol to formaldehyde and oxidation of carbon
monoxide to dimethyl carbonate.6
PdCl2
CuCl2
base
additive
solvent
(mL)
conditions (mmol) (mmol) (3 mmol) (18 mmol)
A
0.10
0.25
0.25
0.10
0.10
0.05
3.0
2.3
2.3
2.3
2.3
2.3
none
none
MeOH (5)
MeOH (2)
MeOH (8)
MeOH (8)
MOA (5)
B-1
B-2
B-2′
B-3
B-3′
AcONa
AcONa
AcONa
none
AcOHb
MOA
MOA
none
none
none
MOA (5)
a
b
7 or 11 (1 mmol) under 1 atm of CO. 5 mL.
In order to suppress such side reactions, we applied a
sodium acetate-acetic acid buffer (conditions B-1, run 4
in Table 2). Eventually, conditions B-1 turned out to be
successful for the reaction of a limited number of endo-
carbamates (e.g., 7a -c, Table 3); however, the conditions
were still not acceptable for the aminocarbonylation of
7e, providing 8e, albeit in a low yield, after an unreason-
ably long reaction time. Finally, we found that the
combination of sodium acetate (3 equiv) and MOA (18
equiv) greatly accelerated the reaction and improved the
yield (conditions B-2, run 5 in Table 2). The reaction was
clean, and the spectroscopically homogeneous 8e was
obtained in a quantitative yield just by extraction of the
reaction mixture.
tion of conditions A, namely, by using sodium acetate (3
equiv) in combination with either acetic acid (5 mL,
conditions B-1, Table 1) or trimethyl orthoacetate (MOA)
(18 equiv, conditions B-2, Table 1). Furthermore, the
reaction of 7 nicely proceeds by using MOA as a solvent
(conditions B-3 or B-3′, Table 1). Significantly, conditions
B-3 and A, the former being effective for aminocarbony-
lation of endo-carbamates 7 and the latter for that of the
other nitrogen nucleophiles 1, 3, 5, differ only in the
solvents used. Conditions B can be successfully applied
to the reaction of endo-carbamates 11, one-carbon higher
homologues of 7 (eqs 8 and 9).
Under conditions B, all the exo-nitrogen nucleophiles
(1, 3, 5, and 9) react very slowly, providing the expected
cyclization products, albeit in low yields, if any. Accord-
ingly, the chemoselective aminocarbonylation of 7l-o at
the endo-carbamate moieties to provide 8l-o (under
conditions B) and at the other nitrogen nucleophiles to
furnish 13a -d (under conditions A) has been achieved
with perfect selectivity (Scheme 2). This paper is a full
account of our preliminary communications.5
Aminocarbonylation of a variety of endo-carbamates
7a -h was examined under the thus optimized conditions
B-1 and B-2 (eq 5). Results are summarized in Table 3,
Resu lts a n d Discu ssion
where analogs 7 are arranged in the order of approximate
increases in the steric bulkiness of the C-1 substituents.
From this table, it is apparent that (1) conditions B-1 are
only acceptable for the reactions of 7a -d bearing the
sterically small substituents on C-1; (2) for all the analogs
of 7 examined, conditions B-2 bring about better yields
within much shorter reaction times; (3) trans-8 are
obtained with higher stereoselectivities under conditions
B-1 than under conditions B-2; and (4) the amount of
PdCl2 may be reduced from 0.25 equiv (conditions B-2)
to 0.10 equiv (conditions B-2′) without serious deteriora-
tion in the yields (runs 12 and 16, Table 3).
Even under the thus optimized conditions B-2, pal-
ladium black still precipitated in the reactions of some
endo-carbamates 7f-h , especially those bearing the
sterically bulky C-1 substituents (runs 19, 21, and 23 in
Table 3). In an attempt to improve the conversions and
yields, we examined the aminocarbonylation of the least
reactive 7g as a probe with sodium carboxylates of lower
basicities than that of sodium acetate in the expectation
that these weak bases might suppress the base-promoted
side reactions (vide supra). The results are summarized
in Table 4. Indeed, with sodium benzoate (run 2), no
further palladium black appeared, and the reaction
reached completion and provided 8g in better yield. A
similar improvement in the yield and conversion was
observed with the use of sodium monochloroacetate as a
base (run 3, Table 4), though the reaction became very
Am in oca r bon yla tion of 2-P r op en yl Ca r ba m a tes
7. We have demonstrated previously that a wide variety
of exo-carbamates, e.g., 5, smoothly undergo intramo-
lecular aminocarbonylation to provide 2-[(methoxycar-
bonyl)methyl]pyrrolidines in excellent yields under con-
ditions A (eq 3).3 endo-Carbamates 7, on the other hand,
would not undergo the expected aminocarbonylation at
all under similar or somewhat forcing conditions. For
example, the reaction of 7e (run 1, Table 2) was very
sluggish and provided a very complex mixture of products
after prolonged reaction time at elevated temperature.
Despite careful examination of the reaction mixture by
TLC and 1H NMR, the expected aminocarbonylation
product 8e was not detected at all. During examination
of the reaction conditions, we noticed that MOA (run 2,
Table 2) and sodium acetate (run 3) were effective in
promoting the reaction. A drawback to these reactions,
however, was the complexity of the obtained products.
In any event, with 18 equiv of MOA (run 2, Table 2), we,
for the first time, succeeded in the isolation of the
expected product 8e in 45% yield by careful purification
(4) Allenyl endo-carbamates (e.g., 2,3-butadienyl tosylcarbamate)
smoothly undergo palladium(II)-catalyzed aminocarbonylation under
the conditions similar to conditions A (in the presence of 3 equiv of
sodium monochloroacetate): Kimura, M.; Saeki, N.; Uchida, S.;
Harayama, H.; Tanaka, S.; Fugami, K.; Tamaru, Y. Tetrahedron Lett.
1993, 34, 7611-7614. For the related reaction of 4,5-hexadienylamines,
see: Lathbury, D.; Vernon, P.; Gallagher, T. Tetrahedron Lett. 1986,
27, 6009-6012.
(5) Tamaru, Y.; Tanigawa, H.; Itoh, S.; Kimura, M.; Tanaka, S.;
Fugami, K.; Sekiyama, T.; Yoshida, Z. Tetrahedron Lett. 1992, 33, 631-
634. Harayama, H.; Okuno, H.; Takahashi, Y.; Kimura, M.; Fugami,
K.; Tanaka, S.; Tamaru, Y. Tetrahedron Lett. 1996, 37, 7287-7290.
(6) Blackburn, T. F.; Schwaltz, J . J . Chem. Soc. Chem. Commun.
1977, 157-158; Tamaru, Y.; Yamada, Y.; Inoue, K.; Yamamoto, Y.;
Yoshida, Z. J . Org. Chem. 1983, 48, 1286-1292.

Palladium(II)-Catalyzed Aminocarbonylation
J . Org. Chem., Vol. 62, No. 7, 1997 2115
Ta ble 2. Effects of Ad d itives, Ba ses, a n d Solven ts on P d (II)-Ca ta lyzed Am in oca r bon yla tion of en d o-Ca r ba m a tes 7ea
run
base (3 mmol)
additiveb (18 mmol)
solvent
conditions
A
temp (°C)/ time (h)
conversion (%)
yield (%)c 8e [trans:cis]
1
2
3
4
5
6
7
8
9
none
none
none
MOA
none
AcOHd
MOA
MOF
DMP
PO
MeOH
MeOH
MeOH
MeOHd
MeOH
MeOH
MeOH
MeOH
MOA
30/74
30/36
30/2
30/72
30/8
25/4
25/4
25/10
35/3
90
100
48e
100
100
100
100
100
100
0
45 [4:1]
43 [3:1]
10
100 [3:1]
94 [3:1]
78 [7:1]
78 [4:1]
60 [>20:1]
AcONa
AcONa
AcONa
AcONa
AcONa
none
B-1
B-2
none
none
a
Reactions were performed under the following conditions: 7e (1.0 mmol), PdCl2 (0.25 mmol), and CuCl2 (2.3-3.0 mmol) under CO (1
b
atm) in MeOH (8 mL) or MOA (5 mL). MOA, trimethyl orthoacetate; MOF, trimethyl orthoformate; DMP, 2,2-dimethoxypropane; PO,
propylene oxide. c Isolated yield based on conversion. AcOH (5 mL)-MeOH (2 mL). e No further reaction owing to precipitation of Pd
d
black.
Ta ble 3. P d (II)-Ca ta lyzed In tr a m olecu la r
Am in oca r bon yla tion of en d o-Ca r ba m a tes 7a -h
analysis of this process is difficult owing to the hetero-
geneous nature of the reaction mixture.
temp
yield
of 8
The results in Table 4 indicate that the time required
for completion of the reaction well corresponds to the base
strength: the higher the base strength, and hence the
higher the concentration of the conjugate base of 7g, the
shorter the reaction time; the pKa value of 7g is ca. 47
and is comparable to those of acetic acid and benzoic acid.
This suggests that the conjugate base of 7g is responsible
for aminocarbonylation and at the same time this ap-
parently explains why endo-carbamates 7 would not
undergo aminocarbonylation under conditions A; 2 mol
of HCl, generated during the reaction, make the reaction
strongly acidic and suppress the dissociation of 7 into its
conjugate base.
In order to clarify the mechanistic role of MOA,8 we
examined the reaction of 7e in the presence of compounds
that would undergo C-O bond cleavage upon contact
with HCl and would neutralize the HCl evolved during
the Wacker-type catalytic cycle (runs 6-9, Table 2).
Trimethyl orthoformate (MOF, run 6), 2,2-dimethoxypro-
pane (DMP, run 7), and propylene oxide (PO, run 8),8 all
turned out to work similarly well to improve the yields
and conversions.
To our surprise, aminocarbonylation of 7e smoothly
proceeded even in the absence of sodium acetate and
methanol; just heating the mixture of 7e (1 mmol), PdCl2
(0.25 mmol), and CuCl2 (3.0 mmol) in MOA alone at 35
°C for 14 h (run 9, Table 2) was effective. Under these
conditions, trans-8e was produced with remarkably high
stereoselectivity (trans-8e:cis-8e ) >20:1). Interestingly,
almost the same results were obtained by using a reduced
amount of PdCl2 (0.05 mmol, conditions B-3′, run 17 in
Table 3). Conditions B-3′ proved to be successful for the
aminocarbonylation of a variety of 7 (runs 3, 6, 9, and
13, Table 3).
