Amination of bis(trimethylsilyl)-1,2-bisketene to ketenyl amides, succinamides, and polyamides: Preparative and kinetic studies

Article abstract of DOI:10.1021/jo9825052

The reaction of the bisketene (Me₃SiC = C = O)₂ (1) with amines is facile and proceeds by two distinct steps forming first ketenylcarboxamides 3 and then succinamides 5. Successive reaction of 1 with two different amines gives mixed succinamides, while phenylhydrazine gives succinimide 7. The reactions of 1.8 equiv of 1 with 1,4-(H₂NCH₂)₂C₆H₄ gives α,ω- bisketenyldiamide 13, while equivalent amounts of 1 and diamines gave polymeric amides. Mixed ester amides 8 are formed by sequential reaction of 1 with an alcohol, followed by an amine, or vice versa. Kinetic studies of the amination reaction of 1 with excess amines in CH₃CN gave rate constants k(obs) for the formation of ketenylcarboxamides that were fit by the relationship k(obs) = k(a)[amine]² + k(b)[amine]³. Further reaction of the n-butyl ketenylcarboxamide 3b with n-BuNH₂ to give the succinamide 5b was first order in [n-BuNH₂], while the further reaction of the CF₃CH₂ ketenylcarboxyamide 3c with CF₃CH₂NH₂ to form 5c was fit by the equation k(obs) = k(c)[amine]²/(k(d)[amine] + 1). The reaction of 3b with CH₃OH to form the ester amide 8a is strongly accelerated compared to CH₃OH addition to the corresponding ketenyl ester and gives significant stereoselectivity for formation of erythro product, and both these effects, as well as the absence of higher order kinetic terms in the reaction of 3b with n-BuNH₂, may arise from coordination by the carboxamido group to the nucleophile.

Full text of DOI:10.1021/jo9825052

4690
J . Org. Chem. 1999, 64, 4690-4696
Am in a tion of Bis(tr im eth ylsilyl)-1,2-bisk eten e to Keten yl Am id es,
Su ccin a m id es, a n d P olya m id es: P r ep a r a tive a n d Kin etic Stu d ies
Annette D. Allen, Patrick A. Moore, Sharif Missiha, and Thomas T. Tidwell*
Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6
Received December 28, 1998
The reaction of the bisketene (Me3SiCdCdO)2 (1) with amines is facile and proceeds by two distinct
steps forming first ketenylcarboxamides 3 and then succinamides 5. Successive reaction of 1 with
two different amines gives mixed succinamides, while phenylhydrazine gives succinimide 7. The
reactions of 1.8 equiv of 1 with 1,4-(H2NCH2)2C6H4 gives R,ω-bisketenyldiamide 13, while equivalent
amounts of 1 and diamines gave polymeric amides. Mixed ester amides 8 are formed by sequential
reaction of 1 with an alcohol, followed by an amine, or vice versa. Kinetic studies of the amination
reaction of 1 with excess amines in CH3CN gave rate constants kobs for the formation of
ketenylcarboxamides that were fit by the relationship kobs ) ka[amine]2 + kb[amine]3. Further
reaction of the n-butyl ketenylcarboxamide 3b with n-BuNH2 to give the succinamide 5b was first
order in [n-BuNH2], while the further reaction of the CF3CH2 ketenylcarboxyamide 3c with
CF3CH2NH2 to form 5c was fit by the equation kobs ) kc[amine]2/(kd[amine] + 1). The reaction of
3b with CH3OH to form the ester amide 8a is strongly accelerated compared to CH3OH addition
to the corresponding ketenyl ester and gives significant stereoselectivity for formation of erythro
product, and both these effects, as well as the absence of higher order kinetic terms in the reaction
of 3b with n-BuNH2, may arise from coordination by the carboxamido group to the nucleophile.
The reactions of 1,2-bisketenes1 with oxygen nucleo-
philes (H2O1a,b,f and alcohols1a,c,g), electrophiles,1b,d diazo-
alkanes,1e alkenes,1e and alkynes1e have been studied in
our laboratory and give a diverse chemistry. The reaction
with amines is a prototypical reaction of ketenes2 and
has recently been the subject of theoretical2b,c and
mechanistic study.2d-j In agreement with our criticism3a
of earlier interpretations3b,c these theoretical studies2b,c
for the reaction of CH2dCdO with NH3 support a
mechanism involving initial attack at the CdO bond with
formation of an intermediate amide enol which then
isomerizes to the product amide (eq 1). A pathway for
addition to the CdO bond involving two molecules of
amine (eq 1) was favored over pathways involving direct
addition to the CdC bond.3b,c
Experimental studies2j of the amination of PhMe2-
SiCHdCdO and t-BuC(i-Pr)dCdO in CH3CN showed
higher than first-order dependences of the observed rate
constants on the [amine], whereas more reactive ketenes
in CH3CN2e,i or H2O2d showed only a first-order depend-
ence of kobs on [amine]. This difference was interpreted2j
to result from irreversibility of reaction of the reactive
ketenes with a single amine molecule, whereas for less
reactive ketenes the initial reaction was reversible and
later steps involving further amine molecules as in eq 1
are kinetically significant.
The reaction of 1,2-bisketenes with amines has not
been previously studied but is an attractive subject
because such reactions provide potential routes to a
variety of useful products. In particular, reactions with
diamines offer the potential of a novel route for the
formation of polyamides, including cyclic derivatives. We
now report an examination of some of these processes.
(1) (a) Zhao, D.-c.; Allen, A. D.; Tidwell, T. T. J . Am. Chem. Soc.
1993, 115, 10097-10103. (b) Allen, A. D.; Ma, J .; McAllister, M. A.;
Tidwell, T. T.; Zhao, D.-c. J . Chem. Soc., Perkin Trans. 2 1995, 847-
851. (c) Egle, I.; Lai, W.-Y.; Moore, P. A.; Renton, P.; Tidwell, T. T.;
Zhao, D.-c. J . Org. Chem. 1997, 61, 118-25. (d) Brown, R. S.; Christl,
M.; Lough, A. J .; Ma, J .; Peters, E.-M.; Peters, K.; Sammtleben, F.;
Sung, K.; Slebocka-Tilk, H.; Tidwell, T. T. J . Org. Chem. 1998, 63,
6000-6006. (e) Colomvakos, J . D.; Egle, I.; Ma, J .; Pole, D. L.; Tidwell,
T. Warkentin, J . J . Org. Chem. 1996, 61, 9522-9527. (f) Liu, R.; Marra,
R.; Tidwell, T. T. J . Org. Chem. 1996, 61, 6227-6232. (g) Dejmek, M.
M.; Selke, R. Angew. Chem. Int. Ed. Engl. 1998, 37, 1540-1542.
