Olier et al.
TABLE 3. Influence of the Nature of the Substituents and of the
Ethylenic Chain Length
involving imine formation/Staudinger reaction/Pauson-Khand
cycloaddition reported herein enabled the preparation of original
fused-tricyclic azetidinones from the reaction of N-tosyl-N-allyl
ketene with complexed acetals derived from propargylic alde-
hydes. The formation of highly functionalized product in a small
number of steps offsets the modest yields. However, the
cleavage of the lactam N1-C4 bond during the cobalt-mediated
cyclization is detrimental to the chemoselectivity of the reaction
(except in the case leading to octahydro-1,3-diaza-cyclobut-
[e]azulen-2,7-dione, 18b).
methoda
Ar
Ph
Ph
PMP Me
PMP Me
R1
Me
Me
product (ratio)b
yield, %c (3 steps)
Experimental Section
1
2
3
4
5
6
7
8
A
B
A
B
A
B
A
B
A
B
A
B
13b:14b (65:35)
13b:14b (35:65)
16b:17b (52:48)
16b:17b (48:52)
53
49
15
49
30:9
33
33:22
27:22
7:16
4:10
30
General Procedure for the Sequential Staudinger/Pauson-Khand
Process. In a typical experiment, aniline (51 µL, 0.56 mmol) and
TMSOTf (166 µL, 0.92 mmol) were successively added to a
solution of complex 1b (220 mg, 0.51 mmol) in CH2Cl2 (2.5 mL)
at 0 °C. After 1.5 h at room temperature, the solution was filtered
through a short pad of basic alumina eluted with CH2Cl2. The filtrate
was concentrated in vacuo with a cold bath to afford the crude
imine as a dark red oil that was used in the next step without further
purification.
Method A. Diisopropyl ethyl amine (240 µL, 1.37 mmol) and
acyl chloride 11 (393 mg, 1.37 mmol) were successively added to
a solution of the crude complexed imine in CH2Cl2 (2.5 mL) at 0
°C. After 2.5 h at room temperature, silica gel (5 g) was added and
the solvent was removed in vacuo at 20 °C. The residue was placed
under argon atmosphere and was heated for 18 h at 40 °C. The
silica gel, which slowly turned blue, was rinsed with CH2Cl2. The
solvent was concentrated under reduced pressure to afford an orange
oil that was purified by column chromatography on silica gel
(pentane/AcOEt 95:5 to 70:30) to give a mixture of 13b/14b as a
white solid (114 mg, 53%) in a ratio 65:35. The mixture was
separated on basic alumina (pentane/AcOEt 80:20) to afford pure
samples of 13b and 14b. Both products were recrystallized from
CH2Cl2/n-heptane.
3-Benzenesulfonyl-7-methyl-1-phenyl-2a,3,4,4a,5,7b-hexahy-
dro-1H-1,3-diaza-cyclobut[e]indene-2,6-dione (13b). Mp 223-225
°C. 1H NMR (300 MHz, CDCl3): δ 7.76 (2H, d, J ) 8.3),
7.34-7.13 (7H, m), 5.72 (1H, dq, J ) 5.5, 1.5), 5.24 (1H, d, J )
5.5), 3.66 (2H, m), 2.97 (1H, br m), 2.73 (1H, dd, J ) 18.4, 7.0),
2.47 (3H, s), 2.24 (1H, dd, J ) 18.4, 3.0), 1.92 (3H, d, J ) 1.5).
13C NMR (75 MHz, CDCl3): δ 206.5 (C), 162.4 (C), 161.3 (C),
144.8 (C), 143.1 (C), 137.1 (C), 136.2 (C), 130.4 (CH × 2), 129.9
(CH × 2), 127.8 (CH × 2), 125.7(CH), 116.9 (CH × 2), 65.1 (CH),
51.8 (CH), 48.6 (CH2), 43.6 (CH2), 32.7 (CH), 22.0 (CH3), 8.8
(CH3). HRMS (TOF MS ES+) for C23H23N2O4S [M + H] calcd
423.1373, found 423.1376.
Ph
Ph
SiMe3 13c:14ad (77:23)
SiMe3 13c
PMP SiMe3 16c:17ad (60:40)
PMP SiMe3 16c:17ad (55:45)
9
Ph
Ph
Ph
Ph
H
H
Me
Me
13a:14ad (29:71)
13a:14ad (29:71)
18b
10
11
12
18b
30
a Conditions A: SiO2, argon, 40 °C, 18 h. Conditions B: NMO ·H2O,
rt, 18 h. b Determined by 1H NMR on the isolated products mixture,
unless otherwise stated. c Isolated yields. d Ratio determined from
isolated products yields.