(°C)/ conversion
trans:
run
7: R )
7a : H
conditionsa time (h)
(%)
(%)b
cisc
1
2
3
4
5
6
7
8
9
B-1
B-2
B-3′
B-1
B-2
B-3′
B-1
B-2
B-3′
B-1
B-2
B-2′
B-3′
B-1
B-2
B-2′
B-3′
B-1
B-2
B-1
B-2
B-1
B-2
30/88
30/2
35/20
30/87
30/3
35/18
30/70
30/5
35/18
30/93
30/9
30/23
35/25
30/72
30/8
35/25
35/14
30/87
30/13
30/91
30/16
30/94
30/18
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
87d
0
8a : 71
8a : 78
8a : 42
8b: 89
8b: 88
8b: 61
8c: 80
8c: 88
8c: 46
8d : 91
8d : 95
8d : 78
8d : 70 >20:1
8e: 10
8e: 100
8e: 90
8e: 60 >20:1
8f: 49 >20:1
8f: 61 >20:1
8g: 0
8g: 57 >20:1
8h : 14
7b: Me
7c: Et
7:1
2:1
5:1
18:1
2:1
12:1
10:1
2:1
10 7d : CH2CHMe2
11
12
13
14 7e: CH2CH2Ph
15
16
17
18 7f: CHMe2
19
20 7g: CMe3
21
22 7h : Me2
23
5:1
3:1
3:1
50d
100
71d
8h : 86
See Table 1. Isolated yield based on conversion. c Ratio
a
b
determined by 1H (400 MHz) and/or 13C (100 MHz) NMR. No
d
further reaction owing to precipitation of palladium black.
Ta ble 4. Mod ifica tion of Rea ction Con tition s B-2a for
Un r ea ctive en d o-Ca r ba m a te 7g: Effects of Ba se a n d
Tem p er a tu r e
temp (°C)/ conversion
yield (%)c
run
base
AcONa
PhCO2Na
ClCH2CO2Na 2.86
ClCH2CO2Na
pKab time (h)
(%)
8g [trans:cis]d
1
2
3
4
5
4.75
4.20
30/16
50e
100
100
100
58
57 [>20:1]
77
77 [>20:1]
65
58
30/110
30/220
65/0.5
30/320
Cl3CCO2Na
0.64
These results clearly indicate that MOA works in many
ways. MOA promotes the reaction by serving as a base
to generate the conjugate base of 7. At the same time,
MOA serves as an efficient scavenger of HCl and keeps
the reaction mixture weakly acidic, under which condi-
tions the conjugate base of 7 may be generated in a
reasonable concentration and, also, palladium(0) may be
oxidized to palladium(II) chloride by copper(II) chloride
at a reasonable rate. Furthermore, as a consequence of
a
b
See Table 1. Values of conjugate acid in water. c Isolated
yield based on conversion. Ratio determined by 1H (400 MHz)
and/or 13C (100 MHz) NMR. e No further reaction owing to
precipitation of Pd black.
d
slow and required an unreasonably prolonged time for
completion. The reaction time, however, could be greatly
shortened by raising the temperature (run 4, Table 4). A
similarly large temperature dependence was observed for
the reaction of 7e using sodium monochloroacetate
instead of sodium acetate under conditions B-2, which
required 46 h at 30 °C but only 10 min at 65 °C to attain
completion (cf. run 15, Table 3). These unusually large
increases in rate, ca. 5-6 times by raising the reaction
temperature by 10 °C, may most probably be associated
with a Pd(0)-CuCl2 redox process, though unfortunately
(7) Taylor, L. D.; MacDonald, R. J .; Rubin, L. E. J . Polym. Sci. Part
A-1, 1971, 9, 3059-3061.
(8) The use of MOA (and PO) was prompted by our previous
experiences; the use of these additives greatly facilitated the
Wacker-type dicarbonylation of homoallyl alcohols to provide
R-[(methoxycarbonyl)methyl]-γ-butyrolactones: Tamaru, Y.; Hojo, M.;
Yoshida, Z. J . Org. Chem. 1991, 56, 1009-1105.

2116 J . Org. Chem., Vol. 62, No. 7, 1997
Harayama et al.
The synthetic utility of the present reaction may be
demonstrated by the transformation of 7i into 8i (eq 6).
The product 8i is a protected form of γ-hydroxy-â-lysine,
an unusual amino acid isolated from tuberactinomycin
A and N.10
Am in oca r bon yla tion of 3-Bu ten yl Ca r ba m a tes 11.
The selective transformation of 7j and 7k into 8j and 8k
(eq 7), respectively, clearly indicates that the aminocar-
bonylation forming five-membered cyclic carbamates
F igu r e 1.
Ta ble 5. P d (II)-Ca ta lyzed Am in oca r bon yla tion of 11a -ga
11
R1
temp
yield
(%)c
condi- (°C)/ conversion
trans:
run
)
R2
H
)
tionsb time (h)
(%)
of 12
cisd
1
2
3
4
5
6
7
8
9
11a
H
B-1
B-2
30/89
30/70
65/3
65/0.5
65/4
65/0.5
65/2
30/15
65/1
100
80e
12a : 9
12a : 0
B-3′
B-2f
B-3′
B-2f
B-3′
B-2
100
100
100
100
100
84e
100
100
100
100
12a : 12
12b: 24
12b: 35
12c: 53
12c: 65
12d : 37
12d : 70
12e: 90
11b Ph
H
H
H
6:1
2:1
5:1
2:1
11c t-Bu
11d Me2
B-2g
B-1
10 11e (CH2)5
11 11fh Ph
12 11g Me2
H
Me
Me
30/90
65/3
65/2
B-2f
B-2f
12f: 42i >15:1
12g: 68
proceeds much faster than the alternative reaction form-
ing six-membered cyclic carbamates. Indeed, the reaction
forming six-membered cyclic carbamates (eq 8) was
generally rather slow. Results obtained for the ami-
nocarbonylation of 3-butenyl carbamates 11a -g are
summarized in Table 5.
a
b
See eqs 8 and 9. See Table 1. c Isolated yield based on
conversion. Ratio of stereoisomers with respect to R1 and
d
CH2CO2Me, determined by 1H (400 MHz) and/or 13C (100 MHz)
e
NMR. No further reaction owing to precipitation of palladium
black. f ClCH2CO2Na (3 mmol) instead of AcONa. g Cl3CCO2Na (3
h
i
mmol) instead of AcONa. syn-11f:anti-11f ) 1:1. Isolated yield
of 12f based on syn-11f.
Among 11, the parent 11a was exceedingly unreactive
and the expected product 12a was obtained in very poor
yields, if at all (runs 1-3, Table 5). The C-1 monosub-
stituted derivatives, 12b,c,f, were slightly more reactive
and provided the expected products in moderate yields
under the modified conditions B-2 (sodium monochloro-
acetate in place of sodium acetate), the conditions being
successful for the unreactive 7g (runs 3 and 4, Table 4).
Under the usual conditions B-2, utilizing sodium acetate
as a base, these reactions hardly reached completion
owing to precipitation of palladium black. Slightly better
yields resulted under conditions B-3′.
the reactions with HCl [e.g., MeC(OMe)3 + HCl f
MeCCl(OMe)2 + MeOH], MOA supplies the methanol
necessary for the methoxycarbonylation of 7.
The contrasting reactivity of endo-carbamates 7 and
the other nitrogen nucleophiles 1, 3, and 5 may be ration-
alized as follows (Figure 1). Both exo- and endo-ureas
possess a nonbonding electron pair in an approximately
3
Nsp orbital that efficiently overlaps with the π* orbital
of olefin. An equivalent nucleophilic nitrogen lone pair
is not available for both the endo- and exo-carbamates
2
owing to their approximate Nsp hybridization. Never-
In these reactions, trans-isomers, being trans with
respect to R1 and (methoxycarbonyl)methyl groups, were
obtained as the major isomers. This is probably because
theless, exo-carbamates may still be reactive owing to
an efficient overlap between the π* orbital of olefin
and the nucleophilic enol-like CdN π orbital. In the case
of endo-carbamates, however, the nitrogen lone pair in
cis-12 is thermodynamically less stable owing to an A1,2
-
strain between the tosyl and the pseudo-equatorial meth-
2
the Nsp orbital that efficiently overlaps with the π*
oxycarbonyl groups.11
orbital of olefin may not be sufficiently nucleophilic and
may become suitably reactive only when its nucleophi-
licity is enhanced by dissociation into the conjugate base.9
(10) Wakamiya, T.; Shiba, T.; Kaneko, T. Bull. Chem. Soc. J pn.
1972, 45, 3668-3672.
(11) (a) Hoffmann, R. W. Angew. Chem. Int. Ed. Engl. 1992, 31,
1124-1134. (b) Bando, T.; Harayama, H.; Fukazawa, Y.; Shiro, M.;
Fugami, K.; Tanaka, S.; Tamaru, Y. J . Org. Chem. 1994, 59, 1465-
1474.
(9) For a similar stereoelectronic effect on cyclization reactions,
see: McCombie, S. M.; Shankar, B. B.; Ganguly, A. K. Tetrahedron
Lett. 1985, 26, 6301-6304.

Palladium(II)-Catalyzed Aminocarbonylation
J . Org. Chem., Vol. 62, No. 7, 1997 2117
Sch em e 1
Sch em e 2. Ch em oselective Am in oca r bon yla tion
of 7n -q
Ta ble 6. Ch em oselective Am in oca r bon yla tion of 7n -qa
Only the syn isomer of the mixture of syn- and anti-
11f (1:1) underwent aminocarbonylation to selectively
furnish trans,cis-4-[(methoxycarbonyl)methyl]-5-methyl-
6-phenyl-N-tosyltetrahydro-2-oxazinone (12f) in 42% yield
(based on syn-11f, eq 9). The anti-isomer of 11f decom-
posed completely during the reaction.
% isolated yieldc
8 [trans:cis]d 13 [trans:cis]d
condi- temp (°C)/
run
7: W )
tionsb time (h)
1
2
3
4
5
6
7
8
9
7l: CO2Me
B-2′
B-3
A
25/35
35/7
25/120
25/20
35/6
25/120
25/48
25/22
25/17
25/17
25/72
8l: 74 [3:1]
8l: 68 [11:1]
13a : 58 [1:3]
8m : 85 [11:1]
8m : 45 [>20:1]
13b: 36 [1:4]
8n : 85 [5:1]
13c: 59 [1:1]
8o: 78 [3:1]
8o: 60 [20:1]
13d : 79 [1:3]
7m : CONHPh B-2′
B-3
A
7n : CONHMe B-2′
A
7o: Ts
B-2′
B-3
A
10
11
a
For the structure of 7n -q, 8n -q, and 13a -d , see Scheme 2.