(2) (a) Tidwell, T. T. Ketenes; Wiley: New York, 1995. (b) Sung, K.;
Tidwell, T. T. J . Am. Chem. Soc. 1998, 120, 3043-3048. (c) Raspoet,
G.; Nguyen, M. T.; Kelly, S.; Hegarty, A. F. J . Org. Chem. 1998, 63,
9669-9677. (d) Andraos, J .; Kresge, A. J . J . Am. Chem. Soc. 1992,
114, 5643-5646. (e) Wagner, B. D.; Arnold, B. R.; Brown, G. W.;
Lusztyk, J . J . Am. Chem. Soc. 1998, 120, 1827-1834. (f) Frey, J .;
Rappoport, Z. J . Am. Chem. Soc. 1996, 118, 3994-3995. (g) Barton,
D. H. R.; Chung, S. K.; Kwon, T. W. Tetrahedron Lett. 1996, 37, 3631-
3634. (h) Birney, D. M.; Xu, X.; Ham, S.; Huang, X. J . Org. Chem.
1997, 62, 7114-7120. (i) Liu, R. Y.-c.; Lusztyk, J .; McAllister, M. A.;
Tidwell, T. T.; Wagner, B. D. J . Am. Chem. Soc. 1998, 120, 6247-
6251. (j) Allen, A. D.; Tidwell, T. T. J . Org. Chem. 1999, 64, 266-271.
(3) (a) Seikaly, H. R.; Tidwell, T. T. Tetrahedron 1986, 42, 2587-
2613. (b) Lillford, P. J .; Satchell, D. P. N. J . Chem. Soc. B 1967, 360-
365. (c) Lillford, P. J .; Satchell, D. P. N. J . Chem. Soc. B 1970, 1016-
1019.
Resu lts a n d Discu ssion
The stable bis(trimethylsilyl)-1,2-bisketene 1,1a formed
from the corresponding cyclobutenedione 2, exists pref-
erentially in a twisted conformation.4 The products from
reaction of 1 with amines are summarized in Scheme 1.
(4) (a) Allen, A. D.; Ma, J .; McAllister, M. A.; Tidwell, T. T.; Zhao,
D.-c.; Acc. Chem. Res. 1995, 28, 265-271. (b) Allen, A. D.; Tidwell, T.
T. Chem. Commun. 1996, 2171-2172.
10.1021/jo9825052 CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/06/1999

Amination of Bis(trimethylsilyl)-1,2-bisketene
J . Org. Chem., Vol. 64, No. 13, 1999 4691
Sch em e 1
Ta ble 1. Id en tifyin g An a lytica l F ea tu r es of Keten yl
Am id es
Partial separation of meso- and d,l-5c was effected by
recrystallization. Analogously to our examination1c of the
formation of succinates from the reaction of 1 with
alcohols, the identity of the separated diastereomers of
5a were ascertained from the chemical shifts and from
the vicinal coupling constants of the protons on C2 and
C3 obtained from the natural abundance 13C satellites in
IR (cm-1
)
13C NMR δ (CâdCRdO)
ketenes
CdCdO
CONH
Câ
CR
3a
3b
13
2081
2077
2085
1653
1653
1649
2.0
10.7
10.7
179.6
179.8
179.6
1
the H NMR,5b with the meso and d,l diastereomers in
the favored conformations shown. Comparable results
had been obtained for the corresponding succinate esters,1c
for which the structural and conformational assignments
were confirmed by X-ray crystallography.1c
Reactions of 1 with 1 equiv of PhCH2NH2 or n-BuNH2 in
CH2Cl2 proceed efficiently to give ketenyl amides 3a ,b,
respectively, as the only observable products, as estab-
lished by their spectral properties, especially the distinc-
tive IR and 13C NMR absorptions of the CdCdO group
(Table 1).
After 8 days at 0 °C in CH2Cl2 3a reacted completely
as shown by 1H NMR and IR to give a product tentatively
identified as a mixture of the succinimide 4a and de-
silylated products, and for characterization this mixture
was converted by n-Bu4NF in THF to benzyl succinimide
4b.5a The reaction of 1 with 1 equiv of CF3CH2NH2
proceeded slowly and after 3 h on the basis of the 1H
NMR spectrum gave 40% unreacted 1, 35% of ketenyl-
amide 3c, and 25% of a product analogous to 4a .
Reaction of 1 with 2 equiv of PhCH2NH2 or n-BuNH2,
or 6 equiv of CF3CH2NH2, in CH2Cl2 at room temperature
gave complete conversion to almost equal amounts of the
diastereomeric meso- and dl-succinamides 5, evidently
through the ketenyl amides 3. Chromatography of 5a
caused significant amounts of desilylation, but the meso
and d,l isomers were separated in a total yield of 30%.
Reaction of 1 in CH2Cl2 with 1 equiv of PhCH2NH2
followed by addition of 1 equiv of n-BuNH2 and evapora-
tion of the solvent gave the mixed diamides 6 in 95%
crude yield and 94% purity by H NMR analysis, as a
2/1 mixture of the erythro and threo diastereomers. These
1
were separated by chromatography and identified by
1
their characteristic H coupling constants.5b
Reaction of 1 with phenylhydrazine in CH2Cl2 gave
complete conversion to succinimide 7 with a 90% prefer-
ence for one stereoisomer, which was separated in 95%
purity by chromatography. The structures of the analo-
gous cis- and trans-succinic anhydrides were established
by X-ray crystallography,1a but even with this comparison
the stereochemistry of 7 is not certain.5b
(5) (a) Puertas, S.; Rebolledo, F.; Gotor, V. Tetrahedron 1995, 51,
1495-1502. (b) See the Experimental Section and the summary in
Table 3 (Supporting Information).

4692 J . Org. Chem., Vol. 64, No. 13, 1999
Allen et al.
The reaction of 3b with CH3OH gave a > 9/1 preference
for formation of the erythro mixed ester amide 8a with a
conformation analogous to that shown for meso-5 on the
basis of the large vicinal H,H coupling constant of 11.5
Hz. The product-forming step in ketene esterification
involves protonation at Câ of an intermediate ester enol,
and a model (9) is shown for the observed selectivity with
assistance by the amide oxygen in proton transfer by
CH3OH. This structure minimizes the interaction be-
tween the bulky Me3Si groups in the transition state.
amides. The bisketene 13 was too sensitive for purifica-
tion but was identified by its spectral characteristics
(Table 1).
Reaction of 1 with 1.2 equiv of 12 at -78 °C in CH2Cl2
followed by warming to 25 °C and evaporation of the
1
solvent gave a white solid which by H NMR in CD3OD
has the structure 14 (eq 3), with a 4/1 preference for the
erythro configuration of the vicinal succinic R-protons (δ
2.15) over the meso configuration (δ 2.45). Integration
showed the benzylamino (s, δ 3.8, CH2NH2) and benzyl-
amido (m, δ 4.2, CH2NHCO) protons in a 1/8 ratio
consistent with a value for n of 8 (eq 3).