Regarding the formation of the [4.6.5]-fused ring system, the
best results were obtained from 1b (Table 3, entries 1-4). The
yields were lower when starting from 1c (Table 3, entries
5-8).21 With the latter, protodesilylation occurred concomit-
tantly with ring opening, which led to 14a. No reaction at all
was detected from 1d.
The instability of acetal 1a under the reaction conditions used
in the first step is likely to explain the overall low yields
registered for the unsubstituted triple bond (Table 3, entries 9
and 10).22
As already stated, the instability of the corresponding imines
precluded the use of aliphatic amines. No tricyclic lactams could
be isolated when using either pent-4-enyl-amine or N-allylgly-
cine methyl ester.
To the best of our knowledge, there are rather few examples
of seven-membered ring closure leading to bicyclo-[5.3.0]-
decanes via Pauson-Khand reaction.23 The [4.7.5]-fused tri-
cyclic azetidinone 18b was obtained as a single isomer in 30%
overall yield from acyl chloride 15 (Table 3, entries 11 and
12).24
Benzenesulfonyl-5-methyl-6-oxo-2,3,4,6,7,7a-hexahydro-1H-
2-pyridine-3-carboxylic Acid Phenylamide (14b). Mp 180-182
1
°C. H NMR (300 MHz, CDCl3): δ 8.73 (1H,br s), 7.75 (2H, d, J
Conclusion
) 8.3), 7.58 (2H, br d, J ) 7.7), 7.29-7.40 (4H, m), 7.18 (1H, t,
J ) 7.7), 4.62 (1H, dd, J ) 6.8, 2.5), 4.11 (1H, dd, J ) 10.2, 5.9),
3.51 (1H, br d, J ) 19.0) 3.07-3.20 (1H, br m), 2.85 (1H, dd, J )
12.5, 10.2), 2.58 (1H, dd, J ) 18.4, 6.5), 2.48 (3H, s), 2.29-240,
(superimposed m), 1.94 (1H, dd, J ) 18.4, 2.5), 1.57 (3H, br s).
13C NMR (75 MHz, CDCl3): δ 205.7 (C), 168.5 (C), 166.6 (C),
144.9 (C), 137.3 (C), 136.3 (C), 134.0 (C), 130.3 (CH × 2), 129.1
(CH × 2), 127.2 (CH × 2), 124.9 (CH), 119.8 (CH × 2), 55.4
(CH), 49.6 (CH2), 38.8 (CH2), 35.7 (CH), 26.3 (CH2), 21.6 (CH3),
7.7 (CH3). HRMS (TOF MS ES+) for C23H25N2O4S [M + H] calcd
425.1529, found 425.1522.
The reactivity of dicobalt hexacarbonyl complexes of alkynyl
imines was investigated. The very simple three-step procedure
(21) Steric hindrance is responsible for the low yield in this particular case;
see ref 4a and Mukai, C.; Uchiyama, U.; Sakamoto, S.; Hanaoka, M. Tetrahedron
Lett. 1995, 36, 5761–5764.
(22) Very similar selectivity and yields were obtained from the p-MeOPh
(PMP) derivative.
(23) (a) Madu, C. E.; Lovely, C. J. Synlett 2007, 2011–2016. (b) Madu, C. E.;
Seshadri, H.; Lovely, C. J. Tetrahedron 2007, 63, 5019–5029. (c) Mukai, C.;
Inagashi, F.; Yoshida, K.; Hara, Y.; Kitagaki, S. J. Am. Chem. Soc. 2005, 70,
7159–7171. (d) Perez-Serrano, L.; Casarrubios, L.; Dominguez, G.; Perez-
Castells, J. Chem. Commun. 2001, 2602–2603. (e) Perez-Serrano, L.; Dominguez,
G.; Perez-Castells, J. J. Org. Chem. 2004, 69, 5413–5418. (f) Park, J. H.; Kim,
S. Y.; Kim, S. M.; Lee, S. I.; Chung, Y. K. Synlett 2007, 453–459. (g) Alcaide,
B.; Almendros, P.; Aragoncillo, C. Chem. Eur. J. 2005, 8, 1719–1729.
(24) The diastereoselectivity, likely to be the same as in the case of six-
membered ring closure, could not be ascertained.
Method B. Diisopropyl ethyl amine (154 µL, 0.93 mmol) and
acyl chloride 15 (280 mg, 0.93 mmol) were successively added to
a solution of the crude complexed imine in CH2Cl2 (2.0 mL) at 0
°C. After 2.5 h at room temperature, the reaction was cooled down
to -20 °C and NMO ·H2O (100 mg, 0.74 mmol) was added in one
portion. The solution was slowly warmed up over a period of 18 h.
8472 J. Org. Chem. Vol. 73, No. 21, 2008