See Table 1. c 100% conversion for all cases. Ratio determined
b
d
by 1H (400 MHz) and/or 13C (100 MHz) NMR.
The C-1 disubstituted derivatives, 11d ,e,g, were much
more reactive and provided the expected products in
moderate to good yields (runs 8-10 and 12, Table 5).
These C-1 substituents of 11 may accelerate the reaction
by buttressing both reaction sites (carbamate nitrogen
and C-3) to bring them into closer proximity.12
The aminocarbonylation of 11 seems to be useful for
the synthesis of naturally occurring â-amino-δ-hydroxy
acids, e.g., negamycin.13
Ch em oselect ive Am in oca r b on yla t ion of en d o-
Ca r ba m a tes a n d th e Oth er Nitr ogen Nu cleop h iles.
As summarized in Scheme 1, under conditions B estab-
lished for the aminocarbonylation of endo-carbamates,
the other nitrogen nucleophiles reacted very sluggishly,
either providing the expected products in poor yields after
prolonged reaction times or only giving rise to decomposi-
tion products. For example, exo-carbamate 5 completely
decomposed under conditions B-3. Under conditions B-2,
exo-tosylamide 9 provided the aminocarbonylation prod-
uct 10 in 5% isolated yield after heating at 30 °C for 1
day with recovery of 9 in 65% yield, these results being
in sharp contrast to the complete conversion of endo-
carbamate 7a into 8a (78% yield, run 2 in Table 3) under
the same conditions within 2 h.
This clear-cut congeniality between the structure type
of nitrogen nucleophiles and reaction conditions suggests
that 7l assembled with two types of nitrogen nucleophiles
(endo- and exo-carbamate) would undergo aminocarbo-
nylation chemoselectively just by changing the reaction
conditions (Scheme 2). Indeed, the endo-carbamate
moiety of 7l selectively underwent aminocarbonylation
under buffered conditions B-2′ and B-3 to provide 8l in
good yields (runs 1,2, Table 6). On the other hand, the
exo-carbamate moiety of 7l reacted selectively under
acidic conditions A to give rise to 13a in reasonable yield
(run 3, Table 6).
A similarly distinctive chemoselective cyclization was
observed for substrates possessing endo-carbamate and
exo-urea (7m ,n , runs 4-8, Table 6) and endo-carbamate
and exo-tosylamide moieties (7o, runs 9-11, Table 6). In
these experiments, the chemoselectivities were complete,
and 8l-o and 13a -d were obtained exclusively.
The reaction of 7n under conditions A (run 8) furnished
the bicyclic product 13c, which presumably was formed
via further imidation of the primary product 13c′.
trans-Selective formation of 8l-o is usual. cis-Selec-
tive formation of 13a -d seems to be unusual on steric
grounds; however, this is in good accord with our previous
observation that palladium(II)-catalyzed aminocarbony-
lation of 3-hydroxy-4-pentenyl carbamates3 and 3-hy-
droxy-4-pentenols14 provides cis-3-hydroxypyrrolidine
2-acetic acid lactones and cis-3-hydroxytetrahydrofuran
(12) Kimura, M.; Tanaka, S.; Tamaru, Y. J . Org. Chem. 1995, 60,
3764-3772.
(13) Wang, Y.-F.; Izawa, T.; Kobayashi, S.; Ohno, M. J . Am. Chem.
Soc. 1982, 104, 6465-6466; Masters, J . J .; Hegedus, L. S. J . Org. Chem.
1993, 58, 4547-4554.

2118 J . Org. Chem., Vol. 62, No. 7, 1997
Harayama et al.
Sch em e 3
leading to thermodynamic control, and hence high trans-
selectivities. Similarly high trans-selectivities under
conditions B-3 (and B-3′) seem to be a natural conse-
quence of the presence of methanol in a limited amount.
Theoretically, 2 equiv at most of methanol should be
present, which corresponds to the amount of HCl evolved.
Practically, however, slightly more methanol may be
present, since water, contained in inorganic reagents,
may produce methanol by hydrolysis of MOA.
Under conditions B-2, on the other hand, methanol is
more nucleophilic, being present as a neat solvent, and
hinders the equilibrium. Accordingly, the reaction be-
comes more kinetically controlled, resulting in the lower
trans-selectivities.
The structure of cis- and trans-8 was elucidated by 13
C
NMR, where the R-carbons of substituents attached to
C-4 and C-5 of cis-8 showed higher field resonances by
ca. 5 ppm as compared with those of trans-8, and/or by
3
1H NMR, where cis-8 showed J H4-H5 ) ca. 7 Hz, while
3
trans-8 J H4-H5 ) ca. 3 Hz.17 The structure of 12 was
determined by comparison of the coupling patterns of
tetrahydro-2-oxazolidinone ring protons with those of the
structurally related compounds11b as well as by NOE
experiments (see Experimental Section).
Con clu sion
2-acetic acid lactones, respectively, in good yields with
excellent stereoselectivities. J udging from these two and
many other related examples,15 the allylic oxygen atom
of 7o-l seems to be responsible for the cis-selective
formation of 13a -d .
Among nitrogen nucleophiles, endo-carbamates display
distinctive reactivity for the Wacker-type aminocarbo-
nylation. Many nitrogen nucleophiles (exo-carbamates,
endo-ureas, exo-ureas, and exo-tosylamides) smoothly
undergo aminocarbonylation under conditions A, but not
under conditions B. endo-Carbamates, on the other
hand, react under conditions B and not under conditions
A. Conditions A are strongly acidic, since 2 mol of HCl
evolve during the catalytic cycle, while conditions B are
buffered, since the HCl evolved is neutralized either by
a base (NaOAc, etc.) or by MOA. Conditions B are
sufficiently basic to generate the conjugate base of endo-
carbamates, a reactive species for aminocarbonylation,
but not so basic as to cause undesirable PdCl2-mediated
side reactions. Conditions B-3 (and B-3′) that can be
successfully applied to a wide variety of endo-carbamates
7 and 11 are only different from conditions A in the
solvent utilized, MOA for the former and MeOH for the
latter. By applying these conditions A and B, completely
chemoselective aminocarbonylation of 7l-o, at the endo-
carbamate moieties under conditions B and at the other
nitrogen nucleophiles under conditions A, can be achieved.
The aminocarbonylation reported here may find wide
application in the synthesis of γ- and δ-hydroxy-â-amino
acids and their derivatives of structural complexity.10,13
Finally, it should be emphasized that the chemoselec-
tive aminocarbonylation of endo-carbamates and the
other nitrogen nucleophiles of 7l-o could be achieved just
by changing the reaction medium: at the endo-carbamate
moiety in MOA alone (conditions B-3) and at the other
nitrogen nucleophiles in methanol alone (conditions A).
Dep en d en ce of St er eoselect ivit y on R ea ct ion
Con d ition s. The aminocarbonylation of 7 shows an
interesting correlation between the stereoselectivity of
cis- and trans-8 and reaction conditions (Tables 3 and 6
and eq 7): in general, trans-8’s are produced in the
highest proportions under conditions B-1, in nearly equal
or slightly lower proportions under conditions B-3 (and
B-3′) and in the lowest proportions under conditions B-2
(and B-2′). The dependence of stereoselectivity on the
reaction conditions may be rationalized according to a
plausible catalytic cycle shown in Scheme 3, which
involves an equilibrium between acylpalladium interme-
diates cis- and trans-I and an irreversible transformation
of these complexes into the final products cis- and trans-
8.16 Through this equilibrium, trans-I may accumulate
at the expense of cis-I, owing to the higher thermody-
namic stability of the former than the latter.
Exp er im en ta l Section
Under conditions B-1, methanol is poorly nucleophilic,
being present as MeOH (2 mL) diluted with AcOH (8
mL), and cis-I and trans-I are allowed to equilibrate,
Melting points are not corrected. Unless otherwise speci-
fied, short-path (bulb-to-bulb) distillations were carried out in
a Kugelrohr apparatus. In these cases, boiling points refer to
the oven temperature. Microanalyses were performed by the
Microanalysis Center of Nagasaki University. Analyses agreed
with the calculated values within (0.3%. Proton magnetic
resonance spectra were determined either at 60, 90, or 400
MHz with TMS as an internal standard. Carbon magnetic
resonance spectra were recorded at 22.5, 75, or 100 MHz.
Chemical shift values were given in ppm downfield from TMS.
(14) Tamaru, Y.; Kobayashi, T.; Kawamura, S.; Ochiai, H.; Hojo,
M.; Yoshida, Z. Tetrahedron Lett. 1985, 26, 3207-3210.
(15) (a) Tamaru, Y.; Higashimura, H.; Naka, K.; Hojo, M.; Yoshida,
Z. Angew. Chem. Int. Ed. Engl. 1985, 24, 1045-1046. (b) Tamaru, Y.;
Hojo, M.; Kawamura, S.; Sawada, S.; Yoshida, Z. J . Org. Chem. 1987,
52, 4062-4072. (c) Tamaru, Y.; Kawamura, S.; Bando, T.; Tanaka, K.;
Hojo, M.; Yoshida, Z. J . Org. Chem. 1988, 53, 5491-5501. (d) Tamaru,
Y.; Harayama, H.; Bando, T.; Nagaoka, H.; Yoshida, Z. Liebigs Ann.
1996, 223-234.
Rf values were measured with Merck Kieselgel 60F254
.
(16) For the related discussion, see: Nilsson, Y. I. M.; Aranyos, A.;
Andersson, P. G.; Ba¨ckvall, J .-E.; Parrain, J .-L.; Plateau, C.; Quintard,
J .-P. J . Org. Chem. 1996, 61, 1825-1829.
(17) Breitmaier, E. Structure Elucidation by NMR in Organic
Chemistry; Wiley: New York, 1993.

Palladium(II)-Catalyzed Aminocarbonylation
J . Org. Chem., Vol. 62, No. 7, 1997 2119
Solven ts a n d Rea gen ts. THF and ether were dried and
distilled from benzophenone sodium ketyl immediately before
use under nitrogen. Triethylamine was distilled over CaH2.