Exposure of 1 to neat MeOH followed by rapid removal
of the excess MeOH gave complete conversion to the
ketenyl ester 10a , as reported previously.1a Reaction of
10a with 1 equiv of PhCH2NH2 in CH2Cl2 led to the
succinyl ester amide 8b as a mixture assigned as the
erythro and threo diastereomers5b together with the
desilylated product 11a in a ratio of 63:27:10, respec-
tively. The regioselectivity for formation of 11a arises
from a greater lability of groups R to the ester as opposed
to amide groupings and was confirmed by the coupled
13C NMR spectrum which showed that the carbon adja-
cent to the ester bears 2 protons. In other similar
experiments, much less of the desilylated product 11a
was observed in the initial product, which contained
erythro- and threo-8b in a 2:1 ratio. Upon chromato-
graphic separation, extensive desilylation occurred, and
the maximum yields of purified erythro- and threo-8b and
11a , were 20, 25, and 15%, respectively.
Reaction of 1 with an equimolar amount of 1,6-hex-
anediamine led to a product with spectra attributable to
the oligomeric amide 15 (eq 4). The IR spectrum showed
the absence of ketenyl absorption near 2100 cm-1 and
the presence of amide absorption at 1650 and 1499 cm-1
,
1
and the H NMR spectrum showed signals at δ 3.15 due
to the CH2 group adjacent to amido nitrogen CONHCH2
and δ 5.9 for the CH2 group next to amino nitrogen
H2NCH2 in a 4/1 ratio, as well as the other signals
expected for 15 with n ) 4.
Reaction of 1 with 0.95 equiv of benzyl alcohol cata-
lyzed by Et3N led to the ketenyl ester 10b, which was
identified by the 1H NMR spectrum of the reaction
mixture. The use of Et3N to catalyze alcohol addition to
1 has not been reported previously and greatly acceler-
ates the process. Addition of PhCH2NH2 to 10b gave the
erythro and threo ester amides 8c, along with the
desilylated product 11b in a ratio of 62:22:16, respectively
as determined by 1H NMR. Upon chromatography,
erythro-8c and 11b were isolated in pure form and fully
characterized.
Kin etic In vestiga tion s
We have also recently utilized the methodology of
reacting bisketene 1 with methyl poly(ethylene glycol)
(MPEGOH) to form a soluble polymer-supported ketenyl
ester analogous to 10 (R2 ) MPEGO) which reacted with
amines to form polymer-supported ester amides analo-
gous to 8.6 These were desilylated and cleaved from the
polymer support to give either succinimides or ester
amides.6
The kinetics of the reaction of 1 with excess n-BuNH2
(0.188 × 10-2 to 4.02 × 10-2 M) and with CF3CH2NH2
(0.0213 to 0.256 M) in CH3CN to form ketenyl amides
3b and 3c (Scheme 1), respectively, were measured by
observing the decrease in absorption near 386 nm using
stopped-flow or conventional UV spectroscopy, and the
derived first-order rate constants are reported in Table
4 (Supporting Information). With [n-BuNH2] from 0.02
to 0.25 M and [CF3CH2NH2] from 0.341 to 2.10 M and
longer time scales, the pseudo-first-order rate constants
for reaction of the intermediate ketenyl amides 3b and
3c to form the bisamides 5b and 5c were measured at
331 nm, as reported in Table 5 (Supporting Information).
Ketenyl amide 3b was also generated in a preparative
reaction (Scheme 1), and its UV spectrum showed the
same λmax at 332 nm observed in the kinetic experiments.
Reaction of 1,4-di(aminomethyl)benzene (12) with 1 in
a 1/1.8 molar ratio in CH2Cl2 at room temperature for
10 min followed by evaporation of the solvent gave a
1
white solid product that by H NMR was identified as
the bisketene 13 (eq 2) containing 8% of succinamide
products, with the latter identified by the characteristic
1H NMR signals at δ 2.03 and 2.33 typical of succin-
(6) Rafai Far, A.; Tidwell, T. T. J . Org. Chem. 1998, 63, 8636-8637.

Amination of Bis(trimethylsilyl)-1,2-bisketene
J . Org. Chem., Vol. 64, No. 13, 1999 4693
Ta ble 2. Su m m a r y of Ra te Con sta n ts a t 25 °C for Rea ction s of Bisk eten e 1 a n d Keten yl Am id es 3 w ith Nu cleop h iles in
CH3CN a n d Com p a r ison to P h Me2SiCHdCdO (16)
ketene
nucleophile
ka (M-2 s-1
)
kb (M-3 s-1
)
ka(1)/ka(16)
kb(1)/kb(16)
1
n-BuNH2
CF3CH2NH2
(1.73 ( 0.10) × 106
(2.39 ( 0.58) × 107
7.6
18
6.3
9.2
(5.37 ( 0.18)
(2.03 ( 0.89)
k
obs(1)/kobs(3)
kobs(16)/kobs (3)
3b
3c
n-BuNH2
CH3OH
CF3CH2NH2
kobs ) (2.11 ( 0.03) M-1 s-1
kobs ) 1.56 × 10-2 s-1
(2.4-3.7) × 104 a
1.4 × 104 b
0.59c
kc ) (6.66 ( 0.39) × 10-4 M-2 s-1
kd ) 0.148 ( 0.044 M-1
9.3 × 103 d
5.4 × 102 d
2.4 × 104 and 3.8 × 104 at [n-BuNH2] ) 0.040 and 0.020 M, respectively. [n-BuNH2] ) 0.050 M. c In neat CH3OH. [CF3CH2NH2]
a
b
d
) 0.256 M.
The further reaction of the ketenyl amide 3b to form
the bisamide 5b gave a linear correlation of kobs with
[n-BuNH2] (Figure 2), while the reaction of 3c with
CF3CH2NH2 to form 5c was fit by eq 8 (Figure 3,
Supporting Information), with a second-order but no
third-order term in [amine] (Table 2). Previously2j this
latter behavior was found for reaction of the monoketene
t-BuC(Pr-i)dCdO with n-BuNH2, and the rate expression
of eq 8 was derived from the reaction scheme in eq 9,
with kc ) k2k1/k-1 and kd ) k2/k-1
.
kobs ) kc[amine]2/(kd[amine] + 1)
(8)
k2
ketene + amine yk1z complex amine8 product (9)
k-1
In the reaction of 3b with n-BuNH2 the initial step is
evidently irreversible. This behavior has been found for
reactive ketenes2d,e but is unusual for 3b which is rather
unreactive and is less reactive than PhMe2SiCHdCdO
by a factor of 1.4 × 104 (Table 2).
Previously2j we suggested that for more reactive ketenes
the instability of the reactant meant that further reaction
of the initial ketene-amine adduct was faster than
reformation of the reactant, and so the initial step was
irreversible. However, as noted, 3b is quite unreactive
compared to 1. As shown in eq 1, the function of the
second amine molecule is to provide assistance in forma-
tion of an amide enol intermediate, and for 3b the amide
present in the molecule may assume this role, as depicted
in 17. A significant rate enhancement for the addition of
CH3OH to 3b is also suggested to involve assistance by
the carboxamido group (vide infra).
F igu r e 1. Fit of kobs versus [CF3CH2NH2] for monoamination
of (Me3SiCdCdO)2 (1) by eq 5.
Reaction of 3b from the preparative reaction with 0.0200
M n-BuNH2 to form 5b gave kobs ) 2.66 × 10-2 s-1, in
satisfactory agreement with the value 2.34 × 10-2 s-1
obtained in the kinetic experiments beginning with 1.
The dependence of the measured rate constants for the
amination of bisketene 1 to form 3b and 3c are fit by eq
5, as summarized in Table 2 and illustrated in Figure 1
for reaction with CF3CH2NH2. Previously2j we found that
rate data for the monoketene PhMe2SiCHdCdO (16)
with amines were also fit by eq 5, and this rate expression
was derived from the reaction scheme in eqs 6 and 7,
which involves a complex of the ketene with two amine
molecules.
kobs ) ka[amine]2 + kb[amine]3
(5)
In the addition of CF3CH2NH2 to 3c, the poorly
nucleophilic amine has a strong tendency to leave and
reversibly reform the starting material, and a second
amine molecule is needed to stabilize a transition struc-
ture analogous to that shown in eq 1. J ust as in the
reaction of t-BuC(Pr-i)dCdO with n-BuNH2, which also
is fit by eq 8,2j the reaction of 3c with a second amine is
a slow process with a crowded substrate and so leads
irreversibly to product.
Because of the different rate expressions for the first
and second reactions of 1 with amines, the rate ratio of
bisketene 1 relative to ketenyl amide 3 depends on
[amine] and varies from (9.3-37) × 103 (Table 2). These
large ratios for amines of widely different reactivity show
k2
9
ketene + 2 amine yk1z complex
8 product (6)
(7)
k-1
k3
9
complex + amine
8 product
The sizable rate constant ratios k(1)/k(16) in Table 2
show that just as in hydration and esterification bis-
ketene 1 is more reactive than less hindered monoketenes.
For 1 the very large rate constant ratios kn-BuNH
/
2
kCF
(Table 2) are comparable to those found for
3CH2NH2
PhMe2SiCHdCdO (16),2j confirming the strong de-
pendence of ketene reactivity on amine basicity.

4694 J . Org. Chem., Vol. 64, No. 13, 1999
Allen et al.
For the monoketene PhMe2SiCHdCdO (16), the ratio
k(n-BuNH2)/k(H2O) is estimated2j at a [nucleophile] of
11.1 M to be as high as 1013, and this is significantly
greater than for 1, which was estimated as 2.9 × 106 (vide
supra). In another comparison,2i the measured rate ratio
k(Et2NH)/k(H2O) in CH3CN is 73 for the highly reactive
oxoketene 19, and both reactions are first order in
[nucleophile]. Although these substrates react by differ-
ent mechanisms with different rate laws, it is neverthe-
less apparent that there are enormous differences in the
selectivities of different ketenes for different nucleophiles.
F igu r e 2. Plot of kobs versus [n-BuNH2] for amination of
carboxamide ketene 3b.
why preparative selective monoamination is feasible. The
rate constant ratios k(1)/k(16) of 6.3-18 illustrate that
even though the bisketene 1 is more crowded than PhMe2-
SiCHdCdO, the former is significantly more reactive.
Previously we have pointed out that 1,2-bisketenes, in
which the adjacent â-carbons of the ketenyl groups both
bear substantial negative charge, suffer from ground-
state destabilization due to repulsive interactions be-
tween the two ketenyl groups.4a This effect, rather than
any stabilization of a conjugated intermediate from
reaction of a bisketene, was assigned as the cause of the
relatively high reactivity of bisketenes. For comparison,
the rate of hydration of 1 is similar to that of 16,1f and
hydration of 1 produces an intermediate ketenyl car-
boxylic acid, which cyclizes to a succinic anhydride with
a rate constant 2.2 times less than the initial hydration.1b
The amination rate constants of the monoketene
PhMe2SiCHdCdO (16)2j are greater than the corre-
sponding values for the ketenyl amides 3 by factors 5.4
× 102 and 1.4 × 104 (Table 2), reflecting the steric
crowding in 3. The rate ratio k(n-BuNH2)/k(H2O) for the
bisketene 1 is concentration dependent, and at the lowest
[H2O] studied,1a 11.1 M, the value of k2 ) kobs[H2O]-1 is
2.7 × 10-4 M-1 s-1, and this value is 2.9 × 106 less than
k2 for reaction with n-BuNH2 found here. This is some-
what larger than the ratio k(n-BuNH2)/k(H2O) ) 7.1 ×
104 estimated2j for Ph2CdCdO in H2O.
The rate constant for reaction of the amide-substituted
ketene 3b in neat CH3OH forming ester amide 8a was
determined as 1.56 × 10-2 s-1 at 25 °C (Table 2), and
this is the first measurement of the rate constant for such
a reaction. Surprisingly this rate constant exceeds that
of 9.21 × 10-3 s-1 found1a for the reaction of bisketene 1
with CH3OH, and the rate ratio k(1)/k(3b) with CH3OH
is 0.59, much less than the ratio k(1)/k(3b) with n-BuNH2
of (2.4 to 3.7) × 104 (Table 2). The further reaction with
CH3OH of the ester-substituted ketene 10a from 1 was
also clearly slower than the first reaction of 1 by a
significant factor, estimated to be at least 10.1a This
suggests a significant accelerating effect of CH3OH
addition by hydrogen-bonding assistance provided by the
amido group as shown in 18. A similar assistance by the
carboxamido group in stabilizing the n-BuNH2 adduct of
3b is represented by 17 (vide supra). As discussed above,
there is also a significant selectivity for forming erythro-
8a and model 9 involving carboxamide assistance of
proton transfer to Câ in an intermediate ester enol was
suggested to explain the stereoselectivity of the process.
In summary, amination reactions of 1,2-bisketene 1 are
facile and proceed in discrete steps to give ketenyl amides
and then succinamides. Mixed succinamides and ester
amides may also be prepared, and the reactions of
diamides lead to new bisketenes and to polyamides. The
rate constants for reaction of 1 with amines depend on
both [amine]2 and [amine]3, but the rate laws for the
further reaction of the resulting ketenyl amides 3 depend
on the particular amine. The reaction of ketenyl amide
3b with MeOH shows a selectivity for erythro product
stereochemistry and a large rate acceleration consistent
with specific interactions of the carboxamido group with
MeOH as shown in 9 and 18, respectively. The rate law
for reaction of 3b with n-BuNH2 also suggests carbox-
amido assistance as shown by 17.
Exp er im en ta l Section
Infrared (IR) spectra were recorded on a Perkin-Elmer FTIR
1000 spectrometer. 1H NMR spectra were recorded on Varian
VXR-200 or Varian Unity-400 instruments referenced to
residual CHCl3 (7.26 ppm). 13C NMR spectra are referenced
to the center line of CDCl3 (77.00 ppm). Reactions were carried
out in flame- or oven-dried glassware under an atmosphere of
N2 or Ar.