Methanol was dried and distilled from Mg and I2 under
nitrogen. Acetic acid was distilled from P2O5. MOA, MOF,
and DMP were distilled from Na under N2 under atmospheric
pressure. Methyl isocyanate, phenyl isocyanate, and methyl
chlorocarbonate were used without purification. Tosyl isocy-
anate was distilled prior to use (120 °C/0.5 Torr). Acrolein
was distilled from CaSO4 in the presence of a small amount
of p-methoxyphenol under N2. PdCl2, CuCl2, AcONa, PhCO2-
Na, ClCH2CO2Na, Cl3CCO2Na, boron trifluoride etherate, and
allylmagnesium chloride (2.0 M in THF) were purchased and
used without purification. Caution! Benzene is highly toxic.
All operations (TLC monitoring and recrystallization) with this
solvent should be carried out in a well-ventilated hood. In most
cases, benzene may be substituted with other solvents (e.g.,
toluene).
2-P r op en yl Tosylca r ba m a tes 7a -k . Carbamates 7a -k
were prepared by the reaction of tosyl isocyanate and the
corresponding 2-propen-1-ols according to the procedure re-
ported from our laboratories.18 2-Propen-1-ol, 1-methyl-2-
propen-1-ol, 1,1-dimethyl-2-propen-1-ol were purchased and
used without purification. 1-Penten-3-ol, 4-methyl-1-penten-
3-ol, 4,4-dimethyl-1-penten-3-ol, and 1,5-hexadien-3-ol were
prepared by the reaction of acrolein with the appropriate
Grignard reagents (ether, 0 °C). 4,4-Dimethyl-1,5-hexadien-
3-ol was prepared as follows: A solution of 3,3-dimethyl-2-
propenyl bromide (50 mmol) in THF (80 mL) was added
dropwise over 3 h into well-stirred suspension of Zn-Cu couple
(55 mmol) over THF (20 mL) at -20 °C under N2. The mixture
was stirred for an additional 1 h at -20 °C. Into this mixture
was added acrolein (75 mmol) dissolved in ether (70 mL) at
-20 °C over 2 h. After stirring for an additional 2 h at room
temperature, the mixture was poured into ether (100 mL) and
the mixture was washed with 2 M HCl (40 mL), brine (20 mL),
and then with saturated NaHCO3. The organic layer was
dried (MgSO4), filtered, and concentrated to give an oil, which
was distilled under reduced pressure (55 °C/10 Torr, 70%
yield).
2-P r op en yl Tosylca r ba m a tes 7l-o. Into a stirred solu-
tion of methyl 3-hydroxy-4-pentenylcarbamate (10 mmol)15c in
THF (20 mL) kept at 0 °C was added dropwise boron trifluoride
etherate (10 mmol) and then tosyl isocyanate (10 mmol) via
syringes. After stirring for 1 h at 0 °C, the temperature was
allowed to rise to room temperature and the mixture was
stirred for an additional 1 h. The mixture was diluted with
ethyl acetate (100 mL) and washed with saturated NaHCO3.
The organic phase was dried (MgSO4), filtered, and concen-
trated. The residue was chromatographed over silica gel
(toluene-ethyl acetate gradient) to give 7l in 60% yield; Rf )
0.55 (benzene-ethyl acetate ) 1/1, v/v). According to the
similar procedure, 7m [56% after purification by column
chromatography over silica gel, ethyl acetate-acetone gradi-
ent; Rf ) 0.6 (acetone-ethyl acetate ) 2/1, v/v)], 7n [49% after
purification by column chromatography over silica gel, ethyl
acetate-acetone gradient; Rf ) 0.45 (acetone-ethyl acetate
) 2/1, v/v)], and 7o [100% after purification by column
chromatography over silica gel, toluene-ethyl acetate gradi-
ent; Rf ) 0.5 (benzene-ethyl acetate ) 2/1, v/v)] were prepared
from N-phenyl-N′-(3-hydroxy-4-pentenyl)urea,15c N-methyl-
N′-(3-hydroxy-4-pentenyl)urea,15c and N-tosyl-3-hydroxy-4-
pentenylamine,15c respectively.
3-Bu ten yl Tosylca r ba m a tes 11a -g. Carbamates 11a -g
were prepared by the reaction of tosyl carbamate and the
corresponding 3-buten-1-ols according to the procedure re-
ported from our laboratories.18 3-Buten-1-ol was purchased
and the other 3-buten-1-ols were prepared as follows: 1-Phen-
yl-3-buten-1-ol (benzaldehyde and allylmagnesium chloride),
1-tert-butyl-3-buten-1-ol (trimethylacetaldehyde and allylmag-
nesium chloride), 1,1-dimethyl-3-buten-1-ol (acetone and al-
lylmagnesium chloride), 1-allylcyclohexan-1-ol (cyclohexanone
and allylmagnesium chloride), 2-methyl-1-phenyl-3-penten-1-
ol (benzaldehyde and 2-butenylmagnesium chloride), and 1,1,2-
trimethyl-3-buten-1-ol (acetone and 2-butenylmagnesium chlo-
ride).
Am in oca r bon yla tion of 7 a n d 11. The aminocarbonyla-
tion of 7 and 11 under conditions A and B was performed
essentially in the same way as typified by the following
reactions of 7l.
Am in oca r bon yla tion of 7l u n d er Con d ition s B-3 (r u n
2, Ta ble 6). Into a flask containing PdCl2 (0.1 mmol) and
CuCl2 (2.3 mmol), purged with carbon monoxide (a balloon),
was added 7l (1 mmol) dissolved in trimethyl orthoacetate (5
mL) via a syringe. The mixture was stirred at 35 °C for 7 h,
during which time the reaction was monitored by TLC (Rf
)
7l
0.55, Rf ) 0.65, benzene-ethyl acetate ) 1/1, v/v). The
8l
mixture was diluted with ethyl acetate (50 mL) and washed
with 5% NH4Cl-5% NH3 (2 × 15 mL). The organic layer was
dried (MgSO4), filtered, and concentrated in vacuo. The
residue was chromatographed over silica gel (hexane-ethyl
acetate gradient) to give a mixture of trans- and cis-8l (11:1)
in 68% yield. Pure trans-8l was obtained by recrystallization
from dichloromethane-hexane.
Am in oca r bon yla tion of 7l u n d er Con d ition s A (r u n 3,
Ta ble 6). Into a flask containing PdCl2 (0.1 mmol) and CuCl2
(3.0 mmol), purged with carbon monoxide (a balloon), was
added 7l (1 mmol) dissolved in methanol (5 mL) via a syringe.
The mixture was stirred at 25 °C for 120 h, during which time
the reaction was monitored by TLC (Rf ) 0.55, Rf ) 0.50,
7l
13a
benzene-ethyl acetate ) 1/1, v/v). After evaporation of the
solvent, the residue was diluted with ethyl acetate and filtered
through a Celite pad on a funnel. The filtrate was concen-
trated and the residue was chromatographed over silica gel
(toluene-ethyl acetate gradient) to provide a mixture of trans-
and cis-13a (1:3) in 58% yield. Pure cis-13a was obtained by
recrystallization from dichloromethane-hexane.
1-Ben zyl-4-[(m eth oxyca r bon yl)m eth yl]-3-p r op yl-2-im i-
d a zolid in on e (4): oil; IR (neat film) 1780 (s), 1690 (s) cm-1
;
1H NMR (300 MHz, CDCl3) δ 0.91 (t, J ) 7.4 Hz, 3 H), 1.48-
1.58 (m, 2 H), 2.39 (dd, J ) 9.1, 16.0 Hz, 1 H), 2.74 (dd, J )
4.1, 16.0 Hz, 1 H), 2.87-2.98 (m, 2 H), 3.38-3.45 (m, 2 H),
3.66 (s, 3 H), 3.93 (m, 1 H), 4.32 (d, J ) 15.0 Hz, 1 H), 4.40 (d,
J
) 15.0 Hz, 1 H), 7.23-7.35 (m, 5 H); HRMS calcd for
16H22N2O3 290.1630, found m/z (relative intensity) 290.1625
C
(M+, 76.4), 262.1 (17.5), 261.1 (100.0), 218.1 (8.7), 217.1 (68.1),
199.1 (7.8).
1-(Meth oxycar bon yl)-2-[(m eth oxycar bon yl)m eth yl]pyr -
1
r olid in e (6): oil; IR (neat film) 1740 (m), 1700 (s) cm-1; H
NMR (400 MHz, DMSO-d6, 100 °C) δ 1.68 (m, 1 H), 1.73-
1.89 (m, 2 H), 2.01 (m, 1 H), 2.37 (dd, J ) 8.8, 15.0 Hz, 1 H),
2.69 (dd, J ) 4.0, 15.0 Hz, 1 H), 3.24-3.36 (m, 2 H), 3.58 (s, 3
H), 3.60 (s, 3 H), 4.04 (tt, J ) 4.0, 8.8 Hz, 1 H); HRMS calcd
for C9H15NO4 201.1001, found m/z (relative intensity) 201.1001
(M+, 24.8), 170.1 (10.9), 142.1 (47.3), 128.1 (100.0), 110.1 (5.0),
82.1 (5.1).
4-[(Met h oxyca r b on yl)m et h yl]-3-t osyl-2-oxa zolid in o-
n e (8a ): mp 120.5-121.1 °C (benzene-hexane); IR (KBr disk)
1
1770 (s), 1730 (s), 1725 (s) cm-1; H NMR (90 MHz, CDCl3) δ
2.45 (s, 3 H), 2.77 (dd, J ) 9.3, 16.9 Hz, 1 H), 3.31 (dd, J )
3.4, 16.9 Hz, 1 H), 3.70 (s, 3 H), 4.13 (dd, J ) 4.0, 8.7 Hz, 1 H),
4.41-4.88 (m, 2 H), 7.35 (d, J ) 8.5 Hz, 2 H), 7.94 (d, J ) 8.5
Hz, 2 H); 13C NMR (22.5 MHz, CDCl3) δ 21.3, 38.1 (CH2CO2-
Me), 51.7 (CO2CH3), 53.2 (C4), 67.8 (C5), 128.2, 129.6, 134.7,
145.5, 151.7 (C2), 169.6 (CO2Me). Anal. Calcd for C13H15
-
NO6S: C, 49.83; H, 4.83; N, 4.47; S, 10.23. Found: C, 49.76;
H, 4.81; N, 4.45; S, 10.20.
tr a n s-4-[(Meth oxyca r bon yl)m eth yl]-5-m eth yl-3-tosyl-
2-oxa zolid in on e (8b): mp 83.0-84.5 °C (benzene-hexane);
IR (KBr disk) 1780 (s), 1720 (s) cm-1 1H NMR (400 MHz,
;
CDCl3) δ 1.35 (d, J ) 6.2 Hz, 3 H), 2.46 (s, 3 H), 2.77 (dd, J )
9.9, 17.2 Hz, 1 H), 3.19 (dd, J ) 2.9, 17.2 Hz, 1 H), 3.71 (s, 3
H), 4.29 (dt, J ) 9.9, 2.9 Hz, 1 H), 4.41 (dq, J ) 2.9, 6.2 Hz, 1
H), 7.37 (d, J ) 8.4 Hz, 2 H), 7.94 (d, J ) 8.4 Hz, 2 H); 13C
NMR (22.5 MHz, CDCl3) δ 20.3 (CHCH3), 21.3, 38.0 (CH2CO2-
Me), 51.7 (CO2CH3), 59.5 (C4), 76.6 (C5), 128.0, 129.6, 134.8,
145.5, 150.1 (C2), 169.6 (CO2Me). [cis-8b: 1H NMR (400 MHz,
(18) Tamaru, Y.; Kimura, M.; Tanaka, S.; Kure, S.; Yoshida, Z. Bull.