N-Ben zyl-2,3-b is(t r im et h ylsilyl)-4-oxob u t -3-en a m id e
(3a ). Bisketene 1 (200 mg, 0.886 mmol) in 3 mL of CH2Cl2
was added in one portion to a stirred solution of PhCH2NH2
(96 µL, 71 mg, 0.98 mmol) in 3 mL of CH2Cl2 at room
temperature. After 5 min the solution was stored at -70 °C,
a 0.5 mL aliquot was removed, and the solvent was evaporated
at room temperature. Analysis by 1H NMR showed the
monoketene as the only identifiable product, in 95% purity by
1H NMR analysis: 1H NMR (CDCl3) δ 0.132 (s, 9, Me3Si), 0.155
(s, 9, Me3Si), 1.92 (s, 1, CHCO), 4.42 and 4.44 (ea s, PhCH2),
6.09 (m, 1, NH), 7.29 (m, 5, Ph);13C NMR (CDCl3) δ -1.9, -1.0,
2.0, 10.8, 44.0, 127.3, 127.8, 128.5, 138.3, 173.1, 179.6; IR
(CDCl3) 3343 (w) NH, 2081 (CdCdO), 1653 (CON) cm-1; EIMS
m/z 333 (M+, 34), 242 (M+ - PhCH2, 61), 91 (C7H7+, 70), 73
(Me3Si+, 100); HRMS m/z calcd for C17H27NO2Si2 333.1580,
found 333.1577.
Cycliza tion of 3a . A solution of 3a (0.50 mmol) prepared
as above in 4.5 mL of CH2Cl2 was left at 0 °C for 8 day, and
upon evaporation of the solvent no remaining 3a was visible
in the IR or 1H NMR spectra, but 1H NMR multiplets in the

Amination of Bis(trimethylsilyl)-1,2-bisketene
J . Org. Chem., Vol. 64, No. 13, 1999 4695
region δ 2.3-3.3 were suggestive of the presence of succinimide
4a and desilylation products. The product mixture was stirred
with n-Bu4NF (1.5 mL, 1.0 M in THF) in 3 mL of THF for 10
min and then diluted with 10 mL of H2O and extracted with
5 mL of ether. The organic extract was dried and evaporated
to give 4b5 as the major product by 1H NMR, and this was
purified by chromatography (2% MeOH in CH2Cl2) and identi-
d,l-5c 1H NMR (CDCl3) δ 0.11 (s, 18, Me3Si), 2.11 (s, 2,
CHSiMe3), 3.75-3.95 (m, 4, CH2CF3), 7.75 (bs, 2, NH); 13C
NMR (CDCl3) δ -1.75, 38.5, 40.7 (q, 2J CF ) 34.4 Hz), 124.2 (q,
1J CF ) 279 Hz), 175.0; 5c IR (CDCl3) 3452, 1670, 1508 cm-1
;
EIMS m/z 424 (46, M+), 73 (100, Me3Si+); HRMS m/z calcd for
C
14H26F6N2O2Si2 424.1437, found 424.1453.
Reaction of 1 (7.7 mg, 0.034 mmol) in 0.7 mL of CD2Cl2 with
1
fied by H NMR (CDCl3) peaks at δ 2.71 (s, 4, CH2CH2), 4.66
(s, 2, CH2), and 7.3-7.4 (m, 5, Ph).
CF3CH2NH2 (2.7 µL, 0.034 mmol) in an NMR tube gave after
3 h a product tentatively assigned by the 1H NMR spectrum
to contain 35% 3c: 1H NMR (CDCl3) 0.17 (s, 9, Me3Si), 2.10
(s, 1, CHSiMe3), 3.8-4.1 (m, 2, CH2CF3), 6.12 (s, 1, NH).
N-Ben zyl-N′-n -b u t yl 2,3-b is(t r im et h ylsilyl)b u t a n ed i-
a m id e (6). To a solution of 3a (0.71 mmol, generated in situ
from 0.71 mmol of 1 and 0.71 mmol of PhCH2NH2) in 8 mL of
CH2Cl2 at room temperature was added n-BuNH2 (70 µL, 0.71
mmol) in one portion. After 3 min of stirring, the solvent was
evaporated, giving 6 as a 2/1 mixture of erythro/threo dia-
stereomers in 95% crude yield and 94% purity by 1H NMR.
Chromatography (2% MeOH in CH2Cl2) gave the purified
isomers. erythro-6 (78 mg, 0.19 mmol, 27%), mp 141-144 °C:
1H NMR (CDCl3) δ 0.051 (s, 9, Me3Si), 0.055 (s, 9, Me3Si), 0.90
(t, 3, CH3), 1.3 (m, 2, CH2Me), 1.4 (m, 2, CH2Et), 2.32 (d, 1, J
) 11.2 Hz, CHCO), 2.36 (d, 1, J ) 11.2 Hz, CHCO), 3.16 (m,
2, NCH2Pr-n), 4.33 (dd, 2, CH2Ph), 5.55 (t, 1, NH), 5.90 (t, 1,
NH), 7.31 (m, 5, Ph); 13C NMR (CDCl3) δ -1.34, -1.30, 13.8,
20.2, 31.7, 37.2, 37.3, 39.3, 44.0, 127.4 128.3, 128.6, 138.1,
173.6, 173.7; IR (CDCl)3 3445, 3330, 1664, 1628 cm-1; EIMS
m/z 406, (M+, 22), 391 (M+ - CH3, 22), 315 (M+ - C7H7, 40),
200 (29), 147 (24), 91 (C7H7+, 100), 73 (Me3Si+, 77); HRMS m/z
calcd for C21H38N2O2Si2 406.2472, found 406.2484. threo-6 (26
mg, 0.064 mmol, 9%) mp 126-128 °C: 1H NMR (CDCl3) δ
0.079 (s, 9, Me3Si), 0.83 (s, 9, Me3Si), 0.92 (t, 3, CH3), 1.37 (m,
2, CH2Me), 1.50 (m, 2, CH2Et), 1.98 (d, 1, J ) 5.2 Hz, CHCO),
2.02 (d, 1, J ) 5.2 Hz, CHO), 3.2 (m, 2, CH2Pr-n), 4.4 (m, 2,
CH2Ph), 7.3 (m, 5, Ph); 7.36 (s, 1, NH); 7.87 (s, 1, NH). 13C
NMR (CDCl3) δ -1.37, -1.30, 13.8, 20.3, 31.7, 38.4, 38.5, 39.6,
43.9, 127.2, 128.1, 128.5, 138.5, 174.3, 174.4; IR (CDCl3) δ 3445,
N-n -Bu tyl-2,3-bis(tr im eth ylsilyl)-4-oxobu t-3-en a m id e
(3b). To bisketene 1 (265 mg, 1.17 mmol) in 4 mL of CH2Cl2
stirred at 25 °C was added n-BuNH2 (114 µL, 84.4 mg, 1.15
mmol) in 3 mL of CH2Cl2. After the exothermic reaction, the
solution was stirred 5 min and then cooled to -70 °C for
storage. A 1 mL aliquot was evaporated to give 3b as a white
solid, mp 73-77 °C: 1H NMR (CDCl3) δ 0.148 (s, 9, Me3Si),
0.155 (s, 9, Me3Si), 0.91 (t, 3, J ) 7.3 Hz, CH3), 1.3-1.6 (m, 4,
CH2CH2), 1.85 (s, 1, CH), 3.2-3.3 (m, 2, NCH2); 13C NMR
(CDCl3) δ -2.09, -1.06, 10.7, 13.6, 20.1, 31.9, 32.1, 39.5, 173.1,
CH CN
179.8; IR (CH2Cl2) 3443, 2077, 1653, 1509 cm-1; UV λmax
3
332 nm, ꢀ ) 40; EIMS m/z 299 (M+, 21), 198 (M+ - CONH2-
Bu-n, 100), 73 (Me3Si+, 67); HRMS m/z calcd for C14H29NO2-
Si2 299.1737, found 299.1738.
N,N′-Diben zyl-2,3-bis(tr im eth ylsilyl)su ccin a m id e (m e-
so- a n d d ,l-5a ). Bisketene 1 (206 mg, 0.912 mmol) in 3 mL of
CH2Cl2 was added in one portion to a stirred solution of
benzylamine (198 µL, 1.81 mmol) in 3 mL of CH2Cl2 at room
temperature, with transient generation of a pink color. After
2 min of stirring, the solvent was evaporated, giving crude 5a
(0.37 mg, 0.84 mmol, 92%) which by 1H NMR analysis
consisted of meso- and d,l-5a in a 1.0/1.0 ratio, with about 4%
of an impurity tentatively identified as a desilylated product.
Radial chromatography on silica gel (2% Et3N in CH2Cl2)
separated the diastereomeric products: meso-5a (89 mg, 0.20
1
mmol, 22%) mp 149-152 °C; H NMR (CDCl3) δ 0.06 (s, 18,
Me3Si), 2.39 (s, 2, J C,H ) 125 Hz, J H,H ) 11.1 Hz, CHSiMe3),
4.31 (d, 4, CH2Ph), 5.89 (t, 2, NH), 7.3 (m, 10, Ph); 13C NMR
(CDCl3) δ -1.2, 37.2, 44.0, 127.4, 128.3, 128.5, 138.0, 173.6;
IR (CDCl3) 3446, 1649, 1499 cm-1; EIMS m/z 440 (M+, 14),
349 (M+ - Bn, 26), 91 (PhCH2+, 100), 73 (Me3Si+, 54); HRMS
m/z calcd for C24H36N2O2Si2 440.2315, found 440.2309. d,l-5a
(32 mg, 0.073 mmol, 8%) mp 146-148 °C;1H NMR (CDCl3) 0.07
(s, 18, Me3Si), 2.05 (s, 2, J C,H ) 119 Hz, J H,H ) 5.1 Hz), 4.35
(m, 4, CH2Ph), 7.3 (m, 10, Ph), 7.82 (bs, 2, NH); 13C NMR
(CDCl3) δ -1.3, 38.4, 44.0, 127.2, 128.1, 128.5, 138.4, 174.3;
IR (CDCl3) 3447, 1649, 1503 cm-1; EIMS m/z 440 (M+, 10),
349 (M+ - PhCH2, 21), 91 (C7H7+, 100), 73 (Me3Si+, 40); HRMS
m/z calcd for C24H36N2O2Si2 440.2315, found 440.2319.
3257, 1656, 1621 cm-1; EIMS m/z 406 (M+, 31), 315 (M+
-
C7H7, 70), 91 (C7H7+, 100); 73 (Me3Si+, 87); HRMS m/z calcd
for C21H38N2O2Si2 406.2472, found 406.2470.
N-P h en ylim in o-3,4-bis(tr im eth ylsilyl)su ccin im id e (7).
To a stirred solution of 1 (173 mg, 0.763 mmol) in 3 mL of
CH2Cl2 at room temperature was added phenylhydrazine (75
µL, 0.76 mmol) in CH2Cl2. After 10 min of stirring, the solvent
was evaporated and 1H NMR analysis showed that one
stereoisomer of 7 was formed to the extent of 90%. Upon
chromatography (10% EtOAc in hexanes, silica gel) the major
stereoisomer was isolated in 95% purity, as a yellow solid, mp
144-158 °C (decomp): 1H NMR (CDCl3) δ 0.16 (s, 18, Me3Si),
2.34 (s, 2, CHCO), 6.08 (s, 1, NH), 6.8-7.2 (m, 5, Ph); 13C NMR
(CDCl3) δ -3.1, 33.4, 115.6, 122.7, 129.1, 132.1, 176.9; IR (CCl4)
3344 (w), 1703 cm-1; EIMS m/z 334 (M+, 42), 242 (M+ - NHPh,
52), 150 (32), 91 (19), 73 (Me3Si+, 100); HRMS m/z calcd for
N,N′-Di-n -bu tyl-2,3-bis(tr im eth ylsilyl)su ccin am ide (me-
so- a n d d ,l-5b). Bisketene 1 (182 mg, 0.804 mmol) in 3 mL of
CH2Cl2 was added in one portion to n-BuNH2 (158 µL, 1.60
mmol) as in the preparation of 5a . The solid product was
obtained in 85% crude yield and 89% purity by 1H NMR, with
a meso/dl ratio of 3/2: meso-5b 1H NMR (CDCl3) δ 0.06 (s, 18,
Me3Si), 0.92 (t, 6, CH3), 1.4 (m, 8, MeCH2CH2), 2.28 (s, 2,
CHSiMe3), 3.32 (m, 4, CH2N), 5.4 (t, 2, NH); d,l-5b 1H NMR
(CDCl3) δ 0.10 (s, 18, Me3Si), 0.92 (t, 6, CH3), 1.4 (m, 8,
MeCH2CH2), 1.96 (s, 2, CHSiMe3), 3.32 (m, 4, CH2N), 7.4 (t,
C
16H26N2O2Si2 334.1533, found 334.1525.
er yth r o-N-n -Bu tyl 2,3-bis(tr im eth ylsilyl)-4-m eth oxy-4-
oxobu ta n a m id e (8a ). Methanol (2 mL) was added to solid
3b (25 mg, 0.084 mmol) at room temperature, and after 5 min
the resulting solution was evaporated to give a pale yellow
2, NH); IR (CDCl3) 3447, 1651, 1508 cm-1
.