Chem. Soc. J pn. 1994, 67, 2838-2849.

2120 J . Org. Chem., Vol. 62, No. 7, 1997
Harayama et al.
CDCl3) δ 1.32 (d, J ) 6.2 Hz, 3 H), 2.45 (s, 3 H), 2.84 (dd, J )
9.5, 17.2 Hz, 1 H), 3.10 (dd, J ) 2.9, 17.2 Hz, 1 H), 3.70 (s, 3
H), 4.75-4.85 (m, 2 H), 7.32 (d, J ) 8.4 Hz, 2 H), 7.82 (d, J )
8.4 Hz, 2 H); 13C NMR (22.5 MHz, CDCl3) δ 14.1 (CHCH3),
21.3, 33.7 (CH2CO2Me), 51.7 (CO2CH3), 56.8 (C4), 74.5 (C5),
128.0, 129.6, 134.8, 145.5, 150.1 (C2), 169.6 (CO2Me).] Anal.
Calcd for C14H17NO6S: C, 51.37; H, 5.23; N, 4.28; S, 9.79.
Found: C, 51.38; H, 5.36; N, 4.30; S, 9.91.
tr a n s-5-Eth yl-4-[(m eth oxyca r bon yl)m eth yl]-3-tosyl-2-
oxa zolid in on e (8c): mp 77.7-78.0 °C (benzene-hexane); IR
(KBr disk) 1780 (s), 1740 (s) cm-1; 1H NMR (400 MHz, CDCl3)
δ 0.91 (t, J ) 7.3 Hz, 3 H), 1.54-1.76 (m, 2 H), 2.46 (s, 3 H),
2.80 (dd, J ) 9.5, 16.9 Hz, 1 H), 3.17 (dd, J ) 3.3, 16.9 Hz, 1
H), 3.70 (s, 3 H), 4.23 (ddd, J ) 3.3, 4.7, 7.3 Hz, 1 H), 4.36 (dt,
J ) 9.5, 3.3 Hz, 1 H), 7.36 (d, J ) 8.4 Hz, 2 H), 7.94 (d, J ) 8.4
Hz, 2 H); NOEs for H5 (0.0%) and one of methylene protons of
ethyl group (3.3%) by irradiation of the signal of H4; 13C NMR
(22.5 MHz, CDCl3) δ 7.9 (CH2CH3), 21.3, 27.4 (CH2CH3), 38.2
(CH2CO2Me), 51.6 (CO2CH3), 57.5 (C4), 80.9 (C5), 128.0, 129.5,
134.8, 145.4, 151.0 (C2), 169.5 (CO2Me). [cis-8c: 1H NMR (400
MHz, CDCl3) δ 1.02 (t, J ) 7.3 Hz, 3 H), 1.54-1.76 (m, 2 H),
2.42 (s, 3 H), 2.85 (dd, J ) 9.7, 17.2 Hz, 1 H), 3.02 (dd, J )
3.3, 17.2 Hz, 1 H), 3.68 (s, 3 H), 4.50 (ddd, J ) 3.3, 7.3, 9.7 Hz,
1 H), 4.83 (ddd, J ) 3.3, 7.3, 10.6 Hz, 1 H), 7.35 (d, J ) 8.4
2 H), 3.67 (s, 3 H), 4.03 (d, J ) 3.4 Hz, 1 H), 4.52 (dt, J ) 3.4,
5.6 Hz, 1 H), 7.35 (d, J ) 8.0 Hz, 2 H), 8.00 (d, J ) 8.0 Hz, 2
H). Anal. Calcd for C17H23NO6S: C, 57.70; H, 6.37; N, 3.54.
Found: C, 57.70; H, 6.28; N, 3.53.
5,5-Dim et h yl-4-[(m et h oxyca r bon yl)m et h yl]-3-t osyl-2-
oxa zolid in on e (8h ): mp 94.5-95.5 °C (benzene-hexane); IR
1
(KBr disk) 1775 (s), 1740 (s) cm-1; H NMR (60 MHz, CDCl3)
δ 1.33 (s, 6 H), 2.45 (s, 3 H), 2.82-3.03 (m, 2 H), 3.70 (s, 3 H),
4.49 (dd, J ) 4.0, 8.4 Hz, 1 H), 7.33 (d, J ) 8.0 Hz, 2 H), 7.93
(d, J ) 8.0 Hz, 2 H). Anal. Calcd for C15H19NO6S: C, 52.78;
H, 5.61; N, 4.10; S, 9.39. Found: C, 52.63; H, 5.51; N, 4.18; S,
9.26.
cis-4-[(Meth oxyca r bon yl)m eth yl]-5-[2-(p h th a loyla m i-
n o)eth yl]-3-tosyl-2-oxa zolid in on e (8i): mp 201.0-201.9 °C
(dichloromethane-hexane); IR (KBr disk) 1770 (s), 1730 (s),
1710 (s) cm-1 1H NMR (400 MHz, CDCl3) δ 1.95 (m, 1 H),
;
2.05 (m, 1 H), 2.45 (s, 3 H), 2.85 (dd, J ) 9.2, 17.6 Hz, 1 H),
3.03 (dd, J ) 3.3, 17.6 Hz, 1 H), 3.66 (s, 3 H), 3.78 (dt, J )
14.3, 7.3 Hz, 1 H), 3.87 (dt, J ) 14.3, 7.3 Hz, 1 H), 4.70 (ddd,
J ) 3.3, 7.3, 10.3 Hz, 1 H), 4.85 (ddd, J ) 3.3, 7.3, 9.2 Hz, 1
H), 7.35 (d, J ) 8.1 Hz, 2 H), 7.73 (dd, J ) 3.3, 5.5 Hz, 2 H),
7.83 (dd, J ) 3.3, 5.5 Hz, 2 H), 7.93 (d, J ) 8.1 Hz, 2 H); NOE
for H5 (10.3%) and one of CH2CO2Me protons (3.1%) by
irradiation at H4; 13C NMR (100 MHz, CDCl3) δ 21.7, 28.0
(CH2CH2CH), 34.0 (CH2CH2CH), 34.7 (CH2CO2Me), 52.3
(CO2CH3), 56.6 (C4), 76.4 (C5), 123.3, 128.3, 128.5, 129.8, 130.0,
132.0, 134.1, 145.8, 150.9 (C2), 168.0, 170.0 (CO2Me). [trans-
8i: 1H NMR (400 MHz, CDCl3) δ 1.95 (m, 1 H), 2.05 (m, 1 H),
2.44 (s, 3 H), 2.82 (dd, J ) 9.2, 17.2 Hz, 1 H), 3.22 (dd, J )
3.3, 17.2 Hz, 1 H), 3.65 (s, 3 H), 3.78 (t, J ) 7.0 Hz, 1 H), 4.35-
4.41 (m, 2 H), 7.35 (d, J ) 8.1 Hz, 2 H), 7.73 (dd, J ) 3.3, 5.5
Hz, 2 H), 7.83 (dd, J ) 3.3, 5.5 Hz, 2 H), 7.93 (d, J ) 8.1
Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ 21.7, 33.7 (CH2CH2-
CH), 33.9 (CH2CH2CH), 38.3 (CH2CO2Me), 52.1 (CO2CH3),
58.2 (C4), 78.3 (C5), 123.3, 128.3, 128.5, 129.8, 130.0, 132.0,
134.1, 145.8, 150.9 (C2), 168.0, 170.0 (CO2Me).] Anal. Calcd
for C23H22N2O8S: C, 56.78; H, 4.52; N, 5.76; S, 6.59. Found:
C, 56.47; H, 4.52; N, 5.74; S, 6.65.
Hz, 2 H), 7.95 (d, J ) 8.4 Hz, 2 H).] Anal. Calcd for C15H19
-
NO6S: C, 52.78; H, 5.61; N, 4.10; S, 9.39. Found: C, 52.87;
H, 5.58; N, 4.14; S, 9.57.
tr a n s-5-Isobu tyl-4-[(m eth oxyca r bon yl)m eth yl]-3-tosyl-
2-oxa zolid in on e (8d ): oil; IR (neat film) 1785 (s), 1735 (s)
1
cm-1; H NMR (400 MHz, CDCl3) δ 0.89 (d, J ) 6.6 Hz, 6 H),
1.41 (ddd, J ) 4.8, 8.4, 14.3 Hz, 1 H), 1.47 (ddd, J ) 5.5, 9.2,
14.3 Hz, 1 H), 1.76 (m, 1 H), 2.46 (s, 3 H), 2.78 (dd, J ) 9.2,
17.2 Hz, 1 H), 3.15 (dd, J ) 3.3, 17.2 Hz, 1 H), 3.70 (s, 3 H),
4.29 (dt, J ) 9.2, 3.3 Hz, 1 H), 4.34 (ddd, J ) 3.3, 4.8, 9.2 Hz,
1 H), 7.37 (d, J ) 8.4 Hz, 2 H), 7.93 (d, J ) 8.4 Hz, 2 H); 13C
NMR (22.5 MHz, CDCl3) δ 21.4, 21.6, 22.7, 23.9, 38.2 (CH2-
CO2Me), 43.6 (CH2-i-Bu), 51.7 (CO2CH3), 58.6 (C4), 78.8 (C5),
128.2, 129.6, 135.0, 145.5, 151.0 (C2), 169.6 (CO2Me). [cis-8d :
1H NMR (400 MHz, CDCl3) δ 0.88 (d, J ) 6.6 Hz, 6 H), 1.37-
1.50 (m, 2 H), 1.76 (m, 1 H), 2.45 (s, 3 H), 2.77 (dd, J ) 9.2,
17.2 Hz, 1 H), 2.99 (dd, J ) 3.3, 17.2 Hz, 1 H), 3.68 (s, 3 H),
4.67 (ddd, J ) 3.3, 7.3, 11.0 Hz, 1 H), 4.82 (ddd, J ) 3.3, 7.3,
9.2 Hz, 1 H), 7.33 (d, J ) 8.4 Hz, 2 H), 7.92 (d, J ) 8.4 Hz, 2
H).] HRMS calcd for C17H23NO6S - CH3 354.1012, found m/z
(relative intensity), 354.1018 (M+ - CH3, 1.0), 338.0 (1.0), 232.0
(6.0), 214.0 (12.0), 155.0 (21.0), 108.0 (100.0).