solid which by H NMR consisted of erythro-8a with less than
1
N,N′-Bis(tr iflu or oeth yl)-2,3-bis(tr im eth ylsilyl)su ccin -
a m id e (m eso- a n d d ,l-5c). To a stirred solution of bisketene
1 (131 mg, 0.58 mmol) in 3 mL of CH2Cl2 was added CF3CH2-
NH2 (0.280 mL, 3.52 mmol) at room temperature, and the
solution was stirred for 3 h. The 1H NMR showed 10% residual
1; therefore, 0.050 mL of additional CF3CH2NH2 was added,
the solution was stirred for 1.5 h, and the solvent was
evaporated to give a pale yellow solid that was not completely
10% of any impurities or isomeric byproducts. This was
recrystallized from pentane to give erythro-8a , mp 102-105
°C: 1H NMR (CDCl3) δ 0.045 (s, 9, Me3Si), 0.064 (s, 9, Me3Si),
0.91 (t, 3, J ) 7.3 Hz, CH3), 1.33 (sextet, 2, J ) 7.4 Hz, CH2),
1.47 (quintet, 2, J ) 7.1 Hz, CH2), 2.45 (d, 2, J ) 11.5 Hz,
CH), 2.66 (d, 2, J ) 11.5 Hz, CH), 3.18 (q, 2, J ) 7.1 Hz, CH2N),
3.59 (s, 3, OCH3), 5.28 (bs, 1, NH); 13C NMR (CDCl3) δ -1.80,
-1.46, 13.7, 20.2, 31.7, 35.4, 37.3, 39.3, 50.9, 173.1, 175.6; IR
(CDCl3) 3450, 1707, 1656, 1505 cm-1; EIMS m/z 331 (M+, 13),
258 (M+ - SiMe3, 41), 73 (Me3Si+, 75); HRMS m/z calcd for
1
soluble in CDCl3 and by H NMR contained meso- and d,l-5c
in a 1.2/1.0 ratio. The solid product was fractionated by partial
dissolution in 4/1 pentane/CH2Cl2 to give a soluble fraction
from which a solid rich in meso-5c crystallized on cooling and
an insoluble fraction rich in d,l-5c was obtained: meso-5c 1H
NMR (CDCl3) 0.079 (s, 18, Me3Si), 2.45 (s, 2, CHSiMe3), 3.9-
4.05 (m, 4, CH2CF3), 5.78 (bs, 2, NH); 13C NMR (CDCl3) δ
-1.59, 37.5, 40.6 (2J CF ) 34.4 Hz), 124.1 (1J CF ) 279 Hz), 174.1;
C
15H33NO3Si2 331.1999, found 331.2005.
N-Ben zyl-2,3-b is(t r im et h ylsilyl)-4-m et h oxy-4-oxob u -
ta n a m id e (8b). Bisketene 1 (259 mg, 1.14 mmol) was slowly
added via syringe to 13 mL of CH3OH at 0 °C, and after 7 min
of stirring, the CH3OH was evaporated at 25 °C to give ketenyl
ester 10a , which was dissolved in 3 mL of CH2Cl2. To the

4696 J . Org. Chem., Vol. 64, No. 13, 1999
Allen et al.
stirred solution of 10a was added PhCH2NH2 (1.12 mg, 1.05
mmol) in 4 mL of CH2Cl2 at 25 °C, and after 15 min of stirring,
the solvent was evaporated to give crude 8b (375 mg, 1.025
mmol, 98%), which by 1H NMR analysis contained erythro- and
threo-8b in a 2/1 ratio. Chromatography on silica gel (10%
EtOAc/hexane) resulted in significant desilylation of 8b to form
11a , and in several experiments the highest purified yields of
the isomers of 8b were obtained using 33% EtOAc in hexane
containing 2% Et3N. erythro-8b (mp 59 °C, 11%):1H NMR
(CDCl3) δ 0.043 (s, 9, Me3Si), 0.063 (s, 9, Me3Si), 2.29 (d, 1, J
) 11.3 Hz, CHSiMe3), 2.69 (d, 1, J ) 11.7 Hz, CHSiMe3), 3.59
(s, 3, OCH3), 4.36 and 4.37 (each d, 1, J ) 3.3 Hz, PhCH2),
5.52 (bs, 1, NH), 7.3 (m, 5, Ph); 13C NMR (CDCl3) δ -1.75,
-1.44, 35.3, 37.2, 44.1, 51.0, 127.6, 128.4, 128.7, 138.1, 173.0,
NMR (CDCl3) δ 0.043 (s, 9, Me3Si), 0.064 (s, 9, Me3Si), 2.12
and 2.39 (each d, 1, J ) 5.2 Hz, CHSiMe3).
N -Be n zyl-2-t r im e t h ylsilyl-4-b e n zyloxy-4-oxob u t a n -
a m id e (11b): 1H NMR (CDCl3) δ 0.072 (s, 9, Me3Si), 2.18 (dd,
1, J ) 11.7, 3.0 Hz, CHCO2), 2.40 (dd, 1, J ) 17.6, 3.0 Hz,
CHCO), 3.07 (dd, 1, J ) 17.6, 11.7 Hz, CHCON), 4.42 (dq, 2,
J ) 15.4, 5.5 Hz, CH2N), 5.07 and 5.13 (each d, 1, J ) 12.4
Hz, PhCH2O), 5.57 (bs, 1, NH), 7.3 (m, 10, Ph); 13C NMR
(CDCl3) δ -2.72, 31.9, 35.7, 43.8, 66.6, 127.4, 128.0, 128.21,
128.24, 128.5, 128.6, 135.8, 138.6, 173.3, 178.4; IR (CDCl3)
3446, 1730, 1655 cm-1; EIMS m/z 369 (M+, 12), 91 (C7H7+, 100)
73 (Me3Si+, 34); HRMS m/z calcd for C21H27NO3Si 369.1760,
found 369.1767.
N,N′-Bis[1′,4′-d ioxo-2′,3′-b is(t r im et h ylsilyl)-1′-b u t -3′-
en yl]-1,4-bis(a m in om eth yl)ben zen e (13). To a stirred solu-
tion of 1,4-bis(aminomethyl)benzene (12) (61 mg, 0.45 mmol)
in 3 mL of CH2Cl2 at 25 °C was added in one portion bisketene
1 (187 mg, 0.825 mmol) in 3 mL of CH2Cl2. After 10 min, the
175.6; IR (CDCl3) 3445, 1708, 1657, 1497 cm-1; EIMS m/z 365
(M+, 8), 350 (M+ - CH3, 38), 292 (M+ - TMS, 14), 91 (C7H7
,
+
100), 73 (Me3Si+, 54); HRMS m/z calcd for C13H31NO3Si2
365.1843, found 365.1854. threo-8b (oil, 12%): 1H 0.068 (s, 9,
Me3Si), 0.083 (s, 9, Me3Si), 2.13 (d, 1, J ) 5.2 Hz, CHSiMe3),
2.36 (d, 1, J ) 5.5 Hz, CHSiMe3), 3.64 (s, 3, OCH3), 4.22 (dd,
1, J ) 14.7, 4.7 Hz, PhCH), 4.59 (dd, 1, J ) 14.3, 6.3 Hz,
PhCH), 7.32 (m, 5, Ph), 8.51 (bs, 1, NH); 13C NMR (CDCl3) δ
-1.55, -1.47, 35.5, 38.2, 43.9, 51.7, 127.1, 128.2, 128.4, 138.8,
173.3, 178.2; IR (CDCl3) 2957, 1699, 1633 cm-1; EIMS m/z 365
(M+, 6), 91 (C7H7+, 100), 73 (Me3Si+, 60); HRMS m/z calcd for
1
solvent was evaporated, giving a white solid identified by H
1
NMR as 13 containing 8% succinamides with H NMR signals
at δ 2.03 and 2.33. 13: 1H NMR (CDCl3) δ 0.122 (s, 18, Me3Si),
0.138 (s, 18, Me3Si), 1.91 (s, 2, CHSi), 4.39 (d, 4, PhCH2, J )
5.6 Hz), 6.15 (s, 2, NH, J ) 5.7 Hz), 7.22 (s, 4, Ar); 13C NMR
(CDCl3) δ -2.0, -1.0, 10.7, 32.1, 43.5, 128.2, 137.8, 173.2,
179.6; IR (CDCl3) 3444, 2085, 1649, 1503 cm-1; EIMS m/z 588
(M+, 24), 73 (Me3Si+, 100); HRMS m/z calcd for C28H48N2O4-
Si4 588.2691, found 588.2710.
C
18H31NO3Si2 365.1843, found 365.1845.
N -B e n zy l-2-t r im e t h y ls ily l-4-m e t h o x y -4-o x o b u t a n -
a m id e 11a (white solid, mp 68-69 °C, 69 mg, 21%): 1H NMR
(CDCl3) δ 0.068 (s, 9, Me3Si), 2.18 (dd, 1, J ) 11.5, 3.0 Hz,
CHCO2CH3), 2.34 (dd, 1, J ) 17.3, 3.0 Hz, CHCO2CH3), 2.99
(dd, 1, J ) 17.3, 11.6 Hz, CHCONH), 3.64 (s, 3, OCH3), 4.43
Rea ction of Bisk eten e 1 w ith 1.2 Equ iv of 1,4-Bis-
(a m in om eth yl)ben zen e. To a stirred solution of 12 (128 mg,
0.940 mmol) in 4 mL of CH2Cl2 at -78 °C was added in one
portion bisketene 1 (184 mg, 0.814 mmol) in 2 mL of CH2Cl2.
After 10 min, the solution was allowed to warm to 25 °C over
(d, 2, J ) 5.7 Hz, PhCH2), 5.70 (bs, 1, NH), 7.3 (m, 5, Ph); 13
NMR (CDCl3) -2.82, 31.2 (t, J CH ) 132.6 Hz), 34.5 (d, J CH
C
)
1
20 min and was evaporated, giving a white solid which by H
125.2 Hz), 43.6, 51.7, 127.2, 127.8, 128.5, 138.6, 173.5, 174.0;
IR (CDCl3) 2931, 1731, 1660, 1503 cm-1; EIMS m/z 293 (M+,
26), 91 (C7H7+, 100), 73 (Me3Si+, 58); HRMS m/z calcd for
NMR was consistent with the formation of 14 without the
presence of other products. 14: 1H NMR (CD3OD) δ -0.01 (s,
Me3Si), 0.04 (s, Me3Si), 2.15 (s, rel area 1, CHSi), 2.45 (s, rel
area 4, CHSi), 3.8 (s, rel area 1, CH2NH2), 4.25 (m, rel area 8,
CH2NHCO), 7.3 (m, rel area 9, Ar).
C
15H23NO3Si 293.1447, found 293.1453.
N-Ben zyl-2,3-bis(tr im eth ylsilyl)-4-ben zyloxy-4-oxobu -
ta n a m id e (8c). Benzyl alcohol (60.6 mg, 0.561 mmol) and 1
mL of Et3N in 2 mL of pentane were added to bisketene 1 (138
mg, 0.611 mmol) in 3 mL of pentane, and the solution was
stirred for 20 min at 25 °C. The solvent was evaporated, and
the spectral properties of the intermediate ketenyl ester
ben zyl 2,3-(bistr im eth ylsilyl)-4-oxobu t-3-en oate (10b) were
recorded: 1H NMR (CDCl3) δ 0.093 (s, 9, Me3Si), 0.131 (s, 9,
Me3Si), 2.01 (s, 1, CHSiMe3), 5.14 (s, 2, PhCH2), 7.35 (m, 5,
Ph); 13C NMR CDCl3) δ -2.35, -1.03, 30.0, 46.0, 66.7, 128.1,
128.4, 128.5, 135.9, 174.8, 180.8; IR (CDCl3) 2959, 2085, 1716
cm-1. Then 2 mL of CH2Cl2 and PhCH2NH2 (66 mg, 0.617
mmol) in 2 mL of CH2Cl2 were added, and the solution was
stirred for 15 min and concentrated at reduced pressure.
Analysis by 1H NMR revealed the presence of erythro- and
threo-8c in a 5/1 ratio, together with traces of 11b. Chroma-
tography (3% Et3N, 33% CH2Cl2/hexane) gave pure erythro-
8c and 11b, but only some of the spectral properties of threo-
8c were obtained from a mixture containing the erythro isomer.
erythro-8c:1H NMR (CDCl3) δ 0.033 (s, 9, Me3Si), 0.056 (s, 9,
Me3Si), 2.30 and 2.73 (each d, 1, J ) 11.5 Hz, CHSiMe3), 4.36
and 4.37 (each d, 1, J ) 3.4 Hz, CH2N), 4.94 and 5.10 (each d,
1, J ) 12.3 Hz, CH2O), 5.50 (bs, 1, NH), 7.4 (m, 10, Ph); 13C
NMR (CDCl3) δ -1.66, -1.35, 35.5, 37.3, 44.1, 66.2, 127.6,
128.2, 128.4, 128.5, 128.7, 135.7, 138.1, 173.0, 174.9; IR
(CDCl3) 1705, 1656, 1498 cm-1; EIMS m/z 441 (M+, 9), 350
(M+ - C7H7, 47), 91 (C7H7+, 100), 73 (Me3Si+, 42); HRMS m/z
calcd for C24H35NO3Si2 441.2156, found 441.2152. threo-8c: 1H
Rea ction of 1,6-Dia m in oh exa n e w ith Bisk eten e 1. A
solution of bisketene 1 (0.5 mmol) in CH2Cl2 at -78 °C was
added to 1,6-diaminohexane (55.8 mg, 0.480 mmol) in 3 mL
of CH2Cl2 cooled to -78 °C, and a pink color developed which
persisted. The solution was stirred 30 min at -78 °C and
warmed to room temperature as the pink color disappeared
and a solid formed. The 1H NMR spectrum of the soluble
portion of the solid was consistent with structure 15: 1H NMR
(CDCl3) δ 0.07, 0.11 (each s, 9, Me3Si), 1.35 (b, CH2CH2CH2-
NH), 1.5 (b, CH2CH2NH), 2.35 (b, CHTMS), 2.7 (b, NH2), 3.15
(b, CH2NH), 5.9 and 7.8 (b, NH); IR (CDCl3) 1650, 1499 cm-1
.
Kin etics. Kinetic measurements were carried out by either
conventional UV spectroscopy or by stopped flow techniques
as reported previously.2j The program SigmaPlot was used to
fit the kinetics, using a statistical error weighted fitting, which
was shown before2j to give the best fit for ketene aminations.
Ack n ow led gm en t. Financial support by the Natu-
ral Sciences and Engineering Research Council of
Canada is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Kinetic data and
NMR spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O9825052