tr a n s-5-Allyl-4-[(m et h oxyca r b on yl)m et h yl]-3-t osyl-2-
oxa zolid in on e (8j): oil; IR (neat film) 1790 (s), 1740 (s) cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.35-2.50 (m, 2 H), 2.46 (s, 3
H), 2.83 (dd, J ) 9.5, 16.9 Hz, 1 H), 3.19 (dd, J ) 3.3, 16.9 Hz,
1 H), 3.70 (s, 3 H), 4.37-4.42 (m, 2 H), 5.03 (dd, J ) 1.5, 9.0
Hz, 1 H), 5.15 (dd, J ) 1.5, 16.9 Hz, 1 H), 5.55 (ddt, J ) 9.0,
16.9, 7.0 Hz, 1 H), 7.37 (d, J ) 8.1 Hz, 2 H), 7.93 (d, J ) 8.1
Hz, 2 H); HRMS calcd for C16H18NO6S - CH2O 322.0750, found
m/z (relative intensity) 322.0740 (M+ - CH2O, 8.7), 312.1 (8.4),
280.1 (8.6), 198.1 (26.3), 155.0 (100.0).
tr a n s-4-[(Meth oxyca r bon yl)m eth yl]-5-(2-p h en yleth yl)-
3-tosyl-2-oxa zolid in on e (8e): mp 125.0-126.0 °C (benzene-
1
hexane); IR (KBr disk) 1790 (s), 1730 (s) cm-1; H NMR (400
tr a n s-5-(1,1-Dim et h yla llyl)-4-[(m et h oxyca r b on yl)m e-
th yl]-3-tosyl-2-oxa zolid in on e (8k ): oil; IR (neat film) 1790
MHz, CDCl3) δ 1.82 (dddd, J ) 4.0, 5.1, 9.2, 14.3 Hz, 1 H),
1.97 (ddt, J ) 9.9, 14.3, 7.0 Hz, 1 H), 2.43 (s, 3 H), 2.60 (ddd,
J ) 7.0, 9.2, 13.9 Hz, 1 H), 2.68 (ddd, J ) 5.1, 9.9, 13.9 Hz, 1
H), 2.75 (dd, J ) 9.9, 16.9 Hz, 1 H), 3.16 (dd, J ) 3.3, 16.9 Hz,
1 H), 3.65 (s, 3 H), 4.25 (ddd, J ) 3.3, 4.0, 7.0 Hz, 1 H), 4.35
(dt, J ) 9.9, 3.0 Hz, 1 H), 7.10 (d, J ) 7.3 Hz, 2 H), 7.19 (t, J
) 7.3 Hz, 1 H), 7.27 (t, J ) 7.3 Hz, 2 H), 7.35 (d, J ) 8.1 Hz,
2 H), 7.93 (d, J ) 8.1 Hz, 2 H). Anal. Calcd for C21H23NO6S:
C, 60.42; H, 5.55; N,3.36; S, 7.68. Found: C, 60.70; H, 5.53;
N, 3.38; S, 7.53.
tr a n s-5-Isop r op yl-4-[(m eth oxyca r bon yl)m eth yl]-3-to-
syl-2-oxa zolid in on e (8f): mp 96.4-96.6 °C (benzene-hex-
ane); IR (KBr disk) 1770 (s), 1745 (s) cm-1; 1H NMR (90 MHz,
CDCl3) δ 0.82 (d, J ) 6.8 Hz, 3 H), 0.92 (d, J ) 6.8 Hz, 3 H),
1.86 (m, 1 H), 2.45 (s, 3 H), 2.80 (dd, J ) 8.5, 16.6 Hz, 1 H),
3.11 (dd, J ) 3.7, 16.6 Hz, 1 H), 3.68 (s, 3 H), 4.09 (dd, J )
2.9, 5.1 Hz, 1 H), 4.44 (ddd, J ) 2.9, 3.7, 8.5 Hz, 1 H), 7.35 (d,
J ) 8.3 Hz, 2 H), 7.94 (d, J ) 8.3 Hz, 2 H); 13C NMR (22.5
MHz, CDCl3) δ 15.4, 17.1, 21.3, 31.9 (CHMe2), 38.6 (CH2CO2-
Me), 51.5 (CO2CH3), 55.6 (C4), 84.0 (C5), 128.0, 129.5, 134.9,
1
(s), 1740 (s) cm-1; H NMR (400 MHz, CDCl3) δ 0.98 (s, 3 H),
1.01 (s, 3 H), 2.46 (s, 3 H), 2.87 (dd, J ) 3.3, 16.1 Hz, 1 H),
2.95 (dd, J ) 6.9, 16.1 Hz, 1 H), 3.65 (s, 3 H), 4.08 (d, J ) 3.0
Hz, 1 H), 4.03 (dt, J ) 6.9, 3.3 Hz, 1 H), 4.94 (d, J ) 10.6 Hz,
1 H), 5.08 (d, J ) 17.4 Hz, 1 H), 5.52 (dd, J ) 10.6, 17.4 Hz,
1 H), 7.35 (d, J ) 8.1 Hz, 2 H), 7.93 (d, J ) 8.1 Hz, 2 H); HRMS
calcd for C18H23NO6S 381.1246, found m/z (relative intensity)
381.1229 (M+, 7.3), 350.1 (100.0).
tr a n s-5-[2-[(Meth oxyca r bon yl)a m in o]eth yl]-4-[(m eth -
oxyca r b on yl)m et h yl]-3-t osyl-2-oxa zolid in on e (8l): mp
108.5-109.0 °C (dichloromethane-hexane); IR (KBr disk) 3400
1
(m), 1785 (s), 1740 (s), 1725 (s), 1700 (s) cm-1; H NMR (400
MHz, CDCl3) δ 1.70-1.91 (m, 2 H), 2.46 (s, 3 H), 2.87 (dd, J )
9.9, 17.2, 1 H), 3.17 (dd, J ) 2.9, 17.2 Hz, 1 H), 3.26-3.37 (m,
2 H), 3.66 (s, 3 H), 3.70 (s, 3 H), 4.36-4.39 (m, 2 H), 5.31 (br
s, 1 H), 7.37 (d, J ) 8.1 Hz, 2 H), 7.92 (d, J ) 8.1 Hz, 2 H).
Anal. Calcd for C17H22N2O8S: C, 49.27; H, 5.35; N, 6.76; S,
7.73. Found: C, 49.37; H, 5.23; N, 6.76; S, 7.60.
tr a n s-4-[(Meth oxyca r bon yl)m eth yl]-5-[2-[(p h en ylca r -
ba m oyl)a m in o]eth yl]-3-tosyl-2-oxa zolid in on e (8m ): mp
109.3-109.8 °C (dichloromethane-hexane); IR (KBr disk) 3380
145.3, 151.1 (C2), 169.3 (CO2Me). Anal. Calcd for C16H21
-
NO6S: C, 54.07; H, 5.96; N, 3.94; S, 9.02. Found: C, 54.05;
H, 6.03; N, 3.98; S, 9.24.
1
(w), 1780 (s), 1735 (m), 1665 (m), 1600 (m), 1555 (s) cm-1; H
tr a n s-5-ter t-Bu tyl-4-[(Meth oxyca r bon yl)m eth yl]-3-to-
syl-2-oxa zolid in on e (8g): mp 109.0-110.0 °C (benzene-
NMR (400 MHz, CDCl3) δ 1.69 (ddt, J ) 8.1, 14.3, 6.2 Hz, 1
H), 1.91 (br m, 1 H), 2.42 (s, 3 H), 2.84 (dd, J ) 8.8, 17.2 Hz,
1 H), 3.07 (dd, J ) 3.3, 17.2 Hz, 1 H), 3.26-3.36 (m, 2 H), 3.61
(s, 3 H), 4.34 (dt, J ) 3.3, 8.8 Hz, 1 H), 4.41 (ddd, J ) 3.3, 4.8,
1
hexane); IR (KBr disk) 1780 (s), 1740 (s) cm-1; H NMR (60
MHz, CDCl3) δ 0.86 (s, 9 H), 2.45 (s, 3 H), 2.93 (d, J ) 5.6 Hz,

Palladium(II)-Catalyzed Aminocarbonylation
J . Org. Chem., Vol. 62, No. 7, 1997 2121
8.1 Hz, 1 H), 5.54 (br d, J ) 5.9 Hz, 1 H), 7.00 (t, J ) 7.0 Hz,
1 H), 7.09 (br s, 1 H), 7.22-7.36 (m, 6 H), 7.90 (d, J ) 8.4 Hz,
2 H). Anal. Calcd for C22H25N3O7S: C, 55.57; H, 5.30; N, 8.84;
S, 6.74. Found: C, 55.27; H, 5.19; N, 8.72; S, 6.71.
6,6-Dim eth yl-4-[(m eth oxyca r bon yl)m eth yl]-3-tosyltet-
r a h yd r o-1,3-oxa zin -2-on e (12d ): mp 113.0-114.0 °C (ben-
zene-hexane); IR (KBr disk) 1740 (s) cm-1; 1H NMR (60 MHz,
CDCl3) δ 1.38 (s, 6 H), 1.98-2.42 (m, 2 H), 2.43 (s, 3 H), 2.76-
3.08 (m, 2 H), 3.65 (s, 3 H), 4.77 (m, 1 H), 7.26 (d, J ) 8.0 Hz,
2 H), 7.93 (d, J ) 8.0 Hz, 2 H). Anal. Calcd for C16H21NO6S:
C, 54.07; H, 5.96; N, 3.94; S, 9.02. Found: C, 53.93; H, 5.83;
N, 3.87; S, 8.99.
tr a n s-4-[(Meth oxyca r bon yl)m eth yl]-5-[2-[(m eth ylca r -
ba m oyl)a m in o]eth yl]-3-tosyl-2-oxa zolid in on e (8n ): oil; IR
(neat film) 3360 (br m), 1785 (s), 1735 (s), 1650 (s), 1565 (s)
1
cm-1; H NMR (400 MHz, CDCl3) δ 1.73 (ddt, J ) 8.4, 14.2,
4-[(Meth oxyca r bon yl)m eth yl]-3-tosyl-3-a za -1-oxa sp ir o-
[5.5]u n d eca -2-on e (12e): mp 88.5-89.5 °C (benzene-hex-
5.5 Hz, 1 H), 1.90 (tt, J ) 5.5, 14.2 Hz, 1 H), 2.46 (s, 3 H), 2.74
(d, J ) 4.8 Hz, 3 H), 2.87 (dd, J ) 8.8, 17.2 Hz, 1 H), 3.13 (dd,
J ) 3.3, 17.2 Hz, 1 H), 3.27 (q, J ) 5.5 Hz, 2 H), 3.67 (s, 3 H),
4.39 (dt, J ) 8.8, 3.3 Hz, 1 H), 4.44 (ddd, J ) 3.3, 5.5, 8.4 Hz,
1 H), 4.80 (br q, J ) 4.8 Hz, 1 H), 5.10 (br t, J ) 5.5 Hz, 1 H),
7.37 (d, J ) 8.1 Hz, 2 H), 7.91 (d, J ) 8.1 Hz, 2 H); HRMS
calcd for C17H23N3O7S 413.1257, found m/z (relative intensity)
413.1262 (2.2), 309.0 (100.0), 258.1 (45.8), 227.1 (63.7), 186.0
(16.8). Anal. Calcd for C17H23N3O7S: C, 49.38; H, 5.61; N,
10.16; S, 7.75. Found: C, 49.18; H, 5.40; N, 10.33; S, 7.65.
1
ane); IR (KBr disk) 1730 (s) cm-1; H NMR (90 MHz, CDCl3)
δ 1.07-2.05 (m, 10 H), 1.87 (dd, J ) 8.8, 14.2 Hz, 1 H), 2.39
(dd, J ) 7.3, 14.2 Hz, 1 H), 2.43 (s, 3 H), 2.69 (dd, J ) 8.8,
16.5 Hz, 1 H), 3.14 (dd, J ) 3.4, 16.5 Hz, 1 H), 3.66 (s, 3 H),
4.79 (ddt, J ) 3.4, 7.3, 8.8 Hz, 1 H), 7.30 (d, J ) 8.5 Hz, 2 H),
7.94 (d, J ) 8.5 Hz, 2 H); 13C NMR (22.5 MHz, CDCl3) δ 21.3,
21.4, 24.7, 34.8, 37.8, 38.1 (CH2CO2Me), 39.8 (C5), 50.5 (C4),
51.4 (CO2CH3), 81.2 (C6), 128.8, 128.9, 136.2, 144.6, 148.7 (C2),
169.8 (CO2Me). Anal. Calcd for C19H25NO6S: C, 57.71; H,
6.37; N, 3.54; S, 8.10. Found: C, 57.92; H, 6.47; N, 3.60; S,
8.16.
tr a n s-4-[(Meth oxyca r bon yl)m eth yl]-3-tosyl-4-[2-(tosy-
la m in o)eth yl]-2-oxa zolid in on e (8o): mp 144.5-145.5 °C
(dichloromethane-hexane); IR (KBr disk) 3540 (w), 1785 (s),
t r a n s,cis-4-[(Me t h oxyca r b on yl)m e t h yl]-5-m e t h yl-6-
ph en yl-3-tosyltetr ah ydr o-1,3-oxazin -2-on e (12f): mp 78.5-
80.5 °C (dichloromethane-hexane); IR (KBr disk) 1740 (s),
1
1735 (s) cm-1; H NMR (400 MHz, CDCl3) δ 1.68-1.92 (m, 2
H), 2.41 (s, 3 H), 2.44 (s, 3 H), 2.80 (dd, J ) 9.5, 17.2 Hz, 1 H),
2.99-3.06 (m, 2 H), 3.12 (dd, J ) 2.9, 17.2 Hz, 1 H), 3.67 (s, 3
H), 4.34 (dt, J ) 2.9, 9.5 Hz, 1 H), 4.41 (ddd, J ) 2.9, 5.1, 8.2
Hz, 1 H), 5.21 (t, J ) 6.6 Hz, 1 H), 7.29 (d, J ) 8.1 Hz, 2 H),
7.35 (d, J ) 8.1 Hz, 2 H), 7.70 (d, J ) 8.1 Hz, 2 H), 7.90 (d, J
) 8.1 Hz, 2 H). Anal. Calcd for C22H26N2O8S2: C, 51.76; H,
5.13; N, 5.49; S, 12.55. Found: C, 51.57; H, 5.05; N, 5.35; S,
12.73.
1
1725 (s) cm-1; H NMR (400 MHz, CDCl3) δ 0.70 (d, J ) 7.0
Hz, 3 H), 2.43 (s, 3 H), 2.38 (m, 1 H), 2.96 (dd, J ) 11.0, 16.1
Hz, 1 H), 3.32 (dd, J ) 3.7, 16.1 Hz, 1 H), 3.79 (s, 3 H), 4.77
(ddd, J ) 1.8, 3.7, 11.0 Hz, 1 H), 5.64 (d, J ) 2.6 Hz, 1 H),
7.22 (d, J ) 8.8 Hz, 2 H), 7.26-7.35 (m, 5 H), 7.93 (d, J ) 8.8
Hz, 2 H); NOE for C5H (8.2%) and one of the CH2CO2Me
protons (3.1%) by irradiation at C6H; HRMS calcd for C21H23
-
2-[(Me t h o x y c a r b o n y l)m e t h y l]-1-t o s y lp y r r o lid in e
NO6S 417.1246, found m/z (relative intensity) 417 1273 (M+,
6.0), 353.2 (69.8), 261.1 (18.1), 195.1 (56.2), 105.0 (51.0), 91.1
(100.0).
(10): oil; IR (neat film) 1740 (s) cm-1 1H NMR (300 MHz,
;
CDCl3) δ 1.51-1.84 (m, 4 H), 2.43 (s, 3 H), 2.51 (dd, J ) 10.0,
16.0 Hz, 1 H), 3.07 (dd, J ) 3.7, 16.0 Hz, 1 H), 3.12 (m, 1 H),
3.46 (m, 1 H), 3.95 (m, 1 H), 7.34 (d, J ) 8.1 Hz, 2 H), 7.73 (d,
4-[(Meth oxycar bon yl)m eth yl]-3-tosyl-5,6,6-tr im eth yltet-
r a h yd r o-1,3-oxa zin -2-on e (12g): mp 153.0-154.6 °C (ben-
zene-hexane); IR (KBr disk) 1730 (s) cm-1; 1H NMR (60 MHz,
CDCl3) δ 1.06 (d, J ) 6.4 Hz, 3 H), 1.21 (s, 3 H), 1.35 (s, 3 H),
2.17 (m, 1 H), 2.46 (s, 3 H), 2.70-3.04 (m, 2 H), 3.47 (s, 3 H),
4.16 (ddd, J ) 2.6, 5.0, 9.2 Hz, 1 H), 7.20 (d, J ) 8.2 Hz, 2 H),
7.93 (d, J ) 8.2 Hz, 2 H). Anal. Calcd for C17H23NO6S: C,
55.27; H, 6.28; N, 3.79; S, 8.68. Found: C, 54.93; H, 6.20; N,
3.75; S, 8.47.
J
) 8.1 Hz, 2 H); HRMS calcd for C14H19NO4S - CH3O:
266.0953, found m/z (relative intensity) 266.0875 (M+ - CH3O,
2.0), 224.1 (53.6), 184.0 (6.0), 156.0 (3.7), 142.0 (100.0), 110.1
(11.6), 91.1 (34.9).
4-[(Met h oxyca r b on yl)m et h yl]-3-t osylt et r a h yd r o-1,3-
oxa zin -2-on e (12a ): mp 128.5-129.5 °C (benzene-hexane);
IR (KBr disk) 1735 (s) cm-1 1H NMR (400 MHz, CDCl3) δ
;
2.15-2.29 (m, 2 H), 2.43 (s, 3 H), 2.76 (dd, J ) 10.6, 16.5 Hz,
1 H), 3.14 (dd, J ) 2.6, 16.5 Hz, 1 H), 3.73 (s, 3 H), 4.30 (dt, J
) 11.4, 3.7 Hz, 1 H), 4.37 (dt, J ) 4.0, 11.4 Hz, 1 H), 5.00 (m,
1 H), 7.32 (d, J ) 8.1 Hz, 2 H), 7.91 (d, J ) 8.1 Hz, 2 H). Anal.
Calcd for C14H17NO6S: C, 51.36; H, 5.24; N, 4.28; S, 9.79.
Found: C, 51.41; H, 5.10; N, 4.21; S, 9.51.
tr a n s-4-[(Meth oxycar bon yl)m eth yl]-6-ph en yl-3-tosyltet-
r a h yd r o-1,3-oxa zin -2-on e (12b): mp 122.0-123.0 °C (ben-
zene-hexane); IR (KBr disk) 1735 (s) cm-1; 1H NMR (400 MHz,
CDCl3) δ 2.21 (m, 1 H), 2.45 (s, 3 H), 2.48 (m, 1 H), 2.89 (dd,
J ) 10.6, 16.1 Hz, 1 H), 3.30 (dd, J ) 3.3, 16.1 Hz, 1 H), 3.77
(s, 3 H), 5.04 (m, 1 H), 5.60 (dd, J ) 2.9, 12.1 Hz, 1 H), 7.21-
7.40 (m, 7 H), 7.94 (d, J ) 8.4 Hz, 2 H); NOE for one of the
CH2CO2Me protons (8.5%) by irradiation at C6H. Anal. Calcd
for C20H21NO6S: C, 59.54; H, 5.25; N, 3.47; S, 7.95. Found:
C, 59.36; H, 5.18; N, 3.44; S, 7.98.
cis-1-[(Meth oxyca r bon yl-2-m eth oxyca r bon yl)m eth yl]-
3-[(tosylca r ba m oyl)oxy]p yr r olid in e (13a ): mp 141.5-142.0
°C (dichloromethane-hexane); IR (KBr disk) 1740 (s), 1665
1
(s) cm-1; H NMR (400 MHz, DMSO-d6, 100 °C) δ 1.73 (m, 1
H), 2.03 (m, 1 H), 2.40 (s, 3 H), 2.66 (dd, J ) 5.5, 17.6 Hz, 1
H), 3.14 (dd, J ) 8.1, 17.6 Hz, 1 H), 3.31 (m, 1 H), 3.43 (m, 1
H), 3.49 (s, 3 H), 3.60 (s, 3 H), 4.15 (dt, J ) 8.1, 5.5 Hz, 1 H),
5.19 (q, J ) 5.5 Hz, 1 H), 6.96 (br s, 1 H), 7.39 (d, J ) 8.1 Hz,
2 H), 7.75 (d, J ) 8.1 Hz, 2 H). [trans-13a : 1H NMR (400
MHz, DMSO-d6, 100 °C) δ 1.73 (dt, J ) 19.1, 6.6 Hz, 1 H),
1.91 (dt, J ) 19.1, 6.6 Hz, 1 H), 2.37 (s, 3 H), 2.54 (d, J ) 7.0
Hz, 2 H), 3.28-3.35 (m, 2 H), 3.56 (s, 3 H), 3.57 (s, 3 H), 4.05
(q, J ) 7.0 Hz, 1 H), 4.25 (q, J ) 6.6 Hz, 1 H), 6.95 (br s, 1 H),
7.32 (d, J ) 8.1 Hz, 2 H), 7.71 (d, J ) 8.1 Hz, 2 H).] Anal.
Calcd for C17H22N2O8S: C, 49.27; H, 5.35; N, 6.76; S, 7.73.
Found: C, 48.87; H, 5.20; N, 6.65; S, 7.81.
cis-2-[(Meth oxycar bon yl)m eth yl]-1-(ph en ylcar bam oyl)-
3-[(tosylca r ba m oyl)oxy]p yr r olid in e (13b): mp 138.5-140.0
°C (dichloromethane-hexane); IR (KBr disk) 3380 (m), 1740
(s), 1650 (s) cm-1; 1H NMR (400 MHz, DMSO-d6) δ 1.85 (m, 1
H), 2.11 (m, 1 H), 2.28 (dd, J ) 9.2, 16.1 Hz, 1 H), 2.40 (s, 3
H), 2.77 (dd, J ) 5.1, 16.1 Hz, 1 H), 3.36-3.54 (m, 2 H), 3.46
(s, 3 H), 4.31 (dt, J ) 9.2, 5.1 Hz, 1 H), 5.22 (q, J ) 5.1 Hz, 1
H), 6.95 (d, J ) 7.3 Hz, 1 H), 7.21 (br s, 1 H), 7.22 (d, J ) 7.3
Hz, 2 H), 7.44 (d, J ) 7.3 Hz, 2 H), 7.46 (d, J ) 8.1 Hz, 2 H),
7.79 (d, J ) 8.1 Hz, 2 H), 8.26 (br s, 1 H); NOE for C2H (7.9%)
and one of the C4H2 methylene protons (3.8%) by irradiation
at C3H. Anal. Calcd for C22H25N3O7S: C, 55.57; H, 5.30; N,
8.84; S, 6.74. Found: C, 55.58; H, 5.26; N, 8.76; S, 6.65.
cis-3-Meth yl-7-[(tosylca r ba m oyl)oxy]-1,3-d ia za bicyclo-
[4.3.0]n on a n e-2,4-d ion e (13c): mp 196.5-197.5 °C (dichlo-
romethane-hexane); IR (KBr disk) 3045 (m), 1750 (s), 1720
tr a n s-6-ter t-Bu tyl-4-[(m eth oxyca r bon yl)m eth yl]-3-to-
syltetr a h yd r o-1,3-oxa zin -2-on e (12c): mp 142.0-143.0 °C
(dichloromethane-hexane); IR (KBr disk) 1730 (s) cm-1 1H
;
NMR (400 MHz, CDCl3) δ 0.92 (s, 9 H), 1.86 (dddd, J ) 1.5,
5.5, 12.5, 14.3 Hz, 1 H), 2.17 (dt, J ) 14.3, 2.6 Hz, 1 H), 2.43
(s, 3 H), 2.72 (dd, J ) 11.0, 15.8 Hz, 1 H), 3.17 (ddd, J ) 1.5,
3.7, 15.8 Hz, 1 H), 3.74 (s, 3 H), 4.06 (dd, J ) 2.6, 12.5 Hz, 1
H), 4.97 (dddd, J ) 2.6, 3.7, 5.5, 11.0 Hz, 1 H), 7.31 (d, J ) 8.1
Hz, 2 H), 7.91 (d, J ) 8.1 Hz, 2 H). [cis-13c: 1H NMR (400
MHz, CDCl3) δ 0.94 (s, 9 H), 1.77 (ddd, J ) 9.9, 11.7, 13.6 Hz,
1 H), 2.43 (s, 3 H), 2.47 (ddd, J ) 1.8, 8.4, 13.6 Hz, 1 H), 2.69
(dd, J ) 7.7, 16.9 Hz, 1 H), 3.03 (dd, J ) 2.9, 16.9 Hz, 1 H),
3.73 (s, 3 H), 3.79 (dd, J ) 1.8, 11.7 Hz, 1 H), 4.75 (dddd, J )
2.9, 7.7, 8.4, 9.9 Hz, 1 H), 7.32 (d, J ) 8.4 Hz, 2 H), 7.99 (d, J
) 8.4 Hz, 2 H).] Anal. Calcd for C18H25NO6S: C, 56.38; H,
6.57; N, 3.65; S, 8.36. Found: C, 56.31; H, 6.43; N, 3.73; S,
8.30.
1
(s), 1670 (s) cm-1; H NMR (400 MHz, CDCl3) δ 1.89 (dd, J )

2122 J . Org. Chem., Vol. 62, No. 7, 1997
Harayama et al.
13.2, 16.1 Hz, 1 H), 1.91 (dd, J ) 7.3, 13.9 Hz, 1 H), 2.35 (dd,
J ) 3.7, 16.1 Hz, 1 H), 2.36 (s, 3 H), 2.90 (ddt, J ) 3.7, 13.9,
10.6 Hz, 1 H), 2.99 (s, 3 H), 3.22 (dt, J ) 10.6, 7.3 Hz, 1 H),
3.47 (t, J ) 10.6 Hz, 1 H), 3.88 (dt, J ) 13.2, 3.7 Hz, 1 H), 5.13
(t, J ) 3.7 Hz, 1 H), 7.36 (d, J ) 8.1 Hz, 2 H), 7.71 (d, J ) 8.1
Hz, 2 H); NOE for C6H (10.8%) and one of the C8H2 methylene
protons (3.6%) by irradiation of the signal of C7H. Anal. Calcd
for C16H19N3O6S: C, 50.39; H, 5.02; N, 11.02; S, 8.40. Found:
C, 50.32; H, 4.91; N, 10.97; S, 8.45.
H), 3.56 (t, J ) 9.9 Hz, 1 H), 3.68 (s, 3 H), 3.93 (dd, J ) 4.8,
9.9 Hz, 1 H), 4.87 (d, J ) 3.3 Hz, 1 H), 6.55 (br s, 1 H), 7.34
(d, J ) 8.2 Hz, 2 H), 7.42 (d, J ) 8.2 Hz, 2 H), 7.61 (d, J ) 8.2
Hz, 2 H), 7.83 (d, J ) 8.2 Hz, 2 H); 13C NMR (75 MHz, CDCl3)
δ 21.7, 21.8, 29.3 (C4), 39.3 (CH2CO2Me), 46.4 (C5), 52.1
(CO2CH3), 79.5 (C3), 128.3, 128.4, 129.8, 129.9, 133.6, 135.1,
144.4, 145.5, 148.5 (CONHTs), 170.4 (CO2Me).] Anal. Calcd
for
C22H26N2O8S2: C, 51.76; H, 5.13; N, 5.49; S, 12.55.
Found: C, 51.77; H, 5.23; N, 5.30; S, 12.41.
cis-2-[(Meth oxyca r bon yl)m eth yl]-1-tosyl-3-[(tosylca r -
ba m oyl)oxy]p yr r olid in e (13d ): mp 151.0-152.5 °C (AcOEt-
hexane); IR (KBr disk) 3260 (m), 1775 (s), 1755 (s), 1745 (s)
Ack n ow led gm en t. We thank Mr. Y. Ohhama, NMR
Facility, for his splendid technical assistance. Support
by the Ministry of Education, Science, Sports and
Culture, J apanese Government, is gratefully acknowl-
edged.
1
cm-1; H NMR (400 MHz, CDCl3) δ 1.43 (m, 1 H), 1.76 (m, 1
H), 2.43 (s, 3 H), 2.44 (s, 3 H), 2.60 (dd, J ) 9.5, 16.9 Hz, 1 H),
3.03 (dd, J ) 4.8, 16.9 Hz, 1 H), 3.03 (dd, J ) 4.8, 16.9 Hz, 1
H), 3.28-3.40 (m, 2 H), 3.59 (s, 3 H), 3.95 (dt, J ) 9.5, 4.8 Hz,
1 H), 5.06 (br s, 1 H), 5.18 (q, J ) 4.8 Hz, 1 H), 7.33 (d, J ) 8.1
Hz, 2 H), 7.35 (d, J ) 8.1 Hz, 2 H), 7.70 (d, J ) 8.1 Hz, 2 H),7.88
(d, J ) 8.1 Hz, 2 H); 13C NMR (75 MHz, CDCl3) δ 21.6, 21.8,
31.6 (C4), 39.6 (CH2CO2Me), 46.9 (C5), 52.0 (CO2CH3), 76.0 (C3),
128.2, 128.3, 129.8, 129.9, 133.6, 135.1, 144.4, 145.5, 148.7
(CONHTs), 170.4 (CO2Me). [trans-13d : 1H NMR (400 MHz,
CDCl3) δ 1.90 (dd, J ) 6.6, 14.3 Hz, 1 H), 2.08 (m, 1 H), 2.44
(dd, J ) 9.9, 15.8 Hz, 1 H), 2.45 (s, 3 H), 2.55 (s, 3 H), 2.88
(dd, J ) 4.8, 15.8 Hz, 1 H), 3.11 (ddd, J ) 6.7, 9.9, 11.4 Hz, 1
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
compounds 4, 6, 8d , 8k , 10, and 12f (9 pages). This material
is contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
J O961